How CRISPR could ignite the debate and bring the woolly mammoths back



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Bringing extinct species back to life may sound like science fiction, but it is a real thing, perhaps the most important thing that has occurred in the past 4.5 billion years. Called “de-extinction”, the resurrection of lost species is one of the many applications that must be revolutionized by the new CRISPR-Cas9 gene editing technology. CRISPR, which stands for “short palindromic repeats at regular intervals,” hit the headlines in October when researchers Jennifer Doudna and Emmanuelle Charpentier received the Nobel Prize in Chemistry for their role in developing a new technique. for gene editing. CRISPR re-proposes a process found naturally in the bacterial immune system that now allows scientists to modify the DNA of nearly all living organisms with extraordinary precision.

The first successful cleanup occurred long before the advent of CRISPR. The Pyrenean ibex (Capra pyrenaica pyrenaica), a type of wild mountain goat commonly known as a bucard, was once a common sight in the French Pyrenees and northern Spain. By the end of the 19th century, hunting had reduced the species to fewer than 100 individuals. When the last, a female known as Celia, died in January 2000, the Pyrenean ibex joined the estimated 5 billion species that have become extinct since life was born on this planet. But in this case, three years later, on July 30, 2003, a team of French and Spanish scientists gathered around a pregnant domestic goat and gave birth by caesarean section to a live baby genetically identical to the extinct bucard. For the next seven minutes (after which the animal died of respiratory failure), the Pyrenean ibex never went extinct.

The extinct bucard was brought back to life thanks to the established technology of cloning by nuclear transfer. This technique, in which a cell containing the complete genome of the extinct species is inserted into the egg of a living animal, was used to clone Dolly the sheep in 1996. But now, with CRISPR, de-extinction does not require a live or frozen cell of the extinct species. Instead, all scientists need are organic remains, such as pieces of bone, which contain fragments of DNA. These fragments allow geneticists to discover the complete genome of the extinct animal (a process that scientists refer to as “sequencing”). Once they have this “recipe” for the extinct species, CRISPR allows scientists to modify the DNA of its closest living relative to create a genome that, as modified, approximates the genetic code of the extinct species. Think of the living animal’s DNA as software version 2.0 – the goal is to go back to version 1.0. Compare all the millions of lines of code to spot the differences, then meticulously edit the lines with differences to restore the code to its original state.

Once the DNA has been modified to reintroduce the key traits of the extinct plant or animal, the modified DNA is inserted into the nucleus of a reproducing cell. The resulting individual may not be genetically identical to the extinct species, but the key traits that made the extinct species unique are reintroduced and the resulting animal or plant has the potential to be the functional equivalent of its extinct relative. So, for example, scientists working on the de-extinction of the woolly mammoth (which last wandered the Earth some 4,000 years ago) are starting with the DNA of an Asian elephant and then using CRISPR to reintroduce the traits. that made the woolly mammoth unique, such as metabolism, subcutaneous fat and bristly hair that allowed it to survive in the sub-arctic tundra.

But why do it? Most proponents of de-extinction make an argument based on ecological restoration. For example, large herbivores such as the woolly mammoth played a vital role, through trampling, grazing and fertilization, in maintaining the grassy cap that insulated the permafrost of the great northern tundra. As these large grazing beasts disappeared, the grassy cap decreased, allowing the underlying permafrost to thaw and release huge volumes of previously trapped greenhouse gases, significantly accelerating global warming. To reverse this effect, Russian scientists in a remote part of eastern Siberia are working on an effort called “Pleistocene Park”. Their vision is a restored mammoth steppe, a place where the Siberian permafrost is again isolated by treeless grasslands extending to the horizon in all directions, on which vast herds of wild horses, bison and destitute mammoths graze in cold savannah symbiosis.

Will we use our power in selfish, shortsighted and reckless ways or will we instead devote ourselves to using new technologies to mitigate our past wrongs and restore a healthy Earth?

Another extinction currently being attempted for ecological restoration purposes is that of the passenger pigeon, once the most abundant bird species in North America, with billions of individuals up to 1870. The entire population was affected, taken with the net, hunted or otherwise slaughtered by humans. In 1914, the last person, Martha, died in a Cincinnati zoo. The consequences of the rapid extinction of a keystone species at this scale are not precisely understood, but we know enough to expect them to be widespread and profound. For example, the loss of the passenger pigeon led to disruption of the forest regeneration cycle and a significant decline in forest health. It may also have accelerated the proliferation of Lyme disease. Advocates of “Re-wilding” such as Stewart Brand’s Long Now Foundation also point out that any de-extinction improves the biodiversity that is the basis for healthy ecosystems.

