If it’s up to the Colossal company, woolly mammoths will soon be stomping the earth again. And if you look at the slick company website, you might just think it’s a runaway race. But is that really so?

Colossal is not a student-oriented start-up. The company was founded by Harvard professor George Church, a top genetics scientist. Church is assisted by numerous other researchers and – not unimportantly – a number of large investors. Together they plan to bring the woolly mammoth back to the Arctic within ten years. Not so much as a place of interest, but to thoroughly transform that area. And in such a way that it is better able to cope with climate change (see box).

mammoth steppe
In the time of the mammoths, the Arctic looked very different than it does today. There was talk of a so-called ‘mammoth steppe’, which was covered with grasslands that eagerly absorbed carbon. Permafrost really lived up to its name and almost never thawed. It is very different today; the steppe has given way to tundra and taiga and the rapid warming of the Arctic is also starting to thaw the once permanently frozen ground. It leads to the release of powerful greenhouse gases – such as methane – which cause the earth to warm even further. And so the thawing permafrost increases our climate problem. Reason enough to do everything possible to keep the remaining permafrost frozen. And the woolly mammoth can help with that, Colossal says. This is done by restoring the mammoth steppe and protecting the permafrost from thawing while grazing and stomping around.

How does it work?

Colossal’s slick corporate website seems to be laying out a foolproof plan to us, where the actual creation of a woolly mammoth seems almost a formality. “Bringing back the woolly mammoth is not just a theory,” the site reports. “It’s a science that George Church and his lab have developed and mastered.” And then, in just a few sentences, it explains how Church and colleagues are going to bring back the woolly mammoth. It all starts with the cell nucleus of an Asian elephant. This contains the complete genome of the elephant. And that genome already corresponds for no less than 99.6 percent with that of the woolly mammoth. It means that – to obtain a woolly mammoth – only 0.4 percent of the genome needs to be tinkered with. And for this the researchers use the fairly new gene technology CRISPR-Cas9. Using this technology, the 0.4 percent of Asian elephant DNA that does not match that of the woolly mammoth is removed and then replaced with DNA from the mammoth. It results in a cell nucleus that harbors genetic material from both the Asian elephant and the woolly mammoth. That nucleus is placed in the enucleated egg of an Asian elephant, after which the egg is exposed to electrical pulses to simulate fertilization. The egg then begins to divide and grow and an embryo is formed. This embryo is placed in a surrogate mother – an African elephant. And if all goes according to plan, that African elephant will give birth to a woolly mammoth 18 to 22 months later.

Feasible?

The people behind Colossal have clearly put a lot of thought into it. But is it really possible to create a woolly mammoth in this way? dr. Bernard Roelen, developmental biologist at the Faculty of Veterinary Medicine at Utrecht University, can be brief. “I do not think so.” This is primarily due to the fact that CRISPR-Cas9 technology is still in its infancy. “And that technology is crucial in Colossal’s plans.”

CRISPR-Cas9

CRISPR-Cas9 is a technology that allows scientists to turn off specific genes in living cells or remove pieces of DNA from cells and replace them with alternative DNA. “In this case, specific genes on the Asian elephant’s genome that do not match those of the woolly mammoth are replaced.” And because of genes from the woolly mammoth. Thanks to well-preserved remains of the woolly mammoth, researchers have previously succeeded in sequencing the genome of this extinct species. “And the Asian elephant genome has also been mapped, so we know where the differences are.” The problem, however, is that there are quite a few differences. “0.4 percent difference may not seem like much, but it means that thousands of genes are abnormal,” says Roelen. “And you have to replace them all in one cell.” It would be an unparalleled achievement. Because although researchers in the lab have been working with CRISPR-Cas9 for years, in all those experiments only one gene per cell is always modified. “Adjusting thousands of cells at once is not an option yet.”

elephants

And that is not the only obstacle that Roelen sees. There is another crucial problem: Church and colleagues’ plan relies on African and Asian elephants. “And working with elephants is not easy.” That starts with getting eggs. “How did you get that? Cattle or cows can be treated with hormones to stimulate egg maturation, but that is a lot more difficult with elephants. Also, you can’t get to the ovaries that easily. I therefore do not see it happening that they will be able to collect enough eggs.” And then the embryos also have to be placed back in an African elephant. “That means that the elephant must be receptive to it and that it must be possible to implant the embryo. In humans and cattle, the success rate of the implant is about 30 percent. It will be the same with elephants.” All these challenges together, therefore, undoubtedly result in things regularly going wrong somewhere in the process – from obtaining the egg to the actual implantation of the genetically engineered embryos. “That means you’re going to need a lot of elephants to be successful.” And those are not up for grabs either. Especially not when we talk about the surrogate mothers. “African elephants are very difficult to keep in captivity.”

stunt

And so the beautiful story of Colossal hides quite a few bumps. Church must know that better than anyone, but seems to have skilfully polished away the bumps on the company website. “To me it feels more like a kind of stunt,” says Roelen. “He likes to shake things up a bit. At the same time – I think – you should also be careful that gene science and technology do not become known as something you can do strange things with. Because that can be at the expense of all the beautiful things we can achieve with it.”

For now, Church’s plans seem unlikely to succeed. However, that does not necessarily mean that the woolly mammoth will remain extinct for good; It seems – also given the great strides currently being made in genetics – it is only a matter of time before someone manages to bring back the woolly mammoth. “That will probably happen at some point. After all, it is a very cuddly idea, such a woolly mammoth.” But it is not much more, according to Roelen. “What to do with such a mammoth? Personally, I would be happier if we used the effort and money to preserve existing species.”

Bringing back the mammoth is therefore not so easy. But suppose that – against all odds – it would succeed. Could the mammoth actually contribute to solving our climate problem? You will read it tomorrow on Scientias.nl!