Raising Health (Andreessen Horowitz, a16z Bio + Health)

Ankit Jain, CEO and cofounder of Infinitus Systems, Inc, joins Julie Yoo, a16z Bio + Health general partner, to discuss Infinitus's work in solving one of healthcare's most pressing challenges: workforce shortages. Leveraging LLMs and AI voice agents, Infinitus automates repetitive tasks, such as benefits verification and prior authorization, freeing up human talent for higher-value roles. Ankit reflects on the company’s journey—from early proof-of-concept calls to scaling over five million patient-centric interactions—and shares their approach to mitigating the risks of AI errors through layered guardrails.

 

More in "The Opportunity for Healthcare in a Post-LLM World":

• Super Staffing in Healthcare with Munjal Shah
• Transforming Clinical Trials with Alexander Saint-Amand

Plus:

• Learn more about a16z Bio+Health
• Learn more about & Subscribe to Raising Health
• Find a16z Bio+Health on LinkedIn
• Find a16z Bio+Health on X

Marta Bralic Kerns, founder and CEO of Pomelo Care, joins Will Shrank, MD, a16z Bio + Health venture partner.

Together, they talk about the innovator’s dilemma with building in the Medicaid space, how Pomelo partners with managed care plans, and the opportunity to potentially lower costs through providing additional support to pregnant women.

This is the third episode in our Medicaid Matters series. Listen to previous guests Mark Smith, MD, and Nikita Singareddy in the Raising Health feed.

Why do we experience physical pain? Is all pain the same, or are there different types? Do people experience pain differently? Professor of Neurobiology at Harvard Medical School Clifford Woolf, and Bio Eats World host Hanne Winarsky talk about everything we know about the biology of pain. Technology is today enabling a new, deeper, and much more complex understanding of the phenomenon of pain. Which pathways and neurons are activated in the brain and when, and what patterns might represent different kinds of pain? In this episode (first aired on the a16z Podcast in September 2019), Woolf describes the four different phenotypes of pain, the purpose of each, and what changes when we begin to understand them as distinct types. What does it mean for how we can treat pain in the future… and where we can intervene?

Jeff Margolis, founder of TriZetto, joins Julie Yoo, a16z Bio + Health general partner, to share the journey of building an iconic company in healthcare infrastructure. From the early days of managed care to creating a three-pronged platform uniting computing power, software, and data analytics, Jeff reflects on TriZetto’s groundbreaking model that reshaped payer-provider transactions and set industry standards. Together, they also delve into the strategic importance of scaling through acquisitions, aligning with industry standards, and crafting innovative pricing models.

with @lifelikephysics, @vijaypande, and @omnivorousread Where does life truly begin? How do we understand the fundamental nature of what is “alive” and what is “not alive”? In this episode of Bio Eats World, Professor Jeremy England discusses his new book, Every Life is on Fire, all about how what we might use physics to understand to be the origins of life—and how we define what being alive is. As biologists, we are taught that life evolved as the result of Darwinian natural selection. But what happens if instead, you use a physicist’s lens to examine what life looks to be—and define it as a specialized order and relationship between matter and the patterns of it’s an environment? England—a senior director in artificial intelligence at GlaxoSmithKline, principal research scientist at Georgia Tech, former associate professor of physics at MIT, and one of Forbes’ “30 Under 30 Rising Stars of Science”—describes this new idea as “dissapative adaptation”. The conversation covers how looking at “life” in these terms changes what we understand to be alive and what the nature of "life" is; sheds new light on the “queasy middle ground” between those definitions, especially in areas like machine learning and AI; and allows us to ask new questions about things like what makes DNA so special, and what life can do.

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.

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. 

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.

"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.

Nikita Singareddy, cofounder and CEO of Fortuna Health, joins Will Shrank, MD, a16z Bio + Health venture partner.

Together, they discuss building a useful and convenient platform for Medicaid enrollees, listening to patient feedback to improve, and the complexities of different states’ Medicaid processes. This is the second episode in our Medicaid Matters series. Listen to previous guest Mark Smith, MD, to hear about Medicaid from a provider's perspective.

with @LauraDeming, @kpfortney, @vijaypande, and @omnivorousread Welcome to the first episode of Bio Eats World, a brand new podcast all about how biology is technology. Bio is breaking out of the lab and clinic and into our daily lives—on the verge of revolutionizing our world in ways we are only just beginning to imagine. In this episode, we talk all about the science of aging. Once a fringe field, aging research is now entering a new phase with the first clinical trials of aging-related drugs. As the entire field shifts into this moment of translation, what have we learned? What are the basic approaches to developing aging-related drugs? How is studying aging helping us understand diseases like cancer and Alzheimer's—and increasing the amount of time we are healthy—today?  In this conversation, Laura Deming, founder of The Longevity Fund; Kristen Fortney, co-founder of BioAge, a clinical-stage company focused on finding drugs to extend healthspan; Vijay Pande, general partner at a16z; and host Hanne Winarsky discuss the entire arc of aging science from one genetic tweak in a tiny worm to changing a whole paradigm of healthcare delivery.

