David Reich is back.
He and collaborator Ali Akbari just published a paper that overturns a long-standing consensus about human evolution — that natural selection has been dormant in our species since the agricultural revolution.
By scaling ancient DNA sequencing and developing a new statistical method, they found that selection has actually sped up.
Selection went especially bonkers during the Bronze Age (around 3,000 years ago).
That’s when gene frequencies for everything from immune function to body fat to intelligence were most in flux.
Over the last 10,000 years, selection pushed the genetic predictor of cognitive performance up by roughly a full standard deviation — most of it between 4,000 and 2,000 years ago.
After we finished recording, David sketched out on a whiteboard his new heretical model about who the Neanderthals really were. Luckily, I took out my iPhone and managed to record it.
He thinks the standard story (that Neanderthals are some separate archaic lineage we interbred with a little) just doesn’t fit the evidence. Instead, he proposes that Neanderthals are essentially genetically-swamped modern humans.
A small population somewhere around the Caucasus invented Middle Stone Age technology roughly 300,000 years ago and expanded outward. The ones that moved into Europe interbred with local archaic humans, got genetically swamped, and became Neanderthals. The same expansion went into Africa, met much more diverged archaic Africans, and that mixture became us.
This means Neanderthals and modern humans share the same cultural ancestry — the only difference is which archaic humans they mixed with afterward.
David is a brilliant and rigorous scholar. It was a real delight to learn from him again.
Watch on YouTube; read the transcript.
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Timestamps
(00:00:00) – Ancient DNA suggests strong selection over last 10,000 years
(00:15:45) – Natural selection intensified during the Bronze Age
(00:35:02) – Why didn’t evolution max out intelligence?
(00:57:21) – Evolution is limited by time, not population size
(01:09:02) – Why no farming before the Ice Age?
(01:17:13) – The Neanderthal puzzle David can’t stop thinking about
(01:54:10) – The methodology behind this breakthrough
Get full access to Dwarkesh Podcast at www.dwarkesh.com/subscribe
This week, OpenAI announced a loosened partnership with Microsoft and an aggressive new strategy to secure computing power. We unpack what these updates signal about OpenAI’s business strategy and whether the company can scale while balancing a trial against Elon Musk and investor concerns over missed financial targets. Then, the A.I. researcher Dr. Adam Rodman, of Harvard Medical School, returns to tell us about the most significant ways A.I. is changing how doctors treat patients. And finally, can an LLM trained only on very old texts predict the future? We’re talking with one of the creators of the chatbot talkie.
Guests:
Dr. Adam Rodman, internal medicine physician at Beth Israel Deaconess Medical Center and assistant professor at Harvard Medical School.
David Duvenaud, associate professor at the University of Toronto, former team lead at Anthropic and co-creator of talkie.
Additional Reading:
Microsoft and OpenAI Loosen Their Partnership
Elon Musk and Sam Altman’s Epic Fight Heads to Court
OpenAI Misses Key Revenue, User Targets in High-Stakes Sprint Toward IPO
Take It From a Doctor: It’s OK if Your Medical Advice Comes From A.I.
We want to hear from you. Email us at hardfork@nytimes.com. Find “Hard Fork” on YouTube and TikTok.
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Scientist and Harvard professor Dr. David Sinclair, A.O., Ph.D., reveals his latest research on how to reverse ageing, insights into vitamins and supplements, why DNA is not your destiny, and the first clinical trials to reverse human ageing and blindness!
Dr. David Sinclair is a world-renowned Professor of Genetics at Harvard Medical School and the leading authority on longevity science. He is Founder of Lifespan.com and multiple biotechnology companies, Co-Chief Editor of the journal Ageing, and bestselling author of ‘Lifespan: Why We Age - And Why We Don’t Have To’.
Dr. Sinclair explains:
◼️The “Information Theory of Aging” that regards ageing as a treatable disease
◼️Advances in resetting biological age using cellular “backup copies”
◼️His specific supplement stack for longevity
◼️Why fasting and “good stress” are science-based longevity strategies
◼️How his lab’s gene therapy is being used to restore eyesight and reverse blindness
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Research document: https://docs.google.com/document/u/0/d/1sarDR85LvkK5hv7HMN_UUDvHO9MIi9bNPhLyIRZQ9vg/edit
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George Church is the godfather of modern synthetic biology and has been involved with basically every major biotech breakthrough in the last few decades.
