Podcast appearances and mentions of Feng Zhang

As US-China relations strain under rising economic rivalry, political divergence, and competing global visions, trust has become more elusive and essential. In this episode, Yale scholar Feng Zhang explores how trust between these two superpowers has frayed—not only through policy missteps and trade tensions, but also through fundamentally different understandings of global order. From Confucian relational thinking to China's Global Civilization Initiative, Zhang offers a rare, nuanced perspective on how trust might be rebuilt—even amid deep ideological divides and historical grievances. He reflects on missed diplomatic opportunities, the fading promise of cooperation post-Sunnylands, and whether China's ambitions can ever align with Western expectations of global leadership.

In this episode of the ChinaPower Podcast, Dr. Feng Zhang joins us to discuss China-North Korea relations in light of the growing Russia-North Korea relationship and deployment of North Korean troops to support Russia. Dr. Zhang discusses how the China-North Korea relationship has suffered in recent years, in part due to China joining UN sanctions against North Korea in 2016, the COVID-19 pandemic, and North Korea's involvement in Russia's war against Ukraine. Dr. Zhang explains that China has a waning influence over North Korea, evidenced most strongly through the recent further alignment between Pyongyang and Moscow. He notes that China still sees itself as a great power on the Korean Peninsula, striving for regional stability to ensure its own national security, but that China struggles to use its economic and diplomatic pressures on North Korea, fearing that it may antagonize Pyongyang against Beijing. Dr. Zhang notes that North Korea is widely viewed in China as an agent of chaos and Beijing does not want to be viewed as a member or leader in the “axis of upheaval” with North Korea, Russia, and Iran. Finally, given China's rising concerns about North Korean foreign policy and growing North Korea-Russia ties, Dr. Zhang predicts Beijing will try to play a bigger role in working with the incoming Trump Administration and other regional actors to curb North Korea's provocative behavior. Dr. Feng Zhang is a Visiting Scholar at Yale Law School's Paul Tsai China Center. He previously held positions at Tsinghua University, Murdoch University, and the Australian National University. He specializes in Chinese foreign policy, international relations in East Asia, and international relations theory. He is the author of Chinese Hegemony: Grand Strategy and International Institutions in East Asian History (Stanford, 2015). He co-authored two books with Richard Ned Lebow: Taming Sino-American Rivalry (Oxford, 2020) and Justice and International Order: East and West (Oxford, 2022). His new book on China's Policy toward Afghanistan since 1949 will be published shortly. His current project examines the causes and management of U.S.-China competition.  

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this quarterly podcast summary (QPS) episode, Peter summarizes his biggest takeaways from the last three months of guest interviews on the podcast. Peter shares key insights from his discussions on diverse topics such as dopamine and addiction with Anna Lembke, the current state and exciting future of CRISPR-mediated gene editing with Feng Zhang, how to build and maintain strong bones from youth to old age with Belinda Beck, how calorie restriction may influence longevity and metabolic health with Eric Ravussin, and the role of testosterone and TRT in prostate cancer with Ted Schaeffer. Additionally, Peter shares any personal behavioral adjustments or modifications to his patient care practices that have arisen from these engaging discussions. If you're not a subscriber and are listening on a podcast player, you'll only be able to hear a preview of the AMA. If you're a subscriber, you can now listen to this full episode on your private RSS feed or our website at the episode #325 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Overview of topics to be covered [1:45]; Anna Lembke episode: addiction, dopamine's role in pleasure and pain, and managing addictive behaviors [4:15]; Follow-up questions about addiction: heritability, cold therapy, exercise, and strategies for breaking addictive behaviors [14:45]; Feng Zhang episode: the potential of gene editing with CRISPR technology for treating diseases, and the challenges ahead [21:00]; Feng Zhang's impactful education experience, and how early exposure and curiosity-driven learning can develop scientific interest for kids [28:30]; The future of CRISPR: weighing the scientific potential to combat complex diseases against ethical considerations around genetic modification [33:45]; Belinda Beck episode: how to build and maintain strong bones from youth to old age [37:30]; How both nutrition and exercise are crucial for bone health at all ages, and why it's never too late to start [54:45]; Eric Ravussin episode: calorie restriction, energy expenditure, exercise for weight maintenance, and more [59:00]; Measuring energy intake and energy expenditure: techniques and challenges [1:09:45]; ed Schaeffer episode: the nuance role of testosterone in prostate cancer, TRT, and the need for better cancer biomarkers [1:14:30]; Peter's favorite bands [1:25:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Drive with Dr. Peter Attia: Read the notes at at podcastnotes.org. Don't forget to subscribe for free to our newsletter, the top 10 ideas of the week, every Monday --------- View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng's personal journey, the impact of mentorship, and the future potential of genetic medicine. We discuss: Feng's background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45]; The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45]; How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00]; The limitations of earlier gene-editing technologies prior to CRISPR [28:15]; How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45]; CRISPR's potential in treating genetic diseases and the challenges of effective delivery [48:00]; How CRISPR is used to treat sickle cell anemia [53:15]; Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15]; How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45]; Advantages of Cas13's ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00]; CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45]; The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45]; Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45]; Feng's early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00]; Feng's optimism about the trajectory of science [1:58:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Drive with Dr. Peter Attia Key Takeaways The human genome was sequenced 25 years ago, what's the delay in editing? We know the sequence of the genes but we don't know what most of the genes do, nor do we fully understand the coding and non-coding sequence (yet)CRISPR is an adaptive immune system: After the first infection, the bacteria has been ‘vaccinated' against the virus The next time the virus comes around, it will inject its genetic information into the bacteria but now the bacteria in the CRISPR area have a signature of the virusDifficulties in application of CRISPR: CRISPR uses a guide RNA to recognize the virus DNA but delivery of the Cas + guide RNA needs to be precise and the protein is too large to insert with ease But, solving the delivery issue doesn't mean CRISPR is suitable for all diseases; its most potent application is for genetic mutations (and likely not cancer which has many different mutations in the cell)Future goals of CRISPR technology: Creating more feasible Cas and guide RNA delivery system; inserting large genes into the genome, precisely and efficientlyEthical considerations of gene editing germline: Slippery slope argument: If we allow X and Y, we will enter an unchartered territory with designer babies, making babies smarter (which we don't know how to do), etc. It's worth noting that athletics, and intelligence, are more complicated than we want to believe; even with the right genetics, environment plays a huge role in realizing genesThinking about how the line should be drawn: Is there an obvious and important medical benefit?Read the full notes @ podcastnotes.org View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng's personal journey, the impact of mentorship, and the future potential of genetic medicine. We discuss: Feng's background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45]; The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45]; How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00]; The limitations of earlier gene-editing technologies prior to CRISPR [28:15]; How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45]; CRISPR's potential in treating genetic diseases and the challenges of effective delivery [48:00]; How CRISPR is used to treat sickle cell anemia [53:15]; Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15]; How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45]; Advantages of Cas13's ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00]; CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45]; The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45]; Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45]; Feng's early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00]; Feng's optimism about the trajectory of science [1:58:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng's personal journey, the impact of mentorship, and the future potential of genetic medicine. We discuss: Feng's background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45]; The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45]; How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00]; The limitations of earlier gene-editing technologies prior to CRISPR [28:15]; How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45]; CRISPR's potential in treating genetic diseases and the challenges of effective delivery [48:00]; How CRISPR is used to treat sickle cell anemia [53:15]; Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15]; How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45]; Advantages of Cas13's ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00]; CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45]; The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45]; Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45]; Feng's early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00]; Feng's optimism about the trajectory of science [1:58:15]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma e Biotech world.The biotech industry saw a surge in IPOs at the beginning of 2024, with industry insiders discussing the potential for continued growth. Bayer has postponed its plans to split up its divisions, causing a drop in company shares. Apogee, a biotech company, revealed promising early results for a potential long-lasting eczema drug. Nocion secured $62 million for its chronic cough drug, aiming to compete with a drug acquired by GSK. CVS and Walgreens will start selling the abortion pill in some states ahead of a Supreme Court case. The biosimilars market in the US has seen more products entering the market after a slow start. Additionally, topics such as gene therapy, FDA approvals, drug pricing, and clinical trials are covered in-depth by Biopharma Dive.Transitioning to the next news segment, Novo Nordisk's Ozempic has shown significant benefits in patients with type 2 diabetes and chronic kidney disease, leading to potential cardiometabolic expansion. Biopharma venture capital funding dropped by 20% in Q4 2023, with companies inking 204 deals totaling $6.3 billion. Other developments include Hugel challenging Botox with FDA approval for a neurotoxin injection for frown lines, Eyenovia and Formosa gaining FDA approval for an anti-inflammatory eye drop, and Vivoryon's stock plummeting after an Alzheimer's candidate failed a mid-stage trial. Pfizer has decided to focus on biologics over small molecules, and a pilot study showed better econsents lead to better human experiences. Bio 2024 is set to be the world's largest biotech event, offering opportunities for collaboration and innovation.Moving on to the next news piece, Dr. Marcus Conant, a doctor who treated some of the first patients with HIV in San Francisco in the 1980s, is now working towards finding a cure for the virus. Despite the lack of action and lessons learned from previous epidemics like AIDS, researchers are getting closer to potentially eradicating HIV. The medical and political landscapes have changed, but the fight against HIV continues. Conant's story sheds light on the progress made in the research for a cure, highlighting the urgency of finding more effective treatments as time passes. The biotech sector has seen an increase in IPOs in 2024, sparking optimism in the industry.Lastly, Abingworth has invested in the development of Trodelvy in a deal with Gilead, while Ginkgo acquired a gene editing startup founded by Feng Zhang. FogPharma received $145 million to support cancer drug research, and Nocion secured $62 million for a chronic cough drug. Cure Ventures backed a cell therapy startup targeting Parkinson's, and former Turning Point executives launched a new startup targeting cancer and autoimmune diseases. The biotech IPO market is heating up in 2024, with emerging trends being closely watched. These developments highlight the dynamic and competitive nature of the biopharma industry, with companies racing to bring innovative treatments to market.

Good morning from Pharma and Biotech daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.Abingworth has invested in Trodelvy development in a deal with Gilead, where one of the investment firm's startups will work with Gilead to expand the cancer drug's label. Cure Ventures has backed a cell therapy startup called Kenai Therapeutics targeting Parkinson's, with $82 million raised and chaired by Jeff Jonas, a former CEO of Sage Therapeutics. Former Turning Point executives have started a new startup with Blossomhill, focusing on cancer and autoimmune diseases and raising over $170 million in funding. Lindus Health, co-founded by a Moderna co-founder Robert Langer, is aiming to address challenges in contract drug research. Ginkgo has acquired Proof Diagnostics, founded by Feng Zhang, to gain gene editing tools for making genetic medicines.In other news, there is an inside look at biotech financing tools, a theory on protein chirality, settlement agreements in price-fixing cases, and upcoming webinars on omnichannel HCP engagement and tech talent recruitment in the life sciences industry. Biopharma Dive provides insights and news on biotech and pharma trends, covering topics such as clinical trials, FDA approvals, gene therapy, drug pricing, and research partnerships.

Good morning from Pharma and Biotech Daily: the podcast that gives you only what's important to hear in Pharma and Biotech world.UnitedHealth is facing an antitrust probe by the DOJ regarding potential anticompetitive effects. Despite challenges like high labor costs, UHS, a hospital operator, saw revenue growth in 2023. Veradigm is set to delist after missing a Nasdaq deadline. Nurse leaders report burnout and turnover in their roles. A ransomware attack at an urgent care provider may have exposed personal information of over 516,000 people. Healthcare Dive provides insights for healthcare leaders, including articles on AI implementation, social determinants of health, and healthcare data breaches, covering a wide range of topics such as hospitals, payers, health IT, government policies, finances, medical groups, and telehealth. Healthcare Dive is operated by Industry Dive, providing journalism and insights for decision-makers in competitive industries.Viatris pays $350 million to acquire two drugs from Idorsia for heart attacks and lupus in phase 3 testing. Ginkgo acquires gene editing tools through the buyout of Proof Diagnostics, founded by Feng Zhang. Incannex reports that psilocybin therapy reduced anxiety in a small study. Women's health company Obseva plans to wind down operations and lay off staff. Viking's obesity drug showed promising results in a phase 2 trial, potentially rivaling drugs from Eli Lilly and Novo Nordisk. The rise of obesity drug treatments is reshaping the pharma industry with significant advancements and changes, as companies make strategic moves to enhance their portfolios and address unmet medical needs.Gatorade has unveiled Gatorade Water, their first unflavored water product, with a digital-heavy marketing campaign focused on wellness. Estee Lauder's marketing mix modeling use was discussed at the eTail Palm Springs conference, showcasing their balance between brand and performance marketing. Dick's Sporting Goods has enlisted Kathryn Hahn and Will Arnett for an ad campaign highlighting e-commerce convenience. Food and beverage brands are putting a modern spin on retro packaging to appeal to consumers' emotions. Mod Op has acquired RTO+P for more creative firepower in a competitive market. Marketing Dive explores mobile messaging's influence on consumer behavior in 2024, as well as upcoming events and industry news.The recent awarding of Johnson & Johnson's Dr. Paul Janssen Award for Biomedical Research to MIT professor and Moderna co-founder Robert Langer is discussed in the text, recognizing his impactful innovations in drug delivery. Langer's work in nanoparticle drug delivery has led to advancements in biopharma, particularly in the technology behind mRNA vaccines. The text also highlights Langer's role as a scientific advisor to a new CRO aiming to improve clinical trials through technology. Additionally, it addresses the staffing challenges faced by CROs since the pandemic and explores strategies for retaining talent in the research industry, emphasizing the importance of adapting to new technologies and approaches to enhance efficiency in clinical trials and improve patient care.

