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Karnofsky, Eva www.deutschlandfunk.de, Sonntagsspaziergang
In this episode, 2024 David Karnofsky Memorial Award winner Lillian L. Siu reviews her career developing novel therapies in the phase I setting, the evolution of her field, and her mentor's dreaded “evil red pencil.” Siu was among the first scientists to read out the signals of safety, pharmacology, and preliminary efficacy of therapeutic agents that ushered in a new era of cancer therapy. She has been involved in the early development of over 50 drugs and has focused on ways to improve efficiency and scientific relevance of clinical trials. Over the course of her career as a phase I clinical trialist, Siu watched as the field moved away from using “maximum tolerated dose,” the growing need for early-phase efficacy data, and the emergence of intermediate biomarkers. After a nearly 30-year-long career, Siu's advice for young oncologists is simple: Don't give up. “Learn from every mistake or every challenge and rise above it and be tenacious,” Siu said. “Be persistent, because there's never an end that is a bad ending. It is always a good ending if you put enough effort in it. Maybe not entirely the way you want it, but at least if you put in the effort, something will return to you that is worth your effort. I truly believe in that, and certainly I see that in my career. “I don't only have positive results, I have very often negative results, but it's fun. Learning from your mistakes is half of the fun, and cherish that kind of moment to learn from it.” Siu spoke with Jacquelyn Cobb, reporter with The Cancer Letter. A transcript of the conversation appears on The Cancer History Project.
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Émile P. Torres's history of dishonesty and harassment, published by anonymous-for-obvious-reasons on May 1, 2024 on The Effective Altruism Forum. This is a cross-post and you can see the original here, written in 2022. I am not the original author, but I thought it was good for more EAs to know about this. I am posting anonymously for obvious reasons, but I am a longstanding EA who is concerned about Torres's effects on our community. An incomplete summary Introduction This post compiles evidence that Émile P. Torres, a philosophy student at Leibniz Universität Hannover in Germany, has a long pattern of concerning behavior, which includes gross distortion and falsification, persistent harassment, and the creation of fake identities. Note: Since Torres has recently claimed that they have been the target of threats from anonymous accounts, I would like to state that I condemn any threatening behavior in the strongest terms possible, and that I have never contacted Torres or posted anything about Torres other than in this Substack or my Twitter account. I have no idea who is behind these accounts. To respect Torres's privacy and identity, I have also omitted their first name from the screenshots and replaced their previous first name with 'Émile'. Table of contents Introduction My story Stalking and harassment Peter Boghossian Helen Pluckrose Demonstrable falsehoods and gross distortions "Forcible" removal "Researcher at CSER" Giving What We Can Brief digression on effective altruism More falsehoods and distortions Hilary Greaves Andreas Mogensen Nick Beckstead Tyler Cowen Olle Häggström Sockpuppetry "Alex Williams" Conclusion My story Before I discuss Torres's behavior, I will provide some background about myself and my association with effective altruism (EA). I hope this information will help readers decide what biases I may have and subject my arguments to the appropriate degree of critical scrutiny. I first heard about EA upon attending Aaron Swartz's memorial in January 2013. One of the speakers at that event was Holden Karnofsky, co-founder of GiveWell, a charity evaluator for which Aaron had volunteered. Karnofsky described Aaron as someone who "believed in trying to maximize the good he accomplished with each minute he had." I resonated with that phrase, and in conversation with some friends after the memorial, I learned that Aaron's approach, and GiveWell's, were examples of what was, at the time, a new movement called "effective altruism." Despite my sympathy for EA, I never got very involved with it, due to a combination of introversion and the sense that I hadn't much to offer. I have donated a small fraction of my income to the Against Malaria Foundation for the last nine years, but I have never taken the Giving What We Can pledge, participated in a local EA group, or volunteered or worked for an EA organization. I decided to write this article after a friend forwarded me one of Torres's critical pieces on longtermism. I knew enough about this movement -- which emerged out of EA -- to quickly identify some falsehoods and misrepresentations in Torres's polemic. So I was surprised to find, when I checked the comments on Twitter, that no one else was pointing out these errors. A few weeks later, I discovered that this was just one of a growing number of articles by Torres that attacked these ideas and their proponents. Since I also noticed several factual inaccuracies in these other publications, I got curious and decided to look into Torres's writings more closely. I began to follow Torres's Twitter presence with interest and to investigate older Twitter feuds that Torres occasionally references. After looking into these and systematically checking the sources Torres cites in support of their various allegations, I found Torres's behavior much more troublin...
Karnofsky, Eva www.deutschlandfunkkultur.de, Fazit
Karnofsky, Eva www.deutschlandfunk.de, Kultur heute
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Solution to the two envelopes problem for moral weights, published by MichaelStJules on February 19, 2024 on The Effective Altruism Forum. Summary When taking expected values, the results can differ radically based on which common units we fix across possibilities. If we normalize relative to the value of human welfare, then other animals will tend to be prioritized more than by normalizing by the value of animal welfare or by using other approaches to moral uncertainty. For welfare comparisons and prioritization between different moral patients like humans, other animals, aliens and artificial systems, I argue that we should fix and normalize relative to the moral value of human welfare, because our understanding of the value of welfare is based on our own experiences of welfare, which we directly value. Uncertainty about animal moral weights is about the nature of our experiences and to what extent other animals have capacities similar to those that ground our value, and so empirical uncertainty, not moral uncertainty ( more). I revise the account in light of the possibility of multiple different human reference points between which we don't have fixed uncertainty-free comparisons of value, like pleasure vs belief-like preferences (cognitive desires) vs non-welfare moral reasons, or specific instances of these. If and because whatever moral reasons we apply to humans, (similar or other) moral reasons aren't too unlikely to apply with a modest fraction of the same force to other animals, then the results would still be relatively animal-friendly ( more). I outline why this condition plausibly holds across moral reasons and theories, so that it's plausible we should be fairly animal-friendly ( more). I describe and respond to some potential objections: There could be inaccessible or unaccessed conscious subsystems in our brains that our direct experiences and intuitions do not (adequately) reflect, and these should be treated like additional moral patients ( more). The approach could lead to unresolvable disagreements between moral agents, but this doesn't seem any more objectionable than any other disagreement about what matters (more). Epistemic modesty about morality may push for also separately normalizing by the values of nonhumans or against these comparisons altogether, but this doesn't seem to particularly support the prioritization of humans ( more). I consider whether similar arguments apply in cases of realism vs illusionism about phenomenal consciousness, moral realism vs moral antirealism, and person-affecting views vs total utilitarianism, and find them less compelling for these cases, because value may be grounded on fundamentally different things ( more). How this work has changed my mind: I was originally very skeptical of intertheoretic comparisons of value/reasons in general, including across theories of consciousness and the scaling of welfare and moral weights between animals, because of the two envelopes problem ( Tomasik, 2013-2018) and the apparent arbitrariness involved. This lasted until around December 2023, and some arguments here were originally going to be part of a piece strongly against such comparisons for cross-species moral weights, which I now respond to here along with positive arguments for comparisons. Acknowledgements I credit Derek Shiller and Adam Shriver for the idea of treating the problem like epistemic uncertainty relative to what we experience directly. I'd also like to thank Brian Tomasik, Derek Shiller and Bob Fischer for feedback. All errors are my own. Background On the allocation between the animal-inclusive and human-centric near-termist views, specifically, Karnofsky ( 2018) raised a problem: The "animal-inclusive" vs. "human-centric" divide could be interpreted as being about a form of "normative uncertainty": un...
Una familia judía marcó en la niñez la vida de Louis Daniel Armstrong, el trompetista y cantante norteamericano de jazz. Louis se destacó como una de las figuras más carismáticas e innovadoras en la historia del jazz y, sin duda, se erige como el músico más icónico de este género, quien logró transformar el jazz en un referente del arte popular. En su niñez fue adoptado por la familia Karnofsky, emigrantes judíos lituanos que llegaron a Estados Unidos con el ánimo de encontrar un lugar donde no fueran perseguidos. Ellos se compadecieron de Armstrong cuando lo conocieron en necesidad en la ciudad de New Orleans a la edad de 7 años, acogiéndole con amor y amabilidad en su hogar. Según contó el mismo artista, la sra Karnovski le cantaba canciones judías de cuna rusa, que le motivaron más tarde a cantar y tocar canciones rusas judías. El Sr. Karnofsky fue quien le compró su primer instrumento musical y lo apoyó desde siempre. Cuando Louis Armstrong se convirtió en músico y compositor profesional, utilizó melodías judías en composiciones como: “St. James's Hospital” y “Go Down Moses”. También, en agradecimiento escribió un libro sobre esta familia judía que lo acogió en 1907 y le dio una oportunidad. Louis Daniel Armstrong visitó Israel en 1959. Orgullosamente hablaba yiddish con fluidez, y en memoria de esta familia y hasta el final de su vida, llevó en su cuello la Estrella de David. El artista dijo que de su familia aprendió a vivir una vida real y con determinación. Finalmente su vida de éxitos, conciertos y canciones terminó en 1971. Te dejamos una parte de uno de sus grandes éxitos.
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Fundamentals of Global Priorities Research in Economics Syllabus, published by poliboni on August 8, 2023 on The Effective Altruism Forum. This is a 6-9 session syllabus on the fundamentals of global priorities research in economics. The purpose is to help economics students and researchers interested in GPR get a big picture view of the field and come up with research ideas. Because of this focus on fundamentals, the readings are rather light on economics and heavy on philosophy and empirics of different cause areas. Previous versions of this list were used internally at GPI and during GPI's Oxford Global Priorities Fellowship in 2023, where the prompts guided individual reflection and group discussion. Many thanks to the following for their help creating and improving this syllabus: Gustav Alexandrie, Loren Fryxell, Arden Koehler, Luis Mota, and Charlotte Siegmann. The readings below don't necessarily represent their views, GPI's, or mine. 1. Philosophical Foundations Topic: Global priorities research is a normative enquiry. It is primarily interested in understanding what we should do in the face of global problems, and only derivatively interested in how those problems work/facts about the world that surround them. In this session, we will focus on understanding what ethical theory is, what some of the most important moral theories are, how these theories relate to normative thinking in economics, and what these theories imply about what the most important causes are. Literature: MacAskill, William. 2019. "The Definition of Effective Altruism" (Section 4 is optional) Prompt 1: How aligned with your aims as a researcher is the definition of Effective Altruism proposed in this article (p. 14)? Trammell, Philip. 2022. Philosophical foundations (Slides 1-2, 5-9, 12-16, 20-24) Prompt 2: What is your best guess theory of welfare? How much do you think it matters to get this right? Prompt 3: What is your best guess view in axiology? What are your key uncertainties about it? Do you think axiology is all that matters in determining what one ought to do (excluding empirical uncertainty)? Trammell, Philip. 2022. Three sins of economics (Slides 1-24, 27) Prompt 4: What are your "normative defaults"? What are views here that you would like to explore more? Prompt 5: Do you agree that economics has the normative defaults identified in the reading? Can you give examples of economics work that avoids these? Prompt 6: Insofar as economists tend to commit the 3 'sins', what do you think of the strategy of finding problems which are underprovided by those views? Extra reading: Wilkinson, Hayden. 2022. "Key Lessons From Global Priorities Research" (watch video here - slides are not quite self-contained) Which key results are most interesting or surprising to you and why? Do you think any of them are wrong? Greaves, Hilary. 2017. "Population axiology" Broome, John. 1996. "The Welfare Economics of Population" 2. Effective altruism: differences in impact and cost-effectiveness estimates Topic: In this session we tackle two key issues in cause prioritization. First, how is impact distributed across interventions (or importance across problems). Second, how to compare the cost-effectiveness of interventions which are differentially well-grounded. Literature: Kokotajlo, Daniel and Oprea, Alexandra. 2020. "Counterproductive Altruism: The Other Heavy Tail" (Skip Sections I and II) Prompt 1: Do you think there is a heavy right tail of opportunities to do good? What about a heavy left tail? Prompt 2: How do the distributions of impact of interventions aimed at the near-term and long-term compare (specifically, in terms of the heaviness of their tails)? Karnofsky, Holden. 2016. "Why we can't take expected value estimates literally (even when they're unbiased)" Prompt 3: What, in your view, is ...
On this episode, Dr. Ronald Love sits down with Alan Karnofsky to discuss leadership skills and the tools needed to be a successful leader in the workplace. Follow us on Social Media: Ron: @dr.ronlove Deonna: @dr.k_psyd Instagram and Facebook: @unpackedanddetangled Twitter: @uanddpodcast Email: unpackedanddetangled@gmail.com
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: The 'Wild' and 'Wacky' Claims of Karnofsky's ‘Most Important Century', published by Spencer Becker-Kahn on April 26, 2023 on The Effective Altruism Forum. Holden Karnofsky describes the claims of his “Most Important Century” series as “wild” and “wacky”, but at the same time purports to be in the mindset of “critically examining” such “strange possibilities” with “as much rigour as possible”. This emphasis is mine, but for what is supposedly an important piece of writing in a field that has a big part of its roots in academic analytic philosophy, it is almost ridiculous to suggest that this examination has been carried out with 'as much rigour as possible'. My main reactions - which I will expand on this essay - are that Karnofsky's writing is in fact distinctly lacking in rigour; that his claims are too vague or even seem to shift around; and that his writing style - often informal, or sensationalist - aggravates the lack of clarity while simultaneously putting the goal of persuasion above that of truth-seeking. I also suggest that his emphasis on the wildness and wackiness of his own "thesis" is tantamount to an admission of bias on his part in favour of surprising or unconventional claims. I will start with some introductory remarks about the nature of my criticisms and of such criticism in general. Then I will spend some time trying to point to various instances of imprecision, bias, or confusion. And I will end by asking whether any of this even matters or what kind of lessons we should be drawing from it all. Notes: Throughout, I will quote from the whole series of blog posts by treating them as a single source rather than referencing which them separately. Note that the series appears in single pdf here (so one can always Ctrl/Cmd+F to jump to the part I am quoting). It is plausible that some of this post comes across quite harshly but none of it is intended to constitute a personal attack on Holden Karnofsky or an accusation of dishonesty. Where I have made errors of have misrepresented others, I welcome any and all corrections. I also generally welcome feedback on the writing and presentation of my own thoughts either privately or in the comments.Acknowledgements: I started this essay a while ago and so during the preparation of this work, I have been supported at various points by FHI, SERI MATS, BERI and Open Philanthropy. The development of this work benefitted significantly from numerous conversations with Jennifer Lin. 1. Broad Remarks About My Criticisms If you felt and do feel convinced by Karnofsky's writings, then upon hearing about my reservations, your instinct may be to respond with reasonable-seeming questions like: 'So where exactly does he disagree with Karnofsky?' or 'What are some specific things that he thinks Karnofsky gets wrong?'. You may well want to look for wherever it is that I have carefully categorized my criticisms, to scroll through to find all of my individual object-level disagreements so that you can see if you know the counterarguments that mean that I am wrong. And so it may be frustrating that I will often sound like I am trying to weasel out of having to answer these questions head-on or not putting much weight on the fact that I have not laid out my criticisms in that way. Firstly, I think that the main issues to do with clarity and precision that I will highlight occur at a fundamental level. It is not that they are 'more important' than individual, specific, object-level disagreements, but I claim that Karnofsky does a sufficiently poor job of explaining his main claims, the structure of his arguments, the dependencies between his propositions, and in separating his claims from the verifications of those claims, that it actually prevents detailed, in-depth discussions of object-level disagreements from making much sense...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: A report about LessWrong karma volatility from a different universe, published by Ben Pace on April 1, 2023 on LessWrong. In a far away universe, a news report is written about LessWrong. The following passages have been lifted over and written into this post... Early one morning all voting on LessWrong was halted It was said that there was nothing to worry about But then GreaterWrong announced their intent to acquire and then un-acquire LessWrong All LessWrong users lost all of their karma, but a poorly labeled 'fiat@' account on the EA Forum was discovered with no posts and a similarly large amount of karma Habryka states that LessWrong and the EA Forum "work at arms length" Later, Zvi Mowshowitz publishes a leaked internal accounting sheet from the LessWrong team It includes entries for "weirdness points" "utils" "Kaj_Sotala" "countersignals" and "Anthropic". We recommend all readers open up the sheet to read in full. Later, LessWrong filed for internet-points-bankruptcy and Holden Karnofsky was put in charge. Karnofsky reportedly said: I have over 15 years of nonprofit governance experience. I have been the Chief Executive Officer of GiveWell, the Chief Executive Officer of Open Philanthropy, and as of recently an intern at an AI safety organization. Never in my career have I seen such a complete failure of nonprofit board controls and such a complete absence of basic decision theoretical cooperation as occurred here. From compromised epistemic integrity and faulty community oversight, to the concentration of control in the hands of a very small group of biased, low-decoupling, and potentially akratic rationalists, this situation is unprecedented. Sadly the authors did not have time to conclude the reporting, though they list other things that happened in a comment below. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.
Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: A report about LessWrong karma volatility from a different universe, published by Ben Pace on April 1, 2023 on LessWrong. In a far away universe, a news report is written about LessWrong. The following passages have been lifted over and written into this post... Early one morning all voting on LessWrong was halted It was said that there was nothing to worry about But then GreaterWrong announced their intent to acquire and then un-acquire LessWrong All LessWrong users lost all of their karma, but a poorly labeled 'fiat@' account on the EA Forum was discovered with no posts and a similarly large amount of karma Habryka states that LessWrong and the EA Forum "work at arms length" Later, Zvi Mowshowitz publishes a leaked internal accounting sheet from the LessWrong team It includes entries for "weirdness points" "utils" "Kaj_Sotala" "countersignals" and "Anthropic". We recommend all readers open up the sheet to read in full. Later, LessWrong filed for internet-points-bankruptcy and Holden Karnofsky was put in charge. Karnofsky reportedly said: I have over 15 years of nonprofit governance experience. I have been the Chief Executive Officer of GiveWell, the Chief Executive Officer of Open Philanthropy, and as of recently an intern at an AI safety organization. Never in my career have I seen such a complete failure of nonprofit board controls and such a complete absence of basic decision theoretical cooperation as occurred here. From compromised epistemic integrity and faulty community oversight, to the concentration of control in the hands of a very small group of biased, low-decoupling, and potentially akratic rationalists, this situation is unprecedented. Sadly the authors did not have time to conclude the reporting, though they list other things that happened in a comment below. Thanks for listening. To help us out with The Nonlinear Library or to learn more, please visit nonlinear.org.
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Time Article Discussion - "Effective Altruist Leaders Were Repeatedly Warned About Sam Bankman-Fried Years Before FTX Collapsed", published by Nathan Young on March 15, 2023 on The Effective Altruism Forum. There is a new Time article Seems certain 98% we'll discuss it I would like us to try and have a better discussion about this than we sometimes do. Consider if you want to engage I updated a bit on important stuff as a result of this article. You may disagree. I am going to put my "personal updates" in a comment Excepts from the article that I think are relevant. Bold is mine. I have made choices here and feel free to recommend I change them. Yet MacAskill had long been aware of concerns around Bankman-Fried. He was personally cautioned about Bankman-Fried by at least three different people in a series of conversations in 2018 and 2019, according to interviews with four people familiar with those discussions and emails reviewed by TIME. He wasn't alone. Multiple EA leaders knew about the red flags surrounding Bankman-Fried by 2019, according to a TIME investigation based on contemporaneous documents and interviews with seven people familiar with the matter. Among the EA brain trust personally notified about Bankman-Fried's questionable behavior and business ethics were Nick Beckstead, a moral philosopher who went on to lead Bankman-Fried's philanthropic arm, the FTX Future Fund, and Holden Karnofsky, co-CEO of OpenPhilanthropy, a nonprofit organization that makes grants supporting EA causes. Some of the warnings were serious: sources say that MacAskill and Beckstead were repeatedly told that Bankman-Fried was untrustworthy, had inappropriate sexual relationships with subordinates, refused to implement standard business practices, and had been caught lying during his first months running Alameda, a crypto firm that was seeded by EA investors, staffed by EAs, and dedicating to making money that could be donated to EA causes. MacAskill declined to answer a list of detailed questions from TIME for this story. “An independent investigation has been commissioned to look into these issues; I don't want to front-run or undermine that process by discussing my own recollections publicly,” he wrote in an email. “I look forward to the results of the investigation and hope to be able to respond more fully after then.” Citing the same investigation, Beckstead also declined to answer detailed questions. Karnofsky did not respond to a list of questions from TIME. Through a lawyer, Bankman-Fried also declined to respond to a list of detailed written questions. The Centre for Effective Altruism (CEA) did not reply to multiple requests to explain why Bankman-Fried left the board in 2019. A spokesperson for Effective Ventures, the parent organization of CEA, cited the independent investigation, launched in Dec. 2022, and declined to comment while it was ongoing. In a span of less than nine months in 2022, Bankman-Fried's FTX Future Fund—helmed by Beckstead—gave more than $160 million to effective altruist causes, including more than $33 million to organizations connected to MacAskill. “If [Bankman-Fried] wasn't super wealthy, nobody would have given him another chance,” says one person who worked closely with MacAskill at an EA organization. “It's greed for access to a bunch of money, but with a philosopher twist.” But within months, the good karma of the venture dissipated in a series of internal clashes, many details of which have not been previously reported. Some of the issues were personal. Bankman-Fried could be “dictatorial,” according to one former colleague. Three former Alameda employees told TIME he had inappropriate romantic relationships with his subordinates. Early Alameda executives also believed he had reneged on an equity arrangement that would have left Bankman-Frie...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Future Matters #7: AI timelines, AI skepticism, and lock-in, published by Pablo on February 3, 2023 on The Effective Altruism Forum. That man is born merely for a few, who thinks only of the people of his own generation. Many thousands of years and many thousands of peoples will come after you; it is to these that you should have regard. Lucius Annaeus Seneca Future Matters is a newsletter about longtermism and existential risk. Each month we collect and summarize relevant research and news from the community, and feature a conversation with a prominent researcher. You can also subscribe on Substack, listen on your favorite podcast platform and follow on Twitter. Future Matters is also available in Spanish. Research Ajeya Cotra's biological anchors model to forecast AGI timelines consists of three parts — an estimate of the compute required to train AGI with 2020 algorithms, a projection of how these compute requirements decrease over time due to algorithmic progress, and a forecast of how the size of training runs will increase over time due to declining hardware costs and increased investment in AI training. Tom Davidson's What a compute-centric framework says about AI takeoff speeds extends Cotra's framework to incorporate a more sophisticated model of how R&D investment translates into algorithmic and hardware progress, and also to capture the “virtuous circle” whereby AI progress leads to more automation in AI R&D and in turn faster AI progress. This results in a model of AI takeoff speed, defined here as the time between AI being able to automate 20% of cognitive tasks to being able to automate 100% of cognitive tasks. Davidson's median estimate for AI takeoff is approximately three years. This is an impressive and significant piece of research, which we cannot summarize adequately here; we hope to feature a conversation with the author in a future issue to explore it in more depth. The full report is available here. Readers are encouraged to play around with the neat interactive model. Zac Hatfield-Dodds shares some Concrete reasons for hope about AI safety []. A researcher at Anthropic (writing in a personal capacity), he takes existential risks from AI seriously, but pushes back on recent pronouncements that AI catastrophe is pretty much inevitable. Hatfield-Dodds highlights some of the promising results from the nascent efforts at figuring out how to align and interpret large language models. The piece is intended to “rebalance the emotional scales” in the AI safety community, which he feels have recently tipped too far towards a despair that feels is both unwarranted and unconstructive. Holden Karnofsky's Transformative AI issues (not just misalignment) [] surveys some of the high-stakes issues raised by transformative AI, particularly those that we should be thinking about ahead of time in order to make a lasting difference to the long-term future. These include not just existential risk from misalignment, but also power imbalances, early AI applications, new life forms, and persistent policies and norms. Karnofsky is inclined to prioritize the first two issues, since he feels very uncertain about the sign of interventions focused on the remaining ones. Lizka Vaintrob argues that we should Beware safety-washing [] by AI companies, akin to greenwashing, where companies misrepresent themselves as being more environmentally conscious than they actually are, rather than taking costly actions to reduce their environmental impact. This could involve misleading not just consumers, but investors, employees, regulators, etc. on whether an AI project took safety concerns seriously. One promising way to address this would be developing common standards for safety, and trustworthy methods for auditing and evaluating companies against these standards. In How we could ...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Discussing how to align Transformative AI if it's developed very soon, published by elifland on November 28, 2022 on LessWrong. Coauthored with equal contribution from Eli Lifland and Charlotte Siegmann. Thanks to Holden Karnofsky, Misha Yagudin, Adam Bales, Michael Aird, and Sam Clarke for feedback. All views expressed are our own. Introduction Background Holden Karnofsky recently published a series on AI strategy "nearcasting”: What would it look like if we developed Transformative AI (TAI) soon? How should Magma, the hypothetical company that develops TAI, align and deploy it? In this post we focus on How might we align transformative AI if it's developed very soon. The nearcast setup is: A major AI company (“Magma,” [following the setup and description of this post from Ajeya Cotra]) has good reason to think that it can develop transformative AI very soon (within a year), using what Ajeya calls “human feedback on diverse tasks” (HFDT) - and has some time (more than 6 months, but less than 2 years) to set up special measures to reduce the risks of misaligned AI before there's much chance of someone else deploying transformative AI. Summary For time-constrained readers, we think the most important sections are: Categorizing ways of limiting AIs Clarifying advanced collusion Disincentivizing deceptive behavior likely requires more than a small chance of catching it We discuss Magma's goals and strategy. The discussion should be useful for people unfamiliar or familiar with Karnofsky's post and can be read as a summary, clarification and expansion of Karnofsky's post. We describe a potential plan for Magma involving coordinating with other AI labs to deploy the most aligned AI in addition to stopping other misaligned AIs. more We define the desirability of Magma's AIs in terms of their ability to help Magma achieve its goals while avoiding negative outcomes. We discuss desirable properties such as differential capability and value-alignment, and describe initial hypotheses regarding how Magma should think about prioritizing between desirable properties. more We discuss Magma's strategies to increase desirability: how Magma can make AIs more desirable by changing properties of the AIs and the context in which they're applied, and how Magma should apply (often limited) AIs to make other AIs more desirable. more We clarify that the chance of collusion depends on whether AIs operate on a smaller scale, have very different architectures and orthogonal goals. We outline strategies to reduce collusion conditional on whether the AIs have indexical goals and follow causal decision theory or not. more We discuss how Magma can test the desirability of AIs via audits and threat assessments. Testing can provide evidence regarding the effectiveness of various alignment strategies and the overall level of misalignment. more We highlight potential disagreements with Karnofsky, including: We aren't convinced that a small chance of catching deceptive behavior by itself might make deception much less likely. We argue that in addition to having a small chance of catching deceptive behavior, the AI's supervisor needs to be capable enough to (a) distinguish between easy-to-catch and hard-to-catch deceptive behaviors and (b) attain a very low “false positive rate” of harshly penalizing non-deceptive behaviors. The AI may also need to be inner-aligned, i.e. intrinsically motivated by the reward. more We are more pessimistic than Karnofsky about the promise of adjudicating AI debates. We aren't convinced there's much theoretical reason to believe that AI debates robustly tend toward truth, and haven't been encouraged by empirical results. more We discuss the chance that Magma would succeed: We discuss the promise of "hacky" solutions to alignment. If applied alignment techniques that feel br...
Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Discussing how to align Transformative AI if it's developed very soon, published by elifland on November 28, 2022 on LessWrong. Coauthored with equal contribution from Eli Lifland and Charlotte Siegmann. Thanks to Holden Karnofsky, Misha Yagudin, Adam Bales, Michael Aird, and Sam Clarke for feedback. All views expressed are our own. Introduction Background Holden Karnofsky recently published a series on AI strategy "nearcasting”: What would it look like if we developed Transformative AI (TAI) soon? How should Magma, the hypothetical company that develops TAI, align and deploy it? In this post we focus on How might we align transformative AI if it's developed very soon. The nearcast setup is: A major AI company (“Magma,” [following the setup and description of this post from Ajeya Cotra]) has good reason to think that it can develop transformative AI very soon (within a year), using what Ajeya calls “human feedback on diverse tasks” (HFDT) - and has some time (more than 6 months, but less than 2 years) to set up special measures to reduce the risks of misaligned AI before there's much chance of someone else deploying transformative AI. Summary For time-constrained readers, we think the most important sections are: Categorizing ways of limiting AIs Clarifying advanced collusion Disincentivizing deceptive behavior likely requires more than a small chance of catching it We discuss Magma's goals and strategy. The discussion should be useful for people unfamiliar or familiar with Karnofsky's post and can be read as a summary, clarification and expansion of Karnofsky's post. We describe a potential plan for Magma involving coordinating with other AI labs to deploy the most aligned AI in addition to stopping other misaligned AIs. more We define the desirability of Magma's AIs in terms of their ability to help Magma achieve its goals while avoiding negative outcomes. We discuss desirable properties such as differential capability and value-alignment, and describe initial hypotheses regarding how Magma should think about prioritizing between desirable properties. more We discuss Magma's strategies to increase desirability: how Magma can make AIs more desirable by changing properties of the AIs and the context in which they're applied, and how Magma should apply (often limited) AIs to make other AIs more desirable. more We clarify that the chance of collusion depends on whether AIs operate on a smaller scale, have very different architectures and orthogonal goals. We outline strategies to reduce collusion conditional on whether the AIs have indexical goals and follow causal decision theory or not. more We discuss how Magma can test the desirability of AIs via audits and threat assessments. Testing can provide evidence regarding the effectiveness of various alignment strategies and the overall level of misalignment. more We highlight potential disagreements with Karnofsky, including: We aren't convinced that a small chance of catching deceptive behavior by itself might make deception much less likely. We argue that in addition to having a small chance of catching deceptive behavior, the AI's supervisor needs to be capable enough to (a) distinguish between easy-to-catch and hard-to-catch deceptive behaviors and (b) attain a very low “false positive rate” of harshly penalizing non-deceptive behaviors. The AI may also need to be inner-aligned, i.e. intrinsically motivated by the reward. more We are more pessimistic than Karnofsky about the promise of adjudicating AI debates. We aren't convinced there's much theoretical reason to believe that AI debates robustly tend toward truth, and haven't been encouraged by empirical results. more We discuss the chance that Magma would succeed: We discuss the promise of "hacky" solutions to alignment. If applied alignment techniques that feel br...
Karnofsky, Evawww.deutschlandfunk.de, SonntagsspaziergangDirekter Link zur Audiodatei
Craig Jordan was one of the first researchers to analyze and describe tamoxifen's preventive properties. His discoveries changed the face of breast cancer prevention and treatment. His career is storied. He received the Karnofsky award for his work as the father of tamoxifen, is a member of the National Academies of Science, Engineering, and Medicine, met and corresponded with Princess Diana while he led the breast cancer program at the Robert H. Lurie Cancer Center, and served in the British military as captain of the Intelligence Service while undergoing his doctoral studies. Jordan's book “Tamoxifen Tales,” outlines the journey of discovery which led to the enormous contribution that antiestrogens, especially tamoxifen, have made to improve treatment as well as the prevention of breast cancer. A transcript of this conversation appears here.
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Responses to the Rival AI Deployment Problem: the importance of a pre-deployment agreement, published by HaydnBelfield on September 23, 2022 on The Effective Altruism Forum. Introduction: The rival AI deployment problem Imagine an actor is faced with highly convincing evidence that with high probability (over 75%) a rival actor will be capable within two years of deploying advanced AI. Assume that they are concerned that such deployment might threaten their values or interests. What could the first actor do? Let us call this the ‘rival AI deployment problem'. Three responses present themselves: acquiescence, an agreement before deployment, and the threat of coercive action. Acquiescence is inaction, and acceptance that the rival actor will deploy. It does not risk conflict, but does risk unilateral deployment, and therefore suboptimal safety precautions, misuse or value lock-in. An agreement before deployment (such as a treaty between states) would be an agreement on when and how advanced AI could be developed and deployed: for example, requirements on alignment and safety tests, and restrictions on uses/goals. We can think of this as a ‘Short Reflection' - a negotiation on what uses/goals major states can agree to give advanced AI. This avoids unilateral deployment and conflict, but it may be difficult for rival actors to agree, and any agreement faces the credible commitment problem of sufficiently reassuring the actors that the agreement is being followed. Threat of coercive action involves threatening the rival actor with setbacks (such as state sanctions or cyberattacks) to delay or deter the development program. It is unilaterally achievable, but risks unintended escalation and conflict. All three responses have positives and negatives. However, I will suggest a pre-deployment agreement may be the least-bad option. The rival AI deployment problem can be thought of as the flipside of (or an addendum to) what Karnofsky and Muehlhauser call the ‘AI deployment problem': “How do we hope an AI lab - or government - would handle various hypothetical situations in which they are nearing the development of transformative AI?”. Similarly, OpenAI made a commitment in its Charter to “stop competing with and start assisting” any project that “comes close to building” advanced AI for example with “a better-than-even chance of success in the next two years”. The Short Reflection can be thought of as an addendum to the Long Reflection, as suggested by MacAskill and Ord. Four assumptions I make four assumptions. First, I roughly assume a ‘classic' scenario of discontinuous deployment of a singular AGI system, of the type discussed in Life 3.0, Superintelligence and Yudkowsky's writings. Personally, more of a continuous Christiano-style take-off seems more plausible to me, and more of a distributed Drexler-style Comprehensive AI Services seems preferable to me. But the discontinuous, singular scenario makes the tensions sharper and clearer, so that is what I will use. Second, I roughly assume that states are the key players, as opposed to sustained academic or corporate control over an advanced AI development and/or deployment project. Personally, state control of this strategically important technology/project seems more plausible to me. In any case, state control again makes the tensions sharper and clearer. I distinguish between development and deployment. By ‘deployment' I mean something like ‘use in a way that affects the world' materially, economically, or politically. This includes both ‘starting a training run that will likely result in advanced AI' and ‘releasing some system from a closed-off environment or implementing its recommendations'. Third, I assume that some states may be concerned about deployment by a rival state. They might not necessarily be concerned. Almo...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Dan Luu: Futurist prediction methods and accuracy, published by Linch on September 15, 2022 on The Effective Altruism Forum. tl;dr: Dan Luu has a detailed post where he tracks in detail past predictions and argues that contra Karnofsky, Arb, etc, the track record of futurists is overall quite bad. Relevantly to this audience, he further argues that this is evidence against the validity of current longtermist efforts in long-range predictions. (I have not finished reading the post). I've been reading a lot of predictions from people who are looking to understand what problems humanity will face 10-50 years out (and sometimes longer) in order to work in areas that will be instrumental for the future and wondering how accurate these predictions of the future are. The timeframe of predictions that are so far out means that only a tiny fraction of people making those kinds of predictions today have a track record so, if we want to evaluate which predictions are plausible, we need to look at something other than track record. The idea behind the approach of this post was to look at predictions from an independently chosen set of predictors (Wikipedia's list of well-known futurists1) whose predictions are old enough to evaluate in order to understand which prediction techniques worked and which ones didn't work, allowing us to then (mostly in a future post) evaluate the plausibility of predictions that use similar methodologies. Unfortunately, every single predictor from the independently chosen set had a poor record and, on spot checking some predictions from other futurists, it appears that futurists often have a fairly poor track record of predictions so, in order to contrast techniques that worked with techniques that I didn't, I sourced predictors that have a decent track record from my memory, an non-independent source which introduces quite a few potential biases. Something that gives me more confidence than I'd otherwise have is that I avoided reading independent evaluations of prediction methodologies until after I did the evaluations for this post and wrote 98% of the post and, on reading other people's evaluations, I found that I generally agreed with Tetlock's "Superforecasting" on what worked and what didn't work despite using a wildly different data set. In particular, people who were into "big ideas" who use a few big hammers on every prediction combined with a cocktail party idea level of understanding of the particular subject to explain why a prediction about the subject would fall to the big hammer generally fared poorly, whether or not their favored big ideas were correct. Some examples of "big ideas" would be "environmental doomsday is coming and hyperconservation will pervade everything", "economic growth will create near-infinite wealth (soon)", "Moore's law is supremely important", "quantum mechanics is supremely important", etc. Another common trait of poor predictors is lack of anything resembling serious evaluation of past predictive errors, making improving their intuition or methods impossible (unless they do so in secret). Instead, poor predictors often pick a few predictions that were accurate or at least vaguely sounded similar to an accurate prediction and use those to sell their next generation of predictions to others. By contrast, people who had (relatively) accurate predictions had a deep understanding of the problem and also tended to have a record of learning lessons from past predictive errors. Due to the differences in the data sets between this post and Tetlock's work, the details are quite different here. The predictors that I found to be relatively accurate had deep domain knowledge and, implicitly, had access to a huge amount of information that they filtered effectively in order to make good predictions. Tetlock was studying peo...
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Dan Luu on Futurist Predictions, published by RobertM on September 14, 2022 on LessWrong. Epistemic status: perspective derived from following Dan Luu's output for the last 5 years or so. Trying to vaguely gesture at a few things at once. Please ask questions if you find something confusing. Dan Luu has written a interesting post analysing the track record of futurists' predictions. The motivation: I've been reading a lot of predictions from people who are looking to understand what problems humanity will face 10-50 years out (and sometimes longer) in order to work in areas that will be instrumental for the future and wondering how accurate these predictions of the future are. The timeframe of predictions that are so far out means that only a tiny fraction of people making those kinds of predictions today have a track record so, if we want to evaluate which predictions are plausible, we need to look at something other than track record. The idea behind the approach of this post was to look at predictions from an independently chosen set of predictors (Wikipedia's list of well-known futurists1) whose predictions are old enough to evaluate in order to understand which prediction techniques worked and which ones didn't work, allowing us to then (mostly in a future post) evaluate the plausibility of predictions that use similar methodologies. I'm primarily going to address the appendix, particularly the section on Holden Karnofsky's analysis on the same subject, but the article is interesting reading and I'd recommend going through the whole thing. (I think Dan is evaluating forecasting track records pretty differently from how I would, and I haven't actually dug into any of the other analysis. On priors I'd expect it to be similar to his analysis of Holden's work.) Karnofsky's evaluation of Kurzweil being "fine" to "mediocre" relies on these two analyses done on LessWrong and then uses a very generous interpretation of the results to conclude that Kurzweil's predictions are fine. Those two posts rate predictions as true, weakly true, cannot decide, weakly false, or false. Karnofsky then compares the number of true + weakly true to false + weakly false, which is one level of rounding up to get an optimistic result; another way to look at it is that any level other than "true" is false when read as written. This issue is magnified if you actually look at the data and methodology used in the LW analyses. The specific claim I have an issue with here is "another way to look at it is that any level other than "true" is false when read as written". Depending on how you want to evaluate it it, it's either technically true but irrelevant, or not even wrong. In the second post, the author, Stuart Armstrong indirectly noted that there were actually no predictions that were, by strong consensus, very true when he noted that the "most true" prediction had a mean score of 1.3 (1 = true, 2 = weakly true ... , 5 = false) and the second highest rated prediction had a mean score of 1.4. Although Armstrong doesn't note this in the post, if you look at the data, you'll see that the third "most true" prediction had a mean score of 1.45 and the fourth had a mean score of 1.6, i.e., if you round to the nearest prediction score, only 3 out of 105 predictions score "true" and 32 are >= 4.5 and score "false". Karnofsky reads Armstrong's as scoring 12% of predictions true, but the post effectively makes no comment on what fraction of predictions were scored true and the 12% came from summing up the total number of each rating given. I'm not going to say that taking the mean of each question is the only way one could aggregate the numbers (taking the median or modal values could also be argued for, as well as some more sophisticated scoring function, an extremizing function, etc.), but summing up ...
Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Dan Luu on Futurist Predictions, published by RobertM on September 14, 2022 on LessWrong. Epistemic status: perspective derived from following Dan Luu's output for the last 5 years or so. Trying to vaguely gesture at a few things at once. Please ask questions if you find something confusing. Dan Luu has written a interesting post analysing the track record of futurists' predictions. The motivation: I've been reading a lot of predictions from people who are looking to understand what problems humanity will face 10-50 years out (and sometimes longer) in order to work in areas that will be instrumental for the future and wondering how accurate these predictions of the future are. The timeframe of predictions that are so far out means that only a tiny fraction of people making those kinds of predictions today have a track record so, if we want to evaluate which predictions are plausible, we need to look at something other than track record. The idea behind the approach of this post was to look at predictions from an independently chosen set of predictors (Wikipedia's list of well-known futurists1) whose predictions are old enough to evaluate in order to understand which prediction techniques worked and which ones didn't work, allowing us to then (mostly in a future post) evaluate the plausibility of predictions that use similar methodologies. I'm primarily going to address the appendix, particularly the section on Holden Karnofsky's analysis on the same subject, but the article is interesting reading and I'd recommend going through the whole thing. (I think Dan is evaluating forecasting track records pretty differently from how I would, and I haven't actually dug into any of the other analysis. On priors I'd expect it to be similar to his analysis of Holden's work.) Karnofsky's evaluation of Kurzweil being "fine" to "mediocre" relies on these two analyses done on LessWrong and then uses a very generous interpretation of the results to conclude that Kurzweil's predictions are fine. Those two posts rate predictions as true, weakly true, cannot decide, weakly false, or false. Karnofsky then compares the number of true + weakly true to false + weakly false, which is one level of rounding up to get an optimistic result; another way to look at it is that any level other than "true" is false when read as written. This issue is magnified if you actually look at the data and methodology used in the LW analyses. The specific claim I have an issue with here is "another way to look at it is that any level other than "true" is false when read as written". Depending on how you want to evaluate it it, it's either technically true but irrelevant, or not even wrong. In the second post, the author, Stuart Armstrong indirectly noted that there were actually no predictions that were, by strong consensus, very true when he noted that the "most true" prediction had a mean score of 1.3 (1 = true, 2 = weakly true ... , 5 = false) and the second highest rated prediction had a mean score of 1.4. Although Armstrong doesn't note this in the post, if you look at the data, you'll see that the third "most true" prediction had a mean score of 1.45 and the fourth had a mean score of 1.6, i.e., if you round to the nearest prediction score, only 3 out of 105 predictions score "true" and 32 are >= 4.5 and score "false". Karnofsky reads Armstrong's as scoring 12% of predictions true, but the post effectively makes no comment on what fraction of predictions were scored true and the 12% came from summing up the total number of each rating given. I'm not going to say that taking the mean of each question is the only way one could aggregate the numbers (taking the median or modal values could also be argued for, as well as some more sophisticated scoring function, an extremizing function, etc.), but summing up ...
Link to original articleWelcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Dan Luu on Futurist Predictions, published by RobertM on September 14, 2022 on LessWrong. Epistemic status: perspective derived from following Dan Luu's output for the last 5 years or so. Trying to vaguely gesture at a few things at once. Please ask questions if you find something confusing. Dan Luu has written a interesting post analysing the track record of futurists' predictions. The motivation: I've been reading a lot of predictions from people who are looking to understand what problems humanity will face 10-50 years out (and sometimes longer) in order to work in areas that will be instrumental for the future and wondering how accurate these predictions of the future are. The timeframe of predictions that are so far out means that only a tiny fraction of people making those kinds of predictions today have a track record so, if we want to evaluate which predictions are plausible, we need to look at something other than track record. The idea behind the approach of this post was to look at predictions from an independently chosen set of predictors (Wikipedia's list of well-known futurists1) whose predictions are old enough to evaluate in order to understand which prediction techniques worked and which ones didn't work, allowing us to then (mostly in a future post) evaluate the plausibility of predictions that use similar methodologies. I'm primarily going to address the appendix, particularly the section on Holden Karnofsky's analysis on the same subject, but the article is interesting reading and I'd recommend going through the whole thing. (I think Dan is evaluating forecasting track records pretty differently from how I would, and I haven't actually dug into any of the other analysis. On priors I'd expect it to be similar to his analysis of Holden's work.) Karnofsky's evaluation of Kurzweil being "fine" to "mediocre" relies on these two analyses done on LessWrong and then uses a very generous interpretation of the results to conclude that Kurzweil's predictions are fine. Those two posts rate predictions as true, weakly true, cannot decide, weakly false, or false. Karnofsky then compares the number of true + weakly true to false + weakly false, which is one level of rounding up to get an optimistic result; another way to look at it is that any level other than "true" is false when read as written. This issue is magnified if you actually look at the data and methodology used in the LW analyses. The specific claim I have an issue with here is "another way to look at it is that any level other than "true" is false when read as written". Depending on how you want to evaluate it it, it's either technically true but irrelevant, or not even wrong. In the second post, the author, Stuart Armstrong indirectly noted that there were actually no predictions that were, by strong consensus, very true when he noted that the "most true" prediction had a mean score of 1.3 (1 = true, 2 = weakly true ... , 5 = false) and the second highest rated prediction had a mean score of 1.4. Although Armstrong doesn't note this in the post, if you look at the data, you'll see that the third "most true" prediction had a mean score of 1.45 and the fourth had a mean score of 1.6, i.e., if you round to the nearest prediction score, only 3 out of 105 predictions score "true" and 32 are >= 4.5 and score "false". Karnofsky reads Armstrong's as scoring 12% of predictions true, but the post effectively makes no comment on what fraction of predictions were scored true and the 12% came from summing up the total number of each rating given. I'm not going to say that taking the mean of each question is the only way one could aggregate the numbers (taking the median or modal values could also be argued for, as well as some more sophisticated scoring function, an extremizing function, etc.), but summing up ...
Karnofsky, Evawww.deutschlandfunk.de, Tag für TagDirekter Link zur Audiodatei
Karnofsky, Evawww.deutschlandfunk.de, Campus & KarriereDirekter Link zur Audiodatei
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Introduction to the sequence: Interpretability Research for the Most Important Century, published by Evan R. Murphy on May 12, 2022 on The AI Alignment Forum. This is the first post in a sequence exploring the argument that interpretability is a high-leverage research activity for solving the AI alignment problem. This post contains important background context for the rest of the sequence. I'll give an overview of one of Holden Karnofksy's (2022) "Important, actionable research questions for the most important century" which is the central question we'll be engaging with in this sequence. I'll also define some terms and compare this sequence to existing works. If you're already very familiar with Karnofsky (2022) and interpretability, then you can probably skip to the second post in this sequence: Interpretability's Alignment-Solving Potential: Analysis of 7 Scenarios The Alignment Research Activities Question This sequence is being written as a direct response to the following question from Karnofsky (2022): “What relatively well-scoped research activities are particularly likely to be useful for longtermism-oriented AI alignment?” (full question details) I'll refer to this throughout the sequence as the Alignment Research Activities Question. Context on the question and why it matters In the details linked above for the Alignment Research Activities Question, Holden first discusses two categories of alignment research which are lacking in one way or another. He then presents a third category with some particularly desirable properties: “Activity that is [1] likely to be relevant for the hardest and most important parts of the problem, while also being [2] the sort of thing that researchers can get up to speed on and contribute to relatively straightforwardly (without having to take on an unusual worldview, match other researchers' unarticulated intuitions to too great a degree, etc.)” He refers to this as "category (3)", but I'll use the term High-leverage Alignment Research since it's more descriptive and we'll be referring back to this concept often throughout the sequence. We want to know more about which alignment research is in this category. Why? Further excerpts from Karnofsky (2022) to clarify: “I think anything we can clearly identify as category (3) [that is, High-leverage Alignment Research] is immensely valuable, because it unlocks the potential to pour money and talent toward a relatively straightforward (but valuable) goal.[...]I think there are a lot of people who want to work on valuable-by-longtermist-lights AI alignment research, and have the skills to contribute to a relatively well-scoped research agenda, but don't have much sense of how to distinguish category (3) from the others. There's also a lot of demand from funders to support AI alignment research. If there were some well-scoped and highly relevant line of research, appropriate for academia, we could create fellowships, conferences, grant programs, prizes and more to help it become one of the better-funded and more prestigious areas to work in. I also believe the major AI labs would love to have more well-scoped research they can hire people to do." I won't be thoroughly examining other research directions besides interpretability, except in cases where a hypothetical interpretability breakthrough is impacting another research direction toward a potential solution to the alignment problem. So I don't expect this sequence to produce a complete comparative answer to the Alignment Research Activities Question. But by investigating whether interpretability research is High-leverage Alignment Research, I hope to put together a fairly comprehensive analysis of interpretability research that could be useful to people considering investing their money or time into it. I also hope that someone t...
