Advanced Cell Technology assembled a board of outside ethicists to weigh the moral implications of therapeutic cloning research, which aims to generate replacement tissues to treat a range of diseases. Here are the five major questions the board considered before the company went forward with cloning the first human embryo.

What is the moral status of the organisms created by cloning?

If a cloned organism were implanted into a womb, as was done in the case of Dolly the sheep, it could possibly go on to full development and birth. Because of this potential, some would argue that the organism produced in human therapeutic cloning experiments is the equivalent of any ordinary human embryo and merits the same degree of respect and protection.

Most members of our advisory board did not agree. We pointed out that, unlike an embryo, a cloned organism is not the result of fertilization of an egg by a sperm. It is a new type of biological entity never before seen in nature. Although it possesses some potential for developing into a full human being, this capacity is very limited. At the blastocyst stage, when the organism is typically disaggregated to create an embryonic stem cell line, it is a ball of cells no bigger than the period at the end of this sentence. (Embryos normally do not attach to the wall of the uterus and begin development until after the blastocyst stage.) It has no organs, it cannot possibly think or feel, and it has none of the attributes thought of as human. Although board members understood that some people would liken this organism to an embryo, we preferred the term "activated egg," and we concluded that its characteristics did not preclude its use in work that might save the lives of children and adults.

Is it permissible to create such a developing human entity only to destroy it??

Those who believe that human life begins at conceptionand who also regard activated eggs as morally equivalent to human embryoscannot ethically approve therapeutic cloning research. For them, such research is equivalent to killing a living child in order to harvest its organs for the benefit of others. Some of those who think this way, however, might nonetheless find acceptable research on human stem cells derived from embryos left over from in vitro fertilization (IVF) procedures. They reason, rightly or wrongly, that these embryos are certain to be destroyed and that at least some good might result from using the cells. But therapeutic cloning remains totally unacceptable to such people because it involves the deliberate creation of what they deem to be a human being in order to destroy it.

Many who do not accord moral status to the entities produced by therapeutic cloning disagree with that view. Like our board members, they argue that the benefits of this research and the possible therapies it could produce far outweigh the claims of the activated eggs. Remarkably, some who share this moral view nonetheless oppose the research on symbolic grounds. They maintain that it is unseemly to create human life in any form only to destroy it. They worry that it might start society down a slippery slope that could lead to the scavenging of organs from adults without their consent.

These symbolic and "slippery slope" arguments often have powerful emotional force, but they are hard to assess. Is it really true that using activated eggs for lifesaving therapies will lead to these imagined abuses? On the contrary, if medical science can increase peoples chances of healthy survival, might not this research even enhance respect for human life? Members of the board took note of the fact that the U.K., until very recently, has legally permitted the deliberate creation and destruction of human embryos in research since the early 1990s [see Cloning and the Law]. There has been no apparent ill effect of this permission on British society. In the end, the symbolic and slippery slope arguments did not persuade board members that therapeutic cloning research should not go forward.

Is it right to seek human eggs for scientific research?

The need to obtain a supply of human eggs leads to one of the most sensitive ethical issues cloning research. In each of her monthly cycles, a woman usually produces only one or two mature eggs. To increase that to a number that can be used in research, she must be given stimulatory medications such as those used in reproductive IVF procedures. In rare cases, these drugs can provoke a so-called hyperstimulation syndrome that can lead to liver damage, kidney failure or stroke. According to some studies, ovulation-stimulating drugs have also been associated with a heightened risk for ovarian cancer. The surgery to retrieve the eggs also carries risks, such as the dangers of general anesthesia and bleeding. Is it ethical to subject a woman to these risks for research purposes? If women are offered payment to undergo these risks, might that cause human reproductive material to become viewed as a commodity that can be commercialized? We do not permit the sale of human organs or babies. Are eggs any different?

In responding to these concerns, members of the board took note of two facts. First, a substantial market in human eggs for reproductive purposes already exists. Young women are being paid substantial sums to provide eggs that can help single women or couples have children. If women can undergo risks for this purpose, we asked, why should they not be allowed to undertake the same risks to further medical research that could save human lives? And if they can be paid for the time and discomfort that egg donation for reproductive purposes involves, why cant they receive reasonable payment for ovulation induction for research purposes?

Second, we noted that research volunteers often accept significant risks to advance medical knowledge. If a person can agree to undergo a dangerous malaria vaccine study to help cure disease, why should they be prevented from donating eggs for similar lifesaving research?

