There are scientific proposals that sound like science fiction. However, current scientific and technological advances allow us to propose many projects that, despite seeming crazy, are no longer impossible.
A notable example is found in the de-extinction of the woolly mammoth, an animal that disappeared from the face of the Earth thousands of years ago. The project to bring it back is the initiative of the company Colossal, founded by Harvard University researcher George Church, which does not take a stitch without a thread and usually delivers what it advertises. To his credit we find historical milestones such as encoding images and movie frames in the genome of bacteria using CRISPR gene editing tools.
The woolly mammoth (Mammuthus primigenius) lived for thousands of years in northern Europe, perfectly adapted to the cold. The oldest remains of the mastodon are 150,000 years old. Their extinction as a species began around 10,000 years ago, probably due to excessive hunting, perhaps helped by climate change. It is believed that the last specimens survived on islands in northern Siberia not inhabited by man, until they completely disappeared 4,000 years ago.
Phylogenetically, the woolly mammoth was the evolutionarily closest relative of the Asian elephant (Elephas maximus), with which it shared a common ancestor from which both separated about 6 million years ago. Paradoxically, it diverged from the American mammoth (Mammut americanum) much longer ago, approximately 24-28 million years ago. That is why the current Asian elephant is the ideal ally for the de-extinction of the woolly mammoth.
To bring back an already extinct animal species we need, first of all, its cells. Or, at least, its genome. In the case of the woolly mammoth, the DNA has been recovered almost entirely from the remains of specimens that, when they died, were trapped in the ice, in the permafrost of the Siberian tundra. One of the best preserved specimens is a baby mammoth, a three- to four-month-old female they named Lyuba, which has been frozen for 37,000 years.
Once a large part of the woolly mammoth’s genome has been obtained, what George Church intends to do through his de-extinction project is to use CRISPR-Cas9 gene editing tools to add, delete, eliminate and, ultimately, modify thousands of sequences of DNA in the genome of some Asian elephant cells until they become as similar as possible to the DNA of the woolly mammoth. As Church acknowledges, they do not know exactly how many modifications they will need, although they estimate that they will be less than 500,000, which are the genetic differences that exist between the two genomes.
Assuming they manage to edit the thousands of genetic modifications necessary with CRISPR, the next step would be to obtain an embryo that can be gestated to give rise to a baby woolly mammoth. To do this, George Church and the Colossal company intend to use cloning technology, specifically the somatic cell nuclear transfer technique that we discovered with the birth of Dolly the sheep.
They would start from an Asian elephant egg, eliminate its nucleus (genetic material) and replace it with the nucleus of one of the cells edited with the mammoth’s genes. That reconstructed embryo would begin to divide in the laboratory, but a few days later it would have to be implanted and gestated.
Equivalent projects have been successfully carried out by cloning from species (or subspecies or breeds) of relatively similar animals, as occurred with the cloning of the Przewalski horse, successfully undertaken by another company in the sector, Revive.
There is another option? Yes. The alternative would be to gestate the mammoth in an artificial womb, something extraordinarily complex, which again sounds like science fiction. But it is not: a team of researchers from the Children’s Hospital of Philadelphia managed to allow a sheep fetus to develop for a month thanks to an artificial uterus in 2017. Therefore, there are already technical advances available that will undoubtedly be optimized and will soon allow much, or perhaps all, of a mammal’s gestation to be completed extrauterinely.
This cocktail of biotechnological tools was missing one more element: we needed to be able to obtain induced pluripotent cells (iPS cells), with characteristics similar to embryonic pluripotent cells. That is, we need cells that could differentiate into any adult tissue, including male gametes (sperm) and female gametes (eggs) that allow an in vitro fertilization procedure to be carried out to give rise to an embryo without the need to resort to the cloning technique. . And this is what the Colossal researchers seem to have achieved, according to an announcement in the journal Nature and a scientific manuscript deposited on the preprint server bioRxiv.
In this paper, Colossal researchers demonstrate that these Asian elephant iPS cells are capable of differentiating into the three embryonic lineages: mesoderm, ectoderm and endoderm, which is proof of their cellular pluripotency. If they manage to obtain all the iPS cells from the Asian elephant, first, and from the woolly mammoth, later, they could differentiate into eggs and sperm. And these gametes could combine with each other to generate embryos that can be gestated. They could even generate so-called synthetic embryos, which are already possible to obtain in mice and also in humans, although, at the moment, they do not seem to have the capacity to develop to term.
Now that we know what is already possible, and also everything that will surely be possible in the future, the question is: why would we want to de-extinct an animal, the woolly mammoth, that disappeared a few thousand years ago? On a whim? As incredible as it may seem, in some ways, in the minds of George Church and the Colossal researchers, the de-extinction of the woolly mammoth represents a complex strategy that, ultimately, aims to fight against climate change and global warming of the planet.
This article was originally published on The Conversation. Lluís Montoliu is a scientific researcher at the National Center for Biotechnology (CNB – CSIC).