Karnofsky, Evawww.deutschlandfunk.de, Umwelt und VerbraucherDirekter Link zur Audiodatei
Se descubrió que la Ozonoterapia aporta con un incremento de la calidad de vida en pacientes con Sarcoma de Karnofsky (cáncer de piel, ganglios y vasos sanguíneos), cuando son tratados con ozono. Hoy lo conversamos con el Dr. Peeter Jaramillo, Especialista en Ozonoterapia.
Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: [linkpost] Peter Singer: The Hinge of History, published by michaelchen on January 16, 2022 on The Effective Altruism Forum. This is a crosspost of Peter Singer's "The Hinge of History", published in Project Syndicate on October 8, 2021. The dangers of treating extinction risk as humanity's overriding concern should be obvious. Viewing current problems through the lens of existential risk to our species can shrink those problems to almost nothing, while justifying almost anything that increases our odds of surviving long enough to spread beyond Earth. PRINCETON – Twelve years ago, during the International Year of Astronomy that marked the 400th anniversary of Galileo's first use of a telescope, I wrote “The Value of a Pale Blue Dot” – a reflection on how astronomy has revealed a vast universe filled with an unimaginable number of stars, thus shrinking the significance of our sun and our planet. The “pale blue dot” refers to how the Earth appears in a 1990 photograph taken by the Voyager spacecraft as it reached the outer limits of our solar system. The essay suggests that the knowledge gained from astronomy “forces us to acknowledge that our place in the universe is not particularly significant.” A recent blog post by Holden Karnofsky has led me to reconsider that thought. Karnofsky is co-CEO of Open Philanthropy, a foundation that researches the best opportunities for philanthropic grant-making, and publishes the reasons for its decisions. Thinking about the long-term significance of today's philanthropic decisions is therefore part of Karnofsky's role. He is thinking very long term indeed. Karnofsky points out that we could be living “at the very beginning of the tiny sliver of time during which the galaxy goes from nearly lifeless to largely populated.” That “tiny sliver of time” began, we might say, with the first use of tools by our ancestors, around three million years ago. It will end when our descendants – who might be digital minds, rather than biological organisms – inhabit the entire galaxy, perhaps ushering in a civilization consisting of an enormous number of conscious beings that would last for tens of billions of years. There is a good chance, Karnofsky argues, that this process of populating the galaxy will begin during this century. By 2100, we could develop the technology to construct self-sufficient settlements on other planets. This thought echoes one expressed in 2011 by the late philosopher Derek Parfit, who wrote, near the end of the second volume of On What Matters: “We live during the hinge of history.” Like Karnofsky, Parfit was thinking of the arrival of technologies that, if used wisely, would enable our species to survive “its most dangerous and decisive period,” and our descendants to spread through our galaxy. Parfit refers to “the next few centuries,” rather than just this one, as the time it may take before humans can live independently on other planets, but even that will be only be a sliver of time compared to what is to come. Our most significant contribution to this development would be to ensure the survival of intelligent life on our planet. Perhaps, though, the idea that we are essential to this process is merely the latest version of the self-important delusion that humans are the center of existence. Surely, in this vast universe, there must be other forms of intelligent life, and if we don't populate the Milky Way galaxy, someone else will. Yet, as the physicist Enrico Fermi once asked fellow scientists over lunch at Los Alamos National Laboratory, “Where is everybody?” He wasn't commenting on empty tables in the lab's dining room, but on the absence of any evidence of the existence of extraterrestrials. The thought behind that question is now known as the Fermi Paradox: if the universe is so stupendous, and has existed for ...
welcome to the nonlinear library, where we use text-to-speech software to convert the best writing from the rationalist and ea communities into audio. this is: List of ways in which cost-effectiveness estimates can be misleading, published by saulius on the effective altruism forum. In my cost-effectiveness estimate of corporate campaigns, I wrote a list of all the ways in which my estimate could be misleading. I thought it could be useful to have a more broadly-applicable version of that list for cost-effectiveness estimates in general. It could maybe be used as a checklist to see if no important considerations were missed when cost-effectiveness estimates are made or interpreted. The list below is probably very incomplete. If you know of more items that should be added, please comment. I tried to optimize the list for skimming. How cost estimates can be misleading Costs of work of others. Suppose a charity purchases a vaccine. This causes the government to spend money distributing that vaccine. It's unclear whether the costs of the government should be taken into account. Similarly, it can be unclear whether to take into account the costs that patients have to spend to travel to a hospital to get vaccinated. This is closely related to concepts of leverage and perspective. More on it can be read in Byford and Raftery (1998), Karnofsky (2011), Snowden (2018), and Sethu (2018). It can be unclear whether to take into account the fixed costs from the past that will not have to be spent again. E.g., costs associated with setting up a charity that are already spent and are not directly relevant when considering whether to fund that charity going forward. However, such costs can be relevant when considering whether to found a similar charity in another country. Some guidelines suggest annualizing fixed costs. When fixed costs are taken into account, it's often unclear how far to go. E.g., when estimating the cost of distributing a vaccine, even the costs of roads that were built partly to make the distribution easier could be taken into account. Not taking future costs into account. E.g., an estimate of corporate campaigns may take into account the costs of winning corporate commitments, but not future costs of ensuring that corporations will comply with these commitments. Future costs and effects may have to be adjusted for the possibility that they don't occur. Not taking past costs into account. In the first year, a homelessness charity builds many houses. In the second year, it finds homeless people to live in those houses. In the first year, the impact of the charity could be calculated as zero. In the second year, it could be calculated to be unreasonably high. But the charity wouldn't be able to sustain the cost-effectiveness of the second year. Not adjusting past or future costs for inflation. Not taking overhead costs into account. These are costs associated with activities that support the work of a charity. It can include operational, office rental, utilities, travel, insurance, accounting, administrative, training, hiring, planning, managerial, and fundraising costs. Not taking costs that don't pay off into account. Nothing But Nets is a charity that distributes bednets that prevent mosquito-bites and consequently malaria. One of their old blog posts, Sauber (2008), used to claim that "If you give $100 of your check to Nothing But Nets, you've saved 10 lives." While it may be true that it costs around $10 or less[1] to provide a bednet, and some bednets save lives, costs of bednets that did not save lives should be taken into account as well. According to GiveWell's estimates, it currently costs roughly $3,500 for a similar charity (Against Malaria Foundation) to save one life by distributing bednets. Wiblin (2017) describes a survey in which respondents were asked "How much do you think it would cost a typical charity working in this area on average to prevent one child in a poor country from dying unnecessarily, by ...
Brustschmerz, Husten und eine Schwellung am Hals treiben den 48-Jährigen in die Klinik - ein halbes Jahr später ist er tot. Warum brachte ihm ausgerechnet ein Kampfgas kurzzeitig Linderung und wie würde man ihn heute behandeln? Wir reisen zurück ins Jahr 1947 und erzählen die Geschichte eines Falles von David. A. Karnofsky und seinen ersten Behandlungsversuchen beim kleinzelligen Lungenkarzinom (SCLC). Im Experten-Interview ordnet Prof. Dr. Wolfgang Schütte (Martha-Maria Halle-Dölau) die Entwicklung beim SCLC von damals bis heute ein und wirft mit uns einen Blick in die Zukunft der Therapie.(00:00) Intro(00:27) Einführung & Interview mit Herrn Prof. Schütte(01:28) Damals Haferzellkarzinom, heute Kleinzeller(01:51) Bestrahlung, Operation, Chemotherapie - seit den 90ern kaum Fortschritte(03:24) “Richtig großer Fortschritt” - die Immuntherapien beim SCLC(05:24) Der Fall des “J.M.”: mit Kampfgas gegen den Krebs(08:10) Karnofsky: “Remission enttäuschend kurz”(09:25) Die Therapie des Kleinzellers: endlich Fortschritte(11:25) OutroMelden Sie sich für E-Mail-Benachrichtigungen an, um keine neue Folge zu verpassen. Klicken Sie hier und gelangen Sie zum Roche-Podcast-Portal. Das Fachportal von Roche finden Sie hier.
Podcast: The Ezra Klein Show Episode: How to Do the Most GoodRelease date: 2021-10-05Do we actually know how much good our charitable donations do?This is the question that jump-started Holden Karnofsky's current career. He was working at a hedge fund and wanted to figure out how to give his money away with the certainty that it would save as many lives as possible. But he couldn't find a service that would help him do that, so he and his co-worker Elie Hassenfeld decided to quit their jobs to build one. The result was GiveWell, a nonprofit that measures the effectiveness of different charities and recommends the ones it is most confident can save lives with the least cost. Things like providing bed nets to prevent malaria and treatments to deworm schoolchildren in low-income countries.But in recent years, Karnofsky has taken a different approach. He is currently the co-C.E.O. of Open Philanthropy, which operates under the same basic principle — how can we do the most good possible? — but with a very different theory of how to do so. Open Phil's areas of funding range from farm animal welfare campaigns and criminal justice reform to pandemic preparedness and A.I. safety. And Karnofsky has recently written a series of blog posts centered around the idea that, ethically speaking, we're living through the most important century in human history: The decisions we make in the coming decades about transformational technologies will determine the fate of trillions of future humans.In all of this, Karnofsky represents the twin poles of a movement that's come to deeply influence my thinking: effective altruism. The hallmark of that approach is following fundamental questions about how to do good through to their conclusions, no matter how simple or fantastical the answers. And so this is a conversation, at a meta-level, about how to think like an effective altruist. Along the way, we discuss everything from climate change to animal welfare to evaluating charities to artificial intelligence to the hard limits of economic growth to trying to view the world as if you were a billion years old.You probably won't agree with every prediction in here, but that is, in a way, the point: We live in a weird world that's only getting weirder, and we need to be able to entertain both the obvious and the outlandish implications. What Karnofksy's career reveals is how hard that is to actually do.Mentioned:The "Most Important Century" Blog Post Series on Holden Karnofsky's blog, Cold TakesGiveWellMore on Open Philanthropy's approach to worldview diversification“What Charity Navigator Gets Wrong About Effective Altruism” by William MacAskill“The Past and Future of Economic Growth: A Semi-Endogenous Perspective” by Charles I. JonesBook recommendations:Due Diligence by David RoodmanThe Lifeways of Hunter-Gatherers by Robert L. KellyThe Precipice by Toby OrdYou can find transcripts (posted midday) and more episodes of "The Ezra Klein Show" at nytimes.com/ezra-klein-podcast, and you can find Ezra on Twitter @ezraklein. Book recommendations from our guests are listed at https://www.nytimes.com/article/ezra-klein-show-book-recs.Thoughts? Guest suggestions? Email us at ezrakleinshow@nytimes.com.“The Ezra Klein Show” is produced by Annie Galvin, Jeff Geld and Rogé Karma; fact-checking by Michelle Harris; original music by Isaac Jones; mixing by Jeff Geld, audience strategy by Shannon Busta. Special thanks to Kristin Lin.
Podcast: The Ezra Klein Show (LS 70 · TOP 0.05% )Episode: How to Do the Most GoodRelease date: 2021-10-05Do we actually know how much good our charitable donations do?This is the question that jump-started Holden Karnofsky's current career. He was working at a hedge fund and wanted to figure out how to give his money away with the certainty that it would save as many lives as possible. But he couldn't find a service that would help him do that, so he and his co-worker Elie Hassenfeld decided to quit their jobs to build one. The result was GiveWell, a nonprofit that measures the effectiveness of different charities and recommends the ones it is most confident can save lives with the least cost. Things like providing bed nets to prevent malaria and treatments to deworm schoolchildren in low-income countries.But in recent years, Karnofsky has taken a different approach. He is currently the co-C.E.O. of Open Philanthropy, which operates under the same basic principle — how can we do the most good possible? — but with a very different theory of how to do so. Open Phil's areas of funding range from farm animal welfare campaigns and criminal justice reform to pandemic preparedness and A.I. safety. And Karnofsky has recently written a series of blog posts centered around the idea that, ethically speaking, we're living through the most important century in human history: The decisions we make in the coming decades about transformational technologies will determine the fate of trillions of future humans.In all of this, Karnofsky represents the twin poles of a movement that's come to deeply influence my thinking: effective altruism. The hallmark of that approach is following fundamental questions about how to do good through to their conclusions, no matter how simple or fantastical the answers. And so this is a conversation, at a meta-level, about how to think like an effective altruist. Along the way, we discuss everything from climate change to animal welfare to evaluating charities to artificial intelligence to the hard limits of economic growth to trying to view the world as if you were a billion years old.You probably won't agree with every prediction in here, but that is, in a way, the point: We live in a weird world that's only getting weirder, and we need to be able to entertain both the obvious and the outlandish implications. What Karnofksy's career reveals is how hard that is to actually do.Mentioned:The "Most Important Century" Blog Post Series on Holden Karnofsky's blog, Cold TakesGiveWellMore on Open Philanthropy's approach to worldview diversification“What Charity Navigator Gets Wrong About Effective Altruism” by William MacAskill“The Past and Future of Economic Growth: A Semi-Endogenous Perspective” by Charles I. JonesBook recommendations:Due Diligence by David RoodmanThe Lifeways of Hunter-Gatherers by Robert L. KellyThe Precipice by Toby OrdYou can find transcripts (posted midday) and more episodes of "The Ezra Klein Show" at nytimes.com/ezra-klein-podcast, and you can find Ezra on Twitter @ezraklein. Book recommendations from our guests are listed at https://www.nytimes.com/article/ezra-klein-show-book-recs.Thoughts? Guest suggestions? Email us at ezrakleinshow@nytimes.com.“The Ezra Klein Show” is produced by Annie Galvin, Jeff Geld and Rogé Karma; fact-checking by Michelle Harris; original music by Isaac Jones; mixing by Jeff Geld, audience strategy by Shannon Busta. Special thanks to Kristin Lin.
Do we actually know how much good our charitable donations do?This is the question that jump-started Holden Karnofsky's current career. He was working at a hedge fund and wanted to figure out how to give his money away with the certainty that it would save as many lives as possible. But he couldn't find a service that would help him do that, so he and his co-worker Elie Hassenfeld decided to quit their jobs to build one. The result was GiveWell, a nonprofit that measures the effectiveness of different charities and recommends the ones it is most confident can save lives with the least cost. Things like providing bed nets to prevent malaria and treatments to deworm schoolchildren in low-income countries.But in recent years, Karnofsky has taken a different approach. He is currently the co-C.E.O. of Open Philanthropy, which operates under the same basic principle — how can we do the most good possible? — but with a very different theory of how to do so. Open Phil's areas of funding range from farm animal welfare campaigns and criminal justice reform to pandemic preparedness and A.I. safety. And Karnofsky has recently written a series of blog posts centered around the idea that, ethically speaking, we're living through the most important century in human history: The decisions we make in the coming decades about transformational technologies will determine the fate of trillions of future humans.In all of this, Karnofsky represents the twin poles of a movement that's come to deeply influence my thinking: effective altruism. The hallmark of that approach is following fundamental questions about how to do good through to their conclusions, no matter how simple or fantastical the answers. And so this is a conversation, at a meta-level, about how to think like an effective altruist. Along the way, we discuss everything from climate change to animal welfare to evaluating charities to artificial intelligence to the hard limits of economic growth to trying to view the world as if you were a billion years old.You probably won't agree with every prediction in here, but that is, in a way, the point: We live in a weird world that's only getting weirder, and we need to be able to entertain both the obvious and the outlandish implications. What Karnofksy's career reveals is how hard that is to actually do.Mentioned:The "Most Important Century" Blog Post Series on Holden Karnofsky's blog, Cold TakesGiveWellMore on Open Philanthropy's approach to worldview diversification“What Charity Navigator Gets Wrong About Effective Altruism” by William MacAskill“The Past and Future of Economic Growth: A Semi-Endogenous Perspective” by Charles I. JonesBook recommendations:Due Diligence by David RoodmanThe Lifeways of Hunter-Gatherers by Robert L. KellyThe Precipice by Toby OrdYou can find transcripts (posted midday) and more episodes of "The Ezra Klein Show" at nytimes.com/ezra-klein-podcast, and you can find Ezra on Twitter @ezraklein. Book recommendations from our guests are listed at https://www.nytimes.com/article/ezra-klein-show-book-recs.Thoughts? Guest suggestions? Email us at ezrakleinshow@nytimes.com.“The Ezra Klein Show” is produced by Annie Galvin, Jeff Geld and Rogé Karma; fact-checking by Michelle Harris; original music by Isaac Jones; mixing by Jeff Geld, audience strategy by Shannon Busta. Special thanks to Kristin Lin.
En este podcast, el Dr. Homero Fuentes de la Peña, oncólogo médico, presidente de PROONCAVI A.C. en Tijuana, Baja California, México, nos comenta algunos highlights del día 2 de ASCO 2021: Cáncer de pulmón de celulas no pequeñas: Resultados del análisis de eventos adversos relacionados con el sistema inmunológico (irAEs, por sus siglas en inglés) agrupados, así como la eficacia de los estudios fase III: IMpower130, IMpower132 e IMpower150 con atezolizumab en pacientes con cáncer de pulmón de células no pequeñas. Carcinoma de células renales avanzado: Resultados de un análisis exploratorio post-hoc que demuestra los beneficios de eficacia observados del estudio fase III, CheckMate-9ER con cabozantinib + nivolumab vs. sunitinib como tratamiento de 1L para el carcinoma de células renales avanzado o metastásico sin tratamiento previo. Resultados del estudio fase IIIb/IV CheckMate 920, de múltiples brazos, de etiqueta abierta, que inscribió a pacientes con carcinoma de células renales (CCR) avanzado, el cual evaluó la seguridad y eficacia de nivolumab + ipilimumab. La aplicación del tratamiento ha demostrado eficacia y tolerabilidad a largo plazo para pacientes con CCR avanzado no tratado previamente y bajo estado funcional de Karnofsky. Resultados del estudio KEYNOTE-426, que evaluó pembrolizumab + axitinib, el cual mejoró significativamente la supervivencia global, la supervivencia libre de progresión, y la tasa de respuesta objetiva vs. sunitinib en 1L para pacientes con carcinoma de células renales avanzado. Cáncer colorrectal: Análisis de la detección de la enfermedad mínima residual de un estudio prospectivo multicéntrico de Reino Unido, con pacientes diagnosticados con cáncer colorrectal, que fueron monitoreados antes y después de la cirugía antes de la quimioterapia adyuvante. Linfoma no Hodgkin: Estudio comparativo de linfoma no Hodgkin entre una institución pública y una privada en un país de ingresos medios en el cual se incluyeron un total de 2,137 pacientes pertenecientes a ambas instituciones. Burnout Is Cancer presentado por la Dra. Shayma Master Kazmi, MD, RPh: Este análisis habla sobre el síndrome del burnout (agotamiento) en el cáncer, mismo que fue descrito por primera vez por el psicólogo Herbert Freudenberger en la década de 1970. Según él, el agotamiento es una condición que ocurre cuando el trabajo, junto con las presiones adicionales de la vida, excede la capacidad de afrontamiento, lo que resulta en angustia física y mental. Ha habido una investigación considerable en este campo que se aplica a los médicos; sin embargo, la educación y la conciencia sobre el agotamiento solo se ha ampliado recientemente.
Dr. Hayes interviews Dr. Norton. TRANSCRIPT SPEAKER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] DANIEL F. HAYES: Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insights into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. [MUSIC PLAYING] Dr. Norton has stock and other ownership interest in Samus Therapeutics, Codagenix Inc, Martell Diagnostic, and Medaptive Health Inc. He's received honoraria from Context Therapeutics, Prime Oncology, the Sarah Lawrence Lecture, Context Advisory Board, Oncology Pioneer Science Lecture Series, Sermonix Pharmaceuticals, the Cold Spring Harbor advisory board, Codagenix, Agenus, and the Cold Spring Harbor external advisory board. He has served as a consultant or provided advice to Context Therapeutics, Prime Oncology, the Context Advisory Board, Oncology Pioneer Science Lecture, Martell Diagnostic, Sermonix, Codagenix, Agenus, Medaptive Health, and the Cold Springs Harbor Laboratories. He has received expense reimbursement for travel and accommodations from the Oncology Pioneer Science Lecture Series, the BCRP Programmatic Review Meeting, the Breast Cancer Research Foundation, the American Association of Cancer Research, and Cold Spring Harbor Laboratory. [MUSIC PLAYING] Today my guest on the podcast is Dr. Larry Norton. Dr. Norton has been instrumental in so many facets of oncology it's hard to go through, but particularly, in breast cancer, and especially related to applying mathematical models of cancer kinetics that he developed with Richard Simon at the National Cancer Institute, and applying them really, to dose density strategies for chemotherapy and breast cancer, which we'll discuss. Dr. Norton was raised in suburban New York. He received his undergraduate degree at Rochester University, his medical degree at the Columbia University College of Physicians and Scientists. And then he did his residency at Einstein Associated Hospitals in the Bronx. He then went on to complete a medical oncology fellowship at the National Cancer Institute from 1974 to 1976 and stayed there an extra year. And then he returned to New York and joined the faculty at Mount Sinai in 1977, where he stayed for about a decade. He then moved to Memorial Sloan Kettering, where I think most of us think he was born and raised and lived his whole life. He's held many positions there. And particularly, he was responsible for really building the breast medical oncology service and starting the Evelyn Lauder Breast Center. He now sits in the Norman S Seraphim-- did I pronounce that correctly, Dr. Norton? LARRY NORTON: Yes, you did. DANIEL F. HAYES: Chair in Clinical Oncology, he's authored over 450 peer reviewed papers. He's won too many awards for me to list, as have most of my guests on this program. But in particular, he's won the triple crown, in my opinion. And that's the Karnofsky, the McGuire, and the Bonnadonna awards. At least those of us in breast cancer would strive to win all three of those. And importantly to this series, he served as president of ASCO from 2001 to 2002, has served many roles at ASCO and has had a major footprint in where ASCO is today. Dr. Norton, welcome to our program. LARRY NORTON: Great pleasure to be here. Thank you, Dan. DANIEL F. HAYES: So we'll start with some of the origin stories. I know you weren't bit by a radioactive spider and got spidey powers. But I've known you for a long time. And I know, really, your first love was music and that you started out to be a professional musician. Can you give us some background? What were your instruments? I know you went to Rochester specifically to be in music. And feel more than free to do some name dropping, because I think some of the people in music are people we'd all recognize. LARRY NORTON: Well, I don't know whether that would be totally right. I've known a lot of people in music. My first love was music. I grew up in Long Island, was able to commute in with one bus and one subway to Greenwich Village in the '60s, which was, really, the hotbed of much of what was going on in music to this day. I didn't even realize it was a golden age. I remember all the giants, Bob Dylan, when he was a very young kid in town, in small coffee houses. But it was also in close proximity where a lot of the jazz scene was happening, and just to take the A Train would be very easy to get up into Harlem, where there's a lot of jazz things going on. Like a lot of kids growing up on Long Island, I had some musical education. I started off with the clarinet, went quickly into saxophone in terms of music. But I played a whole variety of instruments. Like everybody else, I play guitar. I played percussion. I played bongos behind beat poets and was very excited to be really part of that scene. I think one of the major turning points for me, actually, was the Vietnam War. Because like a lot of people of my generation, it did not seem to be reasonable war. And even McNamara wrote a book later saying, yep, sorry, it was a mistake. We were looking for things that could interest us and also help us serve our country in ways other than sacrificing our lives in Vietnam. That's how medicine got into my life. It seemed to be the right compromise. Fortunately, starting off in Rochester which had the Eastman School of Music, which was a great influence on me, and a fantastic school, and has evolved continuously to be an even better school now. It has a very active jazz program now, which didn't exist at that time. We had to do jazz on the sly, which was very easy to do, because there are a lot of jazz clubs in Rochester at that time. And it was really very easy to play jazz all night and then to play classical music all day. And that was totally, totally a great experience. We were young. We didn't have to sleep at all. But I hankered to get back into New York. When the opportunity arose to go to medical school, I was fortunately chosen to go to Columbia, where I actually was able to play music and at the same time go to the medical school. But after a while, as all of us in medicine know, it becomes all consuming. And so the medicine part of it just slipped. When it came to a lot of my friends from the old days up until the present day, very little performing, I've done a couple of benefits. I'll do the one namedrop with Elton John, because he's been so terrific at raising money for breast cancer research through the Breast Cancer Research Foundation. I had the great honor of being able to play with him twice-- DANIEL F. HAYES: How did you meet Elton John? I mean, it's not like you walk down the street and say, oh, hi, I'm Dan Hayes. LARRY NORTON: Mutual friends, mutual friends in the arts, basically, one of our closest friends, close friend of his, close friend of mine, someone named Ingrid Sischy was a fantastic writer and editor, very involved with Andy Warhol in the beginning, and then continued a career in art criticism and art writing. And she was a friend of everybody and a close friend of Elton's and a close friend of mine. And so I think she made the original introduction. And he's really been terrific. But the music is put aside, although I do play every day. I still keep that as a very important part of my zen escape from other stresses of life. Although, music itself has its own stresses. The good thing about jazz is improvisation. So it's an immediate feeling, no such thing as a wrong note. You hit a wrong note, and you play around it. And it becomes a right note. And so music is still a very important part of my life. DANIEL F. HAYES: That's terrific. Actually, I interviewed Hyman Muss a few weeks ago. And he and some others have introduced me to tying flies for fly fishing. And it's sort of the same thing. I can take 15 minutes and tie a fly. I'm not sure it looks like anything official-like. But it's not medicine for a while, and that's good. LARRY NORTON: Yeah, but medicine-- DANIEL F. HAYES: The other thing-- LARRY NORTON: I want to get back to this for a second, because I mean, DANIEL F. HAYES: Yeah. LARRY NORTON: It's not a separate thing. I mean, music and-- especially my early music education just taught me a lot that's really helped me in my career in medicine. I think it's very important for people to know. The talent for music is a talent to practice. Essentially, anybody who can speak can-- has enough control of tones that they can actually do something with music. I'm not sure how much is really inborn ability. I'm not sure there is such a thing as a talent in that regard. But some people can practice for long hours successfully. And some people can't. And I think that that's something that may be inborn. I don't know. I'll leave that to the developmental psychologists. But that is a very important trait, obviously, in medicine. You have to spend a long time studying. You have to learn a lot. You have to concentrate a lot. You have to be able to concentrate on individual patients, when you're taking care of them. And that's been very important, but it's also empathy. Music teaches you to feel what other people are feeling. You're not going to be a good musician unless you know how you're affecting your audience in a profound way. And you can sense when you're losing your audience, and you can change the direction you're going in. And when you hit something right, you can play it. And that ability to feel what other people are feeling, I think, is really essential to be a good clinician. And music teaches you that. I think arts in general teach you that. DANIEL F. HAYES: Actually, I hadn't thought about it. Do you think that your music and your mathematic leanings are tied together too? LARRY NORTON: There is a tendency for mathematicians to be musicians, not true quite vice versa. Although they are-- good musicians really are mathematicians. But they don't know it. A lot of people think math is the written equation, and it's not. It's a certain approach toward nature. Thinking in spatial ways, for me, thinking of shapes, and the way shapes form, the way shapes move over time and space, then you learn the tools for being able to write it down which is the actual mathematical notation. DANIEL F. HAYES: Yeah. LARRY NORTON: And the same thing with music, I mean, music isn't the notes on the page. I mean, that's a very poor reflection of what sounds you're making. It's the sounds. It's the sounds, and they go up and then down. That's spatial, and they go forward in time. And so they're temporal, and they have meaning. It's not just random sounds. They have meaning. They connect to each other, and they tell a story, as we say in the jazz world. And the notes are a poor reflection of that. Some of the best musicians I know can't read music. And as a matter of fact, it used to be said that if you want to be good jazz musician, you shouldn't learn to read. Because if you learn to read, you'll cheat. And you should be able to play by ear. And that's what's going to make you a better musician. So I think math and music are very closely aligned. You have a problem to solve, when you think about it, and in novel ways that are not verbal. And the non-verbal way of thinking in music and in math are very similar, I think. DANIEL F. HAYES: So let me segue onto how you changed paths. I know that it was-- I've heard you talk about it was a discussion with Dr. Ron Bloom, who I think has remained a good friend of yours, and then in association with Dr. Regelson at Roswell Park. Can you tell us about that? LARRY NORTON: Well, Ron got me-- I mean, Ron, great, great oncologist, retired now, and his wife Diane also very, very important in the cancer world through her leadership of organizations. They both went to University of Rochester same time I did. I was actually perplexed at the end of one semester. So both Ron and Diane were at the University of Rochester, the same I was. And I was perplexed at the end of one semester, because I had several opportunities to do things in the summer coming forward. One of which was very music oriented, and it was a very exciting possibility. But I was at that time considering a change in direction very strongly. Math was one of the things that was drawing me. The question, should I become a professional statistician? That was the course that was turning me on mostly at that time. I thought physics was an incredible art form and was intrigued to that. But I also had music that was drawing me. And also the question, of what could keep me helping people, and helping my nation, and keep me from necessarily bearing arms in Vietnam was a big concern. And I met Ron on the stairs of the Rush Rhees Library at the University of Rochester, a famous library, that by the way, has a famous ghost associated with it. That's a whole different story. He said that he had this unbelievably wonderful experience the previous summer by working at Roswell Park Memorial Institute in Buffalo, New York State Cancer Research Institute, particularly under a guy named William Regelson who was just totally inspirational to him. And that was one of his major motivations to spend his career in cancer medicine, which I didn't even know it. I had another connection to Bill Regelson is that my father and his father actually knew each other. Because they were in businesses that touched. His father ran a Catskills resort. And my father was a professional writer and travel editor at The New York Post. And so that there was that connection. So that when I relayed the story to my parents, they said, oh, we know Regelson. So well, one thing led to another. And on a cold and rainy night, I took a bus into Buffalo, New York. And I met Bill Regelson in the laboratory at Roswell Park Memorial Institute. It was late at night, and it was freezing rain, kind of miserable night. And he asked me a lot of very tough questions and was not very pleasant toward me. But the end of the interview, he says, I like the way you think. And I'd like to offer you an opportunity to work with me this summer. And I jumped at that opportunity. And it was really, truly the turning point in my life in many ways. Because I, eventually, many years later ended up marrying Bill Regelson's daughter. My current wife-- DANIEL F. HAYES: I was not aware of that. LARRY NORTON: Yeah. Rachel, the love of my life, it was an extraordinary experience, because I got very close to family. And she was in New York at Columbia, at Barnard, the same time that I was in medical school. And so that's how it all came about. But anyway, Bill was really an inspirational character for many people of my generation who were in contact with him. Because he was just filled with enthusiasm, and energy, and optimism. You remember, the early days of oncology were very special. And by the way, if you want to catch a glimpse of that, it tends to be this book, The Death of Cancer. I'm giving it a big plug, fantastic book that captures the whole history of his life and cancer. But the early days is very important for people to recognize what it was like in those early days. It was just an enormous challenge just to get people to pay attention. The possibility that drugs could actually be useful in the treatment of cancer, and it was often ridiculed. I can tell you a little story later about my early experiences when I came to New York in that regard. DANIEL F. HAYES: So did you know you were going to be an oncologist when you went to med school? Or did that-- LARRY NORTON: I'll tell you two of the turning points in that regard that I think are particularly interesting. One is, at the very beginning of that summer, Bill Regelson brought me-- in those days, the labs were right next to the clinic, the inpatient service. And he brought me right from the lab a few steps in to see a patient who was admitted to the hospital with a pelvic tumor. I don't know what type, didn't register in my mind at that time, but a pelvic tumor that had grown very large. And it actually had eroded out into the skin and was large, and infected, and bleeding, and just awful. And the patient was in terrible pain. And he said, we're going to treat this patient with a new drug that I think is going to help her. And it's called methotrexate. And he treated with methotrexate, and I saw the I saw the medicine go into her arms. And over the next few weeks, during that summer, I saw this tumor shrink down. I saw the skin heal over. I saw the pain go away. And it was, I'm seeing this monster eating this woman from the inside out. And I'm seeing just this yellow chemical going in there, and the monster being defeated. It was like magic. It was something just beyond conception that, actually, you could take something that awful and that terrible, and actually give it medicine, and actually make it go away. And I said, this is a world I can't turn my back on. This is a world I have to be in. This is just a magical, wonderful world, where you can actually heal things that couldn't be healed by other ways, I mean, totally beyond surgery, totally beyond radiation. And here's medicine going in. So that hooked me. But at the very end of the summer, and toward the very end of my time there, another thing happened which would be a good segue. But also very important is the real person running medicine A at Roswell Park at that time was this person named Jim Holland. And Jim Holland was not there all summer, because he was riding a horse. And he had his daughter, one of his daughters on the horse. And the horse was acting very, very jittery. And he was a little afraid of what the horse would do. So he went close to a fence, where he could actually unload the daughter, so she can grab on to the fence. And the horse didn't bolt and crushed his hip against the fence. And so he was out with a fractured hip or pelvis the entire summer. But he was well enough toward the end of the summer to come in and speak to the summer students. And he came in, and he sat in a chair in the middle of the room. And all the summer students who gathered around him-- if I thought Bill Regelson had energy, to see this tornado of a personality in the room, with his loud booming voice and his probing questions, his clear intelligence and enthusiasm for his field and dedication to it was just inspirational. And so it was a crescendo of a summer for me. And that was it. The experience of Bill Regelson, the experience of Jim Holland, I knew that I was stuck. And even though other things were attracting my attention, nothing was going to capture my life as much as the medical oncology. DANIEL F. HAYES: You went on then to work with him for 10 years at Mount Sinai. LARRY NORTON: Right. DANIEL F. HAYES: In addition to what you've said, his obnoxious ties also always stood out for the rest of us. But those 10 years must have been unbelievable. Because the guy never quit thinking, at least in my experience with him. LARRY NORTON: I mean, there's so much to say about Jim Holland. I had the honor to speak his funeral, the sadness to speak at his funeral, but it was the honor to speak at his funeral related some of the stories. But there's so much to talk about him that it's actually worth a whole book, even an opera, with the bigger than life personality he was. But he captured something that I think was very important. And some of the early pioneers that we were talking about before really captured which is, I mean, these were real pioneers. I'll just give you a little side story. I mean, I came into grand rounds once, when I was working with him late, as I usually am to pretty much everything. But nevertheless, I came in a few minutes late, and everybody was gathered around. And I remember it was a thoracic specialist, a pulmonologist, who was actually conducting grand rounds. And as I walked in the door, he says, how come you're late, Larry? Were you out there saving lives? And everybody roared into uproarious laughter. Because medical oncology was the last step before the cemetery. Hopeless situations would all come to us. And then we'd give them drugs and not help people whatsoever. And of course, I felt this deep humiliation. I was a young doctor at the time, and all these great, senior people, great luminaries were arrayed around. But that was the attitude of a lot of people in medicine at that time is that hopeless situations, send it to them, they'll take care of it. They'll hold hands, whatever. And to see where we are today, and how many cases we cured, and how many patients we've cured, and how well we managed things, certainly, we don't cure enough. And you and I and our whole community is working hard on that. But we do cure a whole lot of people, and we do help their lives. And we do keep them functioning for a longer period of time with the medicines. So the people that went into the field at that time and actually established the field of oncology, medical oncology, at that time were really had to have a real pioneering spirit. And so Tom Frei obviously pops to mind in that regard, and many others. I could give a long list-- DANIEL F. HAYES: Well, I should say, I had the great privilege of training with Tom Frei and the pleasure of interviewing Dr. Freireich who, sadly, passed away a few weeks ago. I did not get to interview Dr. Holland. But because of his friendship with Dr. Frei, Dr. Holland adopted me as well, even though I was never working with him directly. And the three of those guys, I think our listeners need to understand, they were really cowboys. And they did things that we would now just, I think, repel, just have you can't do that sort of thing. But they did it, because they had to. As you said, there was nothing else to do. It took a special personality. LARRY NORTON: Totally-- I mean, everything you're saying is-- I agree with. But also, that's why we are where we are today is because they took chances, because they had a vision, and they attacked that vision very, very aggressively. And I'll do one more namedrop in music that is one of my and still friend is Quincy Jones. And Quincy Jones had this wonderful phrase in terms of jazz improvisation that was really very important to me. Sometimes, Larry, you have to jump without a parachute. And how do you get into an improvisation? You just start. And then it has a life of its own. And the better you get, the more experience you get, the better you start it, and the better you're going to develop it. But you just got to start. Hit the first note, doesn't matter what it is. And that kind of spirit of jumping in into it was really, very important. And I think that's something I really miss from modern oncology. If we're going to talk about where we are now compared to where we are then, a lot of things have changed that are very positive. Obviously, the amount of science that we have to draw from now is just astronomically greater than what we had in the early days, when we're talking about very primitive things. The whole Norton-Simon thing was all about attacking cell division, the best way of attacking cell division. We're so far beyond that in so many ways. That's one of the bigger changes. Our access to information, I mean, I had a question. I have to go to the library and got to cart catalogs, and pull books off the shelf, and open them up, and spend hours and spend days finding out one piece of information that now I can find out in about 15 seconds, if my fingers are slow on the keyboard, 15 seconds. And so that's it. But one of the major things is that it was all about concepts then. It was all about principles. The principle that antimitotics could actually make tumors shrink and could be beneficial. That's a principle. Combination chemotherapy is a principle. Dose dense sequential therapy, if you take it into further development of my area as a principle. And the overarching concepts on patient centrality of it also is that the early clinical trials were very small trials. Because each and every patient was a valuable piece of information. They were almost collections of anecdotes. And obviously, we've evolved way past that in very positive ways. But what you learned from the individual patient was extremely important to that generation of pioneers rather than large numbers. And I think we moved away from that. DANIEL F. HAYES: Actually, I'm going to interrupt you, because I think almost everybody I've interviewed has stories like you started out with. I saw a patient who I couldn't believe responded to X or Y. And I have the same stories. And I'm hoping our young folks still believe that's as important as filling out the meaningful use things on their documentation. I told my own son, I want him to be a doctor and not a documenter. You need to document, but you need to be a doctor. Can I segue into-- LARRY NORTON: We ought to spend the whole podcast on that topic someday. DANIEL F. HAYES: No, yeah, let's do that. LARRY NORTON: Because the thing is-- well, because I think that the thing is, when you're taking care of a patient, and you're thinking, obviously, we're always thinking what's best for the patient, all of us. But you're also thinking of gathering information in a verbal way about the patient. So you can talk about that patient to your colleagues, or write it as case reports, a series of case reports is a different mindset than when you're thinking about how am I going to fill out my electronic health record? And I think the mindset differences, and I frequently say to the younger people that I teach or that I'm in contact with, that they grew up in a digital world. And I grew up in an analog world. And the way you think in an analog world is very different than the way you think in a digital world. Maybe it's for the better. I mean, only history will tell, but I just miss that kind of analog thinking. Much of what we have today is because of it. DANIEL F. HAYES: Let me take you into your role in modeling and especially with the so-called Norton-Simon hypothesis. How did you hook up with Richard Simon? And what did he teach you? Because I find him to be a fascinating person. LARRY NORTON: Oh, a fascinating person, and obviously, one of the really important people in my professional career. The math was in there. Because along with, I mean, I studied math. I had studied math in college, and I was-- DANIEL F. HAYES: I should-- describe it. Just for a minute, describe what it is for our listeners. LARRY NORTON: Oh, the Norton-Simon hypothesis and the-- DANIEL F. HAYES: Yes. LARRY NORTON: All right. Oh, yeah, well-- DANIEL F. HAYES: Briefly, briefly. LARRY NORTON: It's very simple is that way before my time, Skipper Schabel and colleagues at Southern Research Institute had described the way experimental tumors in their laboratory grew which was exponential. And they made the observation called the Log Kill hypothesis, which is the Log Kill rule which is a given dose of given drug kills a percentage of the cells that are present rather than an absolute number of cells, which is actually counterintuitive. It shouldn't be that way if you think about it in terms of biochemistry, but it is that way. And we were all taught the Skipper Schabel model and Log Kill hypothesis. We were all taught that. And I was in the clinic taking care of a patient with Hodgkin's disease, nodular sclerosis Hodgkin's disease. And this patient had [INAUDIBLE] involvement with Hodgkin's disease. Remember, I was working with Vincent Davita, a great influence on my life, Bruce Chabner, Bob Young, many people who-- George Canellos, who you know very well, great luminaries doing lymphoma therapy as a clinical associate at the National Cancer Institute. Hampton's patient is they had to Hodgkin's disease, got MOPP chemotherapy, roared into complete remission. Basically, two cycles of MOPP, was in complete remission. I've been involved in oncology since the early days of MOPP to show you how long I've been involved in oncology. And I got four more cycles, because we give six cycles no matter what. We're two cycles beyond complete remission in that setting. And it was about a year. And the patient came back with mediastinal lymphadenopathy. The biopsy showed that was exactly the same lymphoma. Put him back on MOPP chemotherapy, and he responded again and went back into remission. I don't recall whether it was complete remission or partial remission. And I said, this is really fascinating, because the math was already in my head at the time. Because I thought I want to graph it out and show how well it fit the Log Kill hypothesis. And it didn't fit at all. I mean, it just didn't make any kind of sense. From a mathematical point of view, you couldn't make the equations fit. And about that same time, I became aware that others were describing that tumors were not really growing exponentially-- solid tumors were not growing exponentially as Skipper had shown in his laboratory models, a certain leukemia named leukemia 01210. But rather, by a very strange curve called a Gompertz curve, which was developed in 1825 by Benjamin Gompertz to fit actuarial data, actually, not anything in terms of biology. And that's an S shaped curve. So it looks exponential at the beginning. And then it bends over and eventually seems to try to reach a plateau size. And so I went back, and I applied the Skipper Schabel model mathematically to the Gompertz curve. And I realized that, for this individual patient, it would make a whole lot of sense if the tumor, when it was growing quickly, regressed more than when it was growing slowly at a very large size. In other words that the hypothesis is that the rate at which it would shrink is proportional to its rate of growth. And since, in a Gompertz curve, the rate of growth is always changing, the rate of shrinkage changes as a function of time as a tumor shrinking down. And that was of germ the idea. And then the question is how to test it. Under contract Arthur Bogden in Massachusetts did some animal modeling for us. And we published my first paper actually that showed tumors were growing in a Gompertzian fashion. And in fact, a subsequent paper showed that they regressed also in the Gompertzian fashion which is what the Norman-Simon hypothesis is. Almost immediately thereafter, a couple of implications, in terms of cancer therapeutics, and I want to get back to that. Remind me to get back to that later on. Because this is around 1977 or so that all this was really becoming clear. So it was actually one patient that made me think of it. I mean, frankly, it was one patient's experience that made me think of it. And that's what you were saying before, Dan, is the importance of learning from each individual patient. DANIEL F. HAYES: And actually, it's gone on to be tested in many, many trials. But probably the most definitive was run by Marc Citron and CLGB under your guidance. And I just want to say a few words, because Marc passed away just a few weeks ago. He was really instrumental in ASCO and very, very generous to the foundation. We'll miss him greatly. But that trial of 97-- LARRY NORTON: 41. DANIEL F. HAYES: 9741, demonstrated that dose density was superior to giving things in big doses for longer periods of time. Let me ask you about-- LARRY NORTON: I just want to second there what you're saying about Marc. I mean, just an incredible human being, an incredible person, incredible clinical scientist, and he was actually the first community clinician to chair a major national trial from a co-operative group which was just an intentional decision. I believe, you were involved in that decision, actually, Dan, Hyman Muss, certainly. DANIEL F. HAYES: Marc and I started in a group at the same time. And we grew very close. I miss him. Let me ask you to look into your crystal ball for a minute and that is with precision medicine and targeted therapy. Does the Norton-Simon hypothesis still apply to that? Do you think chemotherapy still-- LARRY NORTON: Oh, yes. Oh, yeah, yeah. Well, first of all, I mean, I'm not-- now we're getting into sophisticated science topics here. But the thing is that I'm not, to this day, I'm not sure I have chemotherapy works. I don't think that all of chemotherapy effect is just killing dividing cells. First of all, it's mathematically impossible. Does chemotherapy, does cytotoxic therapy affect the relation cell to its microenvironment? Does it affect its relationship to the immune system? These are all things that are under active investigation and active study at the present time. There's more to what we do every day in terms of giving chemotherapy than just killing dividing cells. Chemotherapy can be very precise. I mean, methotrexate and dihydrofolate reductase, we talked about it before. It's very, very precise therapy, hormone therapy, tamoxifen and the estrogen receptor. So we've been talking about precision medicine for a long time. It's just that our level of sophistication in terms of likely targets has changed. But still, it works. It's a law that fast things, things that grow faster regress more quickly than things growing more slowly how you return them. And I think that there are important lessons there that we still have to learn about cancer biology. And that got me into some very exciting areas with [INAUDIBLE] and colleagues and to cell seeding theory with cancer, for example. And that story is evolving. And more data is becoming available there and much more sophisticated mathematics that will apply to those days that I hope I will have time to work on in the next few years to be able to actually establish those principles. But I still think that we're doing something wrong if you're talking about a crystal ball which is that-- and it relates to what I just said before. We're so self-hypnotized into thinking that cancer is a disease of cell division. The vast bulk of our targeted therapeutics are oriented toward molecules that are related to mitosis. You hear talk, that'll be a very specific talk about molecular pathways starting with genomics and [INAUDIBLE] signaling. At the end of the slide, it says, invasion, metastasis, and growth. It's a nice little package. And that's the answer. Well, I mean, that's a big cloudy area. I mean, those are different things. Those are separate things. Those all have their separate biology. But they're all related. It is totally true. And how are they related? And why are they related is one of the very important topics that we have to wrestle with, because that's what we really have to perturb. And I think that the, again, crystal ball guessing, or at least where I'm putting my energies now is we have all these incredible tools for developing medicinals that can attack molecules. Are we attacking the right molecules by focusing in cell division? Should we be looking more toward perturbing tumor microenvironment relationships? Should we look at more sophisticated ways of using the immune system as one element in the tumor microenvironment, one of many in the tumor microenvironment, to accomplish the goals that we have to accomplish? And are we actually looking at the right things in terms of molecular analysis in cancer by looking at pathways that are concerned with cell division primarily and secondarily with other things? Or should we be looking at molecular networks and molecular pathways in a more sophisticated fashion? Just like the early days of oncology, we have to be willing to take intellectual chances. And that's something I'm seeing much less of now than I did if you go back half a century. DANIEL F. HAYES: We can go on with this one for a long time too. And we probably will the next time we get to sit and have a drink together when the pandemic goes away. I think it relates to dormancy. And I don't think we understand dormancy or how it is broken and how to treat it. I have two things, and we're running out of time. One of those is you probably, in my opinion, have been the king of understanding the importance of philanthropy in our field, especially in relationship to what I see directly, which was your relationship with Evelyn Lauder and her husband, Leonard, of course, in the Breast Cancer Research Foundation. But I'd just like you to emphasize to the folks coming in the field how important that philanthropy is. I think some of them believe it's dirty to get involved with that and ask people to give money. And you and other people I think have taught a lot of us that these folks want to help us. And it's important to address that in a dignified way. LARRY NORTON: We're all in this together. I mean, I think that's the important thing to recognize as a physician or as a scientist. I said in a paper once that just as all of us are either actual or potential healers, all of us are actual or potential patients. Cancer is a very important problem that needs to be solved. And people have to solve in every way they can, with our intellectual ability, our hard work in the clinic, our hard work in the laboratory. And people who are working hard in other fields who accumulate some element of wealth, or even people that just in normal life contribute small amounts, a lot of people doing small amounts adds up to a lot of money also. I mean, they're all part of the same process. I mean, the importance of philanthropy is that-- and it goes back to what Evelyn said which I quote all the time. She was very instrumental in the building of our first breast center at Memorial Sloan Kettering and then our second breast center, which is freestanding building at Memorial Sloan Kettering. She and Leonard involved in every way and not just in terms of philanthropy, but actually thinking through the problems and helping solve them and design in every way. When we built the first building that we had, we actually raised a little bit more money than we needed for the actual physical structure. So the question is, what to do with it? And obviously, a research fund at Memorial was established. But then in terms of where else to go with it, she invited me over to her place in New York overlooking Central Park. And we sat in the kitchen, and we drank tea. And I said, what I perceive, and with my colleagues, I'm not the only one, obviously, who's perceiving this, is an explosion of science, basic science in understanding cancer, and an incredible collection of clinical investigators that can do clinical trials, and do large clinical trials as well as pilot clinical trials in our institutions. But I didn't see the connections being very tight. Because we were in different worlds, speaking somewhat different languages. And we had to tighten those connections somehow and do something translating scientific advances in the laboratory into clinical benefit. It also allowed the scientists to understand what the clinical problems were and how to have the approach, and how we're going to do this. And she said, I've worked around creative people all my life in my professional life. And I know, you've got to identify the right people first of all. So that's a little bit of a talent. But that the main thing is that when you identify them, you've got to give them freedom to use their imagination and the security to know that if they do something good and it doesn't work out, that they're not going to lose their job. Freedom and security is the secret of making progress in the field. And I said, that's what we need. We need a foundation that can give the right people the freedom to use their imagination and the security to know that as long as they do good work, they're not going to lose their funding in a more traditional grant mechanism. And that's really where it started. So the whole thing is all based on that, is to get the right people and to give them freedom and security. And another part of it I just want to mention is networking to give people-- DANIEL F. HAYES: So let me focus this. LARRY NORTON: OK. DANIEL F. HAYES: Breast Cancer Research Foundation, how many people are you supporting? And how much money did you give this year? Just to give-- LARRY NORTON: Oh, about, oh, I mean, it's about 200 or so or more than that. Investigators, it's international at the present time. This year has been a tough year, and the next few years probably, because of COVID, because of the pandemic. It's been a tough year. But in general, we've probably given away about a billion dollars. But it's not given away. It's actually an investment, investment in the future. DANIEL F. HAYES: Yes. I agree. LARRY NORTON: And it's all about bringing people together. New investigators come in, and they're used to gladiatorial combat when it comes to grant acquisition is that they have to fight against the people to beat them out. And what we reward is people working together and sharing ideas. And phenomenal things have occurred in that direction, phenomenal, huge programs in metastasis and molecular biology, Translational Breast Cancer Research Consortium which has been a fantastic thing that we've helped support. So it's really been a joy. DANIEL F. HAYES: It's been great. Final 1 minute, the other thing you've done as well or better than most is mentoring. And I personally want to thank you for helping me in my career. But probably, your greatest success is mentoring Cliff Hudis who's now the CEO of ASCO and is responsible for ASCO continuing to be probably the world's greatest oncology professional society. Actually not probably, in my opinion, for sure. So for that, I thank you. We've run out of time, unfortunately. I think you and I could go on for another hour or so with this stuff which is what's fun about my getting to do this. But I want to thank you for all you've done for the field, for all you've done for so many of us in the field, and most importantly, for the patients who have benefited from what you've done. It's pretty remarkable. This