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Authors: George M. Church

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The Pleistocene epoch lasted from about 2.5 million years ago to about 10,000 years ago. That is getting awfully close to the present. The modern
continents were about where they are today. But if ours is the age of global warming, the Pleistocene was the age of massive glaciation and global cooling. Glaciers covered as much as 30 percent of the earth's total land area, and in North America the ice sheet at one point extended as far south as what is now Chicago.

The Pleistocene witnessed the rise of the charismatic megafauna, animal species that included the woolly mammoth, Neanderthal man, and
Homo sapiens
. It also saw the extinction of many of them, including the mammoth and Neanderthal, although the reasons for the extinctions are unclear. While the advancing glacial ice depopulated the affected regions of plant and animal life, it did not necessarily destroy them: in many cases the animals retreated southward and continued to thrive. The wooly mammoth seems to have evolved in very cold habitats.

One explanation offered for the extinctions is that modern humans hunted many of the species into extinction. And they may have been at least partly responsible for the extinction of the Neanderthals, our genetically closest-related hominid species, as well as for the demise of the woolly mammoth. If this is true, the question arises whether we have an obligation to bring these creatures back, not as circus sideshow attractions but as part of a focused scientific attempt to increase genetic diversity by reintroducing their extinct genomes into the global gene pool.

The mammoth almost cries out for resurrection. Some specimens unearthed from permafrost are so lifelike that they appear to be merely sleeping, not dead, much less extinct. Consider, for example, the baby mammoth Dima, discovered in a northern Siberian gold mine in 1977.

Resurrecting such a beast looks almost easy, but when it was actually attempted, it proved to be anything but. In 1980 Viktor Mikhelson of the Leningrad Institute of Cytology tried to reconstruct a mammoth embryo from cells recovered from Dima, but gave up after several months of failure. In the case of Neanderthal man, moreover, we have only fossils, not cells, making a resurrection attempt even more challenging.

Neanderthal man was first discovered in August 1856, when miners working in a limestone quarry in the Neander Valley, near Düsseldorf, Germany, came upon a pile of bones. The workers thought they were the
remains of a bear. In reality they were a partial skeleton of an ancient, lost species of humans.

Figure 6.1
Dima

Neanderthal man has since become a cultural icon, a fabled creature with a trademark name on the order of Godzilla or King Kong. But the Neanderthals were real, and for all the negative associations called up by their name, they were for a time the pinnacle of the animal kingdom.

They were bigger and stronger than modern humans, with larger skulls. And while “Neanderthal” has long been considered synonymous with “dumb brute,” these people in fact manifested ample signs of reasonably high intelligence. They used stone and wood tools, as well as axes and spears. They applied body ornamentation, made fires, built relatively complex shelters, hunted and skinned animals, and ate meat. Neanderthals also buried their dead, sometimes together with flowers, a practice that suggests that they possessed some sort of primitive ideology or belief system.

Paleontologists have attributed these practices to Neanderthals on the basis of artifacts recovered from sites containing Neanderthal skeletal remains. Further knowledge of these people has come from an analysis of the Neanderthal genome. Scientists had long thought that the reconstruction of ancient DNA sequences was unlikely if not impossible, something that occurred only in the wilder reaches of Michael Crichton–style science
fiction. The argument against it was based on the great age of the samples: any DNA recovered from ancient fossils would probably be too fragmented or corrupt to be readable. But in the 1980s Swedish paleontologist Svante Pääbo demolished that view once and for all.

Even as a child, Pääbo was fascinated by archeology and ancient civilizations, and at thirteen (in 1968) he persuaded his mother, who was a chemist (his father would win a Nobel Prize in Physiology or Medicine in 1982) to take him to Egypt. Later, while enrolled in a PhD program at the University of Uppsala, he obtained skin and bone samples from twenty-three mummies and hoped to extract DNA from them. To prevent contamination from human DNA, he did his work in an exceptionally clean laboratory, with a ventilation system sanitized by ultraviolet light. The lab was run in accordance with hot-zone-style biosafety procedures, with workers clad in sterile gloves, masks, and boots.

Pääbo ended up extracting and analyzing short stretches of DNA from the 2,400-year-old mummy of an infant boy. It was the first time in history that anyone had done such a thing, and his 1985 paper reporting his findings—his very first scientific paper, published while he was still a grad student—ran as a cover story in
Nature
: “Molecular Cloning of Ancient Egyptian Mummy DNA.”

Pääbo then turned his attention to Neanderthal man. In 1997 he obtained from the Rhineland Museum in Bonn a half-inch (1 cm) bone sample of a 42,000-year-old Neanderthal fossil. He ground up the sample, dissolved it in a chemical solution, and extracted recognizable mitochondrial DNA fragments. Later, he and colleagues tested more than seventy Neanderthal tooth and bone samples and obtained useful DNA from six of them.

