Podcast appearances and mentions of joe derisi

Autoimmune neurology is a rapidly evolving subspecialty that focuses on neurologic disorders with atypical immune responses. In this episode, Aaron Berkowitz, MD, PhD FAAN, speaks with Sean J. Pittock, MD, an author of the article “Overview and Diagnostic Approach in Autoimmune Neurology,” in the Continuum August 2024 Autoimmune Neurology issue. Dr. Berkowitz is a Continuum® Audio interviewer and professor of neurology at the University of California San Francisco, Department of Neurology and a neurohospitalist, general neurologist, and a clinician educator at the San Francisco VA Medical Center and San Francisco General Hospital in San Francisco, California. Dr. Pittock is the director for the Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic in Rochester, Minnesota. Additional Resources Read the article: Overview and Diagnostic Approach in Autoimmune Neurology Subscribe to Continuum: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @AaronLBerkowitz Transcript Full transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum, the premier topic-based neurology clinical review and CME journal from the American Academy of Neurology. Thank you for joining us on Continuum Audio, which features conversations with Continuum's guest editors and authors who are the leading experts in their fields. Subscribers to the Continuum journal can read the full article or listen to verbatim recordings of the article and have access to exclusive interviews not featured on the podcast. Please visit the link in the episode notes for more information on the article, subscribing to the journal, and how to get CME.    Dr Berkowitz: This is Dr Aaron Berkowitz, and today, I'm interviewing Dr Sean Pittock about his article, “Introduction to Autoimmune Neurology and Diagnostic Approach”, which he wrote with his colleague, Dr Andrew McKeon. This article is a part of the August 2024 Continuum issue on autoimmune neurology. Welcome to the podcast, Dr Pittock. Could you introduce yourself to our audience?    Dr Pittock: Well, thank you very much, Dr Berkowitz. So, yeah, I'm a neurologist at the Mayo Clinic. I direct the neuroimmunology laboratory with Dr McKeon and Dr Mills here, and I have also been very much involved in the autoimmune neurology section at the American Academy of Neurology.    Dr Berkowitz: So, many of you probably know Dr Pittock - or if you don't know, you've certainly diagnosed diseases that he has described and written about, and so it's a real honor to get to talk to you today and pick your brain a little bit about some of these complex diseases. So, autoimmune neurology is certainly one of the most exciting subspecialties of our field. I feel like when I talk to students and they ask me to make a case for why they should consider neurology as a career, I tell them, “Of course, I have many reasons I love neurology”, but one thing I mention is that, although many other fields of medicine may have made incredible advances as far as treatments, I can't think of too many other fields outside neurology where entirely new diseases have been described since I've been in training and come out of training - and many of those have been in your field of autoimmune neurology. I can think of cases where I've heard you or one of your colleagues on a neurology podcast describing a new antibody, new disease, and a few weeks later, we see that disease and give a patient a diagnosis that had been elusive from other physicians and hospitals. It's a very exciting, gratifying area. It's also daunting, like, every time I go to the AAN and hear one of your colleagues, there's a new disease, and we realize, “Oops! Was I missing that?” or, “Am I going to see this?” And so, hoping to pick your brain a bit today about some of the key concepts and how to keep them in mind so our listeners can recognize, diagnose, and treat these conditions, even if they can't remember every single antibody in your article and all the new ones you and your colleagues will probably discover between now and when this, um, podcast is released. So, before we get into some of the important clinical aspects of these conditions, could you just lay out sort of the broad breaststrokes, the lay of the land of cell-mediated versus antibody-mediated paraneoplastic versus nonparaneoplastic cell surface versus intracellular - how can we sort of organize this area in our minds?    Dr Pittock: Yeah. It's complex, and it's really an evolving story. But the importance, really, from the perspective of the reader and the perspective of the clinician is that we're talking about disorders where we can actually do something - we can actually impact patients.  And we think about the concept of stopping and restoring in neurology now. We're talking about disorders where we have the potential to stop these inflammatory immune-mediated disorders and, potentially, by stopping early, we may be able to restore function - so, a really important new and evolving field in neurology, because you don't want to miss these conditions. Trying to get your head around the complexity of these entities is difficult, but what we've done in this chapter is, really, to try and lay the groundwork for the following chapters, but provide somewhat of a simplistic approach, but a practical approach that really, I think, can help clinicians. So, the way I think of it, a lot of autoimmune neurology really has stemmed from the discovery of antibodies that cause neurological disease, and the examples of those would be going back to myasthenia gravis (with antibodies to the acetylcholine receptor), going back to Lambert-Eaton syndrome. And then, you know, even if you go back to the older traditional paraneoplastic disorders (the Hu, the Ri, the Yo), at the end of the day, you really have two essential entities, if you want to be very simple. The first is disorders that are caused by an antibody, and the second are disorders where the antibodies you detect are not causing the disorder, but they're telling you that there's predominantly a cellular or T-cell mediated attack of the nervous system. And I think thinking about the diseases in those kind of simple terms helps us when we think about what would be the best treatment to use in these types of cases.   Dr Berkowitz: Fantastic. I think that's very helpful. And just to make sure it's clear in the minds of our listeners when we're dividing into these sort of causative antibodies versus antibodies that might be, uh (I don't know if I'm using the word properly), but, sort of epiphenomena (or they're present, but they're not causative) as you said, can you just give some examples of the ones on either side and how making this distinction helps us in practice?    Dr Pittock: Yes. So, antibodies that are causative of disease - I think, you know, the one that I've done a lot of work on is in neuromyelitis optica, where you have antibodies that are targeting a water channel that sits on an astrocyte, and so it causes NMOSD, or what we consider an autoimmune astrocytopathy. And we know that when the antibody binds to the target, many things can happen. So, when aquaporin-4 antibodies bind to aquaporin-4, they can do a lot of things. They can cause internalization, they can activate complement that results in the killing of the cell - but there can be other situations. For example, when NMDA-receptor antibodies bind to the NMDA receptor, then a variety of different things can occur different to water channel autoimmunity - where, for example, the receptor (the NMDA receptor) is downregulated off the cell surface, and that results, to some extent, in the neuropsychiatric phenomenon that we see in NMDA-receptor autoimmunity. And, obviously, when you have a situation where the antibodies are causing the disease, removal of those antibodies, or the reduction in the production of those antibodies, is going to help patients. Now, on the other side, we have antibodies that we detect in the blood or in the spinal fluid, and those antibodies are targeting proteins that are inside the cell - so those antibodies we don't consider as being pathogenic. Now, remember, there are sometimes situations where proteins that are inside the cell occasionally can be available for antibodies to bind at certain situations. So, for example, in the synapse, amphiphysin or the septins, may at times become available. And so, sometimes, there are targets or antibodies that are somewhat in between those two simplistic concepts. But when we're talking about antibodies that are targeting proteins on the inside of the cell, remember that antibodies don't just suddenly occur. There's a whole process of presentation of target antigen at the lymph node, and then both a T- and a B-cell response. The B-cell response potentially produces the antibodies but also triggers and stimulates T-cells, and those T-cells then go on to cause the disease. And those T-cells are very problematic, because those classical paraneoplastic and the newer ones we've described (and many have described) - these are associated with quite severe neurological disability, and they're very, very difficult to treat. And if you ask me, “Where is the holy grail of autoimmune neurology therapeutic research?” It's in trying to actually figure out ways of treating the predominantly T-cell mediated paraneoplastic and autoimmune neurological disorders. We're making great headway in terms of the treatments of the antibody-mediated neurological disorders.   