Last year, Japanese and Russian scientists announced they had found just such a bone and predicted they would be able to clone a mammoth within 5 years. They hope to insert nuclei from the mammoth cells into egg cells from its closest living relative, the elephant, and carry the mammoth embryo in an elephant’s womb.
However, some scientists have cast doubt about whether this is possible. Hendrik Poinar, a palaeo-geneticist at McMaster University in Hamilton, Canada, and his team have uncovered similarly well-preserved mammoth bones and never found viable cells or nuclei. “The likelihood of finding an intact cell that can be rejigged to life – it’s not that it’s an impossibility – but the chances are very, very slim,” he says. “The other hope has been to find frozen testicles and use that for insemination, which is a complete pipe dream.”
Poinar says that genome engineering offers a more realistic shot at resurrecting woolly mammoths and other long-extinct species. Ten-thousand-year-old cells and their nuclei may be too degraded to be used in cloning, but they still contain the animal’s genetic code. This genome is shredded into short fragments, but DNA sequencing machines can read these shards and powerful computers can stitch them into a genome sequence.
These genomes exist in the form of computerised data, but they could serve as a blueprint for altering the DNA of a cell from a closely related species. For instance, the code of a woolly mammoth’s genome differs from an African elephant’s by roughly 240,000 DNA letters out of a total of 4 billion, though most of these changes are not likely to have a biological effect. An elephant iPS cell engineered to contain those mutations would theoretically be capable of producing woolly mammoth sperm.
Better yet, the woolly mammoth stem cells could be implanted besides an elephant embryo early in development, producing a chimera animal with some tissues made from elephant cells and others from mammoths. In some individuals the mammoth cells would contribute to sperm or eggs, and these cells be used to create a genuine mammoth through IVF.
In the absence of a living mammoth, scientists are reconstructing some of its most vital components from DNA fragments to discover how it adapted to life at subzero temperatures. Scientists have already recreated haemoglobin, the oxygen-carrying protein in red blood cells, and found that it is optimised to catch and release oxygen molecules in the cold. Scientists could go one step further and test woolly mammoth red blood cells made from iPS cells, Poinar says.
If the idea of mammoths roaming the Earth still sounds a bit far-fetched, it should. Resurrecting a mammoth or indeed any extinct species would require a dizzying list of technological leaps in genome engineering, reproductive biology, and veterinary medicine, and that is just to surmount the challenges that scientists know about.
What is more, the technologies that scientists are hoping to use have mostly been developed for use in laboratory animals and valuable livestock only.
Basic genetic principles may carry over to more exotic animals, but many steps will not, particularly those involving reproduction and development. For instance, a recent study found that making a chimeric rhesus monkey – a process needed to resurrect a monkey species from frozen cells – is much trickier than a mouse. “I think we are going to encounter numerous problems as we try to figure this out for different species,” says Robert Lanza, chief scientific officer for Advanced Cell Technology, the firm that has tried to clone endangered species.