One of the other justifications for pursuing de-extinction is moral: possessing the power to restore lost species implies a moral duty to use that power, at least in the case of the species whose extinction was caused by humans. In other words, we have a duty to correct our previous wrong. It is notoriously difficult to estimate the number of species whose disappearance can be attributed mainly to human interference. But all scientists agree that humanity’s greed, recklessness, and neglect have greatly accelerated the natural rate of extinction, harming both the planet and ourselves.

The enthusiasm of the supporters of de-extinction is almost equal to the skepticism of its detractors. Many of the issues are practical, such as doubts that humans can create populations with sufficient genetic diversity and number to be sustainable in nature; fears that destroyed animals are not genetically identical to extinct species nor do they benefit from non-genetic factors (such as parental care) that have determined their behavior; and arguments that plants and animals created on the basis of ancient genomes will not thrive in contemporary conditions. For example, the carrier pigeon, if reanimated, would face a world in which the American chestnut, which provided an important part of its habitat and food, has disappeared.

Conservation biologists are divided on the issue. Some argue that the belief in the possibility of de-extinction creates a moral hazard, opening the door to those who economically benefit from habitat destruction to argue that even if a species is lost, it can always be “brought back”. Others simply say that in the current era of man-made mass extinction, society should prioritize those endangered species that can be saved rather than dreaming of bringing lost ones back to life. They argue that CRISPR, instead of being used for disinfection, should be used to increase the genetic diversity of an endangered surviving population, increasing its chances of survival.

One thing is certain. Like Prometheus’ gift of fire to humanity, the cat has come out of the sack. Efforts by governments and NGOs to limit or control the use of genetic technologies, such as the 2020 guidelines issued by an international committee convened by the US National Academy of Medicine, the US National Academy of Sciences, and the Royal Society are unlikely British. further experiments involving the editing of the heritable human genome. What scientists can do, at least some, somewhere, will.

And why do I say the result could be the most important thing to happen on the planet for 4.5 billion years? Since the dawn of life on Earth, species have developed through the process of random genetic mutation followed by natural selection, evolution. But from this point on, things changed. CRISPR-Cas9 gives us the ability to hack evolution. Instead of waiting for mutations to happen randomly, we can modify our genetic inheritance (or that of other life forms). This means the substitution of human desire and choice for the process of natural selection. Is this inevitably the disaster many predict?

Humanity has a long tradition of carrying out interventions to improve, restore and protect the natural world. Virtually no agricultural or horticultural species have been unaffected by hybridization, and most of those altered plants are now esteemed citizens of the natural world. Wheat, grapefruit, and peppermint all come from interspecies farming (as well as other branches of the tree of life, cattle, bison, African bees and honey bees). Gene editing is, without a doubt, a new and different one tool, but the result, species created by man (rather than by the operation of natural selection), it is not.

Those instinctively suspicious of these types of interventions in nature tend to see the natural world as static. But now we understand that nature is not a stable and passive stage on which the dance of life takes place. On the contrary, the relationship between an environment and the life it hosts is highly interactive. Species adapt to their habitat and then change it. Since homo sapiens emerged during the Middle Paleolithic, we entered this dance by transforming the habitats and organisms they sustain. Population growth and technology mean the scale of our impact is now global. With the act of conceiving the current geological era as the Anthropocene, where human activity is the dominant influence on the planet, we have begun to come to terms with the fact that we are now the creators and no longer simply the creation. It is a responsibility that cannot be evaded. Human moral and ethical structures must catch up with our technology. Will we use our power in selfish, shortsighted and reckless ways, or will we instead devote ourselves to using new technologies to mitigate our past mistakes and restore a healthy Earth?

Of course, caution is always important. But too often shyness and hostility to progress disguise themselves under the guise of prudence. If tools like CRISPR allow us to replace keystone species like the woolly mammoth and the passenger pigeon to maintain greenhouse gases in the tundra or to restore healthy ecosystems, then we should use them. We cannot escape choice through inaction. Now that we have the technology for de-extinction, failure to use it to heal the planet is also a choice that we will be held accountable for by future generations.



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