De-extinction: The Second Coming

A pair of thylacines. Credit: Public Domain
A pair of thylacines. Credit: Public Domain

Ten years ago it burst into mainstream popular life: the possibility of resurrecting extinct species.

Touched off by Jurassic Park comparisons, all the talk (and it was mostly talk) was of bringing back woolly mammoths and passenger pigeons, often within ludicrously short timeframes. 

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Then in a flash, the de-extinction fantasy fad faded, the science hill to climb appearing too steep to take the movement seriously.

Fast forward to 2023 and de-extinction is suddenly hot again. Its backers are putting serious money where their mouths are, funding projects to revive two additional species — the thylacine (or Tasmanian tiger) and the dodo. What hasn’t changed is enthusiasts’ wild optimism (investors have bought into the hype that thylacines could be resurrected “in less than six years”) … and most naysayers’ persistent pessimism. Plus critics are saying that all the money chasing the de-extinction dream would be better spent on species facing extinction in the here and now.

But other things have shifted in the last ten years, at least in the background behind the attention-grabbing headlines — changes that perhaps tip the balance more strongly in realizing de-extinction’s potential. 

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How to clone a mammoth (or a thylacine)

Let’s examine both the science of resurrecting extinct species and the ethical controversies that continue to swirl around the idea of bringing long-dead creatures back to life.

While genetic know-how has vastly increased over the past decade, the basic theoretical approach to ‘de-extinction’ remains the same. The extinct organism’s genome, sequenced from preserved remains, is first compared to that of a closely related extant species — the mammoths’ genome with that of the Asian elephant, say, or the thylacines’ with the dunnart, a living near-relative — and the functional genetic differences identified. 

Next, using newly-developed genomic editing tools (such as CRISPR, which emerged at the same time as de-extinction), the targeted genes in the living species’ genome are edited out, with those of the lost species then pasted in their place. In a process similar to that of conventional agricultural cloning, this newly created  ‘synthetic’ genome is then inserted into an enucleated egg from the extant sister species and hence into the womb of a surrogate mother. 

An actual proof of concept occurred in 2003 — the birth of a cloned bucardo or Iberian ibex, a goat-like species that had recently gone extinct (albeit the new-born clone died within minutes). But so much for the theory of de-extinction. What are the ethical considerations?

Ideological objections: Playing God

One frequently-raised ethical concern is that de-extinction amounts to unnatural and hubristic human interference in nature — ‘playing God’. It’s a favorite among many opponents of genetic technology, not just those concerned about de-extinction. Environmentalist activists often play the ‘God card’ in their long-standing hostility to genetically modified/engineered crops. Similar beliefs have also filtered through into the anti-vaccination movement. What they mean by this is never really made clear. 

Through domestication (and the conscious artificial selection of desired traits), humans have been deliberately tinkering with and altering other species’ genomes for millennia. Does this count as ‘playing God’, and if so, why is it wrong or unnatural? Why is slow and gradual traditional selective breeding that has altered thousands of species over hundreds of years legitimate while the quicker process of far more precise genetic manipulation and modification  derided? 

Selective breeding programs for endangered species, or their translocation or reintroduction to particular areas, are also deliberate human interventions in nature. Why is this sort of intercession enthusiastically endorsed while unnatural genomic meddling is rejected? In short, almost any human interaction with the natural world could be dismissed as ‘playing God’. 

Do no harm

A more substantive ethical concern is the potential harm and suffering that de-extinction experiments could bring to living animals. The newborn bucardo clone, which died in considerable distress in 2013, is a case in point. 

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Dozens of goat surrogates were used in the bucardo research program, with only one successfully bringing its fetus to (short-lived) term. Using an Asian elephant — or, rather, numerous Asian elephants — risks causing considerable harm to individual sentient animals, especially given that a mammoth fetus will be developing within an elephant womb. 

In addition, Asian elephants are themselves endangered so using them for unpredictable and potentially cruel experiments would likely be seen as morally repugnant by most people.

Indeed, why fixate on the fantasy of bringing back lost species when so many living ones are themselves on the brink of joining them? Instead of wasting so much money and resources on genetic gimmickry, many conservationists argue that “we should be saving the species that we have before they go extinct”. Or as a skeptical Scientific American editorial put it back in 2013, “with limited intellectual bandwidth and financial resources”, de-extinction threatens “to divert attention” from much more worthy causes such as “the modern biodiversity crisis”. 