David Liu is an gifted molecular biologist and chemist who has pioneered major refinements in how we are and will be doing genome editing in the future, validating the methods in multiple experimental models, and establishing multiple companies to accelerate their progress.The interview that follows here highlights why those refinements beyond the CRISPR Cas9 nuclease (used for sickle cell disease) are vital, how we can achieve better delivery of editing packages into cells, ethical dilemmas, and a future of somatic (body) cell genome editing that is in some ways is up to our imagination, because of its breadth, over the many years ahead. Recorded 29 November 2023 (knowing the FDA approval for sickle cell disease was imminent)Annotated with figures, external links to promote understanding, highlights in bold or italics, along with audio links (underlined)Eric Topol (00:11):Hello, this is Eric Topol with Ground Truths and I'm so thrilled to have David Liu with me today from the Broad Institute, Harvard, and an HHMI Investigator. David was here visiting at Scripps Research in the spring, gave an incredible talk which I'll put a link to. We're not going to try to go over all that stuff today, but what a time to be able to get to talk with you about what's happening, David. So welcome.David Liu (00:36):Thank you, and I'm honored to be here.Eric Topol (00:39):Well, the recent UK approval (November 16, 2023) of the first genome editing after all the years that you put into this, along with many other colleagues around the world, is pretty extraordinary. Maybe you can just give us a sense of that threshold that's crossed with the sickle cell and beta thalassemia also imminently [FDA approval granted for sickle-cell on 8 December 2023] likely to be getting that same approval here in the U.S.David Liu (01:05):Right? I mean, it is a huge moment for the field, for science, for medicine. And just to be clear and to give credit where credit is due, I had nothing to do with the discovery or development of CRISPR Cas9 as a therapeutic, which is what this initial gene editing CRISPR drug is. But of course, the field has built on the work of many scientists with respect to CRISPR Cas9, including Emmanuel Charpentier and Jennifer Doudna and George Church and Feng Zhang and many, many others. But it is, I think surprisingly rapid milestone in a long decade's old effort to begin to take some control over our genetic features by changing DNA sequences of our choosing into sequences that we believe will offer some therapeutic benefit. So this initial drug is the CRISPR Therapeutics /Vertex drug. Now we can say it's actually a drug approved drug, which is a Crispr Cas9 nuclease programmed to cut a DNA sequence that is involved in silencing fetal hemoglobin genes. And as you know, when you cut DNA, you primarily disrupt the sequence that you cut. And so if you disrupt the DNA sequence that is required for silencing your backup fetal hemoglobin genes, then they can reawaken and serve as a way to compensate for adult hemoglobin genes like the defective sickle cell alleles that sickle cell anemia patients have. And so that's the scientific basis of this initial drug.Eric Topol (03:12):So as you aptly put— frame this—this is an outgrowth of about a decade's work and it was using a somewhat constrained, rudimentary form of editing. And your work has taken this field considerably further with base and prime editing whereby you're not just making a double strand cut, you're doing nicks, and maybe you can help us understand this next phase where you have more ways you can intervene in the genome than was possible through the original Cas9 nucleases.David Liu (03:53):Right? So gene editing is actually a several decades old field. It just didn't quite become as popular as it is now until the discovery of CRISPR nucleases, which are just much easier to reprogram than the previous programmable zinc finger or tail nucleases, for example. So the first class of gene editing agents are all nuclease enzymes, meaning enzymes that take a piece of DNA chromosome and literally cut it breaking the DNA double helix and cutting the chromosome into two pieces. So when the cell sees that double strand DNA break, it responds by trying to get the broken ends of the chromosome back together. And we think that most of the time, maybe 90% of the time that end joining is perfect, it just regenerates the starting sequence. But if it regenerates the starting sequence perfectly and the nuclease is still around, then it can just cut the rejoin sequence again.(04:56):So this cycle of cutting and rejoining and cutting and rejoining continues over and over until the rejoining makes the mistake that changes the DNA sequence at the cut site because when those mistakes accumulate to a point that the nuclease no longer recognizes the altered sequence, then it's a dead end product. That's how you end up with these disrupted genes that result from cutting a target DNA sequence with a nuclease like Crispr Cas9. So Crispr Cas9 and other nucleases are very useful for disrupting genes, but one of their biggest downsides is in the cells that are most relevant to medicine, to human therapy like the cells that are in your body right now, you can't really control the sequence of DNA that comes out of this process when you cut a DNA double helix inside of a human cell and allow this cutting and rejoining process to take place over and over again until you get these mistakes.(06:03):Those mistakes are generally mixtures of insertions and deletions that we can't control. They are usually disruptive to a gene. So that can be very useful when you're trying to disrupt the function of a gene like the genes that are involved in silencing fetal hemoglobin. But if you want to precisely fix a mutation that causes a genetic disease and convert it, for example, back into a healthy DNA sequence, that's very hard to do in a patient using DNA cutting scissors because the scissors themselves of course don't include any information that allows you to control what sequence comes out of that repair process. You can add a DNA template to this cutting process in a process called HDR or Homology Directed Repair (figure below from the Wang and Doudna 10-year Science review), and sometimes that template will end up replacing the DNA sequence around the cut site. But unfortunately, we now know that that HDR process is very inefficient in most of the types of cells that are relevant for human therapy.(07:12):And that explains why if you look at the 50 plus nuclease gene editing clinical trials that are underway or have taken place, all but one use nucleases for gene disruption rather than for gene correction. And so that's really what inspired us to develop base editing in 2016 and then prime editing in 2019. These are methods that allow you to change a DNA sequence of your choosing into a different sequence of your choosing, where you get to specify the sequence that comes out of the editing process. And that means you can, for the first time in a general way, programmable change a DNA sequence, a mutation that causes a genetic disease, for example, into a healthy sequence back into the normal, the so-called wild type sequence, for example. So base editors work by actually performing chemistry on an individual DNA base, rearranging the atoms of that base to become a different base.(08:22):So base editors can efficiently and robustly change A's into G's G's, into A's T's into C's or C's into T's. Those four changes. And those four changes for interesting biochemical reasons turn out to be four of the most common ways that our DNA mutates to cause disease. So base editors can be used and have been used in animals and now in six clinical trials to treat a wide variety of diseases, high cholesterol and sickle cell disease, and T-cell leukemia for example. And then in prime editors we developed a few years later to try to address the types of changes in our genomes that caused genetic disease that can't be fixed with a base editor, for example. You can't use a base editor to efficiently and selectively change an A into a T. You can't use a base editor to perform an insertion of missing DNA letters like the three missing letters, CTT, that's the most common cause of cystic fibrosis accounting for maybe 70% of cystic fibrosis patients.(09:42):You can't use a base editor to insert missing DNA letters like the missing TATC. That is the most common cause of Tay-Sachs disease. So we develop prime editors as a third gene editing technology to complement nucleases and base editors. And prime editors work by yet another mechanism. They don't, again, they don't cut the DNA double helix, at least they don't cause that as the required mechanism of editing. They don't perform chemistry on an individual base. Instead, prime editors take a target DNA sequence and then write a new DNA sequence onto the end of one of the DNA strands and then sort of help the cell navigate the DNA repair processes to have that newly written DNA sequence replace the original DNA sequence. And in the process it's sort of true search and replace gene editing. So you can basically take any DNA sequence of up to now hundreds of base pairs and replace it with any other sequence of your choosing of up to hundreds of base pairs. And if you integrate prime editing with other enzymes like recombinase, you can actually perform whole gene integration of five or 10,000 base pairs, for example, this way. So prime editing's hallmark is really its versatility. And even though it's the newest of the three ways that have been robustly used to edit mammalian cells and rescue animal models of genetic disease, it is arguably the most versatile by far,Eric Topol (11:24):Right? Well, in fact, if you just go back to the sickle cell story as you laid out the Cas9 nuclease, that's now going into commercial approval in the UK and the US, it's more of a blunt instrument of disruption. It's indirect. It's not getting to the actual genomic defect, whereas you can do that now with these more refined tools, these new, and I think that's a very important step forward. And that is one part of some major contributions you've made. Of course, there are many. One of the things, of course, that's been a challenge in the field is delivery whereby we'd like to get this editing done in many parts of the body. And of course it's easy, perhaps I put that in quotes, easy when you're taking blood out and you're going to edit those cells and them put it back in. But when you want to edit the liver or the heart or the brain, it gets more challenging. Now, you did touch on one recent report, and this is of course the people with severe familial hypercholesterolemia. The carriers that have LDL cholesterol several hundred and often don't respond to even everything we have on the shelf today. And there were 10 people with this condition that was reported just a few weeks ago. So that's a big step forward.David Liu (13:09):That was also a very exciting milestone. So that clinical trial was led by scientists at Verve Therapeutics and Beam Therapeutics, and it was the first clinical readout of an in vivo base editing clinical trial. There was previously at the end of 2022, the first clinical readout of an ex vivo base editing clinical trial using CAR T cells, ex vivo  base edited to treat T-cell leukemia in pediatric patients in the UK. Ffigure from that NEJM paper below). But as you point out, there are only a small fraction of the full range of diseases that we'd like to treat with gene editing and the types of cells we'd like to edit that can be edited outside of the body and then transplanted back into the body. So-called ex vivo editing. Basically, you can do this with cells of some kind of blood lineage, hematopoietic stem cells, T-cells, and really not much else in terms of editing outside the body and then putting back into the body as you point out.(14:17):No one's going to do that with the brain or the heart anytime soon. So what was very exciting about the Verve Beam clinical trial is that Verve sought to disrupt the function of PCSK9 storied, gene validated by human genetics, because there are humans that naturally have mutations in PCSK9, and they tend to have much lower incidences of heart disease because their LDL, so-called bad cholesterol, is much lower than it would otherwise be without those mutations. So Verve set out to simply disrupt PCSK9 through gene editing. They didn't care whether they used a nuclease or a base editor. So they compared side-by-side the results of disrupting PCSK9 with Cas9 nuclease versus disrupting it by installing a precise single letter base edit using an adenine base editor. And they actually concluded that the base editor gave them higher efficacy and fewer unwanted consequences.(15:28):And so they went with the base editor. So the clinical trial that just read out were patients treated in New Zealand, in which they were given a lipid nanoparticle mRNA complex of an adenine base editor programmed with a guide RNA to install a specific A to G mutation in a splice site in PCSK9 that inactivates the gene so that it can no longer make functional PCSK9 protein. And the exciting result that read out was that in patients that receive this base editor, a single intravenous injection of the base editor lipid nanoparticle complex, as you know, lipid nanoparticles very efficiently go to the liver. In most cases, PCSK9 was edited in the liver and the result was substantial reduction in LDL cholesterol levels in these patients. And the hope and the anticipation is that that one-time treatment should be durable, should be more or less permanent in these patients. And I think while the patients who are at highest risk of coronary artery disease because of their genetics that give them absurdly high LDL cholesterol levels, that makes the most sense to go after those patients first because they are at extremely high risk of heart attacks and strokes. If the treatment proves to be efficacious and safe, then I think it's tempting to speculate that a larger and larger population of people who would benefit from having lower LDL cholesterol levels, which is probably most people, that they would also be candidates for this kind of therapy.Eric Topol (17:22):Yeah, no, it's actually pretty striking how that could be achieved. And I know in the primates that were done prior to the people in New Zealand, there was a very durable effect that went on well over I think a year or even two years. So yeah, that's right. Really promising. So now that gets us to a couple of things. One of them is the potential for off-target effects. As you've gotten more and more with these tools to be so precise, is the concern that you could have off-target effects just completely, of course inadvertent, but potential for other downstream in time known unknowns, if you will. What are your thoughts about that?David Liu (18:15):Yeah, I have many thoughts on this issue. It's very important the FDA and regulatory bodies are right to be very conservative about off-target editing because we anticipate those off targets will be permanent, those off-target edits will be permanent. And so we definitely have a responsibility to minimize adding to the mutational burden that all humans have as a function of existing on this planet, eating what we eat, being bombarded by cosmic rays and sunlight and everything else. But I think it's also important to put off-target editing into some context. One context is I think virtually every substance we've ever put into a person, including just about every medicine we've ever put into a person, has off-target effects, meaning modulates the function of biological molecules other than the intended target. Of course, the stakes are higher when those are gene editing agents because those modifications can be permanent.(19:18):I think most off-target edits are very likely to have no consequence because most of our genome, if you mutate in the kinds of small ways like making an individual base pair change for a base editor are likely to have no consequence. We sort of already know this because we can measure the mutational burden that we all face as a function of living and it's measurable, it's low, but measurable. I've read some papers that estimate that of the roughly 27 trillion [should be ~37] cells in an adult person, that there are billions and possibly hundreds of billions of mutations that accumulate every day in those 27 [37] trillion cells. So our genomes are not quite the static vaults that we'd like to think that they are. And of course, we have already purposefully given life extending medicines to patients that work primarily by randomly mutating their genomes. These are chemotherapeutic agents that we give to cancer patients.(20:24):So I think that history of giving chemotherapeutic agents, even though we know those agents will mess up the genomes of these patients and potentially cause cancer far later down the road, demonstrates that there are risk benefit situations where the calculus favors treatment, even if you know you are causing mutations in the genome, if the condition that the patient faces and their prognosis is sufficiently grave. All that said, as I mentioned, we don't want to add to the mutational burden of these patients in any clinically relevant way. So I think it is appropriate that the early gene editing clinical candidates that are in trials or approved now are undergoing lots and lots of scrutiny. Of course, doing an off-target analysis in an animal is of limited value because the animal's genome is quite different than the human genome. So the off targets won't align, but doing off-target analysis in human cells and then following up these patients for a long time to confirm hopefully that there isn't clinical evidence of quality of life or lifespan deterioration caused by off-target editing, that's all very, very important.(21:55):I also think that people may not fully appreciate that on target editing consequences also need to be examined and arguably examined with even more urgency than off-target edits. Because when you are cutting a chromosome at a target site with a nucleus, for example, you generate a complex mixture of different products of different DNA sequences that come out, and the more sequences you sequence, the more different products you realize are generated. And I don't think it's become routine to try to force the companies, the clinical groups that are running these trials to characterize the top 1000 on target products for their biological consequence. That would be sort of impractical to do and would probably slow down greatly the benefit of these early nuclease clinical trials for patients. But those are actually the products that are generated with much higher frequency typically than the off-target edits. And that's part of why I think it makes more sense from a clinical safety perspective to use more precise gene editing methods like base editing and prime editing where we know the products that are generated are mostly the products that we want are not uncontrolled mixtures of different deletion and insertion products.(23:27):So I think paying special attention to the on-target products, which are generated typically 70 to 100% of the time as opposed to the off targets which may be generated at a 0.1 to 1% level and usually not that many at that level once it reaches a clinical candidate. I think that's all important to do.Eric Topol (23:51):You've made a lot of great points there and thanks for putting that in perspective. Well, let's go on to the delivery issue. You mentioned nanoparticles, viral vectors, and then you've come up with small virus-like neutered viruses if you will. I think a company Nvelop that you've created to push on that potential. What are your thoughts about where we stand since you've become a force for coming up with much better editing, how about much better and more diverse delivery throughout the body? What are your thoughts about that?David Liu (24:37):Yeah, great. Great question. I think one of the legacies of gene editing is and will be that it inspired many more scientists to work hard on macromolecular delivery technologies. All of these gene editing agents are macromolecules, meaning they're proteins and or nucleic acids. None of them are small molecules that you can just pop a pill and swallow. So they all require special technologies to transfer the gene editing agent from outside of the cell into the cell. And the fact that taking control of our genetic features has become such a popular aspiration of medicine means that there's a lot of scientists as measured, most importantly by the young scientists, by the graduate students and the postdocs and the young professors of which I'm no longer one sadly, who have decided that they're going to devote a big part of their program to delivery. So you summarized many of the clinically relevant, clinically validated delivery technologies already, somewhat sadly, because if there were a hundred of these technologies, you probably wouldn't need to ask this question. But we have lipid nanoparticles that are particularly good at delivering messenger RNA, that was used to deliver the covid vaccine into billions of people. Now also used to deliver, for example, the adenine base editor mRNA into the livers of those hypercholesterolemia patients in the Verve/Beam clinical trial.(26:20):So those lipid nanoparticles are very well matched for gene editing delivery as long as it's liver. And they also are particularly well matched because their effect is transient. They cause a burst of gene editing agents to be produced in the liver and then they go away. The gene editing agents can't persist, they can't integrate into the genome despite what some conspiracy theorists might worry about. Not that you've had any encounter with any of those people. I'm sure that's actually what you want for a gene editing agent. You ideally want a delivery method that exposes the cell only for the shortest amount of time needed to make the on-target edit at the desired level. And then you want the gene editing agent to disappear and never come back because it shouldn't need to. DNA edits to our genome for durable cells should be permanent. So that's one method.(27:25):And then there are a variety of other methods that researchers have used to deliver to other cells, but they each carry some trade-offs. So if you're trying to edit hematopoietic stem cells, you can take them out of the body. Once they're out of the body, you have many more methods you can use to deliver efficiently into them. You can electroporated messenger, RNA or even ribonuclear proteins. You can treat with lipids or viruses, you can edit and then put them back into the body. But as you already mentioned, that's sort of a unique feature of blood cells that isn't applicable to the heart or the brain, for example, or the eyes. So then that brings us to viral vectors. There are a variety of clinically validated viral methods for delivery. AAV— adeno associated virus— is probably the most diverse, most relevant, and one of the best tolerated viral delivery methods. The beauty of AAV is that it can deliver to a variety of tissues. AAV can deliver into spinal cord neurons, for example, into retinal cells, into the heart, into the liver, into a few other tissues as well.(28:48):And that diversity of being able to choose AAV capsids that are known to get into the types of tissues that you're trying to target is a great strength of that approach. One of the downsides of AAV for gene editing agents is that their delivery tends to be fairly durable. You can engineer AAVs into next generation capsids that sort of get rid of themselves or the gene editing agents get rid of themselves. But classic AAV tends to stay around in patients for a long time, at least months, for example, and possibly years. And we also don't yet have a good way, clinically validated way of re-dosing AAV. And once you administer high doses of AAV in a patient that tends to provoke high-titer, neutralizing antibodies against those AAVs making it difficult to then come back six months or a year later and dose again with an AAV.(29:57):So researchers are on the bright side, have become very good at engineering and evolving in the laboratory next generation AAVs that can go to greater diversity issues that can be more potent. Potency is important because if you can back off the dose, maybe you can get around some of these immunogenicity issues. And I think we will see a renaissance with AAV that will further broaden its clinical scope. Even though I appreciate that the decisions by a couple large pharma companies to sort of pull out of using AAV for gene therapy seemed to cause people to, I think prematurely conclude that AAV has fallen out of favor. I think for gene therapy, it's quite different than gene editing. Gene therapy, meaning you are delivering a healthy copy of the gene, and you need to keep that healthy copy of the gene in the patient for the rest of the patient's life.(30:59):That's quite different than gene editing where you just need the edit to take place over days to weeks, and then you want the editing agent to actually go away and you never want to come back. I think AAV will used to deliver gene editing agents will avoid some of the clinical challenges like how do we redose? Because you shouldn't need to redose if the gene editing clinical trial proceeds as you hope. And then you mentioned these virus-like particles. So we became interested in virus-like particles as other labs have because they offer some of the best strengths of non-viral and viral approaches like non-viral approaches such as LMPs. They deliver the transient form of a gene editing agent. In fact, they can deliver the fully assembled protein RNA complex of a base editor or a prime editor or a CRISPR nuclease. So in its final form, and that means the exposure of the cell to the editing agent is minimized.(32:15):You can treat with these virus-like particles, deliver the protein form of these gene editing agents, allow the on-target site to get edited. And then since the half-life of these proteins tends to be very small, roughly 24 hours for example, by a week later, there should be very little of the material left in the animal or prospectively in the patient virus-like particles, as you call them, neutered viruses, they lack viral DNA or RNA. They don't have the ability to integrate a virus's genome into the human genome, which can cause some undesired consequences. They don't randomly introduce DNA into our genomes, therefore, and they disappear more transiently than viruses like AAV or adenoviruses or other kinds of lentiviruses that have been used in the clinic. So these virus-like particles or VLP offer really some of the best strengths on paper at least of both viral and non-viral delivery.(33:30):Their limitation thus far has been that there really haven't been examples of potent in vivo delivery of cargoes like gene editing agents using virus-like particles. And so we recently set out to figure out why, and we identified several bottlenecks, molecular bottlenecks that seemed to be standing in the way of virus-like particles, doing a much more efficient job at delivering inside of an animal. (Figure from that paper below.) And we engineered solutions to each of these first three molecular bottlenecks, and we've identified a couple more since. And that resulted in what we call VLPs engineered virus-like particles. And as you pointed out, Keith Joung and myself, co-founded a company called Nvelop to try to bring these technologies and other kinds of molecular delivery technologies, next generation delivery technologies to patients.Eric Topol (34:28):Well, that gets me to the near wrapping up, and that is the almost imagination you could use about where all this can go in the future. Recently, I spoke to a mutual friend Fyodor Urnov, who talked about wouldn't it be amazing if for people with chronic pain you could just genome edit neurons their spinal cord? As you already touched on recently, Jennifer Doudna, who we both know talked about editing to prevent Alzheimer's disease. Well, that may be a little far off in time, but at least people are talking about these things that is not, we're not talking about germline editing, we're just talking about somatic cell and being able to approach conditions that have previously been either unapproachable or of limited success and potential of curing. So this field continues to evolve and you and all your colleagues are a big part of how this has evolved as quickly as it has. What are your thoughts about, are there any bounds to the potential in the longer term for genome editing? Right.David Liu (35:42):It's a great question because all of the early uses of gene editing in people are appropriately focused on people who are at dire risk of having shorter lives or very poor quality of life as it should be for a new kind of therapeutic because the risks are high until we continue to validate the clinical benefit of these gene editing treatments. And therefore we want to choose patients the highest that face the poorest prognosis where the risk benefit ratio favors treatment as strongly as possible. But your question, I think very accurately highlights that our genome and changes to it determine far more than whether you have a serious genetic disorder like Sickle Cell Disease or Progeria or Cystic Fibrosis or Familial Hypercholesterolemia or Tay-Sachs disease. And being able to not just correct mutations that are associated with devastating genetic disorders, but perhaps take control of our genomes in more sophisticated way that you pointed out two examples that I think are very thought provoking to treat chronic pain permanently to lower the risk of horrible diseases that affect so many families devastating to economies worldwide as well, like Alzheimer's disease, Parkinson's disease, the genetic risk factors that are the strongest genetic determinants of diseases like Alzheimer's disease are actually, there are several that are known already.(37:36):And an interesting possibility for the future, it isn't going to happen in the next few years, but it might happen within the next 10 or 20 years, might be to use gene editing to precisely change some of those most grievous alleles that are risk factors for Alzheimer's disease like a apoE4, to change them to the genetic forms that have normal or even reduced risk for Alzheimer's disease. That's a very tough clinical trial to run, but I'd say not any tougher than the dozens of most predominantly failed Alzheimer's clinical trials that have probably collectively accounted for hundreds of billions of dollars of investmentEric Topol (38:28):Easily.David Liu (38:31):And all of that speaks to the fact that Alzheimer's disease, for example, is enormous burden on society by every measure. So it's worth investing and major resources and taking major risks to try to create perhaps preventative treatments that just lower our risk globally. Getting there will require that these pioneering early clinical trials for gene editing are smashing successes. I'm optimistic that they will be, there will be bumps in the road because there always are bumps in the road. There will be patients who have downturns in their health and everyone will wonder whether those patients had a downturn because of a gene editing treatment they received. And ascertaining whether that's the case will be very important. But as these trials continue to progress, and as they continue hopefully on this quite positive trajectory to date, it's tempting to imagine a future where we can use precise gene editing methods. For example, you can install a variety using prime editing, a variety of alleles that naturally occur in people that reduce the risk of Alzheimer's disease or Parkinson's disease like the mutation that 0.1% of Icelandic people and almost nobody else has in amyloid precursor protein changing alanine 673 to threonine (A673T).(40:09):It is very thought provoking, and I don't think society is ready now to take that step, but I think if things continue to proceed on this promising trajectory, it's inevitable because arguably, the defining trait of our species is that we use every ounce of our talents and our gifts and our resources and our creativity to try to improve our lives and those of our children. And I don't think if we have ways of treating genetic diseases or even of reducing grievous genetic disease risk, that we will be able to sit on our hands and not take steps towards that kind of future solon as those technologies continue to be validated in the clinic as being safe and efficacious. It's, I teach a gene editing class and I walk them through a slippery slope at the end of five ethics cases, starting with progeria, where most people would say having a single C of T mutation in one gene that you, by definition didn't inherit from mom or dad.(41:17):It just happened spontaneously. That gives you an average lifespan of 14 and a half years and strongly affects other aspects of the quality of your life and your family's life that if you can change as we did in animals that T back into a C and correct the disease and rescue many of the phenotypes and extend lifespan, that that's an ethical use of gene editing. Treating genetic deafness is the second case. It's a little bit more complicated because many people in the deaf community don't view deafness as a disability. It's at least a more subjective situation than progeria. But then there are other cases like changing apoE4 to apoE3 or even apoE2 with the lower than normal risk of Alzheimer's disease, or installing that Icelandic mutation and amyloid precursor protein that substantially lowers risk of Alzheimer's disease. And then finally, you can, I always provoke a healthy debate in the class at the end by pointing out that in the 1960s, one of the long distance cross country alpine skiing records was set by a man who had a naturally occurring mutation in his EPO receptor, his erythropoietin receptor, so that his body always thought he was on EPO as if he were dosing on EPO, although that was of course before the era of EPO dosing was really possible, but it was just a naturally occurring mutation in this case, in his family.(42:48):And when I first started teaching this class, most students could accept using gene editing to treat progeria, but very few were willing to go even past that, even to genetic deafness, certainly not to changing a ApoE risk factors for Alzheimer's. Nowadays, I'd say the 50% vote point is somewhere between case three and case four, most people are actually say, yeah, especially since they have family members who've been through Alzheimer's disease. If they are a apoE4, some of them are a apoE4/apoE4 [homozygotes], why not change that to a apoE3 or even an ApoE2 or as one student challenged the class this year, if you were born with a apoE2, would you want to change it to a ApoE3 so you could be more normal? Most people would say, no, there's no way I would do that.(43:49):And for the first time this year, there were one or two students who actually even defended the idea of putting in a mutation in erythropoietin receptor to increased increase their endurance under low oxygen conditions. Of course, it's also presumably useful if you ever, God forbid, are treated with a cancer chemotherapeutic. Normally you get erythropoietin to try to restore some, treat some of the anemia that can result, and this student was making a case, well, why wouldn't we? If this is a naturally occurring mutation that's been shown to benefit certain people doing certain things. I don't think that's a general societal view. And I am a little bit skeptical we'll ever get widespread acceptance of case number five. But I think all of it is healthy stimulates a healthy discussion around the surprisingly gentle continuum between disease treatment, disease prevention, and what some would call human improvement.And it used to be that even the word human improvement was sort of an anathema. I think now at least the students in my class are starting to rethink what does that really mean? We improving ourselves a number of ways genetically and otherwise by virtue of our lifestyles, by virtue of who we choose to procreate with. So it's a really interesting debate, and I think the rapid development and now clinical progression and now approval, regulatory approval of gene editing drugs will play a central role in this discussion.Eric Topol (45:38):No question. I mean, also just to touch on the switch from a apoE4 to apoE2, you would get a potential 2-fer of lesser risk for Alzheimer's and a longer lifespan. So I mean, there's a lot of things here. The thing that got me years ago, I mean, this is many years ago at a meeting with George Church and he says, we're going to just edit 60 genes and then we can do all sorts of xeno-pig transplants and forget the problem of donors. And it's happening now.David Liu (46:11):Yeah, I mean, he used a base editor to edit hundreds of genes at once, if not thousands ofEric Topol (46:16):That's why it's just, yeah, no, it's just extraordinary. And I think people need to be aware that opportunities here, as you say, with potential bumps along the way, unquestionably, is almost limitless. So this has been a masterclass thanks to you, David, in where we are, where we're headed in genome editing at a very extraordinary time where we've really seeing things click. And I just want to also add that you're going to be here with a conference in La Jolla in January, I think, on base and prime editing. Is that right? So for those who are listeners who are into this topic, maybe they can also hear the latest, I'm sure there'll be more between now and next. Well, several weeks from now at your, it's aDavid Liu (47:12):Conference on, it's the fifth international conference on base and prime editing and associated enzymes, the somewhat baroque name. And I will at least be giving a virtual talk there. It actually overlaps with the talk I'm giving at Rockefeller that time. Ah, okay, cool. But I'm speaking at the conference either in person or virtually.Eric Topol (47:34):Yeah. Well, anytime we get to hear from you and the field, of course it's enlightening. So thanks so much for joining. Thank youDavid Liu (47:42):For having me. And thank you also for all of your, I think, really important public service in connecting appropriately the ground truths about science and vaccines and other things to people. I think that's very much appreciated by scientists like myself.Eric Topol (48:00):Oh, thanks David.Thanks for listening, reading, and subscribing to Ground Truths. To be clear, this is a hybrid format, roughly alternating between analytical newsletters/essays and podcasts with exceptional people, attempting to achieve about 2 posts per week. It's all related to cutting-edge advances in life science, medicine, and information tech (A.I.)All content is free. If you wish to become a paid subscriber know that all proceeds go to Scripps Research. Get full access to Ground Truths at erictopol.substack.com/subscribe

