Mammoth cloning

The existence of frozen soft tissue remains and DNA of woolly mammoths has led to the idea that the species could be recreated by scientific means. Several methods have been proposed to achieve this.

Model of a woolly mammoth at the Royal BC Museum

Overview

One proposed scientific use of this preserved genetic material, is to recreate living mammoths. This has long been discussed theoretically but has only recently become the subject of formal effort due to advances in molecular biology techniques and cloning of mammals.[1][2][3] Cloning of mammals has improved in the last two decades, but no viable mammoth tissue or its intact genome has been found to attempt cloning.

According to one research team, a mammoth cannot be recreated, but they will try to eventually grow in an "artificial womb" a hybrid elephant with some woolly mammoth traits.[4][5] Comparative genomics shows that the mammoth genome matches 99% of the elephant genome, so some researchers aim to engineer an elephant with some mammoth genes that code for the external appearance and traits of a mammoth.[6] The outcome would be an elephant-mammoth hybrid with no more than 1% mammoth genes.[6] And now separate projects are working on gradually adding mammoth genes to elephant cells in vitro.[1][2][7]

Cloning

Cloning would involve removal of the DNA-containing nucleus of the egg cell of a female elephant, and replacement with a nucleus from woolly mammoth tissue, a process called somatic cell nuclear transfer. For example, Akira Iritani, at the Kyoto University in Japan, reportedly planned to do this.[8][9] The cell would then be stimulated into dividing, and implanted in a female elephant. The resulting calf would have the genes of the woolly mammoth. However, nobody has yet found a viable mammoth cell, and most scientists doubt that any living cell could have survived freezing in the tundra.[10][11][12][13] Because of their conditions of preservation, the DNA of frozen mammoths has deteriorated significantly.[14][15]

Artificial insemination

A second method involves artificially inseminating an elephant egg cell with sperm cells from a frozen woolly mammoth carcass. The resulting offspring would be an elephant–mammoth hybrid, and the process would have to be repeated so more hybrids could be used in breeding. After several generations of cross-breeding these hybrids, an almost pure woolly mammoth would be produced. Whether the hybrid embryo would be carried through the two-year gestation, is unknown; in one case, an Asian elephant and an African elephant produced a live calf named Motty, but it died of defects at less than two weeks old.[16] The fact that sperm cells of modern mammals are viable for 15 years at most after deep-freezing makes this method unfeasible.[15]

Model depicting the calf "Dima", Stuttgart

Gene editing

In April 2015, Swedish scientists published the complete genome (nuclear DNA sequence) of the woolly mammoth.[1][17] Several projects are working on gradually replacing the genes in elephant cells with mammoth genes.[1][2] One such project is that of Harvard University geneticist George M. Church, who is funded by the Long Now Foundation,[1][2] is attempting to create a mammoth–elephant hybrid using DNA from frozen mammoth carcasses. According to the researchers, a mammoth cannot be recreated, but they will try to eventually grow a hybrid elephant with some woolly mammoth traits in an "artificial womb".[4][18] The Harvard University team is attempting to study the animals' characteristics in vitro by replacing or editing some specific mammoth genes into Asian elephant skin cells called fibroblasts that have the potential to become embryonic stem cells.[19] By March 2015 and using the new CRISPR DNA editing technique, Church's team had some woolly mammoth genes edited into the genome of an Asian elephant; focusing on cold-resistance initially,[10] the target genes are for the external ear size, subcutaneous fat, hemoglobin, and hair attributes.[19][20] By February 2017, Church's team had made 45 substitutions to the elephant genome.[4] So far his work focuses solely on single cells.

The Mammoth Genome Project at Pennsylvania State University is also researching the modification of African elephant DNA to create an elephant–mammoth hybrid.[21] If a viable hybrid embryo is obtained by gene editing procedures, implanting it into a female Asian elephant housed in a zoo may be possible,[1] but with the current knowledge and technology, whether the hybrid embryo would be carried through the two-year gestation is unknown.[22][23]

Ethics

If any method is ever successful, a suggestion has been made to introduce the hybrids to a wildlife reserve in Siberia called the Pleistocene Park,[8][24] but some biologists question the ethics of such recreation attempts.[25] In addition to the technical problems, not much habitat is left that would be suitable for elephant-mammoth hybrids. Because both species are [were] social and gregarious, creating a few specimens would not be ideal. The time and resources required would be enormous, and the scientific benefits would be unclear, suggesting these resources should instead be used to preserve extant elephant species which are endangered.[15][26] The ethics of using elephants as surrogate mothers in hybridisation attempts has also been questioned, as most embryos would not survive, and knowing the exact needs of a hybrid elephant–mammoth calf would be impossible.[27]

