MAMMOTH UNCERTAINTIES BEHIND DE-EXTINCTION: How Developing Scientific Techniques Lead to a...

[continued] Possibility of God-Like Creators


Tayah Turocy • 2021 Issue


 

From The Editors:

From dodo birds to dinosaurs, extinct species captivate humans as pseudo-mythical creatures rooted in history, but what if we were able to revive animals we’ve never even seen? Progress in biotechnology has catapulted the prospect of reincarnating long-dead species into reality and generated a host of ethical questions with it. In MAMMOTH UNCERTAINTIES BEHIND DE-EXTINCTION, Turocy uses the woolly mammoth as a case study to survey exciting potential de-extinction techniques and advocates for greater public and regulatory discussion of the practice. As the science continues to progress, we must reckon with what it would mean to create—and own—life itself.

 

Since the dawn of Jurassic Park, extinct species have captivated attention by existing between death and life, playing possible future roles as both public spectacle and a pinnacle of science. The idea of species revival floods the science fiction genre on the big screen and between pages fueled by public adoration. Natural history museums welcome visitors with awe-inspiring displays of massive skeletons and models of ancient animals. Children and adults alike imagine a world populated by dinosaurs, mammoths, and dodo birds. While the birth of Dolly the sheep in 1996 does not compare to the museum or movie depiction of resurrected dinosaurs, speculation surrounding cloning applications for extinct species exploded, and scientists announced immediate plans to generate mammoth elephant hybrids [1].


De-extinction is defined as the recreation of an extinct species or an extinct species resemblant. In 2019, a research group made the world’s greatest leap towards ancient species de-extinction with the help of Yuka, an extremely well-preserved mammoth specimen [2]. Scientists were able to show that 28,000-year-old mammoth cell nuclei, where the genome is located, retained functional structures and unprecedented biological activity. These findings suggested ancient genomic samples could interact with modern cells and lead to further cellular functions including induced embryo development in the future [3]. The possibility of de-extinction is rapidly progressing with technological advancements unlocking previously undetectable information from priceless samples.


Although scientists and science fiction fans alike are thrilled to push the boundaries of ancient species revival, there are numerous ecological and ethical concerns associated with reviving an ancient species. Species introduction would undoubtedly impact the food chain, environment, natural selection, and the species itself. Ethically, species revival generates questions of patentability, captivity, research rights, and conservation efforts as well as the possibility of powerful God-like creators deciding who can and cannot create life. As technology advances towards the exciting possibility of de-extinction, scientists and the public must discuss the critical impacts species revival could play on an unstable environment. More importantly, they must engage in a conversation about the ethics of humanely reintroducing a modified organism to the world.


A successful effort at de-extinction, the revival of a lost species with phenotypic and genotypic resemblance to the extinct organism, begins with the selection of a promising candidate. In general, a favorable candidate would possess desirable reintroduction features such as providing ecological benefit or being adored by the public, having intact DNA samples available, and showing genetic similarity to a current living species. A staple of both movie theatres and museum halls, woolly mammoths are an example of an ideal candidate. In addition to their awe-inspiring existence, humans’ connection with this megafauna species extends far beyond the big screen as early humans used mammoths for tools, food, and art [1].


The possibility of de-extinction is rapidly progressing with technological advancements unlocking previously undetectable information from priceless samples.

Beyond their particular affinity with humankind, mammoths are a promising candidate for de-extinction because of their relatively recent extinction time frame. Since the last surviving mammoths died out only 4,000 years ago, they have a closely related living relative, the Asian elephant, and it is possible to acquire high-quality genomic sequences from ancient samples [4]. Mammoth remains are commonly located in permafrost traps including sinkholes, mudflows, and pools. Permafrost provides an ideal environment, free from bacterial and fungal contamination, for preservation of ancient DNA in easily manipulated tissues like hair [5, 6].


An additional benefit to studying mammoths is the species’ vast genetic diversity. During their pinnacle, mammoth populations spanned the globe from Western Europe, Northern Asia, and the Atlantic seaboard of North America. By analyzing the genomes of wide-spread mammoth specimens, samples could be chosen with sufficient genetic diversity to avoid future inbreeding and support long-term viability of the species. Species viability could be further assisted by using biotechnology to add synthetic differences [7]. These genomic differences would model a close living relative for the most successful outcomes, making it imperative for de-extinction candidates to have genomic similarity to a current species. Genomic studies have confirmed that the Asian elephant is the closest living relative to the woolly mammoth leading to possible roles as a pool for supplemental genetic information or as a potential surrogate for de-extinction [1, 8].


