Recently, the use of biotechnology to resurrect extinct animals has become a hot topic. Not long ago, the American Breakthrough Biological Sciences and Genetic Engineering Corporation ("Colossal") announced the completion of an over-$60 million Series A financing, the company's main personnel are "the godfather of contemporary genomics" George Church, who hopes to use biological sciences, genetic engineering and genomics to promote the development of extinct species conservation and human health. We invited zhang Tiankan, a well-known popular science author, to talk about related topics.
(1) Objects and steps of resurrection
In the past five hundred years, more than 300 species of mammals, birds, reptiles and amphibians have disappeared. The expansion of human activity has deprived these animals of their habitat and become the main cause of their extinction.
The animals at the top of the list of scientists to be resurrected include mammoths, European bison, dodos, passenger pigeons, Pyrenees goats, New England black grouses, monarch woodpeckers, saber-toothed tigers, white-flagged dolphins, thylacines (Tasmanian tigers) and so on. This time, Colossal's main target is mammoths, and European bison are also considered.
Mammoth
wisent
dodo
Passenger pigeons
thylacine
To resurrect an extinct animal, the biotechnology that can now be considered is cloning, which is to extract intact cells from the recently extinct animal, isolate and extract the nucleus, transplant the nucleus into another egg cell, reactivate the synthesized egg cell and implant it into the surrogate host. The world's first cloned sheep Dolly was cloned in this way, and this technology can also be used to resurrect extinct animals.
The second is genetic engineering, which compares the genome of an extinct animal with the genome of its existing close relatives, and then uses gene editing tools to repair the genes of extinct animals with the genes of existing close relatives, or integrates the genes of extinct animals into the genome of existing close relatives to form a complete genome, and activates the complete genome of hybrid repair, and then implants it into the surrogate animal for pregnancy.
The nuclei or complete genomes of extinct animals are difficult to extract because of their age. Moreover, even if the nucleus is preserved in the frozen soil, it will be eroded by various physical and chemical factors, and after extraction, there may be gene deletion, damage, and contamination. Therefore, if extinct animals are resurrected with cloning technology, it is only suitable for animals that have recently become extinct, because intact undamaged and uncontaminated DNA may be extracted, so the cloning method is not suitable for the resurrection of long-extinct animals such as mammoths and passenger pigeons.
Genetic engineering can repair lost genes and thus resurrect old extinct animals, such as mammoths. If you follow the current Colossal technology route to revive mammoths, there are specifically 5 steps - obtaining the DNA of frozen mammoths from Siberia, Russia; using gene editing technology to fuse them into the genome of close relatives asian elephants; implanting the genome into the eggs of Asian elephants that have removed the nucleus; stimulating the eggs to develop into hybrid embryos; putting them into the uterus of surrogate Asian female elephants, or using artificial wombs for breeding.
As you can see, these steps also require cloning techniques and surrogacy, because there are no real mammoths as mothers to conceive offspring, and because the mammoth's genome has some damage, it is necessary to use gene editing tools to repair and fuse the genome into the DNA of Asian elephants. This, in turn, raises the question of whether xenoclonal clones are compatible and valid.
Moreover, Asian elephants are also endangered species, and their small numbers make it difficult to obtain enough recipient oocytes. Asian elephants have a reproductive interval of up to 4-6 years, and even if mammoths can be bred, the cycle will be very long. In addition, the genetic similarity between Asian elephants and mammoths is only 93%, which may lead to the rejection of the fetus by the mother, and may also give birth to animals that do not resemble mammoths or Asian elephants.
(2) A precedent of short-term success
Since resurrecting extinct animals is difficult, is there a precedent for even brief success? There really has been.
In 2003, Spanish and French scientists revived an extinct Pyrenees goat in the same way that dorian dolly cloned sheep. Inhabiting the cliffs of the Pyrenees in southwestern Europe, the Pyrenees wild goat feeds on grass, is hardy, weighs up to 100 kilograms, and has a pair of beautiful curved horns on its head, but has been endangered by human hunting for many years. In 1989, Spanish zoologists counted that there were only more than 10 Pyrenees goats left, but by 1999, only a live female Pyrenees goat had been found, and researchers named it Celia.