Gene editing technology gives us the ability to change our DNA – removing, adding and replacing parts of our genetic code. These technologies have been emerging and improving for some decades, but since the development of CRISPR-based editing technologies, our capacity to edit our DNA has become both more accessible, more accurate and consequently, more powerful. Gene editing could be used to prevent genetic diseases but also alter traits like height and intelligence, presenting both legal and ethical issues.A lecture by Imogen Goold recorded on 17 April 2023 at Barnard's Inn Hall, London.The transcript and downloadable versions of the lecture are available from the Gresham College website: https://www.gresham.ac.uk/watch-now/gene-editing-lawGresham College has offered free public lectures for over 400 years, thanks to the generosity of our supporters. There are currently over 2,500 lectures free to access. We believe that everyone should have the opportunity to learn from some of the greatest minds. To support Gresham's mission, please consider making a donation: https://gresham.ac.uk/support/Website:  https://gresham.ac.ukTwitter:  https://twitter.com/greshamcollegeFacebook: https://facebook.com/greshamcollegeInstagram: https://instagram.com/greshamcollegeSupport the show

(NOTA: aunque este episodio se publica ahora, se grabó el 16 de octubre de 2021). Programa especial, con ocasión de la concesión del premio Nobel 2021 en Fisiología o Medicina. En la Tertulia, Pepe, Francis e Iker celebran una nueva edición de estos célebres premios y comentan el galardón recién concedido a David Julius y Ardem Patapoutian "por su descubrimiento de los receptores para temperatura y tacto". La profesora Teresa Giráldez (Universidad de la Laguna), experta en el estudio de los canales iónicos, tuvo la amabilidad de participar en la sección de Bionoticias para unirse a la celebración y compartir su valoración de este premio. Además de otras noticias de interés, presentadas por Iker en Bionoticias, el episodio incluye el comentario de Francis sobre dos artículos de los grupos de Feng Zhang (https://www.science.org/doi/10.1126/science.abj6856) y Virginijus Siksnys (https://www.nature.com/articles/s41586-021-04058-1) en los que demuestran que algunas transposasas tienen actividad ADN nucleasa guiada por ARN y que, por tanto, pueden ser utilizadas como herramientas de edición genética, similar a las más conocidas CRISPR-Cas, con algunas ventajas adicionales. Esperamos que os guste.

Dr.Feng Zhang, the award-winning biochemist best known for his central role in developing optogenetics and CRISPR technology, joins ARK analyst Ali Urman on this week's episode. Listeners will learn about the role of optogenetics in dissecting circuitries in the brain and Feng's experience of CRISPR. Feng shares some of the biggest hurdles optogenetics has to overcome and tells us where RNA editing could be even more effective than DNA editing. He gives us his predictions on the cost of this kind of technology and medicine, and how it is developing to cover even more genes. We touch on the repertoire of different enzymes, explore diagnostics, and talk about the role of prime editing. You will hear why Feng considers the present to be a golden age for biological research, come to understand his long-term vision for CRISPR's impact on the world, and much more! “There's an ever-expanding repertoire of enzymes that could be harnessed and developed for genome editing. I think, what we're seeing now is probably still the tip of the iceberg.” — @zhangf Key Points From This Episode: Feng's definition of optogenetics: a way to be able to dissect circuitries in the brain. What CRISPR is and what Feng's experience of it has been. One of the biggest hurdles of optogenetics: targeting different circuitries in the brain. How RNA could be even better than DNA editing. The expanding toolbox of different proteins that are allowing us to cover more genes. How the repertoire of different enzymes could be harnessed and developed for genome editing. Feng's thoughts on how quickly the cost will decline. CRISPR's relationship with diagnostics in terms of specificity and sensitivity. How prime editing could be used to change the number of variants. How using RNA for base editing could change the capabilities. One of the biggest roadblocks to genetic medicine: getting it into the right tissue. The challenge posed by regulatory framework. How the new methodologies being developed can improve off-target sensitivity. Why Feng considers the present to be a golden age for biological research. How Feng sees CRISPR affecting the world in the long term. Why he is excited about the future of programmable medicine.

