CHAPTER SIX

ETHICAL AND MORAL ISSUES

Since the 1990s, cloning has been, by far, the most controversial issue in bioethics. The cloning of Dolly conjured up in the public imagination alarming visions of armies of identical human clones, and many legislatures hastened to prohibit the reproductive cloning of human beings. But the public’s reaction resulted more from ignorance and distaste than reflection, which the popular news media did little to encourage. Some bioethicists suggested that in a free society there are no good reasons—apart from the risk that a cloned human may suffer from genetic abnormalities—for cloning to be prohibited. Others viewed cloning as a violation of human dignity, because it would mean that human beings could be designed by other humans. That objection was forcefully stated by bioethicist Leon Kass, who appealed to what he called, in the title of a 1997 essay, The Wisdom of Repugnance.

The culmination of such advances in techniques for influencing human reproduction is the mastery of genetic engineering. By the late 20th century, some couples in the United States paid substantial sums for eggs from women with outstanding test scores at elite colleges. (Payment for eggs or sperm was illegal in most other countries.) In the 21st century, prenatal testing for genetic defects has become common and widespread, especially in older pregnant women. When a defect is discovered, couples may seek the assistance of a genetic counselor, who can help them make informed decisions. In some cases, women may choose to terminate their pregnancy. But in many other instances, information from prenatal testing is used to help expecting parents prepare for the birth of a child affected by a genetic defect.

Owing to advances in techniques used in vitro fertilization (IVF), some genetic tests can be performed on embryos in vitro—before they are implanted into the mother’s uterus. As more genetic tests become available, people increasingly will face the question posed by the title of Jonathan Glover’s probing book What Sort of People Should There Be? (1984). The question addresses one of the most challenging issues for ethics in the 21st century.

REPRODUCTIVE CLONING OF HUMANS

Human reproductive cloning remains universally condemned, primarily for the psychological, social, and physiological risks associated with cloning. A cloned embryo intended for implantation into a womb requires thorough molecular testing to fully determine whether it is healthy and whether the cloning process is complete. In addition, as demonstrated by 100 failed attempts to generate a cloned macaque in 2007, a viable pregnancy is not guaranteed. Because the risks associated with reproductive cloning in humans introduce a very high likelihood of loss of life, the process is considered unethical.

There are other philosophical issues that also have been raised concerning the nature of reproduction and human identity that reproductive cloning might violate. Concerns about eugenics, the once popular notion that the human species could be improved through the selection of individuals possessing desired traits, also have surfaced, since cloning could be used to breed “better” humans, thus violating principles of human dignity, freedom, and equality.

The decision to clone humans, even for the “betterment” of the species, raises the issues of who would be the ideal candidates for cloning and what characteristics should be duplicated. Among some of the issues debated are whether extreme intelligence or great athleticism, creativity or stability, or health or sensitivity should be more valued. Even thornier are the issues of who would be the people to decide what traits are valuable and which people are chosen to be cloned, if the cloning of humans were to become possible and accepted.

In one sense it would be nearly impossible to produce true duplicates of people. Clones are copies of genetic information. The process of cloning cannot reproduce the same sequence of experiences in the clone that the original lived through. Most genes provide potential, but experience and environment determine if and to what degree that potential is realized. Identical twins, for example, even those raised in the same household, often have different personalities, interests, attitudes, and other traits. If Albert Einstein were cloned, there would be no guarantee that his clone would excel in math or physics. American basketball player Michael Jordan received extraordinary support from his parents, and so a clone of Jordan, lacking that support, might turn out to be a poor basketball player. Such a clone also could develop a serious illness early in life and be left with poor vision or reflexes. Achieving a specific set of results from a human clone, then, would not be as simple as, say, providing a clone of a prize dairy cow with the nutrition and conditions that would help her achieve her full potential at producing milk. In addition, it must be pointed out that genes can mutate, or suddenly change, as a result of exposure to normal background radiation or certain chemicals or other influences. (Most mutations are lethal, but some are not.) Genes occasionally mutate in both clones and nonclones. If a gene mutated early in the embryonic life of a clone, the clone would no longer be a clone because it would not be a duplicate of the ancestor. Some mutations could considerably change the potential of the clone, perhaps even contribute to an untimely death.

images

A poster that reads “Evolution Is Dead” is displayed at a news conference that is attended by human rights advocates and scientists in 2002. Some attendees urged an international ban on human cloning.

THE USES AND ETHICS OF CLONING, BY IAN WILMUT (1997)

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 nucleus from an unfertilized egg and replacing it 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 disease.

[In 1997], the only way to induce dedifferentiation [was] 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. [Editor’s note: In 2006 Japanese scientist Shinya Yamanaka succeeded in doing just that. By introducing certain genes into the nucleus of an adult cell, he was able to revert the cell to a pluripotent state. Those cells became known as induced-pluripotent stem (iPS) cells.]

