The Problem of Experimentation on "Decisionally Incapacitated" Humans
Five of the world's 10 leading causes of disability are psychiatric depression, alcohol abuse, bipolar mood disorder, schizophrenia, and obsessive-compulsive disorder. These disorders have genetic determinants and physical correlates. In the past 40 years, great advances in medication have taken place. But there is concern now for the ethical aspects of psychiatric research and the abuse of power when dealing with vulnerable patients. One of the most vexing ethical problems concerns the mentally ill and those with Alzheimer's dementia. These people are in danger because of their diminished capacity to consent to the participation in research. The Nuremberg Code, formulated in 1947 as a result of the trial of Nazi physicians who had experimented on unwilling subjects, stated, "the voluntary consent of the human subject is absolutely essential." Because of the domination of pharmaceutical interests in this country financial incentives are great, and there is an inherent conflict of interest as scientists make their livelihood from research protocols.
The system now in place for the protection of subjects only applies to research that is federally funded. This protection is "based on a succession, or chain, of judgments made by people in the context of federal regulations." It is called the Common Rule and directs a research institution to assure the federal government that it will provide and enforce protection for human subjects. Central to the process of insuring that the rights and well-being of human subjects are protected are institutional review boards (IRBs). The main problem as I see it when dealing with human beings is the problem of informed consent. Henry Beecher, a pioneer of research ethics, wrote in 1959 that this principle would "effectively cripple if not eliminate most research in the field of mental disease." He was talking about the restrictions as outlined in the Nuremberg Code. There is agreement that research on humans requires informed consent but that, "at the same time we must learn as much as possible in order to improve the care of those who suffer from the diseases that impair their capacity to provide informed consent." How do we proceed given this conflict? In 1964, the Declaration of Helsinki softened the absolute ban of the Nuremberg Code by including legal guardians to provide consent, at least for "therapeutic" research. In 1974, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, which was created after the revelation of the exploitation of subjects in the Tuskegee study of syphilis, discussed the special problem of the use and abuse of vulnerable groups as research subjects.
The commission suggested special regulations to govern research on "persons institutionalized as mentally infirm," but these regulations were viewed as "overly burdensome and were never adopted. However, the commission's general comments paved the way for the so-called common rule". The common rule recognizes the problems of "vulnerable populations", including the mentally disabled. It requires that institutional review boards (IRBs) include additional safeguards to protect the rights of such groups but provides no specific guidelines.
The National Bioethics Advisory Commission (NBAC) is the latest federal panel to address the issue. Its 17 members were appointed by Clinton in 1995 to advise the government on bioethical issues, and especially to "consider the problem of the rights and welfare of human research subjects." Its report was released in 1998. With respect to informed consent Dr. Eric J. Cassell, M.D. testified on Dec.9, 1999 that the "NBAC recommends that no person who has the capacity for consent may be enrolled in a study without his or her informed consent."
Yet there have been two proposed bills in Maryland (the first one ended negatively in committee) that would allow research on "decisionally incapacitated "humans without their informed consent. A proxy will make the decision for them. As for who would be experimented on, this would include a broad spectrum of Americans with disabilities including those diagnosed with Alzheimer's, psychiatric disorders, mental handicaps-any claimed brain ailment that impairs a person's ability to give informed consent.
As you might have realized there is big money in all of this. In a recent breakthrough, scientists at Elan Corporation's research facility in San Francisco believe they have developed what could possibly become a treatment or potential vaccine against Alzheimer's disease. Elan's researchers reported in the scientific journal Nature, on their discovery of AN-1792, a form of the same beta amyloid peptide that scientists believe causes Alzheimer's. The corporation's next move is to apply to the FDA for human clinical trials, which could begin by the end of 1999. Zaven Khachaturian a leading Alzheimer researcher recently said the following on the program "Frontiers of Medicine". "Preferably one would want to have the dementia set in an hour before they die. Or, if an hour is not possible, maybe ten days before. Or, if not, a year before. But clearly we cannot afford to have a society whose population - forty to fifty percent in their 80's - have dementia and are going to be demented or disabled for twenty to thirty years". There will be a big push to test this substance on humans because mice do not have a memory as far as we know. The government offers large financial grants for "high risk"/ "high impact" research, while pharmaceutical companies award large unrestricted grants to neuroscience centers across the U.S. Great financial gain can be made as one newly legitimized drug can bring up to a billion dollars of yearly revenue.
Mentally ill persons with impaired decision-making capacity do not have one problem regarding research ethics, they have two. Dr. Michels M.D. Cornell University Medical College states in the New England Journal of Medicine's " Sounding Board" in May that "The focus of the NBAC report (1998) is that the inability of such persons to provide full informed consent may leave them vulnerable to exploitation. The greater problem is that too little research is conducted on their behalf. Psychiatric research is burdened by a long history of public fear of mental illness, prejudice against the mentally ill, and distrust of those who treat or study them." Some of this distrust is legitimate given the history of abuses.
A 1996 court case documents experiments on thousands of indigent pregnant women in Florida without their informed consent. Currently tens of thousands of Americans labeled mentally ill are involved in washout studies, where they are suddenly off their medicines, inducing painful withdrawal symptoms and greatly increasing chances for relapse. Any new drug will have serious side effects and these cannot be anticipated. By an "Orwellian twist of phrase, experimental research is now termed therapeutic research." By its very nature any research that is experimental, especially on the fragile organ on the brain, constitutes a major risk. For example, drugs used in psychiatric research, were held by the New York Appellate Court to constitute a major risk of death and injury. Hence the rush to have a Maryland bill that would allow research on this very group.
And through all this maze of government regulations, confusion, hovers the constant leitmotif of greed, undisclosed failures, profits, etc. In the recent death of Jessie Geslinger a Senate sub-committee is now investigating the consent form he and his family dealt with. A lot was not disclosed; least of all the conflict of interest when former University PhD's establish Bioresearch companies, sometimes with federal monies, whilst pursuing brand new breakthrough therapies without following the guidelines. Someone called this "NASDQ medicine" because of all the new IPO's and stock options for those involved in the companies. Jessie's death then, was it just "a pot hole on the road to gene therapy?"
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