Since the holiday season, we have brought to you a special mini-series looking at how the things that keep us connected – like trade, tech, the internet, and migration – can also tear us apart. But rather than despairing at the state of the world, the geopolitics, and ongoing superpower battles, Mark Leonard is joined by a number of high-level thinkers in this mini-series in order to find strategies for shaping and surviving our new reality. We call it The Age of Unpeace: Therapy for internationalists. Join us on this journey to a more therapeutic approach to international relations. The mini-series brings you five special episodes with guests including today's guests: Anu Bradford, Thomas Wright, and Feng Zhang. We hope you find some healing! For past episodes in this series, check them out here: buff.ly/3ecRbiO _____________ On today's couch, we gathered Anu Bradford, Henry L. Moses Professor of Law and International Organizations at Columbia Law School; Thomas Wright, Senior Fellow and Director of the Center on the US and Europe at Brookings; and Feng Zhang, professor of international relations and executive dean of the Institute of Public Policy at the South China University of Technology. Together with Mark Leonard, they discuss the three empires of connectivity – the US as a gate-keeping power, the EU as rule-making power, and China as a relational power. The big question in this group therapy session is: How can those three powers have a peaceful and constructive relationship with each other? Further reading: • “Brussel effect” by Anu Bradford • “ Aftershocks: Pandemic Politics and the End of the Old International Order”by Thomas Wright • “The rise of Chinese exceptionalism in international relations” by Feng Zhang

In this week's episode of the Spine & Nerve podcast Dr. Nicolas Karvelas and Dr. Brian Joves discuss Post Herpetic Neuralgia (PHN), the most common complication of Herpes Zoster (also known as Shingles, which is caused by reactivation of the Varicella Zoster Virus). PHN is defined by pain that is typically burning or electrical, and may be associated with allodynia or hyperesthesia in a dermatomal distribution. Pain from PHN is typically sustained for at least 90 days after the rash. PHN is caused by nerve injury due to the inflammatory response induced by viral replication within the nerve. Epidemiologic studies have found that PHN occurs in about 20% of patients who have Herpes Zoster. With the relatively recent development of the preventative vaccine Shingrix (which has been found to be 97% effective in preventing Herpes Zoster) it is anticipated that the total prevalence of Herpes Zoster and PHN will decrease. However, research has repeatedly demonstrated that immunocompromised patients are at a significantly increased risk for Herpes Zoster and PHN (20-100 times increased risk of development of PHN). As of today, the Advisory Committee on Immunization Practices has not cleared immunocompromised patients to receive the Shingrex (or Zostavax) vaccine; therefore for multiple reasons PHN will most likely continue to be a prevalent diagnosis. Treatment options for PHN include physical modalities (TENS, desensitization), topical medications (including Lidocaine 5% patch, and Capsaicin), oral medications (including Gabapentin, Pregabalin, Tricyclic Antidepressants), and procedures. Listen as the doctors review Herpes Zoster, PHN, and a recent research article evaluating the effect of the Erector Spinae Plane Block in regards to prevention of PHN once Herpes Zoster has already developed. This podcast is for information and educational purposes only, it is not meant to be medical or career advice. If anything discussed may pertain to you, please seek counsel with your healthcare provider. The views expressed are those of the individuals expressing them, they may not represent the views of Spine & Nerve. References: 1. Zeng-Mao Lin, MD, Hai-Feng Wang, MD, Feng Zhang, MD, Jia-Hui Ma, MD, PhD, Ni Yan, RN, and Xiu-Fen Liu, MD. The Effect of Erector Spinae Plane Blockade on Prevention of Postherpetic Neuralgia in Elderly Patients: A Randomized Double-blind Placebo-controlled Trial. 2021;24;E1109-E1118. 2. Dooling KL, Guo A, Patel M, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR Morb Mortal Wkly Rep 2018;67:103–108.

