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.

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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, host Lauren Richardson (@lr_bio) is joined by Dr. 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. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com

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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"

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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.

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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. 

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Building a software company in healthcare is hard—and comes along with unique challenges no other entrepreneurs face. In this conversation, a16z bio general partner (and previous founder of genomics company Knome) Jorge Conde; and a16z bio partner and former founder Julie Yoo (of patient provider matching system, Kyruus) share their mistakes and hard earned lessons learned with Bio Eats World host Hanne Winarsky in this now classic episode, first aired on the a16z Podcast.

Why is this so damn hard? How should founders think about this space differently? What are the specific things that healthcare founders can do—when, where, and why? You wish you only knew all this when you started your own company. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com

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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? Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com

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with @pmarca and @vijaypande

How come things like healthcare, education, and housing get more and more expensive, but things like socks, shoes, and electronics all get cheaper and cheaper? In this episode of Bio Eats World, a16z founder and internet pioneer Marc Andreessen, and General Partner Vijay Pande, discuss the lesser known law of economics that explains why healthcare, education and housing is so damn expensive, and getting worse.

What’s really at heart is tech’s ability to transform (expensive) services into (affordable) goods: think of the cost of a live string quartet, versus a streamed recorded track; or the cost of a custom-made shoe, versus a factory-made one. Until now, using tech to similarly transform services into goods in healthcare has seemed like an impossible dream — how would you do this for, say, the service of doctors providing care? But in this wide ranging conversation all about technology and society across all industries, Andreessen and Pande talk about the massive new gains recent technologies have begun to make this seem within reach, from eye surgery in malls to using AI in processing medical claims. Is there a future in which what doctors are doing today feels analogous to farmers hand plowing fields 300 years ago? And what would the role of that doctor of the future be? Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com

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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.

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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.

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