Dire wolves and mammoths: how de-extinction really works

What does it mean to bring an extinct animal back? In a Huberman Lab conversation, evolutionary biologist Dr. Beth Shapiro, chief scientific officer at Colossal Biosciences, explains how de-extinction works, why the dire wolf is not a gimmick and how the same tools may protect living species and even inform human genetics.

What is a species, anyway?

Shapiro points out that biology does not care about species. A species is a human concept we use to talk about animals. The familiar biological species concept says that animals that can breed and have fertile offspring are one species, but Neanderthals and modern humans interbred, and polar bears and brown bears still do. Most people today carry 2 to 5% Neanderthal DNA, and since that fraction differs between people, researchers could rebuild more than 90% of the Neanderthal genome from living humans.

How a dire wolf is made

Colossal sequenced genomes from fossil dire wolves, learned which genetic changes made them bigger, more robust and light coated, and engineered 20 edits into a gray wolf genome. The team avoided edits that cause deafness or blindness in living wolves and used variants known to be safe in light colored dogs. Three animals now exist: Romulus, Remus and Khaleesi, hand reared and kept apart from breeding with hormones.

For mammoths, the approach is similar. Mammoths and Asian elephants are about 99% similar in DNA, so the team focuses on places where all mammoths differ from elephants. The result will be an elephant able to live in mammoth habitat, not an exact copy. Shapiro says the strict genetic similarity rule is a distraction, and that if people dislike the name, they do not need to use it.

Why some animals and not others

Choosing a species involves technical, ethical, ecological and social reasons. Dinosaurs are impossible, because the oldest DNA recovered is 1 to 2 million years old and dinosaurs vanished more than 66 million years ago. DNA degrades from UV light, freeze thaw cycles and microbial decay, which is why Siberian permafrost preserves it better than a tropical island. The dodo genome comes from a museum specimen, not from island bones.

Ecology matters too. At Pleistocene Park in Siberia, large herbivores scrape snow off the ground, which keeps soil cold and promotes a more diverse plant mosaic. The thylacine, once Tasmania's top predator, might have helped limit the devil facial tumor disease by removing sick animals.

Conservation is the point

Shapiro insists the work is both de-extinction and prevention. The same stack applies to living species:

• Cloned red wolves add genetic diversity to a tiny captive population.
• Cloning of frozen cells helped black footed ferrets, and editing could make them resistant to plague.
• Northern quolls edited with a single letter change might survive eating toxic cane toads.
• A gene drive could, with safeguards, tamp down invasive cheatgrass or disease carrying mosquitoes.

She also warns that doing nothing is a decision. Many habitats change faster than natural selection can handle, and assisted tools may be the only way for some species to survive. Colossal works with advisory panels, such as the Tasmanian group and a Maori led Moa project, and publishes care reports on ecological impact.

Human genetics and artificial wombs

The conversation then turns to humans. Genetic selection already happens, from IVF embryo screening to mate choice, and ancient DNA shows height genes spread in Northern Europe. Shapiro mentions baby KJ, who was cured of a urea cycle disorder with a bespoke CRISPR base editor in six months. She predicts that editing disease genes in embryos will be common within a few years, and notes that delivery methods shape public acceptance, as pens did for GLP-1 drugs and peptides.

Colossal is also building artificial wombs, motivated by the need to birth many mammoths without using elephants. Such technology could help premature babies or pregnant patients who need cancer treatment.

Trust, ethics and who decides

Shapiro and Huberman discuss why people accept some interventions and reject others. Conservation is never hands off, because people already decide how many animals live, what they eat and whether they are vaccinated, and moving species around is as old as humanity. She argues that robustness matters more than preserving a snapshot of the past, and that overlapping ecological roles make ecosystems stronger. Her own path into the field began in broadcast journalism before an ancient DNA lab at Oxford, and she says the public deserves clear explanations, because awe and curiosity bring investment into conservation.

Conclusion

De-extinction is less about resurrecting a museum piece and more about building tools to make ecosystems and species more resilient. The same stack may one day improve human medicine, and public conversation now will shape how it is used. Her message is that curiosity, careful science and input from local communities can work together.