How to Clone a Mammoth: The Science of De-Extinction

By Beth Shapiro

An insider's view on bringing extinct species back to life

Could extinct species, like mammoths and passenger pigeons, be brought back to life? In How to Clone a Mammoth, Beth Shapiro, an evolutionary biologist and pioneer in ancient DNA research, addresses this intriguing question by walking readers through the astonishing and controversial process of de-extinction. From deciding which species should be restored to anticipating how revived populations might be overseen in the wild, Shapiro vividly explores the extraordinary cutting-edge science that is being used to resurrect the past. Considering de-extinction's practical benefits and ethical challenges, Shapiro argues that the overarching goal should be the revitalization and stabilization of contemporary ecosystems. Looking at the very real and compelling science behind an idea once seen as science fiction, How to Clone a Mammoth demonstrates how de-extinction will redefine conservation's future.

• Language: English
• Publisher: Princeton University Press
• Release date: Sep 8, 2020
• ISBN: 9780691209562

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More Praise for

HOW TO CLONE A MAMMOTH

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This charming volume is a how-to book with a vengeance.

—BRIAN BETHUNE, Maclean’s

This lucid road map . . . examines not only how we can resurrect long-vanished species but also when we cannot or should not.

—Scientific American

Spells out, step by step, how and how soon real scientists might be able to bring an extinct species back to life.

—NANCY SZOKAN, Washington Post

Shapiro makes a good, sensible, balanced case.

—CATHY GERE, Nation

As Shapiro sees it, de-extinction isn’t about geeky genetic sleight of hand or about the resurrection of legendary beasts; it’s a valuable new tool for conserving and enriching the global ecosystem.

—LAURENCE MARSCHALL, Natural History

Readers will emerge with the ability to think more deeply about the facts of de-extinction and cloning.

—Publishers Weekly

The future of de-extinction is real and coming fast.

—JONATHON STURGEON, Flavorwire

Shapiro does an excellent job of showing that the realities of genuine science can be as exciting as the fantasies of science fiction.

—NICK RENNISON, Daily Mail

Explores the vital questions surrounding the whole subject of de-extinction with great clarity.

—CASPAR HENDERSON, Spectator

About as close as you get to sitting down with a nice cup of tea to have a decent chinwag with a mate about resurrecting the woolly mammoth.

—DR. TORI HERRIDGE, BBC Focus Magazine

An informative and at times highly entertaining account of the life of a modern mammoth hunter.

—WILLIAM HARTSTON, Daily Express

HOW TO CLONE A MAMMOTH

HOW TO CLONE A MAMMOTH

THE SCIENCE OF DE-EXTINCTION

WITH A NEW PREFACE BY THE AUTHOR

BETH SHAPIRO

PRINCETON UNIVERSITY PRESS

PRINCETON AND OXFORD

Copyright © 2015 by Princeton University Press

Preface to the new paperback edition,

copyright © 2020 by Princeton University Press

Published by Princeton University Press, 41 William Street,

Princeton, New Jersey 08540

In the United Kingdom: Princeton University Press,

6 Oxford Street, Woodstock, Oxfordshire OX20 1TR

press.princeton.edu

Cover image by Jason Alejandro

Cover design by Michael Boland for thebolanddesignco.com

All Rights Reserved

First published in 2016

New paperback edition, with a new preface by the author, 2020

New paperback ISBN 9780691209005

Library of Congress Control Number: 2020936099

British Library Cataloging-in-Publication Data is available

This book has been composed in Baskerville Original Pro and Trade Gothic

Printed in the United States of America

For my children, James and Henry, who will

inherit whatever mess we make.

CONTENTS

PREFACE TO THE 2020 EDITION

It’s 2020, and we still don’t have a mammoth.

I swear this is not my fault. Yes, the title of the book is How to Clone a Mammoth, but I didn’t actually intend it as an instruction manual. I admit that the title may give the impression that one could, with a copy of the book and a strand or two of mammoth hair (which I have learned can be purchased on the Internet, although I cannot vouch for any of these products’ authenticity), create one’s own mammoth. So as to avoid any unnecessary or additional disappointment, here’s the truth: it’s not possible to clone a mammoth, and you still won’t be able to clone a mammoth after reading this book. Also, my research group is not trying to clone a mammoth, nor are we trying to bring back any other extinct species. So the absence of cloned mammoths five years after publication of this book’s first edition is (probably) not because I am not working hard enough or my instructions were unclear. It’s because it is too late. Mammoths are extinct.

