Beth Shapiro on De-Extinction and Gene Editing

Carl Linnaeus had a naming problem. In the eighteenth century, European explorers kept finding large animals that would make a good coat, and they called every one of them a buffalo. That is how an African buffalo, an Asian water buffalo, and an American bison ended up carrying versions of the same name, even though their DNA shows they are barely related. Linnaeus solved the confusion with Latin binomials, but the deeper problem never went away. What exactly is a species, and who gets to decide where one ends and another begins?

Evolutionary biologist Beth Shapiro, chief scientific officer at the de-extinction company Colossal Biosciences, thinks the question answers itself once you stop expecting biology to cooperate.

"Biology doesn't care what species you are. Species is a, a human concept. We have this incredible proclivity to want to put things into boxes so that we can talk about them." — Beth Shapiro [03:56]

That idea is not academic throat-clearing. It is the hinge her whole career swings on. Take Neanderthals. For decades, textbooks treated them as a separate species from modern humans. Then genome sequencing showed that after people left Africa and met Neanderthals in Europe, the two groups interbred successfully (09:33). Most people alive today carry somewhere between 2 and 5 percent Neanderthal DNA (10:48). But it is a different 2 to 5 percent in each of us. Stitch together everyone's fragments, Shapiro says, and you would reconstruct more than 90 percent of the Neanderthal genome from living humans alone (23:25), evidence that most of that ancient DNA was harmless enough to be carried forward. If Neanderthals and humans could interbreed and produce fertile children, the textbook species line was never as solid as it looked.

The same blurriness shows up in other animals. Polar bears and brown bears split apart roughly 500,000 years ago, adapted to completely different habitats, and still produce fertile hybrids, nicknamed grolar bears or pizzly bears, whenever their ranges overlap (17:42). What keeps the two populations distinct is not biology's refusal to let them mix. It is ecology: a hybrid cub with patchy brown-and-white fur cannot hunt seals well enough to survive as a polar bear, so the hybrid lineage only persists on the brown bear side.

Shapiro's day job, though, is not drawing species boundaries. It is deciding which ones to bring back, and here the limits are not philosophical but chemical. DNA starts breaking down the moment an organism dies, chopped into smaller fragments by ultraviolet light, by the physical stress of freezing and thawing, and by microbial decay (33:27). Cold, dry environments slow the process down. The oldest DNA ever recovered from a bone comes from a mammoth, dated to somewhere between 1 and 2 million years old, preserved by Arctic permafrost (32:48). Dinosaurs went extinct 66 million years ago, an order of magnitude too long for any usable genetic material to remain. Their bones are rock now, not biology.

Twenty Edits, One Wolf

So Shapiro's team works with what DNA allows. The woolly mammoth's closest living relative is the Asian elephant, with genomes about 99 percent identical (49:42), close enough that Colossal is using elephant cells as a chassis for mammoth traits rather than building an animal from scratch. The same logic produced the dire wolf, announced earlier this year to considerable argument about whether it deserved the name. Shapiro's team sequenced fossil dire wolf genomes, worked out which DNA changes produced the animal's larger size, denser muscle, and pale coat, and then made 20 of those changes to a living gray wolf genome (56:33). One detail says a lot about how deliberate the process is: the dire wolf's actual light-coat gene, if copied directly into a gray wolf, risked causing blindness or deafness, a known side effect in dogs carrying similar variants. So the team substituted a different, already-safe light-coat variant borrowed from domestic dogs to get the same look without the risk (58:50). The resulting pups, Romulus, Remus, and Khaleesi, are not being released into the wild. At roughly 120 pounds, they are kept and studied in captivity (61:42).

The same toolkit, Shapiro argues, is what makes her work relevant to animals that are not extinct at all. In northeastern Siberia, a research park called Pleistocene Park has spent years testing what happens when large grazing animals, like bison and horses, are reintroduced to tundra. They trample snow in winter looking for food, which lets summer heat escape the ground instead of being trapped under an insulating layer of snow, which in turn changes which plants can grow back (36:21). In Australia, a small carnivorous marsupial called the northern quoll is heading toward extinction because it dies when it eats a toxic invasive species called the cane toad. Colossal's Australian partners copied a single-letter genetic change, already found naturally in other toad-eating mammals, into quoll cells to make them resistant to the toxin (74:28). None of this required inventing new biology. It required reading what already works elsewhere in nature and moving it.

The same approach has already rescued a species without any editing at all. The black-footed ferret was declared extinct twice: once when the last captive animal died, and again when the last wild one did, before a family dog near Meeteetse, Wyoming, killed one in the 1980s and a taxidermist realized what it was (99:02). The surviving wild population was so small that one male, nicknamed Scarface, ended up siring most of today's ferrets, leaving the species dangerously inbred. Conservationists solved part of that problem by cloning tissue, frozen for 40 years, from a ferret genetically unrelated to the Meeteetse survivors. That clone, named Elizabeth Ann, was born in 2020 (104:44). She could not reproduce herself, but a second clone from the same donor line could, reintroducing lost genetic diversity into a population that now releases about 500 ferrets into the wild each year (103:49). Researchers are now exploring genome edits that could make the ferrets resistant to plague, the disease still killing them in the field.

The Harder Question Is Human

If gene editing a ferret feels uncontroversial, the conversation changes the moment it turns toward people. In 2018, a scientist in China used gene editing to alter the genomes of human embryos, disabling a gene involved in HIV infection, and the resulting births triggered global condemnation (89:18). Since then, at least four companies have launched offering deep genetic screening of embryos, ranking them by predicted traits including height and estimated cognitive ability (90:59). Shapiro points out that humans have been doing a cruder version of this for a long time, just by choosing partners: height in Northern Europe, for instance, rose for thousands of years after a genetic variant entered the population with migrating steppe herders around 4,700 years ago, and has only recently plateaued (93:43). What has actually changed is not the existence of genetic selection. It is the deliberateness of it.

That deliberateness has already produced a cure. Doctors at the Children's Hospital of Philadelphia designed a bespoke CRISPR base editor, a tool that rewrites single letters of DNA without cutting the strand, to treat a six-month-old born with a urea cycle disorder that was letting ammonia build up in his blood. After six months of development and three treatments, the child was cured (97:04). Shapiro notes that nobody has accused those doctors of playing God, which raises an obvious question about where the discomfort with gene editing actually comes from.

Her answer is less about the science than about inertia. Ecosystems around the world are changing faster than natural selection can keep up with, and the only other options on the table, translocation, assisted reproduction, synthetic biology, carry their own risks.

"If we say that those technologies are too risky, we are accepting the outcome of doing nothing, which is also a decision." — Beth Shapiro [85:10]

That is the real argument underneath the dire wolf headlines and the ferret clones: not that every intervention is wise, but that refusing to intervene is itself a choice with consequences, made quietly and by default. Shapiro's hope is that getting people to feel genuine awe about a woolly-coated elephant or a hand-reared wolf pup buys attention, funding, and patience for the slower, less photogenic work of keeping species that are still alive from disappearing in the meantime.