Organism cloning (also called reproductive cloning) refers to the procedure of creating a new multicellular organism, genetically identical to another. In essence this form of cloning is an asexual method of reproduction, where fertilization or inter-gamete contact does not take place. Asexual reproduction is a naturally occurring phenomenon in many species, including most plants and some insects. Scientists have made some major achievements with cloning, including the asexual reproduction of sheep and cows. There is a lot of ethical debate over whether or not cloning should be used. However, cloning, or asexual propagation, has been common practice in the horticultural world for hundreds of years.
Horticultural , such as grape vines, is an ancient form of cloning. The term
clone is used in horticulture to refer to descendants of a single plant which were produced by
vegetative reproduction or
apomixis. Many horticultural plant
cultivars are clones, having been derived from a single individual, multiplied by some process other than sexual reproduction. As an example, some European cultivars of grapes represent clones that have been propagated for over two millennia. Other examples are potatoes and bananas.
Grafting can be regarded as cloning, since all the shoots and branches coming from the graft are genetically a clone of a single individual, but this particular kind of cloning has not come under
ethical scrutiny and is generally treated as an entirely different kind of operation. Many trees,
shrubs,
vines,
ferns and other
herbaceous perennials form
clonal colonies naturally. Parts of an individual plant may become detached by
fragmentation and grow on to become separate clonal individuals. A common example is in the vegetative reproduction of moss and liverwort gametophyte clones by means of
gemmae. Some vascular plants e.g.
dandelion and certain
viviparous grasses also form
seeds asexually, termed
apomixis, resulting in clonal populations of genetically identical individuals.
Parthenogenesis Clonal derivation exists in nature in some animal species and is referred to as
parthenogenesis (reproduction of an organism by itself without a mate). This is an asexual form of reproduction that is only found in females of some insects, crustaceans, nematodes, fish (for example the
hammerhead shark),
Cape honeybees, and lizards including the
Komodo dragon Methods Reproductive cloning generally uses "
somatic cell nuclear transfer" (SCNT) to create animals that are genetically identical. This process entails the transfer of a nucleus from a donor adult cell (somatic cell) to an egg from which the nucleus has been removed, or to a cell from a
blastocyst from which the nucleus has been removed. If the egg begins to divide normally it is transferred into the uterus of the surrogate mother. Such clones are not strictly identical since the somatic cells may contain mutations in their nuclear DNA. Additionally, the
mitochondria in the
cytoplasm also contains DNA and during SCNT this mitochondrial DNA is wholly from the cytoplasmic donor's egg, thus the
mitochondrial genome is not the same as that of the nucleus donor cell from which it was produced. This may have important implications for cross-species nuclear transfer in which nuclear-mitochondrial incompatibilities may lead to death. Artificial
embryo splitting or
embryo twinning, a technique that creates monozygotic twins from a single embryo, is not considered in the same fashion as other methods of cloning. During that procedure, a donor
embryo is split in two distinct embryos, that can then be transferred via
embryo transfer. It is optimally performed at the 6- to 8-cell stage, where it can be used as an expansion of
IVF to increase the number of available embryos. If both embryos are successful, it gives rise to
monozygotic (identical) twins.
