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Day of the (Un)Dead: The De-Extinction Enterprise

2015; Cell Press; Volume: 162; Issue: 1 Linguagem: Inglês

10.1016/j.cell.2015.06.039

1097-4172

R. D. E. MacPhee,

Environmental Philosophy and Ethics

De-extinction is much in the news these days, in no small measure because of the subject of this review—Beth Shapiro’s lively account of the science behind the attempt to bring back lost species. She writes uncommonly well and manages to cover a fairly complex series of issues surrounding this very new initiative, from the bench science involved in creating new life to the unavoidably tough ethical issues such work provokes. As a leading figure in ancient DNA studies, Shapiro—an associate professor of biology at the University of California, Santa Cruz—certainly has the background to speak authoritatively on technical matters, but the value of her outlook is that she is also very good on why we should—or shouldn’t—engage in bringing back the dead. Thankfully, she is especially clear that the future of de-extinction science is not in populating Jurassic World-style theme parks with Pleistocene megafauna like the woolly mammoth (Mammuthus primigenius) and sabertooth cat (Smilodon fatalis) running about. Nor, she thinks, should de-extinction of particular species be undertaken as a form of restorative justice, on the theory that humans were ultimately responsible for their demise. For megafaunal losses in particular, it is far from certain that humans were uniquely responsible. And even if they were, why should de-extinction be seen as an appropriate form of restitution? This, like other questions she poses throughout the book, do not have easy answers, which makes it all the more important that they be asked at this stage, before rather than after the fact. The book’s cookbook title implies that the reader will be taken through the steps one might follow in order to go from finding a frozen bit of woolly mammoth on the tundra to realizing the end product, a frischgebackt baby elephant. Shapiro provides introductory lessons for all of that, but covers the necessary lab science with a light touch, partly by illustrating several incandescently obvious problems with the whole “let’s-clone-the-mammoth” scenario made popular by TV documentaries. Amusingly, she covers several quixotic efforts (including one in which she participated) to find “perfectly” preserved Siberian mammoth carcasses whose genetic material might be recovered intact and thus provide a basis for cloning by somatic cell nuclear transfer. This is not going to happen: Every mammoth mummy that has been found to date shows extensive post-mortem damage, probably because the bodies lay for lengthy periods on the ground where sun, rain, and saprophytes took their toll. A much more likely approach to de-extinction involves determining how woolly mammoths differed genomically from their closest living relative, the Asian elephant. There is already a considerable body of information available on the mammoth transcriptome, thanks to extensive investigations by several teams of ancient DNA specialists during the past decade. The idea is that, by comparing the genomes of these two elephantids, known differences could be changed out using genomic engineering approaches such as CRISPR. This is fine as far as it goes, but many other, increasingly theoretical and untested steps must be achieved before you get the baby. In Shapiro’s view, one crucial development is just around the corner: an elephant stem cell housing a manufactured mammoth nuclear genome. The imagined scenario is as follows: Assuming that the cell in question (and no doubt hundreds more just like it) can be prodded into developing into an embryo, and that the embryo can be successfully implanted in an Asian elephant surrogate mother, the hope is that after a two-year gestation the result should be a healthy hybrid. By creating other hybrids with slightly different genetic endowments, the eventual result might be a small population of long-haired, large-tusked animals that would phenotypically recall what we think such animals looked like. Similar steps might be undertaken for any number of other recently extinct species, assuming there is sufficient museum material to recover a significant part of their genomes. Indeed, the Long Now Foundation, which has played a very active role in promoting de-extinction studies, has compiled a lengthy list of more or less likely candidates to bring back. Among other things, this emphasis on re-establishing viable populations of the un-extinct raises knotty questions that traditional taxonomic approaches are ill designed to answer. Can such creations be regarded as members of the same species as the one that supplied the genetic information when there is no continuity of generations? If not, what are they? Shapiro would consider the de-extincted to be no different from other entities whose genetics have been strongly influenced by human manipulation. They are, quite plainly, genetically modified organisms. The real future of de-extinction, she maintains, lies not with bringing back defunct species in their biological entirety as functioning individuals and populations, but instead with identifying and harvesting packets of genetic code that appear to have conferred specific adaptive advantages to their original bearers (such as especially efficient oxygen uptake in the case of woolly mammoth hemoglobin, a useful thing to possess in cold climates). Such packets would be available for introduction into the germlines of other species, as a sort of genomic version of organ transplanting. Shapiro calls this “adaptational resurrection,” noting that it is just another form of induced genetic modification, differing from standard practice only in that the GMOs get their genetic novelties from extinct rather than extant sources. Could adaptational resurrection be a significant tool for conservation biology? For example, would it not be a positive thing to increase the fecundity of pandas, if that were possible, given that low or diminishing population sizes are a leading indicator of endangerment? Conversely, would it not be desirable to reduce, using genetic drive approaches, the fecundity of mosquito species that carry the malarial parasite, Plasmodium? In a particularly interesting thought experiment, the author wonders whether the next chapter in the story of bringing back the mammoth might be to simply bypass the enormous difficulties involved in recreating a functional population of the unextincted, and aim instead for genetic modification of Asian elephants so that they would be able to live in cold regions, which they currently cannot do. And why would anyone want to do that? So that the re-engineered elephants could undertake one of the unfilled ecosystem jobs in present-day northern Asia—that of animated bulldozer/bush puller specialist. The idea is seductive—a constantly overturned topsoil, richly manured by the elephants and perhaps similarly genetically engineered horses, musk oxen, and bison might transform the wet tundra that now dominates Asian northlands into something like the “mammoth steppe,” the diversified grassland that existed in this region during the late Pleistocene. This might provide habitat for many other kinds of mammals and birds, especially if global climate change forced them from their current ranges. This is clearly science fiction at present, for we have neither the modified animals nor any real notion of the feedback systems that might be affected by taking on what amounts to a continental-scale terraforming project. A final point to emphasize is that de-extinction is a very small part of the current explosion of interest in genome-scale engineering and synthetic biology. We are perched on the cusp of a scientific revolution that will most certainly change the world, for now we can literally create new life, including life that has never existed before in any sense of the term, by mixing and matching code derived from any number of organisms. We are also in a position to speed up evolutionary change with mutagenic chain-reaction techniques, which in principle can drive a chosen gene to saturation in a population or species in a matter of a few generations. Some results of this technology may be hugely beneficial, not only for humans but for the other co-residents we share the planet with. Others might create conditions for a biological Armageddon. But that potential has existed for centuries, if not millennia, for every ecosystem on earth has experienced anthropogenic impacts. Surely the only way forward is to expose both the problems and prospects of this very new biology to public inspection and discussion, as Beth Shapiro’s book does in so effective a manner.