From the Archives: Stemming the Tide

On August 9, 2001, during a speech from his ranch in Crawford, Texas, President George W. Bush put an end to several months of debate surrounding government funding of research on stem cells derived from human embryos. After discussing his administration’s research into the matter and declaring his own “deeply held beliefs” in science and technology and that “human life is a sacred gift from our Creator,” President Bush announced his decision:

As a result of private research, more than 60 genetically diverse stem cell lines already exist.  They were created from embryos that have already been destroyed, and they have the ability to regenerate themselves indefinitely, creating ongoing opportunities for research.  I have concluded that we should allow federal funds to be used for research on these existing stem cell lines, where the life and death decision has already been made.

Leading scientists tell me research on these 60 lines has great promise that could lead to breakthrough therapies and cures.  This allows us to explore the promise and potential of stem cell research without crossing a fundamental moral line, by providing taxpayer funding that would sanction or encourage further destruction of human embryos that have at least the potential for life.

The President’s speech was widely hailed as an acceptable compromise by both advocates of research and pro-life leaders, although there were some notable voices of dissent (the National Conference of Catholic Bishops and Judie Brown’s American Life League most prominent among them). Almost two years later, however, a number of questions remain unaddressed, not least of which is whether the President’s “compromise” has actually restricted the use of government funds to embryos destroyed before 9:00 P.M. EDT on August 9, 2001. Moreover, recent research is calling into question the basic assumption of the President’s speech itself: that embryonic-stem-cell research is likely to provide greater advances in the fight against disease than research using adult stem cells.

What Are Stem Cells?

Stem cells may be a source of therapies for a variety of diseases, including diabetes, Parkinson’s, Alzheimer’s, and heart disease. The National Institutes of Health’s primer on stem cells defines them as undifferentiated cells that can renew themselves and can mature into a variety of other cell types, depending on the stimuli to which the cells are exposed. Embryonic stem cells are derived from three-to-five-day-old embryos that have been “conceived” through in vitro fertilization. They are pluripotent, which means that they can become any type of cell in the body. Adult stem cells are found in a variety of tissues but are most often derived from bone marrow. These cells are multipotent, which means that they can develop into a limited number of cell types. Until recently, researchers believed that an adult stem cell derived from a specific tissue could only differentiate into cells of that same tissue; in other words, a neural stem cell could only make brain cells, while a liver stem cell could only make liver cells. New studies, however, have demonstrated that adult stem cells can mature into a wide variety of cell types.

Stem cells work by three known mechanisms. They can be introduced into tissue and grow into cells of that tissue type. Alternatively, they can be differentiated in cell culture and then introduced into the target tissue, where they function as a cell of that organ. Finally, researchers have recently discovered that stem cells can migrate to an injured organ and fuse with damaged cells there, regenerating the organ. All three mechanisms are potentially of clinical use.

The Practical Limitations of Embryonic Stem Cell Research

Beyond the moral issue of producing embryos and destroying them in order to harvest embryonic stem cells, there are practical limitations to the clinical use of these cells. Scientists have not yet demonstrated that they can control the differentiation of embryonic stem cells. Moreover, as in a heart or lung transplant, embryonic stem cells may be rejected by a patient, since the cells come from a different person. Finally, if all of the embryonic stem cells implanted into a patient do not mature, tumors may develop. Adult stem cells, on the other hand, do not cause rejection, but researchers have been less interested in them because they are found in very small quantities in most tissues, making them harder to isolate and purify. Also, adult stem cells have not been identified for every tissue. They do not multiply as readily, and, as NIH points out, they could have DNA abnormalities from the environment or genetic disease.

Embryonic stem cells were first isolated from mouse embryos in the early 1980’s. They were not isolated from human embryos or fetuses until 1998. To date, no clinical studies have been conducted with embryo-derived stem cells because researchers cannot control their development into various tissue types or prevent rejection.

Adult stem cells, on the other hand, have been used for almost 30 years in bone-marrow transplantation. As early as 1976, reports indicated that bone-marrow-derived cells could be differentiated into bone, cartilage, and fat cells and that these new cells were transplantable. Unfortunately, these observations never became the focus of research, and, by 1999, only a year after they were first isolated from human embryos, more was known about embryonic stem cells than adult stem cells. Recent research on adult stem cells, however, suggests that they may be of more clinical benefit than embryonic stem cells.

In fact, studies indicate adult bone marrow may contain a pluripotent stem-cell population that could potentially repair all of the tissues of the body. These stem cells, called side population cells, are also found within umbilical cords and in adult blood and other tissues. A relatively abundant source of stem cells is fat obtained through liposuction: Fatty tissue can yield up to 200,000 undifferentiated cells per gram.

