Link: https://youtu.be/SFX8FIHFLE4

Duration: 135 min

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Short Summary

The Huberman Lab Podcast episode features Dr. Beth Shapiro, an evolutionary biologist and National Geographic Explorer who leads de-extinction science at Colossal Biosciences. She explains how Colossal's tools—used to make the direwolf via 20 grey wolf edits and pursued for the mammoth, dodo, thylacine, and moa—also rescue living species like the black-footed ferret and northern quoll. The conversation spans Neanderthal admixture, Pleistocene Park, CRISPR cures such as Baby KJ, the Chinese gene-edited babies fallout, and Shapiro's argument that rejecting de-extinction tech amounts to accepting a less biodiverse future.

Key Quotes

1. "So our direwolves, they have 20 edits that we picked and we sequenced genomes from fossil direwolves. We learned from those genomes what genetic changes made those animals bigger, more robust, light colored in coat and then we engineered those changes into a greywolf genome to recreate the direwolf."
2. "And when we excite people with the idea of mammoths and dodos and thyloines, we get more engagement and enthusiasm and investment in developing the technology that we can use to stop living species from becoming extinct."
3. "biology doesn't care what species you are. Species is a a human concept."
4. "Today most people have somewhere between 2 and 5% of their DNA that is from this ad mixture event, this hybridization event between anatomically modern humans dispersing out of Africa and the Neandertols that were already in Europe."
5. "if we were to go around the world today and pick out all of the pieces of Neanderl DNA that exist in humans today, we would put together more than 90% possibly more than 95% of the Neanderl genome just from people who are alive today."

Detailed Summary

Detailed Summary: Dr. Beth Shapiro on De-Extinction, Ancient DNA, and the Future of Life

Interviewee Background & Path to De-Extinction

Dr. Beth Shapiro is Chief Scientific Officer at Colossal Biosciences, which employs roughly 120 scientists, and she is also a National Geographic Explorer, former UC Santa Cruz professor, former Howard Hughes Medical Institute investigator, and Rhodes Scholar. She walked away from a thriving Howard Hughes Investigator lab to pursue de-extinction work full-time. Originally a broadcast journalism major at the University of Georgia, she pivoted to science after a 9-week U.S. national parks honors trip, then studied parasitoid wasps on Barro Colorado Island in Panama before joining Alan Cooper's ancient DNA lab at Oxford, drawn by the prospect of Siberian fieldwork. Her husband Ed Green was on Svante Pääbo's team that assembled the Neanderthal genome; the Denisovan lineage was first isolated by Pääbo's group from a finger bone at Denisova Cave in Russia.

• The first ancient DNA paper was published in 1984 by UC Berkeley's "Extinct Species Study Group," which used pre-PCR molecular cloning to isolate a fragment from a preserved quagga (an extinct zebra).
• That result demonstrated DNA could survive post-mortem and triggered the brief "dinosaur DNA" era, including two papers later proven false.
• Every ancient DNA paper interview begins with the "dinosaur question," which ultimately drew Shapiro toward de-extinction research.

Direwolf Breakthrough & Engineering Approach

Colossal's direwolves were produced by making 20 edits to a grey wolf genome, chosen from genetic changes identified in fossil direwolf genomes that correlate with larger size, more robust build, and lighter coat color. The resulting animals weigh at least 120 lbs, well above typical grey wolf size. Shapiro frames de-extinction as engineering an animal capable of surviving in the relevant ecosystem rather than copying an exact past individual, explicitly pushing back against what she calls Jurassic Park's misleading premise.

• Birds cannot be cloned via somatic cell nuclear transfer (the Dolly technique) because bird egg cells cannot be accessed at the right stage.
• Colossal's synthetic biology stack—multiplex genome engineering, cellular rejuvenation, iPS cell technologies, and linking DNA sequence to phenotype—is applicable across species and to living-species conservation.

Other Colossal De-Extinction Projects

Colossal is actively pursuing the woolly mammoth, dodo, thylacine (Tasmanian tiger), and a moa project led by New Zealand's Ngāi Tahu Research Center on the South Island, with release decisions made by the Māori as long-term stewards. The dodo was selected as the company's first bird project partly for its rounded, cartoonish appeal, and the best dodo genome comes from a specimen held at the Danish Museum of Natural History rather than Mauritian bones, which contain no recoverable DNA.

• The Tasmanian thylacine advisory panel includes politicians, loggers, animal workers, scientists, and conservation biologists.
• Colossal suggests Tasmanian devil facial tumor disease, a transmissible cancer enabled by the species' low genetic diversity, might have been prevented had the top predator persisted.
• Birds are among the most endangered species on the planet.
• A single female condor reproduced asexually because meiosis did not fully reduce chromosomes; some birds carry a germline-restricted chromosome that exists only in sperm and egg cells, complicating extinct-bird genome assembly.
• Other projects referenced include the genuinely pink Mauritian pink pigeon.

