Raising Health

Jonathan Bush, founder and CEO of Zus Health, and Chris Severn, cofounder and CEO of Turquoise Health, join Julie Yoo, general partner, and Colin Rom, head of public policy for a16z Bio + Health.

We’ve long believed that regulatory change can be a catalyst for company creation. In this episode, Jonathan and Chris detail how that was true for them. They also outline a few key takeaways for founders hoping to leverage regulatory change themselves.

In this episode, originally recorded for the a16z Podcast, host Steph Smith interviews Pushmeet Kohli, DeepMind's VP of Research focused on AI for science. They are joined by a16z Bio + Health founding partner Vijay Pande.

Together, they discuss AI at scale, and its power to transform science.

Chronis Manolis, SVP and Chief Pharmacy Officer of UPMC Health Plan, joins Julie Yoo, general partner, Daisy Wolf, investment partner, and Will Shrank, venture partner, of a16z Bio + Health.

Together, they discuss how payors and providers are thinking about anti-obesity medications, as well as pricing and prior authorization considerations. 

This is the third episode in our series on the science and supply of GLP-1s. Listen to last week’s episode to hear from Brooke Boyarsky Pratt, founder and CEO of knownwell, about the importance of patient-centric medical homes. The week before, we spoke with Carolyn Jasik, Chief Medical Officer at Omada Health, on GLP-1s from a clinical perspective.

Brooke Boyarsky Pratt, founder and CEO of knownwell, joins Vineeta Agarwala, general partner at a16z Bio + Health.

Together, they talk about the value of obesity medicine practitioners, patient-centric medical homes, and how Brooke believes the metabolic health space will evolve over time.

This is the second episode in our series on the science and supply of GLP-1s. Listen to last week's episode to hear from Carolyn Jasik, Chief Medical Officer at Omada Health, on GLP-1s from a clinical perspective.

Carolyn Jasik, MD, Chief Medical Officer of Omada Health, joins Vijay Pande, founding partner of a16z Bio + Health.

As Ozempic, Wegovy, Mounjaro, and Zepbound capture the healthcare spotlight, we’ve developed a series of episodes that go beyond the headlines and take you into conversations with the specialists. 

Our first guest is Carolyn Jasik, Chief Medical Officer at Omada Health. She gives us an overview of the science of satiety, the perspective from obesity-focused physicians, and the sometimes surprising lifestyle implications for patients on these medicines.

This series provides insight into what anti-obesity medicines are, where they’re going, and the challenges that have to be overcome along the way.

Vineeta Agarwala, MD, PhD, joins Luke Timmerman's The Long Run podcast on stage at the Life Science Innovation Northwest Conference. They discuss everything from AI for drug discovery to Vineeta's ongoing clinical work as a physician and how that influences her perspective.

Kim Branson, PhD, SVP and Global Head of AI and Machine Learning for GSK, joins Vijay Pande, founding partner at a16z Bio + Health.

Together, they talk about how AI has improved drug discovery and development, as Kim walks through all the ways AI can be deployed in the lab. They also get into detail about what an ideal partner looks like and what kind of solution is attractive to a big biopharma, making this a particularly relevant episode for builders in biotech AI.

In this episode, Carl June, MD, pioneering immunologist and oncologist at the University of Pennsylvania, joins Jorge Conde, general partner at a16z Bio + Health.

Together, they discuss Carl's work on CAR T, a remarkable story of the first use of CAR T in a pediatric patient, and Carl's take on where oncology treatments are headed next.

Though this episode was originally published in September 2023, back when we were called Bio Eats World, we’re republishing it  during this year’s ASGCT conference, where the latest advances in cell and gene therapy—like what Carl describes—are shared and discussed.

Tom Hale, CEO of ŌURA, joins Vijay Pande, founding partner, and Daisy Wolf, investment partner at a16z Bio + Health.

Together, they talk about the potential of wearables to change behavior, and how that can affect health. They also discuss how AI could maximize the usefulness of wearables and power the insights provided to wearers.

Philip Tagari, Chief Scientific Officer of insitro, joins Vijay Pande, founding general partner at a16z Bio + Health.

Together, they discuss the transformative power of drugs in changing human health—and history. They also reflect on the evolution of the drug discovery process as it shifts from serendipitous discovery to AI-enabled engineering. Finally, they chat about where the industry is headed, and how AI might change the competition landscape.

Vijay Pande, founding general partner of a16z Bio + Health, chats with the builders (and siblings) behind Devoted Health, Ed and Todd Park. 

The Park brothers, with decades of expertise in healthcare and policy, including as EVP and COO at athenahealth (Ed) and Chief Technology Officer of the United States (Todd),  started Devoted with the idea of building a healthcare model from scratch. Together, their discussion underscores the sector's urgent need for technological innovation and the game-changing role of AI.

This episode was recorded live at a16z's LP Summit.

Vijay Pande, founding general partner, and Julie Yoo, general partner at a16z Bio + Health, come together to talk through the grand challenges facing healthcare AI today.

The discussion covers the implications of AI integration in healthcare workflows, AI as a potential catalyst for value-based care, and the potential for innovation in clinical trials. They also talk about the AI startup they each wish would walk through the door. 

Greg Meyers, EVP and Chief Digital and Technology Officer at Bristol Myers Squibb (or BMS), joins a16z Bio + Health general partner Jorge Conde.

Together, they talk about how AI could transform drug discovery and development at a large biopharma company—and how a company might have to adapt to harness AI; modalities they’re excited about; and Greg’s do’s and don’ts for startups looking to partner with a company like BMS.

As any healthcare founder knows, it can be difficult to get into a room with the executives making purchase decisions for payors and providers—so we’re bringing the executives to you.

This episode features interviews with payor and provider leaders about what they’re seeing and how they’re thinking about AI. Guided by Julie Yoo, general partner, and Jay Rughani, investment partner at a16z Bio + Health, you'll hear from the executives about how they're utilizing AI, the KPIs they use to gauge effectiveness, and what they consider a good partnership.

Julie and Jay also authored an in-depth guide to commercializing AI in healthcare based on these interviews, available here. All of our go-to-market playbooks are available on our Digital Health Builders page.

"There is a revolution unfolding in biotech. The confluence of new biological methods like CRISPR, virtually unlimited computational capacity, and machine learning has fundamentally transformed our ability to engineer biology for wide-ranging applications."

Vijay Pande, founding general partner at a16z Bio + Health, joins the Software Engineering Daily podcast to talk about innovation in biotech and healthcare, the biotech startup landscape, the impact of AI, and much more.

You can see a transcript of the episode and more information about Software Engineering Daily here.

Rosana Kapeller, CEO of Rome Therapeutics, and Marty Taylor, physician-scientist at Harvard Medical School, join Vineeta Agarwala, general partner, and Bryan Faust, investment partner at a16z Bio + Health.

Together, they discuss Rosana and Marty's recent publication regarding a virus-like element in our genome known as LINE-1. LINE-1, part of our "dark genome," was ignored as junk DNA for years, but is increasingly recognized to contribute to the pathology of autoimmunity, cancer, neurodegeneration, and aging. Rosana and Marty discuss how the discovery was made as well as how Rome Therapeutics is developing a platform to target LINE-1 and other factors that are part of the "dark genome" for the treatment of disease.

Additional reading:

• Structures, functions and adaptations of the human LINE-1 protein

Vijay Pande, founding partner of a16z Bio + Health, dives deep with a16z Podcast host Steph Smith into the potential of DNA as a data storage mechanism.

This episode, a cross-post with the a16z Podcast, draws parallels between Moore's Law and the race for "Moore's Law for DNA." Vijay discusses the density, longevity, and ubiquity of DNA, and how this could be leveraged into a data storage solution. Vijay and Steph mix technical advancements with futuristic speculation as they talk about what the future of biotech might look like.

Julie Klapstein, founding CEO of Availity, long-time healthcare executive, and a16z Bio + Health's newest advisory partner, joins Julie Yoo, general partner at a16z Bio + Health.

Together, they delve into Julie Klapstein's rich career journey, which has spanned several decades of progress in healthcare. They also discussed building Availity, her time at MultiPlan, and the network effects undergirding both businesses. Finally, they talk about how AI could impact healthcare—for payors, providers, and the network businesses in between.

Scribe Therapeutics cofounder and CEO Benjamin Oakes, PhD, joins a16z Bio + Health founding general partner Vijay Pande.

In this episode, Benjamin traces his journey from PhD student to pioneering CEO in genome editing. Benjamin discusses his early exposure to CRISPR technologies, his hands-on experience of transforming these bacterial immune systems into "genome editing scalpels," and the founding of Scribe. The conversation sheds light on the challenges of engineering these molecules, as well as the potential for life-changing therapeutics.

Josh Clemente, cofounder and president of Levels, joins Vijay Pande, founding general partner, and Daisy Wolf, investment partner at a16z Bio + Health.

In this episode, engineer-turned-entrepreneur Josh charts his journey from SpaceX and Hyperloop to cofounding metabolic health-focused company Levels. With a relentless drive for data-led health monitoring, Josh highlights the potential of wearable tech for tracking various biomarkers. Josh, Vijay, and Daisy also discuss how AI can simplify complex wearables data into a comprehensible and actionable health profile, with the potential to democratize healthcare technology.

Former gymnast and current investor Aly Raisman joins general partner Julie Yoo and investment partner Daisy Wolf of a16z Bio + Health.

In this episode, Aly Raisman shares her quest for healthier living—physically, mentally and financially—on her journey from gymnast to a business investor. Having herself transitioned from an intensely structured routine, Aly emphasizes the need for more open conversations about mental health and financial literacy. She speaks passionately about the gap in women’s health solutions and hopes to inspire entrepreneurs to create impactful businesses. Aly’s experiences as a patient, survivor, and global figure adds a unique dimension to her perspective as an investor. This candid conversation with both Aly and Julie Yoo sheds light on Aly’s passion for more education within the investment space  offering invaluable insights for entrepreneurs, particularly in biotech and healthcare.

Max Cohen, cofounder and CEO of Sprinter Health, and Eren Bali, founder and CEO of Carbon Health, join Julie Yoo, general partner at a16z Bio + Health.

Together, they talk about becoming healthcare entrepreneurs despite non-healthcare backgrounds and what they had to learn along the way. They also discuss finding product-market fit, how they track PMF using KPIs, and the evolving investor landscape as the digital health space expands and matures.

Additional reading:

• Digital Health Builder Diaries series

In this episode, Joe Grogan, a senior fellow at the Leonard D. Schaeffer Center for Health Policy and Economics and a former senior government official, joins Vijay Pande, founding partner of a16z Bio + Health to discuss all things regulation.

Together, they dive into Joe’s experience working in the early days of the Covid pandemic, how he thinks about the Inflation Reduction Act’s effect on pharmaceutical R&D, and the future of AI regulation.

Additional reading:

Check out Joe's latest op-ed here, his own podcast here, and his Twitter account here.

Today's episode features the CEO of Tome Biosciences, Rahul Kakkar, alongside John Finn, CSO of Tome. They are joined by Jorge Conde, general partner at a16z Bio + Health.

Together, the three of them discuss the technology underlying Tome's work, known as PASTE, a genome editing technique. They also dive deep into how this technology could be applied to help patients, making cell therapy more accessible for more people.

Editorial note: We mistakenly identified Rahul Kakkar and John Finn as the co-founders of Tome Biosciences. In reality, Rahul serves as the CEO, and John is the CSO of Tome. The actual co-founders of Tome Biosciences are Jonathan Gootenberg and Omar Abudayyeh.

Bio Eats World is now Raising Health!

