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Editorials |
1 From the Department of Radiology, Indiana University Medical Center, 702 Barnhill Dr, Room 1053, Indianapolis, IN 46202-5200. Received April 7, 2003; accepted April 17. Address correspondence to the author (e-mail: rbgunder@iupui.edu).
Index terms: Editorials • Radiology and radiologists, socioeconomic issues
As leaders in both the profession of medicine and the community, radiologists need to be well informed about ethical and political issues confronting our society, particularly those growing out of medicine and biomedical science. One such issue, which also happens to be one of the most momentous moral questions ever to emerge from biomedical science, is the issue of cloning (1). Physicians and scientists working in fields such as reproductive biology could be expected to acquire a firm grasp of the techniques and moral questions surrounding cloning simply by dint of their daily experience, just as radiologists could be expected to have a better grasp than most physicians of the biologic effects of ionizing radiation. Cloning, however, is a subject with which most radiologists have little or no direct contact. In this editorial, I aim to enhance radiologists’ understanding of this important issue by reviewing some of the most salient scientific and moral features of cloning. With such information in hand, radiologists can be better equipped to formulate their own judgments on this vital topic.
What Is Cloning?
To begin with, it is important to recognize that cloning is more than a dream in the mind of some scientists. It is a reality. A variety of plant species have already been cloned commercially, and cloning has been performed successfully in many animal species as well (2). It was in 1997 that the first successful clone of a mammal was produced by Dr Ian Wilmut and colleagues in Scotland. Dolly, a sheep, was the first mammal ever born who had no genetic father or mother. Initially, Dolly appeared to be quite healthy, but over time she developed a variety of ailments that might be likened to premature aging, including severe arthritis, and she was euthanized at the age of 6 years, approximately half the normal life span of sheep (3). Since Dolly, at least eight other mammalian species have been cloned (4). As far as we know, no one has successfully cloned a human being, although a number of scientists around the world are said to be at work on this challenge.
Cloning may be divided into three categories, depending on the purposes for which it is performed (5): reproductive cloning, research cloning, and therapeutic cloning. All three use the same basic technique, called somatic cell nuclear transfer. As applied to human beings, somatic cell nuclear transfer would involve replacement of the nucleus of a human egg cell with the nucleus from another somatic cell, which could be one of the egg donor’s cells or a cell from another person. As a result of this switch, the egg cell would now have the genotype of the person who donated the nucleus and would thus be an almost exact genetic copy of that person.
It is sometimes said that the clone would then have the same genotype as his or her "parent." In fact, however, the genetic relationship between the donor and the recipient would be much closer to that of two identical twins than that of parent and child. In the latter case (parent and child), the degree of genetic overlap is approximately 0.5. That is, embryos produced through sexual reproduction share about half their genes with each of their parents. Human clones, by contrast, would share virtually all of their genes with the nuclear donor, a degree of genetic overlap approaching 1.0. Clones also differ from monozygotic, or identical, twins—although the degree of genetic overlap in both cases approaches 1.0—because the nuclear donor and cloned recipient would have been born and raised years or even decades or more apart. The term "parent" should not be used with respect to cloning, because cloning represents a form of asexual reproduction. Biologically speaking, the clone has no mother or father (6).
By using the technique of somatic cell nuclear transfer, reproductive cloning is undertaken with the intent of producing a genetic copy of a human being. Numerous individuals, some with substantial financial resources, have already expressed interest in cloning their aging or deceased pets. As regards cloning of humans, great political leaders, scientists, poets, and athletes might top the list of public figures that people might choose to clone. Others might prefer to produce clones for personal reasons, such as to replace a lost loved one. Of course, cloning cannot produce an exact copy of another person. For example, the clone’s fingerprints would be different from the donor’s. More important, a person’s identity, including his or her knowledge, experience, skills, and personality, is powerfully influenced by the environment in which the person grows and develops, and this would be impossible to reproduce perfectly. There is no guarantee that Albert Einstein’s clone would be a great scientist or that Michael Jordan’s would be a great basketball player.
Research cloning uses the technique of somatic cell nuclear transfer to produce clones that will be sacrificed at an early age to advance scientific knowledge. Clones are produced and allowed to develop to the blastocyst stage, approximately 5 days after nuclear implantation. At this point, the stem cells of the blastocyst are harvested and the organism develops no further. Once harvested, these stem cells can be used for scientific research. At the blastocyst stage, the cloned organism has not yet developed the distinct organ systems that will appear within the next few weeks. Because the blastocyst is never allowed to implant in the uterus, no pregnancy results.