Dr Berkowitz: That's a helpful overview. So, sticking with this framework, you mentioned as sort of the “causative antibody” category and the antibodies that are predominantly for intracellular antigens, but not believed to be causative - I want to make sure I'm understanding this correctly and we can convey it to our listeners - I believe you said in your paper, then, that the antibodies that are predominantly causative are more likely to be associated with conditions that are very treatable, as compared to the intracellular antibodies that are not thought to be causative, as you just said the disability can be irrecoverable or very hard to treat. And I believe another theme in your paper that you brought out is the antibodies that tend to be causative tend to be cell surface and tend to be less likely to be associated with underlying cancer (although not a perfect rule), and the intracellular antigens more commonly associated with cancer in those cases to look very hard for a cancer before giving up. Are those themes that I understand them from your paper properly, or anything else to add there?    Dr Pittock: Yes, I think that that's exactly the message that we were trying to get across, so that's good news that you've picked up on the themes. I think, yeah, in simple terms, remember that when a cytotoxic T-cell identifies the peptide that its T-cell receptor will target, the ultimate outcome is poor, all right? T-cells are like the marines - they don't mess around. Once they find their target, they eliminate that target, and so, it's really difficult to treat those types of diseases if you get them late. And most patients with cytotoxic T-cell mediated paraneoplastic neurological disorders, oftentimes, by the time they get to a center of excellence, the boat has left the dock in many respects - in other words, it's too late. So, you know, I will often see patients, for example, with progressive cerebellar degeneration (say, in the context of Purkinje cell autoantibody type 1 antibodies and a breast cancer), and if those patients are in a wheelchair at the time that I see them, there's very, very little that we can do. So, you really want to try and get that patient into the office, you know, when they're using a cane (or not), and then, potentially, you have the opportunity - using very aggressive immunosuppressive medications - to make a difference. And that is quite different to other scenarios, where, for example, if you have NMDA-receptor encephalitis - as many of the readers will know, this is a condition that is very treatable, and most patients do very well, because the antibodies, they're disrupting function, but they're not killing the neuron, as we see in those more aggressive, paraneoplastic cytotoxic T-cell mediated diseases.   Dr Berkowitz: Also, in terms of searching for an underlying cancer, another theme in your paper as I understood (but want to make sure I'm understanding and conveying to our listeners and hear your thoughts), that the cell surface and treatable antibody-mediated syndromes, as you mentioned (NMO, NMDA) tend to be less associated with underlying cancers (although can be), whereas the intracellular antigens, um, a much higher percentage of those patients are going to end up having underlying cancers. Is that correct, or any notable exceptions to be aware of in that framework?    Dr Pittock: Yeah, I think the major exception to the rule for the antibodies that are targeting intracellular antigens is the GAD65 antibody story. We generally don't consider the stiff person syndrome, cerebellar ataxia, or other autoimmune neurological disorders associated with very high levels of GAD65 antibodies - those are generally not paraneoplastic. And then there are always exceptions on both sides. You know, one of the benefits of understanding the implications of certain antibodies is trying to understand, you know, what is the likelihood of identifying a malignancy, which antibodies are high-risk antibodies (in other words, high-risk paraneoplastological disorders), and which are low risk in terms of cancer? And, you know, age and the demographic of the individual is often important, because we know, for example, with NMDA-receptor antibodies, the frequency of ovarian teratoma varies with the age of the patient.   Dr Berkowitz: Fantastic. And we encourage our listeners to read your articles – certainly, some very helpful tables and figures that help to elucidate some of these broad distinctions Dr Pittock is making - but just to summarize for the antibody-related part of autoimmune neurology, we have one category of cell-surface antibodies and another of intracellular antibodies. Both can cause very severe and varied neurologic presentations, but the cell surface tend to be more treatable, less likely to be associated with the underlying cancer, and the intracellular less treatable, more likely to be associated with the underlying cancer - but, as with everything in neurology and medicine, exceptions on both sides. Is that a fair aerial view of some of the details we've discussed so far, Dr Pittock?    Dr Pittock: Yeah, I think so. I mean, I also think that, you know, not only, at least, for the antibody-mediated disorders (you know, as we discussed) we have drugs that will reduce the production of those antibodies, but we're also learning a lot more about the cytokine and chemokine signatures of these disorders. For example, NMO, water-channel antibody-mediated diseases are associated with elevated levels of IL-6. We know, for example, in LGI1 encephalitis and other encephalitides, that IL-6 also is elevated at the time of that encephalitic process. And so, the potential to target IL-6 with, you know, drugs that inhibit IL-6 and the IL-6 receptor, these potentially have, you know, a role to play in the management of these types of patients - whereas in the T-cell mediated disorders, you know, no advance has been made in the treatment of those conditions, I would say, in over 50 years. So, for example, the standard of treatment is steroids and then drugs that impact the bone marrow, and so we really haven't moved forward in that respect. And that, I think, is an area that really needs drive and enthusiastic out-of-the-box thinking so that we can try to get better treatments for those patients.   Dr Berkowitz: This has been a helpful overview. I look to dive into some of the scenarios that frontline practitioners will be facing thinking about these diseases. An important point you make in your article is that autoimmune and antibody-mediated neurologic syndromes can affect any level of the neuraxis. Even just our discussion so far, you've talked about anti-NMDA receptor encephalitis, you've talked about myasthenia gravis (that's at the neuromuscular junction), you've talked about paraneoplastic cerebellar degeneration - there can be an “itis” of any of our neurologic structures and that “itis” can be antibody-mediated. So, one of the key messages you give us is, one, that these are sort of in the differential diagnosis for any presenting neurologic syndrome, and, two, sort of one of the key features of the history, really, to keep in mind (since we could be anywhere along the neuraxis) is the subacute presentation when this should really sort of be top of mind in our differential diagnosis - so, many of these patients are going to be mystery cases at the outset. And one striking element you bring out in the paper is that, sometimes, the MRI, CSF, electrophysiology studies may be normal or nonspecifically abnormal, and although it's very helpful when we can send these antibody panels out, in some cases, resources are limited or institutions have certain thresholds before you can send these out (because neurologists love to send them in). Sometimes, they are not necessarily appropriate. So, love to hear your thoughts on when we should be sending these panels. What are some clues? Um we have a subacute neurologic presentation at any level of the neuraxis, and when it's not anti-NMDA receptor encephalitis, that is sort of a clear phenotype in many cases. How you would approach a patient, maybe, where the MRI is either normal or borderline abnormal (or people are squinting at the medial temporal lobe and saying, “Maybe they're a little brighter than normal”), CSF is maybe normal or nonspecifically, um, and the protein is a little high, but no cells? What clues do you use to say, you know, “These are the patients where we should be digging deep into antibody panels and making sure these are sent and not miss this diagnosis?”    