Despite my adamance that it is not possible to clone a mammoth, news reports keep telling me that a cloned mammoth is just around the corner, usually to be revealed within two years. When I hear this, my heart rate spikes. Could I have been wrong? Is it actually possible that a mammoth can be cloned? What technological innovation or miracle of mammoth-preservation did I fail to anticipate?

The paths to cloning a mammoth are few, thanks to one inflexible requirement of cloning technology: if we want to clone a mammoth, we must have a living mammoth cell. The last mammoths died more than 3,000 years ago. All that remains of this last population are de-fleshed bones, teeth, and tusks, none of which are likely sources of living cells. A few teams of would-be mammoth cloners believe they have found a better source of living mammoth cells and have been competing for access to the spectacularly preserved frozen mammoth mummies that continue to be unearthed as the Arctic melts. They have not and will not find living mammoth cells in these frozen mummies, as this would violate everything we know about what happens to cells and DNA when organisms decay after death. A team from Kindai University in Japan are taking a different approach and have been trying to work out how to repair damaged cells; they are essentially sticking broken chromosomes back together to try to bring a dead cell back to life. In 2019, this team tried using mouse enzymes to reconstitute cells recovered from the remains of Yuka, a 28,000-year-old mammoth mummy that was recovered from melting sediments in Russia’s Sakha Republic in 2010. Yuka is widely considered to be the most intact mammoth yet discovered. Even so, her cells are far too degraded to be brought back to life.

I have not yet been proven wrong: no one has found living or resurrectable mammoth cells in the preserved remains of mammoths. If we want a living mammoth cell, we’re just going to have to make one ourselves.

The technology needed to make a mammoth cell from scratch is advancing quickly, but we’re not there yet. This path to mammoth cloning actually begins with an Asian elephant cell. This is because Asian elephants are the closest living relatives of mammoths, and therefore their genomes will be the most similar in sequence to a mammoth’s genome. Unfortunately, mammoths and Asian elephants are not that closely related. The two lineages diverged more than five million years ago, and in that time something like 1.5 million DNA changes have accumulated between the two species. Gene-editing technologies may someday allow us to make all of these changes to the genomes of cells growing in a lab, but even today’s most advanced CRISPR (clustered regularly interspaced short palindromic repeats) molecules cannot make this many changes at once. The record number of edits made simultaneously is currently held by George Church’s lab at the Wyss Institute of Harvard University. His team made 13,000 edits to a human genome in a single experiment. While impressive, their experiment is not entirely comparable to the mammoth deextinction challenge, as all 13,000 edits targeted the same change in a gene that occurs in 3,000 duplicated copies across the genome. Also, 13,000 edits is a lot fewer than the 1.5 million edits necessary to cut-and-paste our way from an Asian elephant genome to a mammoth genome.

George’s team are the furthest ahead in using the tools of genome editing to make a mammoth. George told me recently that his team successfully replaced fifty Asian elephant genes with the corresponding genes from mammoths using CRISPR. They chose these fifty genes based on what we understand the genes to do, focusing on those that may help tropically adapted Asian elephants survive in the cold habitats where mammoths once lived. That’s it for now: edited Asian elephant cells are growing in dishes in George Church’s lab, and in those cells a tiny fraction of the 1.5 million edits that would transform their genomes into mammoth genomes have been made. These are not mammoth cells, but they are a lot closer to mammoth cells than anything we had five years ago.

So are these the cells that are two years away from being mammoths?

The two-year timeline is particularly audacious considering that Asian elephants have an 18–22 month gestation. A two-year timeline means that an Asian elephant is out there somewhere either already pregnant with a partially mammothified Asian elephant embryo or is about to become so. But this cannot be true, as we still have not figured out this next step. We still face technical challenges, like how to harvest eggs for cloning from an Asian elephant’s elephant-sized reproductive system, and ethical hurdles, like solving what a captive Asian elephant needs both physically and psychologically so that she can reproduce successfully.

We might be able to avoid using elephants as surrogates entirely with the advent of another technology straight from science fiction: artificial wombs. Recently, researchers at the Children’s Hospital of Philadelphia developed what they call a biobag—a sterile environment that mimics a womb and in which they can control delivery of the hormones and nutrients that a fetus needs to develop. Their goal is for the biobag to help children born prematurely continue to develop in a natural womblike environment, and their results are promising. In 2017, eight lambs developed normally for more than a month in the biobags. The biobags are not, however, intended to replace the womb entirely. The lambs were transferred to the biobags after at least 105 days of gestation, which is just over the halfway mark of normal gestation. An artificial womb capable of replacing the womb altogether is still a fantasy, but it would benefit both de-extinction (some extinct species have no close living relative to act as a surrogate mom) and conservation more broadly—for example, by increasing the rate at which captive breeding programs can produce offspring for release into wild populations. For now, though, living surrogates are essential, and we are many more than two years from the birth of either a mammoth or anything close.

