How to Clone a Mammoth

by Shapiro, Beth

  THE SIXTH EXTINCTION

  More than 3,700 years after the last mammoth died on Wrangel Island, we are witnessing an alarming number of contemporary extinctions, and the rate of extinction appears to be increasing. Some scientists have gone so far as to refer to the Holocene extinctions as the Sixth Extinction, suggesting that the crisis in the present day has the potential to be as destructive to Earth’s biodiversity as the other five mass extinctions in our planet’s history.

  The word alone—extinction—frightens and intimidates us. But why should it? Extinction is part of life. It is the natural consequence of speciation and evolution. Species arise and then compete with each other for space and resources. Those that win survive. Those that lose go extinct. More than 99 percent of species that have ever lived are now extinct. Indeed, our own species’ dominance is possible only because the extinction of the dinosaurs made space for mammals to diversify, and eventually we outcompeted the Neandertals.

  I think people are scared of extinction for three reasons. First, we fear missed opportunities. A species that is lost is gone forever. What if that species harbored a cure for some terrible disease or was critically important in keeping our oceans clean? Once that species is gone, so is that opportunity. Second, we fear change. Extinction changes the world around us in ways that we both can and cannot anticipate. Every generation thinks of our version of the world as the authentic version of the world. Extinction makes it harder for us to recognize and feel grounded in the world we know. Third, we fear failure. We enjoy living in a rich and diverse world and feel an obligation, as the most powerful species that has ever lived on this planet, to protect this diversity from our own destructive tendencies. Yet we chop down forests and destroy habitats. We hunt and poach species even when we know they are perilously close to extinction. We build cities, highways, and dams and block migration routes between populations. We pollute the oceans, rivers, land, and air. We move around as fast as we can on airplanes, trains, and boats and introduce foreign species into previously undisturbed habitats. We fail to live up to our obligation to protect or even coexist with the other species with which we share this planet. And when we stop to think about it, it makes us feel terrible.

  Extinction is much easier for us to swallow when it is clearly not our fault. Why did the mammoth go extinct? As humans, we want the answer to be something natural. Natural climate change, for example. We would prefer to learn that mammoths went extinct because they needed the grasslands of the steppe tundra to survive and that they simply starved to death as the steppe tundra disappeared after the last ice age. We would prefer not to learn that mammoths went extinct because our ancestors greedily harvested them for their meat, skins, and fur.

  While some of us may not care about extinction as long as we are not personally affected, many of us find extinction unacceptable, particularly if it is our fault. Most contemporary extinctions are easy to ignore, as they have little influence on our day-to-day lives. The cumulative effect of these extinctions is, however, a future of very reduced biodiversity. This future could be one in which so many changes have occurred to the terrestrial and marine ecosystems that we, ourselves, are suddenly vulnerable to extinction. It doesn’t get much more personal than that.

  REVERSING EXTINCTION

  It’s not completely surprising that the idea of de-extinction—that we might be able to bring species that have gone extinct back to life—has attracted so much attention. 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.

  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, also known as a bucardo, was born in 2003 to a mother who was a hybrid of a domestic goat and a different species of ibex. To clone the bucardo, the scientists used the same technology that had been used in 1996 to successfully clone Dolly the sheep. That technology requires living cells, so in April 1999, ten months before her death, scientists captured the last living bucardo and took a small amount of tissue from her ear. They used this tissue to create bucardo embryos. Only one of 208 embryos that were implanted into the surrogate mothers survived to be born. Unfortunately, the baby bucardo had major lung deformity and suffocated within minutes.

  In 2013, Australian scientists announced that they 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 forty 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 bucardo projects are only two of the several de-extinction projects that are under way today. These two projects involve using frozen material that was collected prior to extinction and, consequently, are among the most promising of the existing de-extinction projects. Other de-extinction projects, including mammoth and passenger pigeon de-extinction, face more daunting challenges, of which finding well-preserved material is only one. These projects are proceeding nonetheless and, in the case of the mammoth, along several different trajectories. Akira Iritani of Japan’s Kinki University is trying to clone a mammoth using frozen cells and claims that he will do so by 2016. George Church at Harvard University’s Wyss Institute is working to bring the mammoth back by engineering mammoth genes into elephants. Sergey Zimov of the Russian Academy of Science’s Northeast Science Station worries less about about how mammoths will be brought back than about what to do with them when it happens. He established Pleistocene Park near his home in Siberia and is preparing his park for the impending arrival of resurrected mammoths.

