Commercial animal cloning

Commercial animal cloning is the cloning of animals for commercial purposes, currently, including livestock, competition camels and horses, pets, medical uses, endangered and extinct animals,^[1] as first demonstrated in 1996 for Dolly the sheep.

Cloning methods

Moving or copying all (or nearly all) genes from one animal to form a second, genetically nearly identical, animal is usually done through one of three methods: the Roslin technique, the Honolulu technique, and Artificial Twinning.^[2] The first two of these involve a process known as somatic cell nuclear transfer.^[3] In this process, an oocyte is taken from a surrogate mother and put through enucleation, a process that removes the nucleus from inside the oocyte. Somatic cells are then taken from the animal that is being cloned, transferred into the blank oocyte in order to provide genetic material, and fused with the oocyte using an electrical current. The oocyte is then activated and re-inserted into the surrogate mother. The end result is the formation of an animal that is almost genetically identical to the animal the somatic cells were taken from.^[3][4] While somatic cell nuclear transfer was previously believed to only work using genetic material from somatic cells that were unfrozen or were frozen with cryoprotectant (to avoid cell damage caused by freezing), successful dog cloning in various breeds has now been shown using somatic cells from unprotected specimens that had been frozen for up to four days.^[5] Another method of cloning includes embryo splitting, the process of taking the blastomeres from a very early animal embryo and separating them before they become differentiated in order to create two or more separate organisms. When using embryo splitting, cloning must occur before the birth of the animal, and clones grow up at the same time (in a similar fashion to monozygotic twins).^[3]

Livestock cloning

The US Food and Drug Administration has concluded that "Food from cattle, swine, and goat clones is as safe to eat as food from any other cattle, swine, or goat."^[1] It has also noted that "The main use of agricultural clones is to produce breeding stock, not food. Clones allow farmers to upgrade the overall quality of their herds by providing more copies of the best animals in the herd. These animals are then used for conventional breeding, and the sexually reproduced offspring become the food producing animals." Regardless, a large (million cloned cattle per year) Tianjin animal cloning center was proposed in 2015 "to be put into use in the first half of 2016",^[6], but as of 2022, no opening had been reported. The goals of cloning listed by the FDA include "disease resistance ... suitability to climate ... quality body type .. fertility ... and market preference (leanness, tenderness, color, size of various cuts, etc.")^[1]

Competition horses and camels

Polo horses^[7] and camels^[8] are being cloned for competition use. Horse cloning is often referred to as "equine cloning". In 2012, Féderation Equestre Internationale (FEI) lifted a ban on horse cloning, allowing them to compete.^[9][10][11]

Medical uses

Organs from cloned pigs are beginning to be transplanted into human patients.^[12] (See Xenotransplantation.)

Endangered and extinct animals

The only extinct animal to be cloned as of 2022 is a Pyrenean ibex, born on July 30, 2003, in Spain, which died minutes later due to physical defects in the lungs.^[13][14]

Endangered animals, to add genetic diversity to inbred species, are also being cloned in certain centers, notably ViaGen, aided by the San Diego Frozen Zoo, and Revive & Restore.^[15] This is also referred to as "conservation cloning".^[16][17] Two examples are the black-footed ferret and Przewalski’s horse.^[15]

In a recent study using sturgeons (species of fish in the Acipenseridae family), scientists have been making improvements to a technique called somatic nuclear cell transfer with the ultimate goal being to save endangered species. Sturgeons are endangered due to the high levels of poaching, increased destruction to habitats, water pollution, and overfishing. This makes this species a perfect candidate for improving this type of cloning method, in hopes of preserving natural populations from becoming endangered. The somatic nuclear cell transfer technique is a well-known cloning method that has been used for years but focuses on species that are thriving rather than those endangered or extinct animals. This technique usually uses a single somatic donor cell with a single manipulation and inserts it into a recipient egg of the species of interest. It has recently been found that the position by which that somatic cell is located inside the recipient is very important in order to successfully clone a species. By making adjustments to the original method of using a single somatic cell and instead use multiple somatic donor cells to insert into the recipient egg, the likeliness of the somatic donor cells being in the crucial position on the egg will increase tremendously. This increase will then result in higher success rates with cloning. There is still ongoing research using this improved method happening but from the data collected thus far, it seems to be a reasonable method to continue and soon be able to help stop species like the sturgeons from becoming endangered and possibly stop extinction from occurring.^[18]

When it comes to the cloning of extinct animals, things become quite difficult because when death occurs, the animal's DNA starts to decay. This makes it impossible to fully preserve the entire genome by known cloning methods. New studies using genome editing, have made it possible to bring back traits of the extinct species. Currently, a lab at Harvard University's Wyss Institute, is working on a way to bring back a famously known extinct species referred to as the mammoth (or at least incorporate its traits into a closely related species). The goal is to genetically modify the mammoth's closely related living species, the elephant, in hopes of expanding available habitats of elephants and connecting lost ecological interactions. In order to make this goal possible, the team must first sequence and assemble the mammoth genome from preserved remains. After identifying the genome sequencing, a comparison of the extinct species and its closest living relative's genome can be made using advanced genome editing technology.

