This post first appeared as an issue of the a16z Bio Newsletter. Subscribe to stay on top of the latest trends in bio and healthcare.

The second coming of RNA medicines

The Moderna and Pfizer/BioNTech COVID vaccines mark a major milestone – not just for this pandemic, but for their entire therapeutic class: RNA-based drugs. While companies like Alnylam, Sarepta, and IONIS have received FDA approval for a handful of RNA therapeutics, the design of new RNA drugs has been slower than promised due to some technical and practical challenges, so the excitement for this class has waned over the last two decades. The COVID mRNA vaccines have now re-ignited interest in a huge way – and perhaps most importantly – demonstrated that many of the challenges that plagued these early companies can be resolved. In this blog post, bio deal team partner Judy Savitskaya lays out how the COVID vaccine operation will help validate and accelerate development in key areas of RNA-based drug design, as well as the open problems for the field. And this episode of the Bio Eats World podcast with host Hanne Winarsky, a16z general partner Jorge Conde, and MIT Professor Rick Young, dives into the world of “junk” DNA – which, spoiler alert, turns out to be fueling an RNA revolution.

Swapping data for doses

Real-time data collection about the spread and impact of COVID infection has been a central challenge throughout the global pandemic. This data is critical not just for public health measures like contact tracing, but also for understanding the impact of new medicines. The UK’s RECOVERY trial set the bar for the world on how to conduct randomized, controlled clinical trials for anti-COVID drugs. And now, Israel is setting another, with the creative deal forged with vaccine manufacturers: “Vaccines For Data” (you can actually read a redacted version of the agreement from the Israel Ministry of Health here!). They locked in a supply of the Pfizer/BioNTech vaccine by promising not only a swift vaccine rollout, but also a continuous stream of data from their centralized medical record system to study the real-world efficacy of the vaccines (which, by the way, is looking incredible). It’s hard to even imagine such datasets in the fragmented US healthcare system right now (compare this to our cutting-edge system of hand-annotated, paper CDC vaccine cards)… but these examples from the UK and Israel paint a vision of a future tech-enabled clinical research ecosystem.

-a16z general partner Vineeta Agarwala

Welcome to the “It’s Time to Heal” Clubhouse 

We’ve been jamming on Clubhouse. In our “It’s Time to Heal” room (every Monday at 5pm PT), a16z cofounder Marc Andreessen and general partners Julie Yoo, Vijay Pande, Jorge Conde, and Vineeta Agarwala chat with special guests about the future of bio and healthcare in a live, interactive discussion. We’ve covered a lot of ground:

• A new generation of digital health companies: 6 builders from Firefly Health, Folx Health, Propeller Health, Ribbon Health, TruePill, and Wheel shared what it takes to build a digital health company from the ground up today versus 10 years ago; how the cost to set up a full-stack digital health company from scratch has decreased by an order of magnitude in that same time period; which healthtech companies are creating the new tech stack for virtual-first care; and direct-to-consumer healthcare as one of the fastest growing segments in the market. 
• Stopping food waste, saving the world? Apeel founder James Rogers talked about technologies that work with nature to reduce food waste, changing how food is grown, distributed, and eaten. We talked about how this tech works, what it impacts (from the avocado on your counter to the global food economy); the journey from materials science to strawberry fields; the transition from academia to industry; and most of all, advice for other founders on company building: getting that first contract, building the channel, unknown unknowns, and blue sky possibilities in bioengineering. 
• The past, present, and future of biotech: EQRx cofounder Alexis Borisy and the a16z bio team talked about waves of innovation that have shaped the biotech industry; the pressure to develop new tools that enable us to better elucidate and understand disease, now that we have such sophisticated tools to engineer biology; and the new breed of founders coming into biotech industry.
• Coming soon on Clubhouse: We’ve got a lot more in store. Be sure to follow the ‘a16z bio’ room, or sign up for the waitlist here. 

