CLONING
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Back to Cloning Introduction page.
by: Sebastian Molnar
On February 23 1997, a group of Scottish scientists at the Roslin Institute announced to the world that they had cloned a sheep (Dolly) by transferring the nuclei of adult udder cells into enucleated unfertilized egg cells. The news hit front page headlines the very next day (ref. 1; Kolata 1997a). In the December 19 issue of the journal Science (Pennisi 1997) the cloning of Dolly was considered to be the top breakthrough of 1997 -- a breakthrough defined as "a rare discovery that profoundly changes the practice or interpretation of science or its implications for society" (Bloom 1997). Just one week after Dolly was revealed, scientists at the Oregon Regional Primate Research Center announced they had cloned two rhesus monkeys from embryonic cells also using nuclear transfer (ref. 2; Bradbury 1997). The next step appeared to be the cloning of humans -- the initial public reaction was far from positive (Klugman and Murray 1998 p39). Popular views about cloning come from science fiction (Pence 1998 p4). Science fiction books and films typically portray clones as "mindless drones" and the act of cloning is pictured as ultimately leading to disasterous consequences (as in Jurassic Park). What had existed only in science fiction was becoming a reality (Kolata 1997; Shapiro 1997). Even Ian Wilmut, one of the scientists involved in the creation of Dolly, said "cloning people should be in the realm of science fiction" as it would be "ethically unacceptable" to clone a human (ref. 1). Wilmut stated that he had no intention of cloning humans, and only wanted to use the technology on farm animals. At the first major cloning conference, there appeared to be a general consensus between ethicists, scientists, and theologians that "human cloning should never be done" (Pence 1998 pp xi-xii). The word "clone" is greek for "twig" and it was originally used by botanists to mean an "asexually produced population" (Harper 1985 p1). The Oxford English dictionary defines "clone" as "a group of plants produced vegetatively from one original seedling", however the common modern usage has a more specific meaning: "genetically identical individuals". In 1902, Dr. Gottlieb Haberlandt, an Austrian biologist, introduced the term "totipotency" to describe a cell that has the ability to develop into any other cell type (Hugli 1985 p10). Totipotency plays an important role throughout normal plant growth (e.g. in the development of a root) and the general rule is that plant cells remain totipotent even after cell specialization. Animal development is somewhat different. Animal cells lose their totipotency during development -- for example, a brain cell does not, under the normal conditions of the body, develop into a liver cell. It was believed that animal cells undergo irreversible changes during differentiation and therefore using somatic cells from adult mammals to create clones was "biologically impossible" (McGrath and Solter 1984; Hugli 1985 p11-12). The news about Dolly came as a surprise to the scientific community. No longer could cloning from adult cells be considered impossible (Solter 1996). This technological advance, however, also raised many ethical concerns with its potential applications to humans. The present study will deal with some of the ethical issues and evolutionary implications of cloning.
Dolly was created by Ian Wilmut et al. (1997) using a technique known as nuclear somatic transfer (NST). NST involves the creation of an embryo through fusing -- via an electric shock or by chemical means -- the nucleus of a somatic cell with an enucleated unfertilized egg cell. Nuclear transfer has been known since the early 1950s, however all the experiments done before Dolly used embryonic cells, not adult cells. The contribution to NST by Wilmut and his colleagues involved the discovery that starvation of differentiated cells from adults can cause the nuclei to be reprogrammed into a state of totipotency. A lack of nutrients induces cells to enter G0 (Gap-0) of the cell cycle, and somehow causes the reprogramming of gene expression to a more "primordial state". These reprogrammed nuclei can then be fused with enucleated unfertilized eggs to create embryos, which may be implanted into suitable females for gestation. There was some concern over whether Dolly really was a clone derived from the udder cells of an adult ewe -- there was a possibility Dolly was created from contaminating fetal cells (Sgaramella and Zinder 1998). Further genetic testing, however, showed that Dolly was a clone from an adult cell (Ashworth et al. 1998; Signer et al. 1998), however, she was a genetic chimera made of donor nuclei and recipient egg mitochondrial DNA (Evans et al. 1999). On the global scale, many countries have acted to pass legislation to regulate or ban cloning. In particular, cloning to create a child (or "pregnancy cloning") has met with wide hostility. Other types of cloning, such as therapeutic cloning (or cloning for "spare parts"), have received somewhat less severe disapproval. Several countries have had laws which prohibit even the use of human eggs or human embryos in research, as such, making both pregnancy cloning and therapeutic cloning illegal (Gurdon and Colman 1999). With the announcement of Dolly, some countries, such as the U.S.A, acted immediately in response to the possibility of human cloning. Other countries have endeavored to regulate