Extinction, it seems, may no longer be for ever. Several weeks ago, scientists in George Church’s lab at Harvard University announced that they had created living elephant cells that contained a small component of synthesised mammoth DNA. The announcement stirred both excitement and concern that the mammoth – a hairier cousin of the Asian elephant – might soon be back from the dead. But how close are we really to seeing resurrected mammoths wandering their old stamping grounds, including the Norfolk countryside? The answer depends on how you define mammoth.
Let’s begin by laying out what resources we have today. First, scientists who study the genetics of extinct species have recently decoded most of the mammoth’s genome sequence, which means we have a pretty good genetic blueprint for making a mammoth. Second, by comparing the mammoth genome sequence to the elephant’s, we are beginning to understand how, at the level of their DNA, mammoths and Asian elephants differed. This tells us what parts of the elephant genome we will need to change in order to make a mammoth. Third, recent advances in genome engineering technologies provide a powerful toolkit for editing genomes, including cutting out and replacing specific genes. And fourth, the work at Harvard has proved that these tools can be used to insert mammoth DNA into an elephant cell. Resurrected mammoths no longer seem the stuff of fantasy.
When the Harvard scientists designed their experiment, the goal was to take an elephant genome and make it a little more mammoth-like. They searched scientific literature for genes that might benefit an elephant if it were suddenly to find itself living somewhere cold. They looked for genes that code for denser hair, thicker layers of fat and blood cells that transport oxygen with increased efficiency at low temperatures. They identified 14 such genes and then compared the mammoth and elephant versions of them, looking for differences. Where they found them, they used new genome-editing technologies to delete the elephant version and insert the mammoth version. The result: elephant cells, growing in a dish in a lab, in which elephant genomes contained a small – less than 0.0001% – but important fraction of mammoth DNA.
Creating an animal 100% identical to an extinct species may be an impossible task. Despite the common use of the term “de-extinction”, one cannot actually “clone” an extinct species. Cloning is a specific scientific technique in which a living cell, for example a skin cell, is taken from one animal and its genetic material is inserted into a different animal’s egg cell. The proteins in the egg cell then “reset” the genetic material from the skin cell, which had been programmed during development to express only those genes necessary to be a skin cell. The newly unprogrammed cell then begins to divide and eventually develops into a 100% identical copy – a clone – of the donor. This powerful technology has, since the mid-1990s, been used to create clones of dozens of species. But it requires something that doesn’t exist for any extinct species – a living cell.
When an organism dies, the DNA in its cells begins to decay almost immediately. Chemicals in the cell itself, water, oxygen and UV radiation all contribute to this decay, which will gradually break the DNA down into smaller and smaller fragments until it is completely destroyed. The rate of decay varies depending on where the organism dies. Cold environments with little fluctuation in ambient moisture are best for DNA preservation. In the Arctic, for example, DNA has been recovered from bones buried in frozen soil for 700,000 years (this maximum age of surviving DNA is bad news for proponents of dinosaur de-extinction). In hot climates, DNA may not survive for more than a few months.
The last mammoths lived on Wrangel Island, off north-east Siberia in the Chukchi sea. These became extinct 4,000 years ago and many bones dating from this period have been recovered. As predicted by the combination of their relatively young age and the cold climate, the bones contain recoverable DNA. Recoverable DNA, however, is not the same as intact DNA or living cells. The DNA recovered from the Wrangel Island mammoths tends to be highly fragmented and riddled with errors –the typical sign of decay.
In the past five years, mummified remains of mammoth carcasses have been melting out of the Siberian permafrost with increasing frequency. With each new discovery come renewed claims that mammoth cloning will proceed forthwith. While some of these finds are remarkably well preserved – one was even associated with a substance that some argue might be thickened blood – none has harboured intact cells. And none will. Even mummies cannot escape the damaging rays of the sun or the cell-and-DNA-destroying action of microbes from the animal’s gut or from the soil in which the mummy is buried.
