Frozen

Wonder and disappointment. Two constants in the world of science, both were felt last week after a judge's ruling closed off millions of federal dollars for human embryonic stem-cell research and threatened the future of this field of scientific study.

In the nearly year-and-a-half since President Barack Obama overturned an August 2001 order by President George W. Bush that limited federal funding for human embryonic stem-cell research, scientists have gained growing momentum in this area of biomedical exploration and discovery, which has the potential to cure spinal chord injuries and diseases such as diabetes, Alzheimer's and Parkinson's (March 22, p. 17).

But on Aug. 23, that momentum came to a halt after U.S. District Judge Royce Lamberth granted a preliminary injunction that prevents HHS' guidelines for human stem-cell research—which allow federal funding for embryonic stem-cell research—from taking effect. The Obama administration is expected to appeal.

“NIH has been working with great energy and intelligence to put forward guidance that is scientifically and ethically sound,” Francis Collins, director of HHS' National Institutes of Health, told reporters in a teleconference a day after the ruling was announced. “And as you know, that has resulted in the approval now of many lines for federal funding—a total of 75 now—most of them new, some from the Bush era,” he added. “They've all been reviewed rigorously and found to be eligible scientifically and ethically, but this decision potentially places all of this in jeopardy.”

Robert Kass, vice dean for research at Columbia University Medical Center in New York, said he was disappointed by the decision. He also said most of the work at Columbia—and other medical schools—is funded through the NIH.

“The review process has been stopped and put in limbo,” Kass said. “What that means for researchers is it's like a freeze frame. You have to stop, and it's very disruptive.”

The process to receive funding from the NIH is a long and arduous one that includes various stages of review, both for a grant proposal to be accepted and funded, and again annually while the work of the grant is conducted. As a result of the preliminary injunction, the NIH's Collins explained, 50 grants that were pending peer review have now been pulled and will not be considered because they involve human embryonic stem-cell research. Also, an estimated $15 million to $20 million worth of proposals that have passed the first stage of peer review and were scored with high priority for NIH council consideration in the next month have been stopped. Separately, there are 22 grants for projects totaling $53 million that will be up for annual review.

“The injunction would place a freeze on the renewal of those awards, which were due to be done by the end of September, and therefore would stop research in its tracks,” Collins said, adding later that about $131 million worth of grants already awarded this year is unaffected—“until, of course, they have to come back and ask for their next year's allocation.”

Richard Hynes, a professor at the Massachusetts Institute of Technology, called the ruling “misguided.” Hynes also is an investigator at the Howard Hughes Medical Institute and served as a co-chair for the National Academy of Science committee that created guidelines for embryonic stem-cell research in 2005. He said the decision hinged on funding and will compromise the future of the biomedical research community.

“It will stop bright young people from going into this field because they'll see their careers being threatened,” Hynes said. “The next wave won't do it because they will say, ‘How can I build a career out of this?' ”

Hynes' comment that the decision was about funding is evident in the court filing. The case had actually been tried before with additional plaintiffs, but the U.S. District Court for Washington dismissed it for lack of standing. But on appeal, two of the plaintiffs—who work exclusively with adult stem cells—argued they had competitor standing and that obtaining NIH funding is necessary for their continued research, according to Lamberth's ruling.

“The guidelines, by allowing federal funding for ESC research, increases competition for NIH's limited resources,” Lamberth said in his opinion. “This increased competition for limited funds is an actual, imminent injury. There is no after-the-fact remedy for this injury because the court cannot compensate plaintiffs for their lost opportunity to receive funds.”

In his briefing with reporters, Collins addressed the issue of competition and emphasized that the NIH's standard is, and should always be, scientific peer review.

“Certainly there have been great strides made forward in adult stem cells—we all celebrate that,” Collins said. “In terms of whether things are in competition with each other? Of course. All grants effectively are a bit in competition with each other, in the entire pool of the 50,000 grants or so that we deal with each year,” he added. “But our standard is supposed to be peer-review and other considerations along a scientific nature.”

An essential point of Lamberth's decision is his conclusion that the Dickey-Wicker amendment is unambiguous. Enacted in 1996, the Balanced Budget Downpayment Act included a rider called the Dickey-Wicker Amendment (named for former Republican Reps. Jay Dickey of Arkansas and Roger Wicker of Mississippi; Wicker now serves as U.S. senator). The amendment prohibited the use of federal funds for the creation of a human embryo or embryos for research purposes.

The amendment also prohibited research in which a human embryo or embryos are destroyed, discarded or knowingly subjected to risk of injury or death greater than that allowed on fetuses in utero under applicable federal regulations. Although HHS determined in January 1999 that the amendment was not applicable to this research because human embryonic stem cells are not embryos, Congress has not changed the amendment.

“I think it's a shame,” said Robyn Shapiro, a health law partner with Drinker, Biddle & Reath in Milwaukee, about the decision. “We're going to take a few steps backward in our scientific progress in our efforts,” she added. Shapiro, who had worked as director of the Center for Bioethics and Medical Humanities at the Medical College of Wisconsin for 26 years, said she does not believe the Dickey-Wicker amendment has been violated. “From what I read, the judge was kind of saying it was the fruit of the poisonous tree because the only way you could get those was through destruction” of an embryo, she said of the cells.

Many were upset by the ruling. The American Association for Cancer Research called it a “setback for scientific discovery,” and the privately funded New York Stem Cell Foundation said the decision “allows a vocal minority to hold science hostage to a narrow political agenda.”

Yet others welcomed Lamberth's decision.

“CHA continues to believe that embryonic stem-cell research involves the destruction of human life at its earliest stage and is morally objectionable,” the Catholic Health Association said in a written statement.

Meanwhile, researchers are left wondering whether the decision will be reversed legally, or if Congress will pass new legislation to clarify the Dickey-Wicker amendment. In March, Rep. Diana DeGette (D-Colo.) introduced a bill that would amend last year's Stem Cell Research Advancement Act to require HHS to conduct and support research that uses human stem cells. The bill also would limit research to stem cells that meet the following requirements: They were derived from human embryos donated from in vitro fertilization clinics; it was determined with those seeking reproductive treatment that the embryos would never be implanted in a woman and would otherwise be discarded; and the individuals seeking reproductive services donated the embryos with written, informed consent and received no financial or other inducements, according to a summary of the bill, which was referred to the House Energy and Commerce Committee.

“Everyone in this situation is in a conundrum,” said Tim Kamp, a cardiologist who is the director of the Stem Cell and Regenerative Medicine Center at the University of Wisconsin Medical School. “On the one hand, you hope it will be resolved,” he added. “On the other hand, you have to take into account that it won't be resolved.”

Kamp said most researchers were “blindsided” by the decision. Kamp's research studies normal cardiac function and cardiac disease, and requires human stem cells. He added that it's not feasible to get human heart cells from patients. Kamp has one grant that is currently funded until next year, and another that was under review, which he said won't be reviewed now.

As he waits to see if the decision will be upheld, Kamp expressed concern about America's competitive advantage globally in the world of medicine.

“It's slowing progress in biomedical research,” Kamp said, “and causing us to lose any competitive ability we have with other researchers around the world who haven't created any such barriers to research.”