Vijay Pande, founding partner of Bio + Health, is joined by Daphne Koller, Andrew Ng, Aviv Regev, and Jakob Uszkoreit.

Vijay leads us on a reflective journey through the monumental achievements in AI from the 1980s to today, with a focus on the progress in healthcare and life sciences. This episode is drawn from the episodes we recorded in 2023 with Daphne Koller, Andrew Ng, Aviv Regev, and Jakob Uszkoreit, which are linked below.

This blend of expert commentary and firsthand insights explores the burgeoning impact of AI on healthcare innovation and how it's reshaping the future of health.

• AI and Actionable Insights for Drug Development with Daphne Koller
• Navigating the Future of AI with Andrew Ng
• When Quantity Becomes Quality with Aviv Regev
• Using AI to Take Bio Farther with Jakob Uszkoreit

Bio Eats World is now Raising Health!

On this first episode of Raising Health, Sean Duffy, cofounder and CEO of Omada Health, joins Vijay Pande, founding partner of Bio + Health.

Sean and Vijay discuss the building and growth of Omada, from the early days to now. As the cofounder of one of the original digital health companies, Sean has unique insight into the growth of both the digital health field and the changing venture capital environment.  They also talk about the future of AI, how Omada is leveraging AI, and the challenges that might arise with using a technology in a caregiving environment.

Pranav Rajpurkar, PhD, joins Vijay Pande, founding partner of a16z Bio + Health.

In this episode, Pranav and Vijay discuss a future with generalist medical AI. This is the idea of a medical AI that isn’t narrowly tailored to one specific task. As Pranav notes in the episode, the research and development process in medical AI development so far has been siloed by specialty, but generalist medical AI exists outside those siloes. If generalist medical AI is successful, it could act as a dynamic support system to a physician, almost like a medical resident.

Jordi Mata-Fink, PhD, cofounder of Gate Bioscience, joins Vineeta Agarwala and Ben Portney of a16z Bio + Health.

In this episode, Jordi discusses how he and his cofounders are working to commercialize a novel class of therapeutics, termed 'molecular gates.' His company, Gate, is working to exploit a previously uncharted avenue in cell biology—the secretory translocon—for therapeutic intervention. This approach has the potential to combat diseases otherwise resistant to existing therapeutics.

Jordi also imparts valuable insights on the power of platform-based problem-solving and team building.

Mario Schlosser, cofounder, former CEO, and current President of Technology at Oscar Health, joins Julie Yoo of Bio + Health.

The conversation explores how AI advancements can revolutionize traditional healthcare models by enhancing efficiency, personalizing care journeys, and integrating real-time data insights. Mario also discusses "benefit-less" benefit designs, where healthcare plans learn from and adapt to individual consumer patterns, at least theoretically leading to the holy grail of better health outcomes and cost savings.

Miriam Vogel, President and CEO of EqualAI, cohost of the podcast In AI We Trust?, and Chair of the National AI Advisory Committee, joins Vijay Pande of Bio + Health.

Miriam offers pragmatic insights for founders on ethical integration of AI. She also outlines concrete steps to build trustworthy AI. Finally, she discusses the regulatory landscape and the state of politics around AI today.

AI trailblazer Suchi Saria, in conversation with Vijay Pande, sheds light on the winding path that led her to launch Bayesian Health, a bold effort to infuse intelligence into clinical workflows. With infectious optimism, Suchi describes her vision to create "clinical copilots" that augment human capabilities and unburden care teams. Yet she acknowledges the delicate balancing act required to implement AI ethically, emphasizing the need for continuous monitoring and oversight to build trust. For founders navigating uncertain regulatory seas, Suchi offers a lifeline, suggesting that regulation done right may actually accelerate adoption by fostering confidence. Through candid reflections on lessons from the trenches, Suchi provides a rare glimpse into the mind of an innovator who has one foot planted in research rigor and the other striding towards real-world impact. Steeped in over 20 years of experience, her insights map guideposts for founders aspiring to positively disrupt healthcare with AI.

Fei-Fei Li, PhD,  Professor in the Computer Science Department at Stanford University, and Co-Director of Stanford’s Human-Centered AI Institute, joins Bio + Health founding partner Vijay Pande.

In this candid conversation, Li unfolds her transformation from a young immigrant to an influential figure in AI. The conversation explores the birth of ImageNet, a pivotal step that bridged the gap between visual intelligence and accessible AI technology. They delve into the notion of a 'Dignity Economy,' hinting at a future where technology serves to elevate human experience rather than undermine it. Li also touches on the delicate balance between relentless innovation and life's humble pursuits. This episode peels back the layers on the human side of AI, offering a rare glimpse into the personal and professional realms of a pioneer shaping the AI landscape.

Check out her new book, out November 7, 2023, here: https://us.macmillan.com/books/9781250897930/theworldsisee

Evan Feinberg, PhD, founder and CEO at Genesis Therapeutics, joins Vijay Pande of Bio + Health.

Together, they talk about how Evan’s work in the lab (ironically, Vijay's lab at Stanford!) translated to the creation of Genesis, which is tackling the problem of drug discovery through AI. They also discuss how the Genesis team is building specifically to carry on work at the intersection of ML, biotech, and chemistry.

Olga Troyanskaya, a professor in the department of computer science at Princeton and Deputy Director for Genomics at the Flatiron Institute's Center for Computational Biology, joins Vijay Pande, founding partner of a16z Bio + Health.

Together, they talked about Olga's background and how she got involved in genomics, as well as how evolving biotechnologies have improved scientists’ ability to see different views of the cell. They also discussed social determinants of health, and how, in the future, studies of genomics and SDoH might pave the way to treatment options.

Peter Shalek, a Chief Product Officer, currently at Stellar Health and formerly at AbleTo, and Reena Pande, currently a strategic advisor and formerly the Chief Medical Officer of AbleTo, join Julie Yoo and Justin Larkin of a16z Bio + Health. 

As Julie mentions during the episode, there’s international relations, and then there’s CMO/CPO relations. Peter and Reena talked about working together to improve their relationship and the outcomes of their teams, and they get granular about what worked and what didn’t.

Today’s podcast is for healthcare builders who are struggling to balance clinical with product. They talk through real examples and tactical advice.

Note that due to technical difficulties, the audio quality of this episode may vary.

Surya Ganguli, PhD, an associate professor at Stanford University and a neural dynamics researcher, joins Vijay Pande of Bio + Health.

Together, Surya and Vijay chatted about the interpretability of AI and how the AI black box could someday become a "clear box." They also talk through a future of AI-augmented humans, and where humans might excel compared with AI. 

This episode is live from our recent AI Revolutionaries (AIR) conference. In this episode, Daphne Koller, founder and CEO at insitro and AI expert, chats with Vijay Pande of Bio + Health.

You can check out the full conversation with video and transcript at https://a16z.com/digital-biology/. 

Today's episode features Aviv Regev, PhD, the Head and Executive VP of Genentech Research and Early Development, and founding co-chair of the Human Cell Atlas. She is joined by Vijay Pande of Bio + Health.

Together, Aviv and Vijay talk about how Aviv's love of both abstractions and details led her to biology, how CRISPR really set the field into motion, and how AI could transform the process of biological and medical discovery.

Andrew Ng, PhD, a distinguished authority in the field of AI, is known for founding DeepLearning.AI and multiple other ventures. He also co-founded and led Google Brain and serves as an Adjunct Professor in Stanford University's Computer Science Department. In this episode, he is joined by Vijay Pande, founding partner of a16z Bio + Health.

Andrew has thought deeply about the implications of integrating AI into many areas of our lives, going so far as to put out a public social media call for people who believe AI is dangerous to speak with him. He and Vijay discussed this, as well as how AI could become foundational to many industries — and what needs to happen to make that future a reality.

Carl June, MD, an immunologist and oncologist at the University of Pennsylvania, joins Jorge Conde, general partner at a16z Bio + Health.

Together, Carl and Jorge talked about Carl's pioneering work in CAR T therapy — including the terrifying moment where he thought he had accelerated one of his patient's deaths, how he started working in human immunology, and his take on where cancer treatment is headed next.

Dan Nomura  is a distinguished professor at UC Berkeley and an Investigator at the Innovative Genomics Institute, specializing in Chemical Biology and Molecular Therapeutics. He serves as the Director of the Novartis-Berkeley Translational Chemical Biology Institute and founded Frontier Medicines and Vicinitas Therapeutics. He’s also a16z Bio+Health’s newest advisory partner.

In this episode, Dan joins general partner Jorge Conde and investment partner Becky Pferdehirt to discuss how he got started working in chemical biology and chemoproteomics and his  experience founding companies, along with leading lab and pharma collaborations.

In this exclusive conversation from the Bio + Health BUILD summit, founding partner Ben Horowitz sits down with general partner Jorge Conde. They discuss everything from the inspiration behind Ben’s book The Hard Thing About Hard Things, how the open Internet was secured, the difference between wartime and peacetime CEOs, scaling culture, and understanding how bio and healthcare differs from other forms of technology.

Together, Lloyd and Vijay chatted about how AI could change the practice of medicine, and what the implications are for medical students now and in the future. 

join Lloyd and Vijay as they discuss AI and medical education—from how students learn to how doctors become licensed.

Together, Margaret and Julie chatted about Margaret’s background — and how she taught herself to program — her time at Devoted, and the advice she gives to healthtech CEOs.

Join Margaret and Julie as they discuss building a developer-friendly environment in healthcare, introducing engineers to the complexity of the industry, and how AI might affect engineering in healthcare.

Together, Vijay and Zak talked about having been through AI winters and hype cycles before, and why they think this time could be different. They also talked about how AI could revolutionize the healthcare model — what Zak calls the “flipped clinic.”

Join Zak and Vijay as they talk about how AI could flip the clinic, how foundation models could quickly transform the discovery and development of drugs, and how Zak thinks about the future.

Dan Rosenthal, a provider network expert and the newest advisory partner for a16z Bio + Health, joins Julie Yoo, general partner.

Together, they talk about the 101 and 201 of provider networks, tactical advice for digital health builders, and how AI could theoretically change the way networks are constructed.

The holy grail of company building is finding product-market fit. But what most people don’t tell you is that once you’ve found it, product-market fit brings its own set of challenges, particularly when it comes to scaling rapidly and hiring the right executives at the right time.

Drawing from their extensive experiences, a16z cofounder Ben Horowitz and Databricks cofounder and CEO Ali Ghodsi sit down with Steph Smith of the a16z podcast to talk about the hardest things about executive hiring and firing, and what is at stake.

They dive into the common reasons an exec fails, why sometimes micromanagement is a good idea, and the difference between someone who has written a playbook and someone who has only run one.

When Greg started out in science, he heard other researchers referring to certain targets as “undruggable.” In response, he’s devoted his life to drugging the undruggable, cofounding the field of chemical biology along the way. After a robust career founding multiple biotechs and serving as the cofounder, chairman, and CEO of FogPharma, he is the newest venture partner at a16z Bio + Health.

Join Greg, Vineeta, and Jorge as they talk about Greg's upbringing and career, and how he thinks about the field today.

After his own health scare, Jeffrey got obsessed with how MRIs work—and decided that they were too unscientific to really track human health over time. In response, he built a new kind of imaging, creating a “digital twin” that can be tracked over time. And if health can be tracked over time, in theory it could eventually become as forecastable as the weather.

Join Jeffrey and Vijay as they talk about human imaging, health forecasting, and how a digital twin could change healthcare.

AI has the potential to save the world — that’s the thesis of Marc’s most recent article, linked below. This episode was recorded right after Marc published his article, live from a16z Bio + Health’s first summit.

Join Marc and Vijay as they talk about how AI can save the world, and where it can go wrong.