Studies have shown "cloning" of extinct animals is impossible, unlike currently living animals. As a closely related alternative, genome engineering seems to be the next best thing in making these long-gone species somewhat present in today's time. Methods like CRISPR/caps9 allow scientists to edit the genome of closely related relatives, allowing at least the traits of extinct animals to become present, which is essentially like bringing the extinct species back itself.^[19]

History and commercialization

ViaGen began by offering cloning to the livestock and equine industry in 2003,^[20] and later as ViaGen Pets included cloning of cats and dogs in 2016.^[21] ViaGen's subsidiary, stART Licensing, owns a cloning patent which is licensed to their only competitor as of 2018, who also offers animal cloning services.^[22] (Viagen is a subsidiary of Precigen.^[23])

The first commercially cloned pet was a cat named Little Nicky, produced in 2004 by Genetic Savings & Clone for a north Texas woman for the fee of US$50,000.^[24] On May 21, 2008, BioArts International^[25] announced a limited commercial dog cloning service (through a program it called Best Friends Again) in partnership with a Korean company named Sooam Biotech. This program came after the announcement of the successful cloning of a family dog named Missy, an achievement widely publicized in the Missyplicity Project. In September 2009, BioArts announced the end of its dog cloning service.^[26] In July 2008, the Seoul National University (co-parents of Snuppy, reputedly the world's first cloned dog in 2005) created five clones of a dog named Booger for its Californian owner. The woman paid $50,000 for this service.^[27]

Sooam Biotech continued developing proprietary techniques for cloning dogs^[28] based on a licence from ViaGen's subsidiary, stART Licensing (which owned the original patent for the process of animal cloning.^[29]). (Although the animal itself is not patentable, the process is protected by a patent).^[30] Sooam created cloned puppies for owners whose dogs had died, charging $100,000 per clone.^[31][32] Sooam Biotech was reported to have cloned approximately 700 dogs by 2015^[31] and to be producing 500 cloned embryos of various breeds a day in 2016.^[33] In 2015, the longest period after which Sooam Biotech could clone a puppy was 12 days from the death of the original pet dog.^[34] Sinogene Biotechnology created the first Chinese clone dog in 2017 before commercializing the cloning service and joining in the pet cloning market.^[35] In 2019, Sinogene successfully created the first Chinese cloned cat.^[36]

Controversies

Animal welfare

The mortality rate for cloned animals is higher than for those born of natural processes. This includes a discrepancy pre-birth, during birth, and after birth in survival rates and quality of life, leading to ethical concerns.^[37] Many of these discrepancies are thought to come from maternal mRNA already present in the oocyte prior to the transfer of genetic material as well as from DNA methylation, both of which contribute to the development of the animal in the womb of the surrogate.^[38] Some common issues seen with cloned animals are shortened telomeres, the repetitive end sequences of DNA whose decreasing length over the lifespan of an organism have been associated with aging;^[39] large offspring syndrome, the abnormal size of cloned individuals due to epigenetic (gene expression) changes; and methylation patterns of genetic material that are so abnormal compared to standard embryos of the species being cloned as to be incompatible with life.^[38]

Pet cloning

While pet cloning is sometimes advertised as a prospective method for re-gaining a deceased companionship animal, pet cloning does not result in animals that are exactly like the previous pet (in looks or personality).^[40] Although the animal in question is cloned, there are still phenotypical differences that may affect its appearance or health. This issue was brought to light in the cloning of a cat named Rainbow. Rainbow's clone, later named CC, was genetically identical to Rainbow, yet CC's coloring patterns were not the same due to the development of the kitten inside the womb as well as random genetic disparities in the clone such as variable X-chromosome inactivation.^[41]

Despite its controversies, the study of pet cloning holds the potential to contribute to scientific, veterinary, and medical knowledge, and it is a potential resource in efforts to preserve endangered cousins of the cat and dog.^[39]