This week Harry is joined by Kevin Davies, author of the 2020 book Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing. CRISPR—an acronym for Clustered Regularly Interspaced Short Palindromic Repeats—consists of DNA sequences that evolved to help bacteria recognize and defend against viral invaders, as a kind of primitive immune system. Thanks to its ability to precisely detect and cut other DNA sequences, CRISPR has spread to labs across the world in the nine years since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking 2012 Science paper describing how the process works. The Nobel Prize committee recognized the two scientists for the achievement in 2020, one day after Davies' book came out. The book explains how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused. Today's interview covers all of that ground and more.Davies is a PhD geneticist who has spent most of his career in life sciences publishing. After his postdoc with Harvey Lodish at the Whitehead Institute, Davies worked as an assistant editor at Nature, the founding editor of Nature Genetics (Nature's first spinoff journal), editor-in-chief at Cell Press, founding editor-in-chief of the Boston-based publication Bio-IT World, and publisher of Chemical & Engineering News. In 2018 he helped to launch The CRISPR Journal, where he is the executive editor. Davies' previous books include Breakthrough (1995) about the race to understand the BRCA1 breast cancer gene, Cracking the Genome (2001) about the Human Genome Project, The $1,000 Genome (2010) about next-generation sequencing companies, and DNA (2017), an updated version of James Watson's 2004 book, co-authored with Watson and Andrew Berry.Please rate and review MoneyBall Medicine on Apple Podcasts! Here's how to do that from an iPhone, iPad, or iPod touch:1. Open the Podcasts app on your iPhone, iPad, or Mac. 2. Navigate to the page of the MoneyBall Medicine podcast. You can find it by searching for it or selecting it from your library. Just note that you'll have to go to the series page which shows all the episodes, not just the page for a single episode.3.Scroll down to find the subhead titled "Ratings & Reviews."4.Under one of the highlighted reviews, select "Write a Review."5.Next, select a star rating at the top — you have the option of choosing between one and five stars. 6.Using the text box at the top, write a title for your review. Then, in the lower text box, write your review. Your review can be up to 300 words long.7.Once you've finished, select "Send" or "Save" in the top-right corner. 8.If you've never left a podcast review before, enter a nickname. Your nickname will be displayed next to any reviews you leave from here on out. 9.After selecting a nickname, tap OK. Your review may not be immediately visible.Full TranscriptHarry Glorikian: I'm Harry Glorikian, and this is MoneyBall Medicine, the interview podcast where we meet researchers, entrepreneurs, and physicians who are using the power of data to improve patient health and make healthcare delivery more efficient. You can think of each episode as a new chapter in the never-ending audio version of my 2017 book, “MoneyBall Medicine: Thriving in the New Data-Driven Healthcare Market.” If you like the show, please do us a favor and leave a rating and review at Apple Podcasts.Harry Glorikian: We talk a lot on the show about how computation and data are changing the way we develop new medicines and the way we deliver healthcare. Some executives in the drug discovery business speak of the computing and software side of the business as the “dry lab” —to set it apart from the “wet labs” where scientists get their hands dirty working with actual cells, tissues, and reagents.But the thing is, recent progress on the wet lab side of biotech has been just as amazing as progress in areas like machine learning. And this week, my friend Kevin Davies is here to talk about the most powerful tool to come along in the last decade, namely, precise gene editing using CRISPR.Of course, CRISPR-based gene editing has been all over the news since Jennifer Doudna and Emmanuel Charpentier published a groundbreaking Science paper in 2012 describing how the process works in the lab. That work earned them a Nobel Prize in medicine just eight years later, in 2020.But what's not as well-known is the story of how CRISPR was discovered, how it was turned into an easily programmable tool for cutting and pasting stretches of DNA, how most of the early pioneers in the field have now formed competing biotech companies, and how the technology is being used to help patients today—and in at least one famous case, misused.Kevin put that whole fascinating story together in his 2020 book Editing Humanity. And as the executive editor of The CRISPR Journal, the former editor-in-chief of Bio-IT World, the founding editor at Nature Genetics, and the author of several other important books about genomics, Kevin is one of the best-placed people in the world to tell that story. Here's our conversation.Harry Glorikian: Kevin, welcome to the show. Kevin Davies: Great to see you again, Harry. Thanks for having me on.Harry Glorikian: Yeah, no, I mean, I seem to be saying this a lot lately, it's been such a long time since, because of this whole pandemic, nobody's really seeing anybody on a regular basis. I want to give everybody a chance to hear about, you had written this book called Editing Humanity, which is, you know, beautifully placed behind you for, for product placement here. But I want to hear, can you give everybody sort of an overview of the book and why you feel that this fairly technical laboratory tool called CRISPR is so important that you needed to write a book about it?Kevin Davies: Thank you. Yes. As you may know, from some of my previous “bestsellers” or not, I've written about big stories in genetics because that's the only thing I'm remotely qualified to write about. I trained as a human geneticist in London and came over to do actually a pair of post-docs in the Boston area before realizing my talents, whatever they might be, certainly weren't as a bench researcher. So I had to find another way to stay in science but get away from the bench and hang up the lab coats.So moving into science publishing and getting a job with Nature and then launching Nature Genetics was the route for me. And over the last 30 years, I've written four or five books that have all been about, a) something big happening in genomics, b) something really big that will have both medical and societal significance, like the mapping and discovery of the BRCA1 breast cancer gene in the mid-90s, the Human Genome Project at the turn of the century, and then the birth and the dawn of consumer genetics and personalized medicine with The $1,000 Genome. And the third ingredient I really look for if I'm trying to reach a moderately, significantly large audience is for the human elements. Who are they, the heroes and the anti heroes to propel the story? Where is the human drama? Because, you know, we all love a good juicy, gossipy piece of story and rating the good guys and the bad guys. And CRISPR, when it first really took off in 2012, 2013 as a gene editing tool a lot of scientists knew about this. I mean, these papers are being published in Science in particular, not exactly a specialized journal, but I was off doing other things and really missed the initial excitement, I'm embarrassed to say. It was only a couple of years later, working on a sequel to Jim Watson's DNA, where I was tasked with trying to find and summarize the big advances in genomic technology over the previous decade or whatever, that I thought, well, this CRISPR thing seems to be taking off and the Doudnas and the Charpentiers are, you know, winning Breakthrough Prizes and being feted by celebrities. And it's going on 60 Minutes. They're going to make a film with the Rock, Dwayne Johnson. What the heck is going on. And it took very little time after that, for me to think, you know, this is such an exciting, game-changing disruptive technology that I've got to do two things. I've gotta, a) write a book and b) launch a journal, and that's what I did. And started planning at any rate in sort of 2016 and 17. We launched the CRISPR Journal at the beginning of 2018. And the book Editing Humanity came out towards the end of 2020. So 2020, literally one day before the Nobel Prize—how about that for timing?—for Doudna and Charpentier for chemistry last year. Harry Glorikian: When I think about it, I remember working with different companies that had different types of gene editing technology you know, working with some particularly in the sort of agriculture space, cause it a little bit easier to run faster than in the human space. And you could see what was happening, but CRISPR now is still very new. But from the news and different advances that are happening, especially here in the Boston area, you know, it's having some real world impacts. If you had to point to the best or the most exciting example of CRISPR technology helping an actual patient, would you say, and I've heard you say it, Victoria Gray, I think, would be the person that comes to mind. I've even, I think in one of your last interviews, you said something about her being, you know, her name will go down in history. Can you explain the technology that is helping her and what some of the similar uses of CRISPR might be?Kevin Davies: So the first half of Editing Humanity is about the heroes of CRISPR, how we, how scientists turned it from this bizarre under-appreciated bacterial antiviral defense system and leveraged it and got to grips with it, and then figured out ways to turn it into a programmable gene editing technology. And within a year or two of that happening that the classic Doudna-Charpentier paper came out in the summer of 2012. Of course the first wave of biotech companies were launched by some of the big names, indeed most of the big names in CRISPR gene editing hierarchies. So Emmanuel Charpentier, Nobel Laureate, launched CRISPR Therapeutics, Jennifer Doudna co-founded Editas Medicine with several other luminaries. That didn't go well for, for reasons of intellectual property. So she withdrew from Editas and became a co-founder of Intellia Therapeutics as well as her own company, Caribou, which just went public, and Feng Zhang and others launched Editas Medicine. So we had this sort of three-way race, if you will, by three CRISPR empowered gene editing companies who all went public within the next two or three years and all set their sights on various different genetic Mendelian disorders with a view to trying to produce clinical success for this very powerful gene editing tool. And so, yes, Victoria Gray is the first patient, the first American patient with sickle cell anemia in a trial that is being run by CRISPR Therapeutics in close association with Vertex Pharmaceuticals. And that breakthrough paper, as I think many of your listeners will know, came out right at the end of 2020 published in the New England Journal of Medicine. Doesn't get much more prestigious than that. And in the first handful of patients that CRISPR Therapeutics have edited with a view to raising the levels of fetal hemoglobin, fetal globin, to compensate for the defective beta globin that these patients have inherited, the results were truly spectacular.And if we fast forward now to about two years after the initial administration, the initial procedures for Victoria Gray and some of her other volunteer patients, the results still look as spectacular. Earlier this year CRISPR Therapeutics put out of sort of an update where they are saying that the first 20 or 24 patients that they have dosed with sickle cell and beta thallasemia are all doing well. There've been little or no adverse events. And the idea of this being a once and done therapy appears very well founded. Now it's not a trivial therapy. This is ex-vivo gene editing as obviously rounds of chemotherapy to provide the room for the gene edited stem cells to be reimplanted into the patient. So this is not an easily scalable or affordable or ideal system, but when did we, when will we ever able to say we've pretty much got a cure for sickle cell disease? This is an absolutely spectacular moment, not just for CRISPR, but for medicine, I think, overall. And Victoria Gray, who's been brilliantly profiled in a long running series on National Public Radio, led by the science broadcaster Rob Stein, she is, you know, we, we can call her Queen Victoria, we can call it many things, but I really hope that ,it's not just my idea, that she will be one of those names like Louise Brown and other heroes of modern medicine, that we look and celebrate for decades to come.So the sickle cell results have been great, and then much more recently, also in the New England Journal, we have work led by Intellia Therapeutics, one of the other three companies that I named, where they've been also using CRISPR gene editing, but they've been looking at a rare liver disease, a form of amyloidosis where a toxic protein builds up and looking to find ways to knock out the production of that abnormal gene.And so they've been doing in vivo gene editing, really using CRISPR for the first time. It's been attempted using other gene editing platforms like zinc fingers, but this is the first time that I think we can really say and the New England Journal results prove it. In the first six patients that have been reported remarkable reductions in the level of this toxic protein far, not far better, but certainly better than any approved drugs that are currently on the market. So again, this is a very, very exciting proof of principle for in vivo gene editing, which is important, not just for patients with this rare liver disorder, but it really gives I think the whole field and the whole industry enormous confidence that CRISPR is safe and can be used for a growing list of Mendelian disorders, it's 6,000 or 7,000 diseases about which we know the root genetic cause, and we're not going to tackle all of them anytime soon, but there's a list of ones that now are within reach. And more and more companies are being launched all the time to try and get at some of these diseases.So as we stand here in the summer of 2021, it's a really exciting time. The future looks very bright, but there's so much more to be done. Harry Glorikian: No, we're just at the beginning. I mean, I remember when I first saw this, my first question was off target effects, right? How are we going to manage that? How are they going to get it to that place that they need to get it to, to have it to that cell at that time, in the right way to get it to do what it needs to do. And you know, all these sorts of technical questions, but at the same time, I remember I'm going to, trying to explain this to my friends. I'm like, “You don't understand, this can change everything.” And now a high school student, I say this to people and they look at me strangely, a high school student can order it and it shows up at your house.Kevin Davies: Yeah, well, this is why I think, and this is why one reason why CRISPR has become such an exciting story and receives the Nobel Prize eight years after the sort of launch publication or the first demonstration of it as a gene editing tool. It is so relatively easy to get to work. It's truly become a democratized or democratizing technology. You don't need a million-dollar Illumina sequencer or anything. And so labs literally all around the world can do basic CRISPR experiments. Not everyone is going to be able to launch a clinical trial. But the technology is so universally used, and that means that advances in our understanding of the mechanisms, new tools for the CRISPR toolbox new pathways, new targets, new oftware, new programs, they're all coming from all corners of the globe to help not just medicine, but many other applications of CRISPR as well.Harry Glorikian: Yeah. I always joke about like, there, there are things going on in high school biology classes now that weren't, available, when I was in college and even when we were in industry and now what used to take an entire room, you can do on a corner of a lab bench.Kevin Davies: Yeah. Yeah. As far as the industry goes we mentioned three companies. But you know, today there's probably a dozen or more CRISPR based or gene editing based biotech companies. More undoubtedly are going to be launched before the end of this year. I'm sure we'll spend a bit of time talking about CRISPR 2.0, it seems too soon to be even thinking about a new and improved version of CRISPR, but I think there's a lot of excitement around also two other Boston-based companies, Beam Therapeutics in Cambridge and Verve Therapeutics both of which are launching or commercializing base editing. So base editing is a tool developed from the lab of David Lu of the Broad Institute [of MIT and Harvard]. And the early signs, again, this technology is only five or six years old, but the early signs of this are incredibly promising. David's team, academic team, had a paper in Nature earlier this year, really reporting successful base editing treatment of sickle cell disease in an animal model, not by raising the fetal globin levels, which was sort of a more indirect method that is working very well in the clinic, but by going right at the point mutation that results in sickle cell disease and using given the chemical repertoire of base editing.Base editing is able to make specific single base changes. It can't do the full repertoire of single base changes. So there are some limitations on researchers' flexibility. So they were unable to flip the sickle cell variant back to the quote unquote wild type variants, but the change they were able to make is one that they can live with, we can live with because it's a known benign variant, a very rare variant that has been observed in other, in rare people around the world. So that's completely fine. It's the next best thing. And so that looks very promising. Beam Therapeutics, which is the company that David founded or co-founded is trying a related approach, also going right at the sickle cell mutation. And there are other companies, including one that Matthew Porteus has recently founded and has gone public called Graphite Bio.So this is an exciting time for a disease sickle cell disease that has been woefully neglected, I think you would agree, both in terms of basic research, funding, medical prioritization, and medical education. Now we have many, many shots on goal and it doesn't really, it's not a matter of one's going to win and the others are going to fall by the wayside. Just like we have many COVID vaccines. We'll hopefully have many strategies for tackling sickle cell disease, but they are going to be expensive. And I think you know the economics better than I do. But I think that is the worry, that by analogy with gene therapies that have been recently approved, it's all, it's really exciting that we can now see the first quote, unquote cures in the clinic. That's amazingly exciting. But if the price tag is going to be $1 million or $2 million when these things are finally approved, if and when, that's going to be a rather deflating moment. But given the extraordinary research resources that the CRISPRs and Intellias and Beams and Graphites are pouring into this research, obviously they've got to get some return back on their investment so that they can plow it back into the company to develop the next wave of of gene editing therapies. So you know, it's a predicament Harry Glorikian: One of these days maybe I have to have a show based on the financial parts of it. Because there's a number of different ways to look at it. But just for the benefit of the listeners, right, who may not be experts, how would you explain CRISPR is different from say traditional gene therapies. And is CRISPR going to replace older methods of, of gene therapy or, or will they both have their place? Kevin Davies: No, I think they'll both have their place. CRISPR and, and these newer gene editing tools, base editing and another one called prime editing, which has a company behind it now called Prime Medicine, are able to affect specific DNA changes in the human genome.So if you can target CRISPR, which is an enzyme that cuts DNA together with a little program, the GPS signal is provided in the form of a short RNA molecule that tells the enzyme where to go, where to go in the genome. And then you have a couple of strategies. You can either cut the DNA at the appropriate target site, because you want to inactivate that gene, or you just want to scramble the sequence because you want to completely squash the expression of that gene. Or particularly using the newer forms of gene editing, like base editing, you can make a specific, a more nuanced, specific precision edit without, with one big potential advantage in the safety profile, which is, you're not completely cutting the DNA, you're just making a nick and then coaxing the cell's natural repair systems to make the change that you sort of you're able to prime.So there are many diseases where this is the way you want to go, but that does not in any way invalidate the great progress that we're making in traditional gene therapy. So for example today earlier today I was recording an interview or for one of my own programs with Laurence Reid, the CEO of Decibel Therapeutics, which is looking at therapies for hearing loss both genetic and other, other types of hearing disorders.And I pushed him on this. Aren't you actually joinomg with the gene editing wave? And he was very circumspect and said, no, we're very pleased, very happy with the results that we're getting using old fashioned gene replacement therapy. These are recessive loss of function disorders. And all we need to do is get the expression of some of the gene back. So you don't necessarily need the fancy gene editing tools. If you can just use a an AAV vector and put the healthy gene back into the key cells in the inner ear. So they're complimentary approaches which is great.Harry Glorikian: So, you know, in, in this podcast, I try to have a central theme when I'm talking to people. The relationships of big data, computation, advances in new drugs, and other ways to keep people healthy. So, you know, like question-wise, there's no question in my mind that the whole genomics revolution that started in the ‘90s, and I was happy to be at Applied Biosystems when we were doing that, would have been impossible in the absence of the advances in computing speed and storage in the last three decades. I think computing was the thing that held up the whole human genome, which gave us the book of life that CRISPR is now allowing us to really edit. But I wonder if you could bring us sort of up-to-date and talk about the way CRISPR and computation are intertwined. What happens when you combine precision of an editing tool like CRISPR with the power of machine learning and AI tools to find meaning and patterns in that huge genetic ball? Kevin Davies: Yeah. Well, yeah. I'm got to tread carefully here, but I think we are seeing papers from some really brilliant labs that are using some of the tools that you mentioned. AI and machine learning with a view to better understanding and characterizing some of the properties and selection criteria of some of these gene editing tools. So you mentioned earlier Harry, the need to look out for safety and minimize the concern of off-target effects. So I think by using some of these some algorithms and AI tools, researchers have made enormous strides in being able to design the programmable parts of the gene editing constructs in such a way that you increase the chances that they're going to go to the site that you want them to go to, and nnot get hung up latching onto a very similar sequence that's just randomly cropped up on the dark side of the genome, across the nucleus over there. You don't want that to happen. And I don't know that anybody would claim that they have a failsafe way to guarantee that that could never happen. But the you know, the clinical results that we've seen and all the preclinical results are showing in more and more diseases that we've got the tools and learned enough now to almost completely minimize these safety concerns. But I think everyone, I think while they're excited and they're moving as fast as they can, they're also doing this responsibly. I mean, they, they have to because no field, gene therapy or gene editing really wants to revisit the Jesse Gelsinger tragedy in 1999, when a teenage volunteer died in volunteering for a gene therapy trial at Penn of, with somebody with a rare liver disease. And of course that, that setback set back the, entire field of gene therapy for a decade. And it's really remarkable that you know, many of the sort of pioneers in the field refuse to throw in the towel, they realized that they had to kind of go back to the drawing board, look at the vectors again, and throw it out. Not completely but most, a lot of the work with adenoviruses has now gone by the wayside. AAV is the new virus that we hear about. It's got a much better safety profile. It's got a smaller cargo hold, so that's one drawback, but there are ways around that. And the, the explosion of gene therapy trials that we're seeing now largely on the back of AAV and now increasingly with, with non-viral delivery systems as well is, is very, very gratifying. And it's really delivery. I think that is now the pain point. Digressing from your question a little bit, but delivery, I think is now the big challenge. It's one thing to contemplate a gene therapy for the eye for rare hereditary form of blindness or the ear. Indeed those are very attractive sites and targets for some of these early trials because of the quantities that you need to produce. And the localization, the, the physical localization, those are good things. Those help you hit the target that you want to. But if you're contemplating trying something for Duchenne muscular dystrophy or spinal muscular atrophy, or some of the diseases of the brain, then you're going to need much higher quantities particularly for muscular disorders where, you run into now other challenges, including, production and manufacturing, challenges, and potentially safeguarding and making sure that there isn't an immune response as well. That's another, another issue that is always percolating in the background.But given where we were a few years ago and the clinical progress that we've talked about earlier on in the show it, I think you can safely assume that we've collectively made enormous progress in, in negating most, if not all of these potential safety issues.Harry Glorikian: No, you know, it's funny, I know that people will say like, you know, there was a problem in this and that. And I look at like, we're going into uncharted territories and it has to be expected that you just…you've got people that knew what they were doing. All of these people are new at what they are doing. And so you have to expect that along the way everything's not going to go perfectly. But I don't look at it as a negative. I look at it as, they're the new graduating class that's going to go on and understand what they did right. Or wrong, and then be able to modify it and make an improvement. And, you know, that's what we do in science. Kevin Davies: Well, and forget gene editing—in any area of drug development and, and pharmaceutical delivery, things don't always go according to plan. I'm sure many guests on Moneyball Medicine who have had to deal with clinical trial failures and withdrawing drugs that they had all kinds of high hopes for because we didn't understand the biology or there was some other reaction within, we didn't understand the dosing. You can't just extrapolate from an animal model to humans and on and on and on. And so gene editing, I don't think, necessarily, should be held to any higher standard. I think the CRISPR field has already in terms of the sort of market performance, some of the companies that we've mentioned, oh my God, it's been a real roller coaster surprisingly, because every time there's been a paper published in a prominent journal that says, oh my God, there's, there's a deletion pattern that we're seeing that we didn't anticipate, or we're seeing some immune responses or we're seeing unusual off target effects, or we're seeing P53 activation and you know, those are at least four off the top of my head. I'm sure there've been others. And all had big transient impact on the financial health of these companies. But I think that was to be expected. And the companies knew that this was just an overreaction. They've worked and demonstrated through peer review publications and preclinical and other reports that these challenges have been identified, when known about, pretty much completely have been overcome or are in the process of being overcome.So, you know, and we're still seeing in just traditional gene therapy technologies that have been around for 15, 20 years. We're still seeing reports of adverse events on some of those trials. So for gene editing to have come as far as it's common, to be able to look at these two big New England Journal success stories in sickle cell and ATTR amyloidosis, I don't think any very few, except the most ardent evangelists would have predicted we'd be where we are just a few years ago. [musical transition]Harry Glorikian: I want to pause the conversation for a minute to make a quick request. If you're a fan of MoneyBall Medicine, you know that we've published dozens of interviews with leading scientists and entrepreneurs exploring the boundaries of data-driven healthcare and research. And you can listen to all of those episodes for free at Apple Podcasts, or at my website glorikian.com, or wherever you get your podcasts.There's one small thing you can do in return, and that's to leave a rating and a review of the show on Apple Podcasts. It's one of the best ways to help other listeners find and follow the show.If you've never posted a review or a rating, it's easy. All you have to do is open the Apple Podcasts app on your smartphone, search for MoneyBall Medicine, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments. It'll only take a minute, but it'll help us out immensely. Thank you! And now back to the show.[musical transition]Harry Glorikian:One of your previous books was called The $1,000 Genome. And when you published that back in 2010, it was still pretty much science fiction that it might be possible to sequence someone's entire genome for $1,000. But companies like Illumina blew past that barrier pretty quickly, and now people are talking about sequencing individual genome for just a few hundred dollars or less. My question is, how did computing contribute to the exponential trends here. And do you wish you'd called your book The $100 Genome?Kevin Davies: I've thought about putting out a sequel to the book, scratching out the 0's and hoping nobody would notice. Computing was yes, of course, a massive [deal] for the very first human genome. Remember the struggle to put that first assembly together. It's not just about the wet lab and pulling the DNA sequences off the machines, but then you know, the rapid growth of the data exposure and the ability to store and share and send across to collaborators and put the assemblies together has been critical, absolutely critical to the development of genomics.I remember people were expressing shock at the $1,000 genome. I called the book that because I heard Craig Venter use that phrase in public for the first time in 2002. And I had just recently published Cracking the Genome. And we were all still recoiling at the billions of dollars it took to put that first reference genome sequence together. And then here's Craig Venter, chairing a scientific conference in Boston saying what we need is the $1,000 genome. And I almost fell off my chair. “what are you? What are you must you're in, you're on Fantasy Island. This is, there's no way we're going to get, we're still doing automated Sanger sequencing. God bless Fred Sanger. But how on earth are you going to take that technology and go from billions of dollars to a couple of thousand dollars. This is insanity.” And that session we had in 2002 in Boston. He had a local, a little episode of America's Got Talent and he invited half a dozen scientists to come up and show what they had. And George Church was one of them. I think Applied Biosystems may have given some sort of talk during that session. And then a guy, a young British guy from a company we'd never heard of called Celexa showed up and showed a couple of pretty PowerPoint slides with colored beads, representing the budding DNA sequence on some sort of chip. I don't know that he showed any data. It was all very pretty and all very fanciful. Well guess what? They had the last laugh. Illumina bought that company in 2006. And as you said, Harry you know, I think when, when they first professed to have cracked the $1,000 dollar genome barrier, a few people felt they needed a pinch of salt to go along with that. But I think now, yeah, we're, we're, we're well past that. And there are definitely outfits like BGI, the Beijing Genomics Institute being one of them, that are touting new technologies that can get us down to a couple of hundred. And those were such fun times because for a while there Illumina had enormous competition from companies like 454 and Helicose and PacBio. And those were fun heady times with lots and lots of competition. And in a way, Illumina's had it a little easy, I think over the last few years, but with PacBio and Oxford Nanopore gaining maturity both, both in terms of the technology platforms and their business strategy and growth, I think Illumina' gonna start to feel a little bit more competition in the long read sequence space. And one is always hearing whispers of new companies that may potentially disrupt next-gen sequencing. And that would be exciting because then we'd have an excuse to write another book. Harry Glorikian: Well, Kevin, start writing because I actually think we're there. I think there are a number of things there and you're right, I think Illumina has not had to bring the price down as quickly because there hasn't been competition. And you know, when I think about the space is, if you could do a $60 genome, right, it starts to become a rounding error. Like what other business models and opportunities now come alive? And those are the things that excite me. All right. But so, but you have a unique position as editor of the journal of CRISPR and the former editor of a lot of prominent, you know, publications, Nature Genetics, Bio-IT World, Chemical & Engineering News. Do you think that there's adequate coverage of the biological versus the computing side of it? Because I, I have this feeling that the computing side still gets a little overlooked and underappreciated. Kevin Davies: I think you're right. I mean I think at my own company Genetic Engineering News, we still have such deep roots in the wet lab vision and version of biotechnology that it takes a conscious effort to look and say, you know, that's not where all the innovation is happening. Bio-IT World, which you mentioned is interesting because we launched that in 2002. It was launched by the publisher IDG, best-known from MacWorld and ComputerWorld and this, this whole family of high-tech publications.And we launched in 2002 was a very thick glossy print magazine. And ironically, you know, we just couldn't find the advertising to sustain that effort, at least in the way that we'd envisioned it. And in 2006 and 2007, your friend and mine Phillips Kuhl, the proprietor of Cambridge Healthtech Institute, kind of put us out of our misery and said, you know what I'll, take the franchise because IDG just didn't know what to do with it anymore. But what he really wanted was the trade show, the production. And even though at the magazine eventually we fell on our sword and eventually put it out of its misery, the trade show went from strength to strength and it'll be back in Boston very soon because he had the vision to realize there is a big need here as sort of supercomputing for life sciences.And it's not just about the raw high-performance computing, but it's about the software, the software tools and data sharing and management. And it's great to go back to that show and see the, you know, the Googles and Amazons and yeah, all the big household names. They're all looking at this because genome technology, as we've discussed earlier has been one of the big growth boom areas for, for their services and their products.Harry Glorikian: Right. I mean, well, if you look at companies like Tempus, right. When I talked to Joel Dudley over there on the show it's, they want to be the Amazon AWS piping for all things genomic analysis. Right. So instead of creating it on your own and building a, just use their platform, basically, so it's definitely a growth area. And at some point, if you have certain disease states, I don't see how you don't get you know, genomic sequencing done, how a physician even today in oncology, how anybody can truly prescribe with all the drugs that are being approved that have, you know, genomic biomarkers associated with them and not use that data.Kevin Davies: On a much lower, lo-fi scale, as I've been doing a lot of reading about sickle cell disease lately, it's clear that a lot of patients who are, of course, as you, as you know, as your listeners know, are mostly African-American because the disease arose in Africa and the carrier status gives carriers a huge health advantage in warding off malaria. So the gene continues to stay, stay high in in frequency. Many African-American patients would benefit from some generic drugs that are available in this country that provide some relief, but aren't aware of it and maybe their physicians aren't completely aware of it either. Which is very sad. And we've neglected the funding of this disease over many decades, whereas a disease like cystic fibrosis, which affects primarily white people of Northern European descent that receives far more funding per capita, per head, than than a disease like sickle cell does. But hopefully that will begin to change as we see the, the potential of some of these more advanced therapies.I think as far as your previous comment. I think one of the big challenges now is how we tackle common diseases. I think we're making so much progress in treating rare Mendelian diseases and we know thousands of them. But it's mental illness and asthma and diabetes you know, diseases that affect millions of people, which have a much more complicated genetic and in part environmental basis.And what can we learn, to your point about having a full genome sequence, what can we glean from that that will help the medical establishment diagnose and treat much more common diseases, not quite as simple as just treating a rare Mendelian version of those diseases? So that's, I think going to be an important frontier over the next decade.Harry Glorikian: Yeah. It's complicated. I think you're going to see as we get more real-world data that's organized and managed well, along with genomic data, I think you'll be able to make more sense of it. But some of these diseases are quite complicated. It's not going to be find one gene, and it's going to give you that answer.But I want to go back to, you can't really talk about CRISPR without talking about this specter of germline editing. And a big part of your book is about this firestorm of criticism and condemnation around, you know, the 2018 when the Chinese researcher He Jankui, I think I said it correctly.Yep.Kevin Davies: He Jankui is how I say it. Close. Harry Glorikian: He announced that he had created twin baby girls with edits to their genomes that were intended to make them immune to HIV, which sort of like—that already made me go, what? But the experiment was, it seems, unauthorized. It seems that, from what I remember, the edits were sloppy and the case spurred a huge global discussion about the ethics of using CRISPR to make edits that would be inherited by future generations. Now, where are we in that debate now? I mean, I know the National Academy of Sciences published a list of criteria, which said, don't do that. Kevin Davies: It was a little more nuanced than that. It wasn't don't do that. It was, there is a very small window through which we could move through if a whole raft of criteria are met. So they, they refuse to say hereditary genome editing should be banned or there should be a moratorium. But they said it should not proceed until we do many things. One was to make sure it is safe. We can't run before we can walk. And by that, I mean, we've got to first demonstrate—because shockingly, this hasn't been done yet—that genome editing can be done safely in human embryos. And in the last 18 months there've been at least three groups, arguably the three leading groups in terms of looking at genetic changes in early human embryos, Kathy Niakan in London, Shoukhrat Mitalipov in Oregon, and Dieter Egli in New York, who all at roughly the same time published and reports that said, or posted preprints at least that said, when we attempt to do CRISPR editing experiments in very early human embryos, we're seeing a mess. We're seeing a slew of off-target and even on-target undesirable edits.And I think that says to me, we don't completely understand the molecular biology of DNA repair in the early human embryo. It may be that there are other factors that are used in embryogenesis that are not used after we're born. That's speculation on my part. I may be wrong. But the point is we still have a lot to do to understand, even if we wanted to.And even if everybody said, “Here's a good case where we should pursue germline editing,” we've gotta be convinced that we can do it safely. And at the moment, I don't think anybody can say that. So that's a huge red flag.But let's assume, because I believe in the power of research, let's assume that we're going to figure out ways to do this safely, or maybe we say CRISPR isn't the right tool for human embryos, but other tools such as those that we've touched on earlier in the show base editing or prime editing, or maybe CRISPR 3.0 or whatever that is right now to be published somewhere. [Let's say ] those are more safe, more precise tools. Then we've got to figure out well, under what circumstances would we even want to go down this road? And the pushback was quite rightly that, well, we already have technologies that can safeguard against families having children with genetic diseases. It's called IVF and pre-implantation genetic diagnosis. So we can select from a pool of IVF embryos. The embryos that we can see by biopsy are safe and can therefore be transplanted back into the mother, taken to term and you know, a healthy baby will emerge.So why talk about gene editing when we have that proven technology? And I think that's a very strong case, but there are a small number of circumstances in which pre-implantation genetic diagnosis will simply not work. And those are those rare instances where a couple who want to have a biological child, but have both of them have a serious recessive genetic disease. Sickle cell would be an obvious case in point. So two sickle cell patients who by definition carry two copies of the sickle cell gene, once I have a healthy biological child preimplantation genetic diagnosis, it's not going to help them because there are no healthy embryos from whatever pool that they produce that they can select. So gene editing would be their only hope in that circumstance. Now the National Academy's report that you cited, Harry, did say for serious diseases, such as sickle cell and maybe a few others they could down the road potentially see and condone the use of germline gene editing in those rare cases.But they're going to be very rare, I think. It's not impossible that in an authorized approved setting that we will see the return of genome editing, but that's okay. Of course you can can issue no end of blue ribbon reports from all the world's experts, and that's not going to necessarily prevent some entrepreneur whose ethical values don't align with yours or mine to say, “You know what, there's big money to be made here. I'm going offshore and I'm going to launch a CRISPR clinic and you know, who's going to stop me because I'll be out of the clutches of the authorities.” And I think a lot of people are potentially worried that that scenario might happen. Although if anyone did try to do that, the scientific establishment would come down on them like a ton of bricks. And there'll be a lot of pressure brought to bear, I think, to make sure that they didn't cause any harm.Harry Glorikian: Yeah. It's funny. I would like to not call them entrepreneurs. I like entrepreneurs. I'd like to call them a rogue scientist. Kevin Davies: So as you say, there's the third section of four in Editing Humanity was all about the He Jankui debacle or saga. I had flown to Hong Kong. It's a funny story. I had a little bit of money left in my travel budget and there were two conferences, one in Hong Kong and one in China coming up in the last quarter of 2018. So I thought, well, okay, I'll go to one of them. And I just narrowed, almost a flip of a coin, I think. Okay, let's go to the Hong Kong meeting.It's a bioethics conference since I don't expect it to be wildly exciting, but there are some big speakers and this is an important field for the CRISPR Journal to monitor. So I flew there literally, you know, trying to get some sleep on the long flights from New York and then on landing, turn on the phone, wait for the new wireless signal provider to kick in. And then Twitter just explode on my feed as this very, very astute journalists at MIT Technology Review, Antonio Regalado, had really got the scoop of the century by identifying a registration on a Chinese clinical trial website that he and only he had the foresight and intelligence to sort of see. He had met He Jankui in an off the record meeting, as I described in the book, about a month earlier. A spider sense was tingling. He knew something was up and this was the final clue. He didn't know at that time that the Lulu and Nana, the CRISPR babies that you mentioned, had actually been born, but he knew that there was a pregnancy, at least one pregnancy, from some of the records that he'd seen attached to this registration document. So it was a brilliant piece of sleuthing. And what he didn't know is that the Asociated Press chief medical writer Marilynm Marchion had confidentially been alerted to the potential upcoming birth of these twins by an American PR professional who was working with He Jankui in Shenzhen. So she had been working on an embargoed big feature story that He Jankui and his associates hoped would be the definitive story that would tell the world, we did this quote unquote, “responsibly and accurately, and this is the story that you can believe.” So that story was posted within hours.And of course the famous YouTube videos that He Jankui had recorded announcing with some paternal pride that he had ushered into the world these two gene edited, children, screaming and crying into the world as beautiful babies I think was [the phrase]. And he thought that he was going to become famous and celebrated and lauded by not just the Chinese scientific community, but by the world community for having the ability and the bravery to go ahead and do this work after Chinese researchers spent the previous few years editing human embryos. And he was persuaded that he had to present his work in Hong Kong, because he'd set off such a such an extraordinary firestorm. And I think you've all seen now you're the clips of the videos of him nervously walking onto stage the muffled, the silence, or the only sound in the front row, the only sound in the big auditorium at Hong Kong university—[which] was absolutely packed to the rim, one side of the auditorium was packed with press photographers, hundreds of journalists and cameras clicking—and the shutters clattering was the only, that was the applause that he got as he walked on stage.And to his credit, he tried to answer the questions directly in the face of great skepticism from the audience. The first question, which was posed by David Liu, who had traveled all the way there, who just asked him simply, “What was the unmet medical need that you are trying to solve with this reckless experiment? There are medical steps that you can do, even if the couple that you're trying to help has HIV and you're trying to prevent this from being passed on. There are techniques that you can use sperm washing being one of them. That is a key element of the IVF process to ensure that the no HIV is transmitted.”But he was unable to answer the question in terms of I'm trying to help a family. He'd already moved out and was thinking far, far bigger. Right? And his naiveté was shown in the manuscript that he'd written up and by that point submitted to Nature, excerpts of which were leaked out sometime later.So he went back to Shenzhen and he was put under house arrest after he gave that talk in Hong Kong. And about a year later was sentenced to three years in jail. And so he's, to the best of my knowledge that's where he is. But I often get asked what about the children? As far as we know, there was a third child born about six months later, also gene-edited. We don't even know a name for that child, let alone anything about their health. So one hopes that somebody in the Chinese medical establishment is looking after these kids and monitoring them and doing appropriate tests. The editing, as you said, was very shoddily performed. He knocked out the gene in question, but he did not mimic the natural 32-base deletion in this gene CCR5 that exists in many members of the population that confers, essentially, HIV resistance. So Lulu and Nana on the third child are walking human experiments, sad to say. This should never have been done. Never should have been attempted. And so we hope that he hasn't condemned them to a life of, you know, cancer checkups and that there were no off-target effects. They'll be able to live, hopefully, with this inactivated CCR5 gene, but it's been inactivated in a way that I don't think any, no other humans have ever been recorded with such modifications. So we, we really hope and pray that no other damage has been done. Harry Glorikian: So before we end, I'd love to give you the chance to speculate on the future of medicine in light of CRISPR. Easy, fast, inexpensive genome sequencing, give us access to everybody's genetic code, if they so choose. Machine learning and other forms of AI are helping understand the code and trace interactions between our 20,000 genes. And now CRISPR gives us a way to modify it. So, you know, it feels like [we have] almost everything we need to create, you know, precise, targeted, custom cures for people with genetic conditions. What might be possible soon, in your view? What remaining problems need to be solved to get to this new area of medicine? Kevin Davies: If you know the sequence that has been mutated to give rise to a particular disease then in principle, we can devise a, some sort of gene edit to repair that sequence. It may be flipping the actual base or bases directly, or maybe as we saw with the first sickle cell trial, it's because we understand the bigger genetic pathway. We don't have to necessarily go after the gene mutation directly, but there may be other ways that we can compensate boost the level of a compensating gene.But I think we, we should be careful not to get too carried away. As excited as I am—and hopefully my excitement comes through in Editing Humanity—but for every company that we've just mentioned, you know, you can go on their website and look at their pipeline. And so Editas might have maybe 10 diseases in its cross hairs. And CRISPR [Therapeutics] might have 12 diseases. And Intellia might have 14 diseases and Graphite has got maybe a couple. And Beam Therapeutics has got maybe 10 or 12. And Prime Medicine will hasn't listed any yet, but we'll hopefully have a few announced soon. And so I just reeled off 50, 60, less than a hundred. And some of these are gonna work really, really well. And some are going to be either proven, ineffective or unviable economically because the patient pool is too small. And we've got, how many did we say, 6,000 known genetic diseases. So one of the companies that is particularly interesting, although they would admit they're in very early days yet, is Verve Therapeutics. I touched on them earlier because they're looking at to modify a gene called PCSK9 that is relevant to heart disease and could be a gene modification that many people might undergo because the PCSK9 gene may be perfectly fine and the sequence could be perfectly normal, but we know that if we re remove this gene, levels of the bad cholesterol plummet, and that's usually a good thing as far as heart management goes. So that's an interesting, very interesting study case study, I think, to monitor over the coming years, because there's a company looking at a much larger patient pool potentially than just some of these rare syndromes with unpronounceable names. So the future of CRISPR and gene editing is very bright. I think one of the lessons I took away from CRISPR in Editing Humanity is, looking at the full story, is how this technology, this game-changing gene-editing technology, developed because 25 years ago, a handful of European microbiologists got really interested in why certain microbes were thriving in a salt lake in Southeastern Spain. This is not exactly high-profile, NIH-must-fund-this research. There was a biological question that they wanted to answer. And the CRISPR repeats and the function of those repeats fell out of that pure curiosity, just science for science's sake. And so it's the value of basic investigator-driven, hypothesis-driven research that led to CRISPR being described and then the function of the repeats.And then the story shifted to a yogurt company in Europe that was able to experimentally show how having the right sequence within the CRISPR array could safeguard their cultures against viral infection. And then five years of work people in various groups started to see, were drawn to this like moths to a flame. Jennifer Doudna was intrigued by this from a tip-off from a coffee morning discussion with a Berkeley faculty colleagues, Jill Banfield, a brilliant microbiologist in her own. And then she met meets Emmanuelle Charpentier in Puerto Rico at a conference, and they struck up a friendship and collaboration over the course of an afternoon. And that, why should that have worked? Well, it did, because a year later they're publishing in Science. So it's serendipity and basic research. And if that can work for CRISPR, then I know that there's another technology beginning to emerge from somewhere that may, yet trump CRISPR.And I think the beauty of CRISPR is its universal appeal. And the fact is, it's drawn in so many people, it could be in Japan or China or South Korea or parts of Europe or Canada or the U.S. or South America. Somebody is taking the elements of CRISPR and thinking well, how can we improve it? How can we tweak it?And so this CRISPR toolbox is being expanded and modified and updated all the time. So there's a hugely exciting future for genome medicine. And you know, whether it's a new form of sequencing or a new form of synthetic biology, you know, hopefully your show is going to be filled for many years to come with cool, talented, young energetic entrepreneurs who've developed more cool gadgets to work with our genome and other genomes as well. We haven't even had time to talk about what this could do for rescuing the wooly mammoth from extinction. So fun things, but maybe, maybe another time. Harry Glorikian: Excellent. Well, great to have you on the show. Really appreciate the time. I hope everybody got a flavor for the enormous impact this technology can have. Like you said, we talked about human genome, but there's so many other genomic applications of CRISPR that we didn't even touch. Kevin Davies: Yup. Yup. So you have to read the book. Harry Glorikian: Yeah. I will look forward to the next book. So, great. Thank you so much. Kevin Davies: Thanks for having me on the show, Harry. All the best.Harry Glorikian: Take care.Harry Glorikian: That's it for this week's show. You can find past episodes of MoneyBall Medicine at my website, glorikian.com, under the tab “Podcast.” And you can follow me on Twitter at hglorikian.  Thanks for listening, and we'll be back soon with our next interview.

