Listen to a podcast, please open Podcast Republic app. Available on Google Play Store.
The Biology of Pain
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?
|Oct 19, 2020|
Journal Club: Super-Scaling COVID-19 Testing with DNA Sequencing
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.
|Oct 15, 2020|
Biology by Design
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.
|Oct 13, 2020|
Journal Club: Turning a Toxin into a Genome Editing Tool
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.
|Oct 08, 2020|
Going Back to the Workplace in a Pandemic
It's not normal to talk to your employer about the details of your health: your current temperature, who you've been exposed to, whether your kid is sick, whether or not you've been social distancing. So how do employers handle and manage this entirely new process of employees returning to the workplace in the midst of an ongoing pandemic? In this episode of Bio Eats World, Vineeta Agarwala (general partner at a16z), Phong Nguyen (EVP and General Manager at Accolade), Ryan Sandler (CEO and Cofounder of Truework), and Mark Sendak (Population Health & Data Science Lead at the Duke Institute for Health Innovation) talk about what it means for employers to now have to manage employee health in a whole new way, figuring out when it's safe to come back, how, and what tools you need. From monitoring employee health and preventing transmission to triaging what happens when there is a documented case; temperature checks (do they even make sense?); testing (how often and in what way?); and above all, where can technology help, this is an entirely new world for employers and employees both. All these decision trees involve not just a complex business logic and new tools and procedures, but also big issues around employee privacy and trust, and a fundamental shift in the relationship between employer and employee... as this becomes a new feature of our COVID world.
|Oct 06, 2020|
Journal Club: Modeling Mysterious Brain Structures
The human brain is endlessly fascinating and mysterious, but the majority of brain research to date has focused on neurons and their functions. While the other types of brain cells, such as astrocytes and glia, are starting to get their due, there is another element of the brain that to this day has gone woefully unstudied: the cerebrospinal fluid (CSF) and the brain structure that produces it, the choroid plexus. The CSF is a clear, colorless fluid found in the brain and spinal cord, and is traditionally thought to protect the brain from injury by acting as a shock absorber.
In this episode, Madeline Lancaster, a Group Leader at the MRC Laboratory of Molecular Biology in Cambridge and Lauren Richardson discuss the article "Human CNS barrier-forming organoids with cerebrospinal fluid production" by Laura Pellegrini, Claudia Bonfio, Jessica Chadwick, Farida Begum, Mark Skehel, Madeline A. Lancaster published in Science. The paper describes a new model for studying the CSF and the choroid plexus by creating what’s sometimes called a mini-brain or a brain-in-a-dish, but is more accurately known as a cerebral organoid. With this model, Dr. Lancaster and her team were able to reveal new insights into the composition and function of the choroid plexus, and importantly, how it forms a key barrier between the blood and the brain. We discuss the how these organoids can be used to study brain development, evolution, and improve the drug development process.
|Oct 01, 2020|
Revolutions in Cancer Treament—Past, Present, and Future
with @JorgeCondeBio, @JLimMD, @AmerCancerCEO, and @omnivorousread In this episode of Bio Eats World, we explore all the major revolutions in cancer treatment across the history of medicine—and what’s coming next. Hanne Winarsky delves into the past and future of the fight against cancer with Gary Reedy, CEO of the American Cancer Society; Jonathan Lim, CEO of Erasca, a biotech company with the mission of erasing cancer; and Jorge Conde, a16z general partner. The conversation spans not only the history of cancer treatment from the early days of surgery and the first radiology treatment (with an x-ray!), but also the fundamental nature of cancer—its origins, progressions, and how to stop it; the birth of precision genetic medicine and targeted therapies; our most powerful tools today (both low and high tech); and finally, the coming new tools and revolutions at the very cutting edge of cancer treatment.
|Sep 29, 2020|
Journal Club: Degrading Drugs for Problematic Proteins
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.
|Sep 24, 2020|
The Biology of Aging
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.
|Sep 22, 2020|
Introducing "Bio Eats World"
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.
|Aug 18, 2020|