Dr Pittock: Well, thank you. That's a good question. So, I think, you know, first of all, these are complex cases. So, the patient is sitting in front of you and you're trying to figure out, first of all, Is this a hardware or a software problem? Are we definitively dealing with an encephalitis or an organic neurological entity that's immune-mediated? And, you know, the way I think of it is, for me, you see a patient, it's a twenty-five-piece jigsaw puzzle and you've got two pieces, and you're trying to say, “Well, if I step back and look at those two pieces, do I have any sense of where we're going with this patient?” So, the first thing you need to do is to collect data, both the clinical story that the patient tells you (and I think you make the good point that that subacute onset is really a big clue), but subacute onset, also fluctuating course, sometimes, can be important. The history of the patient - you know, Is the patient somebody who has a known history of autoimmune disease? Because we know that patients that have thyroid autoimmunity are more likely to have diabetes, they're more likely to have gastrointestinal motility or dysmotility, they're more likely to have a variety of different immune-mediated conditions. So, is there a family history or a personal history of autoimmunity? Is the patient at high risk for malignancy? Are there clues that this potentially could be a tumor-initiated immune process affecting the nervous system? The neurological exam also is extremely important because, again, that helps you, first of all, kind of define and get some objectivity around what you're dealing with. So, does the patient have hyperreflexia? Are there signs that there is neurological involvement? And then, really, what I think we need to do is to try and frame the predominant neurological presentation. So, what is the major issue? Because a lot of these patients will have multiple complaints, multiple symptoms, and it's very important to try and identify the major presentation. And that's important, because the neural autoantibody tests are now presentation-defined - in other words, they're built around the neurological presentation, because the old approach of just doing, apparently, a plastic evaluation is gone, because we've got to a stage where we have now so many neural antibodies, you can't test every single neural antibody. So, if you're suspecting that there may be an autoimmune neurological component, then you really need to think about what would be the most appropriate comprehensive evaluation I need to do for this patient. So, for example, if a patient comes in with a subacute-onset encephalopathy, you're probably going to want the autoimmune encephalitis evaluation, and then you have to pick whether it's going to be serum or spinal fluid - and as we outlined in the paper, there are certain antibodies that are better detected in serum versus spinal fluid. So, for example, in adults over the age of 50, LGI1 is much more accurately detected in serum than spinal fluid, and the absolute opposite is true for NMDA-receptor antibody detection. One of the most important components of the neurological evaluation is the spinal fluid, but actually looking at the white cell count - and in fact, sometimes, it's quite interesting to me that I'll often see patients referred with a diagnosis of encephalitis and autoimmune encephalitis, and yet they haven't had a spinal fluid examination. So, the presence of a white cell count, you know, greater than five is hugely helpful - it's like two pieces of that twenty-five-piece jigsaw, because that really tells you that there is something inflammatory going on. And now, in terms of imaging, you're right - some patients will have normal MRI. And if you really do think that there's evidence of - you know, for example, you do an MRI, but you're getting a good sense that there's a temporal lobe seizure occurring, MRI looks normal, the EEG shows some abnormalities in the mesial temporal area - you know, considering additional imaging modalities (like PET scan of the brain), I think, is reasonable. We know that in NMDA-receptor encephalitis cases, 30% of patients will have normal MRI but they'll often have abnormalities on the PET scans. So, I think, what we do is we try to gather data and gather information that allows us to add in pieces of that jigsaw so that, eventually, after we've done this evaluation, we can see now we have ten pieces. If we step back, we say, “Yes, now we know what this condition is”, and then we essentially plan out the therapeutic approach dependent on what we've found. In terms of identification of underlying malignancy, you know, different people have different approaches. Our approach generally has been to try to get a PET-CT scan of the body as our first go-to test, because, actually, we found that CT chest abdomen and pelvis really actually delivers the same amount of radiation - and from a cost perspective, it's about the same - and we have found that PET-CTs really do provide a higher sensitivity for cancer detection.   Dr Berkowitz: Perfect. A lot of very helpful clinical pearls there. So, in closing, Dr Pittock, I've learned a lot from you today. I'm sure our listeners will as well. What does the future hold in this field? What's coming down the pipeline? What are we going to be learning from you and your colleagues that are going to help us take care of patients with these diseases going forward?    Dr Pittock: Well, thank you, Dr Berkowitz, for that question. I think the future is very bright and very exciting, and, hopefully, some of the more junior members will be enthused by this Continuum series, and, hopefully, we'll go into this area. So, let's talk about the future. The future, I think, is going to be of great interest. Firstly, there's going to be continued discovery of novel biomarkers, and the reasons for that is because of the technical and technological advances we've seen. So, for example, there have been many, many antibodies discovered by us and others that have been discovered on the basis of, for example, phage technology. In fact, the Kelch 11 biomarker discovery in collaboration with UCSF and our group was done on the basis of Joe DeRisi and Michael Wilson's phage approach. And we're actually using that now at Mayo Clinic, and we've discovered about three or four new antibodies just in the last couple of years using this technology (and that here is led by John Mills and Div Dubey). And then, we're also going to see, I think, the evolution of protoarrays much more in biomarker discovery, so, we'll have more antibodies, and again, I think, generally, those antibodies will fall into the two categories we kind of described - so, you know, in terms of the approach to those conditions, maybe not so much change. I do think, though, that the introduction and the utility of comprehensive cytokine and chemokine analysis in the future will assist us in making diagnoses of seronegative encephalitis, but also potentially will direct therapy. So, for example, cytokine A is elevated - maybe that would be a potential target for therapy that's available for these patients with rare and potentially very disabling disorders. Then, when we look at the cytotoxic T-cell mediated disorders, I think the major areas of advance are going to be in better understanding the immunophenotype of cytotoxic T-cell mediated diseases, and then the potential development of tolerization strategies using the specific targets, those specific epitope targets that are involved in paraneoplastic and nonparaneoplastic diseases, and seeing if we can vaccinate patients, but move that immune response into more of a tolerogenic immune response rather than a cytotoxic killing response. And then I think, lastly, we're going to see a dramatic revolution in CAR-T therapeutic approaches to these types of disorders moving forward - and not just, you know, CAR-T therapies that are targeting, you know, CD19 or CD20, but CAR-Ts that are actually personalized and developed so that they can target the specific B- and T-cells in an individual patient and actually do a very fine removal of that autoimmune pathologic process that I think would have significant benefit for patients not only in stopping progression, but also in significantly reducing the potential of side effects - so, a much more targeted approach. So, that's where I think the next ten years is going to be. I think it's very exciting. It's going to require the collaboration of neurologists with, you know, immunologists, hematologists, you know, across the board. So, a very exciting future, I think, for this field.    Dr Berkowitz: Exciting, indeed. And we have learned so much from you and your colleagues at the Mayo Clinic about these conditions, and I definitely encourage our listeners to read your article on this phenomenal issue that really gives us a modern, up-to-date overview of this field and what's coming down the pipeline. So, a real honor to get to speak with you, pick your brain about some of the clinical elements, pitfalls and challenges, and also hear about some of the exciting signs. Thank you so much, Dr Pittock, for joining me today on Continuum Audio.   Dr Pittock: Thank you very much.    Dr Berkowitz: Again, today, I've been interviewing Dr Sean Pittock, whose article with Dr Andrew McKeon on an introduction to autoimmune neurology and diagnostic approach appears in the most recent issue of Continuum on autoimmune neurology. Be sure to check out Continuum Audio episodes from this and other issues. And thank you so much to our listeners for joining us today.    Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use this link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at Continpub.com/audioCME. Thank you for listening to Continuum Audio.