The founding CEO of Beam Therapeutics, John Evans explains the new world of precision genome editing (Base Editing). Beam Therapeutics is the base editing company co-founded by David Liu, Feng Zhang and Keith JoungClose to the Edge | Ep. 5 | John Evans, CEO Beam Therapeuticshttps://www.youtube.com/watch?v=ydU-l...Welcome back, tribe members! Today I'm discussing "My Next 4X Stock - Buy Now". If you enjoy this video feel free to SUBSCRIBE! Make sure to follow me on social media for even more coverage of the stock market.The Power of a Tribe: https://www.amazon.com/dp/B096TWBDM3/...Get Surfshark VPN at  https://surfshark.deals/INVESTORS and enter promo code INVESTORS for 83% off and 3 extra months for free!  Facebook: https://www.facebook.com/BestofUSLLC/Instagram: https://www.instagram.com/bestofusinv...Twitter: https://twitter.com/BestOfUsInvestHelp Kerry and Nita win the race against Childhood Cancer and keep their daughter Shay's memory alive. Your support makes a direct impact in the fight against Pediatric Cancer at Children's of Alabama by helping advance research in finding a cure for cancer http://give.childrensal.org/bestofusWe have Up-Graded Our Discord: Kerry's Portfolio, Trades and InsightsThis is the new link: https://discord.io/bestofus. It is now organized by topics and will be easier to navigate and communicate