A related objection is that the very notion of de-extinction might cause ‘moral hazard’ — that is, efforts to save currently threatened organisms may be undermined by the misguided belief that we can always ‘bring them back’, making it even more likely that humans will relax their guard and let endangered species go extinct.

Mammoth mammon

How do de-extinction advocates address these concerns? The claim that ‘money could be better spent’ is based on zero sum thinking — that there is a limited amount of money available and that what’s spent on de-extinction is lost to conservation efforts elsewhere. This objection ignores the possibility that “flamboyant project[s] to resuscitate extinct flora and fauna” (to co-opt Scientific American’s turn of phrase) could draw in new funding that would not otherwise have been spent on conservation causes.

Far from eating up the public’s “limited intellectual bandwidth” with flash-in-the-pan vanity projects, de-extinction could focus more attention and funding on the need for greater conservation. Central to the dodo de-extinction enterprise, for example, is the desire for resurrected birds to flourish in their native Mauritius. For this to occur, major ecological improvements must be made, not least the elimination of destructive invasives such as pigs and goats. Likewise, the eventual reintroduction of Tasmania’s former apex predator to its island home would be a self-imposed marker of success for the thylacine project.

Credit: Science Nordic

Today’s thylacine and the dodo de-extinction projects vindicate a decade-old prediction made by de-extinction’s chief cheerleader, Stewart Brand: that genetically-based resurrection science “will attract significant new sources of funding and interest for conservation”. 

In the same article, Brand also challenged the standard moral hazard concern: if species resurrection is promoted, “the great warning ‘EXTINCTION IS FOREVER!’ will lose its sting”. Much the same fear was raised when San Diego Zoo “founded the Frozen Zoo to cryopreserve cells and DNA from endangered animals,” Brand pointed out. Despite over one thousand species now being thus preserved, there appears “no apparent harm to political support for protecting them”.

Another of Brand’s de-extinction predictions, however — that “the conservation story could shift from negative to positive, from constant whining and guilt-tripping to high fives and new excitement” — has fared less well. As conservationist carping continues, the lack of concrete success means popular de-extinction enthusiasm may again fizzle out.

Resurrection rebranded 

Behind the scenes and away from the periodic bursts of short-lived media hype, de-extinction thinking has matured. There is now greater emphasis on the long-term nature of realistic de-extinction projects. Mammoth revival project advocates no longer mention success within years or decades. They now project much longer time horizons. Where once the leading de-extinction outfit Revive & Restore (co-organized by Brand) trumpeted species resurrection through biotechnology, it now promotes the subtly different mission of “bringing biotechnologies to conservation”. 

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As part of this change of focus, Revive & Restore now suggests that “the bioengineering, genome research, cellular resources, and reproductive techniques being developed for the Woolly Mammoth Revival could also advance conservation for living species”; genomic technologies could be used in the here and now with de-extinction something for the distant future. 

The company is attempting to develop a vaccine for a virulent strain of herpes that threatens Asian elephants. “This effort is one of the world’s first projects using synthetic biology to study and treat a wildlife disease … [in which] the mammoth de-extinction effort may confer significant, near-term benefits to Asian elephant conservation,” the company claims.

This re-branding makes much of the feel good concept of “genetic rescue”, of employing biotech to help save rare or threatened species. Concrete examples are presented, most notably the successful cloning of the endangered black-footed ferret and Przewalski’s horse. Another offshoot of the mammoth revival project is looking at multiplying the numbers of tuskless elephants in an effort to combat poaching. 

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Credit: Wikipedia Commons

While this won’t soothe away the suspicions of “conservative and precautionary” conservationists, it counters the standard criticism that de-extinction equals wasted resources. Given time, and more success stories like the black-footed ferret, environmentalists might come to see ‘genetic rescue’ as an important part of the conservation toolkit. 

Welfare with conservation: How mammoth de-extinction might work

This change of focus is also relevant to the most substantive objection to de-extinction: the possible pain and suffering it may inflict on the sentient animals involved in any resurrection experiments. The new focus is not on creating a whiz-bang mammoth in one go; rather, it focuses on “proof-of-concept experiments” in the laboratory, such as genomic editing of elephant cell cultures. Experiments involving elephant cells and not actual animals are designed to test “the feasibility of gene editing for elephant genomes, a critical step for the Mammoth Revival”.