In 2005, California Assembly Member Lloyd Levine introduced a bill to ban the sale or transfer of pet clones in California.^[42] That bill was voted down.^[43]

See also

• Biobank
• Cultivar: term used in botany to refer to specific breeds (made using selective cross breeding and sometimes genetic modification) that have distinct properties. Often reproduced using cloning to avoid properties being lost due to sexual propagation.
• List of animals that have been cloned
• Working animal

References

1. "A Primer on Cloning and Its Use in Livestock Operations". FDA. May 20, 2021.
2. Regina Bailey (Aug 3, 2021). "Cloning techniques".
3. Keefer, Carol (July 21, 2015). "Artificial cloning of domestic animals". Proceedings of the National Academy of Sciences. 112 (29): 8874–8. Bibcode:2015PNAS..112.8874K. doi:10.1073/pnas.1501718112. PMC 4517265. PMID 26195770.
4. Kim, Min Jung; Oh, Hyun Ju; Kim, Geon A; Setyawan, Erif Maha Nugraha; Choi, Yoo Bin; Lee, Seok Hee; Petersen-Jones, Simon M.; Ko, CheMyong J.; Lee, Byeong Chun (November 10, 2017). "Birth of clones of the world's first cloned dog". Scientific Reports. 7 (1): 15235. Bibcode:2017NatSR...715235K. doi:10.1038/s41598-017-15328-2. PMC 5681657. PMID 29127382.
5. Jeong, Yeonik; Olson, Olof P.; Lian, Cai; Lee, Eun Song; Jeong, Yeon Woo; Hwang, Woo Suk (2020-12-01). "Dog cloning from post-mortem tissue frozen without cryoprotectant". Cryobiology. 97: 226–230. doi:10.1016/j.cryobiol.2020.03.013. ISSN 0011-2240. PMID 32268132. S2CID 215610926.
6. "Animal cloning center to be built in Tianjin". Boyalife. Press release. November 23, 2015
7. Cohen, Haley. "How Champion-Pony Clones Have Transformed the Game of Polo". Vanity Fair. Retrieved 2021-03-07.
8. "How UAE camel cloning became an industry worth millions of dirhams". The National. 2021-02-19. Retrieved 2021-03-07.
9. MEDRANO, KASTALIA (2012-08-05). "Cloned Horses Coming to the Olympics?". nationalgeographic.com. Retrieved 2021-03-07.{{cite web}}: CS1 maint: url-status (link)
10. White, Charlotte (2012-06-29). "Cloned horses may now compete says FEI". Horse & Hound. Retrieved 2021-03-07.
11. "Horse International: Equine cloning: the legal aspects". European Us Asian Equine Lawyers - EUAEL. 2017-08-15. from the original on 2018-03-19. Retrieved 2021-03-07.
12. Eric Spitznagel (March 5, 2022). "How pigs will save thousands of human lives through organ transplants". New York Post.
13. J. Folch; J. Cocero; M. J. Chesne; P. Alabart; J. K. Dominguez; V. Congnie; Y. Roche; A. Fernández-Árias; A. Marti; J. I. Sánchez; P. Echegoyen; E. Beckers; J. F. Sánchez; A. Bonastre; X. Vignon (2009). "First birth of an animal from an extinct subspecies (Capra pyrenaica pyrenaica) by cloning". Theriogenology. 71 (6): 1026–1034. doi:10.1016/j.theriogenology.2008.11.005. PMID 19167744.
14. Zimmer, Carl. "Bringing Them Back To Life". Retrieved September 13, 2014.
15. "Scientists clone the first U.S. endangered species". Associated Press. Feb 18, 2021.
16. Marshall, Andrew (2000-11-01). "Cloning for conservation". Nature Biotechnology. 18 (11): 1129. doi:10.1038/81057. ISSN 1546-1696. PMID 11062403.
17. "Debating Science|Conservation Cloning: Feasible Way to Save Species". blogs.umass.edu. December 2, 2015. from the original on 2019-02-19. Retrieved 2021-03-07.
18. Fatira, Effrosyni; Havelka, Miloš; Labbé, Catherine; Depincé, Alexandra; Pšenička, Martin; Saito, Taiju (2019-07-18). "A newly developed cloning technique in sturgeons; an important step towards recovering endangered species". Scientific Reports. 9 (1): 10453. doi:10.1038/s41598-019-46892-4. ISSN 2045-2322. PMC 6639416. PMID 31320687.