Additional reading:

• Why AI Will Save the World

AI is not just a sci-fi concept anymore; it's being woven into the fabric of healthcare, revolutionizing everything from research to patient care. It has the potential to create more streamlined and efficient processes. The challenge now is how we adapt and regulate this ever-evolving technology, while ensuring safety and trust.

Amy Abernethy, former Principal Deputy Commissioner at the FDA and now the President of Product Development and Chief Medical Officer at Verily Life Sciences, joins Vijay Pande, founding partner of a16z Bio + Health, to discuss.

In this episode, taken from a live a16z event, Bio + Health general partner Vineeta Agarwala moderates a panel of UCSF faculty founders, including Michelle Arkin, Jimmie Ye, and Natalia Jura (full bios below). Together, they discuss fundraising, the decision to stay in or leave  academia after founding a company, and their tips for managing the IP process. 

Michelle Arkin is a professor of pharmaceutical chemistry at UCSF, chair of the Department of Pharmaceutical Chemistry, and a co-director of the Small Molecule Discovery Center at UCSF. Professor Arkin is also a cofounder of both Elgin Therapeutics and Ambagon Therapeutics.

Jimmie Ye is an associate professor of medicine at the Institute for Human Genetics at UCSF and an affiliate investigator at Gladstone Institutes. He is also the cofounder of Dropprint Genomics and Survey Genomics.

Natalia Jura is a professor in the Department of Cell and Molecular Pharmacology and an investigator at the Cardiovascular Research Institute at UCSF. Professor Jura is also an associate director of the Quantitative Biosciences Institute. She is a cofounder of Rezo Therapeutics.

Today’s episode is with Mark Cuban, founder of multiple businesses, owner of the Dallas Mavericks, one of the sharks on Shark Tank, and cofounder of the Mark Cuban Cost Plus Drug Company. He is joined by Vijay Pande, founding partner of a16z Bio + Health. 

Together, they talk market forces in healthcare, the importance of trust to patients, and Mark’s ideas to tackle the Gordian knot that is American healthcare.

Today’s episode is a cross-post with the a16z podcast. It features founders—Chris Severn, Florian Otto, Andrew Adams, Jade Chan, Jimmy Chen, and Fay Rotenberg—chatting with a16z podcast host Steph Smith, about how they're trying to reinvent the healthcare system, using fintech.

Additional reading:

• https://a16z.com/healthcare-meets-fintech/
• https://a16z.com/2023/02/07/healthtech-x-fintechs-biggest-prize/
• https://a16z.com/2022/06/01/payvidors-unbundled-opportunities-in-healthcare-fintech/

Today’s episode is with Greg Meyers, EVP and Chief Digital and Technology Officer at Bristol Myers Squibb (or BMS). He is joined by a16z Bio + Health general partner Jorge Conde.

Together, they talk about how AI could transform drug discovery and development at a large biopharma company—and how a company might have to adapt to harness AI; modalities they’re excited about; and Greg’s do’s and don’ts for startups looking to partner with a company like BMS.

Healthcare payments are difficult, confusing, and opaque. But Julie and David discuss the ways that technology could change that for the better, and where they see the greatest opportunity for founders to solve big challenges.

Additional reading:

• https://a16z.com/healthcare-meets-fintech/
• https://a16z.com/2023/02/07/healthtech-x-fintechs-biggest-prize/
• https://a16z.com/2022/06/01/payvidors-unbundled-opportunities-in-healthcare-fintech/

In this episode, a16z Bio + Health investment partner Becky Pferdehirt chats with Robbie Majzner, an Assistant Professor of Pediatrics in the Division of Hematology and Oncology at Stanford, and co-founder of Link Cell Therapies.

Together, they discuss Robbie's recent paper published in Nature. The paper outlines a new approach to develop logic gated intracellular network, or LINK CAR T cells, as a means to simultaneously enhance both the safety and efficacy of these novel cell therapies.

Additional reading:

• Co-opting signalling molecules enables logic-gated control of CAR T cells, Nature

Today’s episode is with Magi Richani, founder and CEO of Nobell Foods. She is joined by a16z Bio + Health general partner Vijay Pande.

Together, they talk about the details of engineering plants to create the future of food, why Nobell started with soybeans to produce their cheese, and her dream of finding a cheese pizza—with Nobell cheese—at any pizza shop across the country.

This is a crossover episode with The Bioverge Podcast, hosted by Neil Littman. Neil is joined by Vineeta Agarwala, general partner at a16z Bio + Health. Together, they chat about Vineeta's dual role as a clinician and investor, the adoption curve of digital therapeutics, how Vineeta thinks about platforms and a modular, engineering-driven approach to biotech, and much more.

Today’s episode is with a16z’s American Dynamism team: Katherine Boyle and David Ulevitch. Katherine is a general partner focused on national security, aerospace and defense, public safety, housing, education, and industrials. David is a general partner focused on companies promoting American dynamism, as well as enterprise and SaaS companies. They are joined by a16z Bio + Health general partner Vijay Pande, and editorial lead Olivia Webb.

Together, we talk about the idea behind American Dynamism, how the American Dynamism team thinks about building within highly regulated industries, how trust is key to the procurement process, and how the team thinks about the regulation of AI.

Today’s episode is with Sean Duffy, cofounder and CEO of Omada Health. He is joined by a16z Bio + Health general partner Julie Yoo and investment partner Jay Rughani. Together, they talk about Sean’s three rules of partnerships, how Omada plans for large-scale implementation, and how Sean thinks about structuring the economic model of the partnership.

This episode was recorded as part of our research into our forthcoming Go to Market Playbook, focused on channel partnerships. Stay tuned for that, which we’ll be releasing in the coming days at a16z.com/digital-health-builders.

This week, we’re releasing two episodes about all things channel partnerships. Today’s episode is with Florian Otto, cofounder and CEO of Cedar. He is joined by a16z Bio + Health general partner Julie Yoo. 

In today’s episode, Florian and Julie talk about how Cedar began engaging with channel partners, what happens when things go wrong, and how the Cedar team is structured to implement and nurture these partnerships.

This episode was recorded as part of our research into our forthcoming Go to Market Playbook, focused on these partnerships. Stay tuned for that, which we’ll be releasing in the coming days at a16z.com/digital-health-builders. 

In this episode, Daphne Koller, founder and CEO of insitro—as well as the co-founder of Coursera, a MacArthur Award winner, and a former professor in the department of computer science at Stanford University—chats with a16z Bio + Health founding partner Vijay Pande. 

Together, they talk about Daphne’s career journey, how Daphne thinks about the last few decades of progress in AI, and how insitro leverages artificial intelligence and machine learning to explore biology through new models of discovery.

Today marks the reboot of our journal club series, so you can look forward to seeing these episodes as part of our regular feed. 

This episode is a scientific deep dive on recent research published by Ben Cravatt, Professor in the Department of Chemistry at the Scripps Research Institute and co-founder of a diverse suite of chemoproteomic companies such as Vividion and Belharra Therapeutics, and Gene Yeo, Professor of Cellular and Molecular Medicine at the University of California, San Diego and co-founder of Locana Bio, Eclipse Bio, and Trotana Therapeutics. 

Ben and Gene are joined by Vineeta Agarwala, general partner at a16z Bio + Health, and bio deal team member Bryan Faust. 

Together, they’ll discuss some unexpected mechanistic results of finding covalent binders to a class of proteins that we are just starting to understand — RNA binding proteins — and the subsequent translational implications that they described in a recent paper published by the Cravatt and Yeo labs in Nature Chemical Biology. The paper outlines a potentially new therapeutic approach that uses small molecules to fundamentally rewire transcriptional networks in cancer cells.

Additional reading:

• Remodeling oncogenic transcriptomes by small molecules targeting NONO

In this episode, a16z Bio + Health general partner Julie Yoo chats with Bassett Healthcare Network president and CEO Tommy Ibrahim. Together, they talk about Tommy's journey from practicing physician to health system leader, the challenges facing rural healthcare today, and how Tommy thinks about partnering and integrating with digital health entrepreneurs as a hospital executive.

In this episode from the archives, originally published in February 2021, Jennifer Doudna, who won the 2020 Nobel Prize for the co-discovery of CRISPR-Cas9 with Emmanuelle Charpentier, chats with Vijay Pande, general partner at a16z Bio + Health. Together, they discuss  the future of biology, whether discovery itself can be engineered and industrialized, and how biology can shape our future.

In this episode, Jorge Conde, general partner at a16z Bio + Health, talks with Josh Mandel-Brehm, founding CEO of CAMP4. Together, they talk about how CAMP4 focuses on regulatory RNA (and what that means), how Josh thinks about platform companies, and what he’s learned as the founding CEO of the company.

In today's episode, Sam Corcos, CEO and cofounder of Levels Health, chats with Vijay Pande, general partner at a16z Bio + Health, about how Sam cofounded Levels, how to decide who becomes CEO if you have multiple cofounders, Levels’ approach to company culture and meetings, and how Sam thinks about the complicated world of healthcare regulations.

Additional reading:

• Levels' public investor updates, as mentioned by Sam in the episode

In this episode, Kurt Adams, CEO of Optum Financial, chats with Daisy Wolf, investment partner for a16z Bio + Health, and Marc Andrusko, investment partner for a16z focused on fintech, about Optum Financial, how consumers might interact with fintech while seeking care or participating in healthy behaviors, and what a fintech-integrated version of the healthcare experience could look like.

Additional reading from us:

• Payvidors, Unbundled: Opportunities in Healthcare Fintech
• Healthtech x Fintech’s Biggest Prize: The Financial Operating System for Healthcare 

In this episode, Joe Lonsdale, founder and managing partner at 8VC, joins Vijay Pande, founding partner of a16z Bio + Health, and Olivia Webb, editorial lead. Together, we talk about what factors lead to innovation vs stagnation, monopoly power in healthcare, and policy ideas to incentivize change, growth, and dynamism.

In this episode, Julie Yoo, general partner, and Jay Rughani, investment partner at a16z Bio + Health, talk to Kate Ryder, founder and CEO of Maven; Amanda Rees, cofounder and CEO of Bold Health; and Bill Porter, VP and GM, International, of Butterfly Network, about their B2C2B go-to-market motion.

This episode was originally recorded in late 2021, but it's still really relevant to builders, especially those exploring the B2C2B go-to-market motion. We talked about B2C2B in-depth in the second chapter of our Digital Health Builders Founder's Playbooks, also available at: https://a16z.com/digital-health-builders/

And finally, our last chapter of the Founder's Playbooks is coming soon, so hit subscribe and stay tuned!

In this episode, Kevin Parker, cofounder and CEO of Cartography Biosciences, joins Jorge Conde, general partner at a16z Bio + Health, and Olivia Webb, editorial lead, to discuss immuno-oncology, current challenges in drug targeting, and the mechanisms Cartography and others are using to advance the field of immunotherapeutics. 

This episode dives deep into the science behind immuno-oncology — but you don't necessarily have to be a scientist to follow along. You'll never look at a smoothie the same way again.

In this episode, Kristen Fortney, cofounder and CEO of BioAge, joins Vijay Pande, founding partner of a16z Bio + Health, and Olivia Webb, editorial lead, to discuss the biology of aging, how she started a company, and some fun things — like how long a hypothetical venture capitalist can expect to live.  

Additional reading:

• Greg Egan, whose writing inspired Kristen, has a list of his books on his website

In this episode, Paul Keckley, the managing editor of the Keckley Report and a health policy expert, joins Julie Yoo, general partner at a16z, and Olivia Webb, editorial lead at a16z. 