Dolly the sheep body of Dolly the sheep
Dolly, a
Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult somatic cell. Dolly was formed by taking a cell from the udder of her 6-year-old biological mother. Contrary to popular belief, she was not the first animal to be cloned. Dolly's embryo was created by taking the cell and inserting it into a sheep ovum. It took 435 attempts before an embryo was successful. The embryo was then placed inside a female sheep that went through a normal pregnancy. She was cloned at the
Roslin Institute in Scotland by British scientists Sir
Ian Wilmut and
Keith Campbell and lived there from her birth in 1996 until her death in 2003 when she was six. She was born on 5 July 1996 but not announced to the world until 22 February 1997. Her
stuffed remains were placed at Edinburgh's
Royal Museum, part of the
National Museums of Scotland. Dolly was publicly significant because the effort showed that genetic material from a specific adult cell, designed to express only a distinct subset of its genes, can be redesigned to grow an entirely new organism. Before this demonstration, it had been shown by John Gurdon that nuclei from differentiated cells could give rise to an entire organism after transplantation into an enucleated egg. However, this concept was not yet demonstrated in a mammalian system. The first mammalian cloning (resulting in Dolly) had a success rate of 29 embryos per 277 fertilized eggs, which produced three lambs at birth, one of which lived. In a bovine experiment involving 70 cloned calves, one-third of the calves died quite young. The first successfully cloned horse,
Prometea, took 814 attempts. Notably, although the first clones were frogs, no adult cloned frog has yet been produced from a somatic adult nucleus donor cell. There were early claims that Dolly had pathologies resembling accelerated aging. Scientists speculated that Dolly's death in 2003 was related to the shortening of
telomeres, DNA-protein complexes that protect the end of linear
chromosomes. However, other researchers, including
Ian Wilmut who led the team that successfully cloned Dolly, argue that Dolly's early death due to respiratory infection was unrelated to problems with the cloning process. This idea that the nuclei have not irreversibly aged was shown in 2013 to be true for mice.
Colossal dire wolves In 2024,
Colossal Biosciences announced they had brought the
dire wolf back from extinction via cloning and genetic engineering. The biotech company created three grey wolf clones with 14 genes edited to express traits likely similar to those of dire wolves. Many scientists have contested whether the clones can be considered true dire wolves.
Species cloned and applications The modern cloning techniques involving
nuclear transfer have been successfully performed on several species. Notable experiments include: •
Tadpole: (1952)
Robert Briggs and
Thomas J. King successfully cloned northern leopard frogs: thirty-five complete embryos and twenty-seven tadpoles from one-hundred and four successful nuclear transfers. •
Carp: (1963) In China,
embryologist Tong Dizhou produced the world's
first cloned fish by inserting the DNA from a cell of a male carp into an egg from a female carp. •
Zebrafish: (1981)
George Streisinger produced the next in line of the vertebrates. •
Sheep: (1984)
Steen Willadsen produced the first cloned mammal from early embryonic cells. • In June 1995, the
Roslin Institute cloned
Megan and Morag from differentiated embryonic cells. • In July 1996, PPL Therapeutics and the Roslin Institute cloned
Dolly the sheep from a somatic cell. •
Rhesus monkey: (October 1999) The
Oregon National Primate Research Center cloned
Tetra from embryo splitting and not nuclear transfer: a process more akin to artificial formation of twins. •
Pig: (March 2000) PPL Therapeutics cloned five piglets. By 2014,
BGI in China was producing 500 cloned pigs a year to test new medicines. •
Gaur: (2001) was the first endangered species cloned. • Cattle: •
Alpha and Beta (males, 2001) and (2005), Brazil • In 2023, Chinese scientists reported the cloning of three
supercows with a milk productivity "nearly 1.7 times the amount of milk an average cow in the United States produced in 2021" and a plan for 1,000 of such super cows in the near-term. According to a news report "[i]n many countries, including the United States, farmers breed clones with conventional animals to add desirable traits, such as high milk production or disease resistance, into the gene pool". • Cat:
CopyCat "CC" (female, late 2001),
Little Nicky, 2004, was the first cat cloned for commercial reasons • Rat:
Ralph, the first cloned rat (2003) •
Mule:
Idaho Gem, a john mule born 4 May 2003, was the first horse-family clone. • Horse:
