All UCI Medical Research Funding at Risk in Scandal

Less than a year into her tenure as the chancellor of UC Irvine, Laurel L. Wilkening expressed the fervent hope that Orange County’s leading institution of higher learning could become one of the top 50 research universities in the country by 2000.

But that was 1994, well before the startling revelations that Dr. Ricardo H. Asch and his partners allegedly transplanted patients’ eggs without consent and conducted human-subject research without permission. Well before the university sued Asch and two of his colleagues.

Now, the Center for Reproductive Health and even UC Irvine itself are under a cloud. Some fertility experts and medical ethicists predicted last week that the scandal might have a far-reaching impact, extending beyond the university to the research world as a whole.

However, the most devastating impact is likely to end up here, where UC Irvine’s troubles have not only put the school under a microscope for possible research violations, but also for possible crimes.

The Orange County district attorney has opened an investigation, as have the campus police and the California Medical Board. Perhaps mindful of the pending litigation, few of the school’s administrators have addressed the subject publicly.

But some acknowledge that, regardless of how it’s perceived, the controversy poses serious problems in the short term and casts doubt over the school’s ability to fund and conduct research in the long term--and not just research limited to infertility.

“Fundamentally, all of the research depends on federal grants from either the [National Institutes of Health] or the National Science Foundation,” said Carl Cotman, director of the UC Irvine Brain Aging Institute, which has been hailed for its pioneering work on Alzheimer’s disease.

Indeed, the NIH views the unfolding developments at UC Irvine with “great concern,” Don Ralbovsky, a spokesman for the agency, said last week.

“I don’t want to prejudge the situation,” Ralbovsky said. “I can’t say UC Irvine’s funding is in any jeopardy. But our Office for the Protection of Research Risks is looking at the situation very carefully. It’s just not clear at this point if a violation occurred.”

If the allegations against Asch and his colleagues are proven, UC Irvine runs the risk of losing all of its funding for medical research, according to Dr. Joseph Gambone, director of the fertility center at the UCLA School of Medicine.

“It doesn’t take much of an infringement for the [NIH] to just stop the funding--all of it,” Gambone said. “They’re pretty strict. If you don’t follow their regulations, they have a tendency to come down pretty hard.”

And without NIH funding, Gambone said, universities could scarcely function, at least in terms of research. He noted that UCLA, for instance, receives “hundreds of millions of dollars” from the NIH, which has an annual budget in the tens of billions of dollars.

“What they end up doing generally is punishing the institution as a whole,” Gambone said. “They have a tendency to say, ‘You should have been more vigilant.’ ”

Ralbovsky said that, theoretically, Gambone is right: Although no NIH money went specifically to Asch’s center, it is the institution as a whole that agrees to meet “all federal guidelines” when obtaining government assistance.

In the 1993-94 academic year alone, UC Irvine received about $38.6 million from the U.S. Department of Health and Human Services, and about 90% of that came from the NIH, according to Karen Newell Young, a spokeswoman for the university.

Young said that about $11 million of the total was used for research “involving human subjects.” Gambone said that any threat to such a large chunk of its funding pie could devastate a university, especially one with such an ambitious game plan.

Cotman, director of the Brain Aging Institute, guardedly agreed, using his own school as an example.

Cotman’s institute alone receives more than $1 million a year in federal grants for research on studying more efficient ways to diagnose Alzheimer’s disease. He said the university is now rated among the top 12 in the country in neuroscience research.

But he predicted that the swift action by Wilkening will have a lasting impact in terms of righting the university and ensuring that the fertility crisis reaches no farther than the doorstep of the Center for Reproductive Health. He cited the university’s own investigation and the filing a lawsuit against the doctors as examples of the fast action.

“What the chancellor did was act in a responsible fashion [to address the allegations],” Cotman said, “which I agree with. I would emphasize that the university did its job.”

Others are not so charitable. Several bioethicists have criticized the university for delaying action for months. The executive director of the Medical Board of California has said he would have been glad to use his office’s subpoena powers to help university officials obtain medical records crucial to their investigation. But the agency was never asked, he said.

Wilkening remained silent last week as the university took the extraordinary step of filing a lawsuit against three of its prominent researchers.

Other experts from around the country agreed that, in terms of preserving the university’s reputation and its dignity--and, most of all, its funding--the kind of response Cotman described is the only kind that federal agencies will tolerate from an institution beset by scandal.

Robert Levine, a professor at the Yale University School of Medicine, said other schools--such as Harvard University and the University of Minnesota--have recovered from major research crises of their own, and that it needn’t be the end of the world.

To condemn a university such as UC Irvine because of the alleged misdeeds of a few “is like saying the United States is an evil society because somebody blew up a government building,” Levine said. “Like every other institution, there are some who don’t follow the rules.”

Nevertheless, the misdeeds of a few can have a domino effect on the university as a whole, creating not only potential financial problems but also a sense of psychological ennui.

“When there’s a story that something went wrong at a university, it can be very demoralizing to the people within the institution,” he added. “What the effect will be in the long run is hard to predict.”

As chairman of Yale’s institutional review board overseeing human subjects, Levine said that once irregularities are reported, reviewers have the responsibility to talk to researchers to help them fix their faulty methods or, in extreme cases, to turn matters over to federal officials to eradicate the problem quickly.

He said that, in most scenarios, the only time federal grants to an institution are threatened is “if the institution itself is out of line.”

Sidney H. Golub, UC Irvine’s executive vice chancellor, said he believes the university’s image might actually end up benefiting, because of the quick way it investigated allegations of research misconduct and took steps to prevent a repeat of the same abuses or mistakes as alleged.

At the same time, the California Medical Board has accused the university of reporting nothing until news of the scandal reached the press. Golub defended even that action, saying the school had hoped to remedy the problem in private, free from the glare of the media.

“We weren’t the ones who chose to go public with this,” he said, “and it is with great reluctance that we filed a lawsuit,” which he contended was necessary to gain access to records allegedly withheld by the clinic’s doctors.

In the end, Golub said, “We will be known as a university that cares very deeply about having patients protected in our human subjects research, and that will attract faculty here that have those same ethical ideas. I don’t think this will hurt us.”

He said that other institutions, including the Massachusetts Institute of Technology, the University of San Diego and the University of Pittsburgh, have survived research scandals. Even Gambone’s UCLA has survived scandals and kept its funding intact.

In 1980, oncology professor Martin J. Cline proposed a gene therapy experiment on people with beta-thalassemia, a genetic blood disorder. Gene therapy was extremely controversial at the time, and a UCLA review board turned down his studies. So, Cline went to Italy and Israel and performed experiments there, unsuccessfully. The NIH disciplined Cline by requiring him to undergo a more thorough review when he applied for grant monies.

In 1991, a 23-year-old man who was the subject of a UCLA Medical Center psychiatric study on schizophrenia was found dead after he jumped off the roof of a classroom building. After a three-year investigation, NIH officials found that UCLA had violated aspects of the “informed consent” rules governing human-subject experimentation.

But despite the problems, UCLA has maintained its standing among the nation’s leading recipients of grant monies.

Even so, the allegations against Asch pose a problem for the entire biomedical industry, in the view of Gladys White, director of the National Advisory Board on Ethics and Reproduction in Washington.

“Any time there is an absence of a meaningful process of maintaining and ensuring informed consent,” White said, “it has a chilling effect on all research efforts, because the public trust is lost. I’d have to say this is a very serious problem, not only for Dr. Asch and UC Irvine but for any researcher who needs to use that kind of human material. Only time will tell what the final impact will be.”