has been so much fun for me to get to interview so many of the pioneers. But you certainly rank up there at the top. So thank you very much for your time and look forward to talking to you later. LARRY NORTON: Thank you so much for the kind words and for inviting me to do this with you, Dan. Thank you. [MUSIC PLAYING] DANIEL F. HAYES: Until next time, thank you for listening to this JCO's Cancer Stories, the Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, the Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Dr Hayes interviews Dr Ganz on pioneering quality of life studies. PRESENTER 1: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. PRESENTER 2: Welcome to JCO's Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. DANIEL HAYES: Today, my guest on the podcast is Dr. Patricia A., Patti Ganz. Dr. Ganz has been a pioneer in establishing an entire field in our discipline, the discipline of survivorship. And really, this has been based on studies of quality of life and toxicities of therapy in patients with established active cancers that Dr. Ganz was involved with for really, the last four decades. Dr. Ganz was born and raised in Los Angeles. She received her undergraduate degree at Radcliffe, graduating in 1969. And correct if I'm wrong, Patti, I understand you were in the last class before the merger with Harvard. But I see you got your degree from Radcliffe and Harvard. So she received her medical degree and completed her residency and incidentally was chief resident and then medical oncology fellowship, all at UCLA. She then joined the faculty at UCLA and spent much of the early part of her career at the UCLA associated VA hospital. In 1992, she moved back to the mothership where she is now professor of medicine in the David Geffen School of Medicine, a professor of health policy and management in the Fielding School of Public Health, a distinguished professor of medicine and health policy and management, and the associate director for population science research in the Johnson Scott Comprehensive Cancer Center, again, all at UCLA. Dr. Ganz has authored over 400 peer reviewed papers, way too many chapters and reviews for me to recount here. And since 2017, she served as editor-in-chief of the Journal of the National Cancer Institute, one of the leading journals in oncology. She has an enormous list of honors that, again, is too long for me to go through today, except for a few I'd like to highlight. She's received two of ASCO's highest honors, the American Cancer Society award in 2008, and the Joseph B. Simone award for excellence in quality and safety in the care of patients with cancer in 2016. She was also the recipient of the Ellen L. Stovall award for the advancement of cancer survivorship care. She was a founding member of the National Coalition of Cancer Survivorship, and she was inducted into the Institute of Medicine, now designated the National Academy of Medicine, in 2007. And she's really played a major role in the efforts of the Academy to improve quality of care in medicine and particularly in oncology. Dr. Ganz, welcome to our program. PATRICIA GANZ: Thanks, Dan. It's great to be with you. DANIEL HAYES: So just to start out, there are so many things I'd like to talk to you about. One of those, in my opinion, you've been the epitome of role models for women in academics. And a lot of this series has mostly been men, because it was mostly men who started a lot of what we do way back 40, 50, 60 years ago. I know you grew up in LA. What shaped your decision to go into medicine in the first place, and then to stay in academics? PATRICIA GANZ: I went through college at Harvard and Radcliffe in a very turbulent time, in the late 1960s. Social issues were very important to us then, political issues just as they are now. And I was a biology major. And I was thinking about what I would be doing in the future. And for me, I really felt that I had to do something connected with people. And that was part of my decision. But of course, I had a major influence from my father, who was a physician. He actually went to the University of Michigan. And he always encouraged me to think about medicine, although he said ophthalmology, radiology, those are good careers for women. So you know, I had this lurking in the background. I didn't want to necessarily do exactly what my parents said to me. My mother was someone who also had been working in a family business for many years. So I had them behind me saying it was possible to have a career and to move forward in medicine. And of course, summers, doing various kinds of research that was involved with a potential career in medicine. So it wasn't a big surprise. Now why did I come back to LA? I guess that's a good question. Nowadays, when people actually are applying to medical school, I think they apply to 20, 30, 40. In those days, I think I only applied to six, if you can believe it. And three of them were UCs, and three or four of them I guess where on the east coast, or Northwestern with another one. It was a tough time. It was just on the feminist movement, also social change in terms of more African-Americans being admitted to medical school. And it was a tough time for those who were underrepresented, such as women. And in fact, at Harvard Medical School, I think family took 10 women. UCSF maybe took seven or eight women, where I'd gotten accepted there. And when I finally went back to school at UCLA, there were only three women in my class. So again, quite a striking difference than the way things are now. But I did come back to LA because UCLA was pass/fail. Having heard about the competition and medical school people being pretty cutthroat, I said, mm, probably good to go to a place where that wasn't the big issue. In addition, I actually met my future husband in a lab, working in a lab before my senior year in college. And I guess that might have been a motivation as well. DANIEL HAYES: And have you seen major change in attitudes regarding sex/gender in academics now? Do you feel that we've really made advances, or is it all just covering of a system that still exists? PATRICIA GANZ: I could speak for an hour on that, so I'm not going to do that. But I have to say that being a minority in the class was not unusual. Because at Harvard and Radcliffe, there were 300 women in my class at Radcliffe, and 1,200 men. And obviously, in the science classes I took, the women were in the minorities as well. But for women at that time, getting into medical school, they were actually a lot smarter and a lot better than the men because we were highly selected. However, my class, the three women-- one was me coming from an elite Ivy League school. One was a blonde valley girl who was coming from a California State University and another was a Korean immigrant. So we were all quite diverse-- yeah, even then. But by the time I graduated, we had a few women who transferred in. And actually, my husband who was a physicist at that time, went to medical school at UCLA five years later, and his class had about 25% women. So things were rapidly changing then. DANIEL HAYES: So I understand you really started doing hospice care when you were at the VA initially. And how has that colored what you ended up doing in terms of your career? I mean, in the 1980s, there wasn't a lot of hospice care. It must have made you think about and led to what you're doing now, what you've done. PATRICIA GANZ: That's an excellent question, Dan. And it was actually the late-- 1978, where I joined the faculty. And the chief of medicine said, you know, we have this kind of intermediate care unit. We'd like you to start a hospice for our oncology service, et cetera, et cetera. And there was actually a national hospice randomized trial that was going on at one of the other VAs here in Los Angeles. And having come out of my oncology training and thinking about it, I really thought well, you know, lot of those things that we're offering people at the end of life, like pain control and psychosocial support and things like that, we should really be doing that earlier for people. Because why should it just be reserved for those last few weeks? And so as I develop my unit at the VA, I actually called it a palliative care unit, a palliative care ward. Because at the VA I worked at, we had patients who actually often were in the hospital for five or six weeks getting their radiation, traveling by bus to the radiation facility. So they would be in for five days a week and then go home on the weekends. And these-- again, this was 1978, what were we seeing? We were seeing lung cancer. We had men with widespread prostate cancer who needed palliative radiation to the bones. We had a lot of colon cancers. So I was taking care of those patients. And while they weren't in imminent need of end-of-life care, they had trajectories which clearly were not good if they had advanced cancer. And it seemed reasonable-- I had a wonderful team, a physiatris, a psychologist, a social worker, even the pharmacist made rounds with us. It was just wonderful. And I essentially took all of the things that the palliative care end-of-life focus that hospice used and brought it up to the earlier part for some of these patients who, in fact, could be cured. I can think of someone who had localized small cell carcinoma who I took care of for many, many years. He was in getting chest radiation and whole brain. And you know, he lived a long time but he got all the tender, loving care that our nurses and our team were able to provide early in his course. DANIEL HAYES: You know, it segues really into my next question, which is in my own training, in the early 1980s at the Dana-Farber, especially led by Dr. Fry, Tom Fry, who's one of the fathers of medical oncology. We were really trained to learn how to treat and hopefully cure cancer. And there was very little regard to the toxicities. Dr. Fry used to tell us, cure the cancer first, we'll figure out the toxicities later. And at least the shackles begin to fall from my eyes as I began to see what you and others started to say. Well, you know, these people are going to survive. We need to worry about that. And personally, I think you almost-- not quite, but almost single-handedly taken our field beyond just treating the cancer, but worrying about the quality of life of survivorship. When you were starting that, either at the Bay area or when you went back to the main campus, what were the hurdles? Were there people who told you, you were wasting your time? Most have been told this is a fool's errand. You'll never get promoted by doing this kind of research. And you have done OK, I think. PATRICIA GANZ: Yeah. You know, I actually wanted to even go back to my training, you know? Because in the late '70s, there was actually-- in my heme/onc division, it was mostly liquid hematologists who were the leaders. And there were one or two solid tumor oncologists. And because I was interested in medical oncology primarily, I was the mentee of this person in his clinic. And essentially, what happened-- this was in the early days of adjuvant TMF chemotherapy. And you know, I was giving women chemotherapy for 12 months. And they didn't want to take it. They wanted to stop because of the toxicities of treatment. And he typically had me see those patients who needed that kind of support and symptom management and things like that, which were rather primitive, obviously, at that time. Because he was very technocrat in terms of knowing the literature and making those kind of decisions about therapy, but not managing all of this. So because of this collaborative relationship in his clinic for a couple of years, that's essentially where I began to see these issues because patients felt comfortable talking to me about it. Early on actually, at the VA, I was very fortunate, first of all, just to say I was a biology major in college. I never took a psychology class, ever. I took maybe a sociology class, which was on China at the time, but really wasn't trained in behavioral science. And I was very fortunate because there was a psychiatrist who was very interested in understanding the impact of cancer and its treatment on patients. And again, mind you, the five year survival was less than 50% at that time. And certainly, for the patients we saw with lung, colon, prostate that was metastatic, very much shorter. And he got a grant from the VA to do an intervention trial in the veterans and their spouses. But in order to be able to understand what patients were experiencing, Ian, the psychologist he hired as a project director, said, well, we've really got to interview patients and talk to them and find out what they're dealing with. And the psychological or psychosocial literature at that time was rife with issues related to coping. And coping is a concept that is not easy to explain to people. And certainly, it isn't necessarily universal in terms of many cultures. So it was difficult, then, to kind of operationalize this. And again, because I work with this great team, they began to interview our patients in clinic, and really, in detail, understood the day-to-day things that people were dealing with in terms of their cancer and the side effects from the treatment and their social relationships. And then we, all of a sudden, began to think of ourselves as a multidisciplinary team. And in fact, the person, Joe Collin, who was the associate director for population science at the Cancer Center at that time at UCLA, kind of said, gee, you make the ideal multidisciplinary team, you know-- a psychiatrist, a psychologist, and some medical oncologists. And it was from that time forward, that we began working together and I got my first grant. And really, they taught me so much about measurement, reliability, and validity. And in fact, we published our first paper together in JCO the second volume, which was on the Karnofsky performance status we visited, where they compared their ratings of the Karnofsky with my ratings of the Karnofsky for the clinic patients. And because they did a systematic interview about what patients were experiencing, noted that the function of patients was much worse than what I as even a sympathetic clinician would rate them. So that was really so important for me and working with them. And again, I think that's been the hallmark of my career to have had so many psychologists and psychiatrists, behavioral scientists, who embraced working with me, partly because I gave them access to patients if they wanted to study them, but I was also interested in really understanding, in a very rigorous way, how we could measure some of these things. DANIEL HAYES: Yeah, that raises another issue. In my career as a clinical investigator and translational investigator, pretty much inherited the tools to do what I want to do, how to do a clinical trial. It's always struck me that you, and I guess, Charles McKinsey and others had to make up your own tools, basically, to get it out of the realm of touchy-feely, if you will, and into the realm of true quantitative science so you could describe what you've done and how you've done it. How did you go about building those tools? PATRICIA GANZ: So again, a lot of these strategies or approaches to measurement were available in the social science literature. And they were just beginning to be translated into medicine. And again, this goes back to when I was training at UCLA. The Rand Health Insurance Experiment was going on in the '70s. My attendings in clinic were all involved in that. And John Ware, who was a great psychologist/methodologist, developed huge measures to look at patient outcomes in that big insurance experiment trial, which then got adapted into many other instruments that are widely used, such as the SF-36, and more recently, the Promise measures, which are publicly available. So I kind of was-- again, I had these kind of parallel streams of exposure. Health services research was very prominent at UCLA. These were my clinic attendings. And there was a very robust community of health services and health outcomes researchers. So I saw myself as kind of being an oncologist who could use those methods and apply them to the cancer problem. And there certainly weren't too many people out there. In addition, I had good fortune to begin to work in the cooperative groups, Ware and SWOG, with someone like Carol Moinpour, who led the efforts there in terms of patient-reported outcomes for many years, and then actually had a sabbatical in Switzerland, working with some of the IBCSG people and really having a time to just self-educate myself about this methodology. So I'm really self-educated, but have had wonderful collaborators who have kind of held my feet to the fire and said, you know, that's not rigorous enough, on occasion, certainly. DANIEL HAYES: So you were doing team science before the word came up, before the term. PATRICIA GANZ: Yeah, exactly. Certainly, when you have certain gaps in your knowledge, you need those collaborators. DANIEL HAYES: You know, this brings up-- I alluded to her just a moment ago. But when I think of cancer survivorship and quality of life, I think of you. But I think a lot of the late Jimmie Holland, who sadly passed away before I was able to interview her for this series. Can you just-- I think maybe some of our listeners don't know of her, haven't heard of her. We've got a lot of people young people listening to this. Can you just give a little background about Dr. Holland and the things she did? PATRICIA GANZ: Sure. Dr. Holland was a psychiatrist who really invented the field of psycho-oncology. And really, because she was working almost always in a cancer hospital, cancer setting-- I believe first at Roswell Park with her husband, James Holland-- she began to notice the neglect, if you will, of the impact of the cancer on the whole person and on the psychological aspects of cancer. And because of her being within a cancer hospital setting and then later moving to New York and obviously leading this effort at Memorial Sloan Kettering-- and really being very involved with CALGB and now the Alliance-- was able to introduce very early into the cooperative groups, the need for not just looking at the disease and its treatment, but to look at the after effects or show what were going on in the patient and how they were dealing with the illness. And she actually developed one of the first collaborative groups in psycho-oncology, which had people like Gary Morrow, who's at Rochester and who's had one of the big ENCORE research bases and has really continued to carry on a lot of psycho-oncology research across the country. Following what was really an early innovative approach, she developed a whole training program at Memorial. She trained many outstanding psychologists, psychiatrists working in this field and textbooks. I had the good fortune to work with Julia Rowland for a number of years. Julia was a direct descendant, if you will, Dr. Holland, having been at Memorial working with her and leading some of their early survivorship work. But she just trained probably more than a generation of people to take this seriously. As I kind of mentioned in an email to you, just as I would go to the ASCO meeting to listen to what Dr. Fisher or Dr. Bonadonna had to say, because I was interested in breast cancer and it was very exciting to hear the new reports of adjuvant therapy, I would also go to hear her and to Barry Castle, who was another leader in the field at the University of Pennsylvania, who basically were bringing rigor and clinical expertise to characterizing the patient experience, and publishing papers often in high profile journals like the New England Journal. So they were really role models for people who wanted to go into this field, although they weren't oncologists. And I think that's where I had kind of a double opportunity. Number one, I was perceived as a card-carrying oncologist. I was treating patients. I was in a cooperative groups. I was involved in trials, but I was also saying what about this secondary objective to our trial to look at the experience of the patients? So having entree to the patients, being perceived as one of the oncology community was, again, a really good thing to do. Although I must say that there were dozens and dozens of conferences where I was the last speaker on the program because quality of life was down there at the bottom-- not so much anymore. DANIEL HAYES: Your stories are great. I have one brief anecdote again, for the younger listeners. Jim and Jimmie Holland where as different as night and day. And Jim Holland, who was one of the three guys with Dr. Fry and Dr. Freireich-- who decided to put two drugs together and suddenly, we were able to cure some cancers-- was blustery. You might even call him a blowhard. I loved him, but I will never forget as a very junior person in CALGB, and I was appointed to be chair of a committee. And I was running my first committee meeting-- and needless to say, I was nervous anyway. And all of a sudden in the back of the room, Jim Holland, without a microphone, screams out something about, Hayes, if this is the way you think it's sounding, when I'm reading to you now, duh, duh-- so I went ahead and got through the reading. And later, Jimmie walked up to me and said, you know, he really loves you. His bark is much worse than his bite. PATRICIA GANZ: No, and you know, I think the early days of oncology were so much like that. Because again, we would have these wonderful people come to the microphone and ask a question. In the case of Dr. James Holland, he didn't need a microphone. But the point is, that we actually saw these people in real life, posing questions, challenging sometimes what was presented in a meeting, but also being very collaborative. And I think it was wonderful. And I think it's good that we have-- you know, our meetings today, obviously, are quite different because of the pandemic. But in our large meetings, we have scheduled discussions which is good, but it doesn't have the same spontaneity that we obviously were fortunate to experience in an earlier time. DANIEL HAYES: Yeah, I agree. You know, I think probably, of the many, many contributions and things you're known for, I believe your role in the Institute of Medicine then, now the National Academy of Medicine, regarding survivorship may be your greatest impact on what we do. How do you think that's translating now, to use the word translational science, which it really is? And when I was present, I was struck. There are probably 15 million cancer survivors in the United States right now. Have we really changed how they do based on your report, or is that falling on deaf ears? What do you think's going on with that? PATRICIA GANZ: Well, you know, there's several things that have happened. So the report that was in 2006 was led-- actually, Ellen Stovall was actually one of the co-leads of that committee. And you know, that was very seminal in that it was-- it's called the lost in transition report. And it really called out-- at that time, there were 10 million survivors, and that this whole large body of the population didn't really know, didn't have much direction about what to do after treatment and were kind of lost, because the oncology care system didn't really give them any guidance. And if somebody went to their primary care doctor, they would say, uh-oh. I don't know what that's about. You go talk to your oncologist. And then the oncologist would say, oh, that's a weird symptom, but it's not-- you know, you don't have any evidence of disease. That would be the typical thing. But it was usually an ongoing long-term effect of the treatment or possibly a late effect that was emerging, you know, such as a cardiac problem or a neurological problem that might be a secondary to previous treatment. And so the patients really weren't getting good care. And they kind of said we need there to be a group of people-- whether it's an oncologist or someone else-- who will take an interest and really tell us what do we need to be on the lookout for. And that was kind of a way to say, we need an end-of-treatment discharge summary. And it became actually very apparent. I was on the ASCO board actually during that time with the NICCQ report. I don't know if you remember that, but it was a report that ASCO did looking at the quality of care for breast and colorectal cancer patients. And what they found was you could find the op report from the surgeon. You could find the radiation therapist's summary note. But the chemotherapy flow sheets-- and this is, again, before electronic records-- were the only way you could even find out if somebody a series of treatments. And that went on, sometimes, over several years. So there was kind of no summary after the medical oncologists finished their treatment. So they try and figure out, even if you were the treating physician many years later and you needed to retreat someone, it was hard to know what was happening. So in some ways, the treatment summary and care plan had two roles. One was to say, well, what did they actually get? And the patient should know what they got in case many years later, you find out there's the late effects. But also, what do we need to look out for? And so really, again, building on what the childhood cancer survivor people had been doing for many, many years in terms of long term and late effects, this became an issue. Now Ellen Stovall, who was really focused on quality of care for cancer patients, and again, unfortunately, passed away a few years ago from complications of her Hodgkin's disease, really wanted there to be treatment planning and not just the treatment summary and care plan at the end of treatment. So I was actually fortunate in 2013 to lead another-- to lead, at this time, a report on quality of care and quality of care for cancer patients. Because Joe Simone had done one in the late '90s, and this was kind of a catch-up report. But it was also focused on the large and growing number of cancer patients, and many of them older. And with the baby boomers going into an age where cancer is very common, you know, how was our health care system going to approach this? And so we were, in that report, in many ways, echoing what had come about in the earlier survivor report, but saying you need to do this right from the very beginning. And it is very important for survivors. If we're going to be worried about fertility preservation, we need to do it right upfront. If we're going to be worried about potential complications in terms of cardiac toxicity occurring later, we need to be thinking about it in terms of planning the treatment for patients so that maybe they don't need to get chest radiation if they're a lymphoma patient. But chemotherapy and the very targeted therapies and the sensitive PET scans might help us avoid using unnecessary radiation to those individuals. So it has to be upfront thinking about what's going to have happen afterwards. And as part of the 2013 IOM report, we basically had many different recommendations which were kind of, I would say-- I kind of want to say pie in the sky, but futuristic. And one of them was that the insurers-- primarily Medicare, but other insurers-- should insist on patients having a treatment plan at the time of diagnosis, that their needs should be met, that they should have an understanding of the financial impact of the treatment decisions they're making, and that this should be part of a quality of care assessment strategy. And again, the thought was OK, maybe three, four, or five years from now, that will come about. But lo and behold, a year later, CMS picked this up and we had the development of the oncology care model, which in essence, took from our report the 10 or 13 point items that need to be part of initial coordinated care, which also included our survivorship care plan and treatment summary at the end of treatments. So I think to me, actually, that's one of the most significant accomplishments because now I see there's going to be a second version of the oncology care model, that many practices across the country have adopted these things. And as they've been part of the oncology care model, they're delivering this care to everyone, whether patients are insured by CMS or a private insurer. So I think this is an example of how long it takes to implement anything. Again, part of what I see our role, or my role as a health services researcher, is implementation science. If we know what works and what's important, it may take 15 years before it happens, but you need something like CMS to have a bundled payment plan. Or in the case of the treatment summaries and care plans, we have the American College of Surgeons who have championed that. And without these external regulatory policymaking organizations and payers, we don't get a lot of change. A long-winded answer, but to me, that's where the rubber hits the road. DANIEL HAYES: Well, I agree completely. I think that'll be your legacy, among many things. I mean, isn't it also part of the QOPI designation for QOPI accreditation in ASCO, isn't the survivorship plan? PATRICIA GANZ: Yes, the treatment summaries and care plans. I don't know-- I haven't seen any data. Recently, when I was more involved with the ASCO quality care committee, I saw some of those results. I don't know how compliant or adherent people are. But actually, part of the complaints that people have had has been, oh, it's hard to do this treatment summary. But if you actually start out with your initial treatment plan-- and we're actually doing this now on our Epic system at UCLA. There's something called the oncology history. And if you actually begin documenting from the beginning of treatment, you can actually move toward a treatment summary that's easily generated from the electronic record. But it's hard when you have to go back and do it retrospective. DANIEL HAYES: I was going to say, for all the young people who, at the end of a very long day, find themselves also having to do this long-term care plan for their patients, you could blame Patti Ganz for the work she started 30 years ago. PATRICIA GANZ: Yeah, OK. DANIEL HAYES: Actually, in the few remaining moments we've got, I want to bring up your new role as editor-in-chief of JNCI, the Journal of National Cancer Institute. I believe that you and Dr. Disis are the first women who have been editors-in-chief for major oncology journals. In fact, I don't believe it, I know it. You've been in the role now about three years. JNCI has always sort of had a niche that the other journals don't cover very well, in my opinion, and that they do. In taking it over, what are you keeping and what's your vision for the way you'll mold it in new ways and take it in new ways? PATRICIA GANZ: So I've been very fortunate, I was-- you know, I actually had a lot of experience at JCO as an associate editor for many years. And then I was also on the editorial board, and then deputy editor or associate editor and deputy editor of JNCI for quite a while as well. And Carmen Allegra took it over when Barry Kramer stepped down seven, eight years ago. And I knew Carmen from NSABP and RG. We had worked together closely. And I was kind of amazed when he took it over with all the obligations that he had as head of a heme/onc division and other roles, both leading gastrointestinal cancers at the NCI and NSABP Foundation. So he was doing a lot, and I thought, oh my gosh, you know? This is a difficult job to do as well. He basically moved the Journal a bit more towards a clinical perspective. And again, the history really is that JNCI was one of the first cancer journals. And maybe there was cancer research, but it was one of the first journals. And it essentially covered everything from soup to nuts, a lot of basic science. If you go back and see some of the highest cited papers, many different fundamental assays and so forth were published in JNCI. But if you look at the space in oncology, now there are 240-250 cancer journals so that we have many more outlets where some of the more basic science and translational science-- certainly, AACR has many wonderful journals-- so that we actually moved away, I think with Carmen's tenure, from the more basic work. And we really are taking almost no basic work. Things have to be clinical, in a sense that there has to be a translational component, cell line studies. And in vitro and animal models are not something that we're covering anymore. And again, that's a transition that I think occurred in prior years. I'm certainly continuing that. But I think because of my interest in breast cancer, obviously, and outcomes research in psychosocial work, we get more of those papers than perhaps when Carmen was the JNCI editor. But it's stiff competition, you know. We've had a strong epidemiological bent. We still get a lot of epidemiological and genetics papers. And I guess when I think about what I'm doing, it's really cancer prevention and control. That's what I've been doing for over 25 years, both in my academic research leadership position at UCLA, in my own research, and it's very broad. It's really applying all of the disciplines, if you will, of public health to the cancer problem, which means epidemiology, biostatistics, behavioral science, health outcomes research, you know, all of these things-- environmental science. All of these things are very important in both the etiology of cancer, the prevention of cancer, as well as the management of cancer. And so it's this cancer prevention and control swath that I think is our niche, if you will. So it's not as narrow as some journals. We're not just doing clinical trials, although we have them. But we're trying to have the broad scope of cancer prevention and control. That's pretty much how I see it. DANIEL HAYES: OK, thank you so much. Our time has come to an end. I can't tell you how much I appreciate your taking time to talk with us today. But more importantly, taking time to change the field of oncology in the way you have over the last 40 years. I think a lot of the things that our doctors are doing in clinic every day are a direct result of one person, and that's you. And there aren't many people who can say that. So thanks for all you do. Thanks for all your contributions, and I very much appreciate your sharing your history with us today. PATRICIA GANZ: Thanks so much, Dan. It was really a pleasure to speak with you and share what I've learned over time. Thanks so much. PRESENTER 2: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories: The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Dr. Hayes interviews Dr. Bruce Chabner on his experience with cancer drug discovery and development, phase I trials and pharmacology. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO podcast network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.ASCO.org. Today my guest on this podcast is Dr. Bruce Chabner. Dr. Chabner's is widely considered one, or frankly if not the father, of our understanding of the pharmacology principles of anti-neoplastic drugs. And probably more importantly, the translation of these principles to the intelligent application of the agents we use in clinic every day. Among the many accomplishments that Dr. Chabner has had working with his mentor, Dr. Joseph Bertino at Yale, who developed the concept of high dose methotrexate leucovorin rescue, that was completely based on their preclinical understandings of the mechanism of action, and more importantly, resistance to this agent. Dr. Chabner was also instrumental in the development of paclitaxel when he was at the National Cancer Institute, and he was intimately involved in many of the early studies that led to better understanding of AIDS and the ways to treat it. Dr. Chabner was raised in Shelbyville, Illinois, and I'm going to digress for a moment, because I've always had a very special soft spot in my own heart for Bruce Chabner. A, because of his science, but more importantly, because I was raised in Shelbyville, Indiana. Both of these towns were named after Colonel Isaac Shelby, who was a hero in both the Revolutionary War and the War of 1812. By the way, Dr. Chabner, I know you were a big student of history when you were in college, so I thought you'd like this. Dr. Shelby became the first and then the fifth governor of Kentucky, and as a citizen he was a land surveyor. There were actually nine counties and 11 cities and towns spread around the Eastern and Midwest regions that are named after Colonel Shelby. And I don't know about you, Bruce, but I had this drilled into my brain in eighth grade history class. I had to learn all about Colonel Shelby. Anyway, so he and I are brothers in Shelbyville. Dr. Chabner received his undergraduate degree of Yale, where again, he spent a lot of his time in the history department but also in the biology department. And then he got his medical degree at Harvard, where he stayed to complete his residency in internal medicine at the Peter Bent Brigham Hospital before it became the Brigham Women's Hospital. In 1967, Dr. Chabner became a clinical associate in medical oncology at the National Cancer Institute, where he was, in succession, a senior investigator in the laboratory of clinical pharmacology, chief of the clinical branch of the clinical oncology program, associate director of the clinical oncology program, and then he succeeded Dr. Ben [? Stabida, ?] someone I have previously interviewed for this series, as director of the division of cancer therapy. In 1995, after 25 years at the NCI, he moved to Boston as the chief of the division of hematology oncology and the clinical director of the Massachusetts General Hospital Center, where he is now the clinical director emeritus. Dr. Chabner has authored, I counted, over 500 peer reviewed papers. I think even more than that. By the way, his first was in 1969, a case report of shaking chills related to occult lymphoma, authored with Drs. DeVita and the [INAUDIBLE] of the [INAUDIBLE] syndrome. Bruce, that really shows how old you are. He's been the editor of all five editions of the Principles and Practice of Cancer Chemotherapy and Biologic Response Modifiers, which I consider the bible of cancer pharmacology. And I'm looking at my fifth edition on my bookshelf right now. He's trained too many Fellows for me to name, but numerous of them have gone on to be cancer center directors, chiefs of division, department chairs, and other leaders of oncology in the world. He's won way too many awards me to go through, but he received a Karnofsky award from ASCO, and he served on the ASCO board of directors. Dr. Chabner, welcome to our program. Nice, that's a lot of history. It speaks to my name. Well, that's the problem of interviewing all of you folks. It takes a long time to get through all the things you've done. It's a good problem to have, though. First, I want to start out, I understand you carry the flag rank of rear admiral. And I want to know, have you ever even been on a ship? And more importantly, did you and Dr. Shelby actually serve together in the Revolutionary War? I couldn't figure that out. You know, I never bumped into him when I was on the battleship Shelbyville, but who knows. He seemed to be what I call a name dropper. He left his name on so many different things, and I think there's a Shelby County, Tennessee, which is Memphis. Plus I think the smallest thing that he ever created was Shelbyville, Illinois, which was even smaller than your hometown. Yep, that's true. All right, that's the last joke I'm going to tell in this interview, but I like that connection. Anyway, so how did a guy from Shelbyville, Illinois get to Yale and then Harvard and NCI? And more importantly, what made you decide to be an oncologist? I know your father was a general practitioner, but at that time the field barely existed. What was your motivation? Well, OK, I'll tell you a bit of a story. My mother came from Chicago and she had a brother who was pretty smart. And he went to Harvard. And he used to come down to Shelbyville because he liked the pies that she made. And we were 200 miles south, so it was a trip for a pie, but anyway we used to play chess together. And when he was a college student and I was like in fourth grade, I beat him in chess and he said, Jesus, you ought to go to an Ivy League school. So that put the idea in my mind. And then my parents were not really happy with that. They wanted me to go to Washington University or University of Illinois, but I wanted to get away from home. It was a little bit confining to be around my parents for the rest of my life. So I applied to Yale, Harvard, and Princeton, and the deal was I could go to school if I got a scholarship. So I got a scholarship to Yale, so I went there. I was happy with that choice. I really-- it was sort of, you know, life changing, actually. Stayed on the east coast. But I still have many good friends from my Shelbyville days. We all get together once a year to play golf and poker and tell life stories. So I have to interject. My father told me I could go to any college in the United States as long as the tuition was the same as in-state tuition of Indiana University, which at the time was $400 a year. So I ended up going to Indiana University. So how did you-- That was such a great deal. Yeah, that was my-- How did you get into oncology? Well, when I was at the Brigham, I got interested in cancer. There was not much going on there, but one of my residents was a guy named Jack [? Moxley, ?] who had been a part of the initial study with DeVita and others, George [? Kinellas, ?] of the mop treatment for Hodgkin's disease. And I got really interested in that. And actually during my internship my sister got an immediate stromal tumor during her pregnancy, and it turned out to be a thymoma. But cancer really intrigued me at that point. And we all had to apply for positions at NIH as a way to get out of the draft, and I wanted to do research, so that really appealed to me. And I actually applied for cardiology and cancer, and I was interviewed by Gene Brown for cardiology, and he didn't seem very impressed. But the cancer people did like me, particularly George and Vince, who had come back there. And they were young and energetic and they had interesting ideas about combination therapy, so I ended up in oncology. Yeah, I talked with some of the other people I've interviewed about the so-called era of the yellow berets and how that really transformed medicine, in my opinion. Because so many smart people went to the NIH to stay out of Vietnam. It's probably the only good thing that came out the Vietnamese war, as far as I can see, and especially the NCI. So when you went to the NCI, [? Harlan ?] and Frye and [? Freirach, ?] I believe, were gone. So you've already started to say, it sounds like Dr. DeVita and Dr. [? Kinellas ?] were the movers and shakers at the time. Is that fair, or? Yeah, well they were really young. I mean, it was like working for, you know, contemporaries. There were no old people there. And Frye and [? Freirach ?] weren't that old at that time. They were in their 40s with Vince and George, who were in their mid 30s. And I was 28 years old, I guess, when I went down there. I loved it. We had laboratory opportunities, we had patients, we had people that believed that they could change the way cancer was treated. George and Vince, particularly Vince, were so energetic and so committed to the idea of changing therapy, and particularly combination therapy. And then the other thing that made it such a great experience were the colleagues that I had in my first group of clinical Fellows. Bob Young was part of it, and I became very close friends with Bob Young. And in the same group, David Livingston was my next door neighbor, and we had interned together and been arrested together. So we had just constant stimulation from a lot of different people, all of them energetic and interested in research. Who else was in your class besides Dr. Livingston and Young, then? Phil Shine, who made a name for himself in toxicology and then in industry. And let's see-- He was director at the cancer center at Georgetown for a while. Georgetown, right. Subsequently, there was just a long list of wonderful Fellows. When I came back, I actually spent two years at Yale between my NCI time and then coming back to NCI. And I had a wonderful time with Joe Bertino. He was, I think, very important to me, because he was really a great scientist. And I learned a lot about biochemistry enzyme purification and working in the lab. And so when I came back to NCI I had sort of converted to being an anti-folate person from being interested in alkylating agents. And so I was always interested, I guess, in anti-metabolites. But that was a great anti-folate experience with Joe, high dose methotrexate. It was really his idea, not mine. But the thing I worked on was the clinical pharmacology and trying to figure out why it was so toxic to kidneys. So we actually did some really interesting experiments. We gave high dose methotrexate to monkeys, and then when they died, we took the kidneys out and looked at them. And we were doing it because we thought we would see interesting pathology. What we saw were a bunch of yellow gravel in their tubules. And it turned out it was methotrexate, and it became obvious what was happening. The drug was precipitating in the acid urine environment. But that was sort of the beginning of the methotrexate studies. And personally, I don't think we teach pharmacology very well anymore. What made you want to go to high dose methotrexate? Well, interestingly, I was particularly interested in-- Joe was trying head and neck cancer. There was almost simultaneously an article from Frye and Isaac [? Jurassi ?] about adjuvant therapy of osteogenic sarcoma. And there were several interesting things about that. One is that it turned out that 12 patients weren't all patients with osteogenic sarcoma. But prognosis of those patients wasn't apparently obvious. But there seemed to be some success with it, and there was a lot of toxicity that they didn't really know how to deal with. And so I started doing pharmacokinetic monitoring in patients that we had that were on the treatment. And then when they went into renal failure, they just didn't clear the drug. The drug was hanging around for many days and they were getting this horrible toxicity. So we got into this business of why the renal toxicity and the need for hydration and alkylization, particularly. And so first of all, I have to tell you I blamed you for much of my first year as a Fellow, because we had to draw the blood. So there were no study coordinators. Dr. Frye would just run around at all times of day and night drawing blood on patients for getting high dose methotrexate. And I still mumble under my breath when I hear your name. Well, you don't have to do all of that now, but you know, in those days we were trying to get a more complete profile, so we did. There was a woman there at the Farber that was doing similar work. I can't remember her name. Sue Pittman I think, right? Yeah, Sue Pittman. That's right, that's right, that's right. But that was certainly the introduction to the anti-folate. And then I got into a very interesting area of polyglutamation and how it changed the potency of the drug and led to retention, and it was an important determinant of response. That was quite an interesting area of research. Were you the first to report amplification of DHFR? No, that happened in 1978. I was working on MTX at the time and we had noticed that you could select highly resistant cells in culture. But then we were interested in knowing why, and Joe and Joe Bertino had described the fact that increased dihydrofolate reductase activity was found in this circumstance. But the actual demonstration of amplification in mammalian cells was done by Bob [? Shimke ?] when Joe was on a sabbatical with him. And they had a medical student working in the lab on that on that paper, and that was Dan [? Haber ?] actually. Who came back to-- Who is now the cancer center director [INAUDIBLE], right? Yeah, he wrote a key paper. So we had, at the time when that came out, we got interested in that. And we stuck radiolabeled methotrexate in the culture with some tumor cells and found these odd migrating entities that turned out to be polyglutamate. So that led to the whole issue of what were polyglutamates and how did they change the biochemistry? And that was quite interesting, and then actually at the same time we saw a patient. It was a young man who came to NIH with non-Hodgkin's lymphoma and was treated with high dose methotrexate. I can't remember. I think he had CNS involvement or something like this. We found evidence of gene amplification in this patient. So it was actually the first demonstration that gene amplification occurs in people on the drug. There are a lot of interesting things that were happening at that time. How was translational medicine before it was called translational medicine? That was the nice part of NIH, you know? The emphasis was on the labs working with the clinics, and particularly with physician scientists. So, you know, we were one of the few places where our Fellows were expected to work in labs in their second and third years, and they did, and we had a wonderful group of Fellows that came through. The first guy that worked on polyglutamation of MTX was Rich [? Shilske. ?] Who is now the chief medical officer of ASCO, and many, many other accomplishments after that. Right. But many-- Actually, I'd like to change gears for a minute, because I know you had a lot to do with the development of paclitaxel. And I always found that story interesting that, you know, it was in the bark of the Japanese yew tree, which had to do with ultimate supplies. But also the first phase one trials, which some of that was done at the Dana Farber when I was there. Can you just walk through the history of paclitaxel? I think our listeners would love to hear this. Well, it was an accident of history. Believe me. The thing started in 1964, when a group at the research triangle, a chemist, isolated this compound from the yew tree. And they didn't actually know what it was, but it was cytotoxic. And it was an anti-mitotic, and it took him seven years to figure out the structure. So finally in 1971 a guy named Ronnie from that group published the structure. It was a ridiculously complicated structure, And nobody could synthesize it, at least at that point. It hung around in the lab and nobody was interested in developing it, because it was such an odd molecule. It was insoluble. Nobody can put it in solution. So it really wasn't an attractive pharmaceutical. And the thing that happened was, in 1978 or 1979, we had a very hot drug that was called maitansine. And we were very eager to put this into the clinic. And it was an anti-mitotic also, and very, very potent drug. And so Dr. DeVita asked me to personally shepherd this thing and he told me that he didn't want it to fail. And so I put it into patients and it was terrible. And I kept telling him, this is not going to work. He said, it's got to work. He was pretty persistent. Well, it didn't, and he was very disappointed. So was I. And the fact is, we had nothing else to put in the clinic at that time except for paclitaxel. So we said, oh, well, we'll try it. And we put it in a lipid emulsion. It was like putting it in engine oil or something, but it went into the clinic in several places. Peter [? Wernick ?] did it. Einstein. I guess you guys did it at the Farber. And it was causing all sorts of hypersensitivity responses. It looked impossible. And it took about, I don't know, four or five years to get it into a regimen that was tolerable. And there had been responses. The first response was in melanoma, so we were all excited about that. That was the usual circumstance in those days that, when you took a drug into the clinic, melanoma would be the first response. And no one else from melanoma. Everywhere was-- and so but then Peter began noticing responses in ovarian cancer. And a regimen was worked out with antihistamines so it was reasonably tolerable. And finally in 1991, which was eight years after it went into the clinic, we finally decided, well, it was time to license it to industry. There was no patent, but we did it under a co-operative research and development agreement. And the only company that was interested in the US was Bristol-Myers. Everybody else said, this is ridiculous. Nobody wants this drug. And it was too hard to make it. You had to make it from the bark of plants and it was insoluble and it caused hypersensitivity. So they took it. And about a month afterward there was a report from M.D. Anderson saying that it was active in breast cancer. And at that point it just took off like a rocket. And, you know, tried in all sorts of different diseases. Was active in lung and bladder and-- I can't remember all the other things. Head and neck. Anyway, it became the first billion dollar drug in the cancer drug industry. And I think, you know, there are two things that really set off industry to be interested in cancer. One was that, the fact that you could actually make money on it. And the second was the notion of targeted therapies, which was growing at that time. So to my knowledge, this is the only time somebody at the NCI had to work with the US Forest Service and the Bureau of Land Management regarding a new drug. Can you tell that story? Well, yes. The only place where you get the raw material for the drug was from the US Forest Service. And so Texas plants were being sort of cut and burned because they were considered scrub and not worth anything as lumber. So they were cooperating. And finally when we licensed it, Senator Ron Wyden, who's still in the Senate from Oregon, got interested in this whole thing. He said, why isn't the government making money on this license? Why did you license it to Bristol-Myers and you didn't you didn't ask for anything back? And we said, well, you know, that's not the function of NIH. We didn't have a patent. I guess we could have asked for a slice of the pie, but we didn't because no one else wanted it. We really were trying to give it away. And he was giving us a really hard time at this hearing. And then the key thing that happened was a woman who was a forest ranger with ovarian cancer, we found this woman, and she testified to how much good it did for her. And that sort of stopped all the fuss about the license. And we actually, it was the first drug where as part of the licensing agreement we had the chance to fix the price or agree to the price that Bristol-Myers fixed. And the government never has done that since that time. Of course, this was a circumstance where we sort of owned the information, so they had to listen to it. But they set the price at $2,000 a course. And we consider that pretty high, but it was sort of equivalent to what other drugs were costing at the time, so we let that go by. But ever since then, the price of drugs has just escalated remarkably. I hope there are some young people listening, because this story, in my opinion, the story of trastuzumab again, I think people think that these things just happen because the system makes them. And my experience is they happen because the drug or the treatment gets a hero, gets a champion. Ultimately the science has to prove it works, but I'm sure lots of people wanted to walk from Taxol. You know, everybody thought it was a dog. Because it was, you know, caused hypersensitivity, it wasn't all that active in the initial testing, and it was really hard to make the stuff. Well, the same thing is true with platinum I did my residency at UT Southwestern with Donald Sullivan, who's the chair of medicine. He was a renal guy, and a patient with metastatic-- and I had gone to Indiana. So Dr. [? Einhardt ?] taught me how to give it. So I had a patient come in with widespread testicular cancer, I wanted to give him cisplatin, and Dr. Sullivan wouldn't let me do it because it would hurt his kidneys. I said, Dr. Sullivan, he's going to die if we don't do this. And he said, he'll die anyway. And so I did it behind Dr. Sullivan's back and I got a complete response. Fortunately in those days the residents didn't have a lot of oversight so I could do what I wanted to do. There were a lot of people that thought these drugs should be shut down, and it took the courage that you guys had back at the NCI and other places to push them out. Don Sullivan was very anti cancer chemotherapy for the rest of his life. And it was odd for me, because I actually had a relative who was on his faculty and I went down there a couple times to talk. And I always felt very uncomfortable telling him that we were accomplishing something. Because his concept of success in science was getting an RO1 in your lab. Yeah. He finally came to terms because [? Shelfke, ?] myself, Fred [? Lemaitre, ?] and a number of us went into oncology and had been reasonably successful. And I think he decided that it was worthwhile after all. But it wasn't easy for him. We lost him a year ago. I still miss him. Yeah, he was an amazing guy, but he really did have a hard time believing in cancer. So the other question, I wanted to change gears a little bit, because I know just about the time you became the director of the DCT was when the AIDS epidemic was exploding in the early 1980s. That must have been a very confusing situation about who should be in charge of this at the NIH, which institute, and how you approach it. Can you give us some background on that? Again, it was really a crazy time. Because I remember one of the first patients that was identified as having AIDS was a person admitted to the immunology branch at the NCI. Not the medicine branch or the clinical branches. It was a patient who had disseminated tuberculosis and it had no CD4 cells. And, you know, everybody said, oh my god, what is this? This is really a weird, weird circumstance. And then other people began reporting this from San Francisco and New York. So we actually, DCT, the reason we got involved was because of Bob Gallo. Bob Gallo had discovered the HTLV1 virus, which was causing this lymphoma in T cells. And we suspected that this might be a syndrome caused by a T cell virus. So in 1981, really quite early, we convened I think the first meeting about the biology of what was called HTLV2, I think, at the time, or three. I can't remember which one it was. But at any rate, there were a cadre of people at NIH that felt that it was caused by inhaling gases or, I don't know, their various weird theories about it. But this theory that made sense to us was that it was caused by a virus. So Sam [? Brodeur ?] was collecting samples from patients and brought them over to Gallo's lab. And of course Gallo mixed those samples with the French sample and found virus and then made a test kit for the virus, which was really a key event in beginning to control the epidemic. And because of all that work going on at NCI at the time, we were asked-- we had the only drug development system at NIH. We were asked to, well, look, can you set up a drug development system for this? And Sam [? Brodeur ?] set up assays in infected T cells and showed that certain nucleocyte analogs could stop the virus from replicating. The first one was ADT. And his first study was, I think, was 16 patients with AIDS in which he showed that the T cell counts recovered and people didn't die. And from that point on, we were getting significant funding for doing research on treatment development. And it was it was done in conjunction with NIAID and Tony Fauci. What Tony did is he delegated a fellow to work with us and sort of be the liaison. And the first fellow that did that was Margaret Hamburger, who became [INAUDIBLE] FDA subsequently. And, you know, subsequently, four other people from our division-- well, actually one from NGH, became directors of FDA. Ned Sharpless most recently, and then Steve Hahn, who was a Fellow in the medical oncology group at NCI. Yeah, he's just been named. It was, you know, an unusual breeding ground for people interested in therapeutics. That's interesting. You know, I was a third year resident at UT Southwestern. I was at the VA in March and a young man was admitted to our service. He had been a Vietnam veteran and he had red splotches all over him, so I called a dermatologist who biopsied it. And I got a page from the pathologist and I called him back and he said, you have mislabeled the samples. And I said, what do you mean? He said, well, this says it's a 37-year-old man. This is something I've never seen before, but I looked it up and it's called Kaposi sarcoma, and that only happens in old men or people from Africa. And I said, I don't think we mislabeled things. And I think he was probably the first man in Dallas to be diagnosed with this. Because just as the MWR and the new journal paper came out a few months after that. So again, for the young folks listening to this, and we've already hit this a couple of times, it's one or two patients that pique your interest that often change the world in terms of, gee, I wonder why that happened. Yeah, absolutely. I mean, you know, a lot of this is an outcome of the fact that you have research people as physicians who are working with patients, and then they ask questions. Yeah. One of the things I've carried forward, Dr. Frye used to always say, think like a scientist. Think like a doctor. And ask yourself, so what? And I know you do that, because again, you've already told us today and I've seen you do that in other places. You know, so what? Why did this happen to this patient? Why did that happen, yeah. What in my lab actually will change that? And you guys did that in spades, I think, 40, 50 years ago. It's pretty amazing. Yeah. Well, I [INAUDIBLE]. [INAUDIBLE]. Go ahead. Go ahead. No, it's really happening a lot now, you know, in terms of recognizing subsets of diseases. We used to think that non-small cell lung cancer was just one disease. Now it's 20 diseases. It's amazing, you know? It's amazing, you know, as science progresses, you begin to understand the complexity of cancer. And then therapies become meaningful. Yes, I agree. It's so nice. And so I wish, you know, we were curing people. But we are making a difference, and least we're understanding it a little. I agree. Anyone who has not heard or read Bruce Johnston's ASCO presidential address should do so. Because he did point out exactly what you just said. He had a pie chart, and 10 years ago the entire pie chart was chemotherapy for metastatic non-small cell lung cancer with little or no success. And now the pie chart is well over half the patients getting some kind of targeted or immunotherapy. Yeah, it's pretty amazing. It is quite [INAUDIBLE] for young people that are listening to this, is that there are enormous opportunities for doing even better than we did. So we just made a start in this whole thing. OK. With that inspiring message, which I'm glad you said it, we've run out of time. Actually we come at the end of our time. But Dr. Chabner, I want to thank you on behalf of all of us who trained after you, who've learned so much from what you've done, and more importantly, the patients who have benefited from the stuff that you've contributed to the field. It's pretty remarkable and inspiring. I don't use that word too often, but it is. So thank you, and thank you for taking time today. I hope folks listen to this and say, I'm going to go back and make a difference here. Thank you, Dan. I have enjoyed it. It's been a wonderful time in this career. Yeah. Well, my pleasure. Until next time, thank you for listening to this JCO's Cancer Story, the Art of Oncology Podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.ASCO.org.