Despite the efforts of scientists to protect Celia, such as Alberto Fernandez-Arias, a wildlife expert in Spain's Aldeesza National Park, who led researchers to catch it, put it on a radio collar and return it to the forest for supervision and protection, 9 months later, Celia died under a collapsed tree. This also means that the Pyrenees wild goat went extinct in 2000.
Immediately after the discovery of Celia, the researchers extracted a portion of its active cells and preserved them in laboratories in Madrid and Zaragoza, Spain. In later years, wildlife experts in Ordesa National Park tried to revive Celia with these preserved cells. The way it was done was to clone the sheep Dolly. The scientists extracted the nuclei from Celia's cells, injected them into ordinary goat egg cells that had their DNA removed, and then activated the synthetic egg cells and implanted them into the pregnant goat. Although 57 ewes received egg cell implantation, only 7 ewes produced live embryos in their uterus, of which 6 ewes miscarried and only one ewe was conceived and reached the time of delivery.
For insurance purposes, on July 30, 2003, scientists performed a caesarean section on the surrogate ewe and delivered Celia's offspring, but the cloned Pyrenees wild goat had difficulty breathing as soon as it left the mother, and her life was in danger, and it died after only 10 minutes of survival. After an autopsy, it was found that the cloned lamb's lungs were congenitally deformed, with a large and hard lung lobe that could not survive, and that no medical technique could save its life.
This also means that even newly extinct animals are difficult to revive using cloning techniques. If you want to use the Asian wild elephant to resurrect the mammoth, it is more difficult than resurrecting the Pyrenees wild goat. Now, it's not just Colossal researchers who want to resurrect extinct animals, but other researchers are also ambitiously trying to resurrect extinct animals. One of them is the team of developmental biologist Andrew Paske at the University of Melbourne in Australia, who wants to revive the thylacine, one of Australia's iconic animals of the past.
The Paske team believes that the thylacine may be the best candidate for extinction for resurrection. Paske's team sequenced the genomes of the top animals in the food chain, as well as the genomes of several potential alternative species, and found that 5% of the thylacine genome was missing, but that 5% of the genes were mainly repetitive regions that may not affect the resurrection, and the resurrected thylacines did not look or behave differently from the thylacines of the past. However, whether the thylacine can be revived depends not on theory and prediction, but on practical work. Whether it is feasible or not depends on the actual results.
(3) A relatively successful precedent
Cloning endangered wildlife has been a more successful example. On December 10, 2020, American scientists cloned a descendant, Elizabeth Ann, using the cells of a black-footed ferret named Willa who died more than 30 years ago, with a similar technical route to the cloned sheep Dolly.
The black-footed ferret, also known as the black-footed ferret, is a small carnivorous mammal native to North America and the only ferret native to North America, with a body length of 31-41 cm, a tail length of 11-15 cm, and a weight of 0.8-1 kg. In the past, blackfoot ferrets were widely used to live in the western United States, but the gradual expansion of human arable land has slowly made it lose its home. In the 1970s, the species was thought to be extinct, but in 1981, scientists followed a sheepdog to find the location of 18 black-footed ferrets. These survivors were protected and became the basis for captive breeding programs, and later bred 400-500 black-footed ferrets.
Still, black-footed ferrets are also at risk of extinction because they don't just lose their homes, they also face the threat of plague. Therefore, scientists at the Blackfoot Ferret Conservation Center of the Colorado Fish and Wildlife Service hope to resurrect the black-footed ferret in a cloned way, using Willa's cells.
The researchers extracted the nucleus of Willa's cells, transferred them to another egg of a black-footed ferret with the nucleus removed, formed a composite egg, electrically stimulated the egg, made it divide, and transplanted it into a domesticated surrogate ferret mother to conceive.
