Abstract
Efforts to clone some rare, endangered and even extinct species have created controversy amongst conservation bodies who think resources could be much better directed.
The cheetah might be the fastest land animal but it can't seem to outrun its own vulnerability. In India, the last recorded sighting of the cheetah was in 1948 when three young males were shot by hunters. The International Union for the Conservation of Nature (IUCN) — the authority on the conservation status of species — lists the Asiatic cheetah as ‘critically endangered’ in its year 2000 Red List of Threatened Species (http://www.redlist.org/), meaning that the taxon faces an extremely high risk of extinction in the immediate future.
Efforts by India's Central Zoo Authority to acquire a breeding pair of cheetahs have so far been unsuccessful. Scientists at the newly established Laboratory for the Conservation of Endangered Species (LaCONES) in Hyderabad, India, believe the nuclear transplantation technology that led to Dolly, the cloned sheep, offers a solution. They will attempt to fuse skin cells from a male cheetah with enucleated leopard eggs. According to Lalji Singh, who heads the project, the hope is that the resulting embryos will be carried successfully to term using leopards as surrogate mothers.
India is taking its lead from Advanced Cell Technology (ACT), a privately held biotech company in Worcester, Massachusetts. Last year, ACTwas responsible for the first successful cloning of an endangered species, an ox-like animal known as a gaur. The numbers highlight the difficulties of the technique — fibroblast cells from a male gaur were fused to 692 enucleated cow oocytes but only 81 developed into blastocysts; 42 embryos were eventually transferred into 32 cows and eight became pregnant (see Cloning 2000, 2:79-90). One of these gave birth in January this year to a baby gaur christened Noah, the first gestation of a cloned animal in the womb of a different species.
“The success of this new method shows promise for rescuing rare and endangered species… in cases where a relative is available,” remarked Ian Wilmut, the editor-in-chief of Cloning and the leader of the Roslin Institute team that cloned Dolly.
Sadly, Noah died 2 days later of an intestinal Clostridium infection, said to be a common cause of death among young farm animals. ACT scientists say that they are sorry to have lost Noah but are heartened that the technology to produce a “cross-species offspring” has worked.
Interspecies nuclear transfer is also being used to reverse extinctions that have already occurred. In an echo of Jurassic Park, the book and film in which dinosaurs are brought back to life, ACT will attempt to revive the Pyrenees bucardo goat, which is extinct — albeit recently. The Spanish government last year approved ACT's plans to produce bucardo clones, using the ibex — a wild mountain goat — to carry the embryos. Because of poaching and habitat destruction, the numbers of bucardo have dwindled over the years. The last bucardo, a female, was killed by a falling tree at Ordesa National Park in Spain, but tissue was preserved before the animal perished. If the nuclear transfer were to work, in this case all the clones would be female. ACTwill try to create male clones by replacing one of the X chromosomes from the female bucardo's cell with the Y chromosome from a closely related goat species.
These efforts have drawn a mixed response from conservationists. Many express concern that cloning could derail other conservation efforts, for example, by diverting away funds that would otherwise go into habitat preservation. But reproductive biologist Kurt Benirschke, who founded the Center for Reproduction of Endangered Species (CRES) at San Diego Zoo and was its director for 11 years, counters that funds for undertaking cloning would not otherwise have gone into conservation.
Nevertheless, conservationists are incensed by the huge investment in cloning, which they view as essentially a ‘last-ditch effort’. Bill Holt, who heads the reproductive biology group at the Zoological Society of London, says “the investment [in the bucardo cloning project] is particularly ironic when you consider that more modest investment over the past 15 years could have achieved the desired result.”
Other critics point out that the lack of diversity among cloned nanimals could be a problem. “The notion of a uniform gene pool as being disastrous is misplaced,” says Benirschke, citing a recent report of a thriving feral herd of genetically uniform Chillingham cattle in the north of England (see Nature 2001, 409:303). These animals are thought to have been inbred for at least 300 years.
Philip Damiani, the ACT research scientist who led the Noah project, contends that cloning can help preserve genetic variation by adding new individuals to the dwindling gene pools of endangered species. He points out that the fibroblast cell used to clone Noah came from a gaur bull that never mated. Had Noah survived and eventually mated with the captive gaur population at San Diego zoo, the genome of the original dead bull gaur would have been salvaged.
With cloning technology, says Damiani, “we can now go out to the wild and collect tissue samples from a wild population of animals and introduce new genetics to either captive bred or wild populations without having to remove the original animal from the wild”. He adds that this is what conservation biologists are striving for — leaving the animal in its natural habitat. “I believe that both parties win in this situation.”
The fibroblast cell that led to Noah came from a bank of frozen cells at the CRES, which is housed at San Diego Zoo. The bank, which was set up by Benirschke, contains cell samples from over 4,300 animals — half of all mammalian orders are represented. In a letter published in Science, Benirschke appealed for a co-ordinated worldwide effort to bank DNA or cells for every endangered animal species (see Science 2000, 288:275-277). Well-known scientific personalities Sydney Brenner and Anne McLaren lent their support by co-authoring the letter with Benirschke and CRES geneticist Oliver Ryder.
Benirschke and others believe that these ‘frozen zoos’, originally intended for studies of genetic variation, would serve as a ‘genetic trust’ that could be used to ‘revitalize depleted gene pools’. But whether cloning technology can be applied successfully to reverse extinctions depends on finding suitable surrogate mothers to carry the embryos.
David Wildt, who heads the Department of Reproductive Sciences at the Smithsonian's National Zoological Park in Washington DC, believes that there are subtle differences, even among related species, that will not allow an embryo of one species to gestate in another. For Wildt, this is why interspecies transfer technology will never be used routinely. “For the moment, we are limited to animals that are known to hybridize, such as the cow and gaur could”, acknowledges Benirschke.
Both Wildt and Benirschke agree that research into the reproductive physiology of endangered species should be a priority. Wildt points out, “almost all basic research in the reproductive sciences has been limited to a few common species. The fundamental data simply are missing for virtually the remainder of the earth's biodiversity.” Until more is known, Wildt contends that it is unwise to focus on approaches such as interspecies transfer.
Holt and his colleague Amanda Pickard at the Zoological Society of London agree. They are working to develop artificial insemination methodology for highly endangered gazelles, and are convinced that assisted breeding methods can achieve the same goals as cloning.
The Smithsonian's Wildt says that reproductive biologists should “focus on the basics — trying to understand how animals can best naturally reproduce and survive — [rather than] propose and develop techniques that, at best, have the chance of producing a single ‘gee-whiz’ birth that the media will promote, but will do little for conservation.”
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