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.

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.

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.

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.

Seth Hain, SVP of R&D at Epic, joins a16z Bio + Health general partner Julie Yoo to explore technology in healthcare. Reflecting on over two decades of industry shifts, Seth shares how Epic has transitioned from enabling integrated systems within health systems to driving cross-ecosystem collaboration and rapid innovations like generative AI.

They also discuss orchestration of patient care across diverse settings, the transformative impact of AI on clinical workflows, and whether "electronic health record" is really the best term for clinical record-keeping software.

 

• Learn more about a16z Bio+Health
• Learn more about & Subscribe to Raising Health
• Find a16z Bio+Health on LinkedIn
• Find a16z Bio+Health on X

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.

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, 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.

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. 

The way we pay for healthcare in the US has long been by fee-for-service: per doctor visit, per test, per surgery, per hospital stay. But that system has led to rapidly escalating volumes of services and cost to the system—without actually improving outcomes. What if we shifted everything towards paying for value—and outcomes—instead? In this episode, Todd Park, co-founder and executive chairman of Devoted Health, and formerly Chief Technology Officer and technology advisor for President Barack Obama; a16z General Partner Vijay Pande; and Bio Eats World host Hanne Winarsky—talk all about the megatrend of value-based care, and how it is redefining healthcare itself. Why is now the moment for this massive shift? How do we implement it? What does it mean for doctors and patients, insurers and policymakers? What is tech’s role in making it possible, and what's the business model and incentive for creating value?

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.

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.

Healthcare is perhaps unique in that the entire system exists entirely to serve the patient... and yet, in many ways, that same patient is not the customer. 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, or in high level policy debates. In this episode, a16z General Partner Julie Yoo and a16z partner Jay Rughani talk with Freda Lewis Hall—a physician; formerly Pfizer’s Chief Patient Officer and Chief Medical Officer; Chief Medical Officer at Vertex; and who among many other roles was appointed by the Obama Administration to the Board of the Patient-Centered Outcomes Research Institute (PCORI)—all about what happens when you rethink the entire healthcare system from the patient's point of view. We tell patients what they need, instead of asking them what they need—let alone listen to the answer. From drug development to healthcare delivery to clinical trials, what changes in our system when we think about everything from the patient’s perspective? How do we better understand what patients need, and better serve them? What tools and new approaches can we use to truly put the patient at the center of the healthcare system?

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.

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.

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.

We’re at the dawn of a new era where we’re truly able to design biology: from genetically engineered cotton, to meat made from plants, to incredibly complex new therapies composed of engineered cells and genes. And that's just the very beginning. One day, just about everything will be genetically engineered, from our medicines to our materials and manufacturing and much more. The question is no longer, can we design biology? Instead the question now is, what can we build with these tools? So how does that really happen? How can we build precise functions and circuits inside cells? How might we we engineer a cell to sense and perceive its environment, and respond to it? What new generation of companies will be built around these new capabilities? In this episode, Alec Nielsen, co-founder and CEO of Asimov, a company that builds tools to program living cells; Vijay Pande, General Partner at a16z; and Bio Eats World host Hanne Winarsky talk about where we are on the way to this future, what scientific and industry breakthroughs got us here, and the new tools we need—libraries of genetic parts, new platforms, computer simulations and more—to truly design living systems.

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.

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.

Bowen Liu, PhD, investing partner, and Surya Ganguli, PhD, venture partner, join Vijay Pande, PhD, general partner of a16z Bio + Health.

Together, they detail different methods through which AI could assist drug development, the opportunity for AI to flag new targets and compounds for scientists to investigate, and the science fiction-sounding notion of developing a foundation model that untangles biology.

This is an in-depth conversation from three AI experts and biologists, so we’ll also publish the transcript alongside the episode on our website if you want to follow along.

 

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.

