Raising Health

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Journal Club: How to Win an Evolutionary Arms Race Dec 10, 2020

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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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The Google Maps Moment in (Modeling) Biology Dec 07, 2020

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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. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Journal Club: Bioengineering Birth Dec 03, 2020

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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.

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The Story of Schizophrenia Nov 30, 2020

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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. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Food as Medicine Nov 24, 2020

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We all know that eating healthy is better for you—and that following that advice is far harder than it sounds, for a multitude of reasons, from culture to preferences to access and affordability. And yet the reality is that access to good, nutritious food is perhaps the most powerful medical treatment we have, when it comes not just preventing sickness, but helping sick people get better—and potentially saving the healthcare system potentially billions in treating chronic disease. So what happens if we begin to treat food truly as a medicine in the healthcare system? How can we really implement this "medicine" into the healthcare system? What are the different approaches, from food delivery to packaging to the content of the meal itself? How can food as a medicine be distributed, paid for and reimbursed, and what role can technology take in increasing access, distribution, and more? In this conversation, a16z General Partner Julie Yoo talks with Dr. Andrea Feinberg, previously the Founder and Medical Director of Geisinger Fresh Food Farmacy and Josh Hix, entrepreneur and co-founder of the food delivery start up Plated; a16z all about what food as a medicine might look like, whether personal taste and variety matters, how technology might not just help access but shift our snacking tendencies towards health, and the enormous opportunity to impact chronic disease through addressing food insecurity. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Journal Club: Decoding Developmental Disorders Nov 19, 2020

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

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

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Health—at What Price? Nov 16, 2020

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Imagine if the airline industry did not post prices for flights in advance. What if instead of posting fares on travel sites, airlines argued they could only bill you after the flight, because they didn't know what the fuel price will be that day; whether or not you would consume a beverage; if the flight might be diverted or delayed; whether that pilot would have to work harder and bill more in their coding of the flight after they land? And yet, this is exactly what happens in healthcare. Despite the cost crisis in healthcare, we still don't talk about prices—prices for procedures, for visits, for services. But in January 2021, thanks to new regulation, that will change. In this episode, a16z General Partner Julie Yoo talks with Dr. Marty Makary, surgical oncologist at Johns Hopkins University School of Medicine, health policy expert—and a longtime advocate for transparent pricing in the healthcare system. Makary argues that making prices obvious will change all kinds of behaviors in the healthcare system, not just allowing consumers to "shop" for the best value of different healthcare services, but will drive higher quality standards; minimize things like surprise billing and incentives towards volume; increase the rigor of analyzing the medical appropriateness of certain clinical decisions (do we need this elective procedure or not? is it good longterm value?); affect even how we choose our doctors; and much more. Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Journal Club: Defeating Type 1 Diabetes Nov 12, 2020

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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.

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We, the Patients Nov 09, 2020

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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? Hosted by Simplecast, an AdsWizz company. See https://pcm.adswizz.com for information about our collection and use of personal data for advertising.

Journal Club: Architecting an Aggressive Cancer Nov 05, 2020

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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.

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