Therapeutic cloning is similar to research cloning in that it uses somatic cell nuclear transfer and the development of the clone is terminated at the blastocyst stage. In therapeutic cloning, however, the harvested stem cells are used for therapeutic purposes. For example, stem cells capable of differentiating into neurons and producing neurotransmitters could be harvested from a clone and transplanted into the brain of a patient with a disorder such as Parkinson disease, in which there is loss of dopamine-producing neurons. In this situation, the donor would generally be the patient, thus reducing the probability that the transplanted cells would be rejected by the patient’s immune system. To obtain larger quantities of tissue or even whole organs, it is conceivable that clones might someday be allowed to develop beyond the blastocyst stage.
Arguments for Cloning
Numerous arguments have been advanced in favor of reproductive cloning (7). People who are incapable of conceiving a child naturally or by means of fertility treatments such as in vitro fertilization would be able to have children. People mourning the loss of a loved one would be comforted by the prospect of a reunion. When people of special value to society are lost, attempts could be made to replace them with clones. Also, extra copies of especially valuable people could be produced.
Proponents of reproductive cloning must guard against a naive biologic determinism that overlooks the large effect of environmental factors on the development of humans. Just because two people share the same genotype, we should not assume that they will be the same person. Identical twins reared in the same household at the same time differ in many respects, as would clones who would likely be reared in circumstances very different from those of their donors. Most commentators have found the prospect of producing clones of living or deceased people eerie or even ghoulish, and few have advanced arguments in favor of reproductive cloning.
By contrast, there are many proponents of research cloning. The arguments in favor of research cloning hinge on the ability to elucidate fundamental processes of developmental biology by using this technique. For example, the ability to make multiple genetic copies of human cells would illuminate how cells become specialized by differentiating into neurons, connective tissue cells, myocytes, and so on. Moreover, cloned cells could be used to study the cellular substrates of aging, shedding light on why even healthy cells eventually become senescent, lose their ability to reproduce, and die. Such research might eventually make possible extension of the human life span. Clones could also permit better understanding of birth defects. Finally, cloning could contribute to better understanding of carcinogenesis. While research cloning is ultimately grounded in the hope for better preventive and therapeutic interventions, it is not considered therapeutic at this stage because the intent of each cloning procedure is to advance scientific knowledge and not to treat any particular patient.
In therapeutic cloning, by contrast, the intent is to help a particular patient with a particular disease or injury. The principal lure of therapeutic cloning is the ability to provide a source of nonimmunogenic transplantable cells, which might be useful in treating patients with problems ranging from spinal cord injuries to malignancies to neurodegenerative conditions. When cells are of the same genotype as the patient into whom they are transplanted, there is little risk of rejection by the immune system, which thus decreases the need for potentially toxic immunosuppressive therapy and increases the overall rate of transplantation success. For example, cells could be produced for skin grafting in burn patients, for bone marrow transplantation in leukemia patients, and for neuron transplantation in patients with disorders such as Alzheimer disease and Parkinson disease. Moreover, improved gene therapy techniques could be developed with genetically corrected cloned cells.
Another argument for nonreproductive cloning is the fact that it is legal in other parts of the world. If the United States does not permit such work to go forward within its borders, then such work will simply flourish elsewhere. Among the undesirable consequences would be a "brain drain" of some of the nation’s best biomedical scientists, who would migrate to other countries to continue their research. Furthermore, the United States would be placed at a competitive disadvantage because other nations would quickly gain the upper hand in exploiting the economic and strategic potential of such new technologies. From the point of view of world leadership and the promotion of its principles and values, the United States cannot afford to sit idly by while other nations develop cloning. Proponents also argue that nonreproductive cloning does little harm to identifiable persons and that the potential benefits in terms of human health would far outweigh any moral risk.