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

Jonathan Lim is the CEO of Erasca, but his career path took him on a fascinating journey from practicing as a surgeon to leading life science companies. In a recent conversation, Lim shared valuable insights about his transition to the biotech world, his leadership experiences, and the lessons he's learned while founding and guiding organizations through high-stakes decision making. 

Reflecting on a personal trip to the Galapagos Islands, Lim also drew parallels between Darwinian evolution and business. In today’s challenging biotech environment, entrepreneurs need to adapt or die, consistently evolving by reprioritizing, raising funds smartly, and staying agile to survive and thrive. 

Lawrence Ingrassia, author and journalist, joins Vineeta Agarwala, general partner, and Kris Tatiossian, editorial lead at a16z Bio + Health. 

Together, they discuss Larry's recently published book, A Fatal Inheritance: How A Family Misfortune Revealed A Deadly Medical Mystery. In the book, Larry recounts the story of the p53 cancer suppressor gene, also known as the “guardian of the genome.” Mutations in this gene, which can be inherited, remove a natural tumor defense, making it more likely for an individual to get cancer during their lifetime.

He tells the story of the search for this gene and the scientists who unlocked the mystery of high familial incidences of cancer, Drs. Li and Fraumeni. He also shares a more personal aspect of the story: many members of his family inherited Li-Fraumeni Syndrome and suffered from multiple cancers themselves.

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.

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"

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.

Vijay Pande, PhD, founding partner of a16z Bio + Health, joins Derrick Harris, host of the AI + a16z podcast. Together, they discuss how computer science has subsumed biotech.

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

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.

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.

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.

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. 

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

 

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/

 

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.

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. 

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.

Casey Means, MD, a Stanford-trained physician, cofounder of Levels, and author of the new book Good Energy, joins Vijay Pande,  PhD, founding partner of a16z Bio + Health.

Together, they discuss the downsides of physician specialization, the rising tide of chronic illness in the U.S., and how tracking biomarkers might allow people to determine the best nutrition options for their unique physiology. 

Casey's book is available here.

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.

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.

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. 

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.

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

In this episode of Bio Eats World, a16z founder and internet pioneer Marc Andreessen and general partner Jorge Conde zoom out to discuss the large scale societal effects of the current pandemic on society, healthcare, biotech, and innovation. COVID-19 has been catastrophic—but also catalyzed enormous change and a dramatic groundswell of innovation. Where are we now? Which of these changes will stay, and which may recede? What new innovations and impacts might be still to come, and what are we learning that can be applied towards the future? Building on Marc Andreessen's article and call to action, “It’s Time to Build,” Jorge and Marc discuss what needs to be built in healthcare today (for example, would a pandemic warning system help us next time?); the impact of COVID-19 on innovation and mindsets in the biopharma industry; the shift towards measuring output that could spur more innovation; and finally, what biopharma and venture capital have in common in terms of risk and experimentation that might serve as a much broader model.

In this episode, Matt Wilsey joins Jorge Conde to share the profound personal story of his daughter Grace's diagnosis with NGLY1 deficiency and how it catalyzed his journey to founding a biotech startup, Grace Science, aimed at developing a cure for his daughter’s condition.

Matt emphasizes the importance of strategic partnerships, like his collaboration with Nobel laureate Carolyn Bertozzi, and sheds light on the search for gene therapies for rare diseases. 

Check out our previous episode with Carolyn Bertozzi here.

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.

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, 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.

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!

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.

A year ago, none of us would believe that mRNA vaccines would be a household name. And yet here we are, at the end of 2020, counting the days towards a vaccine that could not just save lives but help bring us back into a world that feels “normal” again. In this special episode, airing the day the FDA authorized the vaccine for emergency use, Moderna CEO Stephane Bancel tells the story of not just the vaccine’s development, but the machine that made the vaccine: the platform, the technology, and the moves behind the vaccine’s development. This episode of Bio Eats World takes us from a world of pipette and lab benches to a world of industrial robots making medicines: We used to grow our vaccines, now we can “print” them, getting them to patients faster and more efficiently than ever before. In conversation with a16z general partner Jorge Conde and Bio Eats World host Hanne Winarsky, Bancel describes the exact moment he realized they might actually be able to make a vaccine for Covid-19; what happened next to go from pathogen to design; how this new technology that uses mRNA works (in a chocolate mousse metaphor!), and what makes it different from “old” vaccines; and how to think about managing both innovation and speed in this world. Why is this such a fundamental shift in the world of drug development? And where will this technology go next?

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.

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.

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.