Because of woolly mammoths’ history as a beloved species, ideal extinction time frame, sample preservation methods for relatively intact DNA, and available genetically similar relative, this promising de-extinction candidate has become one of the best characterized extinct animals at a biomolecular level. While woolly mammoths meet the criteria for a positive candidate, there are ecological risks that must be considered before commencing de-extinction efforts. For example, reintroducing woolly mammoths would add a competitive herbivore, disrupting established food chains. Additionally, it is important to consider how mammoths’ diet and travel patterns would impact their released environment. Species reintroduction efforts would also need to assess the possible effects of habitat mismatch, introduction of novel pathogens, and unexpected interspecies interactions associated with homing a mammoth in current, drastically different, environmental conditions. Of course, it is also possible that species reintroduction would confer significant ecological benefits. For example, placement of marmots, hares, and musk oxen in Siberia have assisted grassland restoration, reformed plant distribution, and increased overall biodiversity [9].


Regardless of the potential risks and benefits, the possibility of reintroduction remains remote as it is expected that de-extinct mammoths would initially be reared in captivity for research purposes. Like previously cloned animals, they would likely reside in an exhibit or sanctuary. A humanely regulated life in captivity could create a breeding population and alleviate concerns about reintroduction or environmental impact.


Incredible sequencing advancements, including developments in shotgun and Sanger sequencing, have resulted in multiple sequenced mammoth genomes, consisting of over 4 billion fragmented bases, in a fraction of the time and cost.

Although de-extinction of woolly mammoths had been theorized as early as 1950, the required biotechnologies have only been established in the last decade. Technological advancements have uncovered three candidate methods for de-extinction: back breeding, somatic cloning, and genome engineering. Back breeding and somatic cloning have both been thoroughly demonstrated in extant mammalian species while genome engineering is still in its infancy. Back breeding, or selective breeding, would require the in vitro fertilization of a female Asian elephant with mammoth sperm and subsequent selection of an organism with mammoth-mimicking characteristics. Somatic cloning serves as the current basis for animal cloning as it has been accomplished in nearly 20 extant mammalian species including cats, dogs, horses, and notably, Dolly the sheep [2]. Somatic cloning involves implanting a donor nucleus from a somatic, or body cell, into an egg cell. For mammoths, this would consist of introducing a preserved mammoth nucleus into an Asian elephant egg cell. However, functional mammoth sperm for breeding or properly preserved tissues for cloning are unlikely to be found in even the most well-preserved mammoth samples. The most probable de-extinction technique, therefore, would be genome engineering, in which comparative studies between ancient samples and their extant relatives would be used to re-engineer an Asian elephant genome to resemble that of a woolly mammoth [2]. Importantly, researchers who adopt this technique must adhere to policies stating that no animal may unnecessarily suffer under any research conditions including donor and surrogate animals. They must also conduct detailed analyses of ancient DNA to fully comprehend the complex mammoth genome [2]. Since ancient DNA is fragile and degrades over time, scientists would have to work to fill gaps and uncertainties in genomic information with advancing biotechnologies or sequences of relative species [2].


Well-preserved mammoth remains are the most promising source of genomic information, and in the last 15 years, two of the best-preserved mammoth remains have been discovered. Lyuba, a 42,000-year-old mammoth calf, was discovered in pristine condition in 2007 [10, 1]. In 2012, Yuka, a juvenile mammoth, challenged Lyuba as the best-preserved mammoth sample ever found [3]. From samples taken from Lyuba, Yuka, and other well-preserved mammoths, scientists have used sequencing to discover numerous genomic differences between mammoths and elephants as well as information regarding mammoth behaviors and social structure. The first DNA sequencing of a human genome, created through the Human Genome Project, sequenced roughly 3 billion bases over a 13-year period costing almost $3 billion. Incredible sequencing advancements, including developments in shotgun and Sanger sequencing, have resulted in multiple sequenced mammoth genomes, consisting of over 4 billion fragmented bases, in a fraction of the time and cost [11]. While Asian elephants share 99.96% of their DNA with woolly mammoths, there are still roughly 1.4 million mutations between them. Currently, laboratories are analyzing each genomic difference so that they can be individually edited into elephant cell lines. A majority of the mutations are associated with genes linked to mammoth’s cold adaptations including small ears and tail to minimize heat loss, thick fur, large fat layers, and insulation focused glands. To survive long periods of winter darkness and constant summer sunlight, circadian clock alterations have also been identified in mammoth genomes [12]. These advancements and discoveries are not only fascinating but critical for future genome engineering de-extinction techniques that functionalize Asian elephant genomes to mimic ancient sequencing mutations. Alternatively, genome writing, the use of synthetic biology to build customized organisms to meet specific needs, may one day be used to combine the growing genomic understanding of mammoth mutations and genes to create an entirely synthetic woolly mammoth genome.


