How to Clone a Mammoth

Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz, presents a step-by-step examination of de-extinction, the scientific effort to bring extinct species back to life. Describing herself as an enthusiastic realist, she argues that while true cloning of long-extinct species like the woolly mammoth is impossible, the technologies developed in pursuit of de-extinction hold enormous potential for conserving threatened species and ecosystems. In a 2020 preface, she reaffirms that no one has found or will find living mammoth cells in frozen remains, and reports that George Church's lab at Harvard's Wyss Institute has used CRISPR, a gene-editing tool that cuts and replaces specific DNA sequences, to replace fifty Asian elephant genes with mammoth versions in lab-grown cells. These edits represent only a tiny fraction of the approximately 1.5 million DNA differences separating the two species. She emphasizes that these biotechnologies could also benefit living species, from transferring disease resistance to endangered black-footed ferrets to helping coral populations tolerate rising temperatures.

Shapiro opens with the scientific context of extinction, explaining that mammoths, steppe bison, and wild horses survived multiple warm periods, including an interglacial period around 125,000 years ago as warm as today. Their disappearance after the most recent warming, she argues, resulted from a combination of climate change, habitat loss, and human hunting. She introduces the concept of a Sixth Extinction, in which current species loss rivals the five previous mass extinctions. She traces early de-extinction science, recounting the 2003 birth and immediate death of a cloned bucardo (a subspecies of Spanish ibex) created from frozen cells, and introduces ongoing projects including Akira Iritani's mammoth cloning efforts at Japan's Kinki University, Church's genome-engineering work, and ecologist Sergey Zimov's Pleistocene Park in Siberia, a reserve designed to recreate mammoth-era grasslands.

Turning to which species to bring back, Shapiro proposes seven guiding questions organized around ecosystem impact and technical feasibility. She examines three candidates: the Yangtze River dolphin, valued for its evolutionary distinctiveness; the moa of New Zealand, giant flightless birds with no close living relatives, making genome assembly (reconstructing a species' full genome from recovered DNA fragments) extremely difficult; and the dodo, the international symbol of human-caused extinction but still vulnerable to the rats and cats inhabiting Mauritius. Ideal candidates, she argues, have close living relatives, unique traits, and recent extinction dates so that ecosystems have not fully adapted to their absence. She acknowledges, however, that funding and public appeal often drive species selection, which is why the mammoth and passenger pigeon have become flagship projects.

Shapiro addresses the challenge of recovering usable ancient DNA, recounting her failed attempt to extract DNA from bees preserved in 17-million-year-old amber. She explains that PCR (polymerase chain reaction), a technique that amplifies target DNA sequences, is sensitive enough to copy a single ancient fragment but equally capable of amplifying modern contamination. Most DNA recovered from ancient bones is microbial or environmental rather than from the target species. Cold environments slow DNA decay, and the oldest authenticated ancient DNA comes from 700,000-year-old horse bones found in Yukon permafrost near Thistle Creek.

To explain why traditional cloning cannot work for mammoths, Shapiro narrates her 2008 bone-hunting expedition to Siberia's Taimyr Peninsula. DNA degradation begins immediately after death through enzymes called nucleases, and even Arctic freezing cannot preserve intact cells. Somatic cell nuclear transfer, the process used to clone Dolly the sheep in 1996, requires inserting a body cell's nucleus into an egg cell whose own nucleus has been removed; the egg then reprograms the inserted nucleus to develop into a new organism. This process requires intact genomes, which no mammoth specimen retains. Shapiro recounts failed attempts, including the 1999 extraction of the Jarkov mammoth in a 21,000-kilogram block of frozen dirt, which yielded no intact cells, and the 2007 discovery of Lyuba, a baby mammoth preserved for 42,000 years whose body had been pickled by gut bacteria, degrading her DNA. Though Teruhiko Wakayama of the Tiken Centre for Developmental Biology in Kobe, Japan showed in 2008 that mice could be cloned from cells frozen for sixteen years, mammoth cells remain far too degraded for this approach.

Having established cloning as a dead end, Shapiro introduces two alternatives. The first is back-breeding, or selective breeding for ancestral traits. She describes efforts to recreate the aurochs, the extinct wild ancestors of domestic cattle, by concentrating auroch-like traits from primitive breeds, noting that earlier attempts by German brothers Heinz and Lutz Heck in the 1920s and 1930s produced animals that only superficially resembled aurochs. Back-breeding is slow and imprecise because offspring may not inherit desired traits, and the underlying genes may differ from those in the extinct species.

The second and more promising alternative is genome engineering. Church's approach compares mammoth and elephant genomes, synthesizes mammoth DNA strands, and uses molecular scissors to cut elephant DNA and paste in mammoth sequences. Shapiro describes three generations of these molecular tools, culminating in CRISPR/Cas9, which offers faster programming, greater precision, and the ability to make multiple simultaneous edits. She argues that genetic purity is unnecessary: Even a small number of mammoth-specific edits could produce an elephant capable of surviving in Siberia and performing mammoths' ecological functions. She acknowledges complications, including roughly 70 million genetic differences between the species and epigenetics, the chemical tags on DNA that regulate gene expression based on environmental factors such as diet and stress.

Shapiro then addresses creating living organisms from edited cells. The bucardo project attempted nuclear transfer, but only one of 208 implanted embryos survived to birth, dying within minutes from a lung deformity. For mammoths, challenges include harvesting eggs from elephants and the 18-to-22-month gestation period. Birds cannot be cloned by nuclear transfer because the avian egg contains thousands of partially differentiated cells by the time it is laid. Instead, bird de-extinction relies on primordial germ cell transfer: Edited precursor cells of sperm or eggs are injected into developing bird eggs so the next generation carries the engineered genome.

Shapiro connects de-extinction to rewilding, presenting Zimov's research showing that large herbivores transform barren tundra into grassland and, by trampling winter snow, expose permafrost to colder air, potentially slowing the release of an estimated 1,400 gigatons of carbon trapped in Arctic soils. She notes that captive-bred animals face significant challenges; elephants, for example, have shorter lifespans and show psychological distress in zoos. She uses the California condor recovery program as a case study: By 1982, only 22 condors remained, but techniques including double-clutching (removing first eggs to prompt a second clutch) grew the population to about 400 by 2010. She examines the regulatory landscape, noting that US federal regulations governing genetically modified organisms (GMOs) apply only to organisms intended for consumption, leaving the legal status of released de-extinct animals unclear.

In her final chapter, Shapiro addresses ethical objections, responding to concerns about reviving dangerous pathogens (ancient DNA is too degraded to be infectious), animal welfare, competition with conservation funding (she notes that no federal money is currently spent on de-extinction), habitat availability, ecosystem disruption, and the moral hazard that de-extinction could reduce conservation urgency. She highlights the American chestnut tree as a conservation success: Researchers at the State University of New York engineered fungus-resistant strains, with over 1,000 genetically modified trees growing by publication. Shapiro concludes that de-extinction's true value lies not in recreating identical replicas of lost species but in using biotechnology to restore ecological interactions, help living species adapt to changing environments, and revitalize threatened ecosystems.