In May 2010 Pääbo and an international team published “A Draft Sequence of the Neanderthal Genome” in
Science
. Four of the gene sequences discovered by members of that team have brought us somewhat closer to a more accurate picture of Neanderthal man. Fragments of the MC1R gene suggest that the Neanderthals were likely to have light rather than dark skin. Another discovery was more portentous: the presence of parts of the
FOXP2
gene, which is involved in speech and language. This
means that if we ever clone a Neanderthal into existence, we might actually be able to converse with him or her.

But why resurrect a Neanderthal? Or for that matter, any other animal?

The most obvious reason for resurrecting extinct species is to attenuate, even partially, the wave of mass extinction that is currently taking place and is a hallmark of the Holocene—our own epoch. If the continuing loss of countless species is a tragedy, then the introduction of effective countermeasures, and the increase in species diversity that will accompany them, can only be viewed as a benefit.

If we can rescue one species from permanent extinction, then we can rescue others as well. Zoos are already becoming agents of species conservancy, keeping germ lines intact in living examples. In addition to living zoos there are also “frozen zoos,” repositories of DNA as well as frozen, viable cell cultures, semen, embryos, oocytes, and ova, as well as blood and tissue specimens of extinct, rare, or endangered species. The Frozen Zoo at the San Diego Zoo, for example, houses samples from more than 8,400 individuals representing more than 800 species or subspecies. There is a smaller collection of genetic samples from rare and endangered species in cryo-preservation at the American Museum of Natural History in New York.

Worldwide, there are about a dozen frozen zoos. The genetic material in storage there could be used in the same type of nuclear transfer cloning experiments that produced Dolly and the bucardo clone. Frozen zoos exist to amplify the gene pool, increase genetic diversity, and rescue populations of endangered species; successful efforts to revive species that are already extinct will have the same effect. Extinct species by definition have been removed from the gene pool. Cloning them back into existence will bring their lost genetic material back into circulation.

But how can cloning, which produces only carbon copies, be used to increase genetic diversity? If you clone from frozen tissues of dead animals, cloning them back into existence reintroduces their lost genetic material into the global population.

Some organizations are doing this systematically, for example, the Audubon Center for Research on Endangered Species (ACRES) near New Orleans. Established in 1997 with $20 million in public and private financing, its long-term goal is to “unlock the secrets that could make extinction extinct.” Its immediate goal is to use nuclear transfer cloning to increase the gene pool, genetic diversity, and populations of endangered species.

ACRES researchers have been enormously successful, cloning several examples of a species of endangered African wildcat. But then they did something new: they bred together some of their clones, which then gave birth naturally. This was first done in the summer of 2005; the cloned wildcats produced two litters totaling eight wildcat kittens, all of them through natural birth. ACRES researchers thus have established that cloned animals can mate with each other and produce natural offspring. This creates additional specimens of the endangered animals, specimens that contain entirely new combinations of genetic material. Using these methods, ACRES has been able to increase the population of endangered Mississippi sandhill cranes by more than 20 percent in two years.

The director of the center, Betsy Dresser, makes several good points with respect to the benefits of cloning endangered species:

•  Cloning can help eliminate disease in a population by cloning only the disease-free animals.

•  Cloning versus saving the habitat is a false choice. You need to do both. Cloning provides a safety net.

•  Cloning members of endangered species can help preserve and propagate species that reproduce poorly in captivity.

•  Cloning can introduce new genes back into the gene pool of species that have few remaining members.

•  Clones of healthy animals can be introduced into wild populations to give a “booster shot” to a species undergoing a loss of genetic diversity.

In addition, there are other practical reasons for regenerating lost species, and in particular for regenerating Neanderthal man. For one thing, the reintroduction of Neanderthals would give
Homo sapiens
a sibling
species that would allow us to see ourselves in new ways. It might give us an inkling into another form of human intelligence, or of different ways of thinking. There might even be health benefits if Neanderthals proved to be resistant to diseases like AIDS or tuberculosis, for example, or diseases that coevolved with
Homo sapiens
like smallpox, polio, syphilis, or the next surprise pandemic.

Of course, there are also arguments against extinction reversal. An organism that has been extinct for 30,000 years is more likely to have little or no resistance to diseases that have evolved since then than to have a native resistance to them. Still, as we have seen, the human immune system offers little or no resistance to many of the diseases that our species has coevolved with, and a resurrected Neanderthal might be no worse off than we are in this respect. As a precautionary measure, newly regenerated species could be confined inside sterile environments until their disease resistance was evaluated and perhaps augmented through drugs, vaccines, or other modalities.

Another argument against reviving extinct species is that cloning is hard on the subjects, with any eventual successes being preceded by a long series of failed attempts: stillbirths, as well as misshapen, abnormal, and impaired offspring. Why bring these animals back only to have them suffer in this way?

There are at least two answers to this question. The first is that by the time regenerating these animals becomes economically feasible, cloning technology will have progressed to the point that successes will be far more common than failures. The second is that although nuclear transfer cloning may be hard on the animal, so is natural biological birth. In fact, approximately one in every thirty-three babies born in the United States each year suffers from one or more birth defects, which are the leading cause of infant mortality, accounting for more than 20 percent of all infant deaths annually. Birth is an inherently risky business.

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