But even if trials moved from in vitro to in vivo — from test-tube to living, feeling animal — it would be with the incremental addition of mammoth genes into the Asian elephant genome over generations (for example, genes for greater cold tolerance such as hairiness or increased subcutaneous fat). This could be justified on conservation grounds. Such traits could allow Asian elephants to extend their range, currently restricted to the tropics, to newer habitats,. That would provide a potential lifeline for this endangered species. 

The talk now is of a slow procession of hybrid stages leading from elephants to mammoths. This raises the question of ‘authenticity’ (discussed more fully by philosopher Douglas Campbell in a text I co-authored, Resurrecting Extinct Species). Will the final end-product of this process be authentic mammoths or just hairy elephants? For some conservation-minded biotech enthusiasts, this is beside the point; if a hybrid proxy can be created to fulfill the same important ecological role as the extinct real thing, then that is a worthwhile goal in and of itself.  

This new emphasis on hybridization and of incremental genetic change also addresses the major animal welfare issue surrounding de-extinction — the need for a surrogate mother of one species to carry the embryo/fetus of another. An alternative is the use of artificial wombs. The ongoing mammoth revival project is already investigating creating a ‘vascularized decidua’ — a womb-like “uterine lining with its own vascular structure of blood vessels to support life”. Again, any increase in technical know-how here could be applied to other conservation projects.

The recently-announced thylacine and dodo de-extinction projects largely dodge this surrogacy concern, which may be why these animals have risen to prominence in de-extinction circles. With marsupials like thylacines, offspring are born in an embryonic stage before developing within the mother’s external ‘pouch’. In theory, this appears more straightforward than artificially replicating the internal gestation of placental mammals such as elephants or mammoths. This could do away with the need for a surrogate that could itself suffer.

With egg-laying birds like the dodo, in which the fetus develops externally to the mother, surrogacy worries are also less apparent. However, the peculiarities of avian reproduction create different challenges. The intricacies of cloning birds offer a fascinating glimpse of what modern biotechnology is now capable — and of how sci-fi fantasy is moving rapidly towards scientific reality.

Two birds with one clone

One proposed genetic cloning technique with birds involves primordial germ cell transplantation (PGCT) — transferring sex cells from one bird species into another. More precisely it involves injecting sex cells into eggs that are still developing inside another female. Chicks that hatch from these eggs will be ‘chimeras’, outwardly one species but with the sex cells of another. This technique has already been tested with various degrees of success with chicken/duck and chicken/pheasant combinations, with the respective chimeric chickens producing duck or pheasant hatchlings. Related experiments aimed at preserving the germplasm of bird-flu prone chickens within bird-flu resistant ducks have also been conducted.

Although PGCT is in its infancy and researchers could still end up with egg on their faces it is the current preferred option for dodo de-extinction. According to Colossal, the biotech company behind the dodo project, work is already underway “to advance the state of the art in avian reproduction by demonstrating interspecies germline transfer of pigeon PGCs into a surrogate chicken host”. 

Pigeon PGCs are necessary because the dodo’s closest living relative is the Nicobar pigeon. This pigeon’s genome would likely be used to recreate its extinct Mauritian cousin’s (in the same way that the Asian elephant genome would act as the template for synthetic mammoth DNA). A gene edited dodo genome would be used in the PGCT/chimera process described above with the resultant pigeon chimeras eventually laying eggs that hatch as dodos.

Even if the attempt to bring back the fabled dodo ultimately fails, a huge amount of practical know-how will have been gained — knowledge immensely beneficial to avian conservation efforts elsewhere. If the PGCT technique proves workable, it could potentially be used to grow the populations of endangered birds through the use of chimeras. Perhaps battery hen-type production lines could churn out eggs that would hatch into Californian condors, Canadian burrowing owls or New Zealand giant parrots (kākāpō).

Brave New World?

As happened a decade ago, the flowering of de-extinction fervor may once again fade, only to be resurrected again and again over coming decades. The concept has already changed and adapted, challenging many objections critics have raised. Given this, and rapid advances in biotechnology, it is difficult to argue that ‘genetic rescue’ should play no part in conservation efforts.

And if on some distant day our grandchildren or great-grandchildren see dodos or thylacines or huge hairy elephants once more walking on this Earth, wouldn’t that be the coolest thing?

Patrick Whittle is a freelance writer with a particular interest in the social and political implications of modern biological science. Follow him on his website patrickmichaelwhittle.com or on Twitter @raft_rat

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