See also

• List of animals that have been cloned
• De-extinction

References

1. Mammoth genome sequence completed. BBC News, 23 April 2015.
2. The Long Now Fouldation - Revive and Restore.
3. Timmons, Jeanne (January 7, 2013). "Could Ancient Giants Be Cloned? Is It Possible, And Is It Wise?". Valley News.
4. Reviving woolly mammoth will take more than 2 years Archived 8 October 2017 at the Wayback Machine. BBC News. Helen Pilcher, 22 February 2017.
5. De-extinction and Conservation. Gregory E. Kaebnick, and Bruce Jennings. The Hastings Center Report. 26 July 2017
6. The Mammoth Genome Project. Pennsylvania State University. Accessed: October 2018.
7. "Mammoth: Back from the Dead" Archived 2014-01-06 at the Wayback Machine. National Geographic Channel.
8. Kruglova, Lidia (2 May 2011). "Pleistocene Park: so far without mammoths". The Voice of Russia. Archived from the original on 8 October 2017. Retrieved 2019-03-05.
9. Scientists trying to clone, resurrect extinct mammoth Archived 29 October 2013 at the Wayback Machine. Brad Lendon. CNN News. 17 January 2011.
10. Can scientists bring mammoths back to life by cloning? Archived 8 October 2017 at the Wayback Machine Jackson Landers. February 9, 2015. The Washington Post.
11. Bringing them Back to Life Archived 29 March 2017 at the Wayback Machine. Carl Zimmer, National Geographic. April 2013.
12. Cloning the Mammoth: A Complicated Task or Just a Dream? Archived 15 April 2016 at the Wayback Machine (PDF), Pasqualino Loi , Joseph Saragusty , and Grazyna Ptak. 2014
13. Shapiro, 2015. p. 11
14. Timmons, Jeanne (7 January 2013). "Could Ancient Giants Be Cloned? Is It Possible, And Is It Wise?". Valley News. Archived from the original on 30 March 2015.
15. Lister, 2007. pp. 42–43
16. Stone, R. (1999). "Cloning the Woolly Mammoth". Discover Magazine. Archived from the original on 29 July 2014.
17. Dalén, Love; Palkopoulou, Eleftheria; Mallick, Swapan; et al. (18 May 2015). "Complete Genomes Reveal Signatures of Demographic and Genetic Declines in the Woolly Mammoth". Current Biology. 25 (10): 1395–1400. doi:10.1016/j.cub.2015.04.007. PMC 4439331. PMID 25913407. Retrieved 2017-10-07.
18. Kaebnick, Gregory E.; Jennings, Bruce (2017). "De-extinction and Conservation". Hastings Center Report. 47: S2–S4. doi:10.1002/hast.744. PMID 28746761.
19. Webster, Ben (2015-03-23). "Scientist takes mammoth-cloning a step closer". The Sunday Times.
20. Sarah Fecht (24 March 2014), Woolly Mammoth DNA Successfully Spliced Into Elephant Cells, Popular Science, archived from the original on 26 March 2015
21. Scientists Hoped to Have Cloned a Living Woolly Mammoth by Now — Why Haven't We? Archived 8 October 2017 at the Wayback Machine. Sveta McShane. 17 August 2016. Singularity Hub.
22. The Plan to Turn Elephants Into Woolly Mammoths Is Already Underway Archived 24 April 2015 at the Wayback Machine. 21 May 2014.
23. "Scientists Sequence Woolly-Mammoth Genome". Mammoth Genome Project. Pennsylvania State University. Archived from the original on 2008-12-02. Retrieved 6 November 2014.
24. Zimov, S. A. (2005). "Essays on Science and Society: Pleistocene Park: Return of the Mammoth's Ecosystem". Science. 308 (5723): 796–798. doi:10.1126/science.1113442. PMID 15879196.
25. An Analysis of Potential Ethical Justifications for Mammoth De-extinction And a Call for Empirical Research. Yasha Rohwer and Emma Marris. Ethics, Policy & Environment; Volume 21, 2018; Issue 1; pages: 127-142.
26. Griffin, A. (23 March 2015). "Woolly mammoth could be revived after scientists paste DNA into elephant's genetic code". The Independent. Archived from the original on 25 September 2015.
27. Loi, Pasqualino; Saragusty, Joseph; Ptak, Grazyna (2014). Cloning the Mammoth: A Complicated Task or Just a Dream?. Adv Exp Med Biol. Advances in Experimental Medicine and Biology. 753. pp. 489–502. doi:10.1007/978-1-4939-0820-2_19. ISBN 978-1-4939-0819-6. PMID 25091921.