July 15, 2003 | Last month, the International Society for Stem Cell Research (ISSCR) held its first meeting in Washington, D.C. The venue was significant, for although founding president Len Zon insists it is not a lobby organization, the ISSCR must engage in a political discourse to salvage the extraordinary promise of embryonic stem (ES) cell research — which offers genuine hope to millions of patients suffering from incurable diseases, including Parkinson's disease, Lou Gehrig's disease, diabetes, and muscular dystrophy.
Much of the problem arises from President George W. Bush's infamous decision on Aug. 9, 2001, to restrict federal funding for human ES cell research to the 78 lines in existence before his live television broadcast. What appeared at the time to be a politically shrewd maneuver was seriously misleading. According to the NIH, only 11 of the federally sanctioned ES lines are currently available for distribution (see escr.nih.gov).
More importantly, all of the existing ES lines were produced with mouse "feeder" cells, rendering them unusable in any potential clinical context. Recent studies, however, have shown that human cells can substitute for the mouse feeder layer, leaving many researchers anxious to develop and characterize such lines. But that would require revisiting the Bush policy, which the White House insists is not going to happen.
Meanwhile, frozen human embryos, byproducts of in vitro fertilization (IVF) procedures, are routinely discarded with written parental permission as "medical waste." Some stem cell advocates argue that salvaging ES cells from these embryos is, in fact, the "pro-life" position, because surrogate mothers for all of these surplus embryos will not be found.
In spite of these restrictions, fundamental research continues to grab the headlines. In a recent front-page story, mouse ES cells turn out to be truly totipotent — that is, they have the ability to form oocytes (germ cells). Doug Melton's group at Harvard has detailed signatures of hundreds of genes that define "stemness," which should help identify elusive adult stem cells. And groups from Scotland and Japan recently identified a gene called "nanog" — charmingly named after the Celtic mythological land of the perpetually young, "Tir nan Og" — which plays a key role in maintaining ES cell potency.
| Hanging in the balance: Stem cell research supporters protest in front of the Capitol in Washington, D.C.
But all of these breakthroughs involve the study of mouse ES cells, not human. So what of human ES cell research in biotech, which is not directly affected by federal restrictions? PPL Therapeutics, the Scottish company that owned the rights to Dolly the cloned sheep, dropped its stem cell program last year. And Geron, the San Francisco firm best known for its work on immortalizing cells, reduced its stem cell program in a major restructuring effort to survive. Three years ago, Geron was valued at more than $1 billion. Today, it is clinging to cash reserves of about $50 million. Ironically, this is the same company that funded the now classic work of University of Wisconsin biologist James Thomson and colleagues, who in 1998, along with John Gearhart's group at Johns Hopkins University, cultured human ES cells for the first time.
Some academic institutions — including Stanford, UC-San Francisco, and University of Wisconsin — have established stem cell research facilities, without a dime of federal funding, that enable human ES cell research to continue. At Harvard, Melton shifted his lab's focus to pancreatic development after his son was diagnosed with Type 1 diabetes. The Howard Hughes Medical Institute (HHMI) and Juvenile Diabetes Research Foundation enabled him to furbish a new laboratory exclusively for human ES cell research. HHMI funding has also enabled Melton's group to develop nine new human ES lines from frozen human embryos from the Boston IVF clinic, donated with parental permission, which Melton will make freely available to the research community without licensing fees.
Opponents of ES cell research often cite the potential of stem cells isolated from adult tissues. While the scientific consensus suggests that these cells do not possess the full repertoire of ES cells, Len Zon stresses that the ISSCR is not just promoting ES cell research. "We're for both [embryonic and adult] stem cells," he says. "We perform bone marrow transplants every day; they're adult stem cells." The ISSCR aims to "present a view based on science and academic excellence." Zon says several European governments have already contacted the society for information.
But not, it seems, the United States. The director of the NIH, Elias Zerhouni, has outlined several grant schemes and other initiatives aimed to bolster ES cell research (Science 300, 911; 2003). He pledged to help the community develop "a robust, rigorous portfolio of investigator-initiated research studies that will define and exploit the full potential of stem cells to improve the health of the nation and the world." Such claims strain credulity given the stringent tenets of President Bush's 2001 decision.
All the while, lives that could be extended, brightened, or saved are going begging, including one who left his mark on Washington, D.C. Former first lady Nancy Reagan recently wrote a poignant letter to Sen. Orrin Hatch (R.-Utah), in which she described her husband's decline from Alzheimer's disease and her commitment to the stem cell cause. She concluded: "There are so many diseases that can be cured, or at least helped, that we can't turn our back on this. We've lost so much time already. I can't bear to lose any more."
Kevin Davies, Ph.D.
PHOTO OF DAVIES BY WEBB CHAPPELL; PHOTO BY CHRIS CORDER/UPI