Black-Footed Ferret Case Study

Black-footed ferrets were nearly wiped out by prairie dog eradication efforts and appeared on the first 1966 endangered species list. A surviving wild individual was rediscovered near Meeteetse, Wyoming when a family dog named Shep brought one to a taxidermist; all remaining wild ferrets were eventually collected for captive breeding.

• A single ferret named Scarface sired about 300 litters, partially resurrecting the population.
• The captive program now releases roughly 500 ferrets per year, but suffers from extremely low genetic diversity since all founders came from the same Meeteetse population.
• Elizabeth Anne, born in 2020, was the first clone made from 40-year-old tissues of a long-deceased ferret, but had non-functional ovaries.
• A second clone from the same cell line has successfully reproduced.
• Bubonic plague is the primary killer of wild ferrets; researchers propose using genetic engineering to introduce plague resistance from domestic ferrets.

Conservation Applications for Living Species

The northern quoll, a small carnivorous marsupial, faces likely extinction within decades from toxic introduced cane toads. Some Australian mammals can eat the toads thanks to a single-letter DNA change that alters one amino acid in one gene, and Colossal's Australian partners have made that same change in the quoll, with in-vitro tests showing the toxin can be broken down.

• When announcing the direwolf, Colossal simultaneously announced cloning of red wolves, the most endangered wolf species in North America.
• Princeton researcher Bridget von Halt discovered a coyote-like population with more than 75% red wolf ancestry, which Colossal cloned to inject new genetic diversity into the existing red wolf population.
• Only certain mosquito species carry malaria, dengue, and other diseases, and their populations are unnaturally inflated by standing water in human towns; Shapiro prefers engineering mosquitoes that cannot carry disease over killing them, and notes gene drives can be designed to expire after a fixed number of generations under strong natural selection.
• Mediterranean-origin cheat grass is widespread across western North America, is highly flammable, has shallow roots, and outcompetes native California grasses; a carefully deployed gene drive could tamp it down for a few generations to let natives return.

Pleistocene Park & Ecological Restoration

Pleistocene Park in northeastern Siberia, run by Sergey Zimov (Russian Academy) and his son Nikita, has reintroduced bison from Canada, wild horses, several deer species, and muskox to the tundra. Animals at the park scrape snow off the dirt to find winter food; without them, snow insulates the ground and traps summer heat, accelerating permafrost melt.

• Grazed land becomes a mosaic of moist and exposed dry areas and supports more plant diversity than ungrazed tundra; large herbivores turn soil, knock down trees, and distribute seeds and nutrients.
• The Yellowstone grey wolf reintroduction cascaded through the ecosystem, eventually changing how rivers flowed once overgrazed herbivores were controlled and riverside plants regrew.
• Channel Islands foxes on Anakappa and Santa Rosa were brought there by the Chumash on boats; their post-bottleneck genomes are nearly identical yet the animals thrive, illustrating purging of harmful mutations.
• California native grasses have deeper roots, stay green longer, sequester carbon, and are less flammable than Mediterranean cheat grass.
• Florida panthers were translocated with Texas panthers in the mid-1990s to fix inbreeding depression, which had caused crooked tails, cowlicks, and cryptorchidism; introduced diseases disappeared briefly but inbreeding has resumed because the population is cut off from Texas.

Species Concepts & Admixture

Shapiro argues that "species" is a human construct and that biology does not care about species designations. She uses three concepts: the biological species concept (Ernst Mayr; interbreeding with fertile offspring), the genetic species concept (threshold of sequence similarity), and the geographic species concept (e.g., Florida panther vs. Texas panther).

• Humans and Neanderthals diverged roughly 300,000–500,000 years ago, far more recently than the 3–5 million years between humans and chimps/bonobos.
• Living humans carry about 2–5% Neanderthal DNA, with the specific 2–5% varying by individual.
• Combining all Neanderthal DNA fragments across living humans reconstructs more than 90% (possibly 95%) of the Neanderthal genome, suggesting most Neanderthal DNA was not maladaptive; the ~5% missing across everyone likely contains key "what makes us human" variants.
• A Neanderthal-derived COVID-19 severity allele sits at roughly 50% frequency in some Asian populations, well above the ~3% Neanderthal DNA average, while a separate Neanderthal allele was protective against COVID.
• Brown bears and polar bears diverged about 500,000 years ago and interbreed, producing grolar/pizzly bears; >100,000-year-old polar bear DNA from off Alaska and ~20,000-year-old polar bear ancestry in ABC Islands' brown bears show hybridization is ancient.
• Viable crosses occur when the mother is a polar bear (induced ovulators), and non-white fur prevents hybrids from successful seal hunting, so hybrids persist as brown bears—an illustration of adaptive filtering of admixture.