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. [In 1997] new treatments for cystic fibrosis [were] 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 at the Roslin Institute, near Edinburgh

If society allows the cloning of people, society and individuals will have to cope with the consequences. For example, some clones of law-abiding, virtuous people could develop into criminals or develop vices the originals never had or were able to control. Also, a seemingly perfect clone might carry a gene that causes a deadly disease early in life under some condition the clone is exposed to but which the ancestor never confronted.

Another issue of concern is the effect that a large population of clones—human or otherwise—would have on an organism’s susceptibility to disease and other threats and even on evolution. One advantage to having a wide array of genetic variations within a species is that when a change in the environment arises—such as when a new disease emerges—some individuals may have a gene or genes that allow them to survive the new challenge. Such a gene or genes, though previously not particularly or at all useful and not likely to have been selected for duplication in cloning, might save the species from extinction. Such matters are the basis for much evolution. Swifter and more cunning foxes, for example, catch more rabbits, and therefore are more likely to survive and produce offspring with traits for swiftness and cunning. The fastest rabbits are the most likely to escape and survive and thus the most likely to produce offspring with traits for speed. Thus, the genes that determine all the things that go into improving the speed of those animals are constantly being selected for by nature. If only one rabbit were cloned—even the fastest—and only the rabbit clones existed, sooner or later the foxes, with their greater genetic diversity, would adapt, becoming fast or cunning enough to catch them all.

Without genetic diversity, no species can evolve very well. It may be that even a pure clone population could to some extent adapt to changing conditions. However, it is likely that the speed and the boundaries of such adaptation would be so severely restricted that the rate of environmental change would outpace the clonal population’s ability to adapt, forcing its extinction. It appears very likely, then, that there are no species so perfect or so safe, in an evolutionary sense, that their genetic diversity should be eliminated by replacing diverse individuals with clones.

THE USE OF HUMAN EMBRYOS FOR STEM CELL RESEARCH

As with reproductive cloning, therapeutic cloning also is not without controversy. Of central concern has been the use of human embryos for the generation of ESCs. Some individuals and groups have an objection to the use of human embryos for therapeutic cloning, because the destruction of the embryo is equated with the destruction of a human life, even though that life has not developed past the embryonic stage. Those who are opposed to therapeutic cloning believe that the technique supports and encourages acceptance of the idea that human life can be created and expended for any purpose. However, those who support therapeutic cloning believe that there is a moral imperative to heal the sick and to seek greater scientific knowledge. Many supporters believe that therapeutic and research cloning should be not only allowed but also publicly funded, similar to other types of disease and therapeutics research. Most supporters also argue that the embryo demands special moral consideration, requiring regulation and oversight by funding agencies. In addition, it is important to many philosophers and policy makers that women and couples not be exploited for the purpose of obtaining their embryos or eggs.

There are laws and international conventions that attempt to uphold certain ethical principles and regulations concerning cloning. In 2005 the United Nations passed a nonbinding Declaration on Human Cloning that called upon member states “to adopt all measures necessary to prohibit all forms of human cloning inasmuch as they are incompatible with human dignity and the protection of human life.” The declaration did not provide leeway for member countries to pursue therapeutic cloning. The United Kingdom, through its Human Fertilisation and Embryology Authority, issues licenses for creating human ESCs through nuclear transfer. The licenses ensure that human embryos are cloned for legitimate therapeutic and research purposes aimed at obtaining scientific knowledge about disease and human development. The licenses require the destruction of embryos by the 14th day of development, since that is when embryos begin to develop the primitive streak, the first indicator of an organism’s nervous system.

images

An environmental activist in South Korea protests against a medical team that cloned human cells to create transplant organs. In 2005 the United Nations General Assembly declared an international ban on human cloning, including therapeutic cloning.

The regulation of stem cell research in Europe varied by country. In Austria, for example, research on embryos was banned, but research that made use of imported human ESC lines was permitted. In countries such as Bulgaria and Greece, it was legal to use embryos left over from IVF for the derivation of ESCs. Some countries had outright bans on reproductive cloning but allowed research on ESCs. Still other countries had no specific legislation in place that addressed stem cell research or reproductive cloning. In the United States, the federal government has not passed any laws regarding human cloning, due to disagreement about whether to ban all cloning or to ban only reproductive cloning.

In 1995 the Dickey-Wicker amendment was attached to U.S. appropriations bills. It prevented the use of federal dollars to fund the harm or destruction of human embryos for research. It is presumed that nuclear transfer and any other form of cloning is subject to that restriction. The Dickey-Wicker amendment remains the primary legal barrier to performing research on human ESCs in the United States.

In 2001 U.S. President George W. Bush stated that he would allow federal support of research using ESCs, but only on cell lines that already existed and had been derived from leftover embryos grown in infertility clinics. That restriction, according to Bush, would permit research “without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of human embryos that have at least the potential for life.” Many research scientists considered the decision severely limiting, and in September of that year, a committee of the Institute of Medicine (IOM), a branch of the U.S. National Research Council, issued a report concluding that new cell lines would still be needed down the road, in part because the existing lines would likely accumulate harmful genetic mutations over time.