  Not all de-extinction projects take a species-centric view. George Church’s project is focusing on reviving mammoth-like traits in elephants, for example. While the goal of this project is to create an animal that is mammoth-like, its motivation is to reintroduce elephants into the Arctic. Stewart Brand and Ryan Phelan have taken an even more holistic view. Together, they created a nonprofit organization called Revive & Restore, and are asking people to consider all the ways in which de-extinction and the technology behind it might change the world over the next few decades or centuries. In addition to initiating the passenger pigeon de-extinction project, Revive & Restore is driving several projects to revive living species that have dangerously low amounts of genetic diversity. With Oliver Ryder of San Diego’s Frozen Zoo, for example, Revive & Restore is isolating DNA from archived remains of black-footed ferrets, which are nearly extinct in the present day. They hope to identify genetic diversity that was present in black-footed ferrets prior to their recent decline and, using de-extinction technologies, to engineer this lost diversity back into living populations.

  In March 2013, Revive & Restore organized a TEDx event at National Geographic’s headquarters in Washington, DC, to focus on the science and ethics of de-extinction. This media event was the first attempt to address de-extinction at a more sophisticated level than attention-grabbing headlines. When the event concluded, pubic opinion about de-extinction was mixed. Some people loved and others hated the idea that extinctions might be reversed. Fears were expressed about the uncertain environmental impacts of reintroduced resurrected species. Some ethicists argued that de-extinction is morally wrong; others insisted that it is morally wrong not to bring things back to life, if indeed it were possible to do so. Voices were also raised in opposition to the cost of de-extinction and whether the potential benefits justified this cost. What was lost in the noise of the ensuing public debates, however, was discussion of the current state of the science of de-extinction: what is possible now, and what will ever be possible? And, perhaps more important
ly, there was little conversation and certainly no consensus about what the goal of de-extinction should be. Should we focus on bringing species back to life or on resurrecting extinct ecosystems? Or should the focus be on preserving or invigorating ecosystems in the present day? Also, and importantly, what constitutes a successful de-extinction?

  In this book, I aim to separate the science of de-extinction from the science fiction of de-extinction. I will describe what we can and cannot do today and how we might bridge the gap between the two. I will argue that the present focus on bringing back particular species—whether that means mammoths, dodos, passenger pigeons, or anything else—is misguided. In my mind, de-extinction has a place in our scientific future, but not as an antidote to extinctions that have already occurred. Extinct species are gone forever. We will never bring something back that is 100 percent identical—physiologically, genetically, and behaviorally identical—to a species that is no longer alive. We can, however, resurrect some of their extinct traits. By engineering these extinct traits into living organisms, we can help living species adapt to a changing environment. We can reestablish interactions between species that were lost when one species went extinct. In doing so, we can revive and restore vulnerable ecosystems. This—the resurrection of ecological interactions—is, in my mind, the real value of de-extinction technology.

  A SCIENTIFIC VIEW OF DE-EXTINCTION

  I am a biologist. I teach classes and run a research laboratory at the University of California, Santa Cruz. My lab specializes 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 terrible condition, which is not surprising given that it can be as old as 700,000 years.

  During my career in ancient DNA, I have extracted and studied DNA from an assortment of extinct animals including dodos, giant bears, steppe bison, North American camels, and saber-toothed cats. By extracting and piecing together the DNA sequences that make up these animals’ genomes, we can learn nearly everything about the evolutionary history of each individual animal: how and when the species to which it belonged first evolved, how the population in which it lived fared as the climate changed during the ice ages, and how the physical appearance and behaviors that defined it were shaped by the environment in which it lived. I am fascinated and often amazed by what we can learn about the past simply by grinding up and extracting DNA from a piece of bone. However, regardless of how excited I feel about our latest results, the most common question I am asked about them is, “Does this mean that we can clone a mammoth?”

  Always the mammoth.

  The problem with this question is that it assumes that, because we can learn the DNA sequence of an extinct species, we can use that sequence to create an identical clone. Unfortunately, this is far from true. We will never create an identical clone of a mammoth. Cloning, as I will describe later, is a specific scientific technique that requires a preserved living cell, and this is something that, for mammoths, will never be found.

  Fortunately, we don’t have to clone a mammoth to resurrect mammoth traits or behaviors, and it is in these other technologies that de-extinction research is progressing most rapidly. We could, for example, learn the DNA sequence that codes for mammoth-like hairiness and then change the genome sequence of a living elephant to make a hairier elephant. Resurrecting a mammoth trait is, of course, not the same thing as resurrecting a mammoth. It is, however, a step in that direction.

  Scientists know much more today than was known even a decade ago about how to sequence the genomes of extinct species, how to manipulate cells in laboratory settings, and how to engineer the genomes of living species. The combination of these three technologies paves the way for the most likely scenario of de-extinction, or at least the first phase of de-extinction: the creation of a healthy, living individual.

