Playing God or Saving Nature? Gene Editing, Artificial Wombs & the Return of Extinct Species | Ben Lamm PT 2
Ben Lamm discusses Colossal's work in de-extinction and synthetic biology, covering parallel pathway development for woolly mammoths and dire wolves, the role of P53 in cancer prevention, AI's potential to revolutionize biology within 5-10 years, and applications beyond conservation including longevity science and plastic degradation.
Summary
Ben Lamm, founder of Colossal, discusses the complex science behind resurrecting extinct species and engineering biology. He explains how Colossal employs parallel pathway development—simultaneously conducting computational analysis, cell line growth, genetic editing, and IVF research—to accelerate what would otherwise take a decade per animal down to a more manageable timeline. This approach requires substantial infrastructure: four labs, 172 scientists, 17 academic partners, 40 funded postdocs, and 95 scientific advisors, supported by approximately half a billion dollars in capital.
Lamm details the technical challenges, particularly around P53 gene regulation during editing. Elephants and blue whales naturally express P53 at 20 times higher levels than humans, which suppresses cancer development. When making genetic edits that appear as mutations to cellular machinery, they must temporarily downregulate P53 to allow editing, then reactivate it—a complex reversal of immortalization constructs used in cell biology.
On the dire wolf project specifically, Lamm addresses misconceptions stemming from a 2021-2022 paper that used only 0.15x genome coverage (15% complete) and concluded dire wolves fell somewhere between wolves and jackals. Colossal obtained 500 times more data from two samples with 60,000 years of genetic divergence between them, reconstructing a phylogenetic tree showing dire wolves were closer to gray wolves. They made 14 genes with 20 total edits, using gray wolves (99.5% genetically identical) as donors. The resulting animals display phenotypes matching fossil records: 20-25% larger size, stronger bite force, stockier builds, white coats, and unexpectedly thick hair with ridge-like manes—characteristics unknown from fossils alone.
Lamm explains that AI and big data will transform biology similarly to how it revolutionized language models. Within 5-10 years, AI trained on genome data could match current large language model capabilities. Colossal has built internal software using their extensive editing data to predict optimal editing modalities and efficiency rates based on design parameters.
Regarding longevity escape velocity (one year of life gained per year lived), Lamm believes this is achievable within 20 years through combinations of existing and emerging therapeutics. Current tools already address major death causes: Repatha reduces LDL cholesterol to reverse arterial plaque; metformin controls diabetes; GLP-1 receptor agonists show benefits beyond weight loss including kidney, muscle, and heart function improvements. He predicts a future single longevity shot combining multiple therapeutics to maintain Brian Johnson-level biomarkers.
Lamm addresses why de-extinction matters beyond spectacle: it drives innovation through systems thinking (like the Apollo program), generates technologies applicable to human healthcare, and inspires youth toward science careers. Teachers report classrooms fixate on dire wolves and mammoths.
On ecosystem considerations, Lamm notes that rewilding involves measured introduction through 2,000-acre preserved preserves with 24/7 monitoring, 10 full-time staff, security, and on-site veterinary facilities. For the dire wolf project, surrogate dog mothers are adopted through anonymous programs to prevent exploitation as spectacle.
Colossal's parallel innovations include plastic degradation through engineered enzymes from naturally occurring microbes discovered by the Wyss Institute. These enzymes break chemical bonds in plastics, reducing degradation time from 800 years to approximately 18 months, with goals of 24 hours. Fourteen to sixteen pilot projects are underway with water treatment and textile companies.
Lamm's broader vision includes engineering plants to grow as architectural structures with bioluminescent properties and developing underwater cities by applying radiation-tolerance and thermal-regulation technologies developed for space to oceanic environments 30-70 feet deep where conditions remain stable regardless of surface disruption.
About this episode
<p>Welcome back to the second half of this eye-opening discussion with Ben Lamm, CEO of Colossal Biosciences. In Part 2, Tom and Ben dig even deeper, tackling the massive ethical questions and transformative possibilities that arise when humans hold the keys to edit and design life itself. Whether it’s confronting the future of embryo screening, germline editing, the potential for designer babies, or the international arms race in biotechnology—no topic is off limits.</p> <p><br /></p> <p>Ben shares insider stories on Colossal’s dire wolf project, explains misconceptions about cloning, and reveals the unexpected hurdles and breakthroughs in the world of synthetic biology. They discuss how these advances can directly impact human longevity, environmental crises like plastic pollution, and even set the stage for building the living cities and ocean habitats of tomorrow. This is a no-holds-barred, jam-packed episode for anyone intrigued by the future of engineering life—and the urgent questions we all must face as the bio-revolution unfolds.</p> <p><br /></p> <p><strong>SHOWNOTES</strong> </p> <p>33:30 – The Moral and Ethical Responsibility of ‘Playing God’ </p> <p>34:58 – Human Genome Editing, Embryo Selection, and the Coming Revolution in IVF </p> <p>39:14 – The Personal Side: Ben’s Own IVF Journey and Making Hard Choices </p> <p>44:41 – The Slippery Slope: Intelligence, Disease, and Future Human Potential </p> <p>51:36 – International Competition: US vs. China in Biotech and Human Enhancement </p> <p>58:46 – Accelerating Gene Editing: Multiplexing, Cloning, and Animal Selection </p> <p>1:09:12 – Rewilding and Ecosystem Impact: Fact vs. Jurassic Park Fiction </p> <p>1:22:42 – The Longevity Escape Velocity and Radical Life Extension </p> <p>1:44:08 – Innovations for the Planet: Enzymes That Break Down Plastic & Ocean Engineering </p> <p>1:49:40 – The Future of Synthetic Biology: Designed Environments, Health, and Next-Gen Conservation</p> <p><br /></p> <p><strong>FOLLOW BEN LAMM</strong> </p> <p>Twitter/X: <a href="https://twitter.com/federallamm" target="_blank">@federallamm</a> </p> <p>LinkedIn: <a href="https://www.linkedin.com/in/benlamm/" target="_blank">Ben Lamm</a></p> <p><br /></p> <p><strong>CHECK OUT OUR SPONSORS</strong></p> <p><strong>ButcherBox: </strong>Ready to level up your meals? 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Key Insights
- Colossal uses parallel pathway development where computational analysis, cell line growth, genetic editing, and IVF research happen simultaneously, making multi-year projects feasible rather than requiring a decade per animal.
- Elephants and blue whales express P53 at 20 times higher levels than humans, which explains their dramatically lower cancer rates despite larger body mass and longer lifespans—a phenomenon called Peto's paradox.
- During genetic editing, the process itself appears as a forced mutation that can trigger cancer responses, requiring researchers to temporarily downregulate P53 during edits and then reactivate it afterward.
- A 2021-2022 paper claiming dire wolves fell between wolves and jackals was based on only 15% genome coverage, while Colossal's 500x more data from two samples with 60,000 years of divergence reveals dire wolves skewed closer to gray wolf lineage.
- Dire wolves made by Colossal display unexpected phenotypes including white coats and thick hair with ridge-like manes that were completely unknown from fossil records alone.
- Within 5-10 years, AI trained on genome data could achieve capabilities comparable to current large language models, enabling prediction of optimal gene editing approaches and efficiency rates.
- Longevity escape velocity appears achievable within 20 years through combinations of existing therapeutics: statins reducing LDL cholesterol, metformin for diabetes, and GLP-1 agonists showing benefits beyond weight loss.
- De-extinction serves purposes beyond spectacle by driving systems-level technological innovation, generating spillover applications to human healthcare, and inspiring youth toward science careers—similar to the Apollo program's broader cultural impact.
Topics
Transcript
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