Uses and Ethics of Cloning

▪ 1998

by Ian Wilmut

      The announcement in February 1997 of the birth of Dolly the sheep, the first clone of an adult mammal, attracted international attention because of the new medical and agricultural opportunities and the new ethical concerns raised by the breakthrough. The term cloning (derived from the Greek word klon, meaning "twig") strictly indicates the taking of a cutting, as in plant breeding, but it has also come to be used to describe the production, by means of a process known as nuclear transfer, of genetically identical animals. Nuclear transfer involves removing the chromosomes from an unfertilized egg and replacing them with a nucleus from a donor cell. As it is the transferred nucleus that determines almost all of the characteristics of the resulting offspring, a clone will resemble its "parent," the animal from which the donor cell was taken.

      While the most obvious use of cloning is to produce groups of animals that are genetically identical, nuclear transfer also may be used for the introduction of precise genetic changes in mammals. Although other methods have been employed to add genes to mammals, nuclear transfer makes it possible for the first time to change any function of existing genes. Another application of cloning technology is the production of undifferentiated (embryonic) cells, which could be helpful in treating certain diseases. Before there can be significant use of these applications, however, some practical difficulties must be resolved, as only a small proportion of the embryos thus far produced by nuclear transfer have become live offspring. Ethical choices must also be made. The public response to cloning suggests that countries differ widely in their perceptions of this new technology. Immediately after the announcement of Dolly's birth, for example, Italy banned the cloning of any mammal, whereas a number of groups in the U.S. welcomed the technique.

      All of the different tissues of an adult animal or person are derived from the single cell of a fertilized egg. In the early stages of development, the dividing embryonic cells are able to contribute to all of the tissues of the developing embryo before the cells differentiate, progressively, as a result of changes in gene expression. The birth of Dolly by means of an already differentiated adult cell for nuclear transfer showed that the process of differentiation is reversible, at least in some cases. This raises the revolutionary thought that it may be possible to take cells from a human patient and cause them to dedifferentiate to a state in which they are able to contribute to all tissues. If necessary, a genetic change could be made in the cells before they are stimulated to differentiate to the type required for treating a specific disease before return to the patient. Since the cells are identical to the patient, no immune response is expected. This approach has been suggested for the treatment of such varied conditions as AIDS, Duchenne muscular dystrophy, and Parkinson's disease.

      At present the only way to induce dedifferentiation is to form an embryo from the donor cell and to culture the embryo to the stage when it has a few hundred cells but has not begun to differentiate. As the nervous system would not have begun to develop at that stage, the embryo would have no means of feeling pain or sensing the environment. At this point the cells would be separated and grown in culture. Some people object strongly to this procedure on religious grounds, holding that the embryo has a soul at the moment of conception. As the embryo would have the potential to become a person, they find it deeply disturbing to consider using cells from that embryo for any purpose that would deprive that person of life. An alternative view is that it is justifiable to use the cells since the developing embryo does not become a sentient being until much later in development. Whatever the ethical views, it would be much more practical to develop such cell-based therapies if dedifferentiation could be induced without the production of embryos. Research in 1997 was beginning to assess this possibility.

      Although the use of cloning to produce copies of humans has been suggested, many people would judge this to be morally wrong. In addition, the prospect of cloning humans raises false expectations, since human personality is only partly determined by genes. Cloning a sick or dying relative would provide a genetically identical copy of that person, but this new individual would likely develop a quite different personality. Similarly, a copy of an athlete, movie star, entrepreneur, or scientist might well choose another career because of chance events during his or her lifetime. One hypothetical scenario involves an infertile couple who wish to make a copy of one or the other partner rather than having a child by artificial insemination. The social concern is that the parents would not be able to treat naturally a child who was a copy of one of them.

      The impetus behind the research that led to Dolly was not to find a way to clone humans but rather to develop genetically engineered animals that would serve a variety of purposes. As there are great genetic differences in cattle herds and sheep flocks, breeding copies of selected livestock would increase the efficiency of agricultural productivity and help boost the quality of such commercial products as milk, beef, and wool. As in the management of other breeding schemes, it will be important for scientists to maintain the balance between intense selection of livestock and the maintenance of genetic variability. Preservation of frozen cells from a large number of representatives of different breeds would allow nuclei from those donor cells to be used as required. The ethical issues in animal cloning are perhaps less controversial than with humans; nevertheless, some people worry that producing large numbers of animal clones only increases the likelihood that these animals will be mistreated.

      Genetic modification of livestock will also provide new opportunities in medicine and research. Today many patients in need of transplants die before organs become available from suitable donors. Cloning pigs has been suggested as a means of rapidly achieving xenotransplantation, the use of animal organs to replace organs in human patients. Organs transplanted between species are in danger of being destroyed within minutes by the acute immune response of the body receiving the transplant; however, strategies are being developed to modify pigs genetically so that rejection by the immune system may be effectively prevented.

      Another potential medical application of cloning involves cystic fibrosis research. A common hereditary disease of humans caused by errors in a single gene, cystic fibrosis is characterized by difficulty in breathing due to the accumulation of mucus in the lungs. At present new treatments for cystic fibrosis are assessed by being administered either to human patients or to mice bred with the disease. There is, of course, a limit to the risks that may be taken with human patients, and there are significant differences between the respiratory systems of mice and humans. Cloning sheep bred with cystic fibrosis would provide an inexhaustible supply of animals on which to experiment and would overcome the disadvantages of experimenting on humans and mice.

      There have been a variety of responses to these proposals. To some people it is ethically unacceptable to alter a species genetically, but those advancing this view must acknowledge that conventional genetic selection has already brought about profound changes in livestock and pet animals. While many people welcome the availability of organs from animals, others are disturbed at the suggestion of deliberately making animals ill, and some would prohibit such a practice whatever the benefit. Provided that a judgment is made that the advance in medical treatment justifies the distress caused to the animal, most societies accept the benefits from studies involving animal experimentation. In most countries legislation permits such research only under strict supervision.

      Experience shows that predictions as to the value and uses of new techniques are often wrong and that society changes its assessment of a new procedure over time. Many religious leaders were initially scandalized by the introduction of methods for the artificial insemination of cattle, a procedure that helped eliminate sexually transmitted diseases and provided the single biggest advance in livestock breeding. Great concern was raised at the time of the birth of Louise Brown, the first baby to be produced after in vitro fertilization. Since then thousands of babies have been born to previously infertile couples, and the technique of artificial insemination is widely accepted. It remains to be seen how methods of cloning will be used and how they will be accepted.

Ian Wilmut, leader of the research team that produced the first clone of an adult mammal, is an embryologist at the Roslin Institute, near Edinburgh.

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