Just three years ago, James Thompson's laboratory reported successfully establishing human embryonic stem cell lines in vitro, ultimately sparking not only a new vein of scientific research but also an impassioned national debate. Both the debate and President George W. Bush's August 9, 2001 compromise decision to allow conditional funding for such research were well publicized. The President's determination must appear to many as a straightforward compromise between researchers and the patients who may benefit from their work on one side, and anti-abortion activists on the other. In fact, the decision raises even more moral, economic, and scientific questions. Here I will attempt to clarify some of the many factors leading up to the new policy, as well as its potential effects.

First, the science: Embryonic stem cells can only be derived from an area of a 4-to-7-day-old embryo known as the blastocyst. If extracted and cultured at this stage, they may be induced to replicate indefinitely in vitro without differentiating; otherwise, after the seventh day of development they will begin to form three embryonic tissue layers. The significance of embryonic stem cells (ESCs) to scientists is their pluripotency: that is, their ability to differentiate into any of the 200 varieties of specialized somatic cells found in the adult human body. In order to prevent differentiation in vitro human ESCs must, among other conditions, be grown on a layer of mouse embryonic fibroblasts (which serve as feeder cells) in a medium that includes bovine serum. The feeder cells produce growth factors that are necessary to signal the cells to continue their undifferentiated growth.

While human ESC research is still in its infancy (Thompson's 1998 study was the first of its kind), mouse ESCs have been studied for over 20 years with encouraging results. These cells may be induced to differentiate by such means as adding growth factors to their medium, by inserting specific foreign genes into their genomes through transfection (a process where DNA fragments are introduced to the cellular medium so that a few cells will ingest and incorporate them into their chromosomes), or by simply transplanting the ESCs into a live mouse and studying the effects of exposure to in vivo extracellular signals on ESC development. While these techniques require much further investigation, transplantation of mouse ESCs into animals has recently resulted in the partial alleviation of the symptoms of diabetes, Parkinson's disease and spinal cord injuries, with potentially exciting implications for humans.

Socially, however, human ESC research represents an ethical minefield, touching as it does on the deeply divisive question of when life begins. For many, the destruction of tiny, undifferentiated embryos is well worth the potential long-term lifesaving benefits of ESC research; for others, the prospect of deliberately ending human life at any point after conception is abhorrent. Also, though the stem cell lines currently available were derived from embryos left over from fertility treatments, many researchers suggest that to obtain the quantity, quality, and genetic diversity of stem cell lines ideal for scientific research, a large quantity of embryos would need to be created specially for stem cell derivation, using eggs and sperm donated by selected young, healthy volunteers. This practice might be seen as an unacceptable manipulation of human life even by some who currently support human ESC research. Another potential source of embryos is somatic cell nuclear transfer (SCNT, or cloning), in which a somatic cell's nucleus is reprogrammed through transfer into an enucleated oocyte. The SCNT method, if successfully applied, would have the advantage of avoiding immune system rejection of synthesized replacement tissue or organs, because patients' own DNA would direct the ESCs. However, SCNT is often equated with cloning of whole humans for reproductive purposes, which many people find ethically troublesome. This summer the U.S. House of Representatives passed a blanket ban on cloning of any kind. Should this bill become law, SCNT will no longer be an option for American researchers.

In formulating the new policy regarding government funding of human ESC research, then, President Bush had a host of factors to consider. On one side he faced pressure from such high-profile patients' advocates as Nancy Reagan and Christopher Reeve to fund the research; on the other, many of his anti-abortion constituents and Pope John Paul II urged than no public funding of ESC research be allowed. Is it justified to compel taxpayers to fund this potentially life-saving research even while some of them find it morally objectionable? This was the central question that Bush had to answer in order to reach a decision.

Prior to the August 9 announcement, human ESC research in the United States received no government funding because of a long-standing congressional ban on providing public money for any research that destroyed human embryos. Hence such research in this country was conducted only where private support was available, most notably at the University of Wisconsin where Thompson's lab was supported by the Geron company. Sweden, India, Australia and Israel have also developed stem cell lines, unhampered by the cultural objections that slowed such developments in America. Bush's decision, therefore, represents a liberalization of previous regulations, though not as extensive as many patient advocates and scientists had wished for. In what many view as an important first step, stem cell researchers will be able to apply for an estimated $100 million in National Institutes of Health grants starting early next year. This money will be used for basic research, which is expected to focus on the factors that determine whether stem cells differentiate, and what it is that causes them to start or stop dividing. However, should clinical research into applications of stem cell technology become a possibility, the currently approved cell lines may not be suitable for use because of their small number (and thus low genetic diversity), and because they were exposed to animal matter during development, and so may be infected with undetected viruses.

One possibility is that human ESC research will proceed to a certain point with federal funds, after which it will depend on private funding or be carried out in other countries. It is often the case in science that basic research, whose only objective is pure knowledge, is carried out with government sponsorship, while clinical trials that apply this knowledge in a potentially marketable way are funded by corporations. Public funding is generally considered to facilitate better science, as it encourages researchers to publish their results for purposes of information-sharing and peer review. Private research, in contrast, is often characterized by secrecy, as its objective is to acquire a unique product. One pertinent example of the problems that can arise between these conflicting interests is the ongoing lawsuit over the licensing rights to human ESC methods discovered by University of Wisconsin researchers with Geron funding. Another possibility is that government regulations will continue to change, perhaps eventually allowing the use of new stem cell lines in publicly-funded research. Even now legislation is pending in both the Senate and the House that could restrict or expand the new policy. Where the future of human stem cell research lies is anyone's guess.

Suggested Reading

For a more in-depth treatment of the issues involved in human ESC research, the National Academy of Sciences report Stem Cells and the Future of Regenerative Medicine is available at http://www.nap.edu