The Promise of Adult Stem Cell Research

While researchers cannot control the development of embryonic stem cells into particular tissue types, they have recently demonstrated that adult stem cells derived from one tissue can differentiate into cells of another tissue. Cells derived from skin have been grown into neurons and glial cells, smooth muscle cells, or fat cells, depending on the conditions under which the cells are cultured. An abundant supply of these cells can be obtained through skin biopsies. Bone-marrow cells have been differentiated into cardiac, esophageal, stomach, small and large intestine, kidney, neural, bone, and lung cells in both humans and rodents. Neural stem cells can mature into liver, intestine, kidney, and bone-marrow cells, while pancreatic stem cells can become liver cells. These studies indicate that the ability of adult stem cells to repopulate a variety of tissues may be equal to, or even better than, that of embryonic stem cells.

Doctors at William Beaumont Hospital in Royal Oak, Michigan, isolated stem cells from the bone marrow of a 16-year-old boy and introduced them through his aorta into his heart muscle, which had been damaged when he was shot with a nail gun while working on his home. The boy’s heart regained a significant amount of function after treatment. Moreover, there was no potential for rejection, since the donor cells were his own. In a similar study at the Texas Heart Institute, heart function in patients suffering from congestive heart failure significantly improved after bone-marrow-derived stem cells were injected into their heart muscle.

A 1999 Nature Medicine article reported that stem cells derived from bone marrow were differentiated into bone cells and used to treat three children suffering from osteogenesis imperfecta, which causes short stature and brittle bones. The children’s condition improved dramatically, and they suffered fewer fractures. At the 2001 meeting of the American Association for the Advancement of Science, P. Sanberg reported that stem cells isolated from umbilical-cord blood can be developed in culture into healthy brain cells. When these cells are injected into the bloodstream of rats with brain injury, the cells migrate to the area of injury and repopulate it. In a study of rats who had suffered a stroke, 80 percent of those treated with these differentiated cells recovered, compared with 20 percent of untreated rats. If the procedure works as well in humans, one to two umbilical cords may be enough to treat one stroke victim. This approach may be used to treat stroke patients within two years.

While the usefulness of embryonic stem cells remains unproved, these studies demonstrate the potential of adult stem cells for treating disease. Since there has been less focus on adult-stem-cell research, much is still not known about how adult stem cells function, but, even at this early stage, it seems likely that adult stem cells will be more readily adaptable to cure disease.

Loopholes in President Bush’s “Compromise”

The remarkable advances in adult-stem-cell research over the past two years make the potential loopholes in President Bush’s “compromise” all the more disturbing. While government funding of embryonic-stem-cell research is supposed to be confined to cell lines derived from embryos destroyed before President Bush began his speech, NIH’s implementation of the President’s directive potentially broadens the scope. In a statement released on August 27, 2001, NIH announced that “Such research is now eligible for federal funding as long as the derivation process (which begins with the destruction of the embryo) was initiated prior to 9:00 p.m. EDT on August 9, 2001.” Knowing what was coming—as many labs undoubtedly did, since they were approached by NIH before the President’s speech to determine whether they had eligible lines—labs may well have decided to keep their options open by engaging in mass destruction of embryos before the President went on TV. Already, of the 11 embryonic-stem-cell lines listed in NIH’s Human Embryonic Stem Cell Registry (escr.nih.gov), five are held by ES Cell International, a research lab that had no stem-cell lines listed among the original 64 that NIH had said would be eligible for funding.

Moreover, NIH’s implementation relies entirely on the honesty of grant-seeking researchers. The only proof required to make a line eligible for federal funding is a signed affidavit stating that the destruction of the embryo began before the President’s speech did. No documentation (such as certified lab notes) is required to support the affidavit, nor is any penalty prescribed for submitting a false affidavit. In other words, the only conditions preventing an embryonic-stem-cell line derived from an embryo destroyed after the speech from becoming a publicly funded line are the integrity of the person signing the affidavit and NIH’s willingness to look beyond the affidavit to official research records, which NIH is not required to do.

Of course, these loopholes may be largely irrelevant anyway. By choosing to implement his “compromise” by executive order rather than through legislation, President Bush left the door wide open to its repeal by a future administration—or, for that matter, by his own, if research on the initial pool of embryonic stem cells does not bear the predicted fruit.

The Brave New World of Embryonic Stem Cell Research

As this article goes to press, researchers at the University of Pennsylvania have announced that embryonic stem cells from mice have spontaneously transformed into eggs, before developing into parthenogenic embryos. (Parthenogenesis is a process by which embryos develop from an unfertilized egg. Such embryos do not have a complete set of chromosomes and, therefore, are usually not viable.) Hans R. Scholer of Pennsylvania’s School of Veterinary Medicine declared to the Associated Press his desire “to use these oocytes as a basis for therapeutic cloning and hope that our results can be replicated with human embryonic stem cells.” Other news stories indicate that researchers may eventually use this form of human cloning to allow homosexual couples to “conceive” children—eggs made from the stem cells of one male would be combined with the sperm of the other. Welcome to the brave new world of embryonic-stem-cell research, funded by your tax dollars.

Monica M. Richert is a research scientist in cell and molecular biology at the University of Colorado Health Sciences center. Her brother, Scott P. Richert, is the executive editor of Chronicles.

This article first appeared in the June 2003 issue of Chronicles: A Magazine of American Culture.