On December 10, 2020, the surrogate domestic ferret gave birth to Elizabeth, who has been so healthy so far that researchers hope she will eventually be able to pass on the generations. If all goes well, Elizabeth's grandchildren or great-grandchildren could return to the wild in 2024 or 2025. At the same time, the researchers also wanted to test whether the resurrected black-footed ferret could be integrated into the ecology and had a positive effect on the ecology rather than destructive effect. Specifically, it is necessary to test whether black-footed ferrets and their descendants can survive after being released into the wild and have the ability to hunt grassland marmots to protect the ecological environment.
The successful resurrection of the black-footed ferret Willa means that it is also possible to resurrect other extinct wild animals, but resurrecting mammoths and thylacines is more difficult and complicated than resurrecting black-footed ferrets, and whether it can succeed will take time and practice to test.
Clone of the black-footed ferret "Elizabeth".
(4) Resurrect the puzzle of extinct animals
Tom Gilbert, an evolutionary geneticist at the University of Copenhagen, is working with researchers at Shantou University in China to try to resurrect the Christmas Island rat, which became extinct from an island habitat west of Australia in 1908.
Gilbert et al. extracted DNA from the skin of two well-preserved Christmas Island mouse books, sequenced them several times, and obtained most of the genomes of Christmas Island rats, but there were still some defects. So the team used the genome of a Norwegian rat as a reference to piece together as many disappeared rat genomes as possible. Because the Norwegian rat is a well-studied laboratory animal, it has a complete genome sequence that is known to be available for editing.
After comparing the genomes of the two close relatives, the researchers found that the genomes of Christmas Island rats were still missing nearly 5 percent. The genetic sequences of the lost Christmas Island rats are about 2,500 out of 34,000 genes that encode traits such as round ears that are unique to Christmas Island rats, and some important Christmas Island rats have genes involving the immune system and sense of smell that are either missing or incomplete.
These missing genes may be unique to Christmas Island rats, so it is unlikely that they will be able to revive the original Christmas Island rats. Christmas Island rats and Norwegian rats separated 2.6 million years ago, compared to mammoths and Asian elephants that parted ways 6 million years ago, so it seems more difficult to use Asian elephant genes to compensate for mammoths' missing genes and resurrect mammoths.
However, Church, who works at Colossal and seeks to revive mammoths, believes that the sequencing of DNA in modern and extinct animals is steadily improving, and there is a chance to recover 100% of the genome in the future, making the goal of resurrecting extinct animals possible.
(5) Controversy over the meaning of resurrection
According to Colossal scientists, the goal of reviving mammoths is to develop technologies that have greater application value for human health care, such as developing new drugs and even solving problems in wildlife reproduction. However, there is also controversy over the resurrection of extinct wildlife, the biggest controversy being the significance and role of doing so. Some scientists believe that even if extinct animals can be resurrected, under the existing conditions, the resurrected animals will have difficulty surviving, so they will lose their meaning. Whatever the cause of the extinction of the animals, it means that they are no longer suitable for the environment at that time, and now that they are resurrected and released into the wild, it is difficult to say whether the resurrected animals will adapt to the current environment, and they may also destroy the current ecology. Just as American researchers after resurrecting black-footed ferrets, they are still observing whether the cloned resurrected black-footed ferrets are adapted to the environment, whether it is beneficial to the ecology or harmful.
In addition, there is an important issue of the cost performance of resurrecting extinct animals. According to calculations, the cost of resurrecting 1 extinct species is enough to save 8 endangered species. Instead of resurrecting extinct animals, it is better to save endangered animals. Moreover, even if humans have the ability to resurrect individuals of an extinct animal, it is not the same as humans have the ability to resurrect an entire population; even if humans have the ability to resurrect the population of an extinct animal, the habitat suitable for their growth may have long disappeared. The remaining option is to keep them in captivity in a laboratory or zoo for people to visit, what does this mean to nature?
Image source: Visual China
Source: Beijing Daily Client | Reporter Wang Hongliang
Process Edit: U016
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