cloning, but still remain in the process of deliberation. Upon hearing about the birth of Dolly in late February of 1997, President Bill Clinton immediately imposed a temporary ban on federal funding, and asked for a voluntary moratorium for private funding, of human cloning research. On March 4 1997, Clinton asked the National Bioethics Advisory Commission (NBAC) to review the legal and ethical issues for cloning technology and to give a report within ninety days (Purdum 1997; for a copy of the NBAC report, see their website, references 50 and 51). In their report, the NBAC had concluded that "it is morally unacceptable for anyone in the public or private sector, whether in a research or clinical setting, to attempt to create a child by somatic cell nuclear transfer" (ref. 51). As such, a continuation of the moratorium on human cloning research was recommended, and that a legislative ban be enacted to "prohibit anyone from attempting...to create a child using somatic cell nuclear transfer" (Shapiro 1997). Any legislation, however, is to include a sunset clause so that the technology and issues can be re-evaluated after 3 to 5 years. The NBAC also indicated that legislation "should be carefully worded so as not to interfere with other areas of research", such as the cloning of human DNA sequences or cell lines. Animal cloning was not considered to raise the same issues as human cloning -- existing regulations, such as the review by animal protection committees, were viewed as sufficient. The primary reason for the recommended ban had been the risk of harm (physical harm and/or psychological harm) to the child born through NST (Pence 1998 p131). Psychological harm could come through "unrealistic parental expectations" or through being a "delayed genetic twin" (i.e. there would be a loss of individuality; the clone would perceive itself as having only a limited range of options in which to develop into a person) (ref. 51). Since Dolly was the only success out of 277 embryos, the procedure was viewed as too inefficient to be used for cloning humans (Anderson 1997; Sgaramella and Zinder 1998; Cambell et al. 1998). Physical harm could come about through procedural errors such as improper reprogramming of the donor nucleus, which could result in abnormal development (Gurdon and Colman 1999). According to the NBAC, everyone -- scientists, theologians, ethicists -- agreed that the risk of physical harm to the child was sufficient justification to ban human cloning. Other arguments against cloning came from theologians and ethicists. The religious views were found by the NBAC to be "pluralistic in their premises": some theologians argued that "cloning humans would never be morally justified" while others argued "human cloning could be justified under some circumstances" (Shapiro 1998). Ethicists and theologians alike argued that individuality, family integrity and social values would be compromised by human cloning: children would be treated as objects; there would be a loss of autonomy; eugenics could easily become a dominant force in society and would lead to discrimination and racism. The NBAC's and Clinton's views on cloning -- as well as that of many others -- seems to be quite asymmetrical. Clinton told the press on March 4 1997, that "Each human life is unique, born of a miracle that reaches beyond laboratory science. I believe we must respect this profound gift and resist the temptation to replicate ourselves" (Seelve 1997). And later on, after receiving the NBAC report, Clinton mentions "There is nothing inherently immoral or wrong with these new techniques, used for proper purposes" -- "proper purposes" meaning that the cloning of animals is acceptable, as is biomedical research on human genes and cell lines, but not cloning "for the purposes of creating a child" (ref. 4). Clinton's moratorium may even be viewed as overkill -- in the U.S.A, there had already been a ban on federally funded human embryo research, but Clinton said he "just wanted to make sure we keep it that way" (ref. 3). One argument, acknowledged by the NBAC, might be that legislation to ban human cloning would be unconstitutional -- it would violate a right to procreate (Shapiro 1998). George Annas, a health law professor at the Boston University School of Public Health, has suggested that "cloning is replication, not reproduction, and represents a difference in kind, rather than in degree in the manner in which human beings reproduce" (Annas 1998 p56). As such, Annas argued that there is a constitutional right to reproduce, but it does not necessarily follow that there is a right to replicate. Annas indicated that "human reproduction (even replication) is not like reproducing farm animals, or even pets" and he believes that "there are no good reasons to clone humans" (Annas 1998 p62). Annas also draws an analogy between human cloning and international terrorism: cloning a human "would be like moral terrorism" (Kolata 1997b). Clinton, the NBAC, and many others appear to adopt this view: humans are different from animals, and human cloning to create a child must be avoided, although cloning animals seems to be okay! Initially there was a lot of apprehension towards Dolly and her implications for humans when Wilmut and his colleagues made their announcement in February of 1997. The news hit front page headlines immediately. However, just a few months later, cloning by NST was old news (Klugman and Murray 1998 p4, 35) -- any mention of cloning was relegated to the middle sections of