Prometea, a Haflinger female born 28 May 2003, was the first horse clone. •
Przewalksi's Horse: An ongoing cloning program by the
San Diego Zoo Wildlife Alliance and
Revive & Restore attempts to reintroduce
genetic diversity to this endangered species. • Kurt, the first cloned Przewalski's horse, was born in 2020. He was cloned from the skin tissue of a stallion which was preserved in 1980. • "Trey" was born in 2023. He was cloned from the same stallion's tissue as Kurt. • Dog: •
Snuppy, a male
Afghan hound was the first cloned dog (2005). In 2017, the world's first gene-editing clone dog, Apple, was created by
Sinogene Biotechnology. Sooam Biotech, South Korea, was reported in 2015 to have cloned 700 dogs to date for their owners, including two
Yakutian Laika hunting dogs, which are seriously endangered due to crossbreeding. • Cloning of super
sniffer dogs was reported in 2011, four years afterwards when the dogs
started working. Cloning of a successful rescue dog was also reported in 2009 and of a similar police dog in 2019. Cancer-sniffing dogs have also been cloned. A
review concluded that "qualified
elite working dogs can be produced by cloning a working dog that exhibits both an appropriate temperament and good health." •
Wolf:
Snuwolf and Snuwolffy, the first two cloned female wolves (2005). •
Water buffalo:
Samrupa was the first cloned water buffalo. It was born on 6 February 2009, at
India's Karnal National Dairy Research Institute but died five days later due to lung infection. •
Pyrenean ibex: (2009) was the first extinct animal to be cloned back to life; the clone lived for seven minutes before dying of lung defects. The extinct Pyrenean ibex is a sub-species of the extant
Spanish ibex. • Camel: (2009)
Injaz, was the first cloned camel. •
Pashmina goat: (2012)
Noori, is the first cloned pashmina goat. Scientists at the faculty of veterinary sciences and animal husbandry of
Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir successfully cloned the first Pashmina goat (Noori) using the advanced reproductive techniques under the leadership of Riaz Ahmad Shah. • Goat: (2001) Scientists of
Northwest A&F University successfully cloned the first goat which use the adult female cell. •
Gastric brooding frog: (2013) The gastric brooding frog,
Rheobatrachus silus, thought to have been extinct since 1983 was cloned in Australia, although the embryos died after a few days. •
Macaque monkey: (2017) First successful cloning of a
primate species using
nuclear transfer, with the birth of two live clones named
Zhong Zhong and Hua Hua. Conducted in China in 2017, and reported in January 2018. In January 2019, scientists in China reported the creation of five identical
cloned gene-edited monkeys, using the same cloning technique that was used with Zhong Zhong and Hua Hua and
Dolly the sheep, and the gene-editing
Crispr-
Cas9 technique allegedly used by
He Jiankui in creating the first ever gene-modified human babies
Lulu and Nana. The monkey clones were made to study several medical diseases. •
Black-footed ferret: (2020) A team of scientists cloned a female named Willa, who died in the mid-1980s and left no living descendants. Her clone, a female named Elizabeth Ann, was born on 10 December. Scientists hope that the contribution of this individual will alleviate the effects of inbreeding and help black-footed ferrets better cope with plague. Experts estimate that this female's genome contains three times as much genetic diversity as any of the modern black-footed ferrets. • First artificial
parthenogenesis in mammals: (2022) Viable mice offspring was born from unfertilized eggs via targeted
DNA methylation editing of seven
imprinting control regions.
Human cloning Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissues. It does not refer to the natural conception and delivery of
identical twins. The possibility of human cloning has raised
controversies. These ethical concerns have prompted several nations to pass legislation regarding human cloning and its legality. As of right now, scientists have no intention of trying to clone people and they believe their results should spark a wider discussion about the laws and regulations the world needs to regulate cloning. Two commonly discussed types of theoretical human cloning are
therapeutic cloning and
reproductive cloning. Therapeutic cloning would involve cloning cells from a human for use in medicine and transplants, and is an active area of research, but is not in medical practice anywhere in the world, . Two common methods of therapeutic cloning that are being researched are
somatic-cell nuclear transfer and, more recently,
pluripotent stem cell induction. Reproductive cloning would involve making an entire cloned human, instead of just specific cells or tissues.
