T H E   N I H    C A T A L Y S T MAY  -  JUNE   1 9 9 7 

by Fran Pollner

Bioethics Chair Harold Shapiro

Several humans in sheep's clothing disrupted the first meeting, March 13, of the National Bioethics Advisory Commission to plumb the legal and ethical depths of human cloning. They were animal rights activists, and their message, that "cloning is baaad," was unequivocal.

More ambivalence was expressed by most of the scientists, theologians, and ethicists hastily gathered to help the commissioners meet the request from President Bill Clinton delivered only weeks earlier: to produce a set of policy recommendations on the issue of research related to human cloning. They were given 90 days from the end of February to do the job.

Roman Catholic, Protestant, Judaic, and Islamic scholars interpreted the morality of cloning from their respective traditions, as did medical ethicists and legal experts. And a cell biologist laid out some of the scientific dilemmas that must necessarily inform the ethical considerations.

Distinguishing between cloning human beings and conducting cloning-related research that revolves around other pursuits, such as strategies to thwart cancer and genetic disease, would be among the tasks of the panel in arriving at policy recommendations. So would synthesizing the concerns of disparate schools of thought and beliefs in a pluralistic society and constructing safeguards against potential abuses.


Reflecting Roman Catholicism, Boston College theologian Lisa Cahill warned against "conscienceless science," the "irresistible attraction of research prestige," and profiteering from human beings as a commodity. Cloning, with its "biogenetic link to one lineage only" and the ability to produce offspring without the contribution of a male parent, is a "violation of the essential reality of the human family," she said, and is easily distinguished from genetic research into disease therapies.

Ironically, although the terror of cloning lies largely in a perceived loss of individuality, in truth, cloned individuals would be no more alike than identical twins - and even less so, several speakers noted, since mitochondrial and intrauterine factors would be different, not to mention inputs and responses after birth.

In that sense, the ability to clone genetically equivalent human beings brings into sharp focus a fundamental theological tenet: that human beings are not reducible to their physical beings. Clearly, the same "body" does not equal the same person.

But human cloning, per se, is "intrinsically morally flawed," according to Albert Moraczewski, a scientist and a theologian with the National Conference of Catholic Bishops. Human procreation, he said, ought to be the result of the "sex act between two committed partners," not a "technology that eliminates the need for the male."

Along similar lines, Protestant theologian Gilbert Meilaender, of Valparaiso (Ind.) University, declared that "genesis takes a man and woman" and distinguished between "begetting" and "making" a child. Begetting, he said, frees the man and woman from self-absorption and confers genetic independence from the parents upon the child. He cautioned against using the pursuit of health as a knee-jerk justification. "Progress," he said, "is always an optional goal."

He suspected that cloning is different not only in degree but in kind from other reproductive technologies and that cloned individuals might be designated "another rational species," a concept that inspired a blanket rejection from another Protestant thinker. In the event that children ever result from cloning, admonished Nancy Duff, of the Princeton Theological Seminary, "it is imperative to assume they are the same human beings as the rest of us." She said she did not "rule out completely the morality of cloning research," which she considered acceptable if the potential benefits are compelling. In her own inventory of potential uses, genetic disease research would be on the positive side of the ledger; cloning to replicate a dying child or to replicate soldiers and athletes would not.

"Technology is morally neutral in Jewish tradition," Elliot Dorff, of the University of Judaism, Los Angeles, told the panel. Rather, the uses to which it is put determines its moral status. "Our tradition is not passive regarding the medical cards we are dealt. Illness and healing are ultimately in God's hands, but we are given permission - and the obligation - to heal, as individuals and as a community," he said. Cloning research could be a tool for healing - or for exploitation. "Can we get a hair from Michael Jordan's head, with or without his consent, and clone ten Michael Jordans - and be their agent?" he asked.

Dorff recalled an old cartoon depicting Satan rising from the steam of the then newly invented steam engine. In the minds of some, he reflected, "to go more than 20 miles per hour was to be in league with the devil." As with the steam wafting into the air, the cloning "genie is out of the bottle," he said. In practical terms, it is legislation and professional standards that will bend the technology to morally acceptable uses.

Like Dorff, Moshe Tendler, a rabbi, a professor of Talmudic law, and a teaching biologist at Yeshiva University, urged the panel not to recommend a ban on cloning research. "We have a duty to be constructive in this world," he asserted, noting that, historically, governments the world over have at times promulgated policies undermining this duty - either by issuing blanket bans in areas of biomedical research that could benefit humanity or, conversely, by promoting physician participation in research activities that actually constitute atrocities against humanity.

Aziz Sachedina, of the University of Virginia, prefaced his remarks on the Islamic view of cloning with a "thank you" to the panel. "You have the gratitude of the entire Muslim tradition in North America. This marks the first time a representative of Islam appears in such a forum," he said. He noted that poten tial abuses of other technologies, such as in vitro fertilization, have been addressed by Muslim jurists, but possible human cloning, per se, has not. He presented the general backdrop against which such issues are viewed.

Although the Koran is silent on when humans first possess a soul, Suni Muslims (50% of U.S. Muslims and 80% of Muslims worldwide) place the event at 120 days gestation, before which burial is not required in the event of in utero death (and without bones, a conceptus may not be buried and has no funeral rites). After 120 days, the fetus is considered a biological and moral being who must be buried in the event of death. Shiite Muslims, however, place ensoulment at 21 days.