Dr. Hayes interviews Dr. DeVita about his role as Director of NCI and his time with CHOP and MOPP. TRANSCRIPT [MUSIC PLAYING] The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center. And I'm the past president of ASCO. I'm really privileged to be your host for a series of podcast interviews with the founders of our field. In this series of podcasts, I hope to bring appreciation of the courage and the vision and most importantly the scientific background among the leaders who founded our field of clinical cancer care over the last 70 years. I hope by understanding the background of how we got to what we now considered normal in oncology, we can all work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Vincent T. DeVita, best known as Vince. Dr. DeVita is generally considered one of the so-called Gang of Five, including Doctors Canellos, Young, Chabner, and Schein, who I've been trying to get on for this podcast in the future, all at the NCI, and who brought many of the concepts we now accept as standard into the clinic in the 1960s and '70s. Dr. DeVita is currently a Professor of Medicine and Epidemiology and Public Health at the Yale School of Medicine. I think it's also fair to say, Dr. DeVita was instrumental in the passage of the 1971 National Cancer Act. And I want to hear more about that as we get into this. He was director of the NCI and the National Cancer Program from 1980 to 1988 and then moved to Memorial Sloan Kettering Cancer Center as Physician in Chief and subsequently became the Director of the Yale Cancer Center in 1993. Among his many honors-- and I don't have time to go through them all-- but he has served as President of the American Cancer Society. And I think most dear to me, he was President of ASCO in 1977 and 1978. Dr. DeVita, welcome to our program. Nice to be here, Dan. I've done a little background. I know you grew up in the Bronx. And I know you went to William and Mary for undergrad and George Washington Medical School. And I also read what I didn't know, which is that you did your internship and residency at the University of Michigan. We're recording this just before the NCAA basketball tourney. And I have to say, go blue. We're all excited here in Ann Arbor about our basketball team. [LAUGHTER] What I'm really interested in is, were your parents physicians? Or what made you choose medicine out of the Bronx? Well, no, my father was a banker. And my mother was an interior decorator. So it was kind of a funny mix. But I think it's kind of peculiar. I was growing up, and my mother-- I tell this story in my book. My mother was kind of frightened by the fact that I really, as a seven- or eight-year-old kid, really thought the guy who delivered the ice-- in those days, we had ice boxes-- was terrific. And I wanted to be like Nunzi the iceman. And she panicked and said, no, no. You're going to be a doctor. And every time someone asked me what I was going to be, I just said I was going to be a doctor. And when I went to school, I decided I'd be a doctor. It was sort of Mama driving me in that direction. So you had a choice of being an iceman or a doctor [LAUGHS]. Right. I like-- I mean, biology was always a favorite subject of mine. So it was a good fit. And tell me about how you ended up going to the NIH and choosing oncology. Was that serendipitous? I talked to Bob Young the other day. And he said, fundamentally, he hadn't planned to be an oncologist and got to the NIH and liked it. Was that your role, or did you know you wanted to do cancer from the start? No, I was going to be a cardiologist. In fact, when I was a first-year resident, I did cardiac catheterizations and was a co-author on a paper that for a long time was well-cited in the field. So I applied to both the Heart and Lung Institute and the Cancer Institute. And those are very competitive positions. And I had an interview with Robert Berliner, which didn't go well [LAUGHS]. So I didn't get invited to the Heart Institute. And I went to the Cancer Institute. And when I walked in, Dr. David Rall was the chief of the pharmacology branch. And I asked him if I could work on the pharmacology of digoxin. And he, wise person that he was, said, sure. Go ahead if that's what you want to do. And I was surrounded by people who were working on anti-cancer drugs. And I actually became fascinated with them. And it was only a few months, because I was also on the wards at the time, that I said, oncology is the way to go. It was an exciting new field. It was kind of a funny field in those days. But I found it exciting, so I switched. So just to give you a plug here, I think many of us know that you wrote a book, The Death of Cancer, published a couple of years ago, co-written with your daughter Elizabeth by the way. But in it, you described a number of things. And one of those that I loved were your stories about Gordon Zubrod. And I trained with Dr. Frei at the Dana-Farber. He always had great things to say about Dr. Zubrod. And I wonder if you could tell the folks listening in who he was-- I think most people don't even know that-- and the impact he had on our field. Yeah, I used to call him the great umbrella. The field was very controversial at the time. And so the people who were doing things like saying, I'm going to try to cure this cancer-- leukemia in Frei's case and Hodgkin's in our case-- were considered just a little bit this side of insane. He was somebody who was distinguished. Now, Frei had-- Zubrod had been at St. Louis as a professor and also at Johns Hopkins. And he was a very distinguished-looking man and a very polite, careful man. And so he used to provide sort of the umbrella for all of us, so that [INAUDIBLE] he'd take the heat. And we could go on and do our work. So he was-- he did enormous number of things. I mean, the whole clinical trial structure was established by Gordon Zubrod. The phase I, II, III trials was all done in a paper by Gordon Zubrod in the late 1950s. So I think he was just a guy who had foresight and was a great leader. I ultimately took his job. He got tired of bucking the bureaucracy and retired and went to Florida as the director of their cancer center there. So I got to know him pretty well. And like Frei, I have great admiration with him. I mean, it's interesting how we take phase I, II, and III for granted. And when he came in, and not too long before you came in, those things weren't-- nobody really knew how to do this stuff. Doctors Frei and Freireich were already at the NCI when you got there, correct? Yes, indeed. Yeah, they were. Yeah. And so they must have been inspirational. They were, and especially Freireich. Freireich was always on the wards. And Tom didn't come over to the wards very much. He was sort of the direct-- he was chief of medicine. And Freireich was the chief of the leukemia service. So we saw Freireich all the time. Tom came over once in a while. And Jay was a super doctor. And it was very hard to stay ahead of him. You'd get an x-ray on a patient. And he'd call you up 20 minutes later and tell you what it was. He was already down looking at it. So you had to stay on your toes with Jay. And of course he was, as everybody knows-- Jay-- he was a bold guy, who-- I mean, he looked like he could walk through a wall. So he frightened a lot of people. But he was an inspiration. So I'm always grateful for what Jay Freireich taught me. There's a great story in your book, that Dr. Frei has told me as well, about the first platelet transfusion at the NCI. Can you elaborate on that? I think most folks don't know about that story. Platelet transfusion was, again, one of those radical departures. But Freireich reasoned that we were losing more people from bleeding than we were from leukemia. So he worked out a way of plasma pheresing people and collecting platelets. And we didn't have a lot of the expertise we have now. And they came in quart bags. I mean, they were plasma bags that were huge. And we were treating little kids. So they were-- throwing them into heart failure was a problem. So it was pretty radical. And he was told to stop doing it by the clinical director at that time. And in fact, he was told that if he didn't stop doing it, he was going to be fired. And he told me-- he said, I went back to my office, sat down, and thought about it. And I decided I didn't want to work at a place where I couldn't do that. So I just kept on doing it. And the person who said he was going to fire him never did. But that was Jay Freireich. [LAUGHS] He believed so strongly in it. And when I went to Yale right after I left the Cancer Institute-- I finished my residency up there. And I told them-- when I saw leukemia patients who were bleeding-- and I said, what you should do is platelet transfusions. And they said, they don't work. And I said, I used them. And I saw them work. So I think we're losing patients unnecessarily. It was just very controversial. So eventually I left the program. I was going to take a residency and then a fellowship in hematology there. And I decided to go back to the Cancer Institute where these adventurous things were going on. Times are different now, of course. Dr. Frei once told me a story that he-- you may have been with him-- that he was making rounds in the clinical center. And in those days, apparently, the adults and the kids were in the same ward. And there was a child with essentially no white cells, who'd been induced for leukemia, and a man next to him with CML. And so-- and actually, when Dr. Frei told me this, I kind of said, I don't think I want to hear this story, because he said, well, you know, the kid didn't have any white cells. And the guy next to him had way too many white cells. So [LAUGHS] I said, tell me you didn't do this. He said, yeah, we took platelets out from the guy and gave them to the kid. And the kid got better for a while. It was really exciting. I thought, boy, you don't see that anymore. Yeah, I mean, it was a very reasonable thing to do, because the white cells in a chronic myelogenous leukemia patient work very well in terms of fighting infection. Yeah. So there was no reason. And the kids, otherwise, wouldn't survive. And so, yeah, I was there when we got these-- we gave these. I mean, they weren't easy to give, because they stuck in the lungs. And we didn't have HLA matching at the time. So they were-- a lot of them were mismatched. But for a while, they were effective. And then we went to collecting white cells from normal people. But the white cells had not worked as well as platelets had worked. Platelets have been a lifesaver. Now it's a couple of hundred million dollar business each year now. So it's routinely done, as many things that Jay started are routinely done now. Of the many things for which you are credited, I think it's the use of combination chemotherapy for Hodgkin's and then subsequently non-Hodgkin's that is one of your lasting legacies. There must have been a lot of drama around doing that. I mean, I think we all just assume you're going to start protocol. You write the protocol. You get funding for it. And you go forward. But can you give us some stories about sitting around at night and thinking about how to do this? Or how did you choose those drugs and why and how to give them and the obstacles that were involved? Yeah, actually, it was a very complicated process. And we didn't have the information we have now. What we had was-- I was doing this with Jack Moxley, who left active medicine and became a dean after he left the Cancer Institute. But we're still in touch. And Jack was working with [? Sy ?] [? Perry ?] using the new isotope, tritiated thymidine, looking at the bone marrow of CML patients and also of mice. And I was doing the same thing with the leukemia 1210, which was a model that we used for chemotherapy all the time. And what we were trying to do was figure out the kinetics of human versus mouse marrow, so we could develop schedules that humans would survive. We quickly found out that you can't use the mouse as a model, because their blood cells went through a kinetic phase about half the length of humans. So you had to schedule in a different way. So we worked that out. And then we looked at very simple-- something that people really ignored is that when you give a chemotherapy agent that is toxic to the marrow, you don't get abnormal blood counts right away. For a week, you'll have a normal white cell. And then on day seven or eight, it begins to fall, because the storage compartment in the marrow works well for about a week. And then there's no replenishment. And the white count falls. So between the two, looking at the marrow and looking at the white cells in the periphery, we came up with a schedule for MOPP. And then the other things were simple. We just decided that you'd have to have three or four drugs that worked by themselves. There had been people doing combination chemotherapy before-- Tom Hall in Boston and [? Alan ?] [INAUDIBLE] at Yale. And their rationale was they're looking at a sequential biochemical blockade. But they ignored whether the drugs actually worked against the tumor, assuming that if you gave them together, that the biochemical blockade would dominate. And it didn't work. In fact, it was very discouraging. But we decided the way to do it was take drugs that had some activity in the disease and use them together and use them in full doses in the schedules that we worked out because of the prior work I was telling you about. So it took a while to put that together. And then Jack Moxley and I used to do this at a bar in Georgetown called the Lehigh Grill, where we used to-- my cardiology desire-- I used to go to Georgetown where there was a wonderful cardiologist Proctor Harvey, who used to hold Thursday night sessions. You had an auditorium that was wired. So you could hear heart sounds. And after that, we'd go to the Lehigh Grill. And we sort of put together the protocol. When we presented it to Tom, he thought it was a good idea. But the other people around him thought it was insane and really tried to stop it. Tom Frei? Yeah. Tom Frei, yeah, yeah. Well, Tom was supportive. Yeah, Emil Frei was his real name. But everybody called him Tom. Yeah, he was supportive. But the people around him and my immediate boss was very much against it, because he thought it would interfere with the protocol that they were doing and so forth. So Tom worked out a solution worthy of Solomon. He said, OK, we could do-- the magic number for phase I trials in those days was 14. If you got nothing in 14 patients, then you didn't go any further. So we could do 14 patients with the first protocol, which was called MOMP-- M-O-M-P. And we had to do the workups ourselves. We couldn't use other colleagues to work up the patients. And we had to go get the patients ourselves. So Jack Moxley and I did all those things. And the results were very encouraging. And then Jack left. And I sat down and decided that we'd put procarbazine. I was working on procarbazine. It was then called [INAUDIBLE]. And I was working on it and doing the pharmacology in the phase I study with it in Hodgkin's disease. It was a promising candidate. So we put it in. And that became MOPP. Also in those days, six weeks of therapy was it. They didn't get more than six weeks. We reasoned that the marrow problems would be acute. But you'd have to give it probably for a long period of time to affect the tumor. So we gave it for at least six months or to a complete remission plus two months. And we assumed that there were cells left after we couldn't see them. So it was a lot of good thinking that went into it that turned out to be correct, because most of the-- since then, a lot of protocols follow the same sort of routine. And it really works for a lot of cancers. But it was controversial. I went to the AACR meeting. This was before ASCO. And I presented it as an abstract. And David Karnofsky, who was sort of a god at that time at Memorial Sloan Kettering, just tore me apart. And what was I doing using the term complete remission for a solid tumor. He said, that was a term that was used in leukemia. Now, I didn't say it. But I'm thinking, the reason you use them is you can get complete remission. So we had complete remissions. And I was kind of shaking with the microphone in my hand at the time. So it was a scary but it was a good experience. I have to say-- So it just gives you an idea that people were not receptive [INAUDIBLE]. Those of us who are junior to you can't imagine that you were intimidated by somebody else [LAUGHS]. Well, I was a youngster, then. I was-- Jack Moxley and I, I would say, thinking back, we were cocky. But the big guys in the field could scare me. And Zubrod was a-- I mean, Karnofsky was a big guy in the field. Yeah. He just had a hard time getting out of the leukemia mind frame. And so of course, we've used complete remission since then in any kind of solid tumor where you can get one. In your book, you have a great quote that you presented somewhere. And Dr. Frei was there. And Wayne Rundles was there. Wayne, of course, has been at Duke for 100 years. And he said, do your patients speak with you after you're done? Well, Wayne Rundles-- when he first saw the MOPP protocol, Wayne Rundles said, that's nonsense. He said, I get the same thing with nitrogen mustard by myself. Well, nobody had ever got that with nitrogen mustard. So we actually had to set up a controlled trial and do it and prove that MOPP was better. So when I presented it when we were first starting it-- at a meeting. Tom had arranged this meeting with all the bigwigs in the field. And when I presented it at that, everybody was sort of quiet. And then Wayne Rundles raised his hand. He looked pale. He raised his hand and said to me, Dr. DeVita, do your patients speak to you after you do this? [LAUGHS] So he-- a few years later when we were obviously getting good results, he invited me to grand rounds. And by then, we were good friends. And I was up on the podium. And after I gave the talk, he was sitting down below smiling at me. And I said, Dr. Rundles, if you remember, you asked me if your patients speak to you when you do this. And I can tell you that they do for a lot longer. So it was fun. But it was fun. He was a good friend by then. And I had great respect for him. Actually, he was a very nice man. He was. When did you start thinking that you had a success? Was it during those first 13 patients or 14 patients that you treated? I mean, was it obvious right away, or did you start [INAUDIBLE]-- Well, it was obvious-- --you were in the wrong place? We put-- no. We thought it pretty early, because we were worried. We put patients in reverse isolation. Nobody knew whether you were going to kill them if you gave them all these drugs together. And it turned out the first surprise was, yeah, they had the usual toxicity. But it really wasn't that bad. So it was doable. And the second was-- we had a small number. But we had-- something like 80% of the patients went into a complete remission. And I think nobody had seen that. Now, the question was, how long were they going to last? So we were optimistic. And when we put patients on it, there was no cure for them at that time. And we said, we're optimistic that this is going to be something that will last. But we don't know. And then by three years, it looked pretty good. And I think I presented the first abstract four years after we started. And by that time, we had relapse-free survival curves. And again, nobody before that time had presented relapse-free survival curves in any of the lymphomas. So by then, by four years, I think we felt we had probably cured some patients with the disease. I asked Bob Young this same question. Did you feel a sense of history at the time, that this was really historical? Or did that come later when you looked backwards? I think what people don't realize about those days is neither Freireich nor ourselves were treating leukemia and Hodgkin's disease. In other words, we weren't out to develop a treatment for those diseases. We were out to prove you could cure cancer with drugs, because nobody believed it. If you said that, they really thought you had gone balmy. So we were out to look-- so we knew if we could do it, it would be historic. So we were excited when we looked like maybe it was going to happen. By that time, when we had first reported it, the VAMP program that Freireich did, which was an historic program-- he only had 17 patients. And they actually never published a paper on VAMP. And I asked Jay why they never did that. And he said because he didn't think they would accept it anywhere. So but by that time, they were getting about a 50% complete remission rate going four or five years. And they were thinking they're curing leukemia. And we were getting 80% complete remission rates. So I think everybody felt that we were going to prove that you could cure cancer with the drugs. And we did. So yes, in a sense, we set out to do something that would be historic. And so when it happened, I think, it is. It was a sort of a door opener for medical oncology in Hodgkin's disease. I'd like to turn now for just a minute to your role in politics. You were pretty instrumental, I think, when the National Cancer Act was signed in 1971. And that also sounds like a TV drama to me. It sounds like-- and I know this anyway, but in reading your book, it was not clear that was going to get through. Can you give us some of the playground behind that and Mary Lasker's role and how that happened? Well, Mary Lasker played a big role. The MOPP program actually played a big role, because Mary Lasker was sort of working in the background. Cancer was always a cause for her. But when we did the MOPP program, there was a guy named Luke Quinn, who she had hired to be a lobbyist, who was sort of hidden in the American Cancer Society so they wouldn't realize it was Mary Laskers' lobbyist. And he was referred to me by Sidney Farber. And I didn't want to take him at first, because he was diagnosed as having gall bladder cancer. And I said to them, you know-- I said to Sidney Farber, I don't really treat patients with gall bladder cancer. And there was silence on the phone. And he said, (SOMBER, COMMANDING VOICE) you will take this patient. [LAUGHS] So I took the patient. And when I examined him, when he came down and I examined him, he had adenopathy in both axillae. And gall bladder cancer just doesn't do that. So I had to do another biopsy. He was not a pleasant guy. So it was not easy to do these things. I had to get another biopsy. And it turned out that my pathologist at the time, Costan Berard, when he compared the biopsy, he said, it's a lymphoma, clearly. It was a diffuse, large cell lymphoma. What they had done is, because Claude Welch did the surgery-- a very famous abdominal surgeon-- and he said it was gall bladder cancer, that the pathologist sort of assumed it was. And it was a compression artifact. Long story short, he went into remission. And Mary Lasker went gaga. Wait a minute. We got something here. And that was what pushed her to get her friend, Senator Ralph Yarborough, to put up a committee on cancer to come up with the Cancer Act. And-- So it must have been quite a day when President Nixon signed that. Yeah, well, it was-- I wasn't at the signing. I wasn't high enough up in the chain to be invited to the signing. But yeah, I have all the photos of him signing it. And later when I met him-- I have a picture in the book of he and I shaking hands and him looking like he's having a roaring laugh. People ask me what I said that was funny. And I have no idea. But when I asked him, I said what is your greatest achievement as a president? He said two-- opening up China and signing the Cancer Act. So he was-- Really? Yeah, so I think he was proud that he did that. That's a great story. Actually, the other story I had not heard, but read in your book-- I'd like you to tell me about your lunch with Mr. Featherstone. [LAUGHS] Featherstone Reid, his name was. Well, this was a very-- this was a regular occurrence. Mary Lasker, when she came to town, would stay with Deeda Blair, Mrs. William McCormick Blair, who was a Washington socialite and had a lovely house on Foxhall Road. And they would have lunches and dinners. And they always arranged it so that people-- the scientists sat next to somebody with influence. And this is how they influenced the Congress to put more money into the cancer program. So one time, I got a call in the morning from Deeda Blair, saying, I'm having a lunch. We'd like to have you there. And I said, gee, I-- it's too short notice. I can't do it. And she said, well, Mary really wants you to be there. Mary was hard to say no to. So I rearranged my schedule, drove down to Deeda's house. And there was a big black limo sitting in the front of the house. I went in, and they introduced me to Featherstone Reid. I had no idea who he was. And every time Mary would say, we want more money for research with leukemias and lymphomas. Vince, tell him about what's going on. And I would tell him about. At the end of the lunch, he left. And Mary and I sat down on the couch to have a cup of coffee. And I said, Mary, who is Featherstone Reid? And she said, he's Warren Magnuson's driver. And when she saw the shock on my face-- Senator Warren Magnuson was the chairman of the appropriations committee of the Senate. When she saw the shock on my face, she said, wait a minute. When Mrs. Maggie-- he takes Mrs. Maggie shopping during the day. And Mrs. Maggie-- he fills her with all this information we're giving him. And then Mrs. Maggie is the last person to put her head down on the pillow next to Warren Magnuson. This is the way she worked. She would take someone like Magnuson, who was a good friend, but she would surround him with extraneous people who would say the same thing. So it was sort of like subliminal stimulation for him. He was always hearing these positive things. And then he supported the program. She was a piece of work. I never got to meet her. But it sounds like she was a force of nature. She was. And of course, the Lasker Award is now named for her and her husband and sort of the American Nobel Prize. She's had such [INAUDIBLE]. Yeah, and our crew won it in 1972-- Frei, Freireich, myself, and other people for other things. So I'm very fond of Mary Lasker, obviously. It's just a wonderful story. And I got to know her pretty well, so. I have one other question. And I'm not sure you'll want-- if you don't want to go off on it, we can edit it out. But in your book, you talked about Howard Skipper and Frank Schabel. And Dr. Frei used to talk about them all the time. And I think it's worthwhile to bring them into the history of what we do. Did you actually work with them or collaborate with them, or just base some of your ideas on what they had in mind? When I was starting at the Cancer Institute, I thought Schabel worked at the Cancer Institute-- I mean, Skipper worked at the Cancer Institute, because I would be working in the lab. I was doing the tritiated thymidine studies on L1210 mice. And he would be looking over my shoulder. He was doing the similar studies, but he was just doing it with cell counts in the abdomen of the mice. And he thought that was good enough. And he was there at a weekly meeting we had, which George Canellos named the Society of Jabbering Idiots. It was a great, great meeting, actually. [LAUGHS] And he was there all the time. And my view and Tom's view differ a little bit on Skipper. I think he was a real driving force, that he did the studies in mice that we were doing in the clinic with people. And he actually-- in 1964, he wrote a paper showing that you could cure L1210 leukemia. It was the first example of curing a mouse with leukemia. And I think-- so it was sort of a feedback mechanism between the Cancer Institute and the Southern Research Institute. So and he did-- he used to do these booklets. And I think he published hundreds of these booklets. Some of them, we convinced him to actually publish as papers. But I have the collection. There may be 100 booklets he wrote. And he would take a concept that we were working on and then work through it in mice. It was very, very important. And he was a wonderful person. His only problem was he smoked like a chimney. But he was-- I liked Frank and Howard. Yeah, Dr. Frei had the entire set of monographs on his bookshelf in his office and would encourage us to come in and borrow them and read them and come back. And frankly, he basically predicted what you've done with combination therapy. He predicted adjuvant therapy working. There were just a number of things he saw in these mice that we've gone on to apply in the clinic. It's pretty remarkable, I think, so. Yeah, I mean, it's not only he predicted it. But he actually showed the concept worked in mice. So as we know, mice and human are very different [INAUDIBLE]. There was a guy in Boston, Stuart Schlossman, a very fine scientist. And he didn't like mouse models. And when asked what he would do when he saw a tumor-bearing mouse, he would say, I would step on it, because he didn't believe mouse models. And but Frank and Howard did experiments and made allowances for the difference between humans and mice. So it was always good to know. I mean, I have the summary he wrote on Hodgkin's disease after he saw the MOPP program. So I think they're very instructive booklets. So I kept them. Like Tom, I think that we sort of live by them. Well, thanks for discussing them. I think our listeners need to remember these two guys. They were great. We're running out of time. I've really just touched the surface of what you've done and contributed to the field. And the people you've trained is sort of a who's who of oncology, frankly. But at the end of the day, what's your-- I'll ask you the same question you asked President Nixon. And that is, what is your legacy? What do you want people to remember that Vince DeVita did? I get asked that question a lot. And I don't have one thing that I can say. I mean, I've been lucky in my career that I've had a chance to do many things. Being the Director of the Cancer Institute was wonderful. You could sit on top of the whole field and just sort of scan it and see what's going on. And it was very important, because you've become the spokesman of practicing physicians at the same time. MOPP, of course, was important. Putting out the first comprehensive textbook in the field and watching it-- we just came out with the 11th edition-- is also very exciting. So there-- we were the first to successfully treat Pneumocystis carinii pneumonia. And we reported it in a paper in the New England Journal. I mean, there were a lot of things. I'm best known, I think, for MOPP, probably, and the principles of MOP, which I'm very proud of. But there's so many that I have a hard time. I like opera. And people ask me, what's my favorite opera? And I usually say, it's the one I just saw. It's very hard for me to pick one opera. There's so many that I like. So I'm not dodging it. But I just never can say, well, it's this. That's very fair. Frankly, I think, without your contributions, I probably wouldn't be sitting here doing what I do. And I think there are thousands of us who would say that. So we're-- Well, that's very flattering. Well, not only are we appreciative, more importantly, there are a lot of people who are alive who wouldn't have been without what you and your colleagues did at the NCI that so many years ago, so-- [INTERPOSING VOICES] I was involved in the training of 93 medical oncologist. At one time, something like 40% of all the [INAUDIBLE] directors were our graduates. So they have gotten around. And that was good for the field. They went out with the same principles we were developing at the Cancer Institute, so that's very gratifying. Have you kept in touch with any of the patients that you're treated back at the NCI? I talked to Saul Rosenberg. And he told me he still sees people that he treated 30 or 40 years ago when he first moved to Stanford. We're writing a paper on the 45-year follow-up of the first 188 patients. Again, nobody has 45-year follow-ups. And we called every one of the survivors. And there's something like 60% or so of the complete remissions are alive. So I talked to some of them. But we had a nurse talk to a lot of them. And I got messages from them after the call. And some of them still contact me, after sort of an anniversary of their treatment. So yeah, I've kept up with them. The gratifying thing is most of them are suffering from the same illness as most people who are getting into their 70s or some of them 80s. They have hip problems and so on and prostate cancer. But there doesn't seem to be any really major increase in anything in these long survivors. Now, mind you, these were patients who got MOPP as their only treatment. And so when you see second tumors in these kinds of patients, it's usually patients who got radiation therapy plus MOPP. So these patients who are 45 years had just got MOPP. And they seem to be perfectly fine. That's remarkable. I love your comment that they are getting the same illness as the rest of us get as they get older. That's great. Yeah, we don't cure bad hips and bad knees and-- Yeah, we can't cure old age. When I was at the Dana-Farber, I had a patient who had been one of Sydney Farbor's original patients from the early '50s. And by this time he was obviously an adult. He was older than I was. And he was fine, as you've said. Although he said Dr. Farber kept treating him and treating him and treating him. And then finally, when Dr. Farber passed away, someone else picked up his chair. And they said, why are you still getting this? And they stopped it. Yeah. So he got a lot of treatment. I had one of Freireich's VAMP patients. She was a girl in her early teens. And she was a wildcat. But she had had something else, and it failed. And she was one of the first patients on VAMP. And she went into remission. And she stayed in remission. And I followed her for many years. She went to college. She got married. She had children. She brought her children in to see me. And last time I had any follow-up with her, she was in her 60s. And she was one of the really first long survivors of that particular program. So it's really neat to see these patients. And it's not rare for me to go to a meeting and have people walk up to me and say they got MOPP 25 years ago. Someone else gave it to them. And they're alive and well. So that's one of the great gifts of having a chance to do this kind of work. What a privilege. Well, I think we need to end. Again, I want to thank you for being on with us today and filling us in with some of these stories. Had really good feedback for my podcast series. And it's because of the people I've had on it. So thank you very much for all you've done. It's really good talking to you. And I look forward to listening to all your podcasts. [MUSIC PLAYING] Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcast or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
Dr. Hayes interviews Dr. Young about his time with CHOP and MOPP TRANSCRIPT Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Hayes: Welcome to JCO's Cancer Stories, The Art of Oncology, brought to you by the ASCO Podcast Network, a collection of nine programs, covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all of the shows, including this one, at podcast.asco.org. Welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm a medical oncologist and translational researcher at the University of Michigan, Rogel Cancer Center. And I've also had the pleasure of being past president of the American Society of Clinical Oncology. I'm privileged to be your host for a series of podcast interviews with people I consider the founders of our field. Over the last 40 years, I've really been fortunate to have been trained and mentored and inspired by many of these pioneers. It's my hope that through these conversations we can all be equally inspired by gaining an appreciation of the courage, the vision, and also the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and we can work together towards a better future for our patients and their families during and after cancer treatment. Today, my guest on this podcast is Dr. Robert Young. Among many designations he has, my favorite I think for Dr. Young is that he was considered one of the, quote, "gang of five," end of quote, I think self-named, who were responsible for developing the first curative chemotherapy regimen for Hodgkin's disease and non-Hodgkin's lymphomas at the National Cancer Institute in the early 1970s. Dr. Young is currently president of RCY Medicine, a private consulting firm based in Philadelphia. He was raised in Columbus, Ohio, where he couldn't get into the University of Michigan. So he went to a second-rate community college in Columbus called Ohio State. My bosses made me say it that way, Bob, here at the University of Michigan. Dr. Young: Not the correct way, The Ohio State University. Dr. Hayes: So he received his MD then at Cornell in 1965, followed by an internship at the New York Hospital. He spent the next two years as a clinical associate in the medicine branch at the National Cancer Institute. And then he completed his residency in medicine at Yale New Haven Medical Center. In 1970, he returned to the NCI, where he stayed for the next 18 years, serving during most of that as the chief of the medicine branch. Dr. Young accepted the role as president of the Fox Chase Cancer Center in Philadelphia and served in that role and then chancellor in 2009. Dr. Young has authored over 400 peer reviewed papers regarding a broad range of both scientific and policy issues in oncology. But in addition to the I consider astonishing and precedent-setting reports of cures in Hodgkin's disease and non-Hodgkin's lymphoma, perhaps most importantly with his longtime colleague and friend Dr. Robert Ozols, he led many of the early and groundbreaking studies in ovarian cancer diagnosis and treatment that I think still guide our care today for patients with this disease. He's won too many awards and honors for me to go through. But of the major ones, he won the prestigious Bristol-Myers Squibb award, which he shared with Dr. Ozols in 2002, the Margaret Foley Award for Leadership and Extraordinary Achievements in Cancer Research from the American Association of Cancer Research, and ASCO's Distinguished Service Award, one of our highest awards, for Scientific Leadership in 2004. Of note and close to my own heart, Bob served as the ASCO president 1989/1990, which I consider a really critical time in the evolution of our society. Dr. Young, welcome to our program. Dr. Young: Thank you. Dr. Hayes: So as I noted, you grew up in Columbus, Ohio, or again, as we say in Ann Arbor, that town down south, but more importantly that your father was a surgeon. And I've heard you tell the stories as a boy you went on rounds with him and that inspired it. Was he academic or was he a really community physician or both? Dr. Young: Well he was a little of both. He was primarily a community physician. But he did, particularly at the time of the Second World War, because he was a very skilled hand surgeon, he got involved with a lot of hand surgery related to a company called North American Aviation that produced a lot of World War II planes. And there were a lot of injuries in that setting. And so he became quite a skilled hand surgeon and actually taught at Ohio State's Medical Center. So he had both an academic and community-based practice. But primarily he was a practicing community surgeon. Dr. Hayes: And did you actually go into the OR with him as a boy? Dr. Young: Oh, yeah. Oh, sure. Dr. Hayes: Wow. Dr. Young: You know, in those days, there weren't any rules and regulations about that. And so I went in and watched surgery and held retractors and participated, you know, when I was a youngster. Dr. Hayes: Wow. What a privilege. You're right, that would not be allowed now. That's a good story. What did you see, bad and good, compared to medicine now then. I mean, if you had to say here are a couple things that we've lost that you regret. Dr. Young: Well, I think that it was more under the control of the physician than it is in this day and age in so many ways. For instance, my father practiced in three different hospitals. And he admitted patients depending upon what kind of surgical support and nursing support they needed. If they were complex, he went to a bigger hospital. If they were very straightforward cases, he put them into a smaller hospital. And so he had a lot more control over how his patients were dealt with and the circumstances under which they were cared for. And, of course, most of his practice was before Medicare and all of the insurance sort of thing, so that people paid what they could pay. And so it was a much simpler and much more physician-driven practice than it is today. Dr. Hayes: Just as an aside, there's a wonderful book called The Brothers Mayo, written by a woman named Clapesattle in the 1930s after both Charlie and Will died. And it's a history of the Mayo Clinic. But in it, she says that Will basically charged people what they could afford to pay. So if you were wealthy, he charged you a lot. And if you were poor, he gave it to you for free and everything in between. And he sort started made up the billing schedule the way he wanted it to happen. And one of his more wealthy patients challenged him on this, and he said, go somewhere else. Dr. Young: Yeah, well, that's exactly the kind of practice my father ran. Dr. Hayes: Yeah. Anyway, I'm intrigued by year two-year stint at the NCI in the late '60s before you then went back and finished at Yale. And hopefully this is not insulting and I know you're considered one of the so-called yellow berets. But tell me, tell us all about your choice to interrupt your residency and go to the NIH. I don't think our young listeners really understand the political climate and the circumstances of the time that led so many of you to go there. Dr. Young: Well, I think that's a great question, because it will lead to some of the other discussions we have later. But essentially, I graduated from medical school in 1965 at the height of the Vietnam War. And in those days, there was not only a general draft, there was a physicians draft. So graduating in medical school in those days, you had one of three choices. You could either take your chances-- and again, the numbers, your priority scores at the time, didn't really have anything to do with it, because they took as many doctors of whatever kind of type they wanted for whatever purpose they wanted. So that you couldn't be sure if you had a low number that you'd not be drafted. But you could take your chance. And in those days, a lot of people did. And a lot of people got drafted. Or you could join the Berry Plan, which was at the time an opportunity to continue your specialty training until you were finished. But then you owed back the military the number of years that you had been in specialty training. Or you could do a much less well-known track and that is with the US Public Health Service. And amongst the opportunities for the US Public Health Service were things like the Indian Health Service and the Coast Guard Service and those sorts of things, or the National Institutes of Health, about which at the time I knew almost nothing except that it existed. And I owe it to some of the folks that I worked with at Cornell, primarily a hematologist oncologist by the name of Dick Silver, Richard Silver, who's still at practice at New York Hospital, who when I was working in the labs there, because I was doing some research when I was at Cornell, and they were telling me about the fact that you could actually apply for a position at the NIH. And you would be in the US Public Health Service. So it took me about 3 milliseconds to figure out that for me that was clearly a track that I wanted to explore. And I had done some research in platelet function and platelet kinetics and so forth. And there was a guy by the Raphael Schulman who is at the NIH at the time. And I said, that would be a miracle if I could get this. So the way it worked was that you applied. And then you actually interviewed with a whole bunch of different people. And as it turned out, I didn't get a position with Dr. Schulman. But I was introduced to the National Cancer Institute and both the leukemia service and the then called the solid tumor service. And I applied to various things like that. And I actually got in on the leukemia service. So I walked in after I signed up and was taking care of little kids with acute leukemia, having never been a pediatrician or knowing anything about leukemia. But it was a baptism of fire and a very exciting place even then. Dr. Hayes: I want to get back to that in a second because that's a critical part of this. But, again, going back to the political climate, my opinion, this entire issue and your personal journey and many others had a profound effect on both the scientific and medical community of this country as a whole. I think it was an unintended effect. But because of the Vietnam War and because the NIH was such a great place to train in those days. Do you agree with me? Dr. Young: You are absolutely correct. I mean, one of the things that needs to be said is that this was a transformational phenomenon for cancer research. But it also took place in every other field. And the NIH at the time was just swarming with people of all medical disciplines who were coming to take advantage of the opportunities that existed within the NIH, but also to serve in this capacity as opposed to some of the alternatives that were around. And I think I heard a figure one time, which I'm sure is true, and that is at one point in time, 30% of the chairmen of medicine in the United States had done training at the NIH before they ended up being chairmen of medicine. So that gives you an idea of the impact of this. And you're absolutely right, it was a totally unintended consequence. Nobody ever designed it that way. Nobody ever planned for it to happen that way. But in retrospect, when looked at it and you can see exactly why what happened happened. Dr. Hayes: Yeah. And I interrupted you, but I did it on purpose, because it didn't sound to me like you really had a plan to go into cancer treatment, but sort of landed there serendipitously. Is that true? I mean how do you end up there? Dr. Young: Oh yeah, oh, yeah, I mean I did get very interested in hematology when I was in medical school. I first went to medical school, of course, thinking I was going to be a surgeon, because my father had a great practice and he had a wonderful experience with surgery and it was really cool. But I just found that I just wasn't designed just the same way. And it was increasingly clear that cancer was not my not my goal-- I mean, surgery was not my goal. And so, you know, I knew I wanted to stay in internal medicine. And I got interested in the research. And I had done some significant research and in platelet function, as I said. I knew that's what I wanted to do, some sort of clinically-related research in medicine. If I'd had my choices, of course, I would have gone into a sort of pure hematology track. And, of course, it's worth saying that it's difficult for oncologists nowadays to understand how big an outlier oncology was. There was no subspecialty in oncology at the time I went to train down there. There was a subspecialty in hematology. And, of course, all of us, the Gang of Five that you mentioned, all of us took hematology boards. And that's because it wasn't clear that there was going to be oncology. When oncology came along we all took the first oncology boards ever given. So that gives you an idea of how early in the history of oncology we were in the late '60s, early 1970s. Dr. Hayes: So we're talking 1970 or so right when you started? Dr. Young: Well, 1967 to '69, I was a clinical associate. Then I was at Yale for a year. And then in 1970, I came back on the senior staff. Dr. Hayes: And who were the characters above you when you came in? I know Doctors Frei and Freireich had been there before. Dr. Young: Yes. Frei and Freireich had just left the year before. One went off to MD Anderson, the other went off to the Memorial. And George and Vince-- George Cannellos, Vince DeVita-- had stayed on, with Vince as the head of the medicine branch. And then when we came back, Vince sort of brought two of us back that he'd had before, Bruce Chabner and I. He'd sort of sent us off to Yale and said they could buff us up a little bit. And he didn't offer us a job coming back. But we went off, and we were training up there. And he called us both up and says, why don't you to come back and join the senior staff. He recruited Phil Schein as well. And so that was the Gang of Five that we started out. Four of us ended up being president of ASCO at one time or another. And I suspect the only one who didn't, Bruce Chabner, probably would have except for the fact that he was the director of the Division of Cancer Treatment of the NCI for a long time. And the NCI and the NIH changed its attitude toward allowing people to participate in major leadership positions nationally, a tragedy as far as I'm concerned, which has I think affected the morale of the NIH and a lot of other things and deprived a lot of good people of opportunities to serve nationally. But that was the way it was, otherwise we would all ended up at some point leading-- Dr. Hayes: So the Gang of Five was you Bruce Chabner, George Cannellos, Phil Schein, and Vince DeVita, right? Dr. Young: Right, exactly. Dr. Hayes: And what were the dynamics among you? I mean, so were you and-- Dr. Young: Well, I mean, it was an incredible time. You know, there was enormous talent that had poured into the NIH, as we talked before. And an enormous amount of talent was present and was recruited in during this period of time. I mean, you know, Paul Carbone was still there. John Minna was recruited. Harman Ayer, who was the longtime chief medical officer of the American Cancer Society. Tom Waldman was a world class hematologist. Max Wicha was a part of this group. Sam Broder, Allen Lichter, an other ASCO president, Steve Rosenberg, Phil Pizzo was the head of the pediatric oncology branch, now dean at Stanford. And it goes on and on and on. And so there's a massive amount of talent and a lot of freedom. And so Vince was clearly the leader, he had a lot of ideas and a lot of creativity. But he let out a lot of people do whatever they wanted at the same time. And it was sort of a situation in which we all participated, because we were all attending at the same time. So Vince and George did a lot of the lymphoma and Hodgkin's disease stuff. We all participated. I got interested in ovarian cancer. And you talked about that. Bruce Chabner and Phil Schein were always very pharmacologically oriented. And so they did a lot of the phase 1 and phase 2 trials and a lot of the laboratory backup associated with the studies we did. And everybody shared. And so there was really not a lot of competition in that sense. Everybody was I think very competitive. Because it was all sort of shared, it worked out so that everybody felt that they were getting a substantial part of the recognition that was going on in the group. Another thing that was unusual about the NIH, but it had unintended, but important consequences is that nobody had anything to do with what they got paid. So that you could go to events and say, well, you know, I deserve to be paid more, but it didn't have anything to do with what you got paid. We had no control over anybody's salary. So that I don't think the whole time I was there, the whole 14 years I was chief of the medicine branch, I don't think I ever had a conversation with anybody about money, because I didn't have anything to do with what people got paid. Let me tell you, that's a big change. It actually has a remarkable, remarkable effect on the way people work. Because if for some reason somebody wanted to make more money, they just had to leave. There wasn't any way to do it. So you either had to accept that this is what everybody got paid and that you were rewarded by the opportunities to do the kinds of research that were done. Or you said, look, I need to go on and go somewhere else. Dr. Hayes: Now, just between you and me, and maybe a few thousand other people who are listening to this, who is the first guy to say let's give combination chemotherapy to Hodgkin's disease? Dr. Young: Well, actually, I don't know the answer to that. I think if I had to guess, I would say Vince, because Vince and George had been around in the Frei and Freireich days. And of course, you know, they'd already had experience with the impact of combination chemotherapy in leukemia. And so the concept was you took drugs that were active in the disease and put them together if they had different kinds of toxicity. And you were then able to utilize the combined impact on the tumor and sort of spread around the toxicity. So it was more tolerable. And that was the concept. And I think that because Vince and George were treating chronic leukemias and treating Hodgkin's disease, the notion of combining it with combinations was pretty straightforward evolution from the experience in leukemia. There are other people who claim that. I think from time to time both Jay Freireich and Tom Frei have claimed it. I think that there was a dust up between Vince and Paul Carbone and George because there was some suggestion by somebody that Paul was the one who originated the idea or Gordon Zubrod. And quite frankly, I don't know. If I knew, I would tell you. But I don't actually know. I can tell you this, that the emotional and passionate driver of the concept of combination chemotherapy as a successful modality in Hodgkin's disease and lymphoma was Vincent. Dr. Hayes: Your answer is very consistent with what other people have said the same thing. It must have been somewhere along the line that all of you began to see that there really were cures. And did you realize, as a group, that you were making history? Or was it just day to day-- Dr. Young: Well, you know, it's interesting. I can tell you one of the most transformational experiences that I had in the early days is, of course, we were following all these patients who had started on MOP. And so to do that you had to sort of go back and pull out the charts and all this kind of stuff. You know, we didn't have electronic systems that had all the stuff recorded. You just had to go down and pull off the charts. And what struck me so tremendously was the attitude of the physicians that had first started some of these patients on this therapy, because the notes made it very clear that they were sort of flabbergasted when these people came back after the first couple of months and they were watching their disease disappear, and that they really didn't anticipate at all, initially, that they were going to see these people after a couple of weeks. And it was very clear in the notes. By the time we had gotten there, of course, there were a significant number of people already on the trial. And it was already clear that we were seeing things that nobody had ever seen before. And I think that's when it first began to dawn on everybody. And as soon as we saw it in Hodgkin's disease based on the experience that we'd seen with non-Hodgkin's lymphoma, we had a suspicion that it would likely be the case as well there. Dr. Hayes: So you already bounced across it, but as I was looking through your CV I knew this anyway, you really mentored a who's who of oncology-- Rich Schilsky, Dan Longo, Max Whishaw, Dan Van Hoff-- and you noted already that oncology training has evolved. I mean BJ Kennedy pushed through boards I think in '74 or '75, something around there. What have you seen in the evolution on oncology training that you think is good or bad? Dr. Young: Oh, I think in general, it's much better. And I think it's much better because, of course, there's a lot of success that's been built into what's been accomplished. And that makes it a lot easier to teach people about how to treat Hodgkin's disease well, than we ever could at the time we were doing it because nobody knew the answer to those things. And I think there's also a lot more of it. You know, I think at the time we were at the NIH, you know, I think credibly you could count on both hands the number of really established academic oncology programs in the United States. And now, there are probably 100. And so the quality of training and the quality of mentoring is dramatically better than it was in those days. In those days, you know, hematologist we're doing most of the treatment of cancers. And they were all sort of in the Sidney Farber mode. You take one drug, and you give it as long as it works. And then you switch to another drug and use that as long as it works. And that was pretty much the way hematologists approached the disease. And by all means, you don't cause any toxicity. Dr. Hayes: I picked up several adults who had been Sidney Farber's patient when I was at the Dana-- Sidney Farber Cancer Institute in those days in the early '80s. So I had his handwritten notes. And sadly, I did not photocopy them. I would have love to have had it. But he had a very different mindset in terms of the way-- Dr. Young: Oh, absolutely, absolutely. And as far as I can tell, this is just my own personal reaction, is that I don't think either George or Vince at the time we got here shared any of that attitude. George is a little more cautious than Vince, as everybody knows. But neither one of them for a minute ever suggested that we were being too aggressive, that it was unfair and immoral to treat people with these kinds of toxicities, not that they desired to make people sick. But they were absolutely convinced that aggressive therapy could make a dramatic difference in the natural history of these diseases. Dr. Hayes: Yeah, certainly, Dr. Frei felt that way too. Dr. Young: Yes. And well, they were his mentors. I mean, you know, all these guys were there at the same time. And they were all influencing one another. Dr. Hayes: You know, it's amazing, I think all of us-- there are 44,000 members of ASCO now-- basically are derived from about 10 people in the 1950s and '60s, most of the DNA, not completely-- Karnofsky and some others around, but-- Dr. Young: Oh, yeah. Dr. Hayes: Well, the other thing is actually, you were talking about the safety, what are the war stories? I mean, how did you give chemotherapy? Were you guys mixing it up and giving it yourself? You know, we got all these bells and whistles. Dr. Young: Well, I mean, for instance, you know this is the first time really protocols were written. And the reason that we wrote protocols was simply because we were working with fellows. And they literally needed the recipe of what it was they were supposed to give and when. And so we wrote up these what were the first of the clinical trial protocols. There was no formal informed consent at the time of these studies. We had, of course, informed consent, the same way you do informed consent now, really. And that is you talk to the patient. You explain to the patient what the treatment is and what your expectations for the treatment are. And the patient understands the disease they face and decide that they can do it or not do it. And it's actually still the same today. The only difference is we now have 14, 17-page informed consent documents that make lawyers happy, but don't really impact, at least in my view, whether patients decide to participate or not. But we didn't have those. So I think that was the other one of the great things about the setting at the NIH, not that I'm anti-informed consent, but it was simpler. It was easier to get something done. You could do unconventional treatment and nobody looked at you and said, "you can't do that, that's never been done before, you're not allowed to do that." We didn't have academic constraints. One of the things that always surprised me is when, you know, we would develop a particular technique, like peritoneoscopy or laparoscopy for ovarian cancer staging, and when guys left the program having been well-trained to do this, they couldn't do it when they went to their new institutions because gastroenterologists did this. That was the sort of thing that the constraint wasn't here. There were also very easy-- I mean, all you had to do was to get an idea and write it up. I took a look at ovarian cancer and said, you know, "It seems to me, here's a disease that's now being managed by gynecologic oncologist. Internists never see these patients. They're all treated with the melphalan. And those that happen to live a long time develop acute leukemia from that treatment. They ought to be something better than what we're doing." And so we just decided that we would begin to take patients with advanced ovarian cancer into the NIH. And the rest sort of is history. But you couldn't do that in another hospital. You know, the biggest treaters of ovarian cancer probably program-wise was MD Anderson. But all his patients were treated by gynecologic oncologists. You couldn't have gone into the MD Anderson and said, "OK, we're going to take over the treatment of advanced ovarian cancer." They would have laughed in your face. Dr. Hayes: Actually, you just segued into my next question. And again, you and Dr. Ozols, in my opinion, completely changed the course of ovarian cancer treatment. Did you get a lot of pushback from the gynecologic community? Dr. Young: Well, no, actually. It's interesting. Now I don't know what we got behind the lines, you know when they were all sitting around the bar after the meetings. We really didn't. First of all, one of the other advantages of being at the NIH is that when you said something, people listened. And the other thing is, of course, when we got really going with ovarian cancer-- this was after the passage of the National Cancer Act-- and there was money at the NIH. So one of the things we did, for instance, was to put on a series of symposia about ovarian cancer treatment, what was going on, what wasn't going on, and brought the movers and shakers of this field together in meetings and talked about what was being done and what should be done and what information we didn't have that we needed. And we actually got funded for a period of time, a group called the Ovarian Cancer Study Group, which eventually evolved into the Gynecologic Oncology Cooperative Group, National Cooperative Group. So we had some other tools that we could bring to bear to drum up an interest in new research in ovarian cancer. And, of course, gynecologic oncologists couldn't prevent us from taking patients that were referred to us. And our surgeons, for instance, none of whom were gynecologic oncologists, were happy to help and to operate on them when they needed to be operated on. And Steve Rosenberg's group has fantastic surgeons. So we didn't have any problem getting state of the art surgery done on these people. And, in fact, they are general surgeons learned some gynecologic oncology at the same time. Dr. Hayes: Yeah, you know, it's been interesting to me that the surgeons, the general surgeons, willingly gave a systemic therapy. But that still in this country, there are very few medical oncologist who do GYN oncology. It's still mostly done by GYN oncologists. Dr. Young: Yes. Dr. Hayes: And there are very few trained medical oncologist in this. And I think it's gotten too complicated for a surgeon to do both. I don't really see why that hasn't happened based on, especially your model and Bob's model, that's my own soapbox. Dr. Young: Yeah, that's an interesting point, because at the NIH, when we were there, Steve Rosenberg and Eli Gladstein in radiation therapy, there were no rules that said that they couldn't do chemotherapy. And, in fact, they did it sometimes. And we didn't say anything about it. Usually, they called on us and said, hey, look, you know, we need you to help us or participate with us or whatever. But there were no rules that said that they couldn't. And sometimes they did. But for the most part they said, "look, this is not the business we're in. We want you guys to do the chemotherapy." And so for the most part we were able to do that. Dr. Hayes: The entire NSABP, those guys were all given their own surgery, their own chemotherapy. And they ultimately handed most of it over to medical oncology through the years. But that's not happened so much in GYN. OK, I want to go into your role in ASCO at the end here. And as I noted, I think you were president during a really critical turning point for the society. And just a few things, you already mentioned that I think you were already at Fox Chase when you ran. So you'd left NCI. And what made you run? But more importantly, tell us about your role in the evolution at that time of the society. Dr. Young: I think actually they recruited me to run just at the time that I was looking to leave. And so I left in December of 1988. And I was president of ASCO 1989 to 1990. At the time, I had moved from the medicine branch and ran the cancer center's program for a year. And I decided that I liked it. I thought, well, maybe I'll just stay here for the rest of my life, the way Steve Rosenberg did and others have done very successfully. But I said, well, you know, it's either sort of now or never. And so I decided that I would make the jump. But when I got into the sort of ladder, if you will, of ASCO through the board and so forth, it became clear that there were a couple of things that were a real challenge for the society. The society had at the time for the most part been essentially run on contract, that there was no organization of ASCO at all. It was it was all run by a contract organization. And it was clear that we had grown to a size such that we really needed to begin to recruit our own leadership staff. And so my year as president was actually the first year we hired a full-time employee. And she was based in a law firm that we used for ASCO legal business. But that was the first employee ever hired by ASCO. And that was in 1990, or 1989, I don't remember which, put in that year anyway. The other thing that was going on, which was critical for the society, is that, of course, there's always been a 'town gown' challenge in all aspects of medicine. And medical oncology was no different. So it had originally been the province of academic oncologists. But the numbers began to change dramatically. And it became clear that there was an enormous number of community-based oncologists, who looked at the challenges that face the organization somewhat differently than the academics. And this is one of the things that I think I benefited from growing up with a father that had both his feet in the community-based practice and the academic practice. And I realized how private practicing physicians view academics and view academic control of organizations. And I realized-- and others did too. I wasn't alone on this-- that we really needed to build up the recognition of community-based oncology as a first class citizen in the society. And so we began to create and bring in all of these state society organizations. And we began to get leadership roles who were based in community oncology, rather than just academics. And Joe Bailes was our first head of the Public Relations Committee of the society and grew this into a national presence and became the first community-based president of ASCO. So I think I think those are the two things that I saw that hopefully I made an impact on. And it always amazes me to realize that the society was really that young. I mean, people can't believe that it's just, what, 30 years ago when we had our first employee. Dr. Hayes: Yeah, that's why I'm doing these podcasts. We make sure we get this history. You know, it's interesting, I often give you credit for the ladder. As president myself, it was made very clear to me that 90% of the patients in this country with cancer are treated by community oncologists, maybe 85% or so. And about 2/3 of our membership are community oncologists. So we now have designated seats on the board of directors. We started a Department of Clinical Affairs that Steve Grubbs is running. That's just a few years old. But, boy, it's been fabulous. We now have a designated chair, the state affiliate council is invited to the board of directors and sits in and presents. And the state affiliate councils meets at ASCO headquarters at least once a year. And we've had a couple presidents who are, besides Joe, Doug Blayney and Skip Burris now coming in in June. So I think we've been reaching out. It always struck me when I sat in the headquarters, the seven founding members were, for the most part, community people. They met just to talk about how do you give chemotherapy. It wasn't, you know, about Tom Frei or Freireich or Jim Holland. It was folks in the community. And then it grew into an academic society. And I think you and then Joe Bailes and others kind of brought us back and grounded us. And to me, that's a really critical evolution in our society. I think it's made us much stronger. So those are most of my questions. You've answered almost everything I had written down that I always wanted to ask you if I got a moment in a cab with you. I want to thank you for taking time to do this. But more importantly, I want to thank you for all the contributions you have made to the field. I mean, I don't think I would be here and I don't think most of us who do oncology would be here if it weren't for you and the Gang of Five and the things you've done, both by the courage to moving forward to giving the kinds of chemotherapy and stuff, establishing science in the field, but also the policy stuff. Your articles in The New England Journal over the years, I think have been classics. You should put this all in a book and send them out to everybody because they have to do with not just giving chemotherapy, but the whys and hows of what we do. So I know I'm being long-winded, but that's because I'm a big fan. Well, thank you very much. Dr. Young: You know one of the things, I got to say is that I've just been a very lucky person. I happened to have had great opportunities. And I think I was able to take advantage of those opportunities. But somebody gave me those opportunities and put me at the right place at the right time. And so I am a very lucky guy. Dr. Hayes: Well, and I want to finish up and say how nice it is to see at least one graduate of Ohio State University do well. You know, it doesn't come very often. So congrat-- Dr. Young: Yeah, yeah, yeah, yeah, yeah The team up north, the team that will not be named, yes. Dr. Hayes: Thank you so much. And appreciate all you've done. Again, appreciate your taking time with us. Dr. Young: Thank you very much, Dan. Dr. Hayes: Until next time, thank you for listening to this JCO's Cancer Stories, The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple Podcasts or wherever you listened. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, The Art of Oncology podcast is just one ASCO's many podcasts. You can find all the shows at podcast.asco.org.
