The science of de-extinction—research into how we might be able to bring species that have become extinct back to life—is a rapidly emerging field. It's not completely surprising that the idea has attracted so much attention. It's a fascinating thought that we might be able to revive long-lost species such as the mammoth or even, as Jurassic Park imagines, dinosaurs. But it's also appealing because if extinction is not forever, then it lets us off the hook. If we can bring species that we have driven to extinction back to life, then we can right our wrongs before it is too late. We can have a second chance, clean up our act and restore a healthy and diverse future, before it is too late to save our own species.
I run a research laboratory at University of California, Santa Cruz. My lab specialises in a field of biology called “ancient DNA.” We and other scientists working in this field develop tools to isolate DNA sequences from bones, teeth, hair, seeds, and other tissues of organisms that used to be alive, and use these DNA sequences to study ancient populations and communities. The DNA that we extract from these remains is largely in a terrible condition, which is not surprising given that it can be as old as 700,000 years. But even if we are able to generate a genome sequence, we then have to transform a bunch of letters into a living thing.
While it is still not possible to bring extinct species back to life, science is making progress in this direction. In 2009, a team of Spanish and French scientists announced that a clone of an extinct Pyrenean ibex was born to a mother who was a hybrid of a domestic goat and a different species of ibex. To clone the Pyrenean ibex, the scientists used the same technology that had been used in 1996 to successfully clone Dolly the sheep. That technology requires living cells, so, shortly before her death, scientists captured the last living Pyrenean ibex and took a small amount of tissue from her ear. They used this tissue to create embryos. Only one of 285 embryos that were implanted into the surrogate mothers survived to be born. But unfortunately, the baby ibex had major lung deformity and suffocated within minutes. Similarly, in 2013, Australian scientists announced that they had successfully made embryos of an extinct frog—the Lazarus frog—by injecting nuclei from Lazarus frog cells that had been stored in a freezer for 40 years into a donor cell from a different frog species. None of the Lazarus frog embryos survived for more than a few days, but genetic tests confirmed that these embryos did contain DNA from the extinct frog.
The Lazarus frog and Pyrenean ibex projects are only two of the several de-extinction projects that are underway today but, because they both involve using frozen material that was collected prior to extinction, they are among the most promising. Other de-extinction projects, including mammoth and passenger pigeon de-extinction, face more daunting challenges, but are proceeding nonetheless and, in the case of the mammoth, along several different trajectories. Sergey Zimov, a scientist at the Russian Academy of Science’s Northeast Science Station, is so convinced that mammoths will be brought back to life that he has established Pleistocene Park near his home in Siberia and is preparing it for the impending arrival of the resurrected creatures (one of the challenges of de-extinction work is that, if an ancient species is successfully brought back to life, we will also need to recreate a suitable environment in which they can survive).
Two paths are generally considered when contemplating de-extinction. The first is to do what most people are referring to when they talk about cloning. To clone Dolly the sheep in 1996, scientists at the Roslin Institute, which is part of the University of Edinburgh in Scotland, removed a small piece of mammary tissue from an adult ewe that contained living cells, and used the DNA in these cells to create an identical copy of the adult ewe. This process is called somatic cell nuclear transfer, or, more simply, nuclear transfer. This is not likely to be the process used to bring many extinct species back to life. Cloning by nuclear transfer, unfortunately, requires intact cells. So, unless tissue was taken from a living individual prior to the species’ extinction (as with the Pyrenean ibex), nuclear transfer will not work. If we’re dealing with a species whose genome we have had to sequence and assemble, then we need a different approach.
The other path to creating a living organism is eerily reminiscent of
Jurassic Park. As in real life,
Jurassic Park scientists were only able to recover parts of the dinosaur genome—in the case of the movie, from the mosquito blood that was preserved in amber (at the time the first film was written, scientists really did believe that ancient DNA might be able to be extracted from amber-preserved animals—but this is no longer thought possible). To fill in the holes where they couldn’t get dinosaur DNA, they used frog DNA. Unfortunately, they weren’t able to know beforehand which bits of DNA were important to making a dinosaur look and act like a dinosaur, and which bits were just junk. We can only assume that these fictional scientists were hoping that the frog DNA that they had to use was the junk bit. But, of course, they were wrong, and some of that frog DNA let the unextinct dinos miraculously switch sexes, leading ultimately to disaster and $400m in box office earnings. In real-life de-extinction science, the plan is to know which bits of the genome are important to making the extinct species look and act the way it did prior to de-extinction. Once this is known, the intention is to copy these important bits from the extinct genome, and then find-and-replace those same bits in the genome of a close living relative.
Of course, this is all easier said than done. Let’s say we want to bring a mammoth back to life by editing an elephant genome to look like a mammoth genome. First, we have to learn what all the differences between the elephant genome and the mammoth genome are. Then, because making all the changes might be too much to accomplish (at least in the first de-extinctions), we could narrow down which changes to make by deciding which of the differences are important. We might learn, for example, that mammoths have a different copy of a gene called Ucp1—mitochondrial brown fat uncoupling protein 1—than elephants do. Experiments with mice have shown that Ucp1 is involved with thermoregulation. Since mammoths lived in very cold places and elephants do not, we might hypothesise that the mammoth version of this gene helped them to stay warm. As our goal is to turn an elephant into an animal that can survive in cold places, converting this gene from the elephant version to the mammoth version would help to achieve that goal. So, we construct a molecular tool whose job it is to go into an elephant cell, find the spot in the genome that codes for the Ucp1 gene, and edit that gene so that it looks like the mammoth version.
To make the complete mammoth genome, all we have to do is repeat this for every important difference between mammoths and elephants. Next, we take the cell with the edited genome and inject it into an egg cell that has had its nucleus removed. That cell begins to divide and develop into an embryo, following the familiar path of cloning by nuclear transfer. We then place that embryo into the uterus of a surrogate mother, where it continues to develop and is eventually born.
Genetically pure mammoths, or genetically pure versions of any extinct species, are likely not possible. However, we do not need genetic purity to benefit from de-extinction technology. If we select wisely which 1 per cent of the genome to change, we may be able to resurrect those characteristics that distinguish a mammoth from an elephant. This is what successful de-extinction is likely to look like in the future.
This article is an abridged extract from Beth Shapiro's new book, How To Clone A Mammoth: The Science of De-Extinction (£16.95). © 2015 Princeton University Press. Reprinted by permission.
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