Professor Church thinks that these improvements (e.g., orders of magnitude decrease in sequencing & synthesis costs, precise gene editing tools like CRISPR, AlphaFold-type AIs, & the ability to conduct massively parallel multiplex experiments) have put us on the verge of some massive payoffs: de-aging, de-extinction, biobots that combine the best of human and natural engineering, and (unfortunately) weaponized mirror life.
Watch on YouTube; listen on Apple Podcasts or Spotify.
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Timestamps
(0:00:00) – Aging solved by 2050
(0:07:37) – Finding the master switch for any trait
(0:19:50) – Weaponized mirror life
(0:30:40) – Why hasn’t sequencing/synthesis led to biotech revolution?
(0:50:26) – Impact of AGI on biology research progress
(1:00:35) – Biobots that use the best of biological and human engineering
(1:05:09) – Odds of life in universe
(1:09:57) – Is DNA the ultimate data storage?
(1:13:55) – Curing rare diseases with genetic counseling
(1:22:23) – NIH & NSF budget cuts
(1:25:26) – How one lab spawned 100 biotech companies
Get full access to Dwarkesh Podcast at www.dwarkesh.com/subscribe
This week, President-elect Donald Trump picked Brendan Carr to be the next chairman of the F.C.C. We talk with The Verge’s editor in chief, Nilay Patel, about what this could mean for the future of the internet, and for free speech at large. Then, a new study found that ChatGPT defeated doctors at diagnosing some diseases. One of the study’s authors, Dr. Adam Rodman, joins us to discuss the future of medicine. And finally, court is back in session. It’s time for the Hard Fork Crimes Division.
One more thing: We want to learn more about you, our listeners. Please fill out our quick survey: nytimes.com/hardforksurvey.
Guests:
Nilay Patel, co-founder of The Verge and host of the podcasts Decoder and The Vergecast.
Adam Rodman, internal medicine physician at Beth Israel Deaconess Medical Center and one of the co-authors of a recent study testing the effectiveness of ChatGPT to diagnose illnesses.
Additional Reading:
Trump Picks Brendan Carr to Lead F.C.C.
A.I. Chatbots Defeated Doctors at Diagnosing Illness
Gary Wang, a Top FTX Executive, Is Given No Prison Time
We want to hear from you. Email us at hardfork@nytimes.com. Find “Hard Fork” on YouTube and TikTok.
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I had no idea how wild human history was before chatting with the geneticist of ancient DNA David Reich.
Human history has been again and again a story of one group figuring ‘something’ out, and then basically wiping everyone else out.
From the tribe of 1k-10k modern humans who killed off all the other human species 70,000 years ago; to the Yamnaya horse nomads 5,000 years ago who killed off 90+% of (then) Europeans and also destroyed the Indus Valley.
So much of what we thought we knew about human history is turning out to be wrong, from the ‘Out of Africa’ theory to the evolution of language, and this is all thanks to the research from David Reich’s lab.
Buy David Reich’s fascinating book, Who We Are How We Got Here.
Watch on YouTube. Listen on Apple Podcasts, Spotify, or any other podcast platform. Read the full transcript here.
Follow me on Twitter for updates on future episodes.
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Timestamps
(00:00:00) – Archaic and modern humans gene flow
(00:20:24) – How early modern humans dominated the world
(00:39:59) – How bubonic plague rewrote history
(00:50:03) – Was agriculture terrible for humans?
(00:59:28) – Yamnaya expansion and how populations collide
(01:15:39) – “Lost civilizations” and our Neanderthal ancestry
(01:31:32) – The DNA Challenge
(01:41:38) – David’s career: the genetic vocation
Get full access to Dwarkesh Podcast at www.dwarkesh.com/subscribe
Nathan sits down with Professor Zak Kohane, the Chair of the Department of Biomedical Informatics at Harvard Medical School, and co-author of the new book, The AI Revolution in Medicine, for which Sam Altman, OpenAI’s CEO wrote the foreword to the book.