Thursday, January 25, 2024, 12 Noon WPKN 89.5FM www.wpkn.org Host: Duo Dickinson We are in the time of Tear Downs, Again. And yet feel good, virtue signalling, of 8,000 square foot “Green” homes and $80,000 electric cars simultaneously tell us we are being good stewards of our world. The oxymoron of a new millennium's religion of “sustainability” and the never ending growth in size and cost of the American Home has always been part of our culture. It is so basic as to be be cliche: “It if ain't broke don't fix it.” But we tear down endless viable buildings, throwing away all the energy in them, toxic waste and spending the carbon to make all the parts and build the new building. This is nuts, and people have devoted their lives to offering an alternative to our throw away culture. Joe DeRisi created Urbanminers, Klass Armster has created Armster Reclaimed Lumber and John Hiden is part of Mongers Market: they are walking the talk where others cynically market “Green” as a vehicle for profitting from our hubris and guilt. JOIN US ON HOME PAGE TO SEE A FUTURE IN THE PAST.

A news story was circulating a few months ago—a woman in Australia came into the hospital with abdominal pain. She was increasingly forgetful and struggling with depression. Her doctors were stumped for over a year. What was causing her symptoms? Turns out she had a three-inch parasitic worm living in her brain. They took it out, and she recovered.How do doctors crack cases like this? How do you even know to check for a brain worm? This is the specialty of Dr. Joe DeRisi. When doctors run into a diagnostic dead end they call him. In his world, brain worms aren't even that rare. (Ask him about brain-eating amoebas.)Guest host Flora Lichtman talks with Dr. DeRisi, professor of biochemistry and biophysics at the University of California, San Francisco's School of Medicine and president of the Chan Zuckerberg BioHub San Francisco, about his fascinating work solving some of the most vexing medical mysteries, and how it may even help detect the next pandemic-inducing pathogen.  To stay updated on all-things-science, sign up for Science Friday's newsletters.Transcripts for each segment will be available the week after the show airs on sciencefriday.com.

Best-selling author Michael Lewis has a knack for extracting page-turning drama out of otherwise mundane and complicated subjects (hello, bond trading and baseball stats). Several of those books have been so good they’ve been turned into award-winning dramas starring half of Hollywood (hello, “The Big Short” and “Moneyball). And now, Lewis takes a crack at the pandemic realty still unfolding. His new book is called “The Premonition: A Pandemic Story.” In it, Lewis uses the first-hand accounts of three main characters to unravel the government’s gross mismanagement of the COVID response, which lead to nearly 600,000 deaths (among the world’s worst outcomes). On this episode of Next Question with Katie Couric, Katie and Michael Lewis talk about the CDC’s shocking downfall, the gaping holes in the public health system and the secret group of doctors (the so-called “Wolverines) helping to single handedly patch that system together. We also get to hear from one of those doctors, Dr. Joe DeRisi, a biochemistry professor at the University of California, San Francisco, and co-president of the Chan-Zuckerberg Biohub. Learn more about your ad-choices at https://www.iheartpodcastnetwork.com

On the exact 6-month anniversary of San Francisco's shelter-in-place ordnance, UCSF infectious disease experts look back at what we've learned about the strengths and weaknesses of our public health systems and look forward to the next stage of the fight against COVID-19. Panelists will discuss how the pandemic has taken advantage of inequities in our society to continue spreading despite the region's early response—and the growing understanding that stemming the tide of COVID-19 will require much greater support for low-income essential workers, incarcerated populations, and others least able to protect themselves. They will explore how partnerships between community leaders, UCSF scientists, and public health officials are pointing the way forward to a more just, equitable and effective response to the pandemic. Meet the panelists: Joe DeRisi, Ph.D., is Tomkins Professor in the Department of Biochemistry at UCSF and co-director of the Chan Zuckerberg Biohub, an independent research institute dedicated to eradicating disease. DeRisi has a long history as a “virus detective” and inventor. During the severe testing backlog at the start of the pandemic, his team built a state-of-the-art COVID-19 testing center in 8 days, which soon became the hub for processing test kits from public health departments across the state. Diane Havlir, M.D., is chief of the UCSF Division of HIV, Infectious Disease and Global Medicine. At the start of the pandemic, Havlir—who is a veteran of the fight against AIDS—joined forces with Latinx community leaders such as Jon Jacobo of the Latino Task Force for COVID-19, to document inequalities in the pandemic's impact on low-income workers and their families, and to link those infected with the support they need to go into isolation. This “test-to-care” approach has become a model for similar efforts across the country. Jon Jacobo, of the Latino Task Force for COVID-19, helped spearhead the group's partnership with UCSF, called Unidos En Salud, and has worked for policy changes to support low-income essential workers during the pandemic, in partnership with the City and County of San Francisco Department of Public Health. Jacobo is director of engagement and policy for TODCO Group, a San Francisco affordable housing and advocacy nonprofit, and an appointed commissioner overseeing the San Francisco Department of Building Inspection. Brie Williams, M.D., M.S., is a professor in the UCSF Division of Geriatrics and founding director of UCSF Amend, an initiative dedicated to transforming correctional culture to improve the health of people living and working in America's prisons. Her research has pushed for changes in how California's prisons have handled outbreaks during the pandemic, not only to protect prisoners and prison workers, but to prevent spill-over into the community at large. Moderator Kirsten Bibbins-Domingo, Ph.D., M.D., M.A.S., is vice dean for population health and health equity at the UCSF School of Medicine and director of the UCSF COVID-19 Community Public Health Initiative. She has written about how the pandemic has created “two Californias”—those with the privilege of sheltering in place, and the low-income workers who have been forced to choose between keeping food on the table and protecting their families from the virus In association with UCSF Learn more about your ad choices. Visit megaphone.fm/adchoices

Russ Altman: Today on The Future of Everything, the future of detecting DNA in your blood.Now DNA is the building block of life. It is a relatively simple long molecule or polymer made out of four components or DNA bases which have one letter abbreviations, the famous ATCG, which stand for their chemical names. It's like a string of beans, beads, beads, but it is long. A human genome is made of about three billion DNA bases, divided into 23 chromosomes. So if you add up the beads in each chromosome, you get about three billion. You get a genome from mom and you get one from dad. So you have two copies of the genome, mostly the same but obviously not identical, or six billion total.Now DNA contains the blueprints for how your cells live, how they grow, how they interact with other cells, and like a computer program, it allows the cell to perform simple computations to make decisions about when and where things happen.If this goes wrong, you can get cancer. Mutations in the DNA cause the computations and decisions to go wrong.Other things can happen too. In the last ten years, researchers have learned that they can detect DNA in the blood. Now we knew that the cells in the blood had DNA, so that was not surprising, but what was surprising is that there is sometimes DNA from other cells in the body, often cells that have died and just released their DNA into the bloodstream. This is sometimes called cell-free DNA because it is floating in the blood and it's not really part of a cell. Although this may seem like it's junk, it offers evidence of lots of other processes going on in the body, processes diverse as cancer, pregnancy, stress on organs, or even death and many others.Dr. Stephen Quake is a professor of Bioengineering, Applied Physics