Arguments against Cloning
The arguments against reproductive cloning begin with a refutation of the naive biologic determinism that supposes that cloning would enable us to produce exact copies of any person (8). Critics of reproductive cloning also argue that it denies an important scientific and moral truth: namely, that each human being is unique and irreplaceable. Critics have also argued that reproductive cloning would place an unreasonable psychologic burden on the clone, who would grow up feeling that he or she must live up to the model of dear old "mom" or "dad." People who knew that they had been brought into being to replace or mimic someone else might believe that their own individuality and capacity for self-direction were being suppressed. Critics have also argued that such clones might be labeled second-class citizens due to an accident of birth over which they had no control, thus fostering a new form of bigotry. In general, even proponents of cloning have found the arguments against reproductive cloning morally persuasive, and few have taken the position that we should move forward with reproductive cloning.
Research cloning and therapeutic cloning, by contrast, have many champions, both within and outside the scientific community. Opponents of these forms of cloning have argued against them on several fronts. First, many are disturbed by the fact that it involves the creation of human life with the express intent to terminate it, albeit at a very early stage of development. Some opponents point to the fact that every person who has ever lived was once a 5-day-old blastocyst and argue that it is wrong to create such creatures in order to destroy them. Proponents of research cloning respond that such blastocysts lack differentiated nervous systems and thus do not, as far as we know, suffer or even experience life in any conscious way. Moreover, proponents of research cloning point out that many human pregnancies end spontaneously at an early stage and that some forms of birth control (eg, some intrauterine devices) work by preventing implantation of the blastocyst. To ban research cloning and therapeutic cloning might also jeopardize some forms of infertility treatment and certain reproductive rights, such as elective pregnancy termination (abortion) (9). In response to such rejoinders, opponents of nonreproductive cloning respond that the mere fact that some blastocysts do not survive is not grounds for deliberately killing them.
Another argument advanced against nonreproductive cloning cites the existence of alternative means of achieving many of the same objectives. For example, cloning is not the sole source of totipotent or pluripotent stem cells. (Totipotent stem cells are capable of differentiating into any cell type, while pluripotent stems cells are capable of differentiating into several different cell types.) Even mature adult cells can be "deprogrammed" to serve as stem cells. Examples include some of the cells that make up the placenta, as well as mundane other cells such as those that make up the adipose tissue that many of us carry around our waistline. With so many substitutes available, opponents of nonreproductive cloning argue, why proceed with a technology that is deeply offensive to a large number of people who believe that the intentional destruction of innocent human life is always wrong, no matter what the putative benefits?
Opponents also point out that cloning technology as it currently exists is highly unreliable and hazardous, at least to the clones. In the case of mammalian cloning attempts, the majority of such experiments fail to produce a viable cell. For example, Dolly was the only viable sheep to emerge from 277 cloning attempts (3). Moreover, many of the cells that do go on to divide and develop produce organisms that harbor severe deformities of one kind or another, many resulting in premature death further down the line. Opponents of reproductive cloning also point to Dolly’s fate as an indicator that clones of adults will have a shorter life span and experience premature ravages of aging. Some opponents of cloning have gone on to argue that attempts to improve the technology of cloning are unethical because they would require the sacrifice of too many lives (10).
Another class of arguments against cloning holds that cloning amounts to "playing God" and that human beings have no business meddling in such an arena. Opponents argue that we do not possess sufficient wisdom to determine which sorts of humans we should be creating and that setting ourselves up as creators represents the height of moral folly. Along these same lines, opponents have also argued that cloning turns reproduction into manufacture, necessarily dehumanizing both the clones and the people involved in their production. They argue that reproduction should remain a personal activity between a mother and father and never become an industrial process. Moreover, they find the very idea of "special ordering" a "designer" human being morally repugnant, because it would turn human offspring into artifacts. They envision a bleak future for any society that develops a market in human beings, which they compare to the slave-trading societies of centuries past. They categorically deny that any human being can be reduced to the moral equivalent of a fungible commodity whose value can be determined in dollars and cents.
Conclusion
As this brief rendition of some of the ethical arguments for and against cloning makes clear, there are strongly held convictions on both sides. Because this debate involves some of the most fundamental questions imaginable—about what it means to be human and the uses to which our science and technology should be put in the service of humanity—it is an important discussion about which every physician and scientist should be informed and in which every physician and scientist should be prepared to participate. In the course of thinking it through, we stand to gain a clearer understanding not only of what cloning is and whether we support or oppose it but also of ourselves and what we most care about in life, both as individuals and communities. The questions are complex, but reflection on them and discussion with others have the potential to make us more thoughtful physicians, citizens, and human beings.
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