Hear from Feng Zhang, Omar Abudayyeh and Jonathan Gootenberg about the STOPCovid initiative for point-of-care testing for COVID-19.

On today’s episode of Catalysts for Change, Jill talks to Feng Zhang, a founder of CRISPR, McGovern Investigator and professor in MIT’s Departments of Brain and Cognitive Sciences and of Biological Engineering. A core member of the Broad Institute of MIT and Harvard, today’s conversation with Feng focuses on COVID-19 testing, vaccines, vaccine shortages, virus variants, and more relevant issues. Having graduated from both Harvard and Stanford, Feng joined MIT and the Broad Institute in 2011 and became a full professor in 2018. Feng’s work utilizing CRISPR technology has been nationally recognized and his research and tools have helped further developments in biomedical research. Feng’s recent work has been understanding the COVID-19 virus and helping develop new tests in detecting the virus. We talk to Feng about his work and CRISPR tools, as well as his current endeavors surrounding the COVID-19 pandemic, testing, vaccines, and the rise of new variants in different parts of the world. This information is extremely relevant as the country moves forward in the rollout of different vaccines and addressing the virus. To learn more about Feng’s work at the Broad Institute, you can click here. If you would like to read more about Feng’s background and important information on COVID-19, check out the links below. Resources: Here is more information about Feng and his background Here is the website for Feng’s Lab, The Zhang Lab Here is an article detailing Feng’s work around COVID-19 testing Here is the report on detecting COVID-19 using CRISPR technology Here is more information about how CRISPR technology works

pomeさんをゲストに迎え、ボストン界隈を中心としたCRISPR関連のバイオスタートアップについて話を伺いました。Show notes Top CRISPR Startup Companies Changing the Future of Biotech and Medicine … CRISPR関連スタートアップまとめ Researchat.fm, ep76 … ゲノム編集特集回 Researchat.fm, ep77 … ゲノム編集特集回 Researchat.fm, ep2 … CRISPR特集回 Researchat.fm, ep77 Researchat.fm, ep47 … SHERLOCKについて話しました。 Boston MIT … マサチューセッツ工科大学。Kendall Station近くに位置する。厳密にはボストン市ではなく、ケンブリッジ市である。 Harvard University … ハーバード大学。こちらもメインキャンパスはケンブリッジ市。Oxford Stに位置する建物もあるため、Oxford St., Cambridgeと住所的には何が何だかわからないところもある。 Boston University … BU University of Massachusetts … UMass Tufts University Berklee College of Music … いつもバークリーなのかバークレーなのかわからなくなる。有名な音楽学校。 NOVARTIS Takeda Biogen Bayer Cell Press … いわゆるCell誌。MIT,ハーバードの目と鼻の先にある。 カリフォルニア州 マサチューセッツ州 ニューヨーク州 ニュージャージー州 Akamai Feng Zhang David Liu Researchat.fm, Ep60 … 培養肉などについて話しました。 GMO …Genetically modified organism Plantedit FAD2 Solive … by Plantedit spCas9 Cas12 Cas13 Inscripta mad7 nuclease Unreal Engine Unity C4U BioPallete Cas3 モダリス Beam Therapeutics Researchat.fm, ep22 … Base editorやTarget AIDについて話しました。 in vivo ex vivo 鎌状赤血球 CRISPR Therapeutics 造血幹細胞 CD34+ ヘモグロビン BCL11A eGenesis Bio George Church 胚盤胞置換法 Living cell technologies (LCT) Diatranz Otsuka CAR-T レンチウイルス AAV HIV ゾルゲンスマ TLO … Technology License Organizationの略 Wyss Institute Wyss Instituteのポッドキャスト … めちゃくちゃ良い。tadasuはリピートしまくって聞いている時期が度々ある。 Peng Yin Researchat.fm, ep74 … DNA Origamiについて話しました。 Cambridge Innovation Center (CiC) Venture Cafe Venture Cafe Tokyo … 虎ノ門ヒルズ内にある。木曜日にイベントをやっているようです。 CiC Tokyo … 虎ノ門ヒルズ内にある。 Cambridge City, MA … ケンブリッジ市 スタンフォード大学のパテントに関する資料 … Stanford UniversityのOTLによる資料。 lab central Johnson & Johnson Roche Job Description 四行教授 … とあるブログ様を引用させていただきました。当時修士のtadasuに四行教授や「履歴書を汚せ」と説いた人物は黒川清先生です。 Researchat.fm, ep75 … I’m not sure though. Editorial notes とっても楽しいおしゃべりでした。仕事と関係ないマニアックな話をできる場はあんまりないので貴重です。またやりましょう。(pome) 後編もお楽しみに〜 (soh) 同じ地区に住んでいるのに何にも活かせていません…(tadasu) (coela)

dessanをゲストに迎え、CRISPRの仕組みを利用した様々な技術や遺伝子回路、これからの発展について話しました。Show notes The Nobel Prize in Chemistry 2020…The Nobel Prize in Chemistry 2020 was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing.” Scientifc Background on the Nobel Prize in Chemistry 2020 A TOOL FOR GENOME EDITING…ノーベル財団による詳細なCRISPR研究のレビュー、そしてなぜDoudnaとCharpentierの二人が受賞に値するのかについて説明している。 76. The Chimeric RNA, Researchat.fm…ゲノム編集についてdessanをゲストに迎えて話しました。 A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity. Science 2012…CharpentierとDoudnaによるノーベル賞につながる論文の一つ。CRISPR–Cas9システムがこの論文によってその大枠が明らかにされた。 Multiplex Genome Engineering Using CRISPR/Cas Systems. Science 2013…Feng Zhang labによるヒト細胞におけるゲノム編集技術の報告。 RNA-Guided Human Genome Engineering via Cas9. Science 2012…George Church labによるヒト細胞におけるゲノム編集技術の報告も同時に掲載された。 First rounders: Feng Zhang (Podcast)…Feng Zhangが出演したNatute Biotechnologyのポッドキャスト。おすすめです。 26. Cool tech googlability, Researchat.fm…RNAを標的にできるCas13bについては、エピソード26で紹介しました。 Cas14 (crisp_bio)…“Cas14は、PAMに依存しないssDNA切断活性に加えて、PAMに依存するdsDNA切断活性も帯びている” CasX enzymes comprise a distinct family of RNA-guided genome editors. Nature 2019…CasX Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration. Nature 2019…トランスポゾン型のCasシステムの報告。 RNA-programmed genome editing in human cells. eLife 2013…Doudna labによるヒト細胞におけるゲノム編集技術の報告。FengやChurchらよりも少しだけ遅かった。 Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9. Nature Communications 2014 Ep52. Split into a row Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity. Cell 2013…Double nicking (2つのgRNAとCas9 nickase)によるより正確なゲノム編集方法が示された。 Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 2015…Cas9を用いた転写の活性化手法。 Live visualization of chromatin dynamics with fluorescent TALEs. Nature Structural & Molecular Biology 2013 … TALENを用いた染色体の特定領域のイメージング方法 Dynamic Imaging of Genomic Loci in Living Human Cells by an Optimized CRISPR/Cas System. Cell 2013…dCas9-EGFPによる生細胞のイメージング技術。SpCas9の場合は、D10AとH840Aの２つの変異を入れることで、DNAに結合するが切断しないdead Cas9 (dCas9)として利用することができる。 Live cell imaging of low- and non-repetitive chromosome loci using CRISPR-Cas9. Nature Communications 2017…ガイドRNAにMS2 loopをたくさんつなげることで (14個!)、明るい輝点を得ることができる。 CRISPR-mediated live imaging of genome editing and transcription. Science 2019…こちらは蛍光標識したガイドRNAを利用した生細胞イメージング方法。 A protein tagging system for signal amplification in gene expression and fluorescence imaging. Cell 2014…Sun tagとCas9を用いたイメージング方法。 Split Green Fluorescent Proteins: Scope, Limitations, and Outlook…Split GFP Programmable RNA tracking in Live Cells with CRISPR/Cas9. Cell 2016…PAMmerによるSpCas9のmRNAイメージング CRISPR-Mediated Programmable 3D Genome Positioning and Nuclear Organization. Cell 2018 … CRISPR-GO：CRISPR技術、核内でのゲノム空間構造、ポッドキャスト内ではゲノム同士を寄せるという説明をしていましたが、今調べてみると特定のゲノム領域と核膜やカハール体への再配置ということでした。 Manipulation of nuclear architecture through CRISPR-mediated chromosomal looping. Nature Communications 2017 … こちらがCRISPRの仕組みを用いることで人工的に染色体内部にループを作成した論文。 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 2008 … LacO-LacIの仕組みを用いることでゲノムの特定領域にLacO arrayを差し込み、核膜に局在させたLacIに結合させることである遺伝子領域を核膜側に誘導しようとした論文。最初にこの論文を読んだ時はそのアイデアにたまげました。 9. One-shot beautiful experiment (Researchat.fm)…人工的なDNA領域へ細胞内の情報（細胞系譜）を書き込む技術についてエピソード9で話しました。 CRISPR–Cas encoding of a digital movie into the genomes of a population of living bacteria. Nature 2017…George Churchらは、Cas1-Cas2システムによって馬の動画をバクテリアゲノム書き込み、それを読み出すことに成功した。 Multiplex recording of cellular events over time on CRISPR biological tape. Science 2017…コピー数の異なる2つのプラスミドをCas1-Cas2で取り込ませて、細胞内で人工的な時計のような仕組みを実現した。 Single-Nucleotide-Resolution Computing and Memory in Living Cells. Molecular Cell 2019…Tim Liu Labによる複雑な遺伝子回路の実現。DOMINOについては、プロモーター配列を標的にしているのではなくオペレーター配列でした。 Rewritable multi-event analog recording in bacterial and mammalian cells. Science 2018…David Liu labから報告されたガイドRNAによって連鎖する遺伝子回路（カスケード）の実現。 Terminal Deoxynucleotidyl Transferase, TdT…テンプレートに依存しないDNA合成を可能にする酵素。 Tandem fluorescent protein timers for in vivo analysis of protein dynamics. Nature Biotechnology 2012…GFP Timer Permanent genetic memory with >1-byte capacity. Nature Methods 2014 Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Science 2016…自分で自分のガイドRNAを編集することで、理論的には無限に情報を書き込む方法が提案されたが、領域が壊れてしまう問題もある。 Ten Simple Rules to Win a Nobel Prize. ヘンリー・ブラッグ (Wikipedia) iPS細胞 (Wikipedia) 国境なき医師団 Human Genome Project Xiaowei Zhuang Expansion microscopy (Wikipedia) Renato Dulbecco (Wikipedia) Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nature Biotechnology 2019…LEAPER crisp_bio … 世界広しといえでも、これだけCRISPRの最新情報がまとまっているサイトはCRISP_BIOさんの他に世の中には存在しません。日本語でCRISPRの最先端情報を追える喜び。CRISP_BIOさん、いつもありがとうございます。 Editorial notes 1分でわかるとか無理なのですが、一方で言葉を尽くせばわかる可能性についても同時に信じておりますので…(soh) 思い出しながらどんどん話しているので、後から聞き返すと細部が間違っていたりしています。気になった方はshow notesをご参照ください。(dessan) いい感じのグルーヴがみられてよかったです。ポッドキャストやってきてよかったです。(tadasu) 最初に喋らんと出番が無くなる！と思ってこれまでの流れをまとめてみたんですが細かく色々ミスってました…(coela)

Nobelova nagrada za medicinu: otkriće hepatitisa C (https://www.nobelprize.org/prizes/medicine/2020/summary/) Nobelova nagrada za hemiju: CRISPR/Cas9 (https://www.nobelprize.org/prizes/chemistry/2020/summary/) Ko nije dobio Nobelovu nagradu za hemiju: Feng Ženg (https://en.wikipedia.org/wiki/Feng_Zhang)

Ursula von der Leyen’s first State of the European Union speech was as long as it was broad in topics and calls for action. Host Mark Leonard is joined by Alexander Stubb, ECFR Board Member, Director of the European University Institute’s School of Transnational Governance and Former Prime Minister of Finland and Carlos Moedas Trustee at the Calouste Gulbenkian Foundation and former European Commissioner for Research, Science and Innovation. Together they break down the speech and analyse its various parts, from climate to health policy, from digital sovereignty to Europe’s place in the world. What did the Commission President promise and envision? And did she point out some black sheep? This podcast was recorded on 16 September 2020. Bookshelf: • “Governance in the new global disorder: Politics for a post-sovereign society” by Daniel Innerarity • “The virus in the age of madness" by Bernard-Henri Lévy • “Has China won? The Chinese challenge to American primacy” by Kishore Mahbubani • "Negotiating flexibility in the European Union" by Alexander Stubb • "Taming Sino-American rivalry" by Feng Zhang & Richard Ned Lebow

Erik Milito (National Ocean Industries Association) and Feng Zhang and Max Cohen (Wood Mackenzie) joined us to discuss Wood Mackenzie's August 2020 report "Economic Impact Study of New Offshore Wind Lease Auctions By BOEM." Credits: Content, audio engineering, editing, and sound design by Brandon Burke. Music by Brandon Burke, with contributions from Nathan Ezzo, Steven Reilly, and Miles Taylor. Recorded August 18, 2020. Published September 1, 2020.