Together, they talk about how payors and providers are reacting to changing tailwinds,  how employers are demanding more in today's market, the opportunities and challenges for startups in a consolidated industry, and what the next few years of health policy might bring. 

Additional reading:

• The Keckley Report

Jakob Uszkoreit and Vijay Pande discuss all things AI — from Jakob's time at Google Brain, to how humans (and computers) process language, to Inceptive’s belief in the promise of RNA, and how Jakob believes we’re entering inflection point territory. 

You can also find a full transcript of this episode on our website.

Additional reading:

• Attention is All You Need
• A Decomposable Attention Model for Natural Language Inference

The last few months have seen dramatic—almost magical—applications of expert generative AI released to the public. (One of those applications, incidentally, was in editing the sound mix of this episode.)

But what does this mean for healthcare and bio? Vijay Pande, founding partner of a16z Bio + Health, and Marc Andreessen, cofounder of a16z, sat down for a wide-ranging discussion on AI as an additive superpower…for healthcare as well as screenplays, music, and more.

You can also watch the full episode on our YouTube channel: https://www.youtube.com/@a16z.

From initial inspiration in a sci-fi novel to the current state of “designing biology” in cultivated meat, SCiFi Foods cofounder and CEO Joshua March chats with Bio + Health general partner Vijay Pande and editorial lead Olivia Webb about company building, developing and iterating in biology, and what the future of cultivated meat could be.

AI is here...so why isn't it in every clinic? 

Eric Topol talks with a16z Bio + Health general partners Vijay Pande and Vineeta Agarwala and editorial lead Olivia Webb about what's taking so long, where AI can help patients and providers the most, what needs to happen to speed up adoption, and whether data or policy is more likely to be an obstacle. 

Eric has written extensively about AI in healthcare, including in his most recent book Deep Medicine: How Artificial Intelligence Can Make Healthcare Human Again. He also writes a Substack focused on Covid research, called Ground Truths, linked below.  Finally, as a marker of how AI and AI adoption has (and hasn't) changed over the last few years, check out Eric's 2019 interview with Vijay on the a16z Podcast, also linked below.

• Ground Truths - https://erictopol.substack.com/
• a16z Podcast: AI and Your Doctor, Today and Tomorrow - https://a16z.com/2019/06/13/ai-doctor-deep-medicine-topol/

Perhaps no area of healthcare has undergone such a rapid shift as telehealth during the Covid pandemic. But as the world emerges from the public health emergency, it's an open question what will happen with the regulatory aspects of telehealth. Daisy Wolf, deal partner at a16z Bio + Health, talked to Sarah Thomas, general counsel at Sameday Health, about asynchronous telehealth, working with regulators, how counsel thinks about inducements, and more.

In this episode, a16z Bio+Health general partner Vineeta Agarwala spoke with Bobby Franklin, the president and CEO of the National Venture Capital Association, about whether healthcare can be a bipartisan topic, how regulation can potentially enable care models at scale, and the opportunities for collaboration between DC and startups.

What’s up with the drug channel? Julie Yoo, a general partner at a16z Bio+Health, joins Adam Fein, the CEO of Drug Channels Institute, and Olivia Webb, the editorial lead for a16z Bio+Health, to discuss this question. We talk about PBMs, the 340B drug program, some of the startups working within and around the primary drug channel, and whether there’s room for entrepreneurs to build in such a consolidated space.

For additional reading, see some of Adam’s work on his blog, Drug Channels:

• https://www.drugchannels.net/2022/08/the-340b-program-climbed-to-44-billion.html
• https://www.drugchannels.net/2022/04/the-top-pharmacy-benefit-managers-of.html
• https://www.drugchannels.net/2020/05/insurers-pbms-specialty-pharmacies.html
• https://www.drugchannels.net/2020/08/how-goodrx-profits-from-our-broken.html
• https://www.drugchannels.net/2022/10/five-surprising-facts-about-goodrx-and.html

Can a game be both fun and therapeutic? Vijay Pande, the first employee at Naughty Dog Software and a current Bio+Health general partner at a16z, joins Jon Lai, a Games general partner, and Olivia Webb, the editorial lead for Bio+Health at a16z, to discuss this question. We talk about what constitutes a game, how games and bio can intersect, and what we called the “healthy dessert” problem — the challenge of building a game that’s both fun and therapeutic.

Additional reading discussed during the episode:

• a16z general partner Chris Dixon’s essay “Strong and weak technologies” 

In Bio Eats World's Journal Club episodes, we discuss groundbreaking research articles, why they matter, what new opportunities they present, and how to take these findings from paper to practice. In this episode, Stanford Professor Carolyn Bertozzi and former Bio Eats World host Lauren Richardson discuss the article "Lysosome-targeting chimaeras for degradation of extracellular proteins" by Steven M. Banik, Kayvon Pedram, Simon Wisnovsky, Green Ahn, Nicholas M. Riley & Carolyn R. Bertozzi, published in Nature 584, 291–297 (2020).

Many diseases are caused by proteins that have gone haywire in some fashion. There could be too much of the protein, it could be mutated, or it could be present in the wrong place or time. So how do you get rid of these problematic proteins? Dr. Bertozzi and  her lab developed a class of drugs -- or modality -- that in essence, tosses the disease-related proteins into the cellular trash can. While there are other drugs that work through targeted protein degradation, the drugs created by the Bertozzi team (called LYTACs) are able to attack a set of critical proteins, some of which have never been touched by any kind of drug before. Our conversation covers how they engineered these new drugs, their benefits, and how they can be further optimized and specialized in the future.

On this episode, we discuss three recent papers out in Nature Medicine this week, all examining the deployment of Bayesian Health's AI platform in a clinical setting: Two prospective studies focused on clinician adoption and patient outcomes, and one interview-based study focused on clinical experiences with Bayesian’s AI platform, TREWS. 

First, we get into detail about the design and results of the prospective studies, then we talk about TREWS in context with other clinical decision support tools. Finally, we talk about clinicians’ attitudes toward adoption. 

Featuring Dr. Suchi Saria, PhD, and the CEO of Bayesian Health; Dr. Neri Cohen, MD, PhD, as well as a collaborator with Bayesian Health; and Dr. Vineeta Agarwala, MD, PhD, and a16z general partner. Hosted by Olivia Webb.

On this episode, we are taking a pulse-check on the state of the intersection between biology, healthcare, and technology with two scientists that sit at another intersection, that of academia and industry: Alexander Marson and Patrick Hsu, who are professors at UC San Francisco and UC Berkeley, respectively, who both use cutting edge gene editing technology to create next generation therapies, and are prolific biotech founders. Patrick also recently co-wrote an article on Fast Grants, one of the speediest sources of emergency science funding during the pandemic, which you can read about on our media site Future.com. But in this conversation, Patrick and Alex discuss — with a16z bio general partner Jorge Conde — what is different about this moment in bio. 

On today’s episode we are discussing the results and implications of a recent study that describes the creation of a new set of tools to turn off or on any region in the genome with high specificity. Host Lauren Richardson and a16z general partner Vijay Pande are joined by the senior author of the article, “Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing”, Jonathan Weissman, Professor of Biology at the Whitehead Institute at MIT. Jonathan talks about how they developed these tools using the CRISPR gene editor as a backbone, the advantages of modulating the epigenome as opposed to the genome, and the various applications — both in the lab and in the clinic — for these epigenome editors. 

On today’s episode, we are making the full arc from the theoretical and borderline philosophical to the applied. Let’s start with the theory: embodied intelligence posits that the body, or the physical form, plays an active and significant role in shaping an agent's mind and cognitive capacities. For example, human intelligence is not just the function of our brain, but a combination of our brain, our body, and the environment in which we exist. But when it comes to designing artificial intelligence (AI), a physical form and an environment are typically not part of the equation. It’s a disembodied cognition. Our guests, Li Fei-Fei and Surya Ganguli of the Stanford Institute for Human-Centered AI, set out to develop what they call an “evolutionary playground” to explore the development of embodied intelligence in AI and its connection with the environment and with learning using in silico experiments. They discuss with a16z general partner Vijay Pande and host Lauren Richardson how they created a suite of virtual environments in which agents evolve through a process that mimics aspects of Darwinian evolution. These agents, called the unimal, or universal animal, start off as a central node, and with each generation can add or subtract limbs and change various properties of their physical forms, like how flexible their joints are. Just like in real evolution, different forms arose based on the particularities of the environment, but what is really exciting is what Fei-Fei, Surya, and colleagues discovered about the intelligence encoded in some of these forms, such as an increased ability to learn a novel task. Which brings us to the applied section of our discussion. These results provide new insights for how we think about designing robots capable of performing unique tasks, and for understanding the possible limitations of disembodied AI models, like GTP-3. 

The results are described in the pre-print "Embodied Intelligence via Learning and Evolution" posted on arXiv.org. 

And watch the unimal evolve here!

Today’s episode is all about the history and future of infusing tech into healthcare with the goals of improving outcomes and lowering costs, and features one of the leading voices in this field, Jonathan Bush. Jonathan, aka JB, started his career in healthcare as an ambulance driver and army medic, and then met Todd Park, another Bio Eats World guest, while at Booz Allen. Together they founded Athena Women’s Health Clinic, which evolved from a clinic specializing in maternity care to one of the original digital health companies providing cloud-based services and point-of-care clinical and back office tools for providers, later called Athenahealth. In this conversation with a16z general partner Julie Yoo — who is also a digital health builder — JB discusses this evolution, how it mirrors the bigger trend shifts in healthcare, and how it has informed the mission of his new company, Zus, which he compares to a Github for healthtech. JB and Julie cover what’s changed since the launch of Athena, 25 years ago, how to disrupt an entrenched system like healthcare, the role regulation plays in the space, and the under appreciated importance of bottom-up sales. 

Please note there is some colorful language used in this episode, in case you have young children listening.

Genetic testing is on the cusp of a major revolution, which has the potential to shift not just how we understand our risk for disease, but how we practice healthcare. In the clinic today, genetic testing is used only in cases where we know that mutations have big impact on physiology (BRCA mutations in breast cancer, for example). But our knowledge of how our genetics influences our risk for disease has evolved, and we now know that many (tens of thousands to even millions) small changes in our genes, each of which individually has a tiny effect, combine to influence our risk profile. This new appreciation — coupled with powerful statistical methods and massive datasets — has fueled the creation of a new tool to quantify the risk of a broad range of common diseases: the polygenic risk score. On this episode, which originally aired on January 18, 2021, host Lauren Richardson (@lr_bio) is joined by Peter Donnelly, (@genemodeller Professor of Statistical Science at the University of Oxford and the CEO of Genomics PLC,) and Vineeta Agarwala, (@vintweeta physician-scientist and general partner at a16z), to discuss these scores and how they can reshape healthcare, away from a paradigm of treating illness and towards prevention and maintenance of health.

When it comes to healthcare, the topic of how expensive it is and what we can do to lower costs is always top of mind. One area with particularly steep costs is the emergency department. These are hospital departments that can take care of pretty much anything from a cut to a car wreck. But going to an emergency department for something as simple as a cut can result in a high bill for both the patient and the insurer. This is where the urgent care center comes in. Urgent care centers are walk-in clinics focused on caring for minor illnesses and injuries — or in medical speak — low acuity conditions. They are way less expensive than a trip to the emergency department, so funneling these low acuity visits from the emergency department to urgent care centers should result in lower healthcare costs… right? On today’s episode, host Lauren Richardson is joined by a16z general partner Vineeta Agawala and bio deal team member Justin Larkin (who are both medical doctors and experts in healthcare), to discuss new research published in the journal Health Affairs, examining this key assumption. The conversation covers the issues with care utilization and care navigation, how urgent care centers impact healthcare costs, and the implications of these results for builders in the digital health space. 