  First, we find a well-preserved bone from which we can sequence the complete genome of an extinct species, such as a woolly mammoth. Then, we study that genome sequence, comparing it to the genomes of living evolutionary relatives. The mammoth’s closest living relative is the Asian elephant, so that is where we will start. We identify differences between the elephant genome sequence and the mammoth genome sequence, and we design experiments to tweak the elephant genome, changing a few of the DNA bases at a time, until the genome looks a lot more mammoth-like than elephant-like. Then, we take a cell that contains one of these tweaked, mammoth-like genomes and allow that cell to develop into an embryo. Finally, we implant this embryo into a female elephant, and, about two years later, an elephant mom gives birth to a baby mammoth.

  The technology to do all of this is available today. But what would the end product of this experiment be? Is making an elephant whose genome contains a few parts mammoth the same thing as making a mammoth? A mammoth is more than a simple string of As, Cs, Gs, and Ts—the letters that represent the nucleotide bases that make up a DNA sequence. Today, we don’t fully understand the complexities of the transition from simply stringing those letters together in the correct order—the DNA sequence, or genotype—to making an organism that looks and acts like the living thing. Generating something that looks and acts like an extinct species will be a critical step toward successful de-extinction. It will, however, involve much more than merely finding a well-preserved bone and using that bone to sequence a genome.

  When I imagine a successful de-extinction, I don’t imagine an Asian elephant giving birth in captivity to a slightly hairier elephant under the close scrutiny of veterinarians and excited (and quite possibly mad) scientists. I don’t imagine the spectacle of this exotic creature in a zoo enclosure, on display for the gawking eyes of children who’d doubtless prefer to see a T. rex or Archaeopteryx anyway. What I do imagine is the perfect arctic scene, where mammoth (or mammoth-like) families graze the steppe tundra, sharing the frozen landscape with herds of bison, horses, and reindeer—a landscape in which mammoths are free to roam, rut, and reproduce without the need of human intervention and without fear of re-extinction. This—building on the successful creation of one individual to produce and eventually release entire populations into the wild—constitutes the second phase of de-extinction. In my mind, de-extinction cannot be successful without this second phase.

  The idyllic arctic scene described above might be in our future. However, before a successful de-extinction can occur, science has some catching up with the movies to do. We have yet to learn the full genome sequence of a mammoth, for example, and we are far from understanding precisely which bits of the mammoth genome sequence are important to make a mammoth look and act like a mammoth. This makes it hard to know where to begin and nearly impossible to guess how much work might be in store for us.

  Another yet-to-be-solved problem is that some important differences between species or individuals, such as when or for how long a particular gene is turned on during development or how much of a particular protein is made in the gut versus in the brain, are inherited epigenetically. That means that the instructions for these differences are not coded into the DNA sequence itself but are determined by the environment in which the animal lives. What if that environment is a captive breeding facility? Baby mammoths, like baby elephants, ate their mother’s feces to establish a microbial community capable of breaking down the food they consumed. Will it be necessary to reconstruct mammoth gut microbes? A baby mammoth will also need a place to live, a social group to teach it how to live, and, eventually, a large, open space where it can roam freely but also be safe from poaching and other dangers. This will likely require a new form of international cooperation and coordination. Many of these steps encroach on legal and ethical arenas that have yet to be fully and adequately defined, much less explored.

  Despite this somewhat pessimistic outlook, my goal for this book is not
to argue that de-extinction will not and should never happen. In fact, I’m nearly certain that someone will claim to have achieved de-extinction within the next several years. I will argue, however, for a high standard by which to accept this claim. Should de-extinction be declared a success if a single mammoth gene is inserted into a developing elephant embryo and that developing elephant survives to become an adult elephant? De-extinction purists may say no, but I would want to know how inserting that mammoth DNA changed the elephant. Should de-extinction be declared a success if a somewhat hirsute elephant is born with a cold-temperature tolerance that exceeds that of every living elephant? What if that elephant not only looks more like a mammoth but is also capable of reproducing and sustaining a population where mammoths once lived? While others will undoubtedly have different thresholds for declaring de-extinction a success than I do, I argue that this—the birth of an animal that is capable, thanks to resurrected mammoth DNA, of living where a mammoth once lived and acting, within that environment, like a mammoth would have acted—is a successful de-extinction, even if the genome of this animal is decidedly more elephant-like than mammoth-like.

  MAKING DE-EXTINCTION HAPPEN

  Many technical hurdles stand in the way of de-extinction. While science will eventually find a way over these hurdles, doing so will require significant investment in both time and capital. De-extinction will be expensive. There will be important issues to consider about animal welfare and environmental ethics. As with any other research project, the cost to society of the research needs to be weighed against the gains to society of what might be learned or achieved.