But I don’t really care that we’re not particularly close to having a mammoth, or even that we will never be able to recreate something identical to a mammoth. I am not excited about the idea of bringing something back from extinction when its habitat or ecosystem is also extinct—this seems to me both unnecessary and unfair. I am excited, however, about what the same technologies necessary for de-extinction can do to help us to save species that are not yet extinct. Thanks to our new biotechnologies, we now have the power to change the evolutionary trajectories of species that seem destined to disappear, to rescue and revitalize ecosystems that are threatened by the ever-expanding human footprint or that are struggling to adapt to our planet’s changing climate. We could, for example, transfer the domestic ferret’s resistance to Sylvatic plague to black-footed ferrets that are facing extinction across their native range because of the introduced disease. Or we could transfer heat-tolerance between coral populations that are suffering as the oceans warm, or immunize white-footed mice against Lyme disease so that they can no longer pass the disease to humans. We may even eventually bring something back. Not a mammoth or a passenger pigeon, but instead some trait or function or aspect of an extinct species that can, in its re-establishment, restore some missing ecosystem function and allow other species to thrive in today’s altered world.

There is still work to be done to make technologies broadly useful for conservation. Some technologies still need to be optimized for wild species not normally found in labs, and other technologies do not yet exist. There is little doubt, however, of their potential. In the chapters that follow, I walk through the technologies necessary for de-extinction, describing what we can achieve today, what may be just over the horizon, and what obstacles we may never overcome. I still believe that we will never clone a mammoth. I do not mourn the lack of de-extinct mammoths, however. I know that for some species we are not yet too late.

PROLOGUE

The first use of the word de-extinction was, as far as I can tell, in science fiction. In his 1979 book The Source of Magic,¹ Piers Anthony describes a magician who suddenly finds himself in the presence of cats, which, until that moment, he had believed to be an extinct species. Anthony writes, [The magician] just stood there and stared at this abrupt de-extinction, unable to formulate a durable opinion. I imagine that this is precisely how many of us might react to our first encounter with a living version of something we thought was extinct.

The idea that de-extinction might actually be possible—that science might advance eventually to the point where extinction is no longer forever—is both exhilarating and terrifying. How would de-extinction change the way we live? Would deextinction provide new opportunities for economic growth and galvanize global conservation efforts? Or would it lull us into a false sense of security and ultimately increase the rate of species extinction?

The year 2013 saw de-extinction become its own new branch of science, at least according to the Times.² Despite this lofty status, there is as yet no consensus as to what the goal of deextinction science is. At first, it seems obvious. De-extinction aims to resurrect, via cloning, identical copies of extinct species. For species that have been extinct for a long time, however—the passenger pigeon, the dodo, the mammoth—cloning is not a viable option. In the case of these species, de-extinction will have to mean something else. Most likely, it will mean that specific traits and behaviors of the extinct species will be genetically engineered into living species. The living species would then gain the adaptations necessary to thrive where the extinct species once did. Will society, however, respond favorably to deextinction if the goal is not to bring back an actual mammoth, dodo, or passenger pigeon?

Piers Anthony’s novel was eerily prescient with regard to our reaction to de-extinction. Immediately after his magician accepted that de-extinction was possible and, presumably, in the midst of forming an opinion about it, Anthony’s magician had another thought. Anthony writes, If [the magician] killed these animals, would he be re-extincting* the species?

* A warning to grammarians: In this sentence, Anthony’s magician provides what is perhaps the earliest example of that awkward moment when, while discussing some aspect of de-extinction, it suddenly be-comes clear that there is no satisfying way to complete a thought without offending people like you. How should one designate a species that has been brought back to life? While de-extinction seems perfectly logical with reference to a process, to refer to the end-result of that process as de-extinct seems inappropriate. De-extincted, while more logical, is painful to write down, much less to say out loud. I prefer unextinct to de-extinct, as unextinct seems to describe the state of being, rather than the process of getting there. One might say, for example, The mammoth is unextinct. Of course, The mammoth is no longer extinct is certainly sufficient.

What, then, is the present participle? I shudder when I say that George Church’s lab is de-extincting the mammoth. My reaction to the phrase, however, has nothing to do with the science. At the first formal scientific discussion of de-extinction, some of us suggested using resurrection and its various conjugates, as in, We are resurrecting extinct species. While resurrect makes perfect grammatical sense, however, its religious connotations seemed misleading. Certainly, De-extincting, is terrible, as is re-extincting. Yet, here we are. While it takes longer to say it, perhaps we should stick with something that is simple to understand and entirely inoffensive—at least grammatically: We are developing the science necessary to bring extinct species back to life.