The article at the center of today's episode is: "Urgent Care Centers Deter Some Emergency Department Visits But, On Net, Increase Spending" by Bill Wang, Ateev Mehrotra, and Ari B. Friedman, published in Health Affairs.

If there is one rule in biology, it is that there is an exception to every rule. This includes even the basic biochemistry of DNA, which was once thought to be universal. On this episode, host Lauren Richardson and Judy Savitskaya (a16z bio deal team member and synthetic biology expert), discuss the results and implications three related articles co-published in Science, which all advance our understanding of a very unique kind of DNA. 

If you open any biology text book, it will say that the genetic code is made up of 4 bases: Adenine, Thymine, Cytosine, and Guanine, or ATCG. But, back in 1977, scientists discovered a phage — the technical term a virus that infects bacteria — that encodes its genome in ZTCG. Z is a derivative of A that has an extra amino group tagged on, and while that may sound minor, it changes some of the key properties of DNA. These three new articles seek to understand how Z is made and how it is incorporated into DNA. This is essential information for taking Z from a weird, wild bio story into a practical application. The conversation covers what makes Z different than other bases, what these three articles reveal about the synthesis and polymerization of Z, and how we can use use Z in a wide range of applications, from bio-containment to new therapeutics to DNA storage.

The three articles discussed are:

"A widespread pathway for substitution of adenine by diaminopurine in phage genomes" by  Yan Zhou, Xuexia Xu, Yifeng Wei, Yu Cheng, Yu Guo, Ivan Khudyakov, Fuli Liu, Ping He, Zhangyue Song, Zhi Li, Yan Gao, Ee Lui Ang, Huimin Zhao, Yan Zhang, and Suwen Zhao

"A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes" by Dona Sleiman, Pierre Simon Garcia, Marion Lagune, Jerome Loc’h, Ahmed Haouz, Najwa Taib, Pascal Röthlisberger, Simonetta Gribaldo, Philippe Marlière, and Pierre Alexandre Kaminski

"Noncanonical DNA polymerization by aminoadenine-based siphoviruses" by  Valerie Pezo, Faten Jaziri, Pierre-Yves Bourguignon, Dominique Louis, Deborah Jacobs-Sera, Jef Rozenski, Sylvie Pochet, Piet Herdewijn, Graham F. Hatfull, Pierre-Alexandre Kaminski, and Philippe Marliere

This episode was recorded in March of 2019 to celebrate the 20th anniversary of Folding at Home, the distributed computing project for simulating protein dynamics, and originally aired on The a16z Podcast. Folding at Home is run on millions of devices, is the world’s largest supercomputer, and tackles some of biology’s toughest problems, including COVID-19.

Proteins are molecular machines that must first assemble themselves to function. But how does a protein, which is produced as a linear string of amino acids, assume the complex three-dimensional structure needed to carry out its job? 

That's where Folding at Home comes in. Folding at Home is a sophisticated computer program that simulates the way atoms push and pull on each other, applied to the problem of protein dynamics, aka "folding". These simulations help researchers understand protein function and to design drugs and antibodies to target them. 

Given the extreme complexity of these simulations, they require an astronomical amount of compute power. Folding at Hold solves this problem with a distributed computing framework: it breaks up the calculations in the smaller pieces that can be run on independent computers. Users of Folding at Home — millions of them today — donate the spare compute power on their PCs to help run these simulations. This aggregate compute power represents the largest super computer in the world: currently 2.4 exaFLOPS!

Folding at Home was launched in the lab of Vijay Pande at Stanford. In this episode, Vijay (now a general partner at a16z) is joined by his former student and current director of Folding at Home, Greg Bowman, an associate professor at Washington University in St. Louis, and host Lauren Richardson. The conversation covers the origins of the Folding at Home project and the scientific and technical advances needed to solve the complex protein folding and distributed computing problems.

To find out more about how Folding at Home is contributing to the COVID-19 pandemic, check out the recenty published article from the Bowman lab, "SARS-CoV-2 simulations go exascale to predict dramatic spike opening and cryptic pockets across the proteome", published in Nature Chemistry.

On the path from scientific discovery to new drug, the clinical trial is a huge — and critical — hurdle. Clinical trials are themselves experiments, and to make sure that they are doing the best possible job at determining the safety and efficacy of the new drug, we need to be able to do experiments on those experiments. But how do you do that in such a highly regulated space? 

Host Lauren Richardson talks to James Zou, Assistant Professor of Biomedical Data Science at Stanford University, and a16z general partner Vineeta Agarwala, physician and expert on real world data in healthcare, about new research from the Zou lab that uses AI-powered simulations of clinical trials and real world patient data to understand how different designs influence trial outcomes. In particular, looking for designs that can make trials more inclusive, which is key for getting patients access to potentially life-saving care and for running trials efficiently. The conversation covers the inherited rules and assumptions governing which patients can participate in trials, how Dr. Zou, lead author Ruishan Liu, and colleagues combined real world data and computer simulations to challenge these assumptions via a data-driven approach, and how this can inform smarter trial design. 

The article at the center of today's episode is: "Evaluating eligibility criteria of oncology trials using real-world data and AI" by Ruishan Liu, Shemra Rizzo, Samuel Whipple, Navdeep Pal, Arturo Lopez Pineda, Michael Lu, Brandon Arnieri, Ying Lu, William Capra, Ryan Copping & James Zou, published in Nature.

They say you should never judge a book by its cover, but can you judge a cell by its shape? On this episode, host Lauren Richardson is joined by Maddison Masaeli (CEO and cofounder of Deepcell), and a16z general partner Vijay Pande (whose lab at Stanford focused on the development of novel computational methods for simulating biology), to discuss what we can learn by characterizing a  cell's shape — also known as its morphology. We've long appreciated that morphology can be used to discriminate cells, for example, cancer cells look very different than the surrounding tissue and can be spotted in a biopsy, and the various classes of immune cells all have distinct appearances. But characterization of cell shape — and what it can tell us about the underlying biology of those cells and the health of the organism that they came from — has been stuck in the low-tech, manual, qualitative era. To unlock the potential of cell morphology, Maddison and her colleagues are leveraging the power of artificial intelligence to assess and learn from cell images to create a quantitative, scaleable technology. The conversation covers the untapped potential of studying cells and their shape, how Maddison and her team at Deepcell are building an AI with seemingly limitless applications, and where this technology could take us.

Neuroscientists have long been trying to determine what happens in the brain during sleep, but to date, they have overlooked a key player: astrocytes. These star-shaped cells were once thought to be the glue that held the brain together, but we are now beginning to appreciate their importance in a variety of brain functions. In this episode, host Lauren Richardson talks to Kira Poskanzer, Assistant Professor at the University of California, San Francisco, about her group's work showing that neurons are only one piece of the larger sleep puzzle. The conversation covers the complexity of sleep, how astrocytes control two key attributes of sleep (depth and duration), the technology and methods employed to uncover this novel mode of regulation, and how appreciating the role of astrocytes in governing sleep could lead to new insights into neuropsychiatric conditions and how to treat them. 

The article at the center of today's episode is: “Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways” by Trisha V Vaidyanathan, Max Collard, Sae Yokoyama, Michael E Reitman, and Kira E Poskanzer, published in eLife.

Today we are re-running an episode exploring a question that seems super straightforward, but that on closer examination reveals incredible complexity, and that is "how do we put the patient at the center of the healthcare system?” It almost seems counterintuitive, since aren’t patients always the center of healthcare? But healthcare is a strange industry, in that it is built with the fundamental goal of serving patients, but in many ways, the patient isn’t always the end customer of the system. In fact, the patient — and the patient’s voice — can often be lost or overlooked in the enormous, complex, convoluted business flows between a huge system of providers, in elaborate clinical work flows, in insurance coverage and reimbursements, and in high level policy debates.

In this episode, a16z general partner Julie Yoo and deal team partner Jay Rughani talk with Freda Lewis Hall — a physician who was formerly Pfizer’s Chief Patient Officer and Chief Medical Officer; and who among many other roles was appointed by the Obama Administration to the Board of the Patient-Centered Outcomes Research Institute. They discuss what happens when you rethink the entire healthcare system from the patient’s point of view, from drug development to clinical trials to care delivery. What tools and new approaches can we use to truly put the patient at the center of the healthcare system? And how do we update our Flintstones healthcare system to match our Star Wars medicines?

In 1994, 29 bald eagles were found dead at DeGray Lake in Arkansas. This mass mortality event kicked off a search for the culprit which has last over 25 years. On this episode of the Bio Eats World Journal Club, host Lauren Richardson talks to Susan B. Wilde of the University of Georgia about her group's work finally identifying the eagle killer, and revealing a complex web of ecosystem dysfunction. Solving this mystery required a fresh point of view, a wide range of techniques and technologies, and an international collaborative effort. 

Susan B. Wilde, Ph.D, Associate Professor of Aquatic Science at the University of Georgia, joins host Lauren Richardson to discuss the results and implications of the article "Hunting the eagle killer: A cyanobacterial neurotoxin causes vacuolar myelinopathy" by Steffen Breinlinger, Tabitha J. Phillips, Brigette N. Haram, Jan Mareš, José A. Martínez Yerena, Pavel Hrouzek, Roman Sobotka, W. Matthew Henderson, Peter Schmieder, Susan M. Williams, James D. Lauderdale, H. Dayton Wilde, Wesley Gerrin, Andreja Kust, John W. Washington, Christoph Wagner, Benedikt Geier, Manuel Liebeke, Heike Enke, Timo H. J. Niedermeyer and Susan B. Wilde, published in Science.

Understanding how plants have adapted to natural climate change over millions of years provides a playbook of evolutionary strategies to help us prepare for and respond to man-made climate change. On this episode, host Lauren Richardson talks to Thomas Juenger, Associate Professor at the University of Texas in Austin and co-senior author of the recent article “Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass”, published in Nature. They discuss how studying native plants — like switchgrass — can inform crop improvement strategies, the import role of switchgrass as a possible future source of biofuels, how advances in sequencing technology have unlocked the secrets hidden in plant genomes, and more.

Thomas Juenger, Ph.D, Associate Professor of Integrative Biology at the University of Texas at Austin, joins host Lauren Richardson (@lr_bio) to discuss the results and implications of the article “Genomic mechanisms of climate adaptation in polyploid bioenergy switchgrass”, by John T. Lovell, Alice H. MacQueen, Sujan Mamidi, Jason Bonnette, Jerry Jenkins, Joseph D. Napier, Avinash Sreedasyam, Adam Healey, Adam Session, Shengqiang Shu, Kerrie Barry, Stacy Bonos, LoriBeth Boston, Christopher Daum, Shweta Deshpande, Aren Ewing, Paul P. Grabowski, Taslima Haque, Melanie Harrison, Jiming Jiang, Dave Kudrna, Anna Lipzen, Thomas H. Pendergast IV, Chris Plott, Peng Qi, Christopher A. Saski1, Eugene V. Shakirov, David Sims, Manoj Sharma, Rita Sharma, Ada Stewart, Vasanth R. Singan, Yuhong Tang, Sandra Thibivillier, Jenell Webber, Xiaoyu Weng, Melissa Williams, Guohong Albert Wu, Yuko Yoshinaga, Matthew Zane, Li Zhang, Jiyi Zhang, Kathrine D. Behrman, Arvid R. Boe, Philip A. Fay, Felix B. Fritschi, Julie D. Jastrow, John Lloyd-Reilley, Juan Manuel Martínez-Reyna, Roser Matamala, Robert B. Mitchell, Francis M. Rouquette Jr, Pamela Ronald, Malay Saha, Christian M. Tobias, Michael Udvardi, Rod A. Wing, Yanqi Wu, Laura E. Bartley, Michael Casler, Katrien M. Devos, David B. Lowry, Daniel S. Rokhsar, Jane Grimwood, Thomas E. Juenger & Jeremy Schmutz published in Nature.