Hear from Feng Zhang, Omar Abudayyeh and Jonathan Gootenberg about the STOPCovid initiative for point-of-care testing for COVID-19.

バイオテクノロジーと枯れた技術の水平思考、ピタゴラスイッチ、507 Mechanical Movementsについて話しました。Shownotes 任天堂 (公式サイト) … 任天堂 横井軍平 (Wikipedia) 宮本茂 (Wikipedia) 岩田聡 (Wikipedia) 桜井政博 (Wikipedia) 田尻智 (Wikipedia) 横井軍平ゲーム館 (Amazon) … 横井軍平さんが作ったおもちゃとゲームに対する考えを一通り学ぶことができる。 山内溥 (Wikipedia) … 3代目任天堂社長 ゲーム&ウォッチ (Wikipedia) ウルトラハンド (Wikipedia) ラブテスター (Wikipedia) 枯れた技術の水平思考 … 今回のエピソードでは、枯れた技術について推しすぎたかもしれませんが、もちろん最先端の技術も必要で、バランスが重要です。素晴らしいアイデアとテクニックであっても使えないのであれば意味がありません。この辺りはそれぞれのスタンスによると思いますが。 水平思考 (Wikipedia) Livet et al., Nature (2007) … Brainbowに関する論文。蛍光タンパク質とCre-loxシステムの組み合わせによる美しいメソッド CYP,YFP,RFP … 蛍光タンパク質。それぞれCyan, Yello, Red Fluorescent protein Cre-lox system (Addgene Blog) optical barcoding … 蛍光標識により細胞を染め分けてトラッキングする。 Chen et al., Science (2015) … expansion microscopyに関する論文。組織内外における微細構造を超解像イメージングによって明らかにするのではなく、元の構造を維持しながら膨らませることによって、通常のイメージングでも可視化することに成功した。 Dekker et al., Science (2002) … PCRによってゲノムの高次構造を明らかにしようとした論文。この後発展を遂げ、Hi-Cという名前でクロマチン業界を席巻している。 Researchat.fm, エピソード24 … PCRを発明したKary Mullisや、DNA computingの話をしました。 Adelman, Science (1994) … PCRを利用してグラフの問題を解こうとした論文 Researchat.fm, エピソード47 … SHEROCKについて話しました。 Gootenberg et al., Science (2017) … SHEROCKに関する論文 Researchat.fm, エピソード16 … DNA microscopyについて話しました。 Weinstein et al., Cell (2019) … DNA microscopyに関する論文。 Optogenetics (Wikipedia) … 光遺伝学 ロドプシン van Steensel and Henikoff, Nature Biotechnology (2000) … DamIDの論文 Feng Zhang 佐藤雅彦 (Wikipedia) ピタゴラスイッチ ピタゴラ装置DVDブック1 (Amazon) シャキーン! ウゴウゴルーガ (Amazon) ルーブ・ゴールドバーグ・マシン (Wikipedia) … 一般的に海外におけるピタゴラ装置はこのように呼ばれている。 NHK放送博物館 507 Mechanical Movements (Amazon) … Henry Brown著。様々な歯車や滑車を見ることができる(うまく説明できない)。 507 Mechanical Movements… 上記の本の情報を集めたweb ワンダースワン (Wikipedia) Editorial notes 僕も横井軍平のちくま文庫を読みました。いやあエピソードが増えてshownotesに過去回のエピソードが沢山関連付けられるようになりましたね。(soh) バイオテクノロジーに対する憧れと自分の甘さを露呈してしまいました。シンプルで簡単に見えるものが最も難しい…(tadasu) 任天堂さんにはいつもお世話になっています。D論が煮詰まっていたときは「ワンパラ書いたらブレスオブザワイルドの祠一個やっていい」ルールでモチベーションを保ちました(coela)

新型コロナウィルスの広がりで注目を集めているCas13を用いた簡便かつ高感度な核酸検出法、SHERLOCKという技術について原著論文を紹介しました。Show notes Specific High-sensitivity Enzymatic Reporter unLOCKing…これがSHERLOCKの略！ Nucleic acid detection with CRISPR-Cas13a/C2c2. Science 2017.…SHERLOCKのオリジナル論文。Cas13のもつ無差別なRNA分解活性 (collateral activity)と蛍光プローブを利用することで、ウィルスなど様々な核酸分子の検出を簡便に行う技術の扉を開いた。無料で論文の全文が読めます。 Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6. Science 2018…複数のCas13オーソログと蛍光プローブを組み合わせたSHERLOCK v2により、感度が向上したほか、複数の標的を一度に検出できるようになった。 Sherlock Biosciences…Feng Zhangなど開発者たちはベンチャーを立ち上げSHERLOCKの技術開発、とくに医療応用を目指している。また昨年、大型の資金調達にも成功している (3,500万ドル, 38億円)。 CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity. Science 2018…Jennifer DoudnaらのチームもDETECTRという類似の技術を開発し、Mammoth Biosciencesというベンチャーを立ち上げた。こちらも大型の資金調達 (4,500万ドル, 49億円)に成功しており、競争は激化しており大きな市場が見込まれている。 Mammoth Biosciences 遺伝子編集ツール開発のMammoth Biosciencesが約49億円調達 (TechCrunch) A protocol for detection of COVID-19 using CRISPR diagnostics…SHERLOCKによるコロナウイルスの検出のためのプロトコルが開発チームらによって公開された。まだFDAの認可はおりていない。 Editorial notes 簡便なウィルスなど核酸の検出キットの開発は想像以上に競争が激化しており、大きな盛り上がりを感じますね (Soh) 紙で全部置き換えられるとするなら途轍もないブレークスルーだな (tadasu) バイオ面白名前シリーズもいつかまとめたい (coela)

One of the most significant revolutions in science is underway, and yet most people haven't even heard of it. It's called CRISPR, and it is an easy, inexpensive process for cutting and pasting DNA - the code of life. It is already being used in human trials to cure genetic disease, and it promises to transform agriculture, with drought-resistant crops that will better feed the world. But it also threatens to usher in a frightening era of designer babies and unintended consequences. The two lead scientists behind CRISPR, Jennifer Doudna and Feng Zhang, talk here about their lives and their research, and they sound the alarm about the dangers of their own discovery.

CRISPR-Cas13システムを用いたプログラマブルなRNA編集技術であるREPAIRとRESCUEの原著論文について紹介しました。Show notes Misreading Chat CS の論文読んで話をしよう…おすすめComputer science系の論文紹介ポッドキャストです。 RNA修飾とは？ 疾患におけるA-to-I RNA編集酵素ADAR1の役割…ADARとRNA編集についてとても詳しくわかりやすい総説記事。 RNA editing with CRISPR-Cas13. Cox et al., 2017 Science…1本目に紹介したADARをdCas13bに融合させA-to-I RNA editingを実現させた。PDFがNCBI Pubmedから無料で読めます。REPAIRv2はoff-target効果がさらに軽減されている。 A cytosine deaminase for programmable single-base RNA editing. OO Abudayyeh et al., 2019 Science…こちらは今年にScienceに掲載された改良版。ADAR2にさらに変異を加えることにより、A-to-IのみならずC-to-U RNA編集が実現され、RESCUEと命名。 Editorial notes RNA editingによって、off-targetによる編集が起きても最悪の事態が回避できるというのはなるほどと唸りました。ただ、Feng Zhang研のネーミングセンスの悪さはどうにかしていただきたい。検索がめちゃくちゃになる (tadasu) バリューのある技術をどのように作っていくのか、という観点からもとても勉強になった論文でした (soh) RNA editingは詳しくないので勉強になった。ここから色んなアプリケーションがつくられていきそうでワクワクする。(coela)

Two recent scientific journal papers show what's possible when CRISPR moves from cutting DNA tool to a full-fledged platform -- expanding its toolkit for medicine across R&D, therapeutics, and diagnostics: "Transposon-encoded CRISPR-Cas systems direct RNA-guided DNA integration" in Nature -- by Sanne Klompe, Phuc Vo, Tyler Halpin-Healy, and Samuel Sternberg (of Columbia University) "RNA-guided DNA insertion with CRISPR-associated transposases" in Science -- by Jonathan Strecker, Alim Ladha, Zachary Gardner, Jonathan Schmid-burgk, Kira Makarova, Eugene Koonin, and Feng Zhang (of the Broad Institute) What do these two papers -- both about techniques for getting rid of the need to cut the genome to edit it -- make possible going forward, given the ongoing shift of biology becoming more like engineering? Where are we in the wave of the genome engineering "developer community" building on top of CRISPR with a constantly growing suite of programmable functionalities? a16z bio general partner Jorge Conde and bio deal team partner Andy Tran chat with Hanne Tidnam about these trends -- and these two papers -- in this short internal hallway-style conversation, part of our new a16z Journal Club series. This podcast is also part of our new a16z bio newsletter, which you can sign up for at a16z.com/subscribe

Keith Joung and Feng Zhang explain methods for editing sequences of DNA in living cells.

Feng Zhang runs the Zhang Lab at the Massachusetts Institute of Technology. He's also a faculty member at the Broad Institute of MIT and Harvard, and has co-founded several biotech companies, including Editas Medicine. His conversation with Nature Biotechnology covers immigrating to America as a boy, his moment of discovery with CRISPR, and what massive success before the age of 35 does to a researcher. See acast.com/privacy for privacy and opt-out information.

In late 2012, French microbiologist Emmanuelle Charpentier approached a handful of American scientists about starting a company, a Crispr company. They included UC Berkeley's Jennifer Doudna, George Church at Harvard University, and his former postdoc Feng Zhang of the Broad Institute—the brightest stars in the then-tiny field of Crispr research. Back then barely 100 papers had been published on the little-known guided DNA-cutting system. It certainly hadn't attracted any money.

Dr Eric Topol interviews CRISPR scientist Feng Zhang about his journey from China to the gene editing labs of America.

UC Berkeley undergraduate Megha Majumder was fired up. Just a few weeks after Feng Zhang, MIT, and the Broad Institute won the interference proceeding over Crispr/Cas9 patents against UC Berkeley's Jennifer Doudna, solidifying Zhang's patent claims and the vast rewards they promise, Majumder learned of Zhang's upcoming public talk at her college.

Elena Vázquez Abal é especialista en xeometría diferencial, polo que para esta profesora da USC todas as curvas teñen o seu aquel. Elena tamén é unha apaixonada da divulgación científica, e xunto con actor César Goldi rememoran os gloriosos tempos nos que percorreron o país de bar en bar falando de matemáticas. A tecnoloxía CRISPR de edición xenética esta revolucionando o traballo dos laboratorios de investigación de todo o mundo, pero aínda non chegou a industria. Isto é así por que está aberta unha guerra de patentes entorno a un negocio multimillonario entre a Universidade de California con Jennifer Doudna e Emmanuelle Carpentier (premio Princesa de Asturias de Investigación) e Instituto Broad do MIT liderado por Feng Zhang. Un tribunal de patentes estadounidense ven de determinar que a técnica de Zhang para aplicar CRISPR en células eucariotas é patentable e non interfire coa demanda de patente máis xenérica presentada pola Universidade de California aínda sen resolver. As espadas están no alto, e mesmo pode pasar que sexa necesario pagar licencias aos dous bandos para traballar nestas tecnoloxías nos laboratorios privados. Atentos. E entre medias escoitaremos algún dos mais interesantes aforismos de Jorge Wagensberg na voz do seu autor.

Elena Vázquez Abal é especialista en xeometría diferencial, polo que para esta profesora da USC todas as curvas teñen o seu aquel. Elena tamén é unha apaixonada da divulgación científica, e xunto con actor César Goldi rememoran os gloriosos tempos nos que percorreron o país de bar en bar falando de matemáticas. A tecnoloxía CRISPR de edición xenética esta revolucionando o traballo dos laboratorios de investigación de todo o mundo, pero aínda non chegou a industria. Isto é así por que está aberta unha guerra de patentes entorno a un negocio multimillonario entre a Universidade de California con Jennifer Doudna e Emmanuelle Carpentier (premio Princesa de Asturias de Investigación) e Instituto Broad do MIT liderado por Feng Zhang. Un tribunal de patentes estadounidense ven de determinar que a técnica de Zhang para aplicar CRISPR en células eucariotas é patentable e non interfire coa demanda de patente máis xenérica presentada pola Universidade de California aínda sen resolver. As espadas están no alto, e mesmo pode pasar que sexa necesario pagar licencias aos dous bandos para traballar nestas tecnoloxías nos laboratorios privados. Atentos. E entre medias escoitaremos algún dos mais interesantes aforismos de Jorge Wagensberg na voz do seu autor.

A tecnoloxía CRISPR de edición xenética esta revolucionando o traballo dos laboratorios de investigación de todo o mundo, pero aínda non chegou a industria. Isto é así por que está aberta unha guerra de patentes entorno a un negocio multimillonario entre a Universidade de California con Jennifer Doudna e Emmanuelle Carpentier (premio Princesa de Asturias de Investigación) e Instituto Broad do MIT liderado por Feng Zhang. Un tribunal de patentes estadounidense ven de determinar que a técnica de Zhang para aplicar CRISPR en células eucariotas é patentable e non interfire coa demanda de patente máis xenérica presentada pola Universidade de California aínda sen resolver. As espadas están no alto, e mesmo pode pasar que sexa necesario pagar licencias aos dous bandos para traballar nestas tecnoloxías nos laboratorios privados. Atentos.

A tecnoloxía CRISPR de edición xenética esta revolucionando o traballo dos laboratorios de investigación de todo o mundo, pero aínda non chegou a industria. Isto é así por que está aberta unha guerra de patentes entorno a un negocio multimillonario entre a Universidade de California con Jennifer Doudna e Emmanuelle Carpentier (premio Princesa de Asturias de Investigación) e Instituto Broad do MIT liderado por Feng Zhang. Un tribunal de patentes estadounidense ven de determinar que a técnica de Zhang para aplicar CRISPR en células eucariotas é patentable e non interfire coa demanda de patente máis xenérica presentada pola Universidade de California aínda sen resolver. As espadas están no alto, e mesmo pode pasar que sexa necesario pagar licencias aos dous bandos para traballar nestas tecnoloxías nos laboratorios privados. Atentos.

Feng Zhang är med och utvecklar den nya genkniven som utsågs till 2015 års viktigaste forskningsupptäckt. Det började med att en vän fick depression och han ville förstå mer om psykiatriska sjukdomar. Genkniven CRISPR/Cas9 har både lett till en het patentstrid och etiska debatter. Själv vill Feng Zhang använda genkniven för att förbättra behandlingarna av psykiska sjukdomar.Han kom till USA från Kina som 11-åring, och efter en omvälvande filmupplevelse med Jurassic Parc blev han helt tagen av möjligheten som kunskapen om gener kan ge. Han har nu som 34-årig professor i biomedicinsk ingenjörskonst vid MIT i Boston varit med och utvecklat genkniven CRISPR/Cas9. En kniv som han menar kan vara farlig, eftersom den kan användas till att förändra mänskliga embryon men där han tror att den fungerar bättre till att skapa nya typer av försöksdjur och öppnar möjligheten att förändra genetiska sjukdomar hos vuxna. Han har grundpatentet för kniven i USA, men är ledsen över all uppmärksamhet som har riktats mot den konflikten i stället för själva vetenskapen. Annika Östman annika.ostman@sverigesradio.se 

Keith Joung and Feng Zhang explain methods for editing sequences of DNA in living cells.