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'Nature's Repair Shop'
Promise, Science of Stem Cell Research Explored

By Carla Garnett

On the Front Page...

Science magazine called it the "breakthrough of the year" in its Dec. 17, 1999 issue. Within the last 18 months or so, scientists had discovered the promise of human stem cells to treat or cure perhaps hundreds of life-threatening illnesses. Imagine, for example, a person whose heart is so diseased or damaged that an organ transplant is necessary. Donor organs, however, are rare, and donor hearts among the rarest to find in time to save a person's life. In addition, organ transplantation carries the risk of rejection by the patient's body, further diminishing the chances for survival. But what if doctors could somehow use cells to grow the patient a brand new, disease-free heart, and what if that new heart were made of the patient's own cells, thereby lessening chances of rejection?


Though scientists say advanced applications like this are years away from being realized, the potential for such therapy is real now — with stem cell research. Human stem cell science, however, comes with a price, and many believe the price is too high, morally and ethically. Recently, a STEP Science for All session presented "Stem Cells: Nature's Repair Shop," which helped explain the science and some of its implications to the NIH community.

The Science of Stem Cells

Stem cell science begins with "sex 101," joked Dr. Lana Skirboll, NIH associate director for science policy, and one of two guest speakers at the STEP session. An egg is fertilized by sperm. From that fertilization, an embryo begins to form; a group of cells begins to divide, producing totipotent cells, or "totally potent cells. What we mean by that is: totipotent cells each have the potential to develop into a fetus and a baby," Skirboll explained. Soon, "the totipotent cells begin to differentiate, on their way to becoming the complex organism that human beings are." Next, a blastocyst is formed from the totipotent cells. It is from the inner cell mass of this blastocyst structure that so-called "pluripotent" cells can be extracted. Pluripotent, or "plural potent" cells are capable of becoming almost all cells of the human body. However, unlike totipotent cells, pluripotent cells cannot develop into humans. This distinction between totipotent cells and pluripotent cells is very important, Skirboll pointed out. Because pluripotent cells can never develop into a human, the HHS Office of General Counsel has determined that federal agencies may legally fund research using pluripotent stem cells.

It is the cultivation — by any of three lab methods — and potential application of pluripotent stem cells that has so excited many in the biomedical research community; it is this science that has also caused concern among and provoked protests by many others who feel the destruction of human embryos for research is wrong.

"Let me be clear," Skirboll said, "when you separate the inner cell mass from the blastocyst, you are destroying that embryo.

"We're all here about disease and disability," she continued. "Disease, and disability in one form or another, is often about the degeneration of cells. It's about cells that are injured. Being able to develop very specific cells — liver cells, neuronal cells, skeletal muscle cells, heart muscle cells — you can imagine the range of possibilities this presents to medical research."

Pluripotent stem cell research holds enormous potential for a host of medical areas including drug development and toxicity testing, gene development and control studies, as well as tissue and cell production for therapy, she continued.

"Every institute at NIH put forward the benefits of this kind of research" in a special report to Sen. Arlen Specter (R-Pa.), said Skirboll. In addition, following the report, a group composed of many different patient advocacy organizations formed. "Patient groups came together like never before to support pursuing this research," she said. "However, there are many who do not support this research. There are many who feel strongly ideologically that destruction of an embryo for research purposes, for developing therapies for people who are ill, is not appropriate; they feel it is not ethically appropriate, that it is not moral."

As yet, Skirboll reported, no human stem cell research projects have been undertaken nor funded by the federal government, although they are legally possible. On Dec. 1, 1999, NIH released the first-ever proposed guidelines for conducting human stem cell research; a comment period seeking responses to the proposal is open to the public until Feb. 22, 2000.

NBAC Weighs In

Within a week after the methods to isolate pluripotent stem cells were reported in scientific journals and to the public in early November 1998, President Clinton asked for advice on the issue from the National Bioethics Advisory Commission (NBAC), which gathered 17 individuals from various sectors — health sciences, law, ethics — of the American public to conduct a thorough, balanced review of the ethical and medical issues related to human stem cell research. Dr. Harold Shapiro, president of Princeton University, chaired the commission, which by law conducts all its activities in public. An executive summary of the commission's report, "Ethical Issues in Human Stem Cell Research," was published last September.

Dr. Eric Meslin, NBAC executive director and the second speaker at the STEP session, provided an overview of the commission's deliberations.

"There has been an awful lot of previous thought and commentary in the United States — and indeed elsewhere in the world — on this topic," he began. "There has been an ongoing conversation — about fetal research, embryo research, the use of cell-based therapies in research, the use of IVF [in vitro fertilization] procedures — for now more than 20 years."

The organizing principle for NBAC's current report, he explained, was not to determine the legality or economy of the issue, but "to begin with the science and then to discuss what the ethical and medical implications might be."

The commission examined in depth each source of human stem cells: fetal and cadaveric material, embryos remaining from clinical IVF, and embryos produced purposely for research. Principle issues the commission discussed included the science's association with abortion, and consent and donation of the material from which human stem cells are derived.

Finding even a starting point for formal debate was slow going, reported Meslin. For example, one of the most difficult parts of the deliberations about obtaining stem cells from fetal material, he said, was also one of the most basic: Who is the human subject in this research? Is it the woman who agrees to undergo the therapeutic termination — abortion — of her pregnancy and must decide what to do? Is it her partner, who may help her decide? Is it the fetus? Is it the cells, the organism? "You can see how this becomes not an easy solution," Meslin said.

Another tough issue was whether there should be a distinction between the destruction of an embryo and the use of the products from that destruction, he said.

"The destruction of the embryo causes tremendous concern by a good portion of society, and NBAC was struggling with this for some time," Meslin said.

As is standard procedure for such federal advisory groups, NBAC gathered reports, testimony and other types of direct and indirect input from hundreds of sources. Last May, for example, NBAC — recognizing that many people obtain their ethical guidance from religious precepts and leaders — heard testimony from 11 scholars in religion and theology representing Eastern Orthodoxy, Islam, Judaism, Roman Catholicism and Protestantism. Despite the differences and wide ranges of opinion within and among the individual religions, the group was able to find common ground in several areas. All agreed, for instance, that stem cell research is not inherently immoral and has potential; that if society is to fund this research, then it must do so under conditions of respect for the embryo; and that there should be public oversight of even private stem cell research. The group was unable to agree, however, on the moral status of an embryo, nor the extent — if any — to which federal funds should be used for human stem cell research.

Following several months of reviewing the issues, NBAC itself made 13 recommendations in volume I of its report, which can be read online at Among the recommendations were these: Research involving the derivation and use of human stem cells from cadaveric fetal tissue, and from embryos remaining after IVF treatments, should continue to be eligible for federal funding; federal agencies should not fund research involving derivation or use of stem cells from embryos made solely for research purposes using IVF; embryonic and cadaveric fetal tissue should not be bought or sold; an oversight and review panel should be established by DHHS to ensure that all federally funded human stem cell research is conducted in conformity with the ethical principles NBAC set forth in its report; and private sponsors of stem cell research should voluntarily adopt the same standards and principles in its conduct of the science.

The commission's full report, as well as the source documents upon which the report and recommendations were based, will be posted to the site in the coming weeks, Meslin concluded.

Skirboll reiterated that NIH will not fund research using human pluripotent stems cells until final guidelines are published in the Federal Register and an oversight process is in place.

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