Embryonic Stem Cell Lawsuit Threatens Regenerative Medicine Research

By Jeffrey Norris

Embryonic stem cell research in the United States has a future – but when it comes to federal funding, that future is unclear. Federal funding for the science is in limbo, due to a failure to act by Congress and a legal challenge to current research guidelines. This year federal funds for embryonic stem cell research dried up as the result of an August court injunction that clamped down on the awarding of grants permitted under the guidelines. The injunction was temporarily stayed on appeal in September, but nonetheless may be a harbinger of what could become a long-term ban. UCSF and other leading universities stand to lose research programs worth millions of dollars, and in some cases training programs for graduate students – many of whom would never even enter a stem cell laboratory.

Stem Cell Research Competitiveness Is Not Guaranteed

Medical, pharmaceutical and other technological advances that the United States is known for often emanate from basic discoveries initially driven primarily by university scientists fueled by federal research dollars. Think of the biotech industry and Silicon Valley, for example. Fundamental stem cell discoveries made by academic scientists early on now are leading to specific applications in medicine. In October, Geron Corp. of Menlo Park, CA launched a clinical trial to begin evaluating a treatment for spinal cord injury that was developed from embryonic stem cells. In addition, last week the Food and Drug Administration granted approval to Advanced Cell Technology of Marlborough, MA, to begin clinical trials to treat a childhood form of vision-robbing macular degeneration with retinal cells derived from embryonic stem cells. But in the long run, the nation’s front-running status in the emerging field of regenerative medicine – the use of healthy new cells to replace cells from tissues that die or malfunction in disease – now no longer appears assured. In a recent commentary in the science journal Nature, a team of investment bankers argued that changeable federal policies and an uncertain regulatory environment for stem cell research and development are dampening business investment and threatening US competitiveness in the field. Arnold Kriegstein, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, notes that governments of other countries – including China and some European Union nations – have recently made large commitments to support stem cell research. “If we give up our leadership role in stem cell research by discouraging investment, it’s going to be taken up in other parts of the world,” Kriegstein says. “This is going to create a competitive disadvantage in an area where we should be trying to excel.” Through the National Institutes of Health’s (NIH) peer review process, committees of scientists rate grant proposals submitted by researchers – their peers – who compete with one another for limited funds. Overall, roughly one-in-five proposals have been funded by the NIH in recent years. During the injunction, NIH officials said the agency would stop paying out for embryonic stem cell grants that it had already awarded, including grants that had been expected to fund work over several years.

UCSF Is Vulnerable to Embryonic Stem Cell Research Ban

Kriegstein’s own research is not directly affected. Some of his embryonic stem cell studies are funded privately. Others are funded by the state through the California Institute for Regenerative Medicine (CIRM), a stem-cell funding organization created in 2004 through a voter-approved state bond initiative. The NIH does fund some of Kriegstein’s work on adult stem cells. “At UCSF we are lucky because most embryonic stem cell research is not federally funded – it’s state funded,” he says. But some UCSF research and training programs are under threat. While nobody expects the NIH to disappear, CIRM – initially funded for 10 years – may be less likely to win long-term state funding. UCSF scientists who seek to diversify support for their long-term embryonic stem cell research programs had begun applying for grants from the NIH after the current guidelines were implemented, Kriegstein says. But many now are thinking twice about seeking support from the agency in the future. UCSF educational programs having nothing to do with federally funded embryonic stem cell research may also take a hit, Kriegstein says. Among them are a training grant that provides the bulk of funds for MD/PhD students and a recently awarded five-year grant that funds graduates students enrolled in a new developmental and stem cell biology program. Students in these programs may rotate through the labs of several faculty members before choosing a mentor and research project. A large number of faculty members participate and were listed at the back of the training grant applications, a consideration in the competitive scoring of the applications. “Some of the faculty members in these programs are doing stem cell work that is privately funded, in many cases funded by CIRM,” Kriegstein says. According to Kriegstein, NIH officials indicated that the training grants would no longer be eligible for support if there is a new ban on federal funding for embryonic stem cell research.

Embryonic Stem Cell Research Guidelines Challenged in Court

Current NIH guidelines allow federally funded research on embryonic stem cell lines. The stem cells lines eligible for federal funding must be developed – without federal funding and with donors’ consent – from embryos left over from in-vitro fertilization (IVF).

Arnold Kriegstein, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF, says that if the US continues to ban federally funded embryonic stem cell research other governments will take the lead in the field creating “a competitive disadvantage in an area where we should be trying to excel.”