and Physics and Stanford University. Steve pioneered the detection of DNA in the blood and some its first applications.Steve, what drove your interest in detecting DNA, and what was the first demonstration that this would actually be useful?Stephen Quake: Well, my interest came actually when I became a father. My wife and I were in to see the doctor, and the doctor says you guys should think about getting amniocentesis. And it was seemed like a theoretical question and something we have time to think about. We said yeah, okay, that sounds like the right thing if recommending it.Russ Altman: And this is a super risky procedure in many ways. A needle goes into the uterus near the baby to extract fluids.Stephen Quake: Big needle right in the mom's belly, right next to the fetus to try to grab a few cells, and so to do genetic testing. And we said yeah, it sounds like a good idea, thinking we schedule another appointment for it. Next thing we knew, the guy was turning around with a giant needle, plunges it right into my wife's belly,Russ Altman: Whoa.Stephen Quake: Yeah, whoa, exactly. That was our response. And it's the response of many people who undergo that certain invasive testing. And not surprisingly, there's risk associated with doing that testing. Sometimes, you lose the baby and other health problems that might happen.Russ Altman: How far into the pregnancy were you?Stephen Quake: That's typically done, I don't know, around 14 weeks, something like that, 15 weeks, somewhere around there. And so that sensitized me to holy cow, there's a problem here that you're asking a diagnostic question, and there's a lot of risk associated with it. And so I began to think are there ways to ask these genetic questions and do diagnostics without adding risk? And I eventually stumbled upon this old scientific literature about this cell-free DNA that you were mentioning, which, as it turns out, was first discovered as a phenomenon in 1948.Russ Altman: That's before Watson and Crick even articulated the importance of DNA for genetics.Stephen Quake: It's before the structure, and it's before people knew. It's roughly contemporary people first realized that DNA was the molecule of inheritance.Russ Altman: Right.Stephen Quake: Oswald Avery just that same year was working that out. So it was blood chemistry to those guys who did it. But the field stayed alive, and it was mostly people doing cancer research. And eventually, it was figured out that when you're pregnant, some of the DNA in your blood comes from the fetus, and that was worked out in the late 1970s. And –Russ Altman: And so this is not a large amount, I'm guessing.Stephen Quake: It's not much, just a few percent of what's there, so it's a very challenging measurement problem and the decade-long search to try to figure out how to really use that to build a diagnostic that would allow you to understand the genetics of the baby without having to risk the baby's life. And we saw that at Stanford, and it was through the work of a really terrific graduate student in my lab when the bioengineering department was young, Christina Fan. And that has now been the first real clinical application of cell-free DNA in diagnostics, and that's how I got into it, to answer your question.Russ Altman: So in that initial demonstration or in your first industrial translation, what are the things that we can actually detect from the DNA of a fetus in the mom's blood?Stephen Quake: Well, when we published the paper on this, started getting press inquiries. When is this gonna be available in the clinic? I said, I don't know, decades, something like that.Russ Altman: That's usually the answer.Stephen Quake: It takes a long time, right. It turns out people jumped on like you wouldn't believe. Clinical trials were launched immediately. Within three years, the first real commercial diagnostic products had been launched, and now it's four million women a year, something like that, get the test, and the use of amniocentesis has plummeted.Russ Altman: And so now you do this as a screening before you make the decision about the amnio. Is that the general use of it?Stephen Quake: That was the initial indication, and it's very quickly moving to replacing amnio completely.Russ Altman: Completely, yeah. And what kind of things can we diagnose in the fetus these days?Stephen Quake: So the major genetic disorders you have for live births are things like Down syndrome; that's number one. And it's an aneuploidy is what it's called technically, means the extra copy of a chromosome. And there's a few other disorders, which are extra copies of chromosomes that are also detected with this approach.Russ Altman: Awesome. So that has had big-time market impact, and it's changing people's lives. I think it's on the street now. People know you can get this blood test instead of the amnio, so it didn't stop there. Now you had this hammer, and it worked. You hit one nail. What was the next nail you guys turned your attention to?Stephen Quake: Well, after we published that, word got around Stanford that I was interested in non-invasive diagnostics. And I got a call one day from Hannah Valantine, who's a cardiologist –Russ Altman: Great cardiologist.Stephen Quake: Yep, and she says, well Steve, we got a similar problem in heart transplants. We give people a new heart, and after the operation, we then go biopsy that new heart and rip out pieces of the tissue to make sure it's not being rejected by the body. And we're doing that every couple of months. And so is there a blood test that could replace that? Same sort of problem, patients were having this painful, risky procedure, and there was a question of whether it could be replaced by a simple blood test. And so we thought about that a bit, and –Russ Altman: The key opportunity here is that the DNA and the heart that belongs to the donor is not gonna match the DNA of the person who received the heart, and, like the baby and the mom, because those are different DNAs, you have a chance of picking it up.Stephen Quake: Yeah, the key there is that the DNA is different. A little different with the baby and the mom because we don't use differences in their DNA. But in the case of the transplant, absolutely. The whole principle is based on there being different genomes of every cell in the heart compared to other cells in the recipient's body. And we monitor those so-called polymorphisms, those changes.Russ Altman: And so you went after this, and you were indeed able to show that people who were in rejection were spilling, so to speak, the heart DNA into the blood, and maybe we can avoid some of those biopsies.Stephen Quake: Absolutely. So we did a proof of principle study with some bank samples she had, and then we wrote a grant together and were able to do a very large study on both heart and lung transplants where pretty much every transplant patient at Stanford for those two organs was enrolled in our study over a period of three years, and were able to validate it. It was amazing. One of my kids was in elementary school at the time, and there was a new family who was in the class that year. And at the end of the year, we got a note around saying that, well, there's a family that's in town because they were at the Ronald McDonald House. One of their kids was in the hospital and very ill, and would anyone wanna put them up for the last couple of months because their time had run out there. And so we invited them –Russ Altman: Took them in.Stephen Quake: to our house, yeah, and very interesting family. They were immigrants from Africa. The father had been a nurse there, had some medical training and knew that when his son was infant and very ill that needed serious help and eventually got him to Stanford where the son had had a heart transplant.Russ Altman: Whoa.Stephen Quake: And we were talking around the dinner table one night, and the dad says well, and we're just so proud to be part of this study where people are trying to figure out if they can replace the biopsies. And we enrolled our son in it and drew the blood. I said that's my study. It was amazing and felt very good about it.Russ Altman: Of course, of course.Stephen Quake: And now that's available. So there's now tens of thousands of people every year who are getting that test, and it's saving a lot of pain and suffering for those patients.