Rajaie Batniji, MD, PhD, Afia Asamoah, JD, and Sanjay Basu, MD, PhD, cofounders of Waymark, join Vineeta Agarwala, MD, PhD, a16z Bio + Health general partner, to discuss their transformative approach to Medicaid care delivery. This episode dives into their rising risk signal prediction framework, where cutting-edge machine learning predicts patient needs and enables community-based care teams to reduce preventable ER visits and improve health outcomes at scale. 

The team recently published their real-world results—including a 23% reduction in unnecessary acute care—in the New England Journal of Medicine Catalyst.

Additional resources:

• Supporting Rising-Risk Medicaid Patients Through Early Intervention, NEJM Catalyst
• The Body Economic: Why Austerity Kills, by David Stuckler and Sanjay Basu

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.

In this episode of Bio Eats World, we talk to Dr. Jennifer Doudna—winner of the 2020 Nobel Prize for the co-discovery (with Emmanuelle Charpentier) of CRISPR-Cas9—about the art and science of biology. Huge breakthroughs such as Doudna's—which began with the identification of CRISPR in bacteria and was then built into a highly adaptable genome editing platform—are now fueling the evolution of the field. Fundamental knowledge that has largely come from curiosity-driven science has converged with enabling technologies, allowing scientists and biologists in particular to do things that even a couple of years ago, we would have found unimaginable. And biology has begun to shift from an artisanal process, to an industrial one—shifting from qualitative, descriptive science, to quantitative, predictive, high-throughput, science with increasing automation.  In this conversation, a16z General Partner Vijay Pande and Doudna talk about what happens as CRISPR and other tools to engineer and interrogate biology mature. What does the future of biology look like? Can discovery itself be engineered and industrialized—and how do we recognize the moment that becomes possible? Doudna talks about the arc of her career and work through this lens, from basic research to applied; what can be built tomorrow on today’s discoveries; and what at the end of the day may never be engineerable.

In this episode, Vijay Pande and Daisy Wolf of a16z Bio + Health join a16z Podcast host Steph Smith to make a provocative case for why technologists—not just medical professionals—are key to reinventing healthcare. They argue that to transform a sector representing 20% of U.S. GDP, innovation must move beyond curing diseases toward tackling healthcare’s broken systems. 

By likening the healthcare industry to a logistics challenge, Vijay and Daisy outline how technologists can leverage their expertise in consumer engagement, operational efficiency, and AI to drive the next frontier of health innovation. They also explore high-impact opportunities like improving patient experiences and deploying AI for behavioral change at scale. 

If you’re ready to explore new paths in healthcare, this episode is essential listening for understanding the powerful role technologists can play in shaping its future.

In this episode, Slingshot AI cofounders Daniel Cahn and Neil Parikh join a16z Bio + Health general partner Julie Yoo to explore how their mission to transform mental health care with AI took shape. Drawing from their unique journeys—Daniel as the son of a psychologist and Neil as a former medical student-turned-entrepreneur—they discuss the challenges and opportunities of building AI models to model psychological processes and how this could expand access for subclinical mental health support.

 Listen for candid reflections on Slingshot's innovations, visions for AI's role in preventative care, and a future where technology empowers therapists and patients alike.

 

More in "The Opportunity for Healthcare in a Post-LLM World":

• An Ironman Suit for Doctors with Muthu Alagappan
• Voice AI: Solving Healthcare's Workforce Challenges with Ankit Jain
• Super Staffing in Healthcare with Munjal Shah

Plus:

• Learn more about a16z Bio+Health
• Learn more about & Subscribe to Raising Health
• Find a16z Bio+Health on LinkedIn
• Find a16z Bio+Health on X

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.

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.

Elliot Cohen, cofounder of PillPack, joins Julie Yoo, a16z Bio + Health general partner. Together, they discuss Elliot's experience designing and building a consumer-first pharmacy alongside TJ Parker.

Elliot's journey with PillPack began when he noticed his father struggling with a mail-order pharmacy that couldn’t get the simplest thing right: the correct version of a pill.

Elliot shares the nitty-gritty of building a consumer-centric business in healthcare, including how they had to adapt CSV files and cake boxes to get their initial product off the ground, and how they balanced the needs of a healthcare system with the desires of their customers.

 

• Learn more about a16z Bio+Health
• Learn more about & Subscribe to Raising Health
• Find a16z Bio+Health on LinkedIn
• Find a16z Bio+Health on X

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 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.