While these findings continue to fill in genomic gaps, it is important to consider how new insights influence future de-extinction efforts. Unregulated de-extinction could still impact the mammoth species as reviving a mammoth could result in their placement in a potentially harmful environment. Mammoth sequencing has identified multiple adaptations associated with the intake and processing of nitrogen-rich foods that are no longer widely available, which would be expected to force revived mammoths to feed on alternative sources [13]. Moreover, genome engineering and lab introduction may fail to restore the appropriate microbiome to simulate an ancient species while being able to maintain life in a drastically different environment [10]. Sequencing also revealed that mammoths were social creatures with intricate hierarchy systems and vast genomic diversity, conditions that would be irreplicable for the isolated species members introduced at early stages of de-extinction [5]. Lastly and most importantly, it is unlikely a full understanding of the mammoth genome will ever be achieved through ancient sample analysis alone due to severe fragmentation and degradation of even the best preserved DNA. Because of this, de-extinct mammoth genomes would be expected to be created through genome mixing with Asian elephant elements. While genome mixing may be necessary for de-extinction success, it would likely be implemented regardless for its legal implications.


De-extinction animal patents would presumably be pursued due to the expensive nature of the experiments, as well as the financial, public, and protective power granted through exclusive creation rights [14, 9]. In terms of patentability, an organism is ruled unpatentable if the created animal is identical to an organism that already existed in nature, such as in the case of Dolly the sheep [14]. While de-extinction strictly defined would prevent an organism’s patentability, a de-extinct mammoth would likely consist of both mammoth and Asian elephant genomic information meaning the reintroduced organism would be one that has never previously existed in nature. The patentability of organisms is complicated, but largely depends on the specific technological process used. Genome engineering is, at present, the most likely for successful patent applications. Factors that influence this decision include the biotechnological method being used for de-extinction, characteristics of the animal, interpreted definition of ‘exists in nature,’ and extent of technical or human intervention required [14]. Given these considerations and the precedent set by previous patent rulings, it is likely that researchers in the field would try to secure patentability by making sure that the de-extinct animal contained sufficient DNA modifications. Transgenic mice were granted animal patents through a similar design strategy.


Realistic ecological and ethical concerns are often shadowed by a fear of technology’s uncontrollable nature.

While de-extinction has been a major subject of discussion for the last several decades, it was only in 2016 that the International Union for the Conservation of Nature Species Survival Commission (IUCN SSC) released its ‘Guiding Principles for Creating Proxies of Extinct Species for Conservation Benefit’ [2]. The guide covers general steps for revival and reintroduction, but serious legal and moral concerns remain unaddressed. Mammoths are briefly mentioned in the document, but no distinct regulations for megafauna species revival, like woolly mammoths, are clarified. Before any de-extinction efforts are complete, laws should be passed classifying mammoths as endangered, exotic, or native species, therefore defining which set of current guidelines should be applied to mammoth protection and management. Further, rules should be drafted with respect to woolly mammoth captivity and release regulations, including approximate population numbers and expected care standards.


A woolly mammoth would presumably be revived solely for research purposes and live a life in captivity, bringing up ‘moral hazard’ concerns. A moral hazard is a situation where one party takes more risks because another party willingly or unwillingly will incur the costs if things go poorly [9]. Although de-extinction itself encourages incredible scientific advancement, critics dispute if de-extinction technology has benefits beyond being interesting. To combat the ethical challenges surrounding de-extinction, it is imperative for both scientists and the general public to question if de-extinction is propelled by the right motives and regulated by comprehensive policies.


