Cloning captured public attention when Scottish scientists startled the world by announcing the birth of a sheep named Dolly that had been cloned by combining the nucleus of an adult mammary cell and an enucleated sheep egg. Interest intensified when Richard Seed, a physicist with no expertise in cloning, no institutional affiliation, and no funding, announced that he would clone humans for a fee. Fear that human-cloning factories might soon appear before anyone had a chance to digest the implications of this new technology sent Congress into action. Legislation was introduced in both the Senate and House of Representatives that would ban human cloning indefinitely or impose a long moratorium on it. Such a moratorium was more or less uncontroversial, given the preliminary nature of the technology required to clone animals and the unknown risks of cloning humans. Unfortunately, the abruptly drafted bills in both the Senate (the Bond-Frist bill) and the House (the Ehlers bill) would go far beyond restricting the cloning of humans.
These bills would put a stop to all cloning experiments that use human cells, in particular research into what is known as somatic-cell nuclear-transfer technology. Never before has Congress passed legislation to halt a single kind of scientific or medical research. Any plan to ban research on cloning human cells is seriously misguided. To make this position clear, it is important to explain the biology of somatic-cell nuclear transfer and then point out how this approach — if it ever becomes feasible — may have unique therapeutic applications. The experiments under discussion involve transferring a human diploid nucleus into a human ovum from which its native nucleus has been removed. The donor nucleus could be taken from a fetal stem cell or an adult somatic cell.
If the nucleus comes from an adult somatic cell, many complex and as yet unproved transformations would have to occur. First, the adult cell nucleus would have to fuse with an enucleated ovum and then de differentiate in its new environment. Second, the new cell would have to be capable of dividing into daughter cells, which would have to be pluripotent stem cells with the capacity to differentiate into specific tissues (such as muscle or skin).
Finally, the genetic makeup of these stem cells or the newly differentiated cells might have to be altered so that the tissues could then be used to treat human diseases. Some of these transformations have already been achieved in laboratory animals. For example, scientists have developed models of human disease by adding, subtracting, or altering genes in embryonic stem cells derived from early mouse embryos and then reincorporating these cells into recipient embryos.
The resulting progeny, generally known as “knockout” animals, are invaluable tools for studying the roles of genes in normal development and in disease. Advances in hypertrophic cardiomyopathy and various cancers are examples of such work Research on somatic-cell nuclear transfer might yield numerous benefits. Studies of stem-cell differentiation could provide valuable information about the mechanism of aging or the causes of cancer. Stem cells derived from this technology might also be a rich source of material for transplantation if specific genes or sets of genes in these pluripotent stem cells could be activated and if, as has been described before, the cells could then be coaxed to differentiate. Such a possibility is not strictly theoretical, because differentiated cell types (vascular endothelium, myocardial and skeletal muscle, hematopoietic precursors, and even neurons) have been obtained by culturing embryonic stem cells from mice. If this technology could be applied to human stem cells, the resulting products might revolutionize medical therapeutics.
The treatment of such diseases as diabetes mellitus, leukemia, and genetic disorders might change dramatically with the availability of genetically altered cell lines that would be immunologically compatible with a given patient and therefore not seen by the immune system as foreign. These are heady goals. Nonetheless, enthusiasm for these therapeutic possibilities must be tempered with a strong dose of reality. Proposed therapeutic applications of somatic-cell nuclear transfer remain largely conjectural, and considerable research will be needed to validate the underlying technology.
For example, the evidence that nuclei from fully differentiated adult cells can be reprogrammed is far from conclusive; it may be impossible to activate certain dormant genes in an adult nucleus. In fact, there is still uncertainty about whether the donor nucleus used in the Dolly experiment was derived from a differentiated adult cell or a stem cell. Also, the rapidity with which the nucleus of a fertilized egg must divide may be too much to ask of a nucleus that has long ceased to divide at all. (These technical obstacles would hinder the production of stem-cell lines customized for individual patients, but adult stem cells might be suitable substitutes for differentiated cells as a source of nuclei. ) There is no information whether differentiation of human pluripotent cells can be controlled in vitro, or whether in this altered state they would be viable once transplanted into a patient.
These fundamental questions and many others must be resolved before we can distinguish fact from speculation. Despite enormous hurdles, future clinical applications of research into human-cell cloning should not be dismissed as science fiction. Because this new direction of investigation is in its infancy, it is impossible to predict where it will lead. Research on somatic-cell nuclear transfer needs nurturing before it can be branded a success or failure.
How the public reacts to this line of research will be critically important. Some opponents argue that it is immoral to carry out experiments on human embryonic cells. The arguments against this technology are analogous in many respects to those against abortion. People of good will line up on both sides of the issue. Is there a way to prevent potential abuses of somatic-cell nuclear-transfer technology without legislating against all of it? Discussions about restricting research were held in the 1970 s, when recombinant DNA technology was introduced.
Rather than legislate against such work, coalitions of scientists in conjunction with representatives of the government and the public drew up stringent self-imposed guidelines and standards to regulate it. Needless to say, this technology has yielded enormous benefits in medicine. Many scientific organizations have announced a voluntary five-year moratorium on the cloning of human beings, but they have argued that research involving the use of somatic-cell nuclear transfer should continue. The Bond-Frist bill in the Senate and the Ehlers bill in the House, which would ban all cloning in human-embryo research, are opposed by dozens of medical organizations, biotechnology companies, and distinguished scientists. I oppose to this restrictive legislation. Perhaps voluntary guidelines with oversight by the Food and Drug Administration would be an acceptable solution.
Scientist believe that a bill modeled after the one introduced recently by Senators Feinstein and Kennedy is a reasonable compromise. That bill would ban the implantation of an embryo developed by the technology into a human uterus for the purpose of creating a child, but it would protect research on somatic-cell nuclear transfer to clone molecules, cells, and tissues. It would also preempt all state laws, and it contains a “sunset” clause that would end the prohibition in 10 years. Research on the cloning of human cells holds the promise of medical benefits, but cloning humans is a far more complex and ethically disturbing issue. Some have argued strenuously that human cloning should be barred permanently. They have called it immoral, repugnant, and abhorrent.
Most European countries have already banned it; one U. S. state has done so, and others are considering a proscription. While allowing fundamental research in the field to progress, a wide debate on human cloning is needed.
What if any, circumstances might warrant cloning, as well as the circumstances under which it should never be allowed. At one extreme, cloning of human cells conjures up images of wasted embryos and deformed babies, of infinite life, master races, and duplicates of famous scientists, athletes, and the rich. At the other extreme, cloning is touted in grandiose fashion as a technology with boundless implications for the treatment of infertility and disease. The truth probably lies somewhere in between. The difficult ethical judgments about how to apply this new technology can be made only with full knowledge of the scientific facts. The burden of educating the public about these facts falls squarely on the shoulders of the scientists themselves, whose commitment to full disclosure may never be more stringently tested..