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Steve Quake about detecting DNA, and at this moment, detecting DNA in transplant, hoping to detect rejection. So does the test detect rejection potentially earlier than the old-fashioned biopsy approach would?Stephen Quake: It does, and we've proved that, absolutely. You see rejection weeks, if not a month, earlier than the biopsy.Russ Altman: And then presumably, that gives the docs more option for changing the immunosuppression.Stephen Quake: Oh, absolutely because yeah, as you mention, all these patients are immunosuppressed to try to prevent rejection, and too much of that, and they'll get an infectious disease. Too little of that, you have rejection. So they can dial up the immunosuppressants a little bit and try to avoid the rejection event, and that's much better for the patients. Once they hit rejection, all sorts of bad things happen, and so the whole thing is trying to keep them properly suppressed.Russ Altman: And just to flesh it out a little bit, how frequently are they getting these blood draws? Is this every six months or every three months or –Stephen Quake: The standard of care for the invasive biopsies was every two months, and that's where they initially matched it. But this is the sort of thing that can and should be done more frequently, and I think it's gonna change the way people treat the patients over time.Russ Altman: I know that there are more applications, and I'm interested to know which ones you wanna talk about, but let's talk about one that fascinates me, which is the detection of infectious agents in the blood. Can you tell me how this technology has been used in that regard and what's the future look like?Stephen Quake: Yeah, so when we were doing the large transplant study, my post doc at the time, Ian De Vlaming, was looking at all the sequencing data very carefully and realized that not all of the sequence reads off the sequence that were mapping to the human genome. And he said maybe 98% of it's mapping; there's one or 2% that aren't. And I said that's great. It means we're not having a lot of contamination and it's all good, and he didn't let it go with that, thank goodness. And he started looking at those things that weren't mapping, and he realized it wasn't contamination, and they actually were not human, and it was part of the microbiome of these individuals. So the bacteria and the viruses and funguses that live in our body also release cell-free DNA, and we were measuring that as well. And he realized that we could use that to monitor things like what happens to your microbiome when your immune system gets turned offRuss Altman: Right, because a lot of folks —Stephen Quake: Because a lot of patients are immunosuppressed, exactly.Russ Altman: Right.Stephen Quake: And then we realized ‘cause some of them are getting infectious disease, we could also see infectious disease. And so that has evolved into a new kind of infectious disease diagnostic, which is hypothesis free. You don't have to test for a particular thing. You're essentially testing for a thousand infections all at once, and it's just now reached commercial development. We're seeing the first peer-reviewed studies showing how to use it, and it's a very exciting innovation for infectious disease.Russ Altman: People might find this surprising so let's just unpack this a little bit. We know that there are some bacteria that live in our gut, and we've always expected to see them there. Many of us have assumed that my blood should be pretty much infection free. That's not where the bacteria and the viruses live. I guess the first question is how much of a surprise, what do you see in normal people who are not immunosuppressed, and how do we interpret this? Do we know that these are diseases? Are these pathogens causing problems, or might they be part of some ecosystem of health?Stephen Quake: Yeah, all good questions. So a fun way to think about it is to do an order of magnitude calculation. Could we talk about calculations here?Russ Altman: Yes, this is something that physicists do, folks.Stephen Quake: So there's a statistic going around by the microbiome people. You've got 10 times more bacterial cells in your body than you do human cells. If you take that at face value and you say well, the human genome is 1,000 times longer. You said three billion base pairs, then the typical bacterial genome, which about three million base pairs. You do the math on that, and you say by mass, all the DNA in our body is 99% human, 1% bacterial. And so if you were to mush this all up in a blender, purify the DNA out, that's what would come out.Russ Altman: And that matches what your post doc found.Stephen Quake: Yes, exactly.Russ Altman: So are these normal signs? Are these normal organisms, or are these things that we have to run to the doctor and get treated for?Stephen Quake: The vast majority of it, the vast majority of is our normal microbiome, bugs that live with us commensally and happy, equilibrium, with us as humans.Russ Altman: I'm guessing you saw viruses or bacteria that were either entirely novel or not appreciated as living in humans?Stephen Quake: Absolutely, we have discovered traces of novel organisms that is an area of ongoing research in the group to try to understand what they are and where they fit into the tree of life.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Steve Quake, and now we're talking about infectious disease detection.As a doctor, I know that we have patients come into the emergency room or into the clinic with what we call FUO, fever of unknown origin. They look sick, they have a fever, it's not normal to have a fever, and they look infected, but we can't find an infection. And so I'm guessing that one of the key applications of this technology would be, well, what DNA are we seeing in the bloodstream, ‘cause that might point us to the infectious agent. Is that how the infectious disease community —Stephen Quake: Absolutely, yep.Russ Altman: — is taking this up?Stephen Quake: Absolutely. That's a major application. There's a bunch of others that are really interesting. And to come back to the earlier point you raised about blood infections being a different thing, the point is that the blood is like the septic system of the body, and it's exploring all the tissues and organs. And when cells are dying and they're releasing their DNA, it picks it up and carries it. So even if the infection is not in the blood, you see the remnants of the infection in the blood from that cell-free DNA.Russ Altman: Yes, and so the final area that I wanted to get into, of course, is cancer. And, in fact, you mentioned cancer in your initial comments. Where are we with the detection of cancer from cell-free DNA?Stephen Quake: Yeah, that's been an area of intense interest for decades. That's the one that was primarily driving the field before the prenatal work and because tumors have different genomes than the normal body does. And so people would monitor those differences in the blood and try to understand how the disease was progressing and to try to do detection. And that's been a little later into the clinic than the prenatal stuff, but it's happening now. And it's an area of intense interest. There's a bunch of companies out there that have launched tests or about to launch tests, and it's gonna be very important for helping monitor course of treatment, and that's the first clinical application that's out there.Russ Altman: That's what I was gonna ask. Is this about detection or about monitoring? And it sounds like the monitoring.Stephen Quake: That's the first one. It's the easiest one ‘cause you're in such a high risk group and it makes it an easier technical task.Russ Altman: And you know the cancer, so you've been able to characterize what you're expecting to find if the cancer comes back.Stephen Quake: Correct. But the big thing to go after is early detection, and that would help a lot of people and save a lot of lives. And that's something that is gonna be coming. Maybe it's five years, maybe it's sooner, but there'll be some very valuable tools for that coming down the pike; I'm pretty confident about that.Russ Altman: Yeah, so let's just think about that for a moment because one of the things that I know is an issue is when these new technologies arise, they often move up the time of detection. You could get the cancer detection earlier, you get the rejection. In general, that's a good thing. But in cancer, it's a little tricky because there is some, if I understand the literature, there's some indication that some cancers arise, and it's the body's own immune system suppresses the cancer effectively before it can grow. Have people worked out what actions you should actually take if you see a very early indication of cancer? Is it