Which brings us back to the Harvard team and their 0.0001%-mammoth cell. This intact and living cell might be useful for cloning. But once the clone is born, will it be considered a mammoth? Is changing 14 genes sufficient to claim that mammoths have been resurrected (George Church certainly has not made this claim)? Is it enough to focus on cold tolerance or should we also change genes associated with reproductive strategies, diet and metabolism and susceptibility to disease? Should we, perhaps, change every single place in the genome where the two species differ?
Today, the technology to edit genomes is limited in the number of changes that can be made at once, which is probably one reason why the Harvard team focused on only 14 genes. We can make a rough guess, based on what is known about when the two species diverged and how quickly mammalian genomes change over time, that there are some 70m genetic differences between mammoths and Asian elephants. Today, that is too many changes to make. This technology will improve, of course, and some day it may be possible. Then, we could clone that cell. But, even then, would the animal that was eventually born be considered a mammoth?
Maybe. Importantly, an organism is more than its genetic code. If the only thing to define an individual were the DNA sequence, then identical twins would be truly identical. But they have different attitudes, ideas, inspirations and, as they get older, their different experiences manifest themselves as different physiques. How an organism looks and acts arises from a combination of its genes and its environment. And the influence of environment begins, critically for the purposes of de-extinction, in the womb.
Let’s say we are able to harvest elephant egg cells (which we cannot and probably should not do) and somehow coax these egg cells to accept the genetic material from one of our edited cells. Let’s assume those cells begin to divide and grow into embryos. Let’s then assume that we can transfer those developing embryos into a surrogate elephant (which we cannot do and it seems unlikely will become feasible, given the reproductive biology of elephants) and that a pregnancy is established.
What follows is a key developmental period for the foetus. Hormones are being produced that regulate when genes are turned on and off. Nutrients are being absorbed and turned into energy. But whose genes are regulating the hormones? And whose behaviour is controlling the diet? Will the foetus, even with as many as 70m mammoth-specific changes to its genome (this translates to around 2%), have any role to play in how its development will proceed? How important are the mother’s genes, diet and the environment in which she lives during the gestation period in determining what that baby will look like and how it will behave once born? Although we still have much to learn, the scientific evidence strongly hints that the prenatal environment is critical in determining both neonatal gene expression and behaviour and that some influences of the prenatal environment can be detected well into adulthood.
For the sake of pushing this hypothetical scenario through to the end, let’s say the pregnancy ends with the birth of a healthy baby. Let’s call it a mammoth, for the sake of simplicity. Who will rear the baby mammoth and where will rearing take place? It is most likely that the birth would take place in a captive breeding facility, which is not terrific news for the elephant mother as elephants do not tend to flourish in captive environments. She would then have to teach the baby mammoth how to go about its life – to find food and water, to join and navigate the social ladder, to find a partner and reproduce. She only knows how to be an elephant and, with only one mammoth in existence, there would be neither a social ladder to navigate nor a potential partner to find.
Finally, the time would come to release the mammoth into the wild. Interestingly, figuring out where to release the mammoth might be among the simplest problem facing mammoth de-extinction to solve, as there is a protected habitat in north-eastern Siberia (I’ll say more about this) where resurrected mammoths would be welcomed. However, we could not release just one mammoth into this habitat and expect it to thrive. Mammoths were probably highly social creatures, just as their elephant cousins are, and therefore their persistence in the wild would require complex social groups comprised of individuals of varying age, experience and status.
But is mammoth de-extinction ethical? From an animal welfare perspective, almost certainly not. Elephants struggle to reproduce and even survive in captive breeding facilities, and are struggling to maintain their own populations in their native habitat. Elephants should be provided with the opportunity to make more elephants, and not be subjected to scientific manipulation for what seems like a far-fetched and unrealistic goal. Those who favour mammoth de-extinction paint a rosier picture of the future, in which mice are coaxed to grow elephant egg cells from grafted elephant follicles, and artificial wombs rather than real elephants are used to bring the developing embryos to term. These technological fixes are certainly interesting to contemplate and would no doubt find important uses outside of de-extinction, but even they do not solve every problem that mammoth de-extinction will face. For example, how long will it take? Mammoths are animals that reproduce for the first time when they are teenagers. The first age-structured social complex would not be ready for release until many decades after the first mammoth was born, which corresponds to many decades of life, much of it alone, in captivity.