In the end, we concluded that it would be unduly paternalistic to prohibit women from donating eggs for this research. At the same time, we established a rigorous informed-consent procedure so that egg donors would be made fully aware of the possible dangers. We insisted that ovulation-stimulating medications be administered at safe dosages. And we set payment for participation at a modest level: $4,000 (about $40 an hour), which is roughly the average paid in New England for egg donation for reproductive purposes. We wanted to prevent payment from becoming an undue influence that could blind women to the risks.

What are the ethical issues relating to the person whose cells are being cloned?

It may seem that individuals who provide the cells (usually skin fibroblasts) that are fused with enucleated eggs in therapeutic cloning research face no risk apart from the remote possibility of an infection at the site of the skin biopsy. But cloning is a controversial issue that exposes all research participants to novel risks. Cell donors, for example, might find themselves at the center of a media storm if they are identified as having allowed themselves to be cloned. To prevent this, the ethics advisory board insisted on procedures ensuring strict confidentiality for both egg and cell donors (unless they choose to come forward).

One question that occupied much of our time was whether children could donate cells for this research. We concluded that in general this is not advisable, because on reaching maturity the child may feel morally compromised by having been made to contribute to a cloning procedure. We made an exception, however, in the case of an infant with a fatal genetic disease. We knew that a stem cell line based on the childs DNA might be a powerful tool in research aimed at curing the disease. Although the child would probably not survive long enough to benefit from this research, we concluded that the parents had a right to make this decision on the childs behalf. This childs cells have not yet been used in a cloning procedure.

Will therapeutic cloning facilitate reproductive cloning, the birth of a cloned baby?

A final major question raised by this research is whether it will hasten the day when people undertake human reproductive cloning. This concern presumes that reproductive cloning is and always will be ethically wrong. Many who hold this view cite the incidence of deaths and birth defects in cloned animals. Others worry about more remote dangers. They point to possible psychological risks to children produced in families in which a parent may also be a childs genetic twin. They fear that cloned children may face unrealistic expectations to live up to the achievements of their genetic predecessor. And they worry about possible social risks of cloning if societies decide to replicate a limited number of desired genomes on a large scale for military or other purposes. In opposition to this, some people hail the prospect of cloning. They see it as a new way to provide biologically related offspring for some infertile couples or as a means of reducing the risks of some inherited genetic diseases.

Whatever one thinks about the ethics of reproductive cloning, placing a ban on therapeutic cloning will not make reproductive cloning less likely. Although therapeutic cloning could help scientists perfect techniques for reproductive cloning, it could also make much clearer the dangers of trying to produce a human being in this way. There is already evidence that some cloned animals can experience improper gene expression and disruptions in imprinting, the normal pattern of silencing genes not needed in particular tissues. Such problems could discourage prospective parents from using this technology to have a baby. Thus, therapeutic cloning research could actually reduce the likelihood that cloning would be seen as a viable reproductive option.

A ban on therapeutic cloning also would not prevent unsupervised researchers from going ahead with reproductive cloning efforts on their own [see Reproductive Cloning: They Want to Make a Baby]. Groups such as the Ralians, a religous cult, or renegade scientists such as Richard G. Seed, a physicist based in Riverside, Ill., who has also been involved in embryology, have announced their intent to clone a human being and presumably will try to do so regardless of whether therapeutic cloning research is banned. A ban on therapeutic cloning will block useful research while allowing less responsible people to try reproductive cloning wherever they can find a permissive legal environment. By shutting down responsible research on the cell biology of human cloning, such a ban would also guarantee that the first efforts at cloning a human being would be based on scanty scientific information.

Our ethics board has had to wrestle with new and challenging questions, but we believe we have managed to give Advanced Cell Technology a firm ethical base for its therapeutic cloning research program. After researchers derive stem cells from cloned human activated eggs, ethicists will need to determine at what point it will be safe to try to transplant such cells back into volunteer donors. The tasks ahead for ethics boards like ours are demanding. The reward is assisting at the cutting edge of medical knowledge.

RONALD M. GREEN is director of the Ethics Institute at Dartmouth College and chair of the ethics advisory board of Advanced Cell Technology in Worcester, Mass.

Other current board members are Judith Bernstein of Boston University ; Susan Crockin, a health care lawyer in private practice in Newton, Mass.; Kenneth Goodman, director of the Forum for Bioethics at the University of Miami; Robert Kaufmann of the Southeastern Fertility Center in Mount Pleasant, S.C.; Susan R. Levin, a counselor in private practice in West Roxbury, Mass.; Susan L. Moss of San Diego State University; and Carol Tauer of the Minnesota Center for Health Care Ethics. Michael D. West, president and CEO of Advanced Cell Technology, is an ex officio member of the ethics advisory board.

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