Frequently more embryos are obtained during IVF preparations than are implanted. Couples may choose to freeze embryos, but unneeded embryos normally are discarded by IVF clinics. The pre-implantation embryos used to create stem cell lines contain a few dozen cells. Last year right-to-life and embryo adoption advocates – who are opposed to the destruction of human embryos at any stage, starting with conception – challenged the guidelines. In 2009, the plaintiffs in the lawsuit were initially denied legal standing by Judge Royce Lamberth of the US District Court for the District of Columbia. A three-judge panel of the Circuit Court of Appeals in June 2010 granted standing to two of the original plaintiffs –James Sherley, MD, PhD, and Theresa Deisher, PhD – and returned the case to Lamberth. Sherley and Deisher are scientists who work with adult stem cells. They were granted standing after claiming that their ability to compete for funds was harmed because they had to compete with scientists who submitted proposals for embryonic stem cell research. The plaintiffs claim that the NIH guidelines violate legislation dubbed the Dickey-Wicker Amendment, which has been passed each year since 1996. The plaintiffs also claim that the guidelines were developed without following proper procedures. Lawyers for Sherley and Deisher argue that Dickey-Wicker clearly prohibits federal funding of stem cell research in which embryos are destroyed, and that research on established stem cell lines is indistinguishable from the research to develop the same stem cell lines from embryos. In granting the injunction, Lamberth indicated that he believed the plaintiffs stood a good chance of prevailing in the case. Both sides have submitted documents supporting their arguments to Lamberth and requested summary judgment – asking the judge to rule in their favor without a trial. No oral arguments have been scheduled in Lamberth’s court. But in the same DC Court of Appeals where the injunction was put on hold in September by a different three-judge panel than the one that earlier granted standing to Sherley and Deisher, oral arguments to decide the fate of the injunction will be heard on December 6 before yet another three-judge panel. There is a possibility that a decision by the Court of Appeals could end the case before Lamberth rules, according to University of California (UC) attorney Rachel Nosowsky. But it’s also possible that legal decisions in the case may eventually be appealed to the US Supreme Court, she adds.

UC Weighs In

UC – the largest recipient of NIH grants – attempted to join the US Department of Justice to become a party to the appeal. “The strategy was to make sure that the harm to the extramural research community, and in particular, to the University of California and to the state of California, was understood,” Nosowsky says. “The plaintiffs are seeking to reverse decisions made to fund university research.” The court rejected UC’s motion to join the appeal, but allowed the university to file friend-of-the-court briefs. In an amicus brief, attorneys for UC again argue that the plaintiffs lack standing. Standing is reassessed at every stage of the litigation – sometimes with increasing stringency. Although the plaintiffs had standing for purposes of a motion to dismiss, they may not have standing for purposes of a preliminary injunction. Among the reasons the plaintiffs lack standing, according to UC, is that they have not shown that they would be competitively harmed by continued implementation of the guidelines. According to the UC amicus brief, “Plaintiffs have not shown that they have lost any grants as a result of any government policy. In contrast, the impact of even a short-lived injunction was profound and affected research scientists, and threatened active research as well as teaching programs and jeopardized jobs.” Deisher is a co-founder of Seattle-based AVM Technologies, which aims to develop stem cell therapies without using materials from embryos. She has no NIH grants. Sherley has successfully competed for grants, but as an employee of the Boston Biomedical Research Institute (BBRI). UC argues that Sherley has no right to assert competitive injury independent of BBRI, the actual grantee. Rather than siding with Sherley, BBRI issued a statement in support of the NIH guidelines, and now has even submitted an amicus brief supporting the defendants.

Lawsuit Outcome Is Difficult to Predict

If the appellate court rules that the plaintiffs do not have standing, then the case should end and Lamberth will not rule, according to UC attorney Nosowsky. However, she adds, it’s difficult to forecast all possible permutations of an appellate court’s decision or what might happen if and when the case is returned to the district court. Granting of standing to the plaintiffs based on the argument that they have been competitively harmed is viewed by some as setting a bad example – one that upends the peer-review process by moving funding decisions into the courts. Lamberth’s earlier ruling granting a temporary injunction has baffled commentators. He accepted the argument that there is no distinction between embryo-destroying research performed to create stem cell lines and research on those same stem cells after they have been established. The conclusion drawn is that the Dickey-Wicker amendment prohibits federal funding for all of it. But the same reasoning would also seem to suggest that even federally funded research on pre-existing stem cell lines that was allowed under the Bush Administration should be prohibited by law. In their current appeal Justice Department lawyers are arguing that Congress clearly intended to make the distinction and to exclude embryonic stem cell research from the federal funding ban. In part they argue that on-the-record statements by members of Congress and the failure of legislators to challenge the guidelines point to acceptance for federally funded research.

Embryonic Stem Cell Research – A Legislative Fix?

Bills introduced in the current Congress that would codify the NIH stem cell guidelines have never come up for a vote. Scientists and advocates for research have some hope that legislation will be passed during the “lame duck” legislative session. That would put the research on a more solid footing and render the lawsuit moot. Congress has budget appropriations and other unfinished business to complete before it adjourns for the year. Still, it is possible that legislation could be added to one of these must-pass bills, just as Dickey-Wicker has been added to such bills in past years, according to David Brown, director of health and clinical affairs for the UC Office of the President in Washington, DC. Even if it requires the reintroduction of legislation next year, Brown says, “We will continue to recruit and work with bill co-sponsors from both parties.” The new Congress that opens for business in January will include more Republicans, and they will take over control of the House of Representatives and its legislative agenda. With the GOP takeover in the House of Representatives, the future of stem cell research and other policy issues is uncertain. Photo by Susan Merrell

Related Links:

Lifting of Stem Cell Ban Affects UCSF and Research Community
UCSF Today, March 9, 2009 For Stem Cell Researchers at UCSF – Already at the Forefront – Yamanaka’s Work Galvanizes Field
UCSF Science Café, November 22, 2010 FDA Clearance for Macular Degeneration Embryonic Stem Cell Study Advanced Cell Technology
News Release, November 22, 2010 Geron Initiates Clinical Trial of Human Embryonic Stem Cell-Based Therapy
Geron News Release, October 11, 2010 Ruling by Judge Royce Lamberth, August 23, 2010
United States District Court for the District of Columbia UCSF Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research