Fall 1994 Volume 3, Number 4
CONUNDRUMS IN THE CONDUCT OF RESEARCH
Ruth L. Fischbach, Ph.D.
Dr. Ruth L. Fischbach. (Photo by Liza Green, HMS Media Services.)
Dr. Munificent is the principal investigator of a multi-site clinical trial of a drug that his lab has developed for treating AIDS dementia. The stringent criteria for recruitment of subjects preclude entering some of his patients into the study. Knowing that admission into the trial means the difference between treatment or no treatment for many patients, Dr. Munificent on occasion "fudges" data to ensure that his patients qualify for admission. He is convinced that bending these "arbitrary" criteria offers more benefits