The search for and conjecture about alien life has evolved, from science fiction to just plain science. On this episode, host Lauren Richardson talks to Arik Kershenbaum, Ph.D, author of the new book “The Zoologist’s Guide to the Galaxy: What Animals on Earth Reveal about Aliens — and Ourselves”, about what we can conjecture about alien life, based on the laws that govern life on Earth, and the universe at large. The conversation covers big questions like: Does biology have universal properties like physics does? Will the process of evolution be distinct on different planets? Are limbs, sex, and intelligence Earth-specific features of evolution? And importantly, what does the study of alien life teach us about our place on here on earth.

Arik Kershenbaum, Ph.D, zoologist, and fellow at the University of Cambridge is the author of the new book “The Zoologist’s Guide to the Galaxy: What Animals on Earth Reveal about Aliens — and Ourselves”.  To learn more, check out https://www.zoo.cam.ac.uk/directory/dr-arik-kershenbaum or follow him on twitter at @arikkershenbaum

Today we are re-running a previous episode of Journal Club — our show where we curate breakthrough research and bridge paper to practice — in light of a recent article published in the journal Nature (see show notes below). In this episode, host Lauren Richardson talks to Professor Anthony Atala from the Wake Forest School of Medicine about his lab’s work creating an engineered uterus that can support live births. This work represents a major milestone in regenerative medicine and could be used to address a pressing unmet clinical need — and it might even be laying the groundwork for the ability to gestate babies outside of the body. That is where the recent Nature article, entitled “Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis” by Aguilera-Castrejon et al., comes in. That article describes the creation of a cell culture system that can support embryonic development — up to a certain point, that is.

So in this episode we are talking about creating a tissue engineered uterus, that could be used to replace a defective uterus and that might one day possibly support pregnancy out of the body — whereas in the recent Nature article, they do away with the uterus entirely and culture the embryos in a fully mechanical set up. While this kind of ex vivo pregnancy still seems like sci-fi, both of these articles make steps in that general direction, and more importantly, increase our understanding of the female reproductive system and early development. 

Anthony Atala, MD (the G. Link Professor and Director of the Wake Forest Institute for Regenerative Medicine, and the W. Boyce Professor and Chair of Urology), joins host Lauren Richardson (@lr_bio) to discuss the results and implications of the article "A tissue-engineered uterus supports live births in rabbits" by Renata S. Magalhaes, J. Koudy Williams, Kyung W. Yoo, James J. Yoo & Anthony Atala, published in Nature Biotechnology.

In the introduction, we also discuss the new article "Ex utero mouse embryogenesis from pre-gastrulation to late organogenesis" by Alejandro Aguilera-Castrejon, Bernardo Oldak, Tom Shani, Nadir Ghanem, Chen Itzkovich, Sharon Slomovich, Shadi Tarazi, Jonathan Bayerl, Valeriya Chugaeva, Muneef Ayyash, Shahd Ashouokhi, Daoud Sheban, Nir Livnat, Lior Lasman, Sergey Viukov, Mirie Zerbib, Yoseph Addadi, Yoach Rais, Saifeng Cheng, Yonatan Stelzer, Hadas Keren-Shaul, Raanan Shlomo, Rada Massarwa, Noa Novershtern, Itay Maza & Jacob H. Hanna, published in Nature.

Mosquitoes are the deadliest animals on Earth and for millennia humans have tried to rid themselves of these disease-spreading pests, with shockingly little success. On this episode of the Bio Eats World Journal Club, host Lauren Richardson talks to Leslie Vosshall of Rockefeller University about two articles from her lab investigating the neural and genetic basis of the mosquito's love for us and our blood. The conversation covers how mosquitoes taste blood, the critical differences between male mosquitoes and female mosquitoes, and of course, what this all means for controlling the spread of the deadly pathogens transmitted by the mosquito.

Leslie Vosshall, Ph.D, Professor at Rockefeller University and Howard Hughes Medical Institute (@leslievosshall) joins host Lauren Richardson (@lr_bio) to discuss the results and implications of two recent articles from her lab. First, "Sensory Discrimination of Blood and Floral Nectar by Aedes aegypti Mosquitoes" by Veronica Jove, Zhongyan Gong, Felix J.H. Hol, Zhilei Zhao, Trevor R. Sorrells, Thomas S. Carroll, Manu Prakash, Carolyn S. McBride, and Leslie B. Vosshall, published in Neuron. Second, "Fruitless mutant male mosquitoes gain attraction to human odor" by Nipun S Basrur, Maria Elena De Obaldia, Takeshi Morita, Margaret Herre, Ricarda K von Heynitz, Yael N Tsitohay, and Leslie B Vosshall, published in eLife.

In this episode, we talk with Jeff Hawkins—an entrepreneur and scientist, known for inventing some of the earliest handheld computers, the Palm and the Treo, who then turned his career to neuroscience and founded the Redwood Center for Theoretical Neuroscience in 2002 and Numenta in 2005—about a new theory about how the cells in our brain work to create intelligence. What exactly is happening in the neocortex as our brains process and interpret information and sensory input—like sight, smell, touch, or language, or math—to create a perception of and to navigate through the world around us? 

a16z General Partner Vijay Pande and I talk to Jeff about the basic principles in this new idea of the brain’s learning methodology for creating not just human intelligence, but animal intelligence, artificial intelligence, even alien intelligence, which he lays out in his newly just released book, A Thousand Brains: A New Theory of Intelligence. The conversation covers how the neocortex builds models of the world around us, and what this could mean for how we design the next generation of truly intelligent machines. This episode goes all the way from tiny neurons and how they speak to each other to what’s happening in optical illusions to the future of humanity and beyond.

In a healthy person, your body automatically adjusts blood pressure constantly, and this adjustment is governed by what’s called the baroreflex. However, a spinal cord injury can disrupt this reflex, which has both short term consequences, like passing out, but also long term consequences like an increased risk of heart disease and stroke. On this episode of the Bio Eats World Journal Club, host Lauren Richardson is joined by Dr. Aaron Phillips of the University of Calgary to talk about his lab’s work to reinstate this reflex in patients after a spinal cord injury using a neuroprosthetic device. This device both senses blood pressure changes and then activates the necessary neuronal structures to restore the connection to the blood vessels. We discuss how his group determined which neuronal structures to stimulate, how they developed this medical device, and the exciting results from their studies in rats, non-human primates and humans.

Aaron Phillips, CEP, MSc, PhD (Medicine), Assistant Professor at the University of Calgary, joins host Lauren Richardson to discuss the results and implications of the article "Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury" by Jordan W. Squair, Matthieu Gautier, Lois Mahe, Jan Elaine Soriano, Andreas Rowald, Arnaud Bichat, Newton Cho, Mark A. Anderson, Nicholas D. James, Jerome Gandar, Anthony V. Incognito, Giuseppe Schiavone, Zoe K. Sarafis, Achilleas Laskaratos, Kay Bartholdi, Robin Demesmaeker, Salif Komi, Charlotte Moerman, Bita Vaseghi, Berkeley Scott, Ryan Rosentreter, Claudia Kathe, Jimmy Ravier, Laura McCracken, Xiaoyang Kang, Nicolas Vachicouras, Florian Fallegger, Ileana Jelescu, YunLong Cheng, Qin Li, Rik Buschman, Nicolas Buse, Tim Denison, Sean Dukelow, Rebecca Charbonneau, Ian Rigby, Steven K. Boyd, Philip J. Millar, Eduardo Martin Moraud, Marco Capogrosso, Fabien B. Wagner, Quentin Barraud, Erwan Bezard, Stéphanie P. Lacour, Jocelyne Bloch, Grégoire Courtine & Aaron A. Phillips, published in Nature.

Sea turtles occupy a very special biological niche in our world. And we still know relatively little about these creatures, one of the very few marine reptiles on the face of the planet. But as population growth and activity on coasts has exploded, so have our encounters with sea turtles... including, unfortunately, those that cause injury and disease. So what advances in technology and healthcare are helping us treat these incredible, 150 million year old animals—and what are we learning about them as a result?

Max Polyak, Director of Rehabilitation at Loggerhead Marine Life Center in Juno Beach, Florida, shares with Bio Eats World host Hanne Winarsky the new advances in science and technology that are helping us treat sea turtles when they get sick or injured—and the new understanding about their biology, their behavior, and how they interact with the world around them those advances are leading to. The conversation covers everything from treating boat injuries with sea turtle-specific prosthetics; to using cutting edge human therapeutics on these animals in new ways; to the unique immune systems of these 2,000 pound leatherbacks (immune systems that have dealt with dinosaurs! meteor strikes! ice ages! and more); to how the microbiome of the sea turtle may answer one of the most intriguing mysteries about how these turtles behave; to ultimately, what sea turtle health can teach us about how we are all linked—and about the health of the entire ocean.

On this episode of the Bio Eats World Journal Club, we explore the very compelling question of whether we can use our understanding of developmental biology to create oocytes (aka eggs or female gametes) from stem cells in the lab. If possible, this could be on par with the development of in vitro fertilization in terms of extending fertility. But creating an oocyte from a stem cell has some unique and high-stakes challenges. Host Lauren Richardson is joined by a16z general partner Vineeta Agarwala and deal partners Judy Savitskaya and Justin Larkin to discuss a recent research article in Nature by Hamazaki et al that makes a big step towards this goal. The conversation covers which aspects of oocyte biology the authors were able to replicate, which they were not, and where we think this field might be heading. 

a16z general Vineeta Agarwala, MD Ph.D, and deal partners Judy Savitskaya, Ph.D and Justin Larkin, MD join host Lauren Richardson, Ph.D to discuss the results and implications of the article "Reconstitution of the oocyte transcriptional network with transcription factors" by Nobuhiko Hamazaki, Hirohisa Kyogoku, Hiromitsu Araki, Fumihito Miura, Chisako Horikawa, Norio Hamada, So Shimamoto, Orie Hikabe, Kinichi Nakashima, Tomoya S. Kitajima, Takashi Ito, Harry G. Leitch and Katsuhiko Hayashi, published in Nature.

To date, synthetic biology has been mainly focused on reproducing existing compounds and materials with biomanufacturing. Think of engineering yeast to produce anti-malarial drugs, or bacteria producing spider silk. But as our guest — Professor Tom Ellis of Imperial College London — argues, the future of synthetic biology is in creating materials with fundamentally new and distinct functions. Imagine, a spider silk rope that it is interwoven with cells that can catalyze the dissolution of that rope in certain circumstances. Host Lauren Richardson and a16z bio deal team partner Judy Savitskaya talk to Dr. Ellis about his group's work creating a prototype of an engineered living material (ELM) that can be iterated on and programmed with a huge array of different functions, how ELMs can disrupt established markets, and their varied uses in industry, healthcare, fashion, consumer products, and even potentially in space travel.

Tom  Ellis (@ProfTomEllis), Professor of Synthetic Genome Engineering at Imperial College London, joins host Lauren Richardson (@lr_bio) and a16z bio deal team partner Judy Savitskaya (@heyjudka) to discuss the results and implications of the article "Living materials with programmable functionalities grown from engineered microbial co-cultures" by  Charlie Gilbert, Tzu-Chieh Tang, Wolfgang Ott, Brandon A. Dorr, William M. Shaw, George L. Sun, Timothy K. Lu & Tom Ellis, published in Nature Materials. 

