The short, strange history of gene de-extinction
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This week saw the release of some fascinating news about some very furry rodents—so-called “woolly mice”—created as part of an experiment to explore how we might one day resurrect the woolly mammoth.
The idea of bringing back extinct species has gained traction thanks to advances in sequencing of ancient DNA. In recent years, scientists have recovered genetic blueprints from the remains of dodo birds, more than 10,000 prehistoric humans, and frozen mammoths, a species that went extinct around 2000 BCE.
This ancient genetic data is deepening our understanding of the past—for instance, by shedding light on interactions among prehistoric humans. But researchers are becoming more ambitious. Rather than just reading ancient DNA, they want to use it—by inserting it into living organisms.
Colossal Biosciences, the biotech company behind the woolly mice, says that’s its plan. The eventual goal is to modify elephants with enough mammoth DNA to result in something resembling the extinct pachyderm.
To be sure, there is a long way to go. The mice Colossal created include several genetic changes previously known to make mice furry or long-haired. That is, the changes were mammoth-like, but not from a mammoth. In fact, only a single letter of uniquely mammoth DNA was added to the mice.
Because this idea is so new and attracting so much attention, I decided it would be useful to create a record of previous attempts to add extinct DNA to living organisms. And since the technology doesn’t have a name, let’s give it one: “chronogenics.”
“Examples are exceptionally few currently,” says Ben Novak, lead scientist at Revive & Restore, an organization that applies genetic technology to conservation efforts. Novak helped me track down examples, and I also got ideas from Harvard geneticist George Church—who originally envisioned the mammoth project—as well as Beth Shapiro, lead scientist at Colossal.
The starting point for chronogenics appears to be in 2004. That year, US scientists reported they’d partly re-created the deadly 1918 influenza virus and used it to infect mice. After a long search, they had retrieved examples of the virus from a frozen body in Alaska, which had preserved the germ like a time capsule. Eventually, they were able to reconstruct the entire virus—all eight of its genes—and found it had lethal effects on rodents.
This was an alarming start to the idea of gene de-extinction. As we know from movies like The Thing, digging up frozen creatures from the ice is a bad idea. Many scientists felt that recovering the 1918 flu—which had killed 30 million people—created an unnecessary risk that the virus could slip loose, setting off a new outbreak.
Viruses are not considered living things. But for the first example of chronogenics involving animals, we have to wait only until 2008, when Australian researchers Andrew Pask and Marilyn Renfree collected genetic data from a Tasmanian tiger, or thylacine, that had been kept in a jar of ethanol (the last of these carnivorous marsupials died in a Hobart zoo in 1936).
The Australians then added a short fragment of the extinct animal’s DNA to mice and showed it could regulate the activity of another gene. This was, at one level, an entirely routine study of gene function. Scientists often make DNA changes to mice to see what happens.
The difference here was that they were studying extinct genes, which they estimated accounts for 99% of the genetic diversity that has ever existed. The researchers used almost religious language to describe where the DNA had come from.
“Genetic information from an extinct species can be resurrected,” they wrote. “And in doing so, we have restored to life the genetic potential of a fragment of this extinct mammalian genome.”
That brings us to what I think is the first commercial effort to employ extinct genes, which came to our attention in 2016. Gingko Bioworks, a synthetic-biology company, started hunting in herbariums for specimens of recently extinct flowers, like one that grew on Maui’s lava fields until the early 20th century. Then the company isolated some of the genes responsible for their scent molecules.
“We did in fact insert the genes into yeast strains and measure the molecules,” says Christina Agapakis, Gingko’s former senior vice president for creative and marketing, who led the project. Ultimately, though, Ginkgo worked with a “smell artist” to imitate those odors using commercially available aroma chemicals. This means the resulting perfumes (which are for sale) use extinct genes as “inspiration,” not as actual ingredients.
That’s a little bit similar to the woolly mouse project. Some scientists complained this week that when, or if, Colossal starts to chrono-engineer elephants, it won’t really be able to make all the thousands of DNA changes needed to truly re-create the appearance and behavior of a mammoth. Instead, the result will be just “a crude approximation of an extinct creature,” one scientist said.
Agapakis suggests not being too literal-minded about gene retrieval from the past. “As an artwork, I saw how the extinct flower made different people feel a deep connection with nature, a sadness and loss at something gone forever, and a hope for a different kind of relationship to nature in the future,” she says. “So I do think there is a very powerful and poetic ethical and social component here, a demand that we care for these woolly creatures and for our entanglements with nature more broadly.”
To wrap up our short list of known efforts at chronogenics, we found only a few more examples. In 2023, a Japanese team added a single mutation found in Neanderthals to mice, to study how it changed their anatomy. And in unpublished research, a research group at Carlsberg Laboratory, in Copenhagen, says it added a genetic mutation to barley plants after sifting through 2-million-year-old DNA recovered from a mound in Greenland.
That change, to a light-receptor gene, could make the crop tolerant to the Arctic’s extremely long summer days and winter nights.
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Read more from MIT Technology Review’s archive
How many genetic edits can be made to a cell before it expires? The answer is going to be important if you want to turn an elephant into a mammoth. In 2019, scientists set a record with more than13,000 edits in one cell.
We covered a project in Denmark where ancient DNA was replicated in a barley plant. It’s part of a plan to adapt crops to grow in higher latitudes—a useful tool as the world heats up.
To learn more about prehistoric animals, some paleontologists are building robotic models that fly, swim, and slither around. For more, have a look at this MIT Technology Review story by Shi En Kim.
The researcher who discovered how to make a mouse with extra-long hair, back in 1994, is named Jean Hebert. Last year we profiled Hebert’s idea for staying young by “gradually” replacing your brain with substitute tissue.
Looking for an unintended consequence of genetic engineering? Last year, journalist Douglas Main reported how the use of GMO crops has caused the evolution of weeds resistant to herbicides.
From around the web
The United Kingdom now imports half the donor sperm used in IVF procedures. An alleged donor “shortage” is causing sperm to become more expensive than beluga caviar, on a per-gram basis. (Financial Times)
Jason Bannan, the agent who led the FBI’s scientific investigation into the origins of covid-19, is speaking out on why he thinks the pandemic was started by a lab accident in China. (Vanity Fair)
An Australian company, Cortical Labs, released what it’s calling “the first commercial biological computer.” The device combines silicon chips with thousands of human neurons. (Boing Boing)
The Trump administration is terminating medical research grants that focus on gender identity, arguing that such studies are “often unscientific” and ignore “biological realities.” Researchers vowed to press on. (Inside Medicine).
The US Senate held confirmation hearings for Stanford University doctor Jay Bhattacharya to be director of the National Institutes of Health, which funds nearly $48 billion in research each year. Bhattacharya gained prominence during the covid-19 pandemic for opposing lockdowns. (NPR)
Francis Collins has retired from the National Institutes of Health. The widely admired geneticist spent 12 years as director of the agency, through 2021, and before that he played a key role in the Human Genome Project. Early in his career he identified the gene that causes cystic fibrosis. (New York Times)
