An extinct rat that once lived on an island in the Indian Ocean may have put the kibosh on scientists’ dreams of resurrecting more famous extinct animals like the woolly mammoth. The Christmas Island rat disappeared just over 100 years ago, but researchers now say even its detailed genome isn’t complete enough to bring it back to life.
The work “shows both how wonderfully close—and yet—how devastatingly far” scientists are from being able to bring back extinct species by genetically transforming a close relative in what’s called “de-extinction,” says Douglas McCauley, an ecologist at the University of California, Santa Barbara, who was not involved with the study.
No species has yet been revived, but de-extinction appeals to many geneticists and futurists. “I know a lot of biologists who think, ‘Can I do this?’” says Karen Wendling, an ethicist at the University of Guelph. Part of the fascination is simply the promise of seeing a vanished species come to life. But putting a key animal back into its original habitat could also help restore ecosystems. The mammoth once kept arctic shrubs and trees under control and fertilized grasses with their manure. Indeed, a company called Colossal Laboratories and Biosciences aims to transform elephants into mammoths, or, at least, mammothlike animals. “There is a lot of hope and hype that de-extinction will save us” from ecosystems failing, McCauley says.
To bring back an extinct species, scientists would first need to sequence its genome, then edit the DNA of a close living relative to match it. Next comes the challenge of making embryos with the revised genome and bringing them to term in a living surrogate mother. So far, scientists have sequenced the genomes of about 20 extinct species, including a cave bear, passenger pigeon, and several types of mammoths and moas. But no one has yet reported re-creating the extinct genome in a living relative.
In the new study, Tom Gilbert, an evolutionary geneticist at the University of Copenhagen, thought it best to start small. “If we want to try something so crazy, why not start with a simple model,” he reasoned. So, he, Jian-Qing Lin, a molecular biologist at Shantou University, and their colleagues, focused on the Christmas Island rat (Rattus macleari), which disappeared by 1908 from that island, located about 1200 kilometers west of Australia. This species “should be a dreamy candidate for de-extinction,” McCauley says, given its close relationship with the Norway rat, a well-studied lab animal with a complete genome sequence that scientists already know how to modify.
Gilbert and Lin extracted DNA from the skins of two preserved Christmas Island rats and sequenced it many times over to get as much of the genome as possible. They achieved more than 60 times’ coverage of it. Old DNA only survives in small fragments, so the team used the genome of the Norway rat as a reference to piece together as much as possible of the vanished rat’s genome. Comparing the two genomes revealed almost 5% of the Christmas Island rat’s genome was still missing, Lin, Gilbert, and their colleagues report today in Current Biology. The lost sequences included bits of about 2500 of the rat’s estimated 34,000 genes. “I was surprised,” Gilbert says. The recovered DNA included the genes for the Christmas Island rat’s characteristic rounded ears, for example, but important immune system and olfaction genes were either missing or incomplete.
The amount of missing DNA surprised Henry Greely, a bioethicist at Stanford University. “That’s an important issue that I hadn’t focused on.”
The work “really highlights the difficulties, maybe even the ridiculousness, of [de-extinction] efforts,” says Victoria Herridge, an evolutionary biologist at the Natural History Museum in London.
Many of the missing genes will be the ones that make each species unique, Herridge says. She notes that the more time that has passed since an extinct species and its living relative have diverged, the more genes are likely to be missing; the Christmas and Norway rats split 2.6 million years ago, a blink of an eye in evolutionary time; mammoths and the Asian elephants diverged 6 million years ago. “A lot of the talk has made [de-extinction] seem very straightforward, but of course, it’s not,” Herridge says.
McCauley agrees. He says 5% is a big difference—the human genome differs by just 1% from those of chimps and bonobos. “We could make something, but it seems clear it will never be a Christmas Island rat,” he adds. “In which case, what is the point?”
But Andrew Pask, a developmental biologist at the University of Melbourne, Parkville, who is spearheading an effort to bring back an extinct marsupial called the thylacine, or Tasmanian tiger, is unfazed by the new report. “The thylacine is perhaps the best candidate for [de-extinction],” he says. His team sequenced this predator’s genome as well as the genomes of several potential surrogate species, including the dunnart or marsupial mouse. They find that although 5% of the thylacines’ genome is missing, that 5% is primarily repetitive regions that likely won’t affect how the transformed animal looks or behaves, he says.
Moreover, sequencing is “steadily improving” for both modern and extinct DNA, says George Church, the Harvard University geneticist who helped found Colossal. “Many 100% animal genomes will be arriving faster and faster.”
Gilbert now thinks creating an exact replica of a mammoth or a passenger pigeon will be “impossible.” But such efforts might lead to what the International Union for Conservation of Nature calls “proxies,” animals close enough to carry out the same function in the extinct species’ old ecosystem, such as a cold-tolerant “woolly elephant.” And that’s where Church is headed. “The main goal is not making ‘perfect photocopies,’ but making diverse and selective hybrids,” he explains. Right now, his team is focused on defining the mammoth’s cold-tolerance genes for transferring into elephants.
Herridge cautions that in most cases scientists won’t know in advance how the edited genes will affect the animal’s behavior and ability to survive. “Even if we got it genetically perfect, we are still going to have to gestate it in a different species, so why would you think it would be exactly the same?” Wendling adds.
McCauley and others also think de-extinction efforts may take needed resources away from conservation. “You can save eight extant species for [the cost of] one that you make de-extinct,” Wendling points out.
But even those who are not sure that de-extinction could or should happen still fantasize about the possibility. Wendling wants to know what a dodo bird is like. And, Greely says, “Personally, I would love to see a giant ground sloth or an saber-toothed cat!”