What the heck is "junk DNA"? In this episode, a16z General Partner Jorge Conde and Bio Eats World host Hanne Winarsky talk to Professor Rick Young, Professor of Biology and head of the Young Lab at MIT—all about "junk" DNA, or non-coding DNA. Which, it turns out—spoiler alert—isn’t junk at all. Much of this so-called junk DNA actually encodes RNA—which we now know has all sorts of incredibly important roles in the cell, many of which were previously thought of as only the domain of proteins. This conversation is all about what we know about what that non-coding genome actually does: how RNA works to regulate all kinds of different gene expression, cell types, and functions; how this has dramatically changed our understanding of how disease arises; and most importantly, what this means we can now do—programming cells, tuning functions up or down, or on or off. What we once thought of as "junk" is now giving us a powerful new tool in intervening in and treating disease—bringing in a whole new category of therapies.

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.

John Crowley, President and CEO of Biotechnology Innovation Organization (BIO), joined Jorge Conde, general partner at a16z Bio + Health.

Together, they talk about John’s entry into biotech and his time as a founder, all motivated by his determination to discover and develop a treatment for his children, who have Pompe disease.

They also talk about John’s priorities as head of BIO and how that could translate into policy.

Jonathan Swerdlin, cofounder and CEO, and Mark Hyman, MD, cofounder and Chief Medical Officer of Function Health join Vijay Pande, general partner, and Daisy Wolf, investment partner of a16z Bio + Health.

Together, they discuss their personal health journeys that led to founding Function, how they’re planning to scale Function, and what the future could look like.

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. 

Nobel laureate Carolyn Bertozzi joins Jorge Conde to unravel the concept of bioorthogonal chemistry. 

Carolyn traces her pioneering path from early studies in carbohydrate chemistry to how her lab developed the revolutionary ability to manipulate chemical reactions inside the human body. 

Together, they highlight the intersection of cutting-edge academic research and the challenges of translating discoveries into market-ready solutions. They also discuss navigating the science-to-startup journey, balancing academic and commercial ambitions, and leveraging precision therapies to address unmet medical needs in cancer and beyond. It’s a compelling case study for founders looking to push the frontiers of biotech.

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.

You don't have to build a million planes to test a million aeronautical designs; we have mathematical simulations and models that do that for us. But in biology—once the class you'd take in high school if you loved science, but hated math—that's been impossible... until very recently. In this episode, Markus Covert, Professor of Bioengineering at Stanford, a16z deal partner Judy Savitskaya, and Bio Eats World host Hanne Winarsky, talk all about where we are in our ability to simulate and build models for how biology works. Because biology has been so qualitative in the past, and so complex, it's been extremely difficult to translate samples that are, say, gel smudges on a plate into the kind of qualitative data we need for these simulations and models. But we're finally reaching the “Google Maps” moment in biology, Covert says, beginning to be able to build models at the single molecule level, of genetic circuits, whole cells, the dynamic interactions between different cells, map them onto larger networks like tissue… even, of course, model on a global level the effects of a pandemic. The conversation covers Marcus’ story of the Eureka moment behind the first whole cell model; what this new ability to simulate and model will allow us to understand and predict that we haven’t been able to before; and why it all matters—how these tools are bringing us into a new era of designing new functionalities, even new kinds of biological life.

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

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

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.

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.

Descriptions of the mental illness we today call schizophrenia are as old as humankind itself. And more than likely, we are are all familiar with this disease in some way, as it touches 1% of us—millions of lives—and of course, their families. In this episode, we dive into the remarkable story of one such American family, the Galvins: Mimi, Don, and their 12 children, 6 of whom were afflicted with schizophrenia. In his book, Hidden Valley Road: Inside the Mind of an American Family, Robert Kolker follows the Galvins from the 1950s to today—through, he writes, “the eras of institutionalization and shock therapy, the debates between psycho-therapy versus medication, the needle-in-a-haystack search for genetic markers for the disease, and the profound disagreements about the cause and origin of the illness itself.” Because of that, this is really more than just a portrait of one family; it’s a portrait of how we have struggled over the last decades to understand this mysterious and devastating mental illness: the biology of it, the drivers, the behaviors and pathology, the genomics, and of course the search for treatments that might help, from lobotomies to ECT to thorazine. Also joining Robert Kolker and a16z’s Hanne Winarsky in this conversation is Stefan McDonough, Executive Director of Genetics at Pfizer World R&D, one of the genetic researchers who worked closely with the Galvins. The conversation follows the key moments where our understanding of this disease began to shift, especially with new technologies and the advent of the Human Genome Project—and finally where we are today, and where our next big break might come from.

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

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.

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.

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.

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.

 

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.

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.

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. 

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.

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.