Dentro de nuestro habitual desorden en la cronología del programa, hoy vamos a escuchar Jazz. Nos vamos a centrar en un personaje que, al margen de los gustos musicales de cada uno, te guste el jazz o no, todo el mundo conoce. Ha conseguido salvar las barreras raciales, musicales, temporales y cualquier otra que se os ocurra. Hablamos de Louis Armstrong. Con ningún otro músico de la historia del jazz las opiniones son tan unánimes como sobre él. Hasta la llegada de Dizzy Gillespie en los cuarenta no hubo un solo trompetista de jazz que no hubiera seguido los pasos de Louis Armstrong, o Satchmo, como se le llamaba. El mismo Gillespie dijo: La posición de Louis Armatrong en la historia del Jazz no tiene parangón. Si no fuera por él, no estaríamos nosotros aquí. Por eso quiero agradecer literalmente a Louis Armstrong mi vida”. No podrá decir, en su tumba, que no fue un personaje querido y admirado. Claro que, no siempre fue así. Louis Armstrong nació en el seno de una familia muy pobre y en uno de los barrios marginales de Nueva Orleans. Todo fue a peor cuando su padre, William Armstrong, abandonó a la familia. Louis pasó sus primeros años en un difícil vecindario de las afueras de la ciudad. En 1910 fue detenido por primera vez y a lo largo de una época de su juventud se vería esporádicamente metido en algunos episodios delictivos. Se educó vagabundeando por las calles y trabajando de chatarrero. Desde niño fue consciente del terrible odio racial que existía en los Estados Unidos en las primeras décadas del siglo XX. Trabajó para una familia de inmigrantes judíos lituanos, los Karnofsky, quienes aceptaron al niño como a uno más de la familia. Louis siempre contaba cómo descubrió que esta familia blanca también era discriminada por «otros blancos», «yo tenía sólo siete años, pero podía notar el miserable trato que los blancos le daban a esta pobre familia judía para la cual trabajaba… de la cual aprendí cómo vivir una vida verdadera y con determinación». Esto lo dejó escrito en sus memorias: Louis Armstrong y la familia judía en Nueva Orleans. Vamos a escuchar Sweet Georgia Brown, interpretada por Armstrong en una grabación en directo. No existían antecedentes musicales en su familia, por lo que su interés por este arte surgió a partir de la escucha de las célebres bandas de Nueva Orleans. Cuando la música le llamó y no tenía un centavo para comprar su primera trompeta, el señor Karnofsky se la compró. Eternamente agradecido y a pesar de ser de fe baptista, Louis Armstrong llevó el resto de su vida una estrella de David colgando de su cuello en honor a su mecenas Aprendió, en primer lugar, a tocar la corneta en la banda de la Nueva Orleans Home for Colored Waifs, un reformatorio para niños negros abandonados a donde había sido enviado en varias ocasiones por delitos menores, como por ejemplo el haber disparado al aire durante una Nochevieja. Allí, aconsejado por el director del reformatorio y uno de sus profesores, optó definitivamente por la trompeta. En 1914, tras su salida del reformatorio, trabajó como vendedor de carbón, repartidor de leche, estibador de barcos bananeros y otros empleos del mismo tipo. Empezó también a trabajar en los cabarés de Storyville, donde estaban concentrados todos los locales nocturnos de la ciudad. Fue allí donde conoció y se empapó de la música de los grandes intérpretes del momento: Bunk Johnson, Buddy Petit y, sobre todo, de Joe King Oliver. Entre 1918 y 1919, ya con una bien ganada reputación como trompetista, fue contratado por el director de orquesta Kid Ory, gracias a una recomendación de su mentor Joe King Oliver, en ese momento trompeta principal de esta orquesta. Louis llegó por este camino a tocar en algunas de esas orquestas de Nueva Orleans, incluyendo aquellas que viajaban por los ríos, como la renombrada orquesta de Fate Marable, que realizó una gira en un buque de vapor a lo largo de todo el Misisipi. El propio Armstrong describiría esta época con Marable como «su estancia en la universidad», ya que le proporcionó una enorme experiencia en el trabajo con arreglos escritos. Cuando Joe Oliver abandonó la ciudad en 1919, Armstrong ocupó su lugar en la banda de Kid Ory, por entonces el grupo de swing más importante de la ciudad. En sus primeras grabaciones con la orquesta, allá por 1923, se incluyeron algunos solos como segunda trompeta de la banda; en 1924, sin embargo, ya era el solista más importante y más creativo del grupo. En febrero de este año se casó con Lillian Hardin, pianista de Oliver, quien lo animó a abandonar la orquesta para alcanzar mayores metas artísticas. Así, se separó amistosamente de Oliver y, se marchó a Nueva York. Su fama llegó rápidamente a oídos del mejor director de orquesta afroamericano del momento, Fletcher Henderson, que le ofreció un contrato para que se uniese a su banda, la Fletcher Henderson Orchestra, la principal banda afroamericana de la época. Armstrong debutó con ella el 29 de septiembre de 1924 en el Roseland Ballroom de Nueva York. Tras decidirse a aprender a leer música, en sólo un año revolucionó el estilo y la forma de tocar de sus compañeros y grabó con las mejores cantantes de blues de la época, como Bessie Smith. De esas grabaciones, 1925, escuchamos a la pareja en Careless Love Blues En este mismo año, 1925, empezó a grabar bajo su propio nombre para el sello OKeh acompañando a dos formaciones creadas por él llamadas Hot Five y Hot Seven, dependiendo evidentemente del número de músicos de cada formación, produciendo éxitos como «Potato Head Blues», «Muggles» (una referencia a la marihuana, la cual tendía a consumir desde siempre) o este que vamos a escuchar ahora: «West End Blues». Louis Armstrong West End Blues Armstrong continuó tocando con big bands, como por ejemplo las de Erskine Tate o la Carroll Dickerson. En 1929 vuelve a Nueva York para trasladarse a Los Angeles al año siguiente. Este hombre no podía parar quieto. Desde esta ciudad inicia una gira por Europa que duraría dos años y en la que obtuvo un éxito espectacular, particularmente en París. La aparición de Joe Glaser en 1935 como su representante y la contratación de la orquesta de Louis Russell como formación de apoyo de Armstrong, marcaron el curso de los acontecimientos durante el resto de la década, en la que Armstrong pasó de ser una simple figura del jazz a un destacado miembro de la industria del entretenimiento en general. En 1940, rompió su relación comercial con la big band de Russell y contrató a nuevos músicos: este nuevo grupo fue el principal apoyo con el que contó Armstrong hasta 1947. Tras pasar muchos años de gira, se asentó permanentemente en Queens, Nueva York, en 1943. Aunque no ajeno al control que del negocio musical ejercían los gánsteres por aquella época, Louis continuó desarrollando su técnica y su carrera musical. Durante los siguientes treinta años, Armstrong llegó a actuar una media de trescientas veces por año. En los años cuarenta, las big bands entraron en decadencia debido a los cambios en el gusto del público: muchas salas de baile cerraron y entre los nuevos medios de comunicación como la televisión y el auge de nuevos tipos de música, las big bands y el swing pasaron a un segundo lugar. Se hizo imposible mantener y financiar orquestas itinerantes de 16 músicos o más. Escuchamos ahora a la orquesta de Luis Russel acompañando a Louis Armstrong en Bessie Couldn’t Help It. Hacia 1947, Armstrong redujo su banda a cinco instrumentos, volviendo así al estilo Dixieland que lo había hecho famoso al principio de su carrera. Este grupo se llamaba All Stars y se presentaron el 13 de agosto de 1947 en el club Billy Berg's de Los Ángeles. En 1964, Armstrong grabó el que sería su tema más vendido: «Hello, Dolly». La canción obtuvo el puesto número uno en las listas de Estados Unidos, superando al grupo inglés The Beatles. Armstrong también obtuvo por el disco un premio Grammy al Mejor Cantante masculino y fue nominado a Mejor Disco del año. En este álbum se encuentra, también, otro tema clásico de Armstrong, «Jeepers Creepers». Como Hello, Dolly ya lo escuchamos en el anterior programa, hoy escucharemos este último. Jeepers Creepers. Armstrong trabajó hasta poco tiempo antes de su muerte y, aunque en ocasiones en sus últimos años se inclinase hacia algunas interpretaciones triviales, en otras era capaz de demostrar un todavía asombroso dominio de la técnica y de la intuición musical que dejaba perpleja a su propia banda. Bajo el patrocinio del Departamento de Estado de los Estados Unidos recorrió todo el mundo, tanto, que terminó por ser conocido como «Ambassador Satch» (embajador Satch). Debido a problemas de salud, restringió sus actuaciones a lo mínimo, aunque siguió tocando hasta el día de su muerte. Louis Armstrong sufrió un ataque al corazón en 1959, del cual se pudo recuperar para seguir tocando. Pero un segundo ataque al corazón en 1971, le obligó a guardar reposo durante dos meses. Se reunió nuevamente a tocar con su grupo el 5 de julio de ese mismo año y, al día siguiente, en Corona, Queens (Nueva York) murió mientras dormía por complicaciones de su corazón, casi un mes antes de cumplir 70 años de edad. Esto ha sido una grabación del famoso Saint Louis Blues, realizada en Nueva York en 1929. Armstrong se acercó a muchos tipos de música, desde el blues más enraizado a los arreglos más cursis de Guy Lombardo, desde las canciones folk hispanoamericanas a sinfonías y óperas clásicas. Armstrong incorporó influencias de todas estas fuentes en sus interpretaciones, a veces provocando el aturdimiento de sus fans, que querían que el artista se mantuviese en una línea más convencional. Mackie el Navaja, que es la canción que acabamos de escuchar fue compuesta en 1928. La letra es de Bertolt Brecht, y la música, de Kurt Weill. El año siguiente, 1929, la incorporaron a «La ópera de los tres centavos» obra de teatro escrita por los mismos autores. Durante su larga carrera, Armstrong tocó y cantó con los más importantes instrumentalistas y vocalistas; entre ellos, con Jimmie Rodgers, Bing Crosby, Duke Ellington, Fletcher Henderson, Bessie Smith y, especialmente, con Ella Fitzgerald. Armstrong grabó tres discos con Ella Fitzgerald: Ella and Louis, Ella and Louis Again y Porgy and Bess para Verve Records. Vamos a escuchar a estos dos monstruos: Armstron y Fitzgerald en Summertime. Algunos músicos criticaron a Armstrong por tocar ante audiencias segregadas, o sea, solo para blancos, y por no tomar una postura clara en el movimiento por los derechos civiles, sugiriendo que era un tío Tom, apodo absolutamente despectivo. Por el contrario, Louis Armstrong fue un apoyo financiero muy importante para Martin Luther King y para otros activistas por los derechos civiles, aunque siempre prefiriese trabajar en esos asuntos de forma muy discreta, sin mezclar sus ideas políticas con su trabajo como artista. Ahora bien, cuando se significó, sus declaraciones fueron muy efectivas: la crítica de Armstrong al presidente Eisenhower, llamándole «two-faced» (con dos caras) y «cobarde» debido a su inacción durante el conflicto de la segregación racial escolar en Little Rock, Arkansas, que fue noticia nacional en 1957.También protestó cancelando una gira por la Unión Soviética en nombre del Departamento de Estado diciendo que «por la forma en que están tratando a mi gente en el sur, el gobierno podría ir al infierno» y que él no podía representar a su gobierno fuera del país cuando estaba manteniendo un conflicto con su propio pueblo. También fue un tipo generoso, hasta el punto de decirse de él que había gastado tanto dinero en los demás como en sí mismo. En fin, un buen tipo. What A Wonderful World Y, bueno, para no perder la costumbre, otra vez nos hemos pasado de tiempo. Pero es que, nos venimos arriba y … Espero que os haya entretenido el programa y sabed que volveremos la próxima semana con más historias, más músicos y más música… mucha música. Hasta entonces… Buenas vibraciones.
Dentro de nuestro habitual desorden en la cronología del programa, hoy vamos a escuchar Jazz. Nos vamos a centrar en un personaje que, al margen de los gustos musicales de cada uno, te guste el jazz o no, todo el mundo conoce. Ha conseguido salvar las barreras raciales, musicales, temporales y cualquier otra que se os ocurra. Hablamos de Louis Armstrong. Con ningún otro músico de la historia del jazz las opiniones son tan unánimes como sobre él. Hasta la llegada de Dizzy Gillespie en los cuarenta no hubo un solo trompetista de jazz que no hubiera seguido los pasos de Louis Armstrong, o Satchmo, como se le llamaba. El mismo Gillespie dijo: La posición de Louis Armatrong en la historia del Jazz no tiene parangón. Si no fuera por él, no estaríamos nosotros aquí. Por eso quiero agradecer literalmente a Louis Armstrong mi vida”. No podrá decir, en su tumba, que no fue un personaje querido y admirado. Claro que, no siempre fue así. Louis Armstrong nació en el seno de una familia muy pobre y en uno de los barrios marginales de Nueva Orleans. Todo fue a peor cuando su padre, William Armstrong, abandonó a la familia. Louis pasó sus primeros años en un difícil vecindario de las afueras de la ciudad. En 1910 fue detenido por primera vez y a lo largo de una época de su juventud se vería esporádicamente metido en algunos episodios delictivos. Se educó vagabundeando por las calles y trabajando de chatarrero. Desde niño fue consciente del terrible odio racial que existía en los Estados Unidos en las primeras décadas del siglo XX. Trabajó para una familia de inmigrantes judíos lituanos, los Karnofsky, quienes aceptaron al niño como a uno más de la familia. Louis siempre contaba cómo descubrió que esta familia blanca también era discriminada por «otros blancos», «yo tenía sólo siete años, pero podía notar el miserable trato que los blancos le daban a esta pobre familia judía para la cual trabajaba… de la cual aprendí cómo vivir una vida verdadera y con determinación». Esto lo dejó escrito en sus memorias: Louis Armstrong y la familia judía en Nueva Orleans. Vamos a escuchar Sweet Georgia Brown, interpretada por Armstrong en una grabación en directo. No existían antecedentes musicales en su familia, por lo que su interés por este arte surgió a partir de la escucha de las célebres bandas de Nueva Orleans. Cuando la música le llamó y no tenía un centavo para comprar su primera trompeta, el señor Karnofsky se la compró. Eternamente agradecido y a pesar de ser de fe baptista, Louis Armstrong llevó el resto de su vida una estrella de David colgando de su cuello en honor a su mecenas Aprendió, en primer lugar, a tocar la corneta en la banda de la Nueva Orleans Home for Colored Waifs, un reformatorio para niños negros abandonados a donde había sido enviado en varias ocasiones por delitos menores, como por ejemplo el haber disparado al aire durante una Nochevieja. Allí, aconsejado por el director del reformatorio y uno de sus profesores, optó definitivamente por la trompeta. En 1914, tras su salida del reformatorio, trabajó como vendedor de carbón, repartidor de leche, estibador de barcos bananeros y otros empleos del mismo tipo. Empezó también a trabajar en los cabarés de Storyville, donde estaban concentrados todos los locales nocturnos de la ciudad. Fue allí donde conoció y se empapó de la música de los grandes intérpretes del momento: Bunk Johnson, Buddy Petit y, sobre todo, de Joe King Oliver. Entre 1918 y 1919, ya con una bien ganada reputación como trompetista, fue contratado por el director de orquesta Kid Ory, gracias a una recomendación de su mentor Joe King Oliver, en ese momento trompeta principal de esta orquesta. Louis llegó por este camino a tocar en algunas de esas orquestas de Nueva Orleans, incluyendo aquellas que viajaban por los ríos, como la renombrada orquesta de Fate Marable, que realizó una gira en un buque de vapor a lo largo de todo el Misisipi. El propio Armstrong describiría esta época con Marable como «su estancia en la universidad», ya que le proporcionó una enorme experiencia en el trabajo con arreglos escritos. Cuando Joe Oliver abandonó la ciudad en 1919, Armstrong ocupó su lugar en la banda de Kid Ory, por entonces el grupo de swing más importante de la ciudad. En sus primeras grabaciones con la orquesta, allá por 1923, se incluyeron algunos solos como segunda trompeta de la banda; en 1924, sin embargo, ya era el solista más importante y más creativo del grupo. En febrero de este año se casó con Lillian Hardin, pianista de Oliver, quien lo animó a abandonar la orquesta para alcanzar mayores metas artísticas. Así, se separó amistosamente de Oliver y, se marchó a Nueva York. Su fama llegó rápidamente a oídos del mejor director de orquesta afroamericano del momento, Fletcher Henderson, que le ofreció un contrato para que se uniese a su banda, la Fletcher Henderson Orchestra, la principal banda afroamericana de la época. Armstrong debutó con ella el 29 de septiembre de 1924 en el Roseland Ballroom de Nueva York. Tras decidirse a aprender a leer música, en sólo un año revolucionó el estilo y la forma de tocar de sus compañeros y grabó con las mejores cantantes de blues de la época, como Bessie Smith. De esas grabaciones, 1925, escuchamos a la pareja en Careless Love Blues En este mismo año, 1925, empezó a grabar bajo su propio nombre para el sello OKeh acompañando a dos formaciones creadas por él llamadas Hot Five y Hot Seven, dependiendo evidentemente del número de músicos de cada formación, produciendo éxitos como «Potato Head Blues», «Muggles» (una referencia a la marihuana, la cual tendía a consumir desde siempre) o este que vamos a escuchar ahora: «West End Blues». Louis Armstrong West End Blues Armstrong continuó tocando con big bands, como por ejemplo las de Erskine Tate o la Carroll Dickerson. En 1929 vuelve a Nueva York para trasladarse a Los Angeles al año siguiente. Este hombre no podía parar quieto. Desde esta ciudad inicia una gira por Europa que duraría dos años y en la que obtuvo un éxito espectacular, particularmente en París. La aparición de Joe Glaser en 1935 como su representante y la contratación de la orquesta de Louis Russell como formación de apoyo de Armstrong, marcaron el curso de los acontecimientos durante el resto de la década, en la que Armstrong pasó de ser una simple figura del jazz a un destacado miembro de la industria del entretenimiento en general. En 1940, rompió su relación comercial con la big band de Russell y contrató a nuevos músicos: este nuevo grupo fue el principal apoyo con el que contó Armstrong hasta 1947. Tras pasar muchos años de gira, se asentó permanentemente en Queens, Nueva York, en 1943. Aunque no ajeno al control que del negocio musical ejercían los gánsteres por aquella época, Louis continuó desarrollando su técnica y su carrera musical. Durante los siguientes treinta años, Armstrong llegó a actuar una media de trescientas veces por año. En los años cuarenta, las big bands entraron en decadencia debido a los cambios en el gusto del público: muchas salas de baile cerraron y entre los nuevos medios de comunicación como la televisión y el auge de nuevos tipos de música, las big bands y el swing pasaron a un segundo lugar. Se hizo imposible mantener y financiar orquestas itinerantes de 16 músicos o más. Escuchamos ahora a la orquesta de Luis Russel acompañando a Louis Armstrong en Bessie Couldn’t Help It. Hacia 1947, Armstrong redujo su banda a cinco instrumentos, volviendo así al estilo Dixieland que lo había hecho famoso al principio de su carrera. Este grupo se llamaba All Stars y se presentaron el 13 de agosto de 1947 en el club Billy Berg's de Los Ángeles. En 1964, Armstrong grabó el que sería su tema más vendido: «Hello, Dolly». La canción obtuvo el puesto número uno en las listas de Estados Unidos, superando al grupo inglés The Beatles. Armstrong también obtuvo por el disco un premio Grammy al Mejor Cantante masculino y fue nominado a Mejor Disco del año. En este álbum se encuentra, también, otro tema clásico de Armstrong, «Jeepers Creepers». Como Hello, Dolly ya lo escuchamos en el anterior programa, hoy escucharemos este último. Jeepers Creepers. Armstrong trabajó hasta poco tiempo antes de su muerte y, aunque en ocasiones en sus últimos años se inclinase hacia algunas interpretaciones triviales, en otras era capaz de demostrar un todavía asombroso dominio de la técnica y de la intuición musical que dejaba perpleja a su propia banda. Bajo el patrocinio del Departamento de Estado de los Estados Unidos recorrió todo el mundo, tanto, que terminó por ser conocido como «Ambassador Satch» (embajador Satch). Debido a problemas de salud, restringió sus actuaciones a lo mínimo, aunque siguió tocando hasta el día de su muerte. Louis Armstrong sufrió un ataque al corazón en 1959, del cual se pudo recuperar para seguir tocando. Pero un segundo ataque al corazón en 1971, le obligó a guardar reposo durante dos meses. Se reunió nuevamente a tocar con su grupo el 5 de julio de ese mismo año y, al día siguiente, en Corona, Queens (Nueva York) murió mientras dormía por complicaciones de su corazón, casi un mes antes de cumplir 70 años de edad. Esto ha sido una grabación del famoso Saint Louis Blues, realizada en Nueva York en 1929. Armstrong se acercó a muchos tipos de música, desde el blues más enraizado a los arreglos más cursis de Guy Lombardo, desde las canciones folk hispanoamericanas a sinfonías y óperas clásicas. Armstrong incorporó influencias de todas estas fuentes en sus interpretaciones, a veces provocando el aturdimiento de sus fans, que querían que el artista se mantuviese en una línea más convencional. Mackie el Navaja, que es la canción que acabamos de escuchar fue compuesta en 1928. La letra es de Bertolt Brecht, y la música, de Kurt Weill. El año siguiente, 1929, la incorporaron a «La ópera de los tres centavos» obra de teatro escrita por los mismos autores. Durante su larga carrera, Armstrong tocó y cantó con los más importantes instrumentalistas y vocalistas; entre ellos, con Jimmie Rodgers, Bing Crosby, Duke Ellington, Fletcher Henderson, Bessie Smith y, especialmente, con Ella Fitzgerald. Armstrong grabó tres discos con Ella Fitzgerald: Ella and Louis, Ella and Louis Again y Porgy and Bess para Verve Records. Vamos a escuchar a estos dos monstruos: Armstron y Fitzgerald en Summertime. Algunos músicos criticaron a Armstrong por tocar ante audiencias segregadas, o sea, solo para blancos, y por no tomar una postura clara en el movimiento por los derechos civiles, sugiriendo que era un tío Tom, apodo absolutamente despectivo. Por el contrario, Louis Armstrong fue un apoyo financiero muy importante para Martin Luther King y para otros activistas por los derechos civiles, aunque siempre prefiriese trabajar en esos asuntos de forma muy discreta, sin mezclar sus ideas políticas con su trabajo como artista. Ahora bien, cuando se significó, sus declaraciones fueron muy efectivas: la crítica de Armstrong al presidente Eisenhower, llamándole «two-faced» (con dos caras) y «cobarde» debido a su inacción durante el conflicto de la segregación racial escolar en Little Rock, Arkansas, que fue noticia nacional en 1957.También protestó cancelando una gira por la Unión Soviética en nombre del Departamento de Estado diciendo que «por la forma en que están tratando a mi gente en el sur, el gobierno podría ir al infierno» y que él no podía representar a su gobierno fuera del país cuando estaba manteniendo un conflicto con su propio pueblo. También fue un tipo generoso, hasta el punto de decirse de él que había gastado tanto dinero en los demás como en sí mismo. En fin, un buen tipo. What A Wonderful World Y, bueno, para no perder la costumbre, otra vez nos hemos pasado de tiempo. Pero es que, nos venimos arriba y … Espero que os haya entretenido el programa y sabed que volveremos la próxima semana con más historias, más músicos y más música… mucha música. Hasta entonces… Buenas vibraciones.