19. Shapiro, Beth (2015-11-04). "Mammoth 2.0: will genome engineering resurrect extinct species?". Genome Biology. 16 (1): 228. doi:10.1186/s13059-015-0800-4. ISSN 1474-760X. PMC 4632474. PMID 26530525.
20. Castillo, Michelle (2018-03-08). "This woman paid $50,000 to clone her dead chihuahua...twice". CNBC. Retrieved 2020-06-06.
21. "Viagen Pets take animal cloning from research lab to marketplace". www.wtoc.com. Retrieved 2020-06-06.
22. Baron, Jessica. "If You Love Animals, Don't Clone Your Pet". Forbes. Retrieved 2020-06-06.
23. "PGEN annual report" (PDF). 2019.
24. Roush, Wade (February 17, 2006). "Genetic Savings and Clone: No Pet Project". MIT Technology Review.
25. BioArts International
26. Hawthorne, Lou (10 September 2009). "Six Reasons We're No Longer Cloning Dogs". Bioarts. Retrieved 23 March 2016.
27. Arnold, Paul (14 September 2009). "Animal Cloning: Pet Cloning Controversy". Retrieved 23 March 2016.
28. Agence France-Presse (September 20, 2009). "South Korea scientist wins dog cloning court battle". The China Post.
29. Dean, Josh (22 October 2014). "For $100,000, You Can Clone Your Dog". Bloomberg business. Retrieved 26 February 2016.
30. Kelly Servick (14 May 2014). "No Patent for Dolly the Cloned Sheep, Court Rules".
31. Taylor, Diane (24 December 2015). "UK couple have dead dog cloned in South Korea". The Guardian. Retrieved 24 February 2016.
32. Baer, Drake (8 September 2015). "This Korean lab has nearly perfected dog cloning, and that's just the start". Tech Insider, Innovation. Retrieved 27 February 2016.
33. Zastrow, Mark (8 February 2016). "Inside the cloning factory that creates 500 new animals a day". New Scientist. Retrieved 23 February 2016.
34. "British couple celebrate after birth of first cloned puppy of its kind". The Guardian. 26 December 2015. Retrieved 27 December 2015.
35. "Chinese firm clones gene-edited dog in bid to treat cardiovascular disease". CNN. 2017-12-27. Retrieved 2020-07-09.
36. "His Cat's Death Left Him Heartbroken. So He Cloned It". The New York Times. 2019-09-04. Retrieved 2020-07-09.
37. Heðinsdóttir, K.; Kondrup, S.; Röcklinsberg, H.; Gjerris, M. (2018). "Can Friends be Copied? Ethical Aspects of Cloning Dogs as Companion Animals". Journal of Agricultural and Environmental Ethics. 31 (1): 17–29. doi:10.1007/s10806-018-9706-y. ISSN 1187-7863. S2CID 148814791.
38. Keefer, Carol (July 21, 2015). "Artificial cloning of domestic animals". Proceedings of the National Academy of Sciences. 112 (29): 8874–8. Bibcode:2015PNAS..112.8874K. doi:10.1073/pnas.1501718112. PMC 4517265. PMID 26195770.
39. Ibtisham, F.; Fahd Qadir, M. M.; Xiao, M.; An, L. (2017). "Animal cloning applications and issues". Russian Journal of Genetics. 53 (9): 965–971. doi:10.1134/s102279541709006x. ISSN 1022-7954. S2CID 19932688.
40. Heðinsdóttir, K.; Kondrup, S.; Röcklinsberg, H.; Gjerris, M. (2018-02-01). "Can Friends be Copied? Ethical Aspects of Cloning Dogs as Companion Animals". Journal of Agricultural and Environmental Ethics. 31 (1): 17–29. doi:10.1007/s10806-018-9706-y. ISSN 1573-322X. S2CID 148814791.
41. Shin, Taeyoung; Kraemer, Duane; Pryor, Jane; Liu, Ling; Rugila, James; Howe, Lisa; Buck, Sandra; Murphy, Keith; Lyons, Leslie; Westhusin, Mark (February 14, 2002). "A cat cloned by nuclear transplantation". Nature. 415 (6874): 859. doi:10.1038/nature723. PMID 11859353. S2CID 4431855.
42. Mott, Maryann (February 23, 2005). "Pet-Clone Sales Spur Call for Ban". National Geographic News. Retrieved April 12, 2018.
43. "Cloned pets escape retail sales ban in California". dvm360 magazine. dvm360. July 1, 2005. Retrieved April 12, 2018.