Biotech’s beginnings: A reading list

The origin story of Silicon Valley has become the stuff of legend. The origin story of biotech, on the other hand, is a much less familiar tale. The closest thing we have to a Hewlett-Packard “two-guys-in-a-garage” story in biotech is Robert Swanson and Herb Boyer teaming up to form Genentech. For a crash course in the industry’s history, here’s Jorge Conde’s list of key books on the origins of biotech, with some additional suggestions from our network:

• Genentech: The Beginnings of Biotech, by Sally Smith Hughes. From the company’s founding in South San Francisco through its scientific triumphs, IPO, and eventual acquisition.
• The Billion-Dollar Molecule: The Quest for the Perfect Drug, by Barry Werth. Chronicles the stresses and struggles during the early days of Vertex Pharmaceuticals, one of Boston’s bright lights in biotech.
• The Antidote: Inside the World of New Pharma, by Barry Werth. A sequel to Billion-Dollar Molecule that follows Vertex’s next acts over two decades to become one of the world’s leading biotech companies.
• The Cure: How a Father Raised $100 Million – and Bucked the Medical Establishment – in a Quest to Save His Children, by Geeta Anand. John Crowley starts up Novazyme for his children, eventually selling to Genzyme. 
• From Alchemy To IPO: The Business Of Biotechnology, by Cynthia Robbins-Roth. Published nearly 20 years ago, it details the early history of the biotech industry’s pioneering companies. 
• Science Lessons: What the Business of Biotech Taught Me About Management, by Gordon Binder and Philip Bashe. Co-written by the former CEO, it tells the story of Amgen’s meteoric rise during this era, spurred by the launch of Epogen. (Suggested by Vineeta Agarwala)
• A Cure Within: Scientists Unleashing the Immune System to Kill Cancer, by Neil Canavan. Immuno-oncology giants share their journey. (Suggested by Tmunity CEO Oz Azam)
• Doing Capitalism in the Innovation Economy, by William H. Janeway. The lesson on “never underestimate how bad management can ruin a company” is classic. (Suggested by Stanford Medicine Professor Carlos D. Bustamante)
• HER-2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer, by Robert Bazell. Genentech’s drug Herceptin was a first in many respects, but it’s success was driven by a few individual stories of activist scientists, doctors, and inspirational patients. (Suggested by Judy Savitskaya)

Genomics in action

The application of genomics and genetic testing in healthcare has evolved from a novelty to an incredibly useful tool for certain specific and rare conditions. But genomics is growing up: as we discuss on two episodes of the Bio Eats World podcast, genomics is finally primed to be part of the care journey of every patient. First, on “The Genetics of Risk,” host Lauren Richardson speaks with Peter Donnelly, Oxford Professor and CEO of Genomics PLC, and Vineeta Agarwala about the new era of genetic testing and its potential to reorient our entire healthcare system via genomic prevention. And on Journal Club: Why Do Only Some People Get Severe COVID?, Helen Su, Chief of the Human Immunological Diseases Section at the NIAID, and Lauren discusses the massive international effort to uncover genetic risk factors for severe COVID. DNA might not be entirely deterministic, but it will increasingly determine our healthcare journey.

And finally… expanding your consciousness

“Physicists tell us what’s conceivable, chemists tell us what’s possible, and biologists tell us what actually happened.” —Frank Wilczek Click To TweetBiology doesn’t exist in a vacuum. As Nobel Laureate Frank Wilczek tells Bio Eats World co-hosts Lauren Richardson and Hanne Winarsky, “Physicists tell us what’s conceivable, chemists tell us what’s possible, and biologists tell us what actually happened.” In this wide-ranging and philosophical conversation, Wilczek talks all about the essential principles of modern physics that have built our understanding of reality and the universe around us; the idea of “radical conservatism” and how it pushes every theory to its limit; how biological complexity arises from the elegant simplicity of physics; and much more. And on Journal Club: A Safer Psychedelic, Lauren and UC Davis Assistant Professor David Olson dive into psychedelic medicine – and whether hallucinations are essential for therapeutic benefit.

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