newspapers, even when Polly, a transgenic sheep which produced human clotting factors in her milk, was cloned from embryonic cells (Kolata 1997d). Apparently, people got used to the idea: cloning became familiar territory. With the birth of first test tube baby in 1978, there was initial concern (e.g. there was fear of "playing God"), but things calmed down after some time and now it is common practice to use IVF for infertile couples (Pence 1998 p145). The implication of all this is that human cloning may go the way of IVF: it has become a familiar technology and therefore it seems likely that cloning will eventually come into common use! It seems likely -- but interestingly enough, there was a resurgence of fears a short while after the initial concern died off (at least in the press). All the concerns about human cloning were re-ignited in early 1998 by a 69-year old Chicago physicist. On January 7 1998, Richard Seed (who has a PhD. from Harvard) had told the press he intended to clone a human within two years (ref. 9). Seed indicated that he had a team of doctors assembled, as well as four couples who volunteered to be cloned. His plan was to open a cloning clinic to help infertile couples have children, and he expected to clone about 500 people per year. Seed's views were met with strong opposition. Scientists who rejected Seed's plan believed he was incapable of ever accomplishing it. In the press, Seed was referred to as being "crazy", a "mad scientist", a "scientific renegade", and even "the Bad Seed" (refs. 9-12). In response to his critics, Richard Seed has said "They'll never be persuaded...They have rather small minds and a rather small view of the world and a rather small view of God" (ref. 9). Apparently, Seed is also "enormously encouraged in just one day by calls" he receives "from infertile couples who are in tears" (ref. 13). Some people who have worked with Seed believe he will bbelieve he will be successful in cloning humans, "if anyone can make it happen, it will be someone like Richard Seed" (ref. 11). However, in the early 1980s, Seed had tried to open a chain of infertility clinics, but he ultimately failed (Kolata 1998). Some have indicated that Seed's attempt to clone humans is simply a publicity stunt to achieve fame and fortune (ref. 10). President Bill Clinton and Congress representatives vowed they would pass the legislation to ban human cloning in order to stop people like Seed. The FDA also announced that no one would be able to clone a human in the U.S. without their permission. Seed, however, told the press that if human cloning were banned in the U.S., he would move to Tijuana Mexico to complete his work. Seed indicated that he has enough money to start his venture, but will need an additional two million dollars to complete it (ref. 13). At least one group, the Raelian movement, has offered to fund Richard Seed and any other scientist wanting to engage in human cloning research (ref. 14; see the Raelian website at www.rael.org). Clonaid -- affiliated with the Raelian Movement -- is based in the Bahamas and is the first group to offer cloning services to "wealthy individuals" via its website (for more information on Clonaid, see their website at www.clonaid.com. Human cloning is at the very heart of the controversy, however, there remains a disparity between human cloning and animal cloning. Animal cloning, as indicated earlier, appears to be viewed as less of a concern than human cloning: cloning animals, especially farm animals, is seen as for the benefit of mankind. In fact, one of the reasons Wilmut wanted to do cloning was the application to farm animals -- cloning could be used as a form of genetic engineering to develop animals which produce medically important products. Ian Wilmut and his colleagues created a transgenic sheep, Polly, using donor nuclei from transgenic fetal cells (Schnieke et al. 1997). Polly, born in July of 1997, produces a human blood clotting factor (FIX) in her milk. In humans, a deficiency in FIX results in hemophilia B, thus clones of such transgenic animals would be medically important. The success rate of creating transgenic animals using the standard techniques (i.e. injecting DNA into newly fertilized eggs) is low (Pennisi 1998). Cloning would potentially allow for a much more efficient (i.e. faster and more reliable) means of using genetic engineering in animals -- as such, the pharmaceutical companies are jumping at the opportunity to use cloning for making medically useful transgenic animals (ref. 1; Enserink 1998; Pennisi 1998). Cloned animals would also be useful in scientific research: the effects of drugs tested in cloned animals would allow for reduced confounding variables and consequently, for better control in experimentation. Cloning non-human primates, such as rhesus monkeys, are especially important medically, due to their genetic and physiological similarities to humans (Meng et al. 1997; Web 1999; Chan et al. 2000). Xenotransplantation is another possible application of cloning: pigs (which have a very similar physiology to humans) could be engineered using cloning technology so that organ transplants would have less chance of immuno-rejection by patients (Pennisi 1998). There is however, some concern about the possibility of pathogens crossing over into humans from other animals -- the FDA temporarily stopped clinical trials with pig tissues late in 1997, until suitable tests for detecting a retrovirus could be found (Vogel 1998). Other uses of cloning have