definite that we're gonna hit the patient very hard with chemotherapy and radiation and whatnot, or might we still have to figure out what to do about that?Stephen Quake: Yeah, that's a really good question and important issue, and I think we're so early on that that's being worked out in the clinical community. But the initial thought is not that you would go right to treatment with chemotherapy but that you would reflex to other testing methods that are more expensive and more sophisticated and are not the sort of thing you use to screen people broadly but if you got a hint that something's wrong, you'd use them, things like imaging techniques and such forth.Russ Altman: Makes sense. This is The Future of Everything. I'm Russ Altman. More with Dr. Stephen Quake about DNA, the future of health and biology and bioengineering, next on Sirius XM Insight 121.Welcome back to The Future of Everything. I'm Russ Altman. I'm speaking with Dr. Stephen Quake about the fabulous uses of DNA that's floating around in our cells. Now Steve, we just went through a bunch of really killer apps, but I know that there's yet another one, which is looking at pre-term birth. And that's a funny one to me because it's not immediately obvious how detecting DNA would have anything to do with a pre-term birth. So tell us that story.Stephen Quake: Yeah, so pre-term birth ends up being number one cause of neonatal mortality and complications later in life. It's a huge problem, and there's been, despite decades of effort, no real progress on creating a meaningful diagnostic that tells people who's at risk. And there's been a lot of effort put into –Russ Altman: So the goal would be very early, say this looks like a pregnancy that might have some pre-term problems.Stephen Quake: Exactly. And more generally, when is the baby gonna be due? Even if it's not early, can you predict the due date? And there's been a lot of effort put into understanding the genetics of that, the DNA base part, that has not really had a lot of predictive power or success. And so we turned to looking at RNA, which is carries the message from the genome and tells you about not the inheritance but the state of the cell and body at any given point. And it turns out same guys who discovered cell-free DNA in 1948 also discovered cell-free RNA.Russ Altman: They have a good year.Stephen Quake: They did.Russ Altman: Same year?Stephen Quake: Same paper!Russ Altman: Same paper!Stephen Quake: And so we began looking at cell-free RNA as a way to measure what's going on in the mom's body and with the baby and the placenta at any given point in time and how are things changing and can that signal to us when the baby's gonna be born and if the baby's gonna be born early. And we were able, after a long effort, it took seven or eight years of work by a very large group of people, a number of collaborators here at Stanford, including David Stevenson and Gary Shaw and Yair Blumenfeld, bunch of the MFM docs.Russ Altman: MFM is maternal fetal medicine.Stephen Quake: Fetal medicine, thank you.Russ Altman: It's okay, it's my job.Stephen Quake: But we managed to, we managed to figure it out. And we published a paper last year showing that there's a handful of transcripts which indicate when the mom is gonna give pre-term birth, about two months in advance of that.Russ Altman: Wow, so these are like canaries in the coal mine.Stephen Quake: Exactly. And we found another set of transcripts which were predict gestational age, so you can tell how old the baby is and predict when it's gonna be born. And that turns out to be a really interesting problem as well.Russ Altman: I was gonna say, I thought that good old-fashioned subtract nine months from the date of birth gets you a pretty, and in fact, I must say, I'm born on November 5th, and that's important because if you go back nine months, that gets you to February 14th, Valentine's Day. So that's a side story.Stephen Quake: Okay, I got a couple of stories there for you.Russ Altman: But tell me about this.Stephen Quake: All let me give you a couple of stories.Russ Altman: Tell me about this.Stephen Quake: So when we were having our first kid, the one with the amnio, right, I asked the doctor what's the due date, tells us the due date. I said what's the error of your measurement, your estimate? And he got very offended ‘cause he thought I was questioning his ability as a doctor.Russ Altman: Of course, of course.Stephen Quake: We had a very tense discussion. Finally, I manage to communicate I was asking about the uncertainty in the estimate ‘cause I wanted to know when to adjust the travel schedule to make sure I didn't miss it. And he couldn't tell me the uncertainty, but he told me a number that I could use to derive the uncertainty, and so I did that. Worked out to two sigma three sigma. I had three sigma baby. So the baby was premature by three and a half weeks, and it was fortunate –Russ Altman: Oh, it was at the border of the plus minus.Stephen Quake: Yeah, I was fortunately in town, and fortunately, she turned out fine. But this got me aware of the importance of not only pre-term birth but also understanding, trying to understand when the baby's gonna be born and prediction of due date.Russ Altman: Okay, so you sold me. This is actually an impactful question.Stephen Quake: Yes, exactly.Russ Altman: So what can you guys do?Stephen Quake: Well, it's early still. Our first paper was a small number of women, few dozen women, and yet it seems very promising, and we've now been able to reproduce it in a different cohort that we can predict pre-term birth and gestational age and, from gestational age, hopefully predict when the normal baby's gonna be born. But it's all now going into much larger clinical trials to validate it. It's very much the beginning of the story, but it's an exciting one.Russ Altman: So, great. This is a new molecule for our discussion, this RNA molecule, also from the baby or the placenta or both and a combination of maternal and fetal factors gives you the data you need and a big data mining approach, not to overuse that, to actually draw inferences that might be very impactful both for the actual due date but, more importantly, for uh oh, we have a woman who might be having a pre-term birth, let's do what we can, and again, the ability of doctors to intervene is probably much better if they have two-month warning.Stephen Quake: Correct, correct.Russ Altman: Well, so this has been an amazing ride, and I wanna turn our attention a little bit now to a separate thing but very excited that you're involved with. A few years ago, I think three years ago, the Chan and Zuckerberg Foundation announced the creation of a big biomedical research institute with you and a colleague from UCSF, Joe DeRisi, as co-presidents, and it had a very bold mission. The mission was to, I believe, cure or manage all disease by the end of the century, something like that; you can correct me if I'm wrong.Stephen Quake: Cure, treat, or prevent all human disease by the end of the century.Russ Altman: Bingo. So you agreed to that charge. You've now been doing it for three years. Can you tell us a little bit about how it was set up and why it was set up, and is it really even possible to imagine that level of progress in the next century?Stephen Quake: Yeah. So since we've been talking about becoming parents, and Mark and Priscilla began to turn their attention to philanthropy in a pretty large way when they became parents. And they wrote an open letter before their first daughter was born that launched the Chan Zuckerberg Initiative and ultimately the Biohub with this idea of trying to create a better world.Russ Altman: It's called the Chan Zuckerberg –Stephen Quake: Chan Zuckerberg Biohub.Russ Altman: Biohub, mm-hmm.Stephen Quake: And so in their children's lifetime, so broadly in this hundred-year span, they wanted to see if they could fund scientific research that would help make the world a healthier place for their kids and everyone else, which is a lovely mission. And it sounds crazy, right?Russ Altman: Sounds crazy.Stephen Quake: It sounds absolutely absurd, and for awhile, I couldn't say it even to them with a straight face.Russ Altman: And yet a few moments ago, you said it forcefully and convincingly, so wait to go.Stephen Quake: In, well –Russ Altman: What turned you?Stephen Quake: Well, you think about it for awhile, and it helps to think backwards in time and think about how far medicine has advanced in the last 100 years. And in this country, mortality has been cut in half. And the things that kill us now