To prevent such abuses, as well as subtler hazards, the federal government in 1981 set up a two-tiered system for protecting patients in medical experiments. The design, or "protocol," of a study must be approved by an institutional review board that weighs its risks and benefits. And informed consent must be obtained: the nature of the experiment, its suspected risks and even the pros and cons of not participating in the study are supposed to be clearly explained to potential subjects, who then can choose to sign on.
But is the system working? Are the guidelines strict enough, is the oversight strong enough? Are the safeguards adequate to protect against the conflict that so troubled Enrique Lamadrid? Doctors who are also researchers have a dual allegiance, to their patient-subjects and to their research protocols. Despite the best of intentions, they are, according to one ethicist, "double agents with conflicting loyalties."
Had Tony Lamadrid's social worker alluded to just such a conflict in her telephone message to him? Gioia-Hasick, who declined an interview request, offered one last piece of advice on the answering machine. "Using the staff there (UCLA)," she said, "and trying to get into a better and kind of cleaner program at Saint John's (Hospital) would be great. Anyway," she finished, "I wish you a lot of luck. And let me know what happens. Thanks. Bye-bye."
IT WAS SUMMER OF 1978 WHEN PROFESSOR KEITH NUECHTERLEIN, WHO had just earned his Ph.D in clinical psychology from the University of Minnesota, arrived at UCLA's School of Medicine. He had dreamed of becoming a minister or a physicist, but he picked research psychology because he saw it as the perfect way to combine his talents as a people person and a scientist. About the same time, Michael Gitlin, a bright young graduate of the University of Pennsylvania School of Medicine, was finishing up his psychiatric residency at UCLA.
Nuechterlein was particularly interested in an aspect of neuropsychology--the subtle abnormalities in the way some people perceive things. As he followed the literature, he began to wonder if it might not be possible to look at such factors as a way of measuring and predicting a predisposition for schizophrenia, which includes such devastating perception problems as hearing nonexistent voices and feeling persecuted by nonexistent forces.
Gitlin, meanwhile, was becoming a respected authority on the treatment of mood disorders, especially manic depression and schizophrenia. In his growing practice, he was seeing many young adults having their first manic episode. And the question he kept confronting was this: Should a 21-year-old face a lifetime of lithium use, the drug of choice for manic depression? The cost-benefit ratio is a complicated one. Though the relapse rate is high, without lithium, the drug may have toxic side effects. Gitlin was well aware that the drugs that helped control much worse disorders, like schizophrenia, could also have serious side effects.
It seemed only natural that these two bearded boy wonders--dubbed by colleagues as "compulsively conscientious" (Nuechterlein) and "a real mensch " (Gitlin)--would join forces in research: If doctors could predict the onset of mental disease symptoms they could also better control the use of drugs. Gitlin and Nuechterlein decided to go after a piece of the $5 billion the government annually spends on biomedical research involving human subjects.
Their big break came in 1983, when the National Institute of Mental Health awarded Nuechterlein, as the study's director, the first of what would amount to $2 million in grants over 11 years for the "Developmental Processes in Schizophrenic Disorders" project. The study would include hundreds of subjects, most of them recruited as they were admitted to Camarillo State Hospital, Harbor/UCLA Medical Center, Olive View Medical Center and the UCLA Neuropsychiatric Hospital. These were "recent onset" patients who had experienced their first psychotic breaks within the past two years. The project offered them free treatment at UCLA's prestigious medical center in a program for outpatients called the Aftercare Clinic.
The research included two protocols, approved by the university's Human Subjects Protection Committee and by the government. The first involved putting the patient-subjects on a standardized dose of the antipsychotic drug Prolixin while the researchers tracked their symptoms and tested for factors associated with relapses, defined as a "return to a state of active and severe psychotic symptoms." The variables to be studied included environmental stresses thought to trigger symptoms--"high expressed emotion" within families, for example, things like emotional over-involvement, criticism and hostility--and physiological components such as "smooth pursuit eye movements," breathing rate, blood pressure and the like.