The report of the derivation of multiple viable human embryos through the extraction of cells from a blastocyst at George Washington University in 1993 raised fundamental moral/spiritual questions for Muslims about interpersonal spousal relationships. But cloning calls forth another category of dilemma. A child cloned into being "could not lead a normal life," he said. "In Islamic law," he explained, "the child belongs to the father. The father's identity must be clear. Lineage must be clear. Without proper lineage, there is no inheritance." A lesbian woman pregnant through artificial insemination by an anonymous donor or by implantation of an anonymously donated fertilized egg, for example, would be viewed as a serious problem in Islam, Sachedina indicated. "Female infertility, however, would not be a problem, since multiple wives and temporary marriage for the purpose of childbearing are legal. But a child who exists outside a legitimate spousal relationship would have no guarantee of natural inheritance."


To John Robertson, a professor at the University of Texas Law School, however, the legal implications of human cloning are relatively minor. "It's not qualitatively different from current genetic selection practices. It's not that radical a step away from techniques now used to ensure healthy offspring, like prenatal screens."

In fact, he maintained, cloning, which "takes the genome as it is," is much less ominous than the ability to manipulate the genome.

In the in vitro fertilization setting, he said, cloning embryos by nuclear transfer or blastomere separation "falls within the fundamental freedom of married couples to have biological offspring, with the same legal protection as other noncoital means. If random, leftover embryo donation for the couple who lack gametes is allowed, a couple should also be able to decide to replicate DNA they know (from a consenting adult not involved in the child rearing), and this should have the same legal protections. It's cloning of self for rearing by self that poses more problems."

Since the intent of the procedure is to create life, it would necessarily be deemed a benefit to the child and, therefore, allowable experimentation, he reasoned. The bottom line, Robertson said, is that research must be permitted, as should cloning for infertility - if it proves safe and effective.

The scientific bottom line, however, is that clinical applications of cloning are at the other end of a tunnel lined with question marks. The unknowns
were addressed by Princeton University developmental biologist Shirley Tilghman, whose overall assessment was that the cloning experiment in which a newborn lamb was generated from an adult sheep mammary cell would contribute only "modestly" to answers she and other scientists have long been seeking regarding the process of gene reactivation and the selection of pathways that determine cell type.


Tilghman recapped some of the telling statistics leading to the birth of Dolly: of 277 egg-cell fusions, 247 survived six days in oviduct culture, 29 developed appropriately enough to be implanted into foster mothers, and one of these saw the light of live birth. The report of the work, she said, provided no insight into why only 29 of 247 developed normally.

Embryogenesis, she said, entails the reactivation of silent genes, followed by a selective re-silencing that constitutes cell differentiation. This process takes 18 hours in mice but about three days in sheep and humans. "At least in one cell type - the mammary cell - it is possible to reverse the silencing," Tilghman said of the lessons learned from the experiment. "[Researcher Ian Wilmut] took a cell that was 90% silenced and fused it with an unfertilized egg from which the DNA had been removed. His source of cells - the mammary gland - had been allowed to go into a quiescent state and had not divided for three to four days; he used resting nuclei for this one successful experiment."


A Double-Edged Technology

Speaking at a Senate subcommittee hearing on cloning technology the day before the National Bioethics Advisory Commission met, NIH Director Harold Varmus characterized the "idea of generating human clones of mature individuals" as the stuff of "interesting movies, but poor science and poor ethics." He registered his agreement with the conclusion reached by an NIH advisory panel in 1994 that there is "no justification for federal funding of research involving nuclei transplantation for [the purpose of] cloning an existing human being or making carbon copies of an existing embryo."

However, he said, the technology could be put to beneficial uses, including developing animal models of disease more reflective of humans; developing ways to turn on, turn off, and redirect human genes; and generating cell - therapies such as marrow cells for cancer patients, skin cells for burn patients, and nerve cells for patients with brain diseases.

Tilghman listed several "things that could go wrong" during the course of this and similar experiments.

  • Physical disruption of the egg may occur during the large-needle enucleation.

  • Gene reactivation may be inefficient.

  • Mammary gene products may exert a negative impact on early development. "Perhaps these products are toxic to the egg. This," Tilghman said, "is a critical issue: success may be tissue-specific. Which cells would be poor donors?"

  • Transplantation may be inefficient.

The first and last potential problems are inherent to all embryo manipulations, she noted, but the two in between "are unique to this experiment, and we know very little about these."

"As a scientist," she continued, "I worry about silent somatic mutations in the donor nucleus - which has existed in the sheep for six years, in this case. There could be a somatic mutation innocuous to the mammary gland that is now permanent in every cell of the new organism," she observed.

"We know almost nothing about inefficient reactivation of genes required late in development. That would be most troublesome, and there is precedent for it: 20 years ago in England in experiments in which frogs could not develop past the tadpole stage," she cautioned.

The 18-member panel, chaired by Harold Shapiro, president of Princeton University, anticipated meeting several more times in person and countless times over the wires before delivering its report to the President at the designated time at May's end. As this issue of The NIH Catalyst went to press, it was virtually certain the panel would recommend continuation of the moratorium on human cloning on safety grounds alone - and would attempt to construct a framework for addressing the larger social policy issues should scientific uncertainties be resolved in the future.


Ayes and Nays

Of 19 national scientific societies responding to a survey by the RAND Critical Technologies Institute, 14 felt adult donation of DNA for developmental research should be allowed; the same number felt adult donation of DNA to clone a human should be prohibited.

Return to Table of Contents