Many of the people with whom I interact believe that de-extinction is inevitable. I’ll admit, however, that this is a biased sample of the population, and that most people are likely to care about de-extinction only insofar as it might affect them personally. Some people of course love the idea of de-extinction. They may be swayed and enthused by the idea that resurrected species might improve wild habitats. Or they may just want the opportunity to see and touch a mammoth. Other people, including very sensible and intelligent people, hate the idea of deextinction, citing both the high cost of resurrecting extinct species and the myriad risks of reintroducing organisms into the wild whose environmental impacts are—because they are extinct—necessarily unknown. Those people who fear de-extinction the most, like Anthony’s magician, take solace in its reversibility. This worries me. It is undoubtedly true that history repeats itself and that, if need be, we could re-eradicate any species we brought back. However, our goal as scientists working in this field is not to create monsters or to induce ecological catastrophe but to re-store interactions between species and preserve biodiversity. If we do arrive at a time when science makes it possible to resurrect the past, it might take years or decades to see the results of this work. I certainly hope we do not simply turn around at the first signs of imperfection and destroy what we worked so hard to accomplish.

Certainly, if we are to make room for extinct species—or for hybrids of extinct and living species—in the real world, we as a society will have to alter our attitudes, our actions, and even our laws. Science is paving the way to resurrect the past. The road, however, will be long, not necessarily direct, and certainly not smooth.

With this book, I aim to provide a road map for de-extinction, beginning with how we might make the decision about what species or trait to resurrect, traveling through the circuitous and often confusing path from DNA sequence to living organism, and ending with a discussion about how to manage populations of engineered individuals once they are released into the wild. My goal is to explain de-extinction in a way that separates science from science fiction. Some steps in the de-extinction process, such as finding well-preserved remains of extinct species, will be relatively simple to complete. Others, however, such as cloning extinct species, may never be feasible. My perspective, as a scientist who is actively involved in de-extinction research, is that of an enthusiastic realist. I believe that de-extinction is in many cases scientifically and ethically unjustified. However, I also believe that de-extinction technology has great potential to become an important tool for conserving species and habitats that are threatened in the present day. If that seems paradoxical, read on.

CHAPTER 1

REVERSING EXTINCTION

A few years ago, a colleague of mine practically bit my head off for getting the end date of the Cretaceous period wrong by a little bit. I was presenting an informal seminar about my research to graduate students at my university, which at the time was Penn State. My seminar was about mammoths—in particular, about when, where, and why mammoths went extinct, or at least what we’ve learned about the mammoth extinction by extracting bits of mammoth DNA from frozen mammoth bones. Before talking about this very recent extinction, I opened with a discussion of older and more famous extinctions. My offending slide cited the date for the end of the Cretaceous period and beginning of the Paleogene, also known as the K-Pg boundary and best known as the time of the extinction of the dinosaurs, at around 65 million years ago. That date, I was told, was inexcusably imprecise. The K-Pg boundary occurred 65.5 ± 0.3 million years ago (at least that was the scientific consensus of the time), and I was not to be forgiven those 200,000 to 800,000 years.

While I appreciate that my fellow academics would have preferred meticulous attention to detail, I did not bring up the dinosaurs to discuss the precise timing of their demise. My goal was simply to make the point that while we think we now know why the dinosaurs went extinct so many millions of years ago, we still argue about what caused extinctions that took place within the last ten thousand years. Did the mammoths and other ice age animals go extinct because Earth’s climate was suddenly too warm to support them? Or did our ancestors hunt them to death? The question remains open, perhaps because we are not particularly comfortable with the answer.

The last dinosaurs went extinct after a massive asteroid struck just off the coast of Mexico’s Yucatan Peninsula. Similar cataclysmic events—major explosive volcanic eruptions or impacts of large asteroids or comets—are thought to have caused the other four mass extinctions in Earth’s history. Each time, dense clouds of dust and other debris were suddenly ejected into the atmosphere, blocking out the sunlight. Without sunlight, the plants suffered and many species died. As the plant communities collapsed, so did the animals that ate the plants, and then the animals that ate the animals that ate the plants, and so on up the food chain until somewhere between 50 percent and 90 percent of all species that were alive at the time of the catastrophic event became extinct.