Ancient DNA: Capabilities & Limits

The oldest DNA recovered from a bone is from a mammoth roughly 1–2 million years old, preserved in cold Arctic permafrost; the oldest whole mammoth genomes date to the last 1.5 million years. DNA degrades through three processes: UV light, freeze-thaw cycles, and microbial decay; DNA preserves far longer in cold, rapidly buried Arctic environments than in hot, wet Mauritius.

• Dinosaurs cannot be brought back: they went extinct more than 66 million years ago, their skeletons are fossilized into rock, and no recoverable DNA remains; Shapiro notes Jurassic Park's "frog DNA" gap-filling was already questionable because birds are dinosaurs.
• Mammoth and Asian elephant genomes are about 99% similar, comparable to the human–chimp similarity; mammoths are confirmed as mammals from genome evidence of lactation.
• Every child is born with roughly 100 new DNA changes from copying errors in sperm/egg production.
• MC1R is associated with red hair in humans and reddish hair in mammoths (preserved in mammoth mummies); redheads on average require more anesthesia, and Neanderthals included gingers.
• Dark eyes are likely the ancestral human state based on African populations; blue and other light eye colors likely evolved through sexual selection.
• Shapiro's earlier book "How to Clone a Mammoth" outlines technical, ethical, ecological, and social prerequisites for de-extinction, including understanding the original extinction drivers.
• Iceland and Scandinavia have extensive genetic records due to historically limited mate pools.

CRISPR & Human Applications

A former Stanford postdoc in China used CRISPR to edit babies' genomes, disrupting the HIV receptor (the father was HIV positive). Competing narratives emerged: a benevolent interpretation (HIV protection) versus a eugenics interpretation potentially aimed at enhancing hippocampal/brain circuit function.

• Journalist Antonio Regalado broke the story about one week before a major CRISPR conference; for roughly a week it was unclear whether the scientist would win a Nobel Prize or be imprisoned; China shut down his lab and announced punishment.
• At least four companies have since launched to do deep sequencing of embryos from IVF and non-IVF babies, with some aiming to predict the "highest IQ" or "tallest" embryo.
• Baby KJ was the first child cured of a genetic disease using synthetic biology tools—a urea cycle deficiency causing ammonia buildup.
• A six-month collaboration between academia, industry, NIH, and Children's Hospital of Philadelphia designed a CRISPR base editor targeting KJ's liver; the bespoke medicine was administered three times as a six-month-old and cured his disease.
• Shapiro predicts that within 3–5 years, gene editing like the HIV-receptor edit will become common in fertility contexts to rule out disease gene constellations.
• One threshold-crossing scenario is a pandemic where people with a specific variant would die, making human gene editing the only ethical option.
• Public acceptance hinges on delivery: sperm injection into an egg (IVF) is more comfortable than biased embryo selection; GLP pens de-stigmatized injections; Shapiro argues "fear walls" fall to zero via unpredictable changes in delivery method, messaging, and accessibility (as with computers becoming smartphones).
• Brain-machine interfaces will become non-invasive, removing fears about drilling into skulls.

Artificial Wombs, Height Genetics & Domestication

Shapiro's lab is developing artificial wombs initially for mice to birth many mammoths without requiring Asian elephants to gestate the full 22 months. The technology could also help pregnant cancer patients and preemies needing surgery; modern NICUs are a crude form of artificial womb.

• Height-associated genes entered Europe with the Yamnaya steppe people roughly 4,700 years ago.
• Northern European height has plateaued, suggesting people are at the tallest possible stature with the current gene set.
• Height is relatively heritable and easier to link to DNA than IQ, which is measured differently across cultures.
• Humans domesticated grey wolves into dogs roughly 30,000 years ago by letting puppies live at campsites.
• Teosinte was transformed into corn through human selection—framed as an early example of humans altering other species.

AI, Ethics & Outlook

AI could model multiple ecological variables (mosquito populations, swamp locations, seasonal patterns, quail populations) simultaneously and run 24/7 better than any individual researcher. Digital twins of ecosystems perturbed in many ways to observe outcomes are feasible using big foundational models. Independent care report groups do deep dives for de-extinct species releases, incorporating local stakeholders and conservation biologists (e.g., the blue buck care report).

• Shapiro pushes back on critics who say de-extinction should be replaced by saving living species, arguing Colossal does both and that conservation is underfunded.
• She argues that rejecting translocations, assisted reproduction, genetic modification, synthetic biology, and de-extinction amounts to accepting a less biodiverse future, because ecosystem change is too fast for natural selection alone.
• Shapiro's most recent book is "Life as We Made It," which covers how humans have altered species throughout history and considers future applications of editing technology to humans.