Fetal Stem Cell Research

By Peter McCauley, M.S., J.D. candidate

The Bush Administration is currently grappling with the issue of federal funding for fetal stem cell research. Many feel that fetal stem cell research will lead to major advances in the treatment of diseases such as Parkinson's disease, congenital diabetes, Alzheimer's disease, and spinal cord injuries. Further, it is strongly supported by influential Hollywood celebrities such as Michael J. Fox and Christopher Reeves.
 
By way of background, a stem cell is a cell produced in the normal course of human development that has the capacity to develop into a variety of different tissues. See http://www.nih.gov/news/stemcell/primer.html. Stem cells are classified by their differentiating capacity. Totipotent cells, e.g., the fertilized egg, can develop into any type of tissue. Pluripotent cells, e.g., certain zygote cells that appear at about four days, called the inner cell mass, can give rise to most tissues in the body. Finally, multipotent stem cells can give rise to a specific group of cells, e.g., blood cells. While totipotent and pluripotent cells are found in the developing fetus only, adults and children have multipotent stem cells that allow them to regenerate cells and tissues which have a limited lifespan, such as the blood cells. Often, when a stem cell divides, it produces another stem cell and a more specialized cell, thus allowing for continuous regeneration of the tissue.

The matter in controversy is the source of pluripotent stem cells, which are isolated from aborted fetuses and embryos in storage in fertility clinics that are no longer needed by the donors. Isolation of the stem cells cannot be done without destroying the embryo. Some abortion foes, including Senator Sam Brownback (R-Kan.), feel that this is unethical research, citing the destruction of human life in the process of isolating stem cells. On the other hand, almost all abortion supporters, and even some who oppose abortion, support fetal stem cell research, including Senators Hatch (R-Utah) and Thurmond (R-S.C.). See http://www.nytimes.com/2001/06/19/health/19RESE.html. Senator Hatch stated that a frozen embryo is not equivalent to a developing fetus in the womb.

While there is no significant movement to ban fetal stem cell research in the private sector, the use of federal funds to support fetal stem cell research is a different matter. In fact, Congress banned federal funding for fetal stem cell research in an amendment attached to a 1996 Labor Health and Human Services bill. The law has not been overturned, but in 1999, the Clinton Administration eased the ban by funding the research if the extraction of the cells was done with private funds.

In the final months of the Clinton Administration, the National Institutes for Health published a set of guidelines for federally funded stem cell research. See http://www.nih.gov/news/stemcell/stemcellguidelines.html. Some highlights from the guidelines include: the stem cells can only be obtained from aborted fetuses and embryos whose primary purpose was in fertility treatments, not those that were created for research purposes; cloning is banned; the donors must be given full informed consent, including waiving their intellectual property rights or rights to future commercial profits; all research must comply with federal statutes on fetal tissue research and informed consent (see 42 U.S.C. § 289g-1, -2(b)); donors cannot receive compensation except for their actual expenses; and fertility specialists cannot have any financial relationship with stem cell researchers and the same person must not be both.

President Bush, in conjunction with Health and Human Services Secretary Tommy Thompson, is considering the fate of these guidelines. Federally funded stem cell research appears to be a matter of great division within the Administration, with Thompson supporting the research, and key political advisor Karl Rove advising President Bush against it. At issue is whether President Bush will alienate the religious right, especially Catholics, if he supports federal funding. If he refuses funding, he risks alienating his centrist support. See http://www.abcnews.go.com/sections/politics/Daily_News/Stem_Cells010626.html. President Bush seems to be seeking a compromise, leaning toward a plan that would allow research on fetal stem cells that had already been extracted. It would allow the researchers to continue the work for a limited time, at which time the benefits of the research would be weighed. Id. Bush has said:" I oppose federal funding for stem cell research that involves destroying human life." See http://www.nytimes.com/2001/06/22/science/22BUSH.html. A final decision is expected by the end of July.

Considering the moral controversy that surrounds fetal stem cell research, one might wonder if there are scientific alternatives that are less problematic. In fact, several alternatives have shown promise, and are cited by opponents of the research as evidence that fetal cell transplants are not scientifically necessary.

One source of stem cells is the umbilical cord at birth. This source is not controversial because the cord is regarded as medical waste. One study used cord blood to reconstitute leukemia patient's blood cells following chemotherapy. See http://www.nlm.nih.gov/medlineplus/news/fullstory_2224.html. The results were promising.

A second technique, called autologous donation, is now the most common form of stem cell transplantation. See Lennard and Jackson, Stem Cell Transplantation, 321 BMJ 433 (2001). It is used frequently with leukemia patients. Prior to chemotherapy, stem cells from a patient are isolated and tested to ensure that they are free of cancer, and following complete destruction of the bone marrow, the stem cells are re-injected back into the patient in order to reconstitute their blood cells.

Another technique, pioneered by the scientists who cloned the sheep Dolly, is more spectacular. In this technique, regular adult cells are converted into stem cells. In an unpublished experiment, PPL Therapeutics took normal skin cells and converted them into stem cells, which can then differentiate to a variety of cell types. See http://www.wired.com/news/print/0,1294,42093,00.html. In another experiment, Italian researchers showed that nerve stem cells can, in the right environment, produce muscle cells. See Galli et al., Skeletal Myogenic Potential of Human and Mouse Neural Stem Cells, 3 Nature Neuroscience 986 (2000). Thus, adult cells seem to be more flexible than previously thought.