The mammoth extinction is different. We know of no single catastrophic event that happened within the last 10,000 years that might have caused mammoths to go extinct. Recent genetic research shows that mammoth populations probably started to decline sometime during or just after the peak of the last ice age some 20,000 years ago, as the rich arctic grasslands—often called the steppe tundra—on which they relied for food were gradually replaced by modern arctic vegetation. Mammoths were extinct in continental North America and Asia by around 8,000 years ago but survived for another few thousand years in two isolated locations in the Bering Strait: the Pribilof Islands off the western coast of Alaska, where mammoths survived until around 5,000 years ago, and Wrangel Island off the northeastern coast of Siberia, where they survived until around 3,700 years ago.

We know from the fossil record that mammoths, steppe bison, and wild horses dominated the Arctic landscape for a long time before the peak of the last ice age. In fact, they were the most abundant large mammals in the North American Arctic for most of the last 100,000 years. This was a very cold period of Earth’s history and included two ice ages—one that peaked at around 80,000 years ago and another that peaked around 20,000 years ago—separated by a long cold interval. It was only after the peak of the most recent ice age that the climate really began to warm up, transitioning into the present warm interval (the Holocene epoch) by around

Reviews for How to Clone a Mammoth

[schant-1 · Rating: 5 out of 5 stars]

What a fascinating and thought-provoking book. It covers the science, technology, ethics, and (many!) difficulties of the process of de-extinction. It's a few years old now, but I think very relevant. Highly recommended for anyone interested in the ideas of ecosystem revival, genetic manipulation, and of course conservation.

[trigstarom · Rating: 4 out of 5 stars]

I received this book via NetGalley from in exchange for an honest and completely unbiased review.

I want to start noting that I generally dislike the maltreatment of animals and cruelty enacted in laboratories, so this could not be an unbiased review.

How to Clone a Mammoth is about cloning and the various problems concerned with the technologies used to clone cells. Shapiro explains these problems in the most base way, only touching on much of the scientific jargon that would confuse the average reader. She also explains that cloning would not return a perfect specimen from the Ice Age as popular belief has led us to imagine. Instead, the creatures developed from cloning would be mammoth-like. These species would act to revive ecosystems by filling in the gaps where interactions between species has gone dormant due to the extinction of one or more animal.

Unfortunately, while the conservation of failing ecosystems is a valiant effort, Shapiro goes further by stating that we shouldn’t restrict this technology to de-extintion. In fact. she offers cloning technologies as a method to alter endangered species who lack diversity or cannot adapt to climate change quickly enough. The desire to play with the biology of struggling species is a cold, analytical leap in Shapiro’s logic. It describes the chilling future of this technologies and the lack of morality found in those wielding it.

On top of the desire to alter live species, Shapiro theorizes that if new species are created to fill ecological niches there may come a day when our creations may do more damage than good to the ecosystem we are trying to maintain. The shocking conclusion is that we should eradicate the species if it starts to harm the ecosystem only further destroyed Shapiro’s work. The death of living creatures should never be something brazenly thrown around. Although Shapiro highlights that there would have to be careful consideration this matter, and perhaps even a council should be drawn up to purpose such mass slaughters.

Shapiro covers back breeding as one method for bringing back the mammoth and outlines the struggle for recreating the auroch, they are creating new technologies to slip “scissors” into a nucleus to snip out the genetic code they don’t want, and plan to use “glue” to paste the new genetic code geneticists have created to make sure the new genetic code is fused. The techniques covered in this book are both cutting edge and leading back to the selective breeding practices to rebirth various animals: the Dodo, the auroch and Passenger Pigeon.

I also learned how an egg is made inside a chicken, chickens cannot be cloned, ancient DNA is much trickier than we can imagine, and Asian Elephants just might be the closest relative to the mammoth.

Although I abhor Shapiro’s ethical arguments I enjoyed her work. How to Clone a Mammoth was extremely educational for the average reader over a broad range of topics and it attempts to conquer very delicate moral issues. Although sometimes repetitive with ideas, this book is well worth a look for people who know very little about cloning and biology.

[philogos_1 · Rating: 4 out of 5 stars]

This is a very interesting subject and very rigorously and thoroughly presented. It makes a case for de-extinction and presents the science behind it as of today diving into the significant complexity of this enterprise in a clear and objective analysis of the issues raised by the possibility of de-extinction. Two main criticisms: The first being that the title has been sexed up to sell more books. As Prof Shapiro makes clear, cloning a mammoth is not ever actually going to happen. The best that can be done is to create a genetically engineered elephant with some mammoth characteristics. The second criticism relates to the inconclusiveness inherent in writing a book on a subject that is developing so quickly. It doesn't quite leave things on a cliff edge but it's not far off and it would be nice to have a subscription channel to keep up with what happens next.