Extinct possibility

I am a biologist. I teach classes and run a research laboratory at the 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 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 sabre-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 behaviours 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 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 behaviours, 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.

The lonely mammoth

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 mum gives birth to a baby mammoth.

“What I imagine is the perfect arctic scene, where mammoth families graze the steppe tundra, sharing the frozen landscape with herds of bison, horses and reindeer”

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 faeces 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.

Tusk force

Regardless of how feasible it really is, de-extinction has succeeded in forcing us – by “us” I am referring here to scientists who hope, as I do, that our research will have a positive environmental impact – out of our comfort zones. Stewart Brand would like to see de-extinction do more than that. Along with Ryan Phelan he has created a nonprofit organisation called Revive & Restore, and is 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. His goal for de-extinction is that it will become “a reframing of possibilities as momentous as landing humans on the moon was”. Certainly, if it does become possible to resurrect extinct species or to coax living species to express extinct traits, our perception of what it means to be ‘extinct’ will change fundamentally. The most momentous change, however, will be in our attitudes toward living species – this, I believe, is what Stewart is referring to when he speaks of possibilities reframed. Suddenly, we will have the technical knowhow to engineer sustainability into threatened populations. Will improving rather than protecting species become the new objective of biodiversity conservation? If we turn to the past to identify traits that can be used to improve the plight of living species, where will we draw the line between preventing versus reversing extinction? And will we care?

This, I believe, is why people like me are so captivated by the idea of de-extinction. Not because it is a means to turn back the clock and somehow right our ancestors’ wrongs, but because de-extinction uses awesome, exciting, cutting-edge technology to take a giant step forward.

De-extinction is a process that allows us to actively create a future that is really better than today, not just one that is less bad than what we anticipate. It is not important that we cannot bring back a creature that is 100 percent mammoth or 100 percent passenger pigeon. What matters is that – today – we can tweak an elephant cell so that it expresses a mammoth gene. In a few years, those mammoth genes may be making proteins in living elephants, and the elephants made up of those cells might, as a consequence, no longer be isolated to pockets of declining habitat in tropical zones of the Old World. Instead, they will be free to wander the open spaces of Siberia, Alaska and Northern Europe, restoring to these places all of the benefits of a large dynamic herbivore that have been missing for eight thousand years.

“If it does become possible to resurrect extinct species our perception of what it means to be ‘extinct’ will change fundamentally”

De-extinction is a markedly different approach to planning for and coping with future environmental change than any other strategy that we, as a society, have devised. It will reframe our possibilities. De-extinction will, of course, be risky. We don’t know and cannot predict every outcome of resurrecting the past. The conservation success stories of the present day prove, however, that taking risks can be deeply rewarding. Removing every living California condor from the wild was an extraordinarily risky strategy to preserve the species, but one that undoubtedly saved them from extinction. Restoring grey wolf populations to Yellowstone National Park was both risky and, to a degree, unpopular, but the park is now flourishing in a way that it had not since its establishment in 1872, when wolves and other predators were actively exterminated. Allowing deer, cattle, and other wild animals to take over abandoned land in Europe was touted as both crazy and dangerous, but these re-established wilderness areas stimulated a widespread shift in attitudes toward wildlife. They inspired new policies aimed at protecting natural spaces and the species that occupy these spaces. How will the world react when the first genetically engineered elephants are strolling casually through Siberia?

I can’t wait to find out.

Posted on Tuesday, October 17th, 2023 - Categories: #18 - Jan-Mar 2015, App Issues.