Out of One, Many: Stem Cells Ignite Scientific Inquiry, Controversy in '99

From the WebMD Archives

Dec. 29, 1999 (Boston) -- In the beginning, there was a stem cell -- a single blob of living matter with the potential to grow into blood, bone, or brain. Pretty impressive stuff, but most miraculous of all was the alchemy that in 1999 turned a human embryonic stem cell into a hot potato.

Throughout the year, medical research using human stem cells derived from embryos or placentas sparked scientific spirits and inflamed religious hearts, igniting passions that will smolder well into the new millennium.

In a battle reminiscent of the struggle between Galileo and the Church of Rome, medical researchers, backed by the National Institutes of Health and the presidentially appointed National Bioethics Advisory Commission (NBAC), fought for federal support of research to derive or isolate and use human embryonic stem cells. But because the process consumes embryonic tissues, it has brought down on scientists' heads the wrath of the National Conference of Catholic Bishops (NCCB) and a small coalition of right-to-life advocates and right-of-center politicians.

Despite a Department of Health and Human Services (HHS) ruling holding that stem cells are not embryos and therefore not subject to federal bans on human embryo research, and despite the issuance in early December of National Institutes of Health (NIH) draft guidelines intended to assure that the research is conducted in "a legal and ethical manner," the National Right to Life Committee issued a statement asserting that the guidelines "would result in federal sponsorship and funding of experiments in which living human embryos are dissected and killed -- a clear violation of federal law." Rep. Christopher Smith, R-N.J., displaying unquestionable zeal but imperfect understanding of the underlying science, called the research "truly barbaric and grotesque experiments on human beings."

Putting passions and politics aside for the moment, few would argue that from a purely medical viewpoint the news about stem cell research has been breathtaking in its scope and import, and in the speed with which new developments occur. Consider the following select items reported by WebMD over the last 12 months:

  • In January 1999, Canadian and Italian scientists proved that, contrary to conventional wisdom, you can teach an old stem cell new tricks. As Vescovi and his co-authors reported in the Jan. 22 issue of the journal Science, adult nerve stem cells, previously thought to be unable to develop into other cells, metamorphosed into a multitude of different types of cells when injected into mice with deficient immune systems.
  • In February, Duke University researchers reported in The New England Journal of Medicine the results of a 16-year prospective study showing that stem cell transplants from related donors could reconstitute immune systems in infants with severe combined immunodeficiency (SCID). "There is a way to save the lives of [SCID] children, and you don't need to have a perfect match to do this," lead author Rebecca H. Buckley, MD, professor of pediatrics and immunology at Duke University, told WebMD.
  • The ink had barely dried on the two previous studies when biotech researchers from Osiris Therapeutics and Johns Hopkins University in Baltimore reported in the April 2 Science that human mesenchymal stem cells -- the precursors of mature bone, cartilage, ligaments, fat, and muscle -- can be coaxed to differentiate into the desired tissue type.
  • Investigators at the University of Bonn, Germany, reported in Science on July 30 that embryonic stem cells can be used to recoat defective nerve cells in rats, a process that could one day be used to treat degenerative neuromuscular disorders such as multiple sclerosis or amyotrophic lateral sclerosis (ALS). In a similar study, neurology researchers at Washington University School of Medicine in St. Louis reported in the December issue of Nature Medicine that embryonic stem cell transplants promoted the regeneration of functional neurons and restored some hind-limb function to rats with a thoracic (chest)-level paralyzing spinal injury. The study also indicated continued viability of transplanted cells.
  • In the Oct. 5 Annals of Internal Medicine came word of a case report from Australia in which a man with severe treatment-resistant rheumatoid arthritis who received high-dose chemotherapy followed by a transplant of stem cells from his identical twin had complete remission of symptoms for at least 2 years, the longest follow-up on record.
  • In a fitting bit of symmetry, the year ended as it began, with a new study reported by Baylor College of Medicine researchers in the Dec. 7 Proceedings of the National Academy of Sciences, indicating that skeletal muscle stem cells, when injected into mice whose natural bone marrow was ablated, developed into blood cells. Although the cell-manipulation techniques described in several of the studies cited above may allow researchers to circumvent the tangle of ethical and political issues surrounding embryonic stem cells, there is unflagging and widespread support in the medical community for research using undifferentiated human stem cells.


But while the scientific understanding of stem cells and their potential has become much clearer, things on the political and ethical fronts are still murky. It seems that every time the issue of research using human embryonic cells is raised in the media, entire forests are felled to provide fax paper for outraged abortion foes and passionate research supporters. And whenever the subject comes up for discussion before Congress, the air temperature on Capitol Hill rises a few dozen degrees.

In December 1998, NIH Director Harold Varmus, MD, told a Senate appropriations subcommittee that the ability to control cell specialization would be "an unprecedented scientific breakthrough with the potential to revolutionize the practice of medicine and improve the quality and length of life." But speaking in opposition to stem cell research, Richard Doerflinger of the NCCB told the committee that "Even a good end does not justify an evil means." He recalled the specters of the Tuskegee syphilis study and Cold War-era radiation experiments as examples of good science gone bad.

Undaunted, Varmus told the NBAC in January of '99 that funding for the research could begin later in the year, thanks to a legal ruling from HHS, which held that since stem cells derived from human embryos are not themselves organisms, research that uses the cells is not covered by the federal ban on human embryo research. Federal research that generates and uses stem cells from nonliving fetuses can also be supported, the HHS ruling holds, although not research involving in vitro-fertilized fetuses. A ban on human cloning imposed by President Clinton would apply only to stem cell research used for cloning, HHS said.

It didn't help to clarify the situation when the American Association for the Advancement of Science (AAAS) broke ranks with NBAC and announced preliminary support for federal funding of stem cell research, but did not recommend funding the derivation of cells from human embryos.

In December 1999, the NIH issued a draft version of research guidelines stating that stem cell research would be funded by NIH only if the cells were already removed from the embryos, or removed from fetuses under existing federal guidelines. The guidelines also require that cells in NIH-funded research be derived only from embryos that were "in excess of clinical need" at fertility clinics, and that the donors of the embryos must give fully informed consent to the ultimate use of the embryos.

Additionally, the guidelines call for establishment of a Human Pluripotent Stem Cell Review Group to assure that the rules are followed, excluding from federal funding any research linked to human cloning, excluding research involving adding stem cells to human or animal eggs or embryos, and excluding funding for research using human embryonic stem cells extracted from embryos that were created expressly for research. In effect, all embryos that produce the stem cells must have been discarded by fertility clinics and not created in the laboratory.

For patients of all political and religious stripes, the issue is largely a no-brainer. As the advocacy group Patients' Coalition for Urgent Research said in a statement issued in support of federal funding, stem cell research is "a new area of science with tremendous promise for alleviating and even curing catastrophic illness."

Perhaps we should let Galileo himself have the final say, 377 years after he wrote these words about scientific inquiry: "Philosophy is written in this grand book -- I mean the universe -- which stands continually open to our gaze, but it cannot be understood unless one first learns to comprehend the language and interpret the characters in which it is written."