Ticks are "master scientists of our skin," says our guest — Seemay Chou, Assistant Professor at University of California, San Francisco. On this episode of the Bio Eats World Journal Club, Dr. Chou and host Lauren Richardson discuss how, over millions of years of evolution, ticks have developed a suite of tools to manipulate our skin physiology, all of which are delivered through their saliva as they feed. Pathogens, like the bacteria that cause Lyme Disease, take advantage of the tick's tools to infect new hosts. But what if we could also learn to use these tools? In this conversation, we discuss the dynamic nature of host-pathogen interactions, how ticks stole a tool from bacteria and then modified it to suit their needs, how our microbiome helps to protect us from ticks, how bias can influence how you set up experiments and interpret data, and how an un-fundable research project inspired a startup.

Seemay Chou (@seemaychou), Assistant Professor at the University of California, San Francisco, joins host Lauren Richardson (@lr_bio) to discuss the results and implications of the article “Ticks Resist Skin Commensals with Immune Factor of Bacterial Origin”, by Beth M. Hayes, Atanas D. Radkov, Fauna Yarza, Sebastian Flores, Jungyun Kim, Ziyi Zhao, Katrina W. Lexa, Liron Marnin, Jacob Biboy, Victoria Bowcut, Waldemar Vollmer, Joao H.F. Pedra, and Seemay Chou, published in Cell.

"Superbug" is shorthand for multi-drug resistant bacteria. Infections with superbugs are the most difficult to treat, because these bacteria have evolved ways of evading multiple — and sometimes all! — of our available antibiotics. This multi-drug resistance can arise in the bacteria that are causing disease, meaning doctors have to find new ways to treat the infection, but also in the bacteria that harmlessly live in our gastrointestinal tract. Critically, if these gut bacteria become superbugs, they can spread resistance throughout a hospital setting via fecal-oral contamination. On this episode of the Bio Eats World Journal Club, we discuss a new strategy for protecting those harmless bacteria from antibiotics while still treating the infection. Host Lauren Richardson (@lr_bio) is joined by Professor Andrew Read of Penn State University to discuss his team's work preventing resistance evolution by repurposing an old, FDA-approved drug. The conversation covers the scope of the antibiotic resistance problem, the insights that lead to the discovery of this adjuvant therapy, and the fundamentally novel nature of anti-evolution drugs.

Andrew Read, Ph.D is the director of Huck Institutes of the Life Sciences, the Evan Pugh Professor of Biology and Entomology, and the Eberly Professor of Biotechnology at Pennsylvania State University. He joins host Lauren Richardson to discuss the results and implications of the article "An adjunctive therapy administered with an antibiotic prevents enrichment of antibiotic-resistant clones of a colonizing opportunistic pathogen"  by Valerie J Morley, Clare L Kinnear , Derek G Sim, Samantha N Olson , Lindsey M Jackson, Elsa Hansen, Grace A Usher, Scott A Showalter, Manjunath P Pai, Robert J Woods, and Andrew F Read, published in eLife.

Today we are revisiting a topic and episode that was originally aired back when Journal Club was part of the a16z podcast. We are covering it again in light of a new research article published in Science, as both this episode and this newer research article are trying to find a way to kill senescent cells.

The article we discuss in this episode, "Senolytic CAR T cells reverse senescence-associated pathologies" by Amor et al, published in Nature, selectively targets senescent cells with engineered T cells.

The new article, "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders" by Johmura et al, published in Science, kills senescent cells by inhibiting an enzyme essential for their metabolism.

So what are senescent cells, and why is killing them so important? Senescent cells are those in a non-dividing but metabolically active state, and what’s interesting is that they play both protective and pathological roles in the body. When senescent cells accumulate, as often happens during aging, they kick off an inflammatory process that underlies many age-related diseases. Thus the targeted destruction of senescent cells has the potential to treat a wide range of conditions, and possibly to improve longevity.

Both of the approaches described in these two articles have their pros and cons, and it remains to be seen which will be effective in humans, but together they highlight the interest and importance of senescence-killing, or senolytic, methods for future therapeutics.

On this episode, a16z general partner Jorge Conde (@JorgeCondeBio) and bio deal team partner Andy Tran (@andy23tran) join host Lauren Richardson (@lr_bio) to discuss the results and implications of the article "Senolytic CAR T cells reverse senescence-associated pathologies" by Corina Amor, Judith Feucht, Josef Leibold, Yu-Jui Ho, Changyu Zhu, Direna Alonso-Curbelo, Jorge Mansilla-Soto, Jacob A. Boyer, Xiang Li, Theodoros Giavridis, Amanda Kulick, Shauna Houlihan, Ellinor Peerschke, Scott L. Friedman, Vladimir Ponomarev, Alessandra Piersigilli, Michel Sadelain & Scott W. Lowe, published in Nature.

The introduction also references the article "Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders" by Yoshikazu Johmura, Takehiro Yamanaka, Satotaka Omori, Teh-Wei Wang, Yuki Sugiura, Masaki Matsumoto, Narumi Suzuki, Soichiro Kumamoto, Kiyoshi Yamaguchi, Seira Hatakeyama, Tomoyo Takami, Rui Yamaguchi, Eigo Shimizu, Kazutaka Ikeda, Nobuyuki Okahashi, Ryuta Mikawa, Makoto Suematsu, Makoto Arita, Masataka Sugimoto, Keiichi I. Nakayama, Yoichi Furukawa, Seiya Imoto, Makoto Nakanishi

Move over microdosing, there is a new approach to psychedelic medicine. Psychedelics — like LSD and psilocybin — are some of the most powerful drugs that affect our brains, but their therapeutic potential has been limited due to their adverse side effects. This is where the work of today's guest, Dr. David Olson (@DEOlsonLab) of UC Davis, comes in. He talks to host Lauren Richardson (@lr_bio) about his lab's effort to develop new drugs based off the structure of psychedelics that retain their therapeutic properties, but that have better safety profiles, and that importantly, are non-hallucinogenic. The conversation covers his team’s recent Nature paper creating a non-hallucinogenic derivative of ibogaine, the evidence from animal models of its ability to treat depression and alcohol- and heroin-seeking behaviors, and the unexpected challenges facing the psychedelic medicine field.

David Olson, Ph.D, Assistant Professor at the University of California, Davis, joins host Lauren Richardson to discuss the results and implications of the article "A non-hallucinogenic psychedelic analogue with therapeutic potential" by Lindsay P. Cameron, Robert J. Tombari, Ju Lu, Alexander J. Pell, Zefan Q. Hurley, Yann Ehinger, Maxemiliano V. Vargas, Matthew N. McCarroll, Jack C. Taylor, Douglas Myers-Turnbull, Taohui Liu, Bianca Yaghoobi, Lauren J. Laskowski, Emilie I. Anderson, Guoliang Zhang, Jayashri Viswanathan, Brandon M. Brown, Michelle Tjia, Lee E. Dunlap2, Zachary T. Rabow, Oliver Fiehn, Heike Wulff, John D. McCorvy, Pamela J. Lein, David Kokel, Dorit Ron, Jamie Peters, Yi Zuo & David E. Olson, published in Nature.

Immuno-oncology, which leverages the body's own immune system to fight cancer, is a true medical revolution. But to date, these therapies have only targeted one of the two arms of the immune system: the adaptive immune system. This is the arm that contains T cells, B cells, and antibodies and is what we generally think of when talking about immunity. But the second arm, the innate immune system, is equally important, as it mounts a fast-acting, non-specific immune response to a board range of invaders. Importantly, some cancers co-opt the innate immune system and use it as a shield against attacks by the adaptive immune system. In today's episode, host Lauren Richardson (@lr_bio) is joined by Dr. Willem Mulder (@WillemNANO), Professor at the Icahn School of Medicine at Mt. Sinai, to discuss a new approach to immuno-oncology that engages both arms of the immune system. This method uses engineered, synthetic, nano-scale "germs" to activate the innate immune system, and which works in combination with T cell-activating therapies to destroy cancer cells, even leading to complete tumor remission in mice. The conversation covers how these synthetic germs were developed from an early vaccine to tuberculosis, how they influence immune cell activity, their potential for treating cancer and an array of other conditions, and what is needed to take them out of the lab and into the clinic.

Dr. Willem Mulder is a Professor at the Icahn School of Medicine at Mt. Sinai, Eindhoven University of Technology, and  Radboud University Medical Center and is a co-founder of Trained Therapeutix Discovery. He joins host Lauren Richardson to discuss the results and implications of the article "Trained Immunity-Promoting Nanobiologic Therapy Suppresses Tumor Growth and Potentiates Checkpoint Inhibition" by Bram Priem, Mandy M.T. van Leent, Abraham J.P. Teunissen, Alexandros Marios Sofias, Vera P. Mourits, Lisa Willemsen, Emma D. Klein, Roderick S. Oosterwijk, Anu E. Meerwaldt, Jazz Munitz, Geoffrey Pre ́vot, Anna Vera Verschuur, Sheqouia A. Nauta, Esther M. van Leeuwen, Elizabeth L. Fisher, Karen A.M. de Jong, Yiming Zhao, Yohana C. Toner, Georgios Soultanidis, Claudia Calcagno, Paul H.H. Bomans, Heiner Friedrich, Nico Sommerdijk, Thomas Reiner, Raphae ̈l Duivenvoorden, Eva Zupancic, Julie S. Di Martino, Ewelina Kluza, Mohammad Rashidian, Hidde L. Ploegh, Rick M. Dijkhuizen, Sjoerd Hak, Carlos Pe ́ rez-Medina, Jose Javier Bravo-Cordero, Menno P.J. de Winther, Leo A.B. Joosten, Andrea van Elsas, Zahi A. Fayad, Alexander Rialdi, Denis Torre, Ernesto Guccione, Jordi Ochando, Mihai G. Netea, Arjan W. Griffioen, and Willem J.M. Mulder, published in Cell.

For more on the innate immune system, also check out "Journal Club: Why do only some people get severe COVID-19?" and "Journal Club: How to Win an Evolutionary Arms Race"

For more on brain organoids and their many applications, check out this episode of Journal Club: "Modeling Mysterious Brain Structures." Host Lauren Richardson talks to Dr. Madeline Lancaster, a Group Leader at the MRC Laboratory of Molecular Biology in Cambridge, about her lab's article in Science describing an organoid model for studying the cerebrospinal fluid and the choroid plexus, and how these organoids can be used to study brain development, evolution, and improve the drug development process.

One of the enduring mysteries of COVID-19 is why some people get a severe disease that can be fatal, whereas the majority experience a very mild or even asymptomatic disease. On this episode of the Bio Eats World Journal Club, host Lauren Richardson (@lr_bio) discussed this discrepancy with Dr. Helen Su of the NIH and co-leader of the COVID Human Genetic Effort. This international collaboration set out to investigate whether there is a genetic component to severe COVID and published the first of their findings in two articles in Science. Both papers demonstrate that dysfunction in a very specific part of the immune system leads to severe COVID, but through distinct mechanisms. We break down these results, how they can inform treatment, and how this collaboration was able to uncover these important findings in record time.

Dr. Helen Su, Chief of the Human Immunological Diseases Section at the National Institute of Allergy and Infectious Diseases (part of the NIH) and co-leader of the COVID Human Genetic Effort, joins host Lauren Richardson to discuss the results and implications of the articles "Inborn errors of type I IFN immunity in patients with life-threatening COVID-19"  and "Autoantibodies against type I IFNs in patients with life-threatening COVID-19", both published in Science. 