What is the the most compelling reason to consider bringing mammoths back to life? To me, it is the ecological argument made by Sergey Zimov of the Russian Academy of Science’s Northeast Science Station. Zimov has created a habitat near his home which he calls “Pleistocene Park” and is using this habitat to measure the influence of reintroduced herbivores on the Arctic tundra. Today, Pleistocene Park is grazed by Canadian bison, wild horses and several species of deer. The effects have been immediate and clear. In only a few years, the trampling, grazing and recycling of nutrients carried out by these herbivores has transformed the relatively barren tundra into a rich grassland eerily reminiscent of the steppe tundra of the ice age. These rich grasslands have attracted visits from native fauna, including the extremely rare saiga antelope. The interaction between the grazing herbivores and the plants on which they feed has been restored and both communities are flourishing.
But when he talks about the benefits of grazing herbivores in his park, Zimov highlights one other extraordinary and potentially more important observation. When the animals return to the patches of grass that are maintained into the winter, they trample down the fallen snow and expose the ground to the cold Siberian air. As a consequence of this exposure, the soil beneath grazed in his park is somewhere between 15-20C colder during the winter months than that beneath ungrazed land. Scientists estimate that there may be as much as 1,400 gigatonnes of carbon currently trapped in the frozen Arctic soil, almost twice the amount of carbon that is in the Earth’s atmosphere today. Zimov points out that reintroducing mammoths and other large herbivores into Siberia has the potential to reduce permafrost thaw, potentially slowing the accumulation of greenhouse gases in the Earth’s atmosphere.
So there may be compelling reasons to reintroduce grazing herbivores in some parts of the Arctic. However, while large herbivores such as mammoths clearly have a distinct role to play in their community, it is not clear to me that the specific need for mammoths outweighs the ethical challenges facing mammoth de-extinction.
Of course, not every de-extinction project faces the same ethical or even technical hurdles and mammoths are not the only candidate species for de-extinction whose resurrection might have ecological benefits. Consider the kangaroo rats of western North America. When these tiny environmental engineers become extinct in a particular area, their disappearance transforms the desert plain in which they lived into arid grassland in less than a decade. Plant diversity declines, causing seed-eating birds to disappear. The lack of burrows leaves insects and small animals without shelter. In essence, kangaroo rat extinction places the entire ecosystem in peril of the same. Kangaroo rat de-extinction would be simpler than mammoth de-extinction, as rodent genetics, reproductive biology and behaviour are well understood, and other kangaroo rat species would be ideal surrogate parents. So why are people so much more excited about revived mammoths than revived kangaroo rats? The answer is obvious: mammoths are mammoths and kangaroo rats are, well, rats.
While I cannot come down entirely in favour of mammoth de-extinction, I do appreciate the power of the idea of resurrected mammoths. Far-fetched, crazy ideas stimulate excitement, concern, anger, and – most importantly – creativity. As we face growing threats to global biodiversity, as human populations expand and wild spaces become fewer and further between, we need increasingly creative solutions to conserve and protect living species. Many of the challenges facing de-extinction would not be challenges at all if surrogate mothers and surrogate social groups still existed. Perhaps the technologies behind de-extinction will some day be used, and far more easily, to engineer genetic changes that make extinction less likely.
How to Clone a Mammoth by Beth Shapiro is published by Princeton University Press, £16.95. To buy it for £13.56 click here
Beth Shapiro will be speaking about the Science of De-extinction the Royal Institution, London, May 21. For further information, click here.
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