In general, bone marrow stem cells in adults seem to have the ability to become almost any cell type. See http://www.unisci.com/stories/20012/0504011.html. They can be used to regenerate liver and lung tissue, repair damaged heart tissue, and possibly cure incontinence. See http://www.cmbi.bjmu.edu.cn/news/0104/11.html. Other strategies include isolating stem cells from fat in an individual for use in regenerating other tissue. See http://www.usnews.com/usnews/issue/010423/fat.html.

Another strategy is to create an engineered cell line that can be maintained indefinitely. See http://www.unisci.com/stories/20011/010811.html.The cell line is originally isolated from an embryo, but once isolated, no subsequent fetal tissue is needed, as the line is propagated indefinitely in culture.

Strangely enough, stem cells were even isolated from the brains of human cadavers, after the addition of growth factors to the isolated tissue. See Cell Culture: Progenitor Cells from Human Brain after Death, 411 Nature 42 (2001). The isolated cells were able to differentiate into all the lines of nerve cells found in the brain.

While everyone agrees that stem cell research has great potential, everything has not gone as smoothly as expected. A major study published in the March 7, 2001 New England Journal of Medicine used fetal stem cell transplants to treat Parkinson's disease. See Transplantation of Embryonic Dopamine Neurons for Severe Parkinson's Disease, 344 NEJM 710 (2001). What the researchers found is that younger patients benefited somewhat from the transplants, but older patients did not. Disturbingly, after the first year, some 15% of patients developed substantial involuntary movements and had uncoordinated motor skills that could not be alleviated by modulating traditional medications. This was a sobering result.

To add fuel to the fire that is currently raging on this issue, a new development has been the revelation that some fertility clinics and biotechnology companies have used techniques that are in direct violation of the NIH guidelines on fetal stem cell research. The Jones Institute for Reproductive Medicine in Norfolk, Va., using private funding, has created embryos explicitly for the purpose of harvesting stem cells. See http://www.nytimes.com/2001/07/11/health/genetics/11cell.html. Twelve female egg donors received $1,500 each, and two male sperm donors received $50 each. The scientists obtained 162 eggs, which were fertilized to make 110 viable embryos. Of this group, 50 embryos grew to a solid mass of cells called a blastocyst. Stem cells were obtained from 18 blastocysts. Of this group, 3 were chosen for stem cell lines, which can be propagated in culture indefinitely.

Comments from opponents include such adjectives as "unconscionable" and "ghoulish," and even supporters of stem cell research worry about a backlash against traditional stem cell research. Even some abortion supporters feel that embryos are not the same as just "tissue" and should receive some consideration. At the present time, there are no federal statutes that would limit this activity, but it will be scrutinized as Congress debates the stem cell research issue.

A second development, even more radical and also in violation of the NIH Guidelines, is that Advanced Cell Technology of Worchester, Ma. has announced that it is in the process of conducting experiments in which adult humans are cloned for the purpose of extracting stem cells. See http://www.nytimes.com/2001/07/13/health/genetics/13cell.html. The company said that it would go to great lengths to ensure that the embryos are not implanted into a woman's womb, which is good because that would be human cloning. Rather than using the term embryo, the company prefers to use the term "activated egg".

The company will clone using the same technique that the scientists of PPL Therapeutics used to clone Dolly the sheep. The way this technique works is that a woman donates eggs, receiving a fee of between $3,000 and $5,000. The nucleus of the egg is removed, and replaced with the nucleus from a donor's skin cell. The egg is then grown in culture to the blastocyst stage, at which time the stem cells are harvested, and the embryo is destroyed.

The advantage of this type of research over traditional stem cell research is that this technique would allow the cells grown to be an exact match of the donor's cells. Thus there would be no concern of an immune reaction in the recipient because of the presence of foreign fetal cells. So, for example, in theory it would be possible to use this technique to grow and implant cells for a patient having substantial cell death, as in Parkinson's or spinal cord injuries, without having to worry about using anti-rejection drugs and immunosuppressives.

I think that these two new developments underscore the need for the federal government to get involved with regulating these types of experiments, regardless of whether these companies are receiving federal funding. There needs to be some oversight. I worry that each new experiment, while appearing to be just a small deviation from accepted science, is pushing the threshold inexorably forward.  As Senator Brownback (R.-Kan.) said, "Our technology is ahead of our thinking as a country. I have been saying for some time that this is where we are headed, but we are getting here faster than I thought." We seem to be moving down the slippery slope without any prior public discussion as to whether this research should be allowed, never mind receive federal funding. These companies claim that they have bioethics panels, but then sometimes fail to identify who the panelists are and what their approval process entails. This science should not proceed without a framework or understanding the ethical implications of this research, and a respect for the sanctity of life.

In sum, the debate on the use of fetal stem cells in scientific research will probably continue for some time. Most in the scientific community agree that fetal stem cell research will lead to major breakthroughs. However, some feel that the research is morally problematic and would instead advocate alternative strategies not involving the use of fetal tissue. As the Bush Administration ponders its course of action, it will have to consider the full political ramifications of its decision in this controversial area.

07/25/01