Viruses (like HIV) and their hosts (like humans) are locked in an evolutionary arms race, with each trying to outwit the other. But viruses seem to have a big advantage (MUCH faster evolution), so how can the slowly evolving human arsenal keep pace? On this episode of the Bio Eats World Journal Club, host Lauren Richardson (@lr_bio) talks to Professor Harmit Malik (@HarmitMalik) about new research from his lab determining some surprising characteristics of human antiviral proteins that allow them to persevere in this evolutionary fight and how this information could be used to develop new, possibly curative, treatments for HIV.

Harmit Malik, PhD (Professor and Associate Director of the Basic Sciences Division at the Fred Hutchinson Cancer Research Center) joins host Lauren Richardson to discuss the results and implications of the article "Mutational resilience of antiviral restriction favors primate TRIM5α in host-virus evolutionary arms races", by Jeannette L Tenthorey, Candice Young, Afeez Sodeinde, Michael Emerman, and Harmit S Malik,  published in eLife.

Infertility is a common struggle with limited treatment options, particularly if caused by an issue with the uterus. On this episode of Journal Club host Lauren Richardson (@lr_bio) talks to Professor Anthony Atala about his lab's work engineering a replacement uterus that can -- incredibly! -- support pregnancy and live birth in rabbits. They discuss how the Atala lab created these bioengineered uteruses and tested their functionality, what kinds of conditions they can be used to treat, and potential sci-fi-esque applications.

Anthony Atala, MD (the G. Link Professor and Director of the Wake Forest Institute for Regenerative Medicine, and the W. Boyce Professor and Chair of Urology), joins host Lauren Richardson to discuss the results and implications of the article "A tissue-engineered uterus supports live births in rabbits" published in Nature Biotechnology.

Approximately half of all severe developmental disorders are caused by de novo (new, not inherited) mutations in protein-coding genes. But which genes? In this episode of the Bio Eats World Journal Club, Vineeta Agarwala (@vintweeta) and Lauren Richardson (@lr_bio) discuss a recent article finding new genes linked to developmental disorders and highlighting how many still need to be decoded.

Vineeta Agarwala, physician and a16z general partner, and host Lauren Richardson discuss the Nature article "Evidence for 28 genetic disorders discovered by combining healthcare and research data", its key implications, and how this work can impact patients and parents.  

Type 1 Diabetes is an autoimmune disease with no cure and challenging treatment regimes. The disease is characterized by self-reactive immune cells that attack and destroy cells in the pancreas that produce insulin and are essential for regulating metabolism, called beta cells.

Since the advent of stem cell technology, scientists have dreamed of curing Type 1 Diabetes by replacing the beta cells lost to disease with lab grown, stem cell-derived beta cells. However, it wasn't until recent work from Ronald Evans' lab at the Salk Institute that this dream started to become a reality. First, in 2016, Evans and colleagues identified a critical genetic switch needed to activate stem cell-derived beta cells. Second, in the article we discuss today, they figured out how to produce not just the beta cells from stem cells, but their entire cellular compartment, called the pancreatic islet. They call these synthetic islets HILOs (human islet-like organoids). Even more importantly, they devised a way to shield the HILOs from the immune system. This molecular shield, which they learned about from studying how pancreatic cancer cells evade the immune system, is the key to the long term survival of the HILOs despite this chronic autoimmune response.

In this conversation, host Lauren Richardson and Dr. Evans cover these key breakthroughs, the next steps for moving this proof-of-concept research into the clinic, and how these HILOs might represent a curative treatment for this devastating and life-long condition. 

Mechanical forces and architecture may not sound very "bio", but they are key tools of epidermal stem cells.  These stem cells essentially engineer their environment by producing both the cells above them (the skin cells) and the extracellular matrix mesh (the basement membrane) that they sit on. In this episode we explore whether, when these stem cells acquire oncogenic mutations (the ones that cause cancer), do they now architect in a different way, and does this influence the development of cancer?

Host Lauren Richardson and Professor Elaine Fuchs of Rockefeller University discuss her lab's recent Nature article "Mechanics of a multilayer epithelium instruct tumour architecture and function". The article investigates the differences in mechanical forces and tissue architecture in two distinct types of skin cancer: one that tends to be begin and non-invasive and one that tends to be aggressive and metastatic. The conversation covers how computational modeling played a critical role in uncovering new sources of forces and how changes in architecture influence invasive properties.

On this episode of the Bio Eats World Journal Club, a16z bio deal team partner Judy Savitskaya and host Lauren Richardson discuss a new article that makes the full arc from basic science discovery to application. The article -- "Reverse and forward engineering of Drosophila corneal nanocoatings" by Mikhail Kryuchkov, Oleksii Bilousov, Jannis Lehmann, Manfred Fiebig & Vladimir L. Katanaev, published in Nature -- and the conversation begin by discussing insect eye nanocoatings, which give eyes key properties like anti-reflectiveness and anti-adhesiveness. The authors show these nanocoatings are formed by a self-assembling mechanism known as a Turing Pattern. But why do we care about fly eye nanocoatings and their patterns? Why did Alan Turing spend his time studying the basis biological patterns? As we discuss, understanding this patterning revealed a new method for creating nanostructured materials, which today is a high tech and costly process. We cover the reverse and forward engineering these nanostructures, the beauty of Turing Patterns, and how one could build a startup around this nanostructure technology. 

Neurons do not divide or replicate, so how can we replace neurons killed by neurodegenerative diseases like Parkinson's Disease? On the Bio Eats World Journal Club, UCSD Professor Xiang-Dong Fu and host Lauren Richardson discuss his team's work generating new neurons in the brain by inducing non-neuronal cells to become neurons. The conversation covers how they programmed this cell type conversion, how they verified that these newly created neurons were functioning correctly, and how they demonstrated that these neurons could replace those destroyed in a mouse model of Parkinson's Disease, reversing the disease phenotype. This work paves the way for a potential curative treatment for this and other devastating neurodegenerative and neurological diseases.

"Reversing a model of Parkinson’s disease with in situ converted nigral neurons" by Hao Qian, Xinjiang Kang, Jing Hu, Dongyang Zhang, Zhengyu Liang, Fan Meng, Xuan Zhang, Yuanchao Xue1, Roy Maimon, Steven F. Dowdy, Neal K. Devaraj, Zhuan Zhou, William C. Mobley, Don W. Cleveland & Xiang-Dong Fu. 

There is a wide range of diagnostic tests for COVID-19 that are all well suited for determining whether an individual patient is sick with the virus. But to safely reopen society in the absence of a vaccine, we need tests that can be given broadly across a population, including to people who are asymptomatic. Many of these existing tests cannot be administered at this grand scale. That is where SwabSeq comes in. SwabSeq is an open source COVID-19 diagnostic platform that leverages the power of genomics to vastly increase the scale of testing. 

On this episode of the Bio Eats World Journal Club, host Lauren Richardson discusses the pre-print article "Swab-Seq: A high-throughput platform for massively scaled up SARS-CoV-2 testing" with two of the authors, Sri Kosuri of Octant  and Valerie Arboleda of UCLA. The original concept and design of this sequencing based approach was developed at Octant (a drug discovery startup co-founded by Kosuri, who is also a professor at UCLA), and the conversation covers the origins of of the method, why they decided to develop the test as an open source project and how sequencing increases scalability. Kosuri, Arboleda, and a team at UCLA built SwabSeq into a validated diagnostic platform that recently received an Emergency Use Authorization from the Food and Drug Administration. 

Over the past 15 years we have made huge advances in our ability to engineer the genome, meaning that we now have the ability to edit DNA in a programmable and precise manner. In the lab, these editing tools allow us to create models of disease and to investigate how changes in the genome lead to changes in cell and organismal biology. And excitingly, these genome editing technologies are now entering clinical trials to treat, and possibly cure, diseases like sickle cell anemia. But there is a component of the human genome which even the much lauded and powerful CRISPR system has not been able to touch: the mitochondrial DNA. 

The mitochondria are the powerhouses of the cell and contain their own, much smaller, genomes which encode several essential proteins and RNAs. Mutations in the mitochondrial genome are the cause of over 150 diseases, but to date, fixing these mutations with gene editing and gene therapy has been off the table due to the inaccessibility of this genome. 

In this episode of Journal Club, a16z general partner Jorge Conde and bio deal team partner, Andy Tran – experts in genomics and genome engineering – join Lauren Richardson to discuss groundbreaking research creating the first genome editor able to target the mitochondrial DNA: "A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing" by Beverly Y. Mok Marcos H. de Moraes, Jun Zeng, Dustin E. Bosch, Anna V. Kotrys, Aditya Raguram, FoSheng Hsu, Matthew C. Radey, S. Brook Peterson, Vamsi K. Mootha, Joseph D. Mougous & David R. Liu, published in Nature. 

We discuss what makes the mitochondrial genome distinct, how this new tool – which was derived from a bacterial toxin – was engineered for both safety and specificity, and the important applications for this new editor. 

The human brain is endlessly fascinating and mysterious, but the majority of brain research to date has focused on neurons and their functions. While the other types of brain cells, such as astrocytes and glia, are starting to get their due, there is another element of the brain that to this day has gone woefully unstudied: the cerebrospinal fluid (CSF) and the brain structure that produces it, the choroid plexus. The CSF is a clear, colorless fluid found in the brain and spinal cord, and is traditionally thought to protect the brain from injury by acting as a shock absorber. 

In this episode, Madeline Lancaster, a Group Leader at the MRC Laboratory of Molecular Biology in Cambridge and Lauren Richardson discuss the article "Human CNS barrier-forming organoids with cerebrospinal fluid production" by Laura Pellegrini, Claudia Bonfio, Jessica Chadwick, Farida Begum, Mark Skehel, Madeline A. Lancaster published in Science. The paper describes a new model for studying the CSF and the choroid plexus by creating what’s sometimes called a mini-brain or a brain-in-a-dish, but is more accurately known as a cerebral organoid. With this model, Dr. Lancaster and her team were able to reveal new insights into the composition and function of the choroid plexus, and importantly, how it forms a key barrier between the blood and the brain. We discuss the how these organoids can be used to study brain development, evolution, and improve the drug development process.

In Bio Eats World's Journal Club episodes, we discuss groundbreaking research articles, why they matter, what new opportunities they present, and how to take these findings from paper to practice. In this episode, Stanford Professor Carolyn Bertozzi and host Lauren Richardson discuss the article "Lysosome-targeting chimaeras for degradation of extracellular proteins" by Steven M. Banik, Kayvon Pedram, Simon Wisnovsky, Green Ahn, Nicholas M. Riley & Carolyn R. Bertozzi, published in Nature584, 291–297 (2020).

Many diseases are caused by proteins that have gone haywire in some fashion. There could be too much of the protein, it could be mutated, or it could be present in the wrong place or time. So how do you get rid of these problematic proteins? Dr. Bertozzi and  her lab developed a class of drugs -- or modality -- that in essence, tosses the disease-related proteins into the cellular trash can. While there are other drugs that work through targeted protein degradation, the drugs created by the Bertozzi team (called LYTACs) are able to attack a set of critical proteins, some of which have never been touched by any kind of drug before. Our conversation covers how they engineered these new drugs, their benefits, and how they can be further optimized and specialized in the future.

This new show, from the same team that produces the popular a16z Podcast, will be all about how biology today is where technology was 50 years ago: on the precipice of revolutionizing our world in ways we are only just beginning to appreciate.

Through conversations with scientists, builders, entrepreneurs, and leaders at the intersection of science, tech, and business, the Bio Eats World team, including hosts Hanne Winarsky and Lauren Richardson, examine how biology—and our new ability to engineer it—is going to revolutionize our future, and in ways we are only just beginning to imagine.