In November 2001, a private Massachusetts biotechnology firm, Advanced Cell Technology, provoked fury when it announced that it had taken the first steps toward cloning human embryos. According to the company, the goal was not to clone a human being but to produce stem cells for treating disease. In fact, most of the embryos died before reaching even an eight-cell stage, without producing the desired stem cells. President Bush, religious and political leaders, and many scientists condemned the work as immoral and a dangerous move in the wrong direction.

In 2009, under President Barack Obama, restrictions on federally funded stem cell research were relaxed. With Executive Order 13505, Removing Barriers to Responsible Scientific Research Involving Human Stem Cells, Obama introduced new guidelines on ESC research. The guidelines allowed for federally supported research with human stem cells, including human ESCs, so long as the work was deemed scientifically worthy and within the bounds permitted by law, namely the Dickey-Wicker amendment. Specifically, the guidelines permitted the government to fund research that used ESCs derived from human embryos that had been generated for reproductive purposes with in vitro fertilization but were no longer needed. The embryos could be used only with the informed consent of the donor.

images

President Barack Obama congratulates Representative Jim Langevin of Rhode Island, the first quadriplegic to serve in the U.S. House of Representatives, after Obama signed an Executive Order to reverse the federal government’s ban on funding stem-cell research in 2009.

ETHICAL AND SOCIAL ISSUES: GMOS, DE-EXTINCTION, AND GENE THERAPY

SOCIOPOLITICAL RELEVANCE OF GMOS

While GMOs offer many potential benefits to society, the potential risks associated with them have fueled controversy, especially in the food industry. Many skeptics warn about the dangers that GM crops may pose to human health. For example, genetic manipulation may potentially alter the allergenic properties of crops. However, the more-established risk involves the potential spread of engineered crop genes to native flora and the possible evolution of insecticide-resistant “superbugs.” In 1998 the European Union (EU) addressed such concerns by implementing strict GMO labeling laws and a moratorium on the growth and import of GM crops. In addition, the stance of the EU on GM crops has led to trade disputes with the United States, which, by comparison, has accepted GM foods openly. Other countries, such as Canada, China, Argentina, and Australia, also have open policies on GM foods, but some African states have rejected international food aid containing GM crops.

The use of GMOs in medicine and research has produced a debate that is more philosophical in nature. For example, while researchers in genetics believe they are working to cure disease and ameliorate suffering, many people worry that current genetic approaches to therapy may one day be applied to produce “designer” children or to lengthen the natural human life span. Similar to many other technologies, the production and application of GMOs can be used to address and resolve complicated scientific, medical, and environmental issues, but they must be used wisely.

ETHICAL CONSIDERATIONS OF DE-EXTINCTION

Cloning, stem cell manipulation, genome reconstruction, and genome editing are powerful technologies with significant ethical ramifications when applied to de-extinction. The expense and inefficiency of SCNT, for example, has raised questions about its practicality for resurrecting extinct species.

Perhaps the greatest concern, however, is the potential of those technologies, as well as back breeding, to alter the course of natural history. De-extinction provides an opportunity for humans to rectify past harms inflicted on other species, as well as to expand species diversity. But many extinct species were driven out of existence as a result of habitat loss, and others lived in habitats that have since been altered dramatically. In addition, in the near term, resurrected species would be considered endangered and would therefore require conservation, for which resources often are constrained or lacking. De-extinction, by providing the option to bring species back later, also could have the unintended consequence of condoning extinction and could give impetus to endeavours that threaten biodiversity.

images

A scientist displays a cross-section of a mammoth’s thighbone at the Sakha Republic’s mammoth museum in 2011. Japanese and Russian scientists stated that discovering well-preserved bone marrow in permafrost soil in Siberia might increase the chance of cloning the extinct animal.

Other concerns include unknowns about the fate of resurrected animals, from the health of cloned individuals to whether the animals would be able to adapt to current environmental conditions and whether they would be able to produce viable offspring. The classification of species revived through back breeding, cloning, or genetic reconstruction, all of which could involve divergence from an extinct species’ original genetic constitution, also remains uncertain. The potential to be leveraged as a means of advancing financial and commercial interests has led some to question the motivation of researchers and companies behind certain de-extinction projects.

Nonetheless, de-extinction has helped fuel important progress in science, building particularly on knowledge in developmental biology and genetics. It also has generated interest in endangered species, with many of the tools of de-extinction also being applicable to the conservation of endangered species. The reconstruction of extinct genes could be used, for example, to restore genetic diversity in threatened species or subspecies.

CONCERNS RELATED TO THERAPEUTIC CLONING FOR GENE THERAPY

Therapeutic cloning for gene therapy has likewise raised ethical concerns, most of which centre around gene therapy as a form of genetic manipulation. The correction of genetic defects is seen by some as a means of redesigning the human genome. Of special concern has been germline gene therapy, which if carried out successfully would allow for the correction of genetic mutations that could be passed on offspring. For those who receive such therapy, the gene corrections most likely would be seen as beneficial. Some people have also raised concerns about the possibility for inadvertent effects on the germline from gene therapy intended for only somatic cells.