Ethical issues of cloning There are a variety of
ethical positions regarding the possibilities of cloning, especially
human cloning. While many of these views are religious in origin, the questions raised by cloning are faced by secular perspectives as well. Perspectives on human cloning are theoretical, as human therapeutic and reproductive cloning are not commercially used; animals are currently cloned in laboratories and in
livestock production. Advocates support development of therapeutic cloning to generate tissues and whole organs to treat patients who otherwise cannot obtain transplants, to avoid the need for
immunosuppressive drugs, Advocates for reproductive cloning believe that parents who cannot otherwise procreate should have access to the technology. Opponents of cloning have concerns that technology is not yet developed enough to be safe and that it could be prone to abuse (leading to the generation of humans from whom organs and tissues would be harvested), as well as concerns about how cloned individuals could integrate with families and with society at large. Cloning humans could lead to serious violations of
human rights. Religious groups are divided, with some opposing the technology as usurping "God's place" and, to the extent embryos are used, destroying a human life; others support therapeutic cloning's potential life-saving benefits. There is at least one religion,
Raëlism, in which cloning plays a major role. Contemporary work on this topic is concerned with the ethics, adequate regulation and issues of any cloning carried out by humans,
not potentially by extraterrestrials (including in the future), and largely also not replication – also described as mind cloning – of potential whole brain emulations. Cloning of animals is opposed by animal-groups due to the number of cloned animals that suffer from malformations before they die, and while food from cloned animals has been approved as safe by the US FDA, its use is opposed by groups concerned about food safety. In practical terms, the inclusion of "licensing requirements for embryo research projects and fertility clinics, restrictions on the commodification of eggs and sperm, and measures to prevent proprietary interests from monopolizing access to stem cell lines" in international cloning regulations has been proposed, albeit e.g. effective oversight mechanisms or cloning requirements have not been described.
Cloning extinct and endangered species Cloning, or more precisely, the reconstruction of functional DNA from
extinct species has, for decades, been a dream. Possible implications of this were dramatized in the 1984 novel
Carnosaur and the 1990 novel
Jurassic Park. The best current cloning techniques have an average success rate of 9.4 percent (and as high as 25 percent
Conservation cloning Several tissue banks have come into existence, including the "
Frozen zoo" at the
San Diego Zoo, to
store frozen tissue from the world's rarest and most endangered species. This is also referred to as "Conservation cloning". Engineers have proposed a "lunar ark" in 2021 – storing millions of seed, spore, sperm and egg samples from Earth's contemporary species in a network of lava tubes on the
Moon as a genetic backup. Similar proposals have been made since at least 2008. These also include sending human customer DNA, and a proposal for "a lunar backup record of humanity" that includes genetic information by
Avi Loeb et al. In 2020, the
San Diego Zoo began a number of projects in partnership with the conservation organization
Revive & Restore and the
ViaGen Pets and Equine Company to clone individuals of genetically-impoverished endangered species. A
Przewalski's horse was cloned from preserved tissue of a stallion whose genes are absent in the surviving populations of the species, which descend from twenty individuals. The clone, named Kurt, had been born to a domestic surrogate mother, and was partnered with a natural-born Przewalski's mare in order to socialize him with the species' natural behavior before being introduced to the Zoo's breeding herd. In 2023, a second clone of the original stallion, named Ollie, was born; this marked the first instance of multiple living clones of a single individual of an endangered species being alive at the same time. Also in 2020, a clone named Elizabeth Ann was produced of a female
black-footed ferret that had no living descendants. While Elizabeth Ann became sterile due to secondary health complications, a pair of additional clones of the same individual, named Antonia and Noreen, were born to distinct surrogate mothers, and Antonia successfully reproduced later in the year.