are very different than the things that killed us 100 years ago. Primarily, it was infectious disease then. Now it's things like heart disease and such forth. And so we've eliminated entire classes of diseases, effectively, and cut mortality in half. So you can project forward another 100 years and say if we don't do anything, we should get another factor of two. And with some really serious effort, maybe we can do better than that. It's just very hard for people to think on century-long timescales. We're thinking when's our next grand proposal or something like that or when's our next student gonna graduate, and it's not often that we have the opportunity to think on that sort of timescale.Russ Altman: This is The Future of Everything. I'm Russ Altman. I'm speaking with Steve Quake, now about curing, managing, treating, and what was the other verb?Stephen Quake: Prevent.Russ Altman: Preventing all disease. Do you take a portfolio approach? It sounds like you were talking about the causes of death 100 years ago, so you have to look at the causes of death now. And I guess you have to pick the low-hanging fruit to say how do we make progress. So how have you decided to deploy the assets of the Biohub for the next five to 10 years?Stephen Quake: Yeah, well, a two-fold approach. One approach is to pick a couple of areas that capture a large part of the global burden of disease, and we've chosen two that we focus on in our internal research. One is cell biology, and a lot of diseases are a consequence of disorders of cell biology, cancer, heart disease, pulmonary disease, a number of neurological diseases. And so better understanding how cells work will lead to new therapies and treatments.Russ Altman: Could be a platform of discoveries that will have multiple applications.Stephen Quake: Right, exactly, and that covers a large part of the global burden, as you work out the numbers of that. The other big part is infectious disease.Russ Altman: So it's still a problem.Stephen Quake: Still a problem worldwide, absolutely. There's a bunch of open areas, malaria, HIV. There's a bunch of other ones, TB, number of viral infections. So that's our other big internal effort. And at the Biohub, our researchers have been hired to focus on those two areas. Now the other, all the rest, what we've done is we've partnered with the Bay Area University, to Stanford, UCSF, and Berkeley, and we fund research of nearly 100 faculty at those universities across everything else. We have an open competition. We've committed roughly $100 million to those faculty over the next five years, and we'll do it again for the second five years. And we're encouraging them to work on the riskiest, most exciting ideas, whether they're basic science, technological, or more disease focused, to cover the span of where we think a lot of the great innovations are gonna come over the next decades.Russ Altman: So that does sound compelling. So basically, a two-fold strategy with some top-down projects that you know are gonna be impactful, and then you spread your bets by giving money to a bunch of smart people and say just do what you think is right. And the hope is that that will lead to the next set of challenges that you guys can perhaps adopt as top-down challenges.Stephen Quake: That's right.Russ Altman: So how is it going?Stephen Quake: Well, as you mentioned, we just celebrated our third birthday three weeks ago. Joe and I have been working really hard, but it feels great. I feel like we're at full steam, and great science is happening, and the people we're funding are doing great work, and the future is bright.Russ Altman: And I guess are the donors satisfied? Are the people who put up the funds, are they starting to see their fruits of their vision?Stephen Quake: Well, you'll have to ask them that. It's not my place to say. But they haven't fired us yet, and so we take that as a good sign.Russ Altman: Thank you for listening to The Future of Everything. I'm Russ Altman. If you missed any of this episode, listen anytime on demand with the Sirius XM app.

Genomics-based technologies have revolutionized science. From microarrays to next-generation sequencing, genomics technologies are having a tremendous positive impact on all aspects of human health. Dr. Joe DeRisi is a professor at the University of California San Francisco and co-president of the Chan Zuckerberg Biohub. DeRisi has been at the forefront of developing and using genomics-based technologies to address infectious disease challenges. DeRisi talks about how genomics helped solve the mystery of dying leopard sharks in San Francisco bay, how a “virochip” array helped identify the SARS virus, how genomics can help identify unknown causes of encephalitis, how the sewer may hold the key to predicting infectious disease outbreaks, how computational capabilities represent the current bottleneck to global benefit from genomics technologies, and how the early mysteries surrounding the AIDS epidemic led him into science. microTalk was thrilled to be joined by Julie Wolf, “Meet the Microbiologist” podcast host from ASM, when this podcast was recorded at the ASM Microbe 2019 conference in San Francisco, CA. The microCase for listeners to solve is about Tess Tamoni, a retired teacher who gets a nasty infection while on vacation at a tropical resort. Participants: Karl Klose, Ph.D. (UTSA) Joe DeRisi, Ph.D. (University of California San Francisco) Janakiram Seshu, Ph.D. (UTSA) Mylea Echazarreta (UTSA) Julie Wolf (ASM)

Mark sits down with Dr. Joe DeRisi and Dr. Stephen Quake, who lead the Chan Zuckerberg Biohub, a nonprofit research center that brings together scientists and engineers from Stanford, Berkeley, and UCSF. They talk about how technology is accelerating health research, the new advancements they’re most excited about, how to restore faith in science and what wearables will mean for the future of health.

Science Friction returns with a medical mystery story like none other. A genetic lottery. A chance encounter. A global quest. Science at the cutting edge. And one gutsy young guy.  

Very special guest Joe DeRisi joins Adam and Will this week for a stimulating conversation on his work in molecular biology. And it ends up being possibly our scariest episode yet. Happy Halloween, everyone!

Science Friction returns with a medical mystery story like none other. A genetic lottery. A chance encounter. A global quest. Science at the cutting edge. And one gutsy young guy.  

In this episode, we chat with Dr. Joe DeRisi, UCSF’s resident Sherlock Holmes of infectious diseases. You’ll hear about a surprising discovery that could have enormous implications for controlling - or even preventing - future Ebola outbreaks. One of the big mysteries surrounding Ebola has been where it hides between outbreaks. Here, Dr. DeRisi uncovers an unexpected culprit that could be harboring this deadly virus.

Among the most important global causes of disease are infectious parasites, including unicellular protozoans and multicellular helminths (worms), which are responsible for billions of illnesses and millions of deaths each year. This panel discusses a sampling of basic and translational research at UCSF on parasitic diseases. Maggie Feeney discusses studies of immune responses of children to malaria, including laboratory studies in Uganda and at UCSF. De’Broski Herbert discusses laboratory studies of human immune responses against worm infections. Joe DeRisi discusses basic research toward the development of new drugs to treat malaria. Phil Rosenthal, Professor, Department of Medicine, Division of Infectious Diseases UCSF, moderates. Series: "UC Global Health Institute" [Health and Medicine] [Professional Medical Education] [Show ID: 27755]

Among the most important global causes of disease are infectious parasites, including unicellular protozoans and multicellular helminths (worms), which are responsible for billions of illnesses and millions of deaths each year. This panel discusses a sampling of basic and translational research at UCSF on parasitic diseases. Maggie Feeney discusses studies of immune responses of children to malaria, including laboratory studies in Uganda and at UCSF. De’Broski Herbert discusses laboratory studies of human immune responses against worm infections. Joe DeRisi discusses basic research toward the development of new drugs to treat malaria. Phil Rosenthal, Professor, Department of Medicine, Division of Infectious Diseases UCSF, moderates. Series: "UC Global Health Institute" [Health and Medicine] [Professional Medical Education] [Show ID: 27755]