Over the past five years, 15 patients at a Maryland research institute agreed to take a chemical that rekindled symptoms of their schizophrenia -- hallucinations, voices, feelings of paranoia.
Scientists studied their symptoms and took sophisticated brain scans that highlighted the biochemical changes that occurred as symptoms flared, then subsided.
In so-called "washout" experiments, scores of other patients agreed to be taken off their medications for weeks at a time so that researchers could study relapse and try new ways to treat schizophrenic symptoms as they appear.
Scientists at the institute, the state-run Maryland Psychiatric Research Center in Catonsville, say the experiments are helping them fulfill an important mission: to learn what causes the devastating mental disorder and -- ultimately -- to find better treatments or even a cure.
But in one of the most contentious debates in medical ethics, critics charge that the studies in Maryland and many other states inflict needless suffering upon people who have trouble weighing the risks and consequences before agreeing to take part. Families, they say, gravitate to research institutes in desperate hope for treatment.
"Families are burdened from trying to save their kids," said Vera Hassner Sharav, director of a New York advocacy group called Citizens for Responsible Care in Psychiatry and Research. "They are trying to get treatment. That's one of the reasons why they are encouraged to go into research.
"That's one reason people become guinea pigs."
The issue is now before the National Bioethics Advisory Commission, which is considering changes in federal rules governing the way scientists recruit patients for psychiatric research. Similarly, an advisory group assembled by the Maryland attorney general's office is considering ways to toughen the state's oversight of psychiatric research.
New rules on the state and federal levels could make it harder for psychiatrists to gain consent before enrolling people in experiments. A regulation under review in Maryland, for instance, would bar the use of many patients in high-risk experiments unless they appoint "surrogates" to make decisions for them.
The Maryland Psychiatric Research Center, part of the University of Maryland, Baltimore, is exclusively devoted to the study of schizophrenia, a mental disorder that causes troubling thought disturbances. People withdraw socially and lose the motivation to succeed. In some cases, they hear strange voices and see things that aren't there.
About 1.5 million Americans are afflicted, making it the most common form of psychotic illness.
The Maryland center is one of many across the country whose experiments have come under scrutiny. In hearings over the past several months, the bioethics commission has heard testimony from parents who said their children were exploited at centers in California and New York as well.
Parents recall suffering
Last September, parents of three patients who enrolled in experiments at the Maryland center in the 1980s and early 1990s charged that their children suffered painful relapses during "washout" experiments. Officials with the research center denying that anyone was hurt, maintain that they have worked hard to ensure that patients volunteering for experiments are mentally competent to do so.
"In 20 years, there hasn't been a documented case of any harm to any of our research participants," said Dr. William Carpenter, director of the Maryland research center. "It's not correct to say that the patients would not be able to speak for themselves. They're not incompetent individuals. They often speak for themselves."
Carpenter said he excludes from consideration any patient who appears too ill to make sound decisions about participating in an experiment. He said patients and their families are fully briefed on the nature and risks of the experiments -- and that the patients are quizzed to make sure they understand what they have heard.
He acknowledged that some experiments are designed to help future patients and may not benefit the participants in any way.
"If there are no potential benefits, that has to be clear," Carpenter said. "We also have to lay out the risks."
The parents' complaints led to a recent investigation by the Office for Protection from Research Risks, a watchdog agency in the U.S. Department of Health and Human Services. In March, inspectors interviewed patients and staff and sifted through several years of research documents.
In a report dated April 15, the office found that the informed-consent documents "generally comply" with federal requirements. But the agency found several "issues of concern" and ordered the center to do a better job disclosing the risks posed by experiments.
Consent forms, for instance, must clearly explain symptoms that might occur when medications are stopped; they must point out experiments that offer "no anticipated benefit to subjects."