If Tom Gilbert could bring any extinct animal back to life, he said, it wouldn't be dinosaurs or woolly mammoths or any other megafauna that once roamed the planet. His is a humbler choice: the Christmas Island rat, a species that was wiped out from its island home in the Indian Ocean more than a century ago.
Gilbert, an evolutionary geneticist at the University of Copenhagen, Denmark, admitted that his pick may not be the most sensational, but he said it's likely the most feasible with today's gene-editing technology.
In a study published Wednesday in the journal Current Biology, he and his colleagues examined how the Christmas Island rat could be revived, as well as the current limitations to "de-extinction." The research raises big questions about how successful de-extinction efforts can be, which types of animals should be brought back, and the ethical quandaries of tinkering with nature.
"We did this as a proof of principle that you might not get back what you think you're going to get," Gilbert said.
The researchers focused on how the gene-editing tool CRISPR could be used to alter the genetic blueprint of a closely related living species to essentially re-create one that went extinct. This method of editing genomes for the purposes of de-extinction was most famously pioneered by Harvard University biologist George Church, who has spent nearly a decade trying to splice the DNA of Asian elephants with woolly mammoth genes in hopes of resurrecting the extinct, shaggy-haired beasts.
Gilbert and his colleagues started by sequencing the genome of the Christmas Island rat (Rattus macleari) and found that they were able to recover almost all of the rodent's genetic information. The extinct animal is also closely related to a living rat species, sharing around 95 percent of its genome with the Norway brown rat, according to the study.
This made the Christmas Island rat an ideal test case, he said, because the scientists could directly compare the two genomes and identify where they differ. These divergences could signal distinct traits of Christmas Island rats and thus serve as a map for how to tweak the DNA of Norway brown rats to match their extinct relatives.
The idea works in theory, he said, but scientists rarely have all the genetic information they need from extinct species. Often, all that remains of some animals that lived tens of thousands or millions of years ago are small fragments of degraded DNA.
"If I give you a book and say, 'Tell me about this book,' you can look at it and read it and share all kinds of things from it, but if I take the book and put it through a paper shredder first, it's much harder," Gilbert said. "The information is all there, but it's in tiny, tiny fragments. Ancient DNA samples are like that."
While the researchers were able to reconstruct almost all of the Christmas Island rat's genome, almost 5 percent of it was unrecoverable, according to the study. The scientists determined that the missing genes were related to olfaction, or the rat's sense of smell, and the animal's immune functions.
If Gilbert and his colleagues were to revive the Christmas Island rat with the missing genes, it's not known what the outcome might be. It's possible, for instance, that the most important traits of the extinct rats would be preserved, but there also could be unintended consequences of improperly editing its genome.
"People tend to forget that genes are not independent in your genome," Gilbert said. "A lot of them have evolved to work with other ones and when one gene changes, another gene changes at the same time."
In other words, the unrecoverable parts of the Christmas Island rat genome could make it so that the rodents have immune systems that aren't properly adapted to their habitats or are unable to process smells the way they were when the species was alive.
These issues could have significant ethical implications for the resurrected animals, said Ross MacPhee, a senior curator at the American Museum of Natural History and a co-author of the study.
"The science of de-extinction is fantastically interesting, but the proposition that we've lost species and so we'll just bring them back is not thinking it through with respect to animal welfare," he said.
Rather than reviving long-extinct animals such as woolly mammoths, MacPhee said CRISPR could instead be a valuable tool to make genetic tweaks to vulnerable living species in order to help them survive better in the wild. With the endangered California condor, for example, perhaps genetic changes could ensure the species' survival, he said, but added that de-extinction doesn't necessarily address the root problem of why these animals are at risk in the first place.
"There are situations where you'd dearly love a species to do better, but we also need to recognize that it's what people have done to the environment that has limited the opportunities for these species to have any kind of decent life," MacPhee said.
Susan Haig, a professor of wildlife ecology at Oregon State University who was not involved with the study, similarly said the technology today could be best used to save species on the brink of extinction. But she disagreed with the study's authors about the limits of using CRISPR for de-extinction projects. For one, she said, CRISPR may be in its infancy now, but the technology has evolved significantly since it was first developed more than a decade ago.
"Not only is CRISPR getting better, but the artificial intelligence that they're developing to sort out the function of the genes that are being sequenced is getting much better," she said.
These advances will eventually make it easier to fill in the missing 5 percent of genes in the case of the Christmas Island rat, she added.
Haig said one of the central tensions within the scientific community is that de-extinction projects can appear to be at odds with conservation efforts, even when they are trying to achieve similar aims.
"Let's say you have a million dollars — should you spend it trying to preserve habitats and making sure whatever species in the wild has what it needs to survive," she said, "or should you spend it fiddling around with CRISPR?"
Many scientists are also loath to present de-extinction as a broad solution, for fear that it could one day be used as a crutch or seen as a get-out-of-jail-free card for the effects of climate change, which is already threatening many species and their ecosystems.
Gilbert said he is not against de-extinction but rather hopes the new study helps people critically consider the benefits of such projects — and their potential outcomes.
Societies should also think twice about how to avoid species going extinct in the first place, MacPhee said.
"It's not always the case that because we've lost something in the past, it's worth bringing back," he said. "What's worth anything now is to preserve what we've got going forward."