Realistic ecological and ethical concerns are often shadowed by a fear of technology’s uncontrollable nature. This is a fear that has been repeatedly explored in the Jurassic Park franchise, pointing to what may be the biggest hurdle facing de-extinction: public skepticism. As with genetically modified organisms on grocery store shelves, the science behind de-extinction balances delicately between fantasy and fear. While the product of de-extinction would not, as with GMOs, require public buy-in, public support is nonetheless key for securing research and business funding. For example, numerous scientific barriers halting woolly mammoth de-extinction could be addressed through public support and financing. Due to public interest, many mammoth samples reside in natural history museums or traveling displays around the globe, limiting the amount of time they can spend in a lab. With public backing of de-extinction ideals, mammoth specimens may more often be excused from traveling exhibits allowing scientists time to thoroughly examine ancient materials. In addition to the challenges of collecting enough samples, ancient studies struggle with cost and technological barriers because exploring genomes of extinct species requires cutting edge technology that is expensive to use and even more costly to develop. Public backing of de-extinction would financially support further necessary technological advancements.


Another inquiry posed by the public is how de-extinction influences conservation. Opponents fear that de-extinction may undermine current conservation efforts if society no longer views endangered animals as worth protecting because extinct species now appear to be ‘easily revivable’ [2, 9]. Conversely, proponents argue that de-extinction may incentivize new funding sources and public enthusiasm to address the extinction crisis [1]. An overall positive view of de-extinction pairs with promising business ventures. The creation of a woolly mammoth would acquire capital funding through the assurance of public interest and entertainment because while many may question the ethics behind de-extinction, not many would pass on the opportunity to see a revived woolly mammoth in person.


Examining questions of creatorship throughout each step of the de-extinction process may help guide the debate of necessary ecological, ethical, and legal regulations.

De-extinction raises another critical question about who controls the creation of life. In the words of opponents, is de-extinction a hubristic attempt for human creators to ‘play God’? The practice of science is a race to discovery, publication, and public attention, and de-extinction is no exception. While the race towards mammoth de-extinction currently rests in the hands of scientists and those allocating research funding, it would be followed by those behind patent applications and business ventures. If a de-extinction patent is approved, it may grant exclusive rights to the patent holder for mammoth usage, management, and creation. It is important to consider which of these endeavors corresponds to ‘playing God.’ Further, can the public’s mammoth adoration and excitement be in part held responsible for scientists’ de-extinction motivation? De-extinction is unique in its joint interest from scientists, philanthropists, curators, entrepreneurs, journalists, and the general public, creating a complicated lattice of possible motives and priorities. Examining questions of creatorship throughout each step of the de-extinction process may help guide the debate of necessary ecological, ethical, and legal regulations.


Coinciding with power-hungry leaders creating new life and overall skepticism instilled by Blockbusters, opponents to de-extinction fear efforts may disrupt ecological systems, detract from current conservation resources, and riddle scientific progression with ethical dilemmas. Nevertheless, the world is excited by the idea of a new species being brought back from the dead. De-extinction proponents lobby on possible ecosystem improvements, satisfying a moral obligation to revive extinct animals, and re-invigorated passion for biodiversity and science. Scientists are excited to push biological boundaries with ever evolving technology, racing to come up with the newest techniques and discoveries. Incredible advancements in studying ancient genetic information, including shotgun and Sanger sequencing, paired with the likelihood of overcoming scientific hurdles through the current construction of a mammoth-like genome, promise a world where mammoths can exist as past, present, and future. Dolan says it best in that “there are many unknowns surrounding de-extinction. Whether it will happen or not, however, is likely not to be one of them” [15]. After scientists observed Yuka’s ancient nuclei activity, suggesting potential for future induced cellular function including embryo development, scientists, conservationists, entrepreneurs, and the public wereastounded by the nearing possibility of de-extinction. However, the lack of guidelines surrounding de-extinction are even more shocking. By considering all technological, environmental, and ethical challenges before species revival and ensuring proper governance is in place, de-extinction could smoothly evolve from a classic movie concept into a ground-breaking scientific achievement.


 

References


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9. Valdez, R. X., Kuzma, J., Cummings, C. L., & Nils Peterson, M. (2019). Anticipating risks, governance needs, and public perceptions of de-extinction. Journal of Responsible Innovation, 6(2), 211–231. https://doi.org/10.1080/23299460.2019.1591145

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14. Mcmahon, A., & Doyle, D. M. (2020). Patentability and de-extinct animals in Europe: the patented woolly mammoth? Journal of Law and the Biosciences, 1–28. https://doi.org/10.1093/jlb/lsaa017

15. Donlan, J. (2014). De-extinction in a crisis discipline. Frontiers of Biogeography, 6(1). https://doi.org/10.21425/f5fbg19504


 

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