Bringing Extinct Species Back to Life | Dr. Beth Shapiro
Dr. Beth Shapiro discusses de-extinction and synthetic biology, explaining how genetic engineering is being used to bring back extinct species like woolly mammoths and dodos while also applying these tools to save endangered living species. The conversation covers the science of ancient DNA, species concepts, ecosystem restoration, and the ethical implications of genetic modification in both animals and humans.
Summary
Dr. Beth Shapiro, Chief Scientific Officer at Colossal Biosciences, joins Andrew Huberman to discuss de-extinction and synthetic biology. The conversation begins with foundational concepts: species are human constructs based on various classification systems (biological, genetic, geographic), and DNA similarity percentages are calculated in multiple ways—humans and chimpanzees share roughly 99% of their DNA, similar to mammoths and Asian elephants. Shapiro explains that de-extinction isn't about recreating identical extinct animals but rather engineering animals capable of filling the ecological niches their ancestors occupied.
The technical approach involves sequencing ancient DNA from fossils, identifying the genetic changes that made extinct species distinct, and inserting those changes into closely related living species. For example, dire wolves were created by making 20 specific edits to grey wolf genomes based on analysis of fossil dire wolf DNA, resulting in larger, more robust animals with lighter-colored coats. Currently, three dire wolves (Romulus, Remus, and Klesia) exist and are being studied rather than released into the wild.
Shapiro discusses the broader ecosystem implications and why de-extinction matters for conservation. She argues these tools simultaneously develop technology for saving currently endangered species. Examples include: using cloning and genetic editing to restore genetic diversity to black-footed ferrets (which were nearly extinct but recovered from a single founder population named Scarface), and engineering quolls in Australia to resist toxic cane toads through a single amino acid change that already exists in other mammals. The woolly mammoth project could help restore tundra ecosystems by recreating large herbivore interactions that promote vegetation diversity and carbon sequestration—demonstrated through Pleistocene Park in Siberia where introduced megafauna have visibly restored plant communities.
The conversation explores Neanderthal admixture in modern humans (2-5% of non-African DNA comes from Neanderthals), explaining that while humans and Neanderthals diverged 300,000-500,000 years ago, they interbred when modern humans migrated out of Africa. This demonstrates that closely related species can produce viable, fertile offspring despite significant evolutionary separation. Shapiro notes that 95% of the Neanderthal genome now exists in living humans, meaning the remaining 5% represents traits that were apparently maladaptive and selected against. Some Neanderthal genes show evidence of adaptive introgression—certain populations retain high frequencies of Neanderthal alleles because they were protective against historical diseases (e.g., immune-related genes that protected against medieval plagues but increased COVID-19 susceptibility in some populations).
Regarding human genetic modification, Shapiro discusses the spectrum from acceptable to controversial interventions. Genetic selection through IVF and embryo screening is increasingly common, and gene editing for disease prevention is advancing (exemplified by the recent FDA approval of gene-edited treatments and the case of baby Khalif, who was cured of a genetic disease through CRISPR base editing). She predicts routine genetic disease screening in fertility will become commonplace within 3-5 years. However, she acknowledges that enhancement traits (intelligence, height, attractiveness) raise different ethical concerns. Interestingly, humans have already been genetically selecting for traits like height through mate choice—Northern European populations received tall alleles from Yamna steppe populations 4,700 years ago, and natural selection for height has essentially plateaued as people have maximized this trait with current genetic variation.
Shapiro addresses common misconceptions and public concerns directly. She explains why dinosaur de-extinction is impossible (DNA degrades completely over 66+ million years, whereas mammoth DNA survived 1-2 million years in Arctic permafrost), and clarifies that the direwolf announcement generated necessary public engagement with conservation genetics. She discusses the importance of advisory panels including local stakeholders, conservation biologists, and politicians—Colossal's Tasmanian devil project is led by Māori researchers who will be long-term stewards of the species. She emphasizes that doing nothing is also a decision, accepting biodiversity loss, whereas thoughtful intervention with proper safeguards offers better outcomes.
The discussion includes technological innovations supporting de-extinction: artificial wombs for developing mammoths without requiring 22-month elephant pregnancies, genome-scale CRISPR applications, and digital ecosystem modeling to predict intervention outcomes. Shapiro notes that concerns about gene drives (self-propagating genetic modifications released into wild populations) can be addressed through safety switches limiting persistence to specific generations, yet acknowledges that carefully controlled gene drives could solve problems like eliminating cheatgrass (a highly flammable invasive species) to restore California native grasslands.
Key Insights
- Species classifications are human conceptual constructs rather than biological absolutes; different species concepts (biological, genetic, geographic) can yield different classifications for the same organisms, as illustrated by the biological species concept allowing Neanderthals and humans to interbreed successfully while genetic species concepts focus on sequence similarity thresholds
- De-extinction tools are simultaneously conservation tools—the same genetic engineering technologies developed to bring back extinct species directly apply to preventing living endangered species from becoming extinct, with Colossal's direwolf announcement serving as a public engagement mechanism that drove student interest in conservation genetics
- Approximately 95% of the Neanderthal genome persists in modern humans in fragmented form across different individuals; identifying the remaining 5% of the genome where no living person has Neanderthal DNA reveals which mutations were truly critical for human-specific traits because those are the locations where hybridized infants would not have survived
- Natural selection for human height in Northern Europe occurred through mate preference over millennia—tall alleles were introduced by Yamna steppe populations 4,700 years ago and have now plateaued because populations have maximized height given current genetic variation, demonstrating humans have been conducting genetic selection on themselves throughout evolutionary history
- Inaction on ecosystem conservation is itself a decision with consequences; declining to use genetic modification and translocation technologies for species preservation guarantees acceptance of lower future biodiversity, whereas thoughtful deployment of these tools with proper advisory structures and safety measures offers better ecological outcomes
Topics
Transcript
[0:00] 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. You know, I often get the question of why are you thinking about bringing extinct species back to life? Why aren't you thinking about helping living species not become extinct? And the answer is we are doing both. It is the same tools. It's the [0:34] same technology. It's the same needs. And when we excite people with the idea of mammoths and dodos and thyloines, we get more engagement…
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