Professor Kohane was among a select few people to receive early preview and research access to GPT-4 in the fall of 2022, and his approach to exploring and characterizing how AI is about to transform medicine.
The book is out May 13, 2023 and can be ordered here (or on Amazon by searching for "The AI Revolution in Medicine")
Regardless of the field you're in, Dr. Kohane's combination of deep immersion, enthusiastic exploration, pragmatic optimism, risk awareness, realism, and forward-thinking vision make this a worthy example for others to study and emulate.
--
We're hiring across the board at Turpentine and for Erik's personal team on other projects he's incubating. He's hiring a Chief of Staff, EA, Head of Special Projects, Investment Associate, and more. For a list of JDs, check out: eriktorenberg.com.
RECOMMENDED PODCAST:
The HR industry is at a crossroads. What will it take to construct the next generation of incredible businesses – and where can people leaders have the most business impact? Hosts Nolan Church and Kelli Dragovich have been through it all, the highs and the lows – IPOs, layoffs, executive turnover, board meetings, culture changes, and more. With a lineup of industry vets and experts, Nolan and Kelli break down the nitty-gritty details, trade offs, and dynamics of constructing high performing companies. Through unfiltered conversations that can only happen between seasoned practitioners, Kelli and Nolan dive deep into the kind of leadership-level strategy that often happens behind closed doors. Check out the first episode with the architect of Netflix’s culture deck Patty McCord.
https://link.chtbl.com/hrheretics
TIMESTAMPS:
(00:00) Episode preview
(05:29) Dr. Isaac Kohane’s story
(15:00) Sponsor: Omneky
(16:29) Advice to others thinking of applying AI to their own disciplines
(20:33) The tension of using AI in medicine
(25:04) The Trial Paradigm of AI
(31:15) Is it possible to use GPT as a healthcare provider in population studies?
(34:14) The Trainee Paradigm of AI
(36:09) The Partner Paradigm of AI and how doctors should use AI
(40:33) AI provided interaction and how that can improve patient care
(42:26) The Torchbearer Paradigm of AI
(42:59) Can GPT independently conduct medical research?
(46:58) The future for impactful use cases of AI in medicine
(51:04) Integrating AlphaFold into language models
(54:10) AI-alignment and patient data in medicine
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More show notes and reading material released in our Substack: cognitiverevolution.substack.com
John Abramson is faculty at Harvard Medical School and a family physician for over two decades. He’s the author of the new book Sickening about how big pharma broke American healthcare and how we can fix it. Please support this podcast by checking out our sponsors:
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OUTLINE:
Here’s the timestamps for the episode. On some podcast players you should be able to click the timestamp to jump to that time.
(00:00) – Introduction
(14:29) – Biggest problem with big pharma
(23:30) – Advertising
(43:22) – Corruption
(59:38) – Pfizer vaccine data
(1:08:30) – Vaccine profits
(1:19:25) – Censorship
(1:40:11) – FDA
(1:48:45) – NIH
(1:57:42) – Live longer
(2:01:13) – Medications
(2:09:37) – Doctors
(2:13:44) – Advice for young people
(2:14:40) – Big pharma’s influence
(2:19:24) – Mortality
(2:21:15) – Meaning of life
David Sinclair is a geneticist at Harvard and author of Lifespan. Please support this podcast by checking out our sponsors:
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EPISODE LINKS:
David’s Twitter: https://twitter.com/davidasinclair
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OUTLINE:
Here’s the timestamps for the episode. On some podcast players you should be able to click the timestamp to jump to that time.
(00:00) – Introduction
(09:34) – Staying young at heart
(13:31) – Bringing people back to life
(19:05) – Wearables and tracking health data
(28:18) – How to solve aging
(38:23) – Why do we age?
(43:50) – Genetic reset switch that reverses aging
(46:20) – AI in biology
(48:52) – Health data
(56:58) – Fasting
(1:04:29) – Diet
(1:12:41) – Exercise
(1:18:01) – Sleep
(1:26:29) – Data
(1:32:00) – Extending lifespan
(1:34:42) – Immortality
(1:40:28) – Denial of death
(1:43:45) – Meaning of life without death
Today we’re joined by Sherri Rose, Associate Professor at Harvard Medical School. We cover a lot of ground in our conversation, including the intersection of her research with the current COVID-19 pandemic, the importance of quality in datasets and rigor when publishing papers, and the pitfalls of using causal inference.