been proposed, such as saving endangered species or resurrecting extinct ones. Some argue that "cloning will have little if any application" in conservation, as habitat restoration should be the primary concern (Mazurek 1999). However, a group of scientists in China plan to clone the giant panda by 2003. In fact, the researchers have created panda embryos by inserting panda donor nuclei into white rabbit eggs and will possibly use a surrogate species, such as the black bear, for implantation and gestation of the embryos (Mazurek 1999). Cross-species cloning (e.g. using the egg cells of one species and the donor nuclei of another) would be useful in cloning endangered (or extinct) species where egg cells are scarce. However, whether any detrimental effects would result remains to be seen and will depend on how closely related the two species are (Mazurek 1999). A Japanese group of scientists, led by Kazufumi Goto and Akira Iritani, want to go even further -- they want to clone a wolly mammoth (Duke 1999). There are two potential methods that can be used to bring back the wolly mammoth -- both methods require a well preserved mammoth (Duke 1999). One way is to find viable mammoth sperm cells and fuse them to elephant eggs to create an elephant-mammoth hybrid. The hybrid animal would be used to breed a lineage that would become increasingly mammoth-like. Elephant gestation, however, takes about 600 days, thus generating a "pure" mammoth through breeding would take about 30 years. The alternative would be to use cloning technology. The advantage with cloning, is that a mammoth could be created in a single generation; however, intact mammoth DNA would be necessary. Late in 1999, a group of Russians excavated and retrieved a preserved mammoth from Taimyr, Siberia. A documentary of the expedition, Raising the Mammoth, was aired on @Discovery.ca. Tissue samples were taken from the specimen in order to find intact DNA. Previously, only fragments of DNA have been retrieved from other specimens -- even in apparently "pristine samples", the DNA was degraded (Wade 1999). Thus, it seems likely that DNA from the Taimyr mammoth specimen would also be degraded. Even if intact DNA were found, one difficulty in bringing back extinct animals would be a low abundance of genetic diversity. A clonal population, where every individual is genetically identical, could easily go extinct in a single epidemic caused by a lethal pathogen. As such, a reasonable objection against human cloning would be that cloning will ultimately decrease variation in the gene pool, leaving the human population vulnerable to attack by pathogens. A counter argument against this concern would be that sexual reproduction can be used alongside cloning to maintain diversity. In fact, Dolly was mated (twice) to a Welsh mountain ram, giving birth to a lamb in April of 1998, named Bonnie, and again to three lambs in March of 1999, showing that healthy offspring can be obtained from cloned farm animals. In the Plant Kingdom, many of the most successful species can reproduce asexually as well as sexually, and there is abundant phenotypic and genetic variation present in natural clonal populations (Silander 1985). "Sexuality even at low levels provides sufficient genetic variation through recombination to permit evolution. Only complete loss of sexual reproduction represents an evolutionary dead end" (Silander 1985 p140-141). Hughes and Cancino (1985 p155) have indicated that "cloning occurs in two-thirds of the metazoan phyla" -- various animal species may have both clonal and aclonal modes of reproduction and will use either method depending on the environmental conditions (Huges and Cancino 1985 p 175). Even if only cloning is used as a means of reproduction, there are other sources of variation that may be present. George Seidel, Jr. (1983) has indicated that cytoplasmic inheritance, epigenetic phenomena, and the uterine environment all play a role in early development and cause variations in cloned mammals. In fact, Dolly was later found to be a genetic chimera -- Dolly's mitochondrial DNA was derived only from the recipient egg, not from the donor cytoplasm (Evans et al. 1999). It is predicted that human clones created (if ever created) by NST would also be such genetic chimeras, however, there would still be genetic variation in the population by using donor nuclei and egg cells from different individuals. On the other hand, a true genetic clone may be made if the donor nuclei and the recipient egg were used from the same female. As long as sexual reproduction is used along with cloning in population of livestock, endangered species, or even in humans, a lack of genetic diversity should not be of much concern. And yet, many people are concerned that cloning will ruin humanity. This concern seems to arise from such popular and misleading notions as "genetic determinism". Richard Lewontin (1997) has indicated that "the fallacy of genetic determinism is to suppose that the genes 'make' the organism". As mentioned earlier, it is feared that cloning will lead to a "loss of individuality" as if genetic identity is the sole determinant in the development of a person. Even in Aldous Huxley's Brave New World in which cloning technology (i.e. "twinning") is used in a civilization that is segregated into various castes, psychological conditioning plays the predominate role in maintaining those castes. Twins are genetically identical, and may have many physical similarities, but they are separate individuals -- they each have their own unique development; they each have their own mind. As noted earlier, the NBAC concluded that the risk of harm to the child was sufficient justification to ban human cloning. There was also concern as to what would happen to society if human cloning were allowed. So, there are two major implications in regulating cloning: the impact to society as a whole, and the impact on the individual. As noted by Klugman and Murray (1998 p42) the emphasis of the issues on cloning in the past few decades have shifted increasingly towards the individual. If cloning is carried out, what will be the harm to society? The answer remains speculative until human cloning is actually done. As such, what is left is harm to the individual. Psychological harm to the individual would have been just as speculative as harm to society, had there been nothing else to compare cloning to. Many of the objections to cloning are very similar to the objections raised when IVF was first used. Psychological harm to the child was a concern: there was a possibility that the first "test tube baby" would grow up and be damaged mentally by virtue of being a "test tube baby" (e.g. they would be targets of discrimination). Louise Brown, the first test tube baby, grew up to lead a normal healthy life -- as did many other test tube babies (Pence 1998 p152). Thus, with the individual, the only legitimate (and immediately testable) argument against human cloning is the risk of physical harm -- and various governments are banning the very thing that will answer the question. A logical assumption would be that once the technological procedures improve in efficiency, and therefore improves the safety of the technique, cloning may very well come into common use. Harold Varmus, director of NIH, has argued that human cloning to create children will never be widespread, since the technology is too expensive and the number of couples who would want to have children by this method are few in number (Pence 1998 p130). The human population is over six billion: the cloning done by a few hundred thousand people would have little impact, since the rest of the population would be reproducing sexually (Pence 1998 p130). At least at the global scale, cloning would not appear to have any immediately significant effect. Gurdon and Colman (1999) have indicated that therapeutic cloning (versus pregnancy cloning) is likely to be widely used, at least as a medical tool, once the efficiency improves. However, one ethical concern has been the use of human embryos in medical research. When does an embryo become a person? This concern over the potentiality of becoming a person is still debated, and banning the use of human embryos in research directly has an impact on research in cloning. In May of 1999, Roslin Bio-Med (a company set up by the Roslin Institute) was bought by an American company, Geron Corporation, based in California. One of the goals of the joint venture is to determine how nuclear reprogramming occurs in enucleated eggs and then "to confer the same ability on generic, enucleated cells that are not eggs" -- for the ultimate purpose of creating a "generic reprogramming cytoplast" (Wadman 1999). This engineered cytoplast would be used to reprogram somatic cell nuclei instead of eggs, thus removing the ethical concerns associated with using human embryos in cloning research. This particular strategy would be used in therapeutic cloning, however there are some people, such as Norton Zinder, who are skeptical and doubt that it will work (Wadman 1999). Where might cloning be heading in the future? Various governments want to put a stop, at least temporarily, on human cloning. Research, nevertheless, continues on in countries without such bans. On January 19 of 2000, the Roslin Institute received two British patents on their cloning technique covering a wide variety of applications, except in human reproductive cloning (Wadman 2000). Critics have argued that the patents will put Roslin and Geron Corporation in control of future medical advances -- medical research may be inhibited, since some "organizations, including charities may not have the money to pay to use this patent technology" (Wadman 2000). David Earp, vice-president of intellectual property at Geron Corporation, has said that although the patents put his company in a "dominant position" they have "absolutely no intention" of inhibiting medical research (Wadman 2000). So, now there is a question of ownership rights and of control in cloning (Pence 1998 p140). Can the technology itself be owned? So far, in some cases, the answer seems to be yes. Who will control it? As seen earlier, various governments are trying to control the use of the technology through legislation. However, it seems that the inventors of the 'Dolly technique' may try to follow up on applications, which extend into human uses (Wadman 2000). Can a human cloned from using nuclear somatic transfer be owned? If a parent wants to clone him or her-self, is there ownership in this case? And if so, by whom? These questions are currently being debated, but no consensus has been reached (Zaner 1998 p132-133). With people like Richard Seed who apparently want to help infertile couples, and with the on-going research in animal cloning taking place around the world, it seems that at sometime in the near future, someone will clone a human. It will be interesting to see what events unfold in the next few decades.
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