Episode 1: Jessica Morris.Jessica Morris is a strategic communications consultant and founder of OurBrainbank, a ground-breaking movement designed by, with and for people with glioblastoma (GBM), after being diagnosed with the disease herself in January 2016. She is a vocal patient advocate for exploring new options to treat GBM and has recently taken part in a phase 1 trial using the herpes simplex virus to treat recurrence of her disease. In this episode we discuss virotherapy, clinical trials, and how the Ourbrainbank initiative can benefit patients.Time-Stamps:2.08 GBM diagnosis3.09 Aim following diagnosis. Staying alive and enjoying life, coming up to 4thyear.3.38 Background, insights on GBM and pathology.5.05 Strategy to tackle the disease5.45 Adding Nivolamab (Opdivo)- a checkpoint inhibitor form of immunotherapy alongside the ketogenic diet, intermittent fasting, and the Optune device.6.50 Interaction between the Optune device and immunotherapy7.09 Recurrence and surgery7.50 Plan of action following recurrence8.23 Clinical trials in the U.S.9.09 Being part of an ‘N of 1' clinical trial.10.37 Ourbrainbank10.52 Virotherapy- Being a candidate for the polio virus trial for GBM and how it works12.16 Insights on the clinical trial framework and eligibility for the herpes virus trial12.35 Being a part of the herpes virus trial (as a phase 1 trial) and how it works13.34 Herpes virus trial- Experiences having the procedure15.23 Herpes virus trial- How did it feel when the adapted virus was being administered via the catheter?15.49 Symptoms of trial- indication of how long spells of fatigue are expected17.01 What was the exclusion criteria for the herpes trial? The clinical trial model and the Karnofsky score19.43 Polio and herpes virus vaccinations. Vaccination before virotherapy trials?21.07 Personalised medicine vs one size fits all virotherapy trials22.18 Were you given any guidelines or recommendation on lifestyle factors that could compliment the treatment and further boost your immune system? Ketogenic diet and intermittent fasting. Oncologist response.24.30 Ourbrainbank- why was it set up? A more patient centred approach with psychological support and second opinions.25.30 advocating for second opinions26.26 How do you feel about patient awareness and access of clinical trials28.30 Ourbrainbank and clinical trials29.11 Ourbrainbank event in London, repurposed drugs and experimental treatments away from the standard of care. Compassionate use programmes.30.12 Ourbrainbank launch and app33.03 more information about the app.34.37 How do you see the future in terms of your endeavours and what do you see the most potential in?37.54 Have you heard about any other patient experiences on the herpes virus trial?39.42 MRI monitoring following virotherapy- effects of initial inflammatory response on tumour?41.28 Perspectives on having a ‘terminal' diagnosis.- views on cancer terminology42.50 How do you deal with apprehension and the mental side of dealing with the disease?45.55 App.- Looking at symptoms. Reactions from clinicians?50.33 Are you able to compliment these forms of documenting symptoms with wearables? Surprising highlight 53.0353.03 Availability of the app and how to find it- share 53.4354.48 Final words and advice to other patients
Dr. Hayes interviews Dr. Muggia about his time at NCI. TRANSCRIPT: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care, and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. [MUSIC PLAYING] Welcome to JCO's Cancer Stories, the Art of Oncology, brought to you by the ASCO Podcast Network-- a collection of nine programs carrying a range of educational and scientific content, and offering enriching insight into the role of cancer care. You can find all of the shows, including this one, at podcast.asco.org. [MUSIC PLAYING] Hi, and welcome to Cancer Stories. I'm Dr. Daniel Hayes. I'm the medical oncologist, and I'm also a researcher at the University of Michigan local cancer center. And I'm the past president of the American Society of Clinical Oncology. I am truly privileged to be your host for a series of podcast interviews with the founders of our field. Over the last 40 years, I've really been fortunate. I've been trained, mentored, and I've been inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired and gain an appreciation of the courage and the vision, and frankly, the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. I hope that by understanding how we got to the present and what we now consider normal in oncology, we can also imagine and work together towards a better future for our patients and their families during and after cancer treatment. Today, I'm pleased to have, as my guests on this podcast, Dr. Franco Muggia. He's generally considered one of the pioneers of new drug development oncology going all the way back to the 1960s. Dr. Muggia is currently a professor of medicine and co-chair of the GYN Cancer Working Group at NYU, and a member of their breast cancer program. He was born in Turin, Italy before the war. But when he was about three years old, his family fled to Ecuador to escape Mussolini's fascism. After growing up there at the age of 18, he moved to the United States in Danbury, Connecticut, to finish high school. And then he received his undergraduate degree in biophysics from Yale in 1957. In 1964, he became a US citizen. But he's remained true to his roots and has been very involved with both US/Italian cancer collaborations and mentorship, and also with South America for decades. He went to medical school at Cornell, followed by an internship at Bellevue in New York City, and a residency at Hartford Hospital in Connecticut. He completed a fellowship in medical oncology hospital in 1964-1967. And we're going to talk about that, Franco. And since he's had a number of important academic positions at Einstein, the NCI, University of Southern California, and New York University on two different occasions, and that's where he still practices. He's been involved in the development of clinical trials of hundreds of new drugs through the years, perhaps most notably, cisplatinum. In regards to ASCO, he served on our cancer education committee and on the editorial board of JCO. In fact, I understand you were the first editor of the Spanish edition of JCO. Correct. Correct. And perhaps more importantly, he's been a direct, and an indirect, mentor of hundreds of medical oncologists of the decades at that many institutions he's served, including myself, frankly, in my association with his good friend, George Canellos. Dr. Muggia, welcome to our program. Thank you very much, Dan. And I would just say, just a comment on the citizenship. So once I became a citizen, I actually became eligible for the draft. And that was the main reason why I ended up at the National Cancer Institute. So it had a-- it was a great effect on my career, that I actually volunteered for the Public Health Service in 1969. Because Lyndon Johnson changed the rules for physicians. And if you hadn't served, you had to serve up to age 35. So I decided I should join, not head to Vietnam like the rest of my classmates-- like many of my classmates from Cornell. And it really was a career change for me. Actually, that's a recurring theme in my podcast series. I have interviewed several people at the NCI in the mid to late '60s and early '70s sort of pejoratively, but actually not. You all became known-- as you've put in some of the things you've written-- as the yellow berets. Right. But in fact, it's really, I think, fundamentally changing-- NIH in general, and especially the NCI. We'll talk about that more later. I know your father was a pediatrician. Leaving Europe in the 1930s must have been extraordinarily painful for him and your family. Can you tell us more about that, and getting to Ecuador? Well, he was-- he never joined the fascist party. In fact, he was best friends with the socialists that remained at that time. Mussolini was brutal. He wanted everybody to become a fascist. And anybody who served at the University lost their jobs. He was in a bit of hot water as well. So that, plus the racial laws, which made Jews not be citizens, led to a big decision in the family. It was a phone call, whether we wanted to join an enterprise-- whether he wanted to join an enterprise in Quito, Ecuador in a pharmaceutical company. And my mother said, I don't know where the place is, but let's go. So that's how it happened. So in a matter of a few weeks, we were gone. And I was three years old. So how did you end up getting to Connecticut? Well, that was-- the American School of Quito, which I was a founding member in kindergarten. There was this person who became Ecuadorian, who was actually born in New York because his father was a consult here in the early 1900s, Galo Plaza Lasso. He decided, hey, we need a school-- a private school that-- non-religious, that competes with the German school that's there. We're going to call it the American School of Quito. So I was a founding kindergarten pupil, and ended up going right through to graduation with my class, except that the last year, I was an exchange student in Danbury, Connecticut. Because our principal, who was a champion swimmer-- Ashby Harper-- and John Verdery, who was at the Wooster School principal, they were together in Princeton. And they decided to make this exchange program, which ended when-- I was the last one, actually, of six years. My brother, he was there three years before. But they sent a person, or two people, to be there for their last year. And now I know you went on to Yale to study biophysics. I'm always fascinated by why people end up making decisions. So you were biophysics major. Why did you go into medicine? Was it your father? Well, my father and my two grandfathers were physicians, actually. So my brother was already-- he preceded me at the Wooster School, and then he went to Harvard College. I decided to go with some of the-- it was a small class. We had 16 people. Four of us went to Yale. So I decided to join the group that went to Yale. And my father thought that I should go into the sciences, but not medicine. One doctor was enough. So I started off, and I was actually doing very well in math and physics. And I was friends with a lot of premeds. But I didn't want to take any pre-medical-- the usual biochemical courses that were given at the medical school. So I decided to go with the head of biophysics major, and that suited me fine. So I started with that. And then I decided, well, you know, that's good. But let me head to medical school. So you had no choice. Actually, the really great story, I know you went to Cornell Medical School. Tell us about the lecture by Dr. Karnofsky, which I think has ended up changing oncology. Yeah, so-- yeah, actually, it was the first lectures we had in medical school as freshman. And we had-- in our 30th reunion a few years later, I talked about Karnofsky, how he inspired me to think about the clinical matters in cancer and his performance status evaluation. I remember that very well. Nobody else did. I have to tell you-- I guess it resonated with me, but not with my other mostly surgeons in my medical school. Well, this is, frankly, a recurring theme in these podcasts too, which is many of our pioneers hadn't thought about going into cancer. In fact, in those days, it almost didn't exist. And then one person made a light bulb come on. I have the same issue in my own career with Dr. Einhorn. So I think all of us need to keep in mind, you never know what influence you're going to have on a medical student. Yes, mentorship is extremely important. And going to class, face-to-face meetings are important. I know you've told me some of the stories too, but when you were at Cornell and located through Memorial, that you ran into some of the luminaries-- Joe Burchenal, Irwin Krakoff, Miriam Isaacs-- Well, I took-- well, that's partly mixed with my internship because I did my internship at Bellevue Cornell division. Yeah. And also, my clerkship. So yeah, that's when I took some electives, too, at Memorial as well. What did Miriam Isaac bring into this one? I think a lot of us know about-- Miriam Isaac was head of the metabolism group. Where did you know her from? I've just heard her name, yeah. Yeah, she was part-- Parker Vanamee and Miriam Isaac ran this physiology. It was called physiology elective. And it was ideal for a third year student. I learned everything, because you saw so many derangements that were concomitant with what was happening with the progression of cancer. But they examined all the issues regarding what led to hyperuricemia, hyperkalemia, any electrolyte imbalance. So you really learned a lot. So that almost gets to the birth of translational medicine, in many respects. We think this is new. It's not. It goes way back. Right. It goes way back. I know then you went on and finished your residency. And most importantly, you are an alumnus of the Francis Delafield Hospital. And that spurred me. I've heard this hospital's reputation my entire career. But I never knew who he was, or what it's all about. Tell us about-- Well, so the city of New York, the city of New York, they really had very good outstanding commissioners of health who decided that cancer hospitals were important to take care of New Yorkers with cancer. And they set up one at Cornell, which was called James Ewing Hospital, which was right inside Memorial Hospital. So they were-- I mean, people don't really remember the James Ewing Hospital because it was annexed into Memorial Sloan Kettering. But the one at Columbia was a separate building. And it was Francis Delafield Hospital. And it had real luminaries from the Columbia faculty, including Alfred Gellhorn, who was a professor of medicine and very charismatic. It was an outstanding group of individuals. Gellhorn presided over a group of about 10-12 internists who were dedicated to cancer and also translational research, as you say. And one of my papers that I wrote to my fellows was on hypercalcemia malignancy with Henry Heinemann, who was one of the internists. He devoted all his effort into physiology, so to speak. So it was kind of the same segue to what we I had at Memorial as a student. But the Francis Delafield Hospital had problems. They had staffing problems because the head of medicine would not send their residents to-- stop sending their residents through the oncology services-- I guess that's what it would be, if you're taking care of medical oncology services. They were in all that way. But it was the Department of Medicine at Francis Delafield. And it was kind of a bit of envy, in part, as one interprets, that Gellhorn was so popular with the students. And so there was all this internal discord with these services at Columbia and Francis Delafield, although Francis Delafield was part of Columbia. So at one point, when the residency finally stopped including, the Bellevue first division residents did rotate through. The first division residents were Columbia service at Bellevue. And they rotated through. So when Gellhorn and another name, the president of ASCO later, Jon Altman-- who was a terrific teacher whom I worked with-- he then left and went to the University of Chicago. And Gellhorn left and became dean at the University of Pennsylvania. I was told to get another job. I was there, starting to be an attending physician. And I went to Albert Einstein. So as you see, I've moved around. I've moved around a lot, but I've moved around always twice to the same place, except the University of Southern California. And there, I go every year. I've maintained my ties with the Trojans. I know that Ezra Greenspan came out of there, and Jim Holland. Jim has told several of us this story, that he was in the military. And when it ended, he thought he was going to go back and be an internist with Dr. Loeb at Columbia at the main hospital. Dr. Loeb called him, and told him there was no space. And why don't you go work at Francis Delafield? And apparently, Dr. Loeb said because somebody always gets mental problems or tuberculosis. And we have to replace them anyway. And so Holland went to Francis Delafield and took care of a young girl with leukemia who sadly died. But it changed his life. That's what made him go into oncology. I deeply regret that I won't get the interview Jim Holland. Yeah, Jim Holland was the first alumnus of that program of the Francis Delafield Hospital. And, yeah, 10 years before I went there. And Jim and I remained friends for many years. We had that friendship in common. Jim gave a-- he was an extremely articulate individual. And when Alfred Gellhorn died in 2007, he gave one of the most touching memorials in his honor. We actually interacted recently through various collaborations here in New York, with first, Jim Holland set up this New York gynecology/oncology group. He was kind of the leader in that, even though he was not involved in gynecology. But he loved to host a group-wide effort. And it happened to coalesce first in gynecologic oncology, because everybody-- they all loved Jim Holland, teaching the gynecologists, but chemotherapy in general. And he's a great leader. So he became very active in the Chemotherapy Foundation, which is a New York foundation, and spoke at the meetings. And his wife, Jenny Holland, was on the board of the Chemotherapy Foundation. We gave them-- we gave Jim an award last year in November, of the Chemotherapy Foundation, for scientific excellence. And he gave one the most unbelievable talks there. Everybody who was there, which were fellows from the New York institutions and lay audience that was there at that event, they really learned a lot by Jim's presence. And unfortunately-- unfortunately, two months later, Jimmy Holland passed away-- less than two months. And of course, Jim passed away in March of 2018. We all miss him. And any of us who had been to the Chemotherapy Foundation, especially when Dr. Greenspan was running it, I always loved that meeting. Actually, when you were at Francis Delafield, what was giving chemotherapy like? It can't be as well-organized. Well-- [LAUGHS] Well, it was organized in the lymphoma service, which John Altman ran. And I was-- so my fellowship at Francis Delafield, it was a bit unusual. It was six months of hematology, six months chief resident, six months again hematology/general oncology, then six months chief residency. So we were involved during the fellowship in running some of the-- and orchestrating the work for the medical residents. In our spare time, we did work in the clinics. And in hematology, I worked with Jon Altman. Did you guys mix up your own chemotherapy in those days? Oh, sure. Yes. Well, that went on when-- actually, that went on when I became attending here at New York University. When I came back from the NCI, we mixed the chemotherapy. So yes. Our younger colleagues don't know this. Nowadays, it's all the pharmacists do it. And the nurses hang it up and start the IVs. And in those days, you guys were on the front lines doing the whole thing, right? Yeah. I mean, we gave vinblastine primarily, but the clinic stereo was vinblastine that we gave. Because the other drugs were procarbazine, nitrogen mustard, of course. There is Chuck Martel of Mayo Clinic fame and florouracil fame. He said he used to do morning rounds to give florouracil at the Mayo Clinic. I don't know who mixed the florouracil for him. I mean, it came in already mixed. But he used to deliver the drugs. Life was different then. Actually, I want to change tracks a little bit, and that is because I know you had a lot to do with the development of supplying them when you were at CTEP at the NCI. You and I were fortunate enough to get to attend the 40th anniversary of the approval of cisplatinum by the FDA. It was held in east Lansing. And that's because Professor Barnett Rosenberg discovered it at Michigan State. Can you give me just some history of that, of what your role was, and why Dr. Rosenberg thought that cisplatinum was a good idea in the first place? Well, I mean, it goes of the drug development program, which was one of the major efforts of the chemotherapy program that was the first program that had oncology involved in it. It was mostly the team in lymphoma, with Gordon Zubrod being the head. And he's the one who recruited Fry/Frederick, and then Carbonne/DeVita group. And they were doing the clinical oncology part. Drug development was a very much part of it. And of the drugs that-- they developed drugs for some of the pharmaceutical industries because pharmaceutical industries had no trials. They had their own pipeline. Now their own pipeline had drugs like nitrosoureas, which didn't go anywhere, and dacarbazine. They were not so robust related to the screens that they used for drug development. But they also had drugs from academia and from the Department of Agriculture. And from academia, they got cisplatin, which was isolated by Barnett Rosenberg at Michigan State, as you heard in that great event that they had, the 40th anniversary of its approval. And he was running electrical currents in bacterial cultures and found that the bacteria were developing-- stopped dividing and developing filamentous forms, which were very unusual. And then he thought it was electricity at first, but then only platinum electrodes had that property. And he and his co-workers made the right assumption that it was platinum. They isolated cisdichlorodiamine dichloroplatinum which was known from a century before to be an inorganic platinum salt. That drug, when I was first at the NCI, my first tour duty as a senior investigator, was broadcasted because it had tremendous anti-tumor activity in the screens. And so when there were press releases, like it often happens, lay people call in and they want the drug for their relatives, or for themselves. And I remember answering phones and saying, no. We don't have that drug. It hasn't been given to people. But the story in 1972, the phase I study was-- I attended the ACR, where they presented. Chuck [? Kerlia, ?] from the University of Illinois, he did the first study. And it had activity. But it bumped off some kidneys and some hearing. And I said, well, who needs a drug in head and neck cancer, or Hodgkin's, where you have such terrible toxicities? Well, guess what? I was wrong. First, you deal with the cancer, then you deal with the toxicity. But it was Jim Holland. Actually, Higby, Don Higby, who worked with Jim Holland at the Roswell Park in the Holland service, who identified remarkable activity in testicular cancer. And that's what carried it. And then Larry Einhorn, of course, carried the ball on that on the development of cisplatin in testicular cancer. The group in the [INAUDIBLE] showed tremendous activity. Eve Wilshaw showed tremendous activity in ovarian cancer, but not quite curative, which is an interesting facet. And then, well, the rest is history. The FDA, that was my second time at the NCI. I had the pleasure of sitting with Vince DeVita at the FDA with Bob Kraut, who said, no, this drug is too toxic. You've got to do some randomized studies. And that was 1978 then. Vince pounded the table and said, the best thing that's happened to oncology, you can't recognize it? You know, there's something wrong with your procedures. So that led to some rethinking. And sure enough, it was approved. No need for randomized studies, given that it was curing testis cancer, but a need for educating how to deal with and cope with the toxicities. Actually, I have-- So that's the story of cisplatin. And it was even further detailed by-- when you were there at that meeting-- by Larry Einhorn and his patient. Yeah. Actually, I have three remarks to this. One is that when I was a fellow, Dr. Fry used to teach us that if the drug works and is curing cancer, we'll figure out the toxicities later. That's a little ruthless, but it's always stuck with me. Yeah. Yeah, we don't want to say it too loudly because toxicities are very important in anything you do. But of course, if you are-- you know, if it's the last resort you're looking for, for something to help the patient-- and it is helping-- you kind of have to bite the bullet sometimes. Those were the days where we had many cures anyway. The other thing that struck me at that meeting is cisplatinum is now used in more than half of all cancers-- adult cancers. I didn't realize it was that common. But that's true. The other thing that I didn't realize, that the number of publications continued in research, continued to increase more than imatinib and trastuzumab. Yeah. And that's the other thing I heard. And the final thing, just, if there are any chemists listening, to get lucky from all this-- it turns out, that trans-diaminoplatinum doesn't work, and cisdiamine does-- dichloro, I'm sorry. And the reason why is entry into the cells, is that the trans doesn't get in the cells. And the cis does. And it just goes to show how important that clinical chemistry is in our drug development. I think a lot of us forget that in the pharmacology. Right. There are actually a lot more things to learn in how the platins interact with DNA. Yes. Actually, another layer I want to go into is your importance and the really remarkable growth in the cooperative groups in the late '90s. Can you kind of give us a brief history starting in 1955, when Drs. Fry and Frederick and Holland started? And then what your role was later on in making it really take off? You're talking about the chemotherapy program? Well, weren't you involved with the qualitative groups and-- With our comparative groups, yeah. Oh, yeah, they came together. Yes, no, for sure. I was there first as an intramural person. And I was briefly on loan to the solid tumor service with Vince DeVita and George Canellos. And then I was in their new-- Paul Carbone had put me in the lung cancer study group there, that led on. So I was strictly intramural. When I returned to Einstein after to doing my service, Vince DeVita became the director of the Division of Cancer Treatment, which is the evolution of the chemotherapy program. As director of the division, he gave me a choice of couple of positions. And I actually took the cancer therapy program position as his associate director for CTEP. His predecessor had been-- my predecessor in that position had been Steve Carter. I don't know if you know about Stephen Carter. No, I met Dr. Carter. He was encyclopedic in the knowledge of all the trials that were done in the-- sponsored by the National Cancer Institute and also abroad. So he became a great face of the NCI internationally. And he spurred the development of the EORTC as well. So that was developed initially through a grant of the National Cancer Institute. So he was involved in the EORTC. But the cooperative groups had started during the leukemia program with the acute leukemia group B, which was the counterpart of acute leukemia group A, which was the intramural program. Jim Holland became the chair of the group. He was such an inspiring leader of the cooperative group. His cooperative group was amazing, to go to one of his meetings, which lasted two afternoons. He really commanded-- it was like a plenary session, and doled out all the projects in one afternoon. And then, in the second day, they kind of review whatever had developed. But other groups started. And the Eastern Cooperative Oncology Group became-- I had joined that when I had gone back to Einstein. It developed under founder Paul Carbone. He had assumed chairman-- no, Paul Carbone became the chairman later on. Initially, it was run by-- it'll come to me right now. I have a lapse on who was the group chair. But it was kind of Boston nurtured. And they were primarily devoted in solid tumors. And they started with making inroads into solid tumor beyond the acute leukemia. But in GI, for example, where I was in the GI committee, Chuck Martel did a number of studies. He ran those meetings, floated ideas. A week later-- we didn't have emails, but a week later, he had the protocol on your desk. Let me ask you a final question, to begin to tie it up here. When you were at the Delafield and then at the NCI, was there a sense that you guys were doing historic stuff? Or was it just day-to-day, same old, same old. Then you look back and say, boy, look what we did. Was there a sense that something big was happening in those days? Oh, no. There was always a sense. Well, when senior investigators, there was always a sense there are a lot of things here developing of interest, you know? And there was a full head of steam in part related to the combination chemotherapy. Now in acute leukemia, it was obvious. But the big thing about the solid tumor service since DeVita and Tom Fry, who started the work in lymphomas. Peter Wernick, George Canellos, they found that the combination chemotherapy did something in lymphomas, and also later on with, also, Jim Holland's work. And you've mentioned Ezra Greenspan. They had seen that combinations of drugs did help, to a large degree, breast cancer. Now the same drugs didn't tried to be extended-- the same principles-- to other solid tumors. It didn't work so well. But breast was somewhat sensitive to the drugs, the alkylating agents and the antimetabolites. So those were the first combinations, and the vinca alkaloids. Let me ask you this, my final question. But I've been a breast cancer guy all my life. And Cushman Haagensen, of course, is a giant. That's the name from the past. Yes. So when you were at Delafield, did he try to oppose the chemotherapy because he felt that a chance to cut is a chance to cure? I mean, he was one of the biggest knives of all time. Yes. Actually, no, he opposed it for different reasons. I never understood why. He didn't only oppose chemotherapy, he opposed hormone therapy, which was coming along. Because he thought that any sex hormones were detrimental to the course of disease. But it was also mostly rivalry with a medical service, I think. Because we saw responses. I did my first trial with progestational agents. So I did some clinical trials, actually, when I was a fellow. So we published an observational series of patients treated with medroxyprogesterone acetate, and presented at the American College of Physicians in '67. So you know, he opposed Gellhorn's intervention in breast cancer medical intervention. He liked to give steroids. And we used to see the patients because the patient developed diabetes. So that's how we got involved in some of the disseminate at the patients with metastatic breast cancer. He wouldn't refer them. So I got involved because I saw a lot of diabetes. And then we started our own treatments. We bonded with the patients and started our own treatments. Again, a recurring theme is how much courage it took for you and your predecessors to do what you do. And the confrontation, if not hostility, between the surgeons. I have to say, that what that really does is it brings up Bernie Fisher and Umberto Veronesi, and the courage they had to adopt systemic therapy as opposed to obstruct it. I don't think our younger colleagues are aware of the battle. Oh, yeah, no. Bernie deserves a lot of credit. And I can tell you of arguments he had with Jerry Urban and other surgeons when he came to a meeting in New York. And Sam Hellman was there. He said, Bernie, we agree with you. I think it's taken us some time to process what you just-- the great thing you have done, to rely on other than surgery. Because they came after him, even I'm talking early 1980. Oh, I was at a meeting. I was at a meeting maybe '83 or '4. It was the first time I'd ever met Dr. Fisher. And he and Urban were sharing a podium. I thought there was going to be a fistfight. Yes. I mean, it was really contentious. And that was an eye-opener for me, where I thought, there's a surgeon up there telling us we should do things that will put him out of business. That's a very interesting approach. Well, yes. And the one thing about Bernie Fisher, he understood trials. And I remember, they said-- Jerry Urban said, why do you think that that curve isn't just going to go down and plummet? He said, it's called probability, Doctor. [CHUCKLES] All right. Well, we've run out of time. I hate to say that because these are great stories. But I want to thank you for taking time. Thank you, Dan, for the interview, for sure. And we do share some common background. And we didn't get to talk about all the international things that came out of the National Cancer Institute. As Jim Holland said in that congressional hearing, the National Cancer Institute was the best international weapon we have had. Yeah, I think that's a great point. And I do regret we've run out of time here. Maybe we can do that in another interview. But I want to also thank you for all you've done for the field and the hundreds of people you've trained. I don't go anywhere where I don't bring up your name, and somebody goes, oh, yeah. I worked with that guy. Well, that's a motive a great satisfaction, I have to say, for sure. It takes just the ability to listen to what your fellows are saying and responding to them. Yeah. That's been my secret. And you're very good at that. I've seen you in action. So thanks again. I appreciate this, and look forward to seeing you soon. Thank you, Dan. I appreciate very much all your questions, and your interview, and your friendship. [MUSIC PLAYING] Until next time, thank you for listening to this JCO's Cancer Stories, the Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or a review on Apple Podcast, or wherever you listen. While you're there, be sure to subscribe so you never miss an episode. JCO's Cancer Stories, the Art of Oncology podcast is just one of ASCO's many podcasts. You can find all the shows at podcast.asco.org. [MUSIC PLAYING]
King Oliver, the Karnofsky's, baby Clarence, that beautiful horn, the end of the whores, drinking with momma and it's time to leave New Orleans...life in Storyville gets more exciting and more dangerous but that beautiful horn just might be the ticket out for Louis via Knit
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Welcome to ASCO's podcast series of cancer stories. I'm Dr. Daniel Hayes, a medical oncologist and a translational researcher at the University of Michigan Rogel Cancer Center, and I'm also the past president of ASCO. Over the next several podcasts, I'm privileged to be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and inspired by many of these pioneers. It's my hope that through these conversations, we can all be equally inspired by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and we can work together towards a better future where we offer patients better treatments, and we're also able to support them and their families during and after cancer treatment. Today, I'm fortunate to have my guest on this podcast as Dr. Saul Rosenberg, who is generally considered one of the pioneers of cancer chemotherapy, especially for lymphomas. Dr. Rosenberg is currently a professor emeritus at Stanford University, where he served as the director of the lymphoma program for several decades dating to the early 1960s. Dr. Rosenberg was raised in Cleveland, where he went to medical school at Case Western Reserve and followed that with an internship at University Hospitals in Cleveland. He then did his residency at Harvard's Peter Bent Brigham, now the Brigham and Women's Hospital in Boston, and completed a fellowship at Memorial Sloan Kettering in 1958. He then moved to the west coast, where he joined the radiation oncologist, Dr. Henry Kaplan, to transform the approach towards lymphoma from one that was principally radiation-based to using radiation and combination chemotherapy. Dr. Rosenberg has authored over 150 peer reviewed papers. He has edited several textbooks, in particular one of the classic textbooks on lymphoma. And his teaching and his mentoring skills are legendary among Stanford trainees and frankly as well as the rest of us. Dr. Rosenberg has won more awards than I can count, but most importantly to me is that he also served as president of ASCO in 1982 and 1983. Dr. Rosenberg, welcome to our program. Thank you. I'm glad to be there. One thing you did not mention [INAUDIBLE] was I spent six years in the radiation oncology laboratory while I was in medical school. That helped start me on my career very much. Actually, you beat me to the punch. I didn't mention it, but I was going to ask you if you had trained there. In fact, that segues. I know you grew up in Cleveland. Can you tell us just a bit more about your background? I know that you entered college at a pretty young age during World War II and then had to step out for a while. Can you give us the background and your circumstances and what led to all that? All that's true. I tried to get into medical school when I was 17 in order to not get into World War II. That wasn't successful at the medical school for various reasons. They thought I was too young and they'd [? hit ?] Jewish quota, so I dropped out for a while, went back to night school, and then reapplied when I was 22. They didn't accept me at that time because of my unusual activities, and so they assigned me to a research lab that I did not pick, which was the atomic energy research lab in Cleveland. It had the initial goal to teach radiation oncologists and to use radioisotopes, but that set my whole career toward radiation. And during the two years in the lab and then four years in medical school, I studied radiation oncology, radioisotopes, tumors, and I developed a great interest in the lymphomas at that time. So did you ever actually then do clinical radiation oncology, or this was all when you were in med school before you became faculty? It was all before my faculty, but I've always been a member of the radiotherapy department. I've taken courses in radiation research and physics, and I'm an honorary member of the radiation societies. That's terrific. And so that must have served you well when you worked with Dr. Kaplan. It was necessary because I presented papers at the radiation meetings, and he recognized me, and when I was searching for a job and the one worked out perfectly at Stanford. And that's how we connected. So can we go back for a moment? I'm very interested in these interviews in why, for example, you chose to go into medicine in the first place. What led to that? And more importantly, especially in the 1950s, when there was no real medical oncology, what got you into doing medical oncology? Well, medical oncology was all an accident because I went into this laboratory and studied radiation in tumors. Before I went to medical school, I didn't have any particular interest in that. When I was a youngster-- five, six, 10 years old-- no one in my family had ever gone to college. Nobody was a professional. But the most respected man in our community was our primary care physician. And since I was a good student, my family and my teachers all encouraged me to try to continue to go to college and be a doctor. And that's what I did. You sure did. [LAUGHTER] Actually, the other thing that was fascinating to me when I looked over your background was your days at Memorial. And so that must have overlapped for sure with Dr. Karnofsky. Can you give us some war stories of that time and what he was like? Well, again, there was a great mistake that turned out so well. There was no oncology program when I left the Brigham, and I wanted to study chemotherapy and medical oncology. The only fellowship was called medical neoplasia, which I applied to at Memorial where David Karnofsky was. I received that fellowship, and in July of 1957, I went to Dr. Karnofsky's office. And he said, "You didn't have a fellowship with me. You have one with Lloyd Craver." So in fact I spent that time not with Dr. Karnofsky but with Dr. Lloyd Craver, who turned out to be the leading lymphoma specialist in the world. And I learned more about lymphoma during that year than anyone could possibly teach me. I did, of course, know Dr. Karnofsky and during that fellowship period, I was acquainted with chemotherapy, nitrogen mustard, [INAUDIBLE] antagonists and [INAUDIBLE] antagonists. So it was a combination of some chemotherapy but mostly lymphoma research. And that set my whole career-- that mistake. I didn't have a fellowship with Karnofsky. [LAUGHTER] I actually always worry about someone I interview who knows exactly what they want to do. I usually say, you know, most of what I did was by luck. [LAUGHS] So sounds like you were too. Oh, absolutely. You know, with both of them, how are they putting things together for the treatment of one problem, though? Is it just let's pull stuff off the shelf, or was there actually some direction in terms of the science they understood at the time? What was the atmosphere at the time? Well, it was very minimal. We had only three lymphomas that we knew we diagnosed-- giant follicular lymphoma, small cell lymphoma, and reticulum cell sarcoma, and of course Hodgkin's disease. But the pathology was so crude that there were very little specific therapies or much difference among the approaches to them. We, of course, used radiation therapy for local treatment. And of interest was that with Dr. Craver, I would make rounds, and we would decide where to give the radiotherapy. We'd outline it on the patient with a red crayon, and we'd write a prescription for the radiotherapy and send them down to radiotherapy. Now that's a remarkable story, because nobody nowadays could even believe that internists could do that. It's unbelievable. Actually, I interviewed Dr. [? Hellman ?] for a previous one, and he gave a similar story that there were very few technicians, and you just kind of drew crayons on the patient and sent them down. [LAUGHS] It's a lot different than it is today. Yes, it is. That's amazing. But the interesting thing was there were no computers at that time, and Dr. Craver's experience with lymphoma-- there were 1,269 cases that I reviewed for him and wrote a wonderful paper, I thought. It was published in Medicine in 1961 on 1,269 cases of a lymphosarcoma. And that set my whole career and my experience that was far above most other people of my age and my training. And that's what really made my career was that study. Now, we had no computer, but we had a IBM cell sorter-- card sorter. And I completed 240 questions on each of 1,269 patients according to their charts, and the data I had was terrific. So you did that with shoe boxes full of punch cards? Oh, at least eight box-fuls because we had 1,269 cases-- three cards for each patient. But the card sorter could just spin out anything that I wanted to know and had so much data that there was no computer. And we had that-- was the first of the data systems that made it possible. And-- That's amazing. It is. And you did all the chart reviews yourself? I did all of it myself because I was disappointed I wasn't with Dr. Karnofsky. But I made the best I could. And it was actually a wonderful experience with Lloyd Craver. Now, were most of those patients treated with radiation or was chemotherapy part of the game yet? Well, we didn't have much chemotherapy at that time. We had steroids. We had radiation. We began to have some Leukeran and Cytoxin by the time I left there, but most of it was radiation and medical treatments with steroids. And very few patients had prolonged survivals, except for the follicular lymphomas which have such a good natural history. Yeah. You mentioned that the very few classifications of the lymphomas-- can you give us some insight into when-- I live in Ann Arbor, for example, so the Ann Arbor classification, of course, is near and dear to the hearts here. But how did that all begin? I know you were involved in that early on too. Well, I did very much. And the important work was done by three people-- Henry Rapoport, who at the time was in Chicago, Robert Lukes, who was in USC, and the German group. And they began to separate out the different forms of lymphoma. Henry Rapoport described the difference between follicular and small cell. And Lukes was careful about the Hodgkin's disease. So their classifications began to be used in the 1950s and in the early 1960s. And they make dramatic differences. Ron Dorfman was a student of Rapoport at the time, though he came from South Africa. And fortunately, he came to Stanford, and that gave us a really-- step ahead on good classification. Eventually, there was great debate about which the right classification it was. And we did a study for three years comparing six classifications around the world and which one gave the most data. And I was the principal investigator of that, and that led to a unusual classification called the National-- I can't even remember the name of it now. But it was a very unusual name, and nobody adopted it. Eventually this classification was dropped, and the new classification came out with immune markers and made a great difference. But that classification in pathology was the stimulus that led to the more modern treatments of that time. And that was one of the great advances that led to two important research studies-- one in Paris and one in Rye, New York, which were virtually entitled "The obstacles to the control of Hodgkin's disease." But the pathology classification systems facilitated that along with tremendous advances in radiotherapy. And I would assume almost-- what's called precision medicine now and targeted therapies-- those allowed you to begin to separate out patients who really didn't need systemic therapy and those who were more likely to benefit from the chemotherapy part of it. That must have really been an eye opener for you as you began to realize that. Well, chemotherapy began to become more successful, of course, for leukemias and lymphomas during that period of the 1960s-- the early '60s. But radiotherapy was the only successful treatment that could control disease for long periods of time until good chemotherapy and combination chemotherapy became available. But the radiotherapy advances really advanced the treatment of Hodgkin's disease and some of the lymphomas dramatically. So that actually, in some ways, segues to my next set of questions. How do you get from New York to Stanford? You said Dr. Kaplan had seen you present. Did he see you as joining him as another radiation oncologist, or did he see you as bringing in the therapy to complement what he did? Well, the truth is I was offered a job at Harvard by Farber, and he told me I could treat patients with cancer at the Brigham, but not lymphoma and leukemia. So then I went back to Cleveland, where they did offer me a job in radiotherapy. But the new chairman of medicine did not think that oncology was an appropriate field for medicine. So I had to call Henry Kaplan as a third choice. And he rapidly accepted me and insisted that I had a role in the department of medicine, which they gave me. So I had faculty appointments in both, which I still have today. Why did Farber not allow you to treat lymphoma? Because he thought it was his property. He didn't want it over in the other hospital. Ah ha. That's-- he had passed away before I got to what was then the Sidney Farber Cancer Institute, but I've heard stories like that. So when you got to Stanford then, how did you all start working at chemotherapy? I know that was before the time that the folks at the NCI had really reported the high response rates with combinations. You must have taken that along with you. Well, I knew that, but the treatments with more than one drug wasn't really popular at least until the early '60s. When I got to Stanford, they put me in the hematology department where I was supposed to do hematology, which I only had minimal training in. But I had a lab in radiation oncology, and I was in the clinic with Henry Kaplan, and we decided that we would treat Hodgkin's disease because of the development in radiotherapy. But I insisted that I would treat cancer in the department of medicine, and that was not popular anywhere in the country. And after they found out I couldn't do much red cell medicine, I started a program for cancer patients, and we needed a name for it. And I got together with four people, BJ Kennedy, Paul Carbone, and the fellow at Hopkins-- what's his name? I'll remember it. But with four of us decided that we would have cancer treatments in the departments of medicine, and we would call it oncology. And that's where the name began. And several of them at Hopkins and at Minnesota had separate departments of oncology-- eventually departments of cancer. So it was very unpopular in departments of medicine, and hematologists to try to prevent us from treating cancer in departments of medicine for at least 10 or 15 years. Gradually, we established what we were, and now it's one of the largest divisions of most departments of medicine. Yeah, I think most of our younger colleagues would be surprised by that. I came in in the early '80s and was struck by the fact that most of the major departments of medicine had given oncology away because they felt that the smart folks were working on in red cell stuff, as you pointed out, and the dumb folks could go get 5-FU. What they didn't realize was that there was a tsunami of academic interest and advances just down the pike. And it's interesting that you had to go make your own department just to be able to do that. What were the facilities you had at Stanford to give chemotherapy? Did you just have a nurse that followed you around and gave it, or did you actually have a fusion space or-- Nothing like that. I separated from the hematology clinic, and I would see patients in my own room. There was only one room. I found one fellow who had trained as an [? NCI ?] named Richard Shaw. And we began treating patients with breast cancer and ovarian cancer and children with various childhood malignancies and leukemia. And curiously, when we gave nitrogen mustard, we did it in the hallway of our clinic, and start an IV and mix up the nitrogen mustard and inject it rapidly. There were no infusions facilities whatsoever. It took many months and years to develop what you now think of as a cancer clinic. So you mixed up your own chemotherapy? We did, and I treated any kind of cancer, including children. And we began to see some responses. But the drugs began to come in in which we had a little bit of benefit, but before we could get combination chemotherapy, especially for the lymphomas and leukemias, we didn't have a lot of success. And how did you get Referrals As the department of medicine didn't like what you were doing, did they all come from the surgeons and the radiation oncologist or-- Yes. Where'd they come from? Mostly referrals, but also Stanford began to let it be known that we would see patients with cancer and make a diagnosis and refer them to the proper departments for treatment, and that we had medical treatment. So we attracted patients from the community. Stanford didn't have a big clinical program until it was transferred from San Francisco, but our cancer program became known. I must give great credit to Henry Kaplan, who was a tremendous power and leader of the field. And that attracted a lot of cancer patients to Stanford. And of course, you know that Henry Kaplan and his colleagues invented the linear accelerator, and that made a huge difference in the way we treat patients even today. So he and Ed Gintzon, who is a linear accelerator man, invented the linear accelerator which provided us with super voltage therapy of one million electron volts or more. And that completely revolutionized the treatment of cancer. Yeah, even when I broke in in the early '80s, that was not universally around, but you would see patients who basically were put in front of the machine. They turned it on for a couple seconds-- not at Harvard but outside the Harvard. I know nothing about radiation oncology, except I knew that wasn't right. [LAUGHS] And so we owe Dr. Kaplan for lots of reasons, really-- in great debt, but that probably is one the greatest step forwards. Can I ask another question. I've always been struck that you were one of the early proponents of randomized trials of lymphoma. That must have taken a lot of courage. Well, it was necessary for me because Henry Kaplan wanted to use very broad fields in high doses, and he thought that he was improving the cure and survival of patients. And I admired that and accepted it, but I thought that he was giving too much-- too wide a field and too high a dose for various reasons. So I insisted that if I were to see patients in radiotherapy that we would do trials that would compare two strengths of treatment primarily with radiotherapy-- one with very extended fields and high dose and to just the involved sites. And that's what my program was. And he wanted to extend the fields beyond where the disease was. And we did randomized studies beginning in 1962. They were one of the very first clinical trials that were done in cancer and certainly the first ones in lymphoma. And those clinical trials modified and went on for years. We gradually proved that both of us were correct. Neither of us had an advantage over one or the other, but we learned a great deal about the diseases and their natural history and how to modify the treatments. And of course, eventually chemotherapy came in, and we combined it. But it's a very long story the trials continue to today. We've treated over 3,000 patients with Hodgkin's disease on these trials. And we couldn't have been more successful. Yeah, I think and again that was just about the time that Dr. Fry and others were starting the cooperative groups that could do randomized trials in those days. And you couldn't have had many role models. And again, "courage" is the word I coming up with to get patients to agree to be in a trial where the treatment wasn't assigned until after they signed up. These days we take it for granted, but it was not then true. Well, it's true, but also Dr. Kaplan and I were very good clinicians, and patients trusted us. And they all accepted going on trial as long as both of us agreed that we didn't know the best thing to do. So that was the basis for a randomized trial. And our numbers of our patients were very small-- would never be accepted today as a trial. In fact, we could-- our statistics would not really show the advantage of one treatment over the other. But what our statistics showed was we had patients surviving with a relapse free period-- a plateau-- that went beyond 10 years. And that was unknown in Hodgkin's disease at the time. It became unknown in large cell lymphoma as well as at the time. The late Jim Holland who I loved and helped mentor me in some ways, but when I first joined [? TLGB ?] was sitting in the back of the room when I was presenting the proposal for randomized trials and yelled from the back of the room, "Hayes, if you need a statistician, it's not worth doing." I said, "With all due respect, Dr. Holland, I think it is-- we're doing. But we need a statistician for that." [LAUGHS] All right, so Dan, I had this same argument with J. Fry, right? He said that it was a scandal to have a control group. And I remember in public meetings, I would tell him only you and God know the difference between these two groups. [LAUGHTER] We argued for 50 years until he finally came to Stanford as a visiting professor, and we connected and admired each other's work tremendously. Well, justifiably. I want to ask another question. You've been involved with ASCO almost from the start, I think, and I noted you were present in the early 1980s. What made you run for president of ASCO? In those days, there wasn't much of an organization. It was 3,000 or 4,000 people. What did you see in ASCO that maybe others didn't at the time? Well, I was forced to join by Vince DeVita. He was a member a few years before I was, and he talked about what he thought was right. And I thought that I was right. But the society made a big difference about bringing us together. And then Al Owens, who was at Hopkins, became president, and he invited me to be on the board and then to be his program director. So that's how I got in. Both DeVita and Owens forced me to join them. Then I became a member of the group and committed to it because there was so much value in sharing our information and data. Well, I don't want to put you on the spot. This year we had 43,000 attendees at the meeting, I believe, in Chicago. Do you recall what year and where your first meeting was, and how many people were there? I can't recall. [LAUGHTER] I think when I was president, there were about 8,000 attendees at the meeting. And we all went from one city to the other-- San Diego, New Orleans, St. Louis, San Francisco. But it got out of hand when we got up to $25,000, and the only place we can meet was in Chicago, which was a great loss because Chicago is a great city, but it was great fun to go all over the country. Yeah, I think we'd agree with both of those, but Chicago handles this pretty well. So it's worked pretty well. We're starting to run out of time a little bit, and I want to ask you a big picture question. And you've hit some of these. So what really is your legacy? How would you like the world to remember what Saul Rosenberg has contributed to the field? Is it your science or the administration issues you set up so that people actually accepted our field or the teaching and mentoring? I mean, you've mentored, in my opinion, some of the great oncologists in the world. How do you think this will come out for you? There's only three things that I'm going to leave after me-- my children, my students, and my patients. And my advances for treatment were tremendous but are all now overturned and built upon. But my students, whether it be medical students or postdocs or my colleagues, were my greatest advance. I am so proud that they have succeeded so much. I felt that I have been a trunk of a tree, and every branch that comes off carries twigs and flowers and plants and exaggerate or emphasize-- multiply what I have done just because I started them off. So nothing has been more important to me than to be a good teacher. And my students all know that I'm a wonderful doctor. That's what they tell me. And to be a careful, caring physician, how to talk to patients, how to examine them, how to tell them good news and bad news-- the skill of being a medical oncologist, and actually to be a physician in general is such a joy. I mean, to have these people depend on us and believe in us the moment you walk in the room, if you're gentle and you know how to touch them and to talk to them-- this is such a joy. I can't think of any other word in being a physician but especially being a medical oncologist. It has been a joy. And are you still seeing patients? I saw several this week. I've cut way back. Yeah. I see patients every other Monday. I see mostly my old patients or recent Hodgkin's patients, but gradually fewer and fewer. But there's-- I have 20 patients, perhaps, I won't give up. None of them have lymphoma anymore, but they all have complications of treatment, and they will not let me retire. And 60 years ago, did you think you'd say that you have a bunch of patients who look like they're cured of lymphoma? Never. Yeah, it's something else. Well, Dr. Rosenberg, you've been a great role model for all of us in the field, and we very much appreciate what you've contributed. I have to say your final statement is very similar to what other people have said to me as well-- George Canellos and others-- about their greatest accomplishments are the people they trained, and those of us who you have trained take that very seriously. So thank you. It's a great honor to talk to you. I hope the new therapies-- immunotherapies-- are going to make a big difference. I think they have promised to do so. And sometimes I get to be cynical. I mean, I've been through about six waves of great enthusiasm in treating cancer, chemotherapy, immunotherapy, the old-time advances in radiotherapy, genetics. And gradually there's been improvements but not the great breakthroughs that I want to see. Maybe this new approach will make a difference. I hope so. Yeah, it looks like it. I said to a first year fellow last week that never in my lifetime could I think I'd say it looks like 20% of people with metastatic melanoma may be cured, and that looks like what's happening. That's pretty exciting, I think. How about 90%-- Yeah. --of Hodgkin's patients? Well, actually a lot of that you had already knocked off before I got in the field. [LAUGHTER] Yeah, and I thought this is going to happen again. And it didn't for quite some time. But I agree with you. I think things right now are really, really starting to happen. And we actually have just scratched the surface of the immunotherapy world. I think there are a bunch more checkpoints that are going to be discovered and therapies for them. So the toxicities are considerable, but as Dr. Fry always taught us, "Cure the cancer first, and we'll figure out how to take care of the toxicities later." And I think that's a pretty good strategy, actually. Thank you. I actually-- [INAUDIBLE] Yeah. OK, that's all. Thank you very much. I really enjoyed this. You know, I've told other people it's like if I hop in a cab with Saul Rosenberg, what would I ask him for the next 35 or 40 minutes on the way to the airport? So this is fun for me. All right. Thank you for asking me. For more original research, editorials, and review articles please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.
The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnoses or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Hello. Welcome to "Cancer Stories." I'm Dr. Daniel Hayes, a medical oncologist, and translational researcher at the University of Michigan Rogel Cancer Center, and I've also been the past president of ASCO. I'll be your host for a series of interviews with the founders of our field. Over the last 40 years, I've been fortunate to have been trained, mentored, and inspired by many of these pioneers. It's my hope that through these conversations we can all be equally inspired, by gaining an appreciation of the courage, the vision, and the scientific understanding that led these men and women to establish the field of clinical cancer care over the last 70 years. By understanding how we got to the present and what we now consider normal in oncology, we can also imagine and work together towards a better future, where we offer patients better treatments and we're also able to support them and their families during and after cancer treatment. Today, My guest on this broadcast is Dr. Samuel Hellman, who is generally considered one of the fathers of modern radiation oncology in the United States and frankly, worldwide. Dr. Hellman is currently a professor emeritus at the University of Chicago Pritzker Medical School, where he served as the dean from 1988 to 1993. And he's been the A.N. Pritzker Professor of the Division of Biological Sciences. He's also served as the vice president of the University of Chicago Medical Center. Prior to moving to Chicago in the late 1980s, he had previously been physician in chief and the professor of radiation oncology at the Memorial Sloan Kettering Cancer Center. He served there from 1983 to 1988, and he was also chair of the Department of Radiation Therapy at the Harvard Medical School, where he served as the co-founding director of the Joint Center for Radiation Therapy. Dr. Hellman has authored over 250 peer-reviewed papers, and he's been one of the co-editors of one of the leading textbooks on oncology, Cancer, Principles and Practice. Dr. Hellman has won many awards and honors, including being named a fellow of the National Academy of Medicine, formerly the Institute of Medicine, and of the American Association for the Advancement of Science. He is frankly, one of the few individuals to serve as president of both the American Association of Cancer Research and the American Society of Clinical Oncology, for which he was actually, I believe-- correct me if I'm wrong Dr. Hellman-- the first radiation oncologist to hold that position, which he served in 1986 to 1987. Dr. Hellman, welcome to our program. Thank you for having me. I hope I got all that right. Your introduction has taken longer than some of the others. You have been so prominent in the field. I have a series of questions. The whole point of this is sort of like Jerry Seinfeld's Riding in a Cab with Friends. I've always said, if I had an opportunity to right with some of the giants in our field, what would I ask them during a cab ride? So I get to ask the questions, and you get to answer. I know you grew up in the Bronx. Can you tell us a little bit more about your background? I'm particularly intrigued about the fact that a boy from the Bronx ended up at Allegheny College in Pennsylvania. Why'd you go there? What was your interest? Was it always in science and medicine, or did you have something else in mind? OK. Well, start with the Bronx. I was born in 1934 in the Bronx in a nice part of the city, which doesn't often go with descriptions of the Bronx today, but it was at that time. And about well, 1950, which was when I entered my senior year in high school, I had gone to high school at DeWitt Clinton High School. And as I say, my senior year, we moved to Long Island, and I spent my senior year at Lawrence High School. The important part of this is that Clinton had about 4,500 to 5,000 boys, and Lawrence High School was much smaller and most importantly, coeducational, and that made me very much want to go to a smaller school for college and definitely one that was coeducational. And so my mother and I took a little tour of colleges not too far from New York, but Allegheny was the farthest, I think. It's in Western Pennsylvania, very close to the Ohio border. And it was a beautiful day. I had a very nice two people showing me around, and I became enamored of the place. It was a very good fit for me, but I must say, my method was not a very analytic one, but that's how I got to Allegheny College. And was science and medicine in your thoughts then, or did you have other things that you thought you'd do? No, no. I was a middle-class Jewish boy from the Bronx. You're programmed to be interested in medicine. The old comment was, you know what a smart boy who can't stand the sight of blood becomes? The answer is a lawyer. And I was not offended by the sight of blood. So I actually heard about your decision to go to SUNY Upstate Syracuse and the serendipity involved. And I'm always struck by how so many of us have what we plan and what we end up doing. Can you give us that story? I though it was really fascinating. Well, I'm not sure what part of it you want, but I went to Syracuse Upstate because I won a state scholarship, and I hadn't applied to any New York state schools. And fortunately, the medical school advisor and a former Alleghenian, who was at Upstate, arranged an expedited interview, et cetera. So anyway, that's why I ended there. Why I ended up in radiation oncology-- Well, that was my next question is, how did we get lucky that you decided to go into oncology? Well, I interned at Boston at the Beth Israel Hospital, which was essentially very oriented to cardiovascular disease. Our chairman was a renowned cardiologist. He was the first one to use radioactive tracers. He used radium, as it turned out, and there is an award given by the nuclear medicine society. Their big award, their annual award is the Hermann Blumgart Award, and Blumgart was my chairman. And Paul Zoll, the external defibrillator inventor, was there. Louis Wolff of Wolff-Parkinson-White syndrome was there. So it was a cardiac place. And internal medicine was what I wanted to do, but my father was quite hard of hearing and had a lot of trouble making a living, because he was so impaired. And electronic devices, of course, weren't available at that time. And it was widely thought that otosclerosis which is what he had, was a hereditary disease. And so I was discouraged somewhat from entering medicine, not being able to be sure I could use a stethoscope. Parenthetically, I have never had any trouble, and the disease is no longer thought to be hereditary but rather the sequelae of infectious diseases, either diphtheria or influenza. This was the great influenza epidemic. The two, one of those two. But anyway, that's what he had, so I sought to do something else. And I was a little bit put off by taking care of disease which we really could not alter the course of. We could modify it. We could palliate, but probably if I were more dexterous, I would have become a surgeon. But I wasn't, and so I decided I didn't know what to do. I'd take a radiology residency and see where that led. This was late in the year, and there were no radiology residences, literally, in Boston that were available. But a new chief had come to Yale, and he was starting a new program. And one of radiologists in a neighboring institute told me go there. So I did. Well, he turned out to be a radiation oncologist, and he, Morton Kligerman and Henry Kaplan, were the two chairmen of departments of radiology who were radiation oncologists. And Henry had been at the NIH and got them to, with the National Cancer Institute, I guess, to start a fellowship program to encourage radiation oncology. And Kligerman applied for one, got one. I was there. I was captivated by the opportunity to do some curative treatment. I was a chemistry major in college, and physics and chemistry were things I enjoyed. Sounded like a good choice, so that's what happened. So there could not have been very many specific radiation oncology fellowship programs at that time in the United States. Is that true? Yeah, very much true. The ones that stood out was, I say, Henry Kaplan's. There was a very good one at UCSF. And there was one in Penrose Cancer Hospital and one at the MD Anderson, and those were the ones. So your decision to go oncology then, really your decision to go into radiology-- diagnostic radiology originally, sorry-- didn't sound like you were-- Not really. I took a radiology residency, because I thought it would be helpful whatever I decided to do. I really didn't expect to go into diagnostic radiology, but I figured that's something I could do. I didn't have much training or any training in that before. There was a great dynamic radiologist at the Beth Israel Hospital, and he captivated me. And so I figured, there's a lot to learn there, and I'll try it. I think a lot of the younger doctors don't realize that the two were together for a long time. What's your perspective of the split between diagnostic and therapeutic radiology-- I've actually heard you talk about this, so I think I know what you're going to say-- and bringing them back together? Well, I was a great proponent of it. The whole fields are entirely different. But having diagnostic radiology is extremely helpful in radiation oncology, because we depend on images to determine how we treat, where we treat, and so forth, so it was there. But they were interested in entirely different things. And just parenthetically, when I took the Harvard job, I wasn't going to take it unless I had a promise that we could start a Department of Radiation Oncology. Shortly after I came, and the decision was made with just a shake of the hand that, after a year or two, I'd be able to do that, and that's what happened. Actually, that segues into another question I had is I was looking over your background. I met you first when I was a first-year fellow at the medical oncology. That was 1982, by the way, a long time ago, when it was still the Sidney Farber. And I'd heard about your legendary efforts starting the Joint Center and also your teaching methods with your own residencies. But you were rubbing shoulders with Sidney Farber and Francis "Franny" Moore and Tom Frei. That must have been pretty intimidating for a relatively young guy trying to start a whole new department. What was the impetus behind that? It was an interesting experience. Dr. Farber was, of course, the dominant figure in cancer at Harvard, and nationally, he was one of, if not the great leader. I mean, but he was a difficult man, and I don't like to speak disparaging, but we had a rocky relationship. When the Joint Center-- I'm getting ahead of my story, but it's appropriate to this question. When the Joint Center was started, it was started by Harvard Medical School, and the dean for hospital affairs was a man named Sidney Lee. Dr. Lee had formerly been the head of the Beth Israel Hospital, the director, not the chairman of medicine but the director. And he got the idea that all the hospitals in the Harvard area were relatively small, the Mass General was across town and quite large, but that was not true for the Brigham or the BI or the Deaconess or what at that time was the Boston Hospital for Women. And so he got them all together. So there were those, and I think I left out the Children's, but Children's was amongst them, as well as the Sidney Farber, as you say. Or at that time, it wasn't called that. It was called the Jimmy Fund, but that's another story, and one you know better than I, I suspect. But anyway, those six were to get together when I started the Joint Center. Because Dr. Farber and I had so much difficulty with each other-- he wanted really for me to be reporting to him and being part of the Jimmy Fund but that wouldn't have worked with the other hospitals. He was not liked by any of the places, including Children's, which is where he was the pathologist. So those six initial institutions, when we finally came to sign, turned out to be only four because the Children's wouldn't come in, and the Jimmy Fund wouldn't come in. For a number of reasons, two years later, they acquiesced, mostly because we were successful, and they were without supervoltage treatment, and it was just not sensible for them not to join. But that's my relationship with Sidney. Franny Moore is a different story. Franny Moore was an internationally-known surgeon and expected to have his way, but he was very graceful, very nice. I had very few disagreements with him. He expected, and I think, deserved certain deferences. Sydney did, too, but it just made it too difficult to do that but Franny was not that way. Franny and I came to the treatment, conservative treatment of breast cancer from different points of view. He didn't agree with it, but he was entitled to his opinion, and he was fine. Tom is a different story. I got there ahead of Tom, and he came, and if anything, I helped out Tom, although he was much senior. Harvard has its own culture, as you know, and he needed at least an introduction. I mean, he sailed along fine after that. And in fact, at one time, he and I wanted to start a joint residency program. It was to be a four-year program, which would have people take two years together and two years in their respective specialty. But the boards were not in agreement, so it was dropped. But Tom and I always got along fine. Actually, that raises one of my other questions. I spent a lot of time in Europe, and the field of so-called clinical oncology still remains, combining radiation and medical oncology. In fact, they style it as a particular specialty in Great Britain. How did it evolve not that way in the United States? Radiation oncology went off on its own. And I think you had a lot to do with really professionalizing radiation oncology as a specialty in this country. Is that not true? I'd be interested in your perspectives on this, too. Well, I should parenthetically say that I spent a year in the National Health Service in 1965, while I was a fellow at Yale, in clinical oncology at the Royal Marsden Hospital, their major teaching hospital for cancer. And I always believed in the joint efforts of a non-surgical oncology program. You can include the surgeons, mostly because their lives are so different and their technical training is much more extensive, but you can work closely with them, and I've been fortunate to be able to do that. But medical oncology and radiation, in my judgment, would be better off close together. And your comment about me and ASCO, being the first president as a radiation oncologist, and I never call myself a radiation oncologist, at least not initially. I always call myself an oncologist. But I do, I agree and then describe what I do as radiation. But I agree with you, they have the best title-- clinical oncologists. And why it occurred the way it occurred, I'm not sure. I know we started in radiology and medical oncology started in hematology. I mean, the real revolution, and leaving aside Dave Karnofsky and his work, the real changes occurred in acute leukemia. And the real founders of the specialty, Dave was surely one of them, but a great many of them were all hematologists, leukemia doctors, and it grew from there. It grew out of hematology. And a lot of major oncology papers were in Blood, the journal Blood before they were in JCO. So that's the best I can do with it. Our big thing was to separate from diagnostic. Getting closer to medical oncology is much easier, because we have the same book. You said I wrote the textbook with Vince and Steve, and so I did. And that was very easy. We spoke the same languages. We saw the same things, not completely. I saw more head and neck. Vince saw more of the hematologic malignancies, but the rules were similar. It was no-- it was easy. And I've heard Dr. Frei-- I trained with him when he was alive and obviously, Dr. DeVita talked about what it was like to give chemotherapy when they started. And how we really professionalized, in many ways, and split up giving chemotherapy, the different responsibilities. What was it like with radiation oncology back 40 years ago? I mean, how did you-- the safety issues, were you all cognizant of the safety issues related to radiation at the time? How did you do your planning? What was that like? Well, safety was-- Hiroshima made everybody know a lot. In fact, if anything, we were more conservative than we probably needed to be because of radioactivity being an evil and all the things that happened after '45 and at Hiroshima and Nagasaki experience. And so safety wasn't a problem that way. But there were a lot of people in the field who were using the field, who are not radiation oncologists. Some of them were radiologists, diagnostic radiologists and did it part time. They had a cobalt unit, before that, just an orthovoltage, conventional energy, much less effective and more damaging. And also gynecologists, and when I visited Memorial Hospital early on in my training, and the surgeons would send a prescription blank, a regular prescription dying down to the radiation therapist. And that's what they were, technicians, or often were. And they may have differed with the prescription but only by being careful and discussing it with the surgeons and convincing them that some change should be. That's very different. How was the planning done? How was the planning done? The planning was fairly primitive. Well, most places had a physicist, usually a physicist, who did both diagnostic machines and conventional radiation oncology, and they were important in that department and those people subspecialized, too. And in fact, when I came to Boston in 1968, Herb Abrams, who was the new chairman of radiology-- he's the one who chaired the committee that selected me-- but he and I jointly started a physics department. So it was still in diagnosis as well as therapy, but we realized that wasn't a good idea and separated. So physics was evolving, but treatment planning before supervoltage, and even with supervoltage before multileaf collimators and a lot of the newer, what then were newer techniques, was reasonably rudimentary. When I did my residency, we did our own planning, and usually, it got checked by the physicist but not all the time. It's a lot different now. Yes, it is. I want to turn this to an area that's more personal to me and that is your role, out of all the many contributions you've made to the field, your role in the field of breast-preserving therapy. I came in just as you and Jay Harris were really making that institutionalized. Just for our listeners, what were the hurdles there? They must have been both personal and professional and technical. And did you ever doubt that this be successful in the long run? You must have had some second thoughts about getting into this. Well, I have to back up. It was well before Jay, but it was at Yale. And apropos of how many-- going back to our previous question-- how few radiation oncologists there were. There was a club. Before there was a specialty, before there was a society, there was the American Club of Radiation Therapy. And all you had to do to belong to it was do radiation therapy without doing diagnostic radiology. And I was in the low 200ths of the consecutive order of people who belonged to the specialty from its very inception at the turn of the century. So there were very few of us, and we knew each other extremely well and had these little conversing meetings. And a number of people would talk about patients who had medical diseases which wouldn't allow them to have their breasts removed. They still had localized, apparently localized breast cancer, and the radiation therapist took care of them, and I did, too. I had these people. And we also had the Europeans, especially the French, who were treating breast cancer with radiation. In fact, they were doing it with a fundamental difference with what we did from the beginning and they do now. And that is, they did it without removing the breast cancer, because they were doing it primarily for cosmetic reasons. And they felt that taking out the breast cancer might damage the cosmetic effect. So we weren't alone. We weren't first. So I knew that other people had done it. Some people who did, Simon Kramer in Pennsylvania at Jefferson, Thomas Jefferson, did a great deal of it. And we did it, because we had a surgeon at Yale who was interested in sending patients. You mentioned Jay, but really, before Jay, there was Lenny Prosnitz, who you may or may not know of, who was a long-time chairman at Duke. But Len was a medical oncologist at Yale, who was about, I don't know, three or four years behind me in training, and I was either a young assistant professor there at the time or a fellow, I can't remember which. And he came over to me and said, you've got a nice life. You do interesting things. I'm not so crazy with this. Can I get into it? And Lenny, obviously, being trained in medical oncology, being a boarded internist was also interested in breast cancer. Because that's the one disease, even in the beginning that medicine, or one of the few diseases that medicine was interested in for the hormonal aspects of the disease. So Lenny took over when I left with the surgeon Ira Goldenberg, and he kept it up. And when I went to Harvard, I had all those different hospitals, and I had a very good colleague there, who was the only radiation oncologist in those hospital complex, and he also treated some. So we continued to do it. One of the nice things about Harvard at that time was, at least for this purpose, was we had this women's hospital, Boston Hospital for Women. And gynecologists in those days did everything for women and that included breast surgery. And those guys delivered their babies and when they got breast cancer, took care of them. They weren't interventional. They were their private primary care docs, and they were much more sensitive to the cosmetic aspects and the self-image aspects of breast cancer surgery. And so they knew we did it, and they became a big source of suggesting patients and sending them to us. Anyway, Marty, Marty Levine, the fellow I was talking about, and I developed a reasonable number of them. One of my residents, Eric Weber said, why don't you write a paper about this? I said, it's all done. The French have it. The Brits have it. Even the Canadians have it. He said, we don't. So I said all right. We sent out the paper, and the first paper is with Eric and Marty and me, and it was a JAMA paper and that gets to another point. What year was that? I had to bully pulpit. What year was that, the JAMA paper? The JAMA paper? About '75-- '74, '75. And it made a big splash. And then Lenny and Simon Kramer and Luther Brady, two Philadelphia people who had big experience, and us put all of our stuff together. And Lenny brought it all together, and so there was another big paper. I think that one was in JCO, but maybe not. I can't remember. And I think that's how it got started. And my issue with it and my involvement in it is, yes, pioneering the treatment in America. I don't claim to have pioneered it anywhere else. It wouldn't be true. But what I did do is use the bully pulpit of being the Harvard professor, and I went everywhere and talked about it. And I took on the surgeons in a number of places and talked about it. And if I made a contribution to it, it was that. I can remember being in an audience and hearing you talk about the Halstead theory and then the Fisher theory and what became known, in my opinion, as the Hellman theory, which is a combination of the two. That both local and systemic therapies make a difference, and the mortality rate of breast cancer has dropped by almost one-half over the last 30 years, and you should be proud of that. Oh, I'm proud of it. I'm proud of it. But people don't do things in a vacuum. You build on people and on their doings. Well, I want to be respectful of your time, if I can finish up here. I really just touched the surface of many of the contributions you've made. I wanted to talk a little bit about your role in getting radiation oncologists to think about what we now call translational science. But at the end here, what do you think are your greatest accomplishments? What do you think your legacy has been to the field? Do you think it's the science or your administration or your teaching and mentoring or all of those together? I think all of us would like to think about what our legacies would be. Oh, I would say, it's an interesting and not an easy question, because I'm interested in all of those things. But I like to remind people that, and it's been commented on by others, I am one of the few people who maintained a practice of medicine, a real practice, all through being a dean. I always think of myself first as a doctor. And I am an investigator, and I am interested in research, both basic and clinical, and did both of them, but I'm a doctor first, that's number one. Second to that, I was very involved in teaching and believe-- and that's why I became a dean and before that, started a department in Harvard and gave courses in oncology, and my residents are my greatest legacy, if you really want to know. Nobody lives forever, and what you did in the lab and your patients, that passes, but your residents are your history. They continue it, and their residents continue it and so forth. And just to end on a high note that you mention, is that the Karnofsky lecturer this year was one of my residents. Yes, he was. Of course, that's Ralph Weichselbaum. He was. I actually chaired the selection committee, and I can't tell you how proud I was to stand up and introduce him. He did a wonderful job. In addition to your own residents, I'm going to tell you, you're also passing this on to the medical oncology fellows who were hanging around the Farber in those days. And to this day, I tell patients I wear two hats. My first hat is to take care of them as I can with the knowledge I have today, and my second hat is to do research to make it better. But my first hat always wins, because Dr. Hellman said you're a doctor first. So there you go. Well, I haven't changed on it. That's very nice to hear though. OK. I think on that note, we'll end up. I had planned over about half an hour. We're just over that. So thank you very much, both from me, personally, and from those of us in the field and from our patients who have benefited. Dr. Hellman, you are truly a pioneer and a giant in our field. So thank you so much. Well, you're very kind to say so. For more original research, editorials, and review articles, please visit us online at jco.org. This production is copyrighted to the American Society of Clinical Oncology. Thank you for listening.