We also touch on Sherri’s work in algorithmic fairness, the shift she’s seen in fairness conferences covering these issues in relation to healthcare research, and a few recent pape
What is the nature of physical pain? Why do we even experience it? Is there one type, or many? Do people experience pain differently? What is happening in our brains and our bodies when we experience pain? What is the biological link between pain and addiction? In this episode Clifford Woolf, Professor of Neurobiology at Harvard Medical School and a renowned expert on understanding pain, shares with with a16z's Hanne Tidnam all we know about the biology of pain.
Technology is enabling a new, deeper, and much more complex understanding of pain—which pathways and neurons are activated in the brain when, what patterns might represent which experiences of pain. We now understand that the notion of pain as a simple switch that can be switched on or off (you have pain/you don't have pain) and measured by categories like mild, moderate, or severe is just incorrect. Woolf describes the 4 different broad types of pain we in fact experience, what the purpose of each is, and what it means now that we can phenotype them and begin to understand them as distinct. Now that we have this deeper and much more complex understanding of pain, what does it mean for how we can treat pain in the future, and where we can intervene?
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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.
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with George Church (@geochurch) and Jorge Conde (@JorgeCondeBio)
Renowned scientist George Church is known for his groundbreaking work and methods used for the first genome sequence, and for his work in genome editing, writing & recoding -- in fact, Church’s innovations have become an essential building block for most of the DNA sequencing methods and companies we see today. In this conversation, a16z bio general partner Jorge Conde -- who also founded a company with Church out of the George Church Lab -- take us on a wild journey into the scientist’s mind and work, starting with what the leading pioneer in the space makes of where we are today with CRISPR (especially given recent news about CRISPR babies in China), to the broader implications of all of this on a cultural level, and finally to what it really takes to go from science fiction, to lab, to reality.
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with Jorge Conde (@jorgecondebio), David Reich, and Hanne Tidnam (@omnivorousread)
Trying to reconstruct the deep past of ancient humans out of present-day people has until now been like trying to reconstruct a bomb explosion in a room from bits of shrapnel, says David Reich, Professor of Genetics at Harvard Medical School and author of the new book, Who We Are and How We Got Here: Ancient DNA and the New Science of the Human Past. But technological advances and new tools available only in the last few years have suddenly revolutionized this field, opening up an entirely new window into the past as well as our present humanity.
This conversation, with a16z bio general parter Jorge Conde, and Hanne Tidnam, dives into this new scientific revolution of the study of the ancient genome. Beginning with the so-called "black hole" of Mitochondrial Eve to the most revelatory discoveries from new knowledge and scientific tools, this episode of the a16z Podcast delves into the ways archaic humans and ancient DNA tell us not just about our biology, but about ourselves.
image: Ben Casey, Wikimedia Commons
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with Kristen Fortney (@kpfortney), Jeff Kaditz (@jeffkaditz), David Sinclair (@davidasinclair), and Hanne Tidnam (@omnivorousread)
Even without a mythical fountain of youth, scientific advances have already dramatically increased how long humans live. But those advances to date have also largely been due to lower mortality rates, less infectious disease, and better nutrition. So when will modern medicine increase not just our healthspan, but our lifespan -- slowing down and possibly even reversing aging? What tools will it take? And what else, beyond the biology and technology involved, would change -- in our healthcare system and society as a whole?
In this episode of the a16z Podcast -- recorded at a16z's November 2017 Summit -- Kristen Fortney, CEO and cofounder of BioAge Labs; Jeff Kaditz, CEO and cofounder of Q.Bio; David Sinclair, Co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School; and Michael Snyder, Professor and Department Chair of Genetics at Stanford University (as well as co-founder of and advisor to Q.Bio), in conversation with Hanne Tidnam, break down the science from the science fiction around the topics of longevity, health, and aging.
image credit: Garry Knight/ Flickr
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