De-extinction One of the most anticipated targets for cloning was once the
woolly mammoth, but attempts to extract DNA from frozen mammoths have been unsuccessful, though a joint Russo-Japanese team is currently working toward this goal. In January 2011, it was reported by Yomiuri Shimbun that a team of scientists headed by Akira Iritani of Kyoto University had built upon research by Dr. Wakayama, saying that they will extract DNA from a mammoth carcass that had been preserved in a Russian laboratory and insert it into the egg cells of an
Asian elephant in hopes of producing a mammoth embryo. The researchers said they hoped to produce a baby mammoth within six years. The challenges are formidable. Extensively degraded DNA that may be suitable for sequencing may not be suitable for cloning; it would have to be synthetically reconstituted. In any case, with currently available technology, DNA alone is not suitable for mammalian cloning; intact viable cell nuclei are required. Patching pieces of reconstituted mammoth DNA into an Asian elephant cell nucleus would result in an elephant-mammoth hybrid rather than a true mammoth. Moreover, true de-extinction of the wooly mammoth species would require a breeding population, which would require cloning of multiple genetically distinct but reproductively compatible individuals, multiplying both the amount of work and the uncertainties involved in the project. There are potentially other post-cloning problems associated with the survival of a reconstructed mammoth, such as the requirement of
ruminants for specific
symbiotic microbiota in their stomachs for digestion. Many such "de-extinction" projects are being championed by the non-profit
Revive & Restore. In 2022, scientists showed major limitations and the scale of challenge of genetic-editing-based de-extinction, suggesting resources spent on more comprehensive de-extinction projects such as
of the woolly mammoth may currently not be well
allocated and substantially limited. Their analyses "show that even when the extremely high-quality Norway brown rat (
R. norvegicus) is used as a reference, nearly 5% of the genome sequence is unrecoverable, with 1,661 genes recovered at lower than 90% completeness, and 26 completely absent", complicated further by that "distribution of regions affected is not random, but for example, if 90% completeness is used as the cutoff, genes related to immune response and olfaction are excessively affected" due to which "a reconstructed Christmas Island rat would lack attributes likely critical to surviving in its natural or natural-like environment". In a 2021 online session of the Russian Geographical Society, Russia's defense minister
Sergei Shoigu mentioned using the DNA of 3,000-year-old
Scythian warriors to potentially bring them back to life. The idea was described as absurd at least at this point in news reports and it was noted that Scythians likely weren't skilled warriors by default. The idea of cloning
Neanderthals or bringing them back to life in general is controversial but some scientists have stated that it may be possible in the future and have outlined several issues or problems with such as well as broad rationales for doing so.
Unsuccessful attempts In 2001, a cow named Bessie gave birth to a cloned Asian
gaur, an endangered species, but the calf died after two days. In 2003, a
banteng was successfully cloned, followed by three
African wildcats from a thawed frozen embryo. These successes provided hope that similar techniques (using surrogate mothers of another species) might be used to clone extinct species. Anticipating this possibility, tissue samples from the last
bucardo (
Pyrenean ibex) were frozen in
liquid nitrogen immediately after it died in 2000. Researchers are also considering cloning endangered species such as the
Giant panda and
Cheetah. In 2002, geneticists at the
Australian Museum announced that they had replicated DNA of the
thylacine (Tasmanian tiger), at the time extinct for about 65 years, using
polymerase chain reaction. However, on 15 February 2005 the museum announced that it was stopping the project after tests showed the specimens' DNA had been too badly degraded by the (
ethanol) preservative. On 15 May 2005 it was announced that the thylacine project would be revived, with new participation from researchers in
New South Wales and
Victoria. In 2022
Colossal Biosciences and
University of Melbourne announced further efforts to de-extinct the Thylacine, creating the Thylacine Integrated Genetic Restoration Research (TIGRR) Lab, which claims it has made a series of significant advancements, including having produced a thylacine genome that is "more than 99.9-per-cent accurate". In 2003, for the first time, an extinct animal, the Pyrenean ibex mentioned above was cloned, at the Centre of Food Technology and Research of Aragon, using the preserved frozen cell nucleus of the skin samples from 2001 and domestic goat egg-cells. The ibex died shortly after birth due to physical defects in its lungs.
Lifespan After an eight-year project involving the use of a pioneering cloning technique, Japanese researchers created 25 generations of healthy cloned mice with normal lifespans, demonstrating that clones are not intrinsically shorter-lived than naturally born animals. Other sources have noted that the offspring of clones tend to be healthier than the original clones and indistinguishable from animals produced naturally. Some posited that Dolly the sheep may have aged more quickly than naturally born animals, as she died relatively early for a sheep at the age of six. Ultimately, her death was attributed to a respiratory illness, and the "advanced aging" theory is disputed. A 2016 study indicated that once cloned animals survive the first month or two of life they are generally healthy. However, early pregnancy loss and neonatal losses are still greater with cloning than natural conception or assisted reproduction (IVF). Current research is attempting to overcome these problems. ==In popular culture==