Background: Despite the high prevalence and impact of episodic breathlessness, information about characteristics and patterns is scarce. Aim: To explore the experience of patients with advanced disease suffering from episodic breathlessness, in order to describe types and patterns. Design and participants: Qualitative design using in-depth interviews with patients suffering from advanced stages of chronic heart failure, chronic obstructive pulmonary disease, lung cancer or motor neurone disease. As part of the interviews, patients were asked to draw a graph to illustrate typical patterns of breathlessness episodes. Interviews were tape-recorded, transcribed verbatim and analysed using Framework Analysis. The graphs were grouped according to their patterns. Results: Fifty-one participants (15 chronic heart failure, 14 chronic obstructive pulmonary disease, 13 lung cancer and 9 motor neurone disease) were included (mean age 68.2 years, 30 of 51 men, mean Karnofsky 63.1, mean breathlessness intensity 3.2 of 10). Five different types of episodic breathlessness were described: triggered with normal level of breathlessness, triggered with predictable response (always related to trigger level, e. g. slight exertion causes severe breathlessness), triggered with unpredictable response (not related to trigger level), non-triggered attack-like (quick onset, often severe) and wave-like (triggered or non-triggered, gradual onset). Four patterns of episodic breathlessness could be identified based on the graphs with differences regarding onset and recovery of episodes. These did not correspond with the types of breathlessness described before. Conclusion: Patients with advanced disease experience clearly distinguishable types and patterns of episodic breathlessness. The understanding of these will help clinicians to tailor specific management strategies for patients who suffer from episodes of breathlessness.
Inventor and self-described hacker Mitch Altman talks about Noisebridge, the San Francisco hackerspace he co-founded. Altman is responsible for co-founding 3-ware is now the President and CTO of Cornfield Electronics. His many inventions include TV-B-Gone and NeuroDreamer sleep mask.TranscriptSpeaker 1: Spectrum's next Speaker 2: [inaudible]. Welcome to spectrum the science and technology show on k l x Berkeley, a biweekly Speaker 1: 30 minute program bringing you interviews, featuring bay area scientists and technologists as well as a calendar of local events and news. Speaker 3: Good afternoon. My name is Brad Swift on today's show. Rick Carnesi and I interview Mitch Altman. [00:00:30] Mitch is an inventor and self-described hacker. He cofounded the company three where and is now the president and CTO of cornfield electronics. We're talking to him about Noisebridge, the San Francisco hackerspace that he co founded, as well as some of his many inventions. These include the TVB gone a remote that turns off most TVs and his recently successful Kickstarter project, the neuro dreamer sleep mask. Mitch Altman. Welcome to spectrum. [00:01:00] Thanks. Would you mind telling us sort of that career path? Speaker 4: How I got to sitting here today? Uh, I've been a geek all my life. You know, I dreamed about this stuff when I was a little kid. I actually did a, I remember having this recurring dream where I saw the inside of my mom's radio, which, uh, they were tubes. I didn't know what tooks were though. They were just glowing. They look cool. And I dreamed about pushing it off the counter to see what was in it. And in my dreams I actually did it. But in real life [00:01:30] I was always too timid. But I really wanted to see what was inside. And eventually I started taking apart my parents things and somehow they let me and eventually I learned to put them back together, making my own things from scratch. It's been fun in electronics, I always want to know how things work. I mean that's, that's what makes us geeks tick, you know. Speaker 4: But the thing that fascinated me the most was electronics. So I started playing with wires and alligator clips and putting forks into electrical outlets and having my parents scrape me off the ceiling [00:02:00] and learning from my mistakes, learning and growing. And eventually I was making my own intercoms between my brother's bunk bed and mine below him in high school, making an electronic bong. And, uh, that was one of the things that actually got me talking to other kids rather than just being alone geek. So, uh, inventing, making things. It's been part of my life since I can remember thinking. But you've also had this entrepreneurial spirit as well, I suppose. Yeah. And I'm not really sure [00:02:30] where that came from. Maybe from my parents. My father was an architect, you know, and I see a lot of what I do as art, you know, expressing ourselves truthfully and doing things in a way that give other people an opportunity to think about themselves in the world around them. Speaker 4: And my father did his art architecture and it made him a living without really being conscious of it. That's probably the path that I followed. I actually quit the job that I had created for myself, which was consulting in electronics [00:03:00] for usually small companies. But I quit that so I could explore ways of doing more of what I loved and that's how I came across TV be gone. And I was lucky enough that it actually makes me a living. It's really cool to be able to make a living by doing what you love, making enough money, doing what you love to keep doing what you love. I mean, that's my idea of success. Where does the inspiration come from your projects? Well, that's a good question. Where does inspiration come from? You know, obviously, uh, other people can be inspiring random [00:03:30] events in our lives and people are a great random elements in our lives. Speaker 4: And if we relate to people when they throw something at us that really sticks in our [inaudible] and uh, nibbles away at us, uh, it's like sticking in there. Maybe it's subconscious. Eventually it becomes an idea for a project that screaming to come out, TV gone. I got the idea of sitting in a Chinese restaurant in 1993 talking with some friends and we were there [00:04:00] to talk to each other, not to watch TV. And yet there was a TV on and we were watching the TV and that was crazy. So we started talking about that and then I thought, wouldn't it be wonderful if I could just turn off these horrible distractions everywhere I went? And instantly I knew I could because I'm a geek. Of course. It took me 10 years to get to a point in my life where I had time and energy to do it. Speaker 4: And I'm glad I did. And I had to make that time though. You know, inspiration is really important. Ideas are really important, but they don't go anywhere unless [00:04:30] you make the time to do something with them. And you just prioritize it because you're passionate about it. Or how, how do you make sure that you actually finish something? You start o finishing what you start. Well, you know, I think that's overrated. I've done zillions of projects as have we all that we have that I haven't finished. That's great. You know, and if I'm not motivated to finish it, that leaves time for doing something else. TV began I think is the first project in my entire life where I actually finished it. Totally. And I had to, if I was going to make [00:05:00] it a product, you know, and uh, I don't think we've mentioned TV beyond for people that don't know, it is a key chain that turns TVs off in public places and it really does work. Speaker 4: And I did it cause I got rid of TV in my life at home. I am a TV addict. Uh, I watched it every waking moment of my life as an unhappy child, but I didn't have to keep doing it later in life. And I chose not to, but in public, no one chooses those things to be on. People don't leave their home to watch television except me for sports [00:05:30] bars or something. But I don't like bars and I don't like sports so I don't go to those but everywhere else. So I made it so I could turn them off and other people wanted them. And then when their friends wanted them in friends of friends, that's when I decided I would make a bunch. So, um, I started it like many projects and it got on a roll unlike many projects. But I actually was so passionate about it continually and I had so many people that are kept asking me when's that going to be done? That that probably helped me follow through and actually finish it [00:06:00] and get it to a point where it's a manufacturable product. Speaker 2: [inaudible] you are listening to spectrum Inka LX Berkeley. Our guest is inventor Mitch Altman. Speaker 4: And once you get something at that point, what's next? Do you tinker and invent more stuff or do you spend time supporting TVB gone or, yeah. Well when you do what you love, all sorts of [00:06:30] interesting things open up that you might notice where you wouldn't if you're consumed doing something that just exhausts you like a job, you know, you don't like that too. Many of us, unfortunately on our planet are in that position. I have been working on many other projects along the way. I started getting into hacker conferences and maker fairs as a result of TVB gone. People invited me to these things and I, um, would give talks, [00:07:00] which is kind of bizarre for me. A totally introverted geek, terrified of public speaking. Like so many other of us introverted geeks. But, uh, it turned out I liked it. It makes it easier to talk about something you love. Speaker 4: Yeah. I don't like being pedantic. Uh, I like making things fun and if other people relate then maybe they'll learn something, maybe make a new choice in their life that serves them better and I don't want to tell anyone else what to do. Well sometimes I do, but I like making it more fun for people to choose for themselves what's good for themselves. [00:07:30] I found a place where at hacker conferences, at maker fairs where I could teach doing what I really love, which is soldering and making cool things with electronics and that led to me finding things to teach with. So I started making my own little kits for total beginners and I started doing that by hacking other people's kids and then making my own and that's been supplementing my income a little bit, but mostly it's been paying for me to be able to travel around the world and teach doing this, which I also [00:08:00] love. Speaker 4: That led to going to more hacker conferences and maker fairs and things related and going to hacker spaces that existed but not too many back then. Back then was 2007 okay. The first maker fair was 2006 which led me to meet people who invited me to the first hacker conference also in 2006 that I went to a hope in New York every other year. And I've been actually helping organize those now, which is another thing I make time for at one [00:08:30] of these hacker conferences in Germany, put on by the chaos computer club who have been responsible for creating hackerspaces in Germany and then the world for over a quarter century now of in 2007 it was about a quarter century of that and they gave a presentation on how to start your own and I was way inspired to come home and do that in my home town and with my friend Jake, we Noisebridge and instantly we just put out the word and we got lots [00:09:00] of way cool people to help and with our ideas and their ideas collected more people. Speaker 4: And Noisebridge was a just a natural growth out of all of our enthusiasm and inspiration for having the energy and the high really of being at one of these hacker conferences where people do what they love, explore it, they love Sharon, teach and learn from each other. Uh, but not just once a year, uh, but every day, all night, all day, all year round. [00:09:30] And Wow. Hundreds of us go through there every week. And it constantly amazes me how many cool people are doing cool things there now. And what kinds of things happen at Noisebridge? It's very diverse. A, it's not just tech. You know, I teach soldering and electronics, but [inaudible] Mondays. Yeah. So every Monday, uh, since 2007, I've been teaching how to solder and I love doing that. I'm really good at it by now too. And when I'm not in town, I'm on the road. Other people do [00:10:00] it on Wednesdays. Speaker 4: There's a similar kind of thing for craft and art folks to get together and that's called scow sewing, crafting or whatever. Also on Mondays is people. There's someone who's teaching a class on how to do your own website. There's a python language class, there's German language, human language class, there's a space exploration program, there's food classes. We have a full kitchen, we have a dark room, there's lithography classes. He printing three d printers. We got lots of those. And we understood [00:10:30] sewing machines and lots of cool, uh, electronics equipment as well as the machine shop and laser cutter and a library. We've got classrooms, we've got events, spaces, all this and more. And everything happens just because people think it would be cool to do. And they, they do it and people help. And this is just one of about a thousand hackerspaces in the world. Now it's another thing I love doing is going around helping people start these supportive communities, which are hackerspaces for people to explore and do what they love and hopefully even make a living out of it [00:11:00] so they can do what they enjoy and find fulfillment in their lives. Speaker 4: You know, now there's only a thousand in the world. What will the world be like when there's a million? Uh, more opportunities for people to do. Way more cool things. Earlier guests on our show did talk about the makerspace project of which you're fairly vocal critics. So can you say why you're a critic? I wouldn't say I'm a critic. I love maker fair and I love make magazine. They've created opportunities for so many people and my life has been [00:11:30] changed for the positive by it and so it was so many other people and it will continue to be that kind of positive role model for others as well. They recently sought and received a grant for $10 million from DARPA, which is an arm of a research arm of the u s military. Their goal is to help create new technology for the u s military. That's their stated goal. So they have a bunch of grants now available. Speaker 4: Most of them are because they [00:12:00] see the u s education system as horribly flawed as do I. People in the u s military see that just as clearly as many of us too. And making grants for hands on learning is a way to give more people opportunity to at least have a start and becoming high quality engineers, which they need to further the goals of their organizations, which is in my view, simply put to hurt and kill people. Of course, that's [00:12:30] my personal view. You know, other people will see it differently. What I would love to see happen is for people to explore and continually reevaluate what it means to them to receive funding from organizations or people whose goals don't align with your own cause. There's consequences, so anything we do, there's consequences. There's pluses and minuses for everything. When you accept funds from sources that have goals that don't [00:13:00] align with your own, of course you're helping your goals because you have funding to do so, but you're also helping the goals of the funding source, which don't align with your own. Speaker 4: How do you actually weigh the pluses and minuses in that way? It's not easy, but for me, after struggling with it for months, I can't feel good about associating myself with helping the goals of DARPA. Even though good things come from what DARPA has [00:13:30] done, I would rather put my energy directly into doing things that I believe are helping people rather than helping the goals of an organization that does things that I find well, use the word reprehensible, so I'm not trying to talk anyone into not associating with makerfair or make magazine. I still respect many of the people at make and a maker fair, great deal. I think they'll do great things. I just can't feel [00:14:00] good about helping myself and I really would hope that people do consider the funding sources because it does change what you'll do maybe consciously, maybe subconsciously. So what are you willing to do that you might not have done to make it more likely to get funding renewed funding? Speaker 4: What are they going to stop doing that they might have done because it doesn't look so good to the funding source? I see these as very, very much related. It's really important [00:14:30] to explore these things before making a conscious choice about whether to accept these funding sources. Maybe it's worth it. Maybe it isn't. It's up to each and every individual. I need a couple points of clarification just to make sure we got everything right. Yeah. So the DARPA funding at all go to maker fair to your knowledge? Uh, sort of the, with some of the other projects that those same people were doing well before making my choice. I talk to the person who started maker fair and make magazine, [00:15:00] uh, Dale Dougherty and he's a great guy. We've done lots of cool things through the years together. And my main goal was to explore the possibility of helping with maker fair without being associated with DARPA funding. And the funding that they got is for a program they call mentor program a but that's intertwined with making makerfair. So there's no way to dissociate the funding Speaker 2: [inaudible] [00:15:30] this is spectrum k a l x Berkeley. Our guest is Mitch Altman, Co founder of the hackerspace Noisebridge. Speaker 4: I also see this theme of wanting to help people. So for instance, you host these depression and Geek meetups. Life isn't all totally wonderful. Life is full of things that are amazingly wonderful and rapturous and blissful and it's full of things [00:16:00] that totally suck and anything in between up, down and all around. And any given life, no matter how wonderful your life is, uh, there's ups and downs. And I, um, started off my life as a totally depressed geek and, um, I was brutally bullied. I was, you know, I'm introverted geeks when I was a little kid, did not farewell. And not only that, but, uh, I was an am queer and little kids take any difference big and small, and they brutalize [00:16:30] people for it. Uh, life was horrible for me and my parents were terrible parents. Lucky for me. They turned out to be cool people as adults for me when I was at adult. Speaker 4: And uh, no matter what childhood can be rough for people and there's unhealed stuff and we carry all of that with us if we survive into adulthood. And here we all are as adults living our lives, hopefully exploring and doing what we love with the help of, uh, our supportive communities, including hackerspaces, but still there was a huge [00:17:00] amount of depression in geek communities. Uh, last November a friend of mine killed himself. It was the first time in my life where I felt close to someone who killed themselves. And, uh, it's rough. It really, really sucks. There's nothing like it. And still, uh, by this time in my life I tried to see opportunity in anything to help not only myself but other people. It's part of my healing process. So I wrote up [00:17:30] a very personal blog post on the Noisebridge blog site about my feelings and hundreds or more people responded. Speaker 4: It was overwhelming. And, uh, it really showed me that way more people are dealing with depression than I could imagine. And, and my friend, I had no clue he was, and I'm very sensitive to it. He hit it so well and I hit it well when I was a first half of my life living with depression. But yeah, a lot of us in the geek world. And in our planet are suffering [00:18:00] with depression. So after all these responses, I thought, you know, maybe we could have a meetup where we can talk about this and openly and if we talk about this openly as a community, maybe maybe someone will reach out for help rather than harm themselves and maybe someone will live another night. And any case, these geek and depression meetups that I started are now happening in various cities around the world and hopefully more as, as we become [00:18:30] more open about this cause, you know, I think we really can benefit all of us, each of us and as a community, if everyone is able to be totally open about all of who we are and not have to be shameful or secretive about something, you know, we can be open about everything but this then, then soon we're closing off huge parts of our lives and we have this part we can't even explore ourselves cause we can't talk about it to anyone. Speaker 4: We're not open about it with ourselves and not just about being queer or [00:19:00] whatever, but also being depressed, feeling suicidal, has a lot of shame associated with it. And a lot of people feel, unfortunately, sadly, tragically, that the easiest way out is killing themselves rather than just asking for help. And that's just so awful and unnecessary. So, uh, there are geeking depression meetups now that happened in San Francisco. I would like to see more happen elsewhere, bigger, small, whatever, and I'm [00:19:30] always available if anyone wants to contact me for any reason, project help how to start a company. Uh, if you're depressed, if you want someone to talk you into quitting a job, you don't like anything. I'm totally willing to communicate any time. Just please email me mitch@cornfieldelectronics.com. Speaker 2: [inaudible]. Our Guest Today on spectrum is Mitch Altman, enter hackerspace activist. This is KALX Berkeley. Speaker 4: [00:20:00] You had, uh, mentioned this sort of lackluster state of science, technology, engineering and math education or education in general. Do you see other possible solutions to bringing that up? Yes. This is one of the huge reasons why I started Noisebridge and why help other hackerspaces start. These are places where education happens in a very real wonderful way. Noisebridge is a 500 C3 public [00:20:30] benefit corporation in the state of California, but it's not your traditional kind of education organization. We teach and learn and share through hands on whether it's with computers, whether it's in a kitchen, a sewing machine, a soldering iron, a machine shop, whether it's exploring biology and growing mushrooms or using a laser cutter or exploring space. It's all about learning and teaching and sharing. People can try stuff if they know they love something, they can blurt more, they can [00:21:00] teach it. Speaker 4: It's really fantastic and this is an opportunity for some people to actually learn what they want to learn to live lives that they want to live. I wish the u s education system were more of that way, but it's very unfortunate that the only schools, well most of the schools that actually provide that opportunity are very expensive. Private schools in our country and there are fortunately some exceptions. I was just teaching some kids over at them, met West School in [00:21:30] Oakland who are providing hands on learning for their kids and it's public. It's really cool that, that, that exists. But it's only, I think 165 kids are allowed there. I would love to see more of that. So hackerspaces around the world are providing these opportunities right now. It's very few opportunities compared to what we need. There's only a thousand hackerspaces in the world and we need a million and we'll get there. Speaker 4: Uh, because hackerspaces are incredibly cool. People are [00:22:00] spontaneously creating them. There's all sorts of ways we can create these niches within which we can provide ourselves the services that our governments are not providing us. Hackerspaces just happened to be a really wonderful way near and dear to my heart and Mitch, our hackerspaces able to reach out to younger students populations that are stuck in those schools that you were talking about that aren't doing any of this hands on stuff. Yeah, well they, it's already, uh, it's already there. I mean, Noisebridge has [00:22:30] always been welcoming to people of all ages and most hackerspaces are, although some are afraid of liability issues a and they only have 18 and over, which I think is absurd. Yeah, there's, there's no age limit for learning. Not If we don't have it beaten out of us. That is, I'm not doing hackerspaces to get rid of schools. Speaker 4: I would love schools to become places where people can actually learn, but kids can have these often totally free and it Noisebridge [00:23:00] it's always free opportunities as an alternative during lunch or before or after school, they can come to Noisebridge over weekends, uh, with or without their parents. People are always welcome to come. Hopefully as there were more and more hackerspaces, there'll be more opportunities for these kids. There are hackerspaces in the East Bay, there's ace monster toys. There's one that's just forming now called pseudo room, s u d o room, [00:23:30] and there's mothership hacker moms, which is primarily for moms who are hackers and there's also a lowel space. I can't remember what the acronym stands for, unfortunately, but therefore liberating ourselves locally. There you go. Liberating ourselves locally. There are a bunch of cool people primarily for, uh, hackers of color, of various sorts and we need more. There's actually people just now starting to talk about another hackerspace in [00:24:00] San Francisco. What I would love to see is a hackerspace in every neighborhood of San Francisco, every neighborhood of every city around the country. We need a million of these things. Okay. Well, Mitch, thanks for joining us. Yeah, it's been great being here. Thanks for having me. Awesome. Speaker 5: Mm. Speaker 6: A regular feature of spectrum is to mention a few of the science and technology events happening locally over the next two weeks. Rick Kaneski at Lisa kind of joined me for the calendar. The next science [00:24:30] at cal lecture will be given at 11:00 AM on August the 18th in genetics and plants biology room 100 the lecture will be given by Dr Anton Trypsin and will be titled, can one see a flower through a granite wall? Amazing capabilities of neutron imaging. The detection technology developed for NASA astrophysical missions at UC Berkeley space science lab has been successfully extended to such diverse areas as synchrotron instrumentation, biomedical imaging, ground-based astronomy [00:25:00] and neutron micro tomography. Dr Trypsin will talk about his experience with neutron imaging and how it's useful find new applications. He got his phd in Applied Physics in 1992 at the Russian Academy of Sciences and was then a British royal society fellow with University of Lye Chester and joined the space scientist lab at UC Berkeley in 1996 where he is currently a research associate Speaker 7: on Saturday, August 18th the exploratorium at three six zero one line street at the Palace of fine arts in San Francisco [00:25:30] and celebrating founder of Frank Oppenheimer's hundredth birthday. Standard admission is $25 but college students, seniors, teachers, persons with disabilities and youths age six to 17 pay only $19 members and children five and under are free during regular museum hours of 10:00 AM to 5:00 PM visitors can take part in a variety of events and activities. Honoring Frank at the explorer bowls table from 11:00 AM to 2:00 PM you can make a spinning top when [00:26:00] a Frank's favorite DIY projects throughout the day in the mine theater. You can see a series of exploratorium home movies featuring the early days of the museum as well as footage of frank engaging with visitors and staff. Today's events will also feature a frank themed presentation in the McBean theater and screenings of some of his favorite films from the museums, cinema arts archives, including the Em's classic powers of 10 there will also be birthday cake exploratory members can go [00:26:30] to a special celebration from six [inaudible] 9:00 PM for more information, visit exploratorium.edu no news with [inaudible] Speaker 6: Karnofsky and Lisa Katovich. The Berkeley Earth surface temperature reports that the average temperature of the earth land has risen by 2.5 Fahrenheit over the past 250 years, including an increase of 1.5 degrees over the most recent 50 years. The good match between the new temperature record and historical carbon dioxide records suggest [00:27:00] that the most straightforward explanation for this warming is human greenhouse gas emissions. Five Times more station records were used than in previous analyses and a new statistical approach allowed Berkeley Earth to go about a hundred years farther back in time than previous studies allowing the team to conclude that the contribution of solar activity to global warming is negligible. Five scientific papers including the raw data are available online@berkeleyearth.org Elizabeth Mueller Co founder and executive director [00:27:30] of Berkeley Earth says that one of our goals at Berkeley Earth is complete transparency. We believe that everyone should be able to access raw climate data and do their own analysis. Mueller was a guest on spectrum and her interview is available on iTunes university Speaker 7: science daily reports that UCLA researchers found that older adults who regularly used a brain fitness program played on the computer demonstrated significantly improved memory and language skills. The team studied 59 participants with an [00:28:00] average age of 84 recruited from local retirement communities in southern California. The volunteers were split into two groups. The first group you used the brain fitness program for an average of 73 and a half, 20 minute sessions across a six month period. Well a second group. You use it less than 45 times. During that same period, researchers found that the first group demonstrated significantly higher improvement in memory and language skills compared to the second group. The study's findings add to the field exploring whether such brain fitness tools may help improve language [00:28:30] in memory and may ultimately help protect individuals from the cognitive decline associated with aging and Alzheimer's disease. Age-Related memory decline affects approximately 40% of older adults and is characterized by self perception of memory loss and decline in memory performance. Previous studies have shown that engaging in mental activities can help improve memory. That little research has been done to determine whether the numerous brain fitness games or memory training programs on the market are effective. This is one of the first studies to assess the cognitive effects [00:29:00] of the computerized memory training program. Speaker 1: [inaudible]Speaker 2: [inaudible]Speaker 1: [inaudible].Speaker 2: The music heard during the show is by Anna David from his album folk acoustic made available by a creative Commons license 3.0 attribution. [00:29:30] Thank you for listening to spectrum. If you have comments about the show, please send them to us via email. Our email address is spectrum.at Speaker 1: yahoo.com join us in two weeks at the same time. [inaudible]. See acast.com/privacy for privacy and opt-out information.
Inventor and self-described hacker Mitch Altman talks about Noisebridge, the San Francisco hackerspace he co-founded. Altman is responsible for co-founding 3-ware is now the President and CTO of Cornfield Electronics. His many inventions include TV-B-Gone and NeuroDreamer sleep mask.TranscriptSpeaker 1: Spectrum's next Speaker 2: [inaudible]. Welcome to spectrum the science and technology show on k l x Berkeley, a biweekly Speaker 1: 30 minute program bringing you interviews, featuring bay area scientists and technologists as well as a calendar of local events and news. Speaker 3: Good afternoon. My name is Brad Swift on today's show. Rick Carnesi and I interview Mitch Altman. [00:00:30] Mitch is an inventor and self-described hacker. He cofounded the company three where and is now the president and CTO of cornfield electronics. We're talking to him about Noisebridge, the San Francisco hackerspace that he co founded, as well as some of his many inventions. These include the TVB gone a remote that turns off most TVs and his recently successful Kickstarter project, the neuro dreamer sleep mask. Mitch Altman. Welcome to spectrum. [00:01:00] Thanks. Would you mind telling us sort of that career path? Speaker 4: How I got to sitting here today? Uh, I've been a geek all my life. You know, I dreamed about this stuff when I was a little kid. I actually did a, I remember having this recurring dream where I saw the inside of my mom's radio, which, uh, they were tubes. I didn't know what tooks were though. They were just glowing. They look cool. And I dreamed about pushing it off the counter to see what was in it. And in my dreams I actually did it. But in real life [00:01:30] I was always too timid. But I really wanted to see what was inside. And eventually I started taking apart my parents things and somehow they let me and eventually I learned to put them back together, making my own things from scratch. It's been fun in electronics, I always want to know how things work. I mean that's, that's what makes us geeks tick, you know. Speaker 4: But the thing that fascinated me the most was electronics. So I started playing with wires and alligator clips and putting forks into electrical outlets and having my parents scrape me off the ceiling [00:02:00] and learning from my mistakes, learning and growing. And eventually I was making my own intercoms between my brother's bunk bed and mine below him in high school, making an electronic bong. And, uh, that was one of the things that actually got me talking to other kids rather than just being alone geek. So, uh, inventing, making things. It's been part of my life since I can remember thinking. But you've also had this entrepreneurial spirit as well, I suppose. Yeah. And I'm not really sure [00:02:30] where that came from. Maybe from my parents. My father was an architect, you know, and I see a lot of what I do as art, you know, expressing ourselves truthfully and doing things in a way that give other people an opportunity to think about themselves in the world around them. Speaker 4: And my father did his art architecture and it made him a living without really being conscious of it. That's probably the path that I followed. I actually quit the job that I had created for myself, which was consulting in electronics [00:03:00] for usually small companies. But I quit that so I could explore ways of doing more of what I loved and that's how I came across TV be gone. And I was lucky enough that it actually makes me a living. It's really cool to be able to make a living by doing what you love, making enough money, doing what you love to keep doing what you love. I mean, that's my idea of success. Where does the inspiration come from your projects? Well, that's a good question. Where does inspiration come from? You know, obviously, uh, other people can be inspiring random [00:03:30] events in our lives and people are a great random elements in our lives. Speaker 4: And if we relate to people when they throw something at us that really sticks in our [inaudible] and uh, nibbles away at us, uh, it's like sticking in there. Maybe it's subconscious. Eventually it becomes an idea for a project that screaming to come out, TV gone. I got the idea of sitting in a Chinese restaurant in 1993 talking with some friends and we were there [00:04:00] to talk to each other, not to watch TV. And yet there was a TV on and we were watching the TV and that was crazy. So we started talking about that and then I thought, wouldn't it be wonderful if I could just turn off these horrible distractions everywhere I went? And instantly I knew I could because I'm a geek. Of course. It took me 10 years to get to a point in my life where I had time and energy to do it. Speaker 4: And I'm glad I did. And I had to make that time though. You know, inspiration is really important. Ideas are really important, but they don't go anywhere unless [00:04:30] you make the time to do something with them. And you just prioritize it because you're passionate about it. Or how, how do you make sure that you actually finish something? You start o finishing what you start. Well, you know, I think that's overrated. I've done zillions of projects as have we all that we have that I haven't finished. That's great. You know, and if I'm not motivated to finish it, that leaves time for doing something else. TV began I think is the first project in my entire life where I actually finished it. Totally. And I had to, if I was going to make [00:05:00] it a product, you know, and uh, I don't think we've mentioned TV beyond for people that don't know, it is a key chain that turns TVs off in public places and it really does work. Speaker 4: And I did it cause I got rid of TV in my life at home. I am a TV addict. Uh, I watched it every waking moment of my life as an unhappy child, but I didn't have to keep doing it later in life. And I chose not to, but in public, no one chooses those things to be on. People don't leave their home to watch television except me for sports [00:05:30] bars or something. But I don't like bars and I don't like sports so I don't go to those but everywhere else. So I made it so I could turn them off and other people wanted them. And then when their friends wanted them in friends of friends, that's when I decided I would make a bunch. So, um, I started it like many projects and it got on a roll unlike many projects. But I actually was so passionate about it continually and I had so many people that are kept asking me when's that going to be done? That that probably helped me follow through and actually finish it [00:06:00] and get it to a point where it's a manufacturable product. Speaker 2: [inaudible] you are listening to spectrum Inka LX Berkeley. Our guest is inventor Mitch Altman. Speaker 4: And once you get something at that point, what's next? Do you tinker and invent more stuff or do you spend time supporting TVB gone or, yeah. Well when you do what you love, all sorts of [00:06:30] interesting things open up that you might notice where you wouldn't if you're consumed doing something that just exhausts you like a job, you know, you don't like that too. Many of us, unfortunately on our planet are in that position. I have been working on many other projects along the way. I started getting into hacker conferences and maker fairs as a result of TVB gone. People invited me to these things and I, um, would give talks, [00:07:00] which is kind of bizarre for me. A totally introverted geek, terrified of public speaking. Like so many other of us introverted geeks. But, uh, it turned out I liked it. It makes it easier to talk about something you love. Speaker 4: Yeah. I don't like being pedantic. Uh, I like making things fun and if other people relate then maybe they'll learn something, maybe make a new choice in their life that serves them better and I don't want to tell anyone else what to do. Well sometimes I do, but I like making it more fun for people to choose for themselves what's good for themselves. [00:07:30] I found a place where at hacker conferences, at maker fairs where I could teach doing what I really love, which is soldering and making cool things with electronics and that led to me finding things to teach with. So I started making my own little kits for total beginners and I started doing that by hacking other people's kids and then making my own and that's been supplementing my income a little bit, but mostly it's been paying for me to be able to travel around the world and teach doing this, which I also [00:08:00] love. Speaker 4: That led to going to more hacker conferences and maker fairs and things related and going to hacker spaces that existed but not too many back then. Back then was 2007 okay. The first maker fair was 2006 which led me to meet people who invited me to the first hacker conference also in 2006 that I went to a hope in New York every other year. And I've been actually helping organize those now, which is another thing I make time for at one [00:08:30] of these hacker conferences in Germany, put on by the chaos computer club who have been responsible for creating hackerspaces in Germany and then the world for over a quarter century now of in 2007 it was about a quarter century of that and they gave a presentation on how to start your own and I was way inspired to come home and do that in my home town and with my friend Jake, we Noisebridge and instantly we just put out the word and we got lots [00:09:00] of way cool people to help and with our ideas and their ideas collected more people. Speaker 4: And Noisebridge was a just a natural growth out of all of our enthusiasm and inspiration for having the energy and the high really of being at one of these hacker conferences where people do what they love, explore it, they love Sharon, teach and learn from each other. Uh, but not just once a year, uh, but every day, all night, all day, all year round. [00:09:30] And Wow. Hundreds of us go through there every week. And it constantly amazes me how many cool people are doing cool things there now. And what kinds of things happen at Noisebridge? It's very diverse. A, it's not just tech. You know, I teach soldering and electronics, but [inaudible] Mondays. Yeah. So every Monday, uh, since 2007, I've been teaching how to solder and I love doing that. I'm really good at it by now too. And when I'm not in town, I'm on the road. Other people do [00:10:00] it on Wednesdays. Speaker 4: There's a similar kind of thing for craft and art folks to get together and that's called scow sewing, crafting or whatever. Also on Mondays is people. There's someone who's teaching a class on how to do your own website. There's a python language class, there's German language, human language class, there's a space exploration program, there's food classes. We have a full kitchen, we have a dark room, there's lithography classes. He printing three d printers. We got lots of those. And we understood [00:10:30] sewing machines and lots of cool, uh, electronics equipment as well as the machine shop and laser cutter and a library. We've got classrooms, we've got events, spaces, all this and more. And everything happens just because people think it would be cool to do. And they, they do it and people help. And this is just one of about a thousand hackerspaces in the world. Now it's another thing I love doing is going around helping people start these supportive communities, which are hackerspaces for people to explore and do what they love and hopefully even make a living out of it [00:11:00] so they can do what they enjoy and find fulfillment in their lives. Speaker 4: You know, now there's only a thousand in the world. What will the world be like when there's a million? Uh, more opportunities for people to do. Way more cool things. Earlier guests on our show did talk about the makerspace project of which you're fairly vocal critics. So can you say why you're a critic? I wouldn't say I'm a critic. I love maker fair and I love make magazine. They've created opportunities for so many people and my life has been [00:11:30] changed for the positive by it and so it was so many other people and it will continue to be that kind of positive role model for others as well. They recently sought and received a grant for $10 million from DARPA, which is an arm of a research arm of the u s military. Their goal is to help create new technology for the u s military. That's their stated goal. So they have a bunch of grants now available. Speaker 4: Most of them are because they [00:12:00] see the u s education system as horribly flawed as do I. People in the u s military see that just as clearly as many of us too. And making grants for hands on learning is a way to give more people opportunity to at least have a start and becoming high quality engineers, which they need to further the goals of their organizations, which is in my view, simply put to hurt and kill people. Of course, that's [00:12:30] my personal view. You know, other people will see it differently. What I would love to see happen is for people to explore and continually reevaluate what it means to them to receive funding from organizations or people whose goals don't align with your own cause. There's consequences, so anything we do, there's consequences. There's pluses and minuses for everything. When you accept funds from sources that have goals that don't [00:13:00] align with your own, of course you're helping your goals because you have funding to do so, but you're also helping the goals of the funding source, which don't align with your own. Speaker 4: How do you actually weigh the pluses and minuses in that way? It's not easy, but for me, after struggling with it for months, I can't feel good about associating myself with helping the goals of DARPA. Even though good things come from what DARPA has [00:13:30] done, I would rather put my energy directly into doing things that I believe are helping people rather than helping the goals of an organization that does things that I find well, use the word reprehensible, so I'm not trying to talk anyone into not associating with makerfair or make magazine. I still respect many of the people at make and a maker fair, great deal. I think they'll do great things. I just can't feel [00:14:00] good about helping myself and I really would hope that people do consider the funding sources because it does change what you'll do maybe consciously, maybe subconsciously. So what are you willing to do that you might not have done to make it more likely to get funding renewed funding? Speaker 4: What are they going to stop doing that they might have done because it doesn't look so good to the funding source? I see these as very, very much related. It's really important [00:14:30] to explore these things before making a conscious choice about whether to accept these funding sources. Maybe it's worth it. Maybe it isn't. It's up to each and every individual. I need a couple points of clarification just to make sure we got everything right. Yeah. So the DARPA funding at all go to maker fair to your knowledge? Uh, sort of the, with some of the other projects that those same people were doing well before making my choice. I talk to the person who started maker fair and make magazine, [00:15:00] uh, Dale Dougherty and he's a great guy. We've done lots of cool things through the years together. And my main goal was to explore the possibility of helping with maker fair without being associated with DARPA funding. And the funding that they got is for a program they call mentor program a but that's intertwined with making makerfair. So there's no way to dissociate the funding Speaker 2: [inaudible] [00:15:30] this is spectrum k a l x Berkeley. Our guest is Mitch Altman, Co founder of the hackerspace Noisebridge. Speaker 4: I also see this theme of wanting to help people. So for instance, you host these depression and Geek meetups. Life isn't all totally wonderful. Life is full of things that are amazingly wonderful and rapturous and blissful and it's full of things [00:16:00] that totally suck and anything in between up, down and all around. And any given life, no matter how wonderful your life is, uh, there's ups and downs. And I, um, started off my life as a totally depressed geek and, um, I was brutally bullied. I was, you know, I'm introverted geeks when I was a little kid, did not farewell. And not only that, but, uh, I was an am queer and little kids take any difference big and small, and they brutalize [00:16:30] people for it. Uh, life was horrible for me and my parents were terrible parents. Lucky for me. They turned out to be cool people as adults for me when I was at adult. Speaker 4: And uh, no matter what childhood can be rough for people and there's unhealed stuff and we carry all of that with us if we survive into adulthood. And here we all are as adults living our lives, hopefully exploring and doing what we love with the help of, uh, our supportive communities, including hackerspaces, but still there was a huge [00:17:00] amount of depression in geek communities. Uh, last November a friend of mine killed himself. It was the first time in my life where I felt close to someone who killed themselves. And, uh, it's rough. It really, really sucks. There's nothing like it. And still, uh, by this time in my life I tried to see opportunity in anything to help not only myself but other people. It's part of my healing process. So I wrote up [00:17:30] a very personal blog post on the Noisebridge blog site about my feelings and hundreds or more people responded. Speaker 4: It was overwhelming. And, uh, it really showed me that way more people are dealing with depression than I could imagine. And, and my friend, I had no clue he was, and I'm very sensitive to it. He hit it so well and I hit it well when I was a first half of my life living with depression. But yeah, a lot of us in the geek world. And in our planet are suffering [00:18:00] with depression. So after all these responses, I thought, you know, maybe we could have a meetup where we can talk about this and openly and if we talk about this openly as a community, maybe maybe someone will reach out for help rather than harm themselves and maybe someone will live another night. And any case, these geek and depression meetups that I started are now happening in various cities around the world and hopefully more as, as we become [00:18:30] more open about this cause, you know, I think we really can benefit all of us, each of us and as a community, if everyone is able to be totally open about all of who we are and not have to be shameful or secretive about something, you know, we can be open about everything but this then, then soon we're closing off huge parts of our lives and we have this part we can't even explore ourselves cause we can't talk about it to anyone. Speaker 4: We're not open about it with ourselves and not just about being queer or [00:19:00] whatever, but also being depressed, feeling suicidal, has a lot of shame associated with it. And a lot of people feel, unfortunately, sadly, tragically, that the easiest way out is killing themselves rather than just asking for help. And that's just so awful and unnecessary. So, uh, there are geeking depression meetups now that happened in San Francisco. I would like to see more happen elsewhere, bigger, small, whatever, and I'm [00:19:30] always available if anyone wants to contact me for any reason, project help how to start a company. Uh, if you're depressed, if you want someone to talk you into quitting a job, you don't like anything. I'm totally willing to communicate any time. Just please email me mitch@cornfieldelectronics.com. Speaker 2: [inaudible]. Our Guest Today on spectrum is Mitch Altman, enter hackerspace activist. This is KALX Berkeley. Speaker 4: [00:20:00] You had, uh, mentioned this sort of lackluster state of science, technology, engineering and math education or education in general. Do you see other possible solutions to bringing that up? Yes. This is one of the huge reasons why I started Noisebridge and why help other hackerspaces start. These are places where education happens in a very real wonderful way. Noisebridge is a 500 C3 public [00:20:30] benefit corporation in the state of California, but it's not your traditional kind of education organization. We teach and learn and share through hands on whether it's with computers, whether it's in a kitchen, a sewing machine, a soldering iron, a machine shop, whether it's exploring biology and growing mushrooms or using a laser cutter or exploring space. It's all about learning and teaching and sharing. People can try stuff if they know they love something, they can blurt more, they can [00:21:00] teach it. Speaker 4: It's really fantastic and this is an opportunity for some people to actually learn what they want to learn to live lives that they want to live. I wish the u s education system were more of that way, but it's very unfortunate that the only schools, well most of the schools that actually provide that opportunity are very expensive. Private schools in our country and there are fortunately some exceptions. I was just teaching some kids over at them, met West School in [00:21:30] Oakland who are providing hands on learning for their kids and it's public. It's really cool that, that, that exists. But it's only, I think 165 kids are allowed there. I would love to see more of that. So hackerspaces around the world are providing these opportunities right now. It's very few opportunities compared to what we need. There's only a thousand hackerspaces in the world and we need a million and we'll get there. Speaker 4: Uh, because hackerspaces are incredibly cool. People are [00:22:00] spontaneously creating them. There's all sorts of ways we can create these niches within which we can provide ourselves the services that our governments are not providing us. Hackerspaces just happened to be a really wonderful way near and dear to my heart and Mitch, our hackerspaces able to reach out to younger students populations that are stuck in those schools that you were talking about that aren't doing any of this hands on stuff. Yeah, well they, it's already, uh, it's already there. I mean, Noisebridge has [00:22:30] always been welcoming to people of all ages and most hackerspaces are, although some are afraid of liability issues a and they only have 18 and over, which I think is absurd. Yeah, there's, there's no age limit for learning. Not If we don't have it beaten out of us. That is, I'm not doing hackerspaces to get rid of schools. Speaker 4: I would love schools to become places where people can actually learn, but kids can have these often totally free and it Noisebridge [00:23:00] it's always free opportunities as an alternative during lunch or before or after school, they can come to Noisebridge over weekends, uh, with or without their parents. People are always welcome to come. Hopefully as there were more and more hackerspaces, there'll be more opportunities for these kids. There are hackerspaces in the East Bay, there's ace monster toys. There's one that's just forming now called pseudo room, s u d o room, [00:23:30] and there's mothership hacker moms, which is primarily for moms who are hackers and there's also a lowel space. I can't remember what the acronym stands for, unfortunately, but therefore liberating ourselves locally. There you go. Liberating ourselves locally. There are a bunch of cool people primarily for, uh, hackers of color, of various sorts and we need more. There's actually people just now starting to talk about another hackerspace in [00:24:00] San Francisco. What I would love to see is a hackerspace in every neighborhood of San Francisco, every neighborhood of every city around the country. We need a million of these things. Okay. Well, Mitch, thanks for joining us. Yeah, it's been great being here. Thanks for having me. Awesome. Speaker 5: Mm. Speaker 6: A regular feature of spectrum is to mention a few of the science and technology events happening locally over the next two weeks. Rick Kaneski at Lisa kind of joined me for the calendar. The next science [00:24:30] at cal lecture will be given at 11:00 AM on August the 18th in genetics and plants biology room 100 the lecture will be given by Dr Anton Trypsin and will be titled, can one see a flower through a granite wall? Amazing capabilities of neutron imaging. The detection technology developed for NASA astrophysical missions at UC Berkeley space science lab has been successfully extended to such diverse areas as synchrotron instrumentation, biomedical imaging, ground-based astronomy [00:25:00] and neutron micro tomography. Dr Trypsin will talk about his experience with neutron imaging and how it's useful find new applications. He got his phd in Applied Physics in 1992 at the Russian Academy of Sciences and was then a British royal society fellow with University of Lye Chester and joined the space scientist lab at UC Berkeley in 1996 where he is currently a research associate Speaker 7: on Saturday, August 18th the exploratorium at three six zero one line street at the Palace of fine arts in San Francisco [00:25:30] and celebrating founder of Frank Oppenheimer's hundredth birthday. Standard admission is $25 but college students, seniors, teachers, persons with disabilities and youths age six to 17 pay only $19 members and children five and under are free during regular museum hours of 10:00 AM to 5:00 PM visitors can take part in a variety of events and activities. Honoring Frank at the explorer bowls table from 11:00 AM to 2:00 PM you can make a spinning top when [00:26:00] a Frank's favorite DIY projects throughout the day in the mine theater. You can see a series of exploratorium home movies featuring the early days of the museum as well as footage of frank engaging with visitors and staff. Today's events will also feature a frank themed presentation in the McBean theater and screenings of some of his favorite films from the museums, cinema arts archives, including the Em's classic powers of 10 there will also be birthday cake exploratory members can go [00:26:30] to a special celebration from six [inaudible] 9:00 PM for more information, visit exploratorium.edu no news with [inaudible] Speaker 6: Karnofsky and Lisa Katovich. The Berkeley Earth surface temperature reports that the average temperature of the earth land has risen by 2.5 Fahrenheit over the past 250 years, including an increase of 1.5 degrees over the most recent 50 years. The good match between the new temperature record and historical carbon dioxide records suggest [00:27:00] that the most straightforward explanation for this warming is human greenhouse gas emissions. Five Times more station records were used than in previous analyses and a new statistical approach allowed Berkeley Earth to go about a hundred years farther back in time than previous studies allowing the team to conclude that the contribution of solar activity to global warming is negligible. Five scientific papers including the raw data are available online@berkeleyearth.org Elizabeth Mueller Co founder and executive director [00:27:30] of Berkeley Earth says that one of our goals at Berkeley Earth is complete transparency. We believe that everyone should be able to access raw climate data and do their own analysis. Mueller was a guest on spectrum and her interview is available on iTunes university Speaker 7: science daily reports that UCLA researchers found that older adults who regularly used a brain fitness program played on the computer demonstrated significantly improved memory and language skills. The team studied 59 participants with an [00:28:00] average age of 84 recruited from local retirement communities in southern California. The volunteers were split into two groups. The first group you used the brain fitness program for an average of 73 and a half, 20 minute sessions across a six month period. Well a second group. You use it less than 45 times. During that same period, researchers found that the first group demonstrated significantly higher improvement in memory and language skills compared to the second group. The study's findings add to the field exploring whether such brain fitness tools may help improve language [00:28:30] in memory and may ultimately help protect individuals from the cognitive decline associated with aging and Alzheimer's disease. Age-Related memory decline affects approximately 40% of older adults and is characterized by self perception of memory loss and decline in memory performance. Previous studies have shown that engaging in mental activities can help improve memory. That little research has been done to determine whether the numerous brain fitness games or memory training programs on the market are effective. This is one of the first studies to assess the cognitive effects [00:29:00] of the computerized memory training program. Speaker 1: [inaudible]Speaker 2: [inaudible]Speaker 1: [inaudible].Speaker 2: The music heard during the show is by Anna David from his album folk acoustic made available by a creative Commons license 3.0 attribution. [00:29:30] Thank you for listening to spectrum. If you have comments about the show, please send them to us via email. Our email address is spectrum.at Speaker 1: yahoo.com join us in two weeks at the same time. [inaudible]. Hosted on Acast. See acast.com/privacy for more information.
Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information.
In critical spawning and overwintering habitat for salmonids Hwan studies the effects of temporal stream fragmentation across three organizational levels of ecology: population, community, and ecosystem levels.TranscriptSpeaker 1: Spectrum's next Speaker 2: [inaudible].Speaker 1: [00:01:00] Welcome to spectrum the science and technology show on k a l x Berkeley, a biweekly 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news. Speaker 3: Hi, my name is Brad Swift. I'm the host of today's show. Our interview is with Jason won a third year phd student in the Carlson lab, which is [00:01:30] part of the environmental science policy and Management Department of the College of natural resources. Professor Stephanie Carlson directs the lab and she is a fish ecologist. Jason is researching the effects of summertimes stream drying on fish ecology in the John West fork, a creek in Marin county. The John West fork is the spawning grounds for two varieties of salmon the summer of 2011 Woolmark the third year of his research on this stream. [00:02:00] His research will continue for two and possibly three more years. This interview is prerecorded and edited. Speaker 4: Jason, welcome to spectrum. Thanks for coming in. Thank you. Wanted to ask if you could, uh, give us a brief overview of your research and add in there how it's being funded. My research is looking at the effects of low summer flow on juvenile steelhead, on the insect communities out in the stream and [00:02:30] on certain ecosystem processes such as Algal production and leaf decomposition. And it's currently being funded by, mostly by my, by my guiding professor, Stephanie Carlson. And I also have some funding from our department and the division within our department. All right. We get out a sperm wildlife grant, which helps fund the research. And also I'm currently on an NSF graduate research fellowship. Described the, the general [00:03:00] area of the site that you chose. Sort of put it in context of where it is. So my study say, uh, the John West work is in point Reyes national seashore, which is about an hour north of Berkeley in a national park in and surrounded by some state parks. Speaker 4: Also. Can you explain the watershed and the area that you're working, how it all interrelates to the watershed? So I'm, I'm working in the Lagunitas watershed. I'm working [00:03:30] in a creek that is a tributary of a tributary of a creek to the lock Anitas to log in neatest creek and log Anitas creek flows into Tomas Bay in point rays. The creek that I'm working in is a little different in that there are only two species of fish up there. Both our salt Monets, there are still head and coho salmon. This is because it's not that the creek went dry, completely dry one year and there's, there [00:04:00] was a culvert that was put in place and other fish species weren't able to recolonize the creek, but someone had adults can jump over the barrier. And so they were able to recolonize the creek and they're actually jumping through the culvert. Speaker 4: Yeah. And through this culvert and swimming up swimming into the two John West work. And what's the drop on the culvert like from, from the the bottom lip to the dead of the bid. Lower part [00:04:30] of the creek. It's about four feet. Four feet drop-off. Yeah. So that's quite a leap for the salmon. Yeah. And so with this study, what is it that you're trying to learn? That is not already known. So I'm basically trying to look at the effects of low flow and my study is really looking at what the affects are at a really fine scale. So I'm tracking, uh, juvenile steel head growth, movement and survival and I'm tracking them on a weekly basis. So [00:05:00] it's pretty fine scale monitoring, which is something that hasn't really been been carried out before. And the low-flow period is when, uh, the low, the low flow start after the last records. Speaker 4: And as the, as a temperature gets warmer, the stream starts to dry and it pretty much lasts throughout the summer until the first rains of the following year. Are you collaborating with other people on your project? Not directly with my lab mates on [00:05:30] my project. Sometimes they might come out and help me, but for the most part I've been working alone with the help of some undergraduates. There are certain side projects that we collaborate on. Um, there's also a person who is working with me from, uh, from a different department. He's not really working on my project, but, uh, something that's related to my project out on my field site. It mean it helps both of you? Yeah, definitely. And is that going to have some bearing is his, his [00:06:00] work or her work and I have some impact on your results. It definitely is connected. It is connected to, I'm more at the temperature and looking at how stratification and pull temperature stratification in pools might affect fish behavior. Speaker 4: So where, where they kind of hang out in the pool. So that's something that could definitely help us fold into your report. Yeah, exactly. So in doing your research [00:06:30] and working in the field as opposed to, uh, if you're working in the field and the lab, how much time do you spend in the field and in the lab? Um, when I'm out during the summer, uh, during my field season, it's a pretty big chunk of it. About 80 to 85% is probably spent in the field and the remainder is spent in the lab. Um, but once the summer is over and on, the field season is over. Most of the time is spent in the lab, um, [00:07:00] crunching data, processing samples and stuff like that. Speaker 5: [inaudible]Speaker 2: you're listening to spectrum on KALX Berkeley. Today we're talking with Jason Juan about his research into summertime streaming drying its effect on Fish CollagenSpeaker 5: [00:07:30] [inaudible]. Speaker 4: And so was there fish breeding going on in this part of the Stream? I would assume that that's the reason they're up there. Yeah. So one of the adults jump up into the stream. They breed typically during the winter when the rains, they come back with the rains [00:08:00] and they breed and the eggs hatch and spring. And then I kind of track the juveniles once they get to a large enough size to be able to monitor to them. So as you start to go up in the early spring, you're seeing lots of of small fish. Yeah. And it's so the fish that have spawned, have they left then or are do some stay? Yeah, but most of them have left. They're too large to stay in some of these pools. So most of them leave and with the Coho that or [00:08:30] they die right after they breed because they just breed once and they die. Speaker 4: But with the, with the steelhead, they're able to breed multiple times. And Are you tracking it all that mortality of the coho that are coming up and breeding? No, but the park service is definitely keeping track of adults, adult spawners they go up every winter and quantify the amount of a salmon reds, which are the nests that someone is build. And they also try to [00:09:00] keep track of how many fish, adult fish that they see. Talk about the insects in the fish in the same context of the frequency. So with, with the insects, um, it's, it's a pretty disturbing method to go and collect them. So we try not to collect them too frequently. We recollect them once at the beginning of the summer and again at the end of the summer. So we don't want to disturb the habitat too much that we have to kind of dig in [00:09:30] to the stream and it just disrupts, disrupts things a lot. Speaker 4: So we try to keep the frequency down and with the fish, um, we go out again, it's similar to to the insects that's we have to go and shock them and which as you can imagine, um, is quite stressful to the fish. So we shock them once in the beginning, beginning of the summer and we place pit tags into them, um, which allows us to monitor them across [00:10:00] the summer without having to actually handle them. Also, while we, um, capture them during the first event, we weigh them and measure them. And then during the late season capture event, we weigh them and measure them again and we're able to identify which the fish that were tagged, we were able to determine their growth rates and their survival. In addition, we can monitor them using the pet tags. We have a, a [00:10:30] handheld antenna that we take out and we just place it over the stream and we're able to find out where they're located or, and also if they're other still alive. Speaker 4: So that happens pretty much once a week. So the pet tag is like a radio. Gotcha. Yeah, it's an audio id, tariff id similar to what is found in a for pets, the microchips that they use for pets. And then you can also measure the mortality with that as well I guess if, yeah, so we go [00:11:00] out and we try to track their movement and also if we find a pit tag, we just kind of disturb the area around, uh, around the tag lightly. And if, if the tag isn't moving, then we kind of can surmise that there has been a mortality event that that occurred. Do you remove the fish or the die or now it's pretty hard to find them because we don't track them every day. So, so things happen [00:11:30] within the week and sometimes we kind of look around for the tag but it's pretty hard to find the tag. Speaker 4: But if we do come across any fish we do, we do take you back to the lab. Any dead Fisher and they are often tagged or have they not? Some of them are just untagged. We try to tag as many fish that we can capture at that are a certain size. They to be a certain size and size for them. So we do try to capture and tag every fish that is of [00:12:00] a certain size, but whether we do within that period of time that you can do the, that you're doing the tagging because you try to limit that. Yeah. How long is that period? What do you do? I've tried to do it all in a week. Three to four days. The tagging, the taking takes about three to four days. The caption and taking. And what's that like in terms of a process? Is it, is it you and a bunch of people doing it together? Speaker 4: Yeah. Take a little group out. Yeah, we actually took a group out, um, and we actually stayed out there for the three, three or four days. We wanted to get an early start [00:12:30] in the day and it takes about an hour to get, get out there each day. So we just decided to stay out there and it's actually quite fun. Um, most, most people really everybody volunteers to do to do like fish capturing. They're like, oh yeah, I want to do that. It's something that the interns really enjoyed. So is that time that you're in the creek, are you actually standing in the creek? So I, yeah, I actually get into the creek and I have a, an electrical Fisher and I move through the creek, [00:13:00] shocking the fish and there are a couple of them matters beside me on the scoop up any fish that had been shocked and we placed them into a bucket and then from there we kind of weigh them and measure them after, after all the fish have been captured for a certain pool. So you do this pool by Paul? Yeah, exactly. Speaker 5: You [00:13:30] are listening to spectrum on KLX Berkeley. We're talking with Jason y about his researching the summertime scream drying and its effect. Speaker 4: So Jason, how did you get interested in science when you were in high school, say or college? [00:14:00] I've always kind of really been interested in science as a kid. I really enjoyed reading science textbooks and it was as one of my favorite subjects and I just decided to stick with it. And I, I majored as a, as a biology student. And what about it appealed to you when you were young? It was like, it was the investigative process, [00:14:30] I guess that that appealed to me. It was just something that you can go out and observe and I really like that, that you can, you can actually just go out and see how nature works. And I was really fascinated by that. So biology was sort of the entree and then as you went through high school, College, yeah, I majored in biology and I really enjoyed my ecology class, just getting up out [00:15:00] there and I wasn't too keen on the molecular side of biology, but the ecological part aspect of it was really fun to get out there and observe things. And, and so it was it field work then that led you to streams? Yeah, I actually worked as a, as an undergraduate. I worked with a professor of mine and he would take me out into streams in southern California and it was quite a great experience for me. And what sort of work and studies research [00:15:30] was he doing? He was, he was doing, uh, population, uh, studies of endangered and threatened fish in southern California. Speaker 4: So when you're in the lab, what sort of data are you gathering? So for instance, with the leaf litter bags and the Algo production, um, when we come back from the field we have to process those samples. So we deploy tiles and we have to scrape off the LG from the tiles. And then we [00:16:00] have to run an analysis to quantify chlorophyll production. With the leaflet or bags that we set out, we bring them back and we, we way leaves in them and quantify how much leaf litter mass has been lost across time. What is it about the algae that you want to know in the river? With both the algae and the leaf litter, we want to see how the stream drying effects say Algal PR productivity or leaf litter decomposition. So we want [00:16:30] to see how much, how much Algo productivity there is in the early part of the summer when or when the stream is still pretty connected. Speaker 4: And then again, we want to track that change over time to see how productivity changes as the string gets dry and dry and with the leaf decomposition, same thing, seeing it over the, over the time, yeah. We want to see how decomposition rates change as the stream gets dryer and with that we're finding that decomposition rates slowed down quite a bit. [00:17:00] As the stream dries, there's less microbial activity, less insect funner to shut up the leaves. Are there other key data points that you're collecting out of the stream? Yes. I'm trying to measure the volume of water in the creek. Mostly the volume of water in between the pools of the fast flowing portions called riffles. I tried to measure how much water is in these portions and I go out pretty much every week and measure the dimensions [00:17:30] of the riffles and I'm able to get volume on every week and I'm able to quantify how this volume gets smaller and smaller every week. Eventually these, these pools are isolated and there's no more flow exactly. Between pools. Yeah. The, the riffles just most of them completely dry up by the end of summer. Speaker 3: And so the fish are then isolated in these, yeah, they're isolated. Speaker 4: The there aren't able to move among the different pools Speaker 3: at this point. Is it too soon in your study to, to [00:18:00] reflect on what you might conclude? Well, I'm, Speaker 4: I'm already seeing some pretty drastic inter-annual variation and precipitation in the area. So as I mentioned earlier, 2009 was a very dry and that was your first year? Yeah, 2009 was a very dry year, so I noticed that there was quite a bit of a mortality for the fishes. Uh, this past year, 2010 and during that summer was a lot wetter. There was a lot more habitat for the fish. A survival was a lot higher. So [00:18:30] Marty seen, uh, some significant results in terms of inter annual variation and how more extreme temperatures and extreme dry might influence the fish population. Speaker 3: Is there any part of water quality that you're measuring? Speaker 4: Temperature and a dissolved oxygen levels? Not In terms of pollution really, but a temperature and dissolved oxygen are are really key for [00:19:00] some almond species in particular, they require cool temperatures that are pretty well oxygenated. Speaker 3: The information that you're getting from your study will have an impact on other streams and creek management potentially. Yeah, that's, that's my hope Speaker 4: is that especially in certain areas where water withdrawals occur and there needs to be a certain amount of a water, hopefully our findings can maybe influence these areas where water withdrawals occur in the [00:19:30] stream comes even more dry than they typically should naturally. Speaker 3: Jason, thanks very much for coming in and talking about your research. Yes. Speaker 6: Oh, Speaker 7: [inaudible].Speaker 3: A regular feature of spectrum is dimension. [00:20:00] A few of the science and technology events happening locally over the next few weeks. Joining me this week to bring you the calendar is Rick Karnofsky. Speaker 8: In 1848 gold was discovered in the Sierra Nevada mountains luring people by the thousands to California. Join Ranger Tammy on Saturday, August 13th from 11 to noon to find out how this event changed the San Francisco Bay forever at the Bay model visitors center in Sausalito. This is a free event on Saturday August 13th at 4:30 PM Christopher de Carlo [00:20:30] will present how to be a really good pain in the ass. A critical thinkers guide to asking the right questions at Kelly's Irish pub, five 30 Jackson Street, San Francisco visit. Reason for reason.org for more info. That's r. E a s o n, the number four R e a. S. O. N. Dot. O. R. G. Speaker 3: The science at Kow lecture series for August will be presented by Dr Willie Michaelson and is entitled nanotechnology, Enabling Environmental Monitoring. [00:21:00] Dr Michelson is the executive director of the center of Integrated Nano Mechanical Systems known as coin's, a nanoscale science and Engineering Center headquartered at UC Berkeley dedicated to enabling and realizing novel environmental monitoring applications using nanotechnology. The date of the lecture is Saturday, August 20th at 11:00 AM in the genetics and plant biology building room. 100 Speaker 8: August 17th center night takes [00:21:30] place at the rickshaw. Stop. One 55 [inaudible] street at Van Ness in San Francisco from seven 30 to 10:00 PM at this $8 old age of show you'll hear talks about winery building, a virtual reality chocolate factory and neutrophils, one of the first immune cells to reach infection sites. Be there and be square. Visit SF dot [inaudible] Dot Com that's SF dot n e r, d an ite.com Speaker 8: nightlife takes place Thursday nights from 6:00 PM to 10:00 PM at the California [00:22:00] Academy of Sciences in San Francisco's Golden Gate Park. It is 21 and over and pictures music, cocktails and exhibits centered around a theme. In addition, the regular exhibits such as the rainforest and planetarium will be open. August 25th nightlife is on dinosaurs. Paleo lab will present a fossil shone till featuring trilobytes Coprolites, Aka fossilized dyno poop and other amazing fines that are 65 to 500 million years old. Check out additional specimens from the academy's research collections and at dyno burlesque. Show [00:22:30] the planetarium will feature cosmic collisions, a fulldome show depicting the hypersonic impacts that drive the evolution of the universe, including a recreation of the meteorite impact that hastened the end of the age of dinosaurs 65 million years ago. Clearing the way for mammals like us to thrive admission is $12 for more info and for tickets, visit www.cal academy.org that's www dot c a l a c a d e m y dot o r g Speaker 3: [00:23:00] and now several news stories. This item from the inside science news service scientists battle the dramatic declines of honeybee colonies with targeted breeding. There are a handful of pests and diseases that individually and in combination are causing unprecedented mortality in [00:23:30] honeybee colonies in Europe and North America. Serious efforts are being made to find solutions that can eradicate the pests and diseases. While the search for a solution continues. Researchers in Canada and the United States are attempting to bees that are resistant to Mites and viruses that attack bee colonies. The breeding process exposes the Queens to high levels of what is termed disease pressure. According to Rob Curie, professor of entomology [00:24:00] at the University of Manitoba. The survivors are then bred next season and so on. Seven generations have been bred so far. We are looking for bees that are resistant to mites and with a greater tolerance to viruses because they appear to be the two main factors behind colony loss. Speaker 3: QRI said and added breeding attribute pursued by the Canadian breeders is the ability to withstand the brutal North American winters. Curious said [00:24:30] that normally only 46% of the species known as European honeybees survive the Canadian winter, but the newest generations have a 75% survival rate. The total losses from managed honeybee colonies in the United States were 30% from all causes for the 2010 2011 winter according to the annual survey conducted by the US Department of Agriculture and the apiary inspectors of America. [00:25:00] This is roughly similar to the losses reported in similar surveys done in the four previous years. This story from Metta page today, lab grown trickier implanted in patient June 9th, 2011 at the Karolinska University Hospital in hunting, Stockholm, Sweden. Dr Paolo Macchiarini implanted the first ever bio artificial trachea grown on a synthetic [00:25:30] substrate using the patient's own stem cells. The patient was a 36 year old cancer patient for this procedure. Dr Macchiarini and his colleagues collected stem cells from the patient who had late stage tracheal cancer since no suitable donor windpipe was available. The researchers used a nano composite tracheal scaffold designed and built by Alexander Se Follian Phd of the University College London. [00:26:00] They seated the polymer model with auto Lucas stem cells. These are blood forming stem cells and grew them for two days in a bioreactor. Dr Mk Jadine says there's no room for rejection because of the cells are the patient's own. Thus, there is no need for him to be on immuno suppressive drugs. Speaker 2: [inaudible] [00:26:30] occurred during the show is pointless on a David Kearns album, folk and acoustic made available for creative Commons license 3.0 attribution [inaudible] mm editing assistance provided by Judith White Marceline production assistance provided by [00:27:00] Karnofsky [inaudible]. Thank you for listening to spectrum. We are happy to hear if you have comments or questions, please send them to us via email address. Is Spectrum. K A l s yahoo.com Speaker 5: [00:27:30] genius at this same time. [inaudible] Speaker 2: [inaudible]Speaker 5: [inaudible] [inaudible] [inaudible] [00:28:00] [inaudible]. Hosted on Acast. See acast.com/privacy for more information.
In critical spawning and overwintering habitat for salmonids Hwan studies the effects of temporal stream fragmentation across three organizational levels of ecology: population, community, and ecosystem levels.TranscriptSpeaker 1: Spectrum's next Speaker 2: [inaudible].Speaker 1: [00:01:00] Welcome to spectrum the science and technology show on k a l x Berkeley, a biweekly 30 minute program bringing you interviews featuring bay area scientists and technologists as well as a calendar of local events and news. Speaker 3: Hi, my name is Brad Swift. I'm the host of today's show. Our interview is with Jason won a third year phd student in the Carlson lab, which is [00:01:30] part of the environmental science policy and Management Department of the College of natural resources. Professor Stephanie Carlson directs the lab and she is a fish ecologist. Jason is researching the effects of summertimes stream drying on fish ecology in the John West fork, a creek in Marin county. The John West fork is the spawning grounds for two varieties of salmon the summer of 2011 Woolmark the third year of his research on this stream. [00:02:00] His research will continue for two and possibly three more years. This interview is prerecorded and edited. Speaker 4: Jason, welcome to spectrum. Thanks for coming in. Thank you. Wanted to ask if you could, uh, give us a brief overview of your research and add in there how it's being funded. My research is looking at the effects of low summer flow on juvenile steelhead, on the insect communities out in the stream and [00:02:30] on certain ecosystem processes such as Algal production and leaf decomposition. And it's currently being funded by, mostly by my, by my guiding professor, Stephanie Carlson. And I also have some funding from our department and the division within our department. All right. We get out a sperm wildlife grant, which helps fund the research. And also I'm currently on an NSF graduate research fellowship. Described the, the general [00:03:00] area of the site that you chose. Sort of put it in context of where it is. So my study say, uh, the John West work is in point Reyes national seashore, which is about an hour north of Berkeley in a national park in and surrounded by some state parks. Speaker 4: Also. Can you explain the watershed and the area that you're working, how it all interrelates to the watershed? So I'm, I'm working in the Lagunitas watershed. I'm working [00:03:30] in a creek that is a tributary of a tributary of a creek to the lock Anitas to log in neatest creek and log Anitas creek flows into Tomas Bay in point rays. The creek that I'm working in is a little different in that there are only two species of fish up there. Both our salt Monets, there are still head and coho salmon. This is because it's not that the creek went dry, completely dry one year and there's, there [00:04:00] was a culvert that was put in place and other fish species weren't able to recolonize the creek, but someone had adults can jump over the barrier. And so they were able to recolonize the creek and they're actually jumping through the culvert. Speaker 4: Yeah. And through this culvert and swimming up swimming into the two John West work. And what's the drop on the culvert like from, from the the bottom lip to the dead of the bid. Lower part [00:04:30] of the creek. It's about four feet. Four feet drop-off. Yeah. So that's quite a leap for the salmon. Yeah. And so with this study, what is it that you're trying to learn? That is not already known. So I'm basically trying to look at the effects of low flow and my study is really looking at what the affects are at a really fine scale. So I'm tracking, uh, juvenile steel head growth, movement and survival and I'm tracking them on a weekly basis. So [00:05:00] it's pretty fine scale monitoring, which is something that hasn't really been been carried out before. And the low-flow period is when, uh, the low, the low flow start after the last records. Speaker 4: And as the, as a temperature gets warmer, the stream starts to dry and it pretty much lasts throughout the summer until the first rains of the following year. Are you collaborating with other people on your project? Not directly with my lab mates on [00:05:30] my project. Sometimes they might come out and help me, but for the most part I've been working alone with the help of some undergraduates. There are certain side projects that we collaborate on. Um, there's also a person who is working with me from, uh, from a different department. He's not really working on my project, but, uh, something that's related to my project out on my field site. It mean it helps both of you? Yeah, definitely. And is that going to have some bearing is his, his [00:06:00] work or her work and I have some impact on your results. It definitely is connected. It is connected to, I'm more at the temperature and looking at how stratification and pull temperature stratification in pools might affect fish behavior. Speaker 4: So where, where they kind of hang out in the pool. So that's something that could definitely help us fold into your report. Yeah, exactly. So in doing your research [00:06:30] and working in the field as opposed to, uh, if you're working in the field and the lab, how much time do you spend in the field and in the lab? Um, when I'm out during the summer, uh, during my field season, it's a pretty big chunk of it. About 80 to 85% is probably spent in the field and the remainder is spent in the lab. Um, but once the summer is over and on, the field season is over. Most of the time is spent in the lab, um, [00:07:00] crunching data, processing samples and stuff like that. Speaker 5: [inaudible]Speaker 2: you're listening to spectrum on KALX Berkeley. Today we're talking with Jason Juan about his research into summertime streaming drying its effect on Fish CollagenSpeaker 5: [00:07:30] [inaudible]. Speaker 4: And so was there fish breeding going on in this part of the Stream? I would assume that that's the reason they're up there. Yeah. So one of the adults jump up into the stream. They breed typically during the winter when the rains, they come back with the rains [00:08:00] and they breed and the eggs hatch and spring. And then I kind of track the juveniles once they get to a large enough size to be able to monitor to them. So as you start to go up in the early spring, you're seeing lots of of small fish. Yeah. And it's so the fish that have spawned, have they left then or are do some stay? Yeah, but most of them have left. They're too large to stay in some of these pools. So most of them leave and with the Coho that or [00:08:30] they die right after they breed because they just breed once and they die. Speaker 4: But with the, with the steelhead, they're able to breed multiple times. And Are you tracking it all that mortality of the coho that are coming up and breeding? No, but the park service is definitely keeping track of adults, adult spawners they go up every winter and quantify the amount of a salmon reds, which are the nests that someone is build. And they also try to [00:09:00] keep track of how many fish, adult fish that they see. Talk about the insects in the fish in the same context of the frequency. So with, with the insects, um, it's, it's a pretty disturbing method to go and collect them. So we try not to collect them too frequently. We recollect them once at the beginning of the summer and again at the end of the summer. So we don't want to disturb the habitat too much that we have to kind of dig in [00:09:30] to the stream and it just disrupts, disrupts things a lot. Speaker 4: So we try to keep the frequency down and with the fish, um, we go out again, it's similar to to the insects that's we have to go and shock them and which as you can imagine, um, is quite stressful to the fish. So we shock them once in the beginning, beginning of the summer and we place pit tags into them, um, which allows us to monitor them across [00:10:00] the summer without having to actually handle them. Also, while we, um, capture them during the first event, we weigh them and measure them. And then during the late season capture event, we weigh them and measure them again and we're able to identify which the fish that were tagged, we were able to determine their growth rates and their survival. In addition, we can monitor them using the pet tags. We have a, a [00:10:30] handheld antenna that we take out and we just place it over the stream and we're able to find out where they're located or, and also if they're other still alive. Speaker 4: So that happens pretty much once a week. So the pet tag is like a radio. Gotcha. Yeah, it's an audio id, tariff id similar to what is found in a for pets, the microchips that they use for pets. And then you can also measure the mortality with that as well I guess if, yeah, so we go [00:11:00] out and we try to track their movement and also if we find a pit tag, we just kind of disturb the area around, uh, around the tag lightly. And if, if the tag isn't moving, then we kind of can surmise that there has been a mortality event that that occurred. Do you remove the fish or the die or now it's pretty hard to find them because we don't track them every day. So, so things happen [00:11:30] within the week and sometimes we kind of look around for the tag but it's pretty hard to find the tag. Speaker 4: But if we do come across any fish we do, we do take you back to the lab. Any dead Fisher and they are often tagged or have they not? Some of them are just untagged. We try to tag as many fish that we can capture at that are a certain size. They to be a certain size and size for them. So we do try to capture and tag every fish that is of [00:12:00] a certain size, but whether we do within that period of time that you can do the, that you're doing the tagging because you try to limit that. Yeah. How long is that period? What do you do? I've tried to do it all in a week. Three to four days. The tagging, the taking takes about three to four days. The caption and taking. And what's that like in terms of a process? Is it, is it you and a bunch of people doing it together? Speaker 4: Yeah. Take a little group out. Yeah, we actually took a group out, um, and we actually stayed out there for the three, three or four days. We wanted to get an early start [00:12:30] in the day and it takes about an hour to get, get out there each day. So we just decided to stay out there and it's actually quite fun. Um, most, most people really everybody volunteers to do to do like fish capturing. They're like, oh yeah, I want to do that. It's something that the interns really enjoyed. So is that time that you're in the creek, are you actually standing in the creek? So I, yeah, I actually get into the creek and I have a, an electrical Fisher and I move through the creek, [00:13:00] shocking the fish and there are a couple of them matters beside me on the scoop up any fish that had been shocked and we placed them into a bucket and then from there we kind of weigh them and measure them after, after all the fish have been captured for a certain pool. So you do this pool by Paul? Yeah, exactly. Speaker 5: You [00:13:30] are listening to spectrum on KLX Berkeley. We're talking with Jason y about his researching the summertime scream drying and its effect. Speaker 4: So Jason, how did you get interested in science when you were in high school, say or college? [00:14:00] I've always kind of really been interested in science as a kid. I really enjoyed reading science textbooks and it was as one of my favorite subjects and I just decided to stick with it. And I, I majored as a, as a biology student. And what about it appealed to you when you were young? It was like, it was the investigative process, [00:14:30] I guess that that appealed to me. It was just something that you can go out and observe and I really like that, that you can, you can actually just go out and see how nature works. And I was really fascinated by that. So biology was sort of the entree and then as you went through high school, College, yeah, I majored in biology and I really enjoyed my ecology class, just getting up out [00:15:00] there and I wasn't too keen on the molecular side of biology, but the ecological part aspect of it was really fun to get out there and observe things. And, and so it was it field work then that led you to streams? Yeah, I actually worked as a, as an undergraduate. I worked with a professor of mine and he would take me out into streams in southern California and it was quite a great experience for me. And what sort of work and studies research [00:15:30] was he doing? He was, he was doing, uh, population, uh, studies of endangered and threatened fish in southern California. Speaker 4: So when you're in the lab, what sort of data are you gathering? So for instance, with the leaf litter bags and the Algo production, um, when we come back from the field we have to process those samples. So we deploy tiles and we have to scrape off the LG from the tiles. And then we [00:16:00] have to run an analysis to quantify chlorophyll production. With the leaflet or bags that we set out, we bring them back and we, we way leaves in them and quantify how much leaf litter mass has been lost across time. What is it about the algae that you want to know in the river? With both the algae and the leaf litter, we want to see how the stream drying effects say Algal PR productivity or leaf litter decomposition. So we want [00:16:30] to see how much, how much Algo productivity there is in the early part of the summer when or when the stream is still pretty connected. Speaker 4: And then again, we want to track that change over time to see how productivity changes as the string gets dry and dry and with the leaf decomposition, same thing, seeing it over the, over the time, yeah. We want to see how decomposition rates change as the stream gets dryer and with that we're finding that decomposition rates slowed down quite a bit. [00:17:00] As the stream dries, there's less microbial activity, less insect funner to shut up the leaves. Are there other key data points that you're collecting out of the stream? Yes. I'm trying to measure the volume of water in the creek. Mostly the volume of water in between the pools of the fast flowing portions called riffles. I tried to measure how much water is in these portions and I go out pretty much every week and measure the dimensions [00:17:30] of the riffles and I'm able to get volume on every week and I'm able to quantify how this volume gets smaller and smaller every week. Eventually these, these pools are isolated and there's no more flow exactly. Between pools. Yeah. The, the riffles just most of them completely dry up by the end of summer. Speaker 3: And so the fish are then isolated in these, yeah, they're isolated. Speaker 4: The there aren't able to move among the different pools Speaker 3: at this point. Is it too soon in your study to, to [00:18:00] reflect on what you might conclude? Well, I'm, Speaker 4: I'm already seeing some pretty drastic inter-annual variation and precipitation in the area. So as I mentioned earlier, 2009 was a very dry and that was your first year? Yeah, 2009 was a very dry year, so I noticed that there was quite a bit of a mortality for the fishes. Uh, this past year, 2010 and during that summer was a lot wetter. There was a lot more habitat for the fish. A survival was a lot higher. So [00:18:30] Marty seen, uh, some significant results in terms of inter annual variation and how more extreme temperatures and extreme dry might influence the fish population. Speaker 3: Is there any part of water quality that you're measuring? Speaker 4: Temperature and a dissolved oxygen levels? Not In terms of pollution really, but a temperature and dissolved oxygen are are really key for [00:19:00] some almond species in particular, they require cool temperatures that are pretty well oxygenated. Speaker 3: The information that you're getting from your study will have an impact on other streams and creek management potentially. Yeah, that's, that's my hope Speaker 4: is that especially in certain areas where water withdrawals occur and there needs to be a certain amount of a water, hopefully our findings can maybe influence these areas where water withdrawals occur in the [00:19:30] stream comes even more dry than they typically should naturally. Speaker 3: Jason, thanks very much for coming in and talking about your research. Yes. Speaker 6: Oh, Speaker 7: [inaudible].Speaker 3: A regular feature of spectrum is dimension. [00:20:00] A few of the science and technology events happening locally over the next few weeks. Joining me this week to bring you the calendar is Rick Karnofsky. Speaker 8: In 1848 gold was discovered in the Sierra Nevada mountains luring people by the thousands to California. Join Ranger Tammy on Saturday, August 13th from 11 to noon to find out how this event changed the San Francisco Bay forever at the Bay model visitors center in Sausalito. This is a free event on Saturday August 13th at 4:30 PM Christopher de Carlo [00:20:30] will present how to be a really good pain in the ass. A critical thinkers guide to asking the right questions at Kelly's Irish pub, five 30 Jackson Street, San Francisco visit. Reason for reason.org for more info. That's r. E a s o n, the number four R e a. S. O. N. Dot. O. R. G. Speaker 3: The science at Kow lecture series for August will be presented by Dr Willie Michaelson and is entitled nanotechnology, Enabling Environmental Monitoring. [00:21:00] Dr Michelson is the executive director of the center of Integrated Nano Mechanical Systems known as coin's, a nanoscale science and Engineering Center headquartered at UC Berkeley dedicated to enabling and realizing novel environmental monitoring applications using nanotechnology. The date of the lecture is Saturday, August 20th at 11:00 AM in the genetics and plant biology building room. 100 Speaker 8: August 17th center night takes [00:21:30] place at the rickshaw. Stop. One 55 [inaudible] street at Van Ness in San Francisco from seven 30 to 10:00 PM at this $8 old age of show you'll hear talks about winery building, a virtual reality chocolate factory and neutrophils, one of the first immune cells to reach infection sites. Be there and be square. Visit SF dot [inaudible] Dot Com that's SF dot n e r, d an ite.com Speaker 8: nightlife takes place Thursday nights from 6:00 PM to 10:00 PM at the California [00:22:00] Academy of Sciences in San Francisco's Golden Gate Park. It is 21 and over and pictures music, cocktails and exhibits centered around a theme. In addition, the regular exhibits such as the rainforest and planetarium will be open. August 25th nightlife is on dinosaurs. Paleo lab will present a fossil shone till featuring trilobytes Coprolites, Aka fossilized dyno poop and other amazing fines that are 65 to 500 million years old. Check out additional specimens from the academy's research collections and at dyno burlesque. Show [00:22:30] the planetarium will feature cosmic collisions, a fulldome show depicting the hypersonic impacts that drive the evolution of the universe, including a recreation of the meteorite impact that hastened the end of the age of dinosaurs 65 million years ago. Clearing the way for mammals like us to thrive admission is $12 for more info and for tickets, visit www.cal academy.org that's www dot c a l a c a d e m y dot o r g Speaker 3: [00:23:00] and now several news stories. This item from the inside science news service scientists battle the dramatic declines of honeybee colonies with targeted breeding. There are a handful of pests and diseases that individually and in combination are causing unprecedented mortality in [00:23:30] honeybee colonies in Europe and North America. Serious efforts are being made to find solutions that can eradicate the pests and diseases. While the search for a solution continues. Researchers in Canada and the United States are attempting to bees that are resistant to Mites and viruses that attack bee colonies. The breeding process exposes the Queens to high levels of what is termed disease pressure. According to Rob Curie, professor of entomology [00:24:00] at the University of Manitoba. The survivors are then bred next season and so on. Seven generations have been bred so far. We are looking for bees that are resistant to mites and with a greater tolerance to viruses because they appear to be the two main factors behind colony loss. Speaker 3: QRI said and added breeding attribute pursued by the Canadian breeders is the ability to withstand the brutal North American winters. Curious said [00:24:30] that normally only 46% of the species known as European honeybees survive the Canadian winter, but the newest generations have a 75% survival rate. The total losses from managed honeybee colonies in the United States were 30% from all causes for the 2010 2011 winter according to the annual survey conducted by the US Department of Agriculture and the apiary inspectors of America. [00:25:00] This is roughly similar to the losses reported in similar surveys done in the four previous years. This story from Metta page today, lab grown trickier implanted in patient June 9th, 2011 at the Karolinska University Hospital in hunting, Stockholm, Sweden. Dr Paolo Macchiarini implanted the first ever bio artificial trachea grown on a synthetic [00:25:30] substrate using the patient's own stem cells. The patient was a 36 year old cancer patient for this procedure. Dr Macchiarini and his colleagues collected stem cells from the patient who had late stage tracheal cancer since no suitable donor windpipe was available. The researchers used a nano composite tracheal scaffold designed and built by Alexander Se Follian Phd of the University College London. [00:26:00] They seated the polymer model with auto Lucas stem cells. These are blood forming stem cells and grew them for two days in a bioreactor. Dr Mk Jadine says there's no room for rejection because of the cells are the patient's own. Thus, there is no need for him to be on immuno suppressive drugs. Speaker 2: [inaudible] [00:26:30] occurred during the show is pointless on a David Kearns album, folk and acoustic made available for creative Commons license 3.0 attribution [inaudible] mm editing assistance provided by Judith White Marceline production assistance provided by [00:27:00] Karnofsky [inaudible]. Thank you for listening to spectrum. We are happy to hear if you have comments or questions, please send them to us via email address. Is Spectrum. K A l s yahoo.com Speaker 5: [00:27:30] genius at this same time. [inaudible] Speaker 2: [inaudible]Speaker 5: [inaudible] [inaudible] [inaudible] [00:28:00] [inaudible]. See acast.com/privacy for privacy and opt-out information.
Background: HIV has fuelled the TB epidemic in sub-Saharan Africa. Mortality in patients co-infected with TB and HIV is high. Managing factors influencing mortality in TB patients might help reducing it. This study investigates factors associated with mortality including patients' HIV serostatus, CD4 cell count, laboratory, nutritional and demographic characteristics in AFB smear positive pulmonary TB patients. Methods: We studied 887 sputum smear positive PTB patients, between 18 and 65 years of age receiving standard 8 months anti-TB treatment. Demographic, anthropometric and laboratory data including HIV, CD4 and other tests were collected at baseline and at regular intervals. Patients were followed for a median period of 2.5 years. Results: Of the 887 participants, 155 (17.5%) died, of whom 90.3% (140/155) were HIV-infected, a fatality of 29.7% (140/471) compared to 3.6% (15/416) among HIV-uninfected. HIV infection, age, low Karnofsky score, CD4 cell counts and hemoglobin, high viral load, and oral thrush were significantly associated with high mortality in all patients. Conclusion: Mortality among HIV-infected TB patients is high despite the use of effective anti-TB therapy. Most deaths occur after successful completion of therapy, an indication that patients die from causes other than TB. HIV infection is the strongest independent predictor of mortality in this cohort.
Objective: The aim of the current prospective study was to analyse the validity of MRI based diagnosis of brainstem gliomas which was verified by stereotactic biopsy and follow-up evaluation as well as to assess prognostic factors and risk profile. Methods: Between 1998 and 2007, all consecutive adult patients with radiologically suspected brainstem glioma were included. The MRI based diagnosis of the lesions was made independently by an experienced neuroradiologist. Histopathological evaluation was performed in all patients from paraffin embedded specimens obtained by multimodal image guided stereotactic serial biopsy technique. Histopathological results were compared with prior radiological assessment. Length of survival was estimated with the Kaplan–Meier method and prognostic factors were calculated using the Cox model. Results: 46 adult patients were included. Histological evaluation revealed pilocytic astrocytoma (n=2), WHO grade II glioma (n=14), malignant glioma (n=12), metastasis (n=7), lymphoma (n=5), cavernoma (n=1), inflammatory disease (n=2) or no tumour/ gliosis (n=3). Perioperative morbidity was 2.5% (n=1). There was no permanent morbidity and no mortality. All patients with ‘‘no tumour’’ or ‘‘inflammatory disease’’ survived. Patients with low grade glioma and malignant glioma showed a 1 year survival rate of 75% and 25%, respectively; the 1 year survival rate for patients with lymphoma or metastasis was 30%. In the subgroup with a verified brainstem glioma, negative predictors for length of survival were higher tumour grade (p=0.002) and Karnofsky performance score (70 (p=0.004). Conclusion: Intra-axial brainstem lesions with a radiological pattern of glioma represent a very heterogeneous tumour group with completely different outcomes. Radiological features alone are not reliable for diagnostic classification. Stereotactic biopsy is a safe method to obtain a valid tissue diagnosis, which is indispensible for treatment decision.
Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07
This cumulative doctoral thesis contains 4 publications. Aim of the first study was to evaluate the influence of feline interferon-ω on the survival time and quality of life of cats with feline infectious peritonitis. In this placebo-controlled doubleblind study, 37 cats suffering from feline infectious peritonitis were included. Inclusion criterion was a confirmed diagnosis of FIP. Cats were included from August 2004 to April 2006. They were treated randomly with either feline interferon-ω or placebo. Additionally, glucocorticoids, antibiotics, passive immunization, and symptomatic treatment were given. There was no statistically significant difference in survival time, quality of life, or any other clinical or laboratory parameter (including complete blood count, serum biochemistry profile) in cats treated with feline interferon-ω versus cats treated with placebo besides number of lymphocytes. The number of lymphocytes was significantly lower in cats treated with feline interferon-ω. The cats survived between 3 and 200 days. One cat treated with feline interferon-ω lived for 200 days. This cat showed no symptoms for approximately 6 months, but had to be euthanized after 200 days due to a recurrence of FIP following secondary upper respiratory tract infection. The aim of the second prospective study was to evaluate if clinical symptoms or laboratory parameters correlate with the survival time and to evaluate median survival time after diagnosis. In this study, 43 cats with confirmed feline infectious peritonitis were included between August 2004 and April 2006. Median survival time was 8 days and mean survival time was 15 days after diagnosis. Karnofsky´s score, number of thrombocytes, number of lymphocytes, concentration of bilirubin in serum, and the amount of effusion significantly correlated with survival time. A low Karnofsky´s score, low numbers of thrombocytes and lymphocytes, a high concentration of bilirubin, and a high amount of effusion were associated with a poor rognosis. The third publication is a review about treatment of cats with feline infectious peritonitis summarizing all published reports and studies in the literature. A lot of drugs have been tested, but very few had proven efficacy. Nearly all the mentioned studies had no confirmed diagnosis of feline infectious peritonitis and no control group. The fourth publication is a case report. In this report clinical signs, laboratory values, diagnosis, treatment, and outcome of a cat with feline infectious peritonitis were described.
Background: The prognosis for patients with malignant astrocytoma or brain metastases is often fatal despite intensive therapy. Therefore we wished to elucidate whether the quality of life (QoL) is a determinant of overall survival (OAS). Patients and Methods: From 1997 to 2000 153 patients with brain tumours were screened; 39 patients (26%) refused to participate and further 47 patients were excluded (cerebral impairment 14%, amaurosis/language problems 3%, Karnofsky performance score < 50% 7%, death 8%, non-compliance 7%). Thus, 57 patients were analysed (33 with primary brain tumours, 24 with brain metastases). With the FACT-G questionnaire cancer-specific aspects of health-related QoL were assessed. Results: Patients with metastases showed a lower QoL in the physical sphere than patients with astrocytoma, but there were no significant differences in OAS. Median survival of patients with good QoL was 31.3 months versus 14.2 months in patients with bad QoL. Only the two variables `living with a spouse' and FACT-G sum score had a statistically significant influence on survival (p = 0.033 and p = 0.003) modelled by the Cox-PH regression. Patients who did not live with a spouse had shorter survival times than the other patients. Conclusion: Health-related QoL can serve to identify a patient group with higher risks of death.
Background: In the framework of a prospective longitudinal study, the quality of life (QoL) and support requirements of patients from a university hospital department of radiotherapy were evaluated for the first time by means of established psychodiagnostic questionnaires. Patients and Methods: At first, 732 patients were screened, of whom 446 (60.9%) fulfilled the criteria for inclusion; 39.1% did not (refusals 21.0%, low Karnofsky performance status 6.6%, management problems 3.4%, language barriers 3.0%, cognitive restrictions 2.6%, death 2.5%). Disease-specific aspects of QoL (Functional Assessment of Cancer Treatment - General, FACT-G) and moderating variables {[}Social Support Scale (SSS), Disease Coping (FKV), Self-Assessment Depression Scale (SDS), and Self-Defined Care Requirements (BB)] were self-rated by patients with different tumor types before radiotherapy (T1), after radiotherapy (T2), and 6 weeks after the end of radiotherapy (T3). We studied 265 patients (157 male, 108 female; median age 58.6 years) with complete data of three time points. Results: In general, QoL of patients decreased significantly over all time points in all subscales. Social support was rated high and remained constant throughout the treatment. Apparent coping mechanisms were active problem-oriented coping, leisure activities, and self-support. The patients' depression proved to be an important and constant factor without significant changes. The support requirement is characterized by the need for more medical information and dialogue with a physician. Conclusions: Early specific support from personnel with radiotherapeutic skills, during the disease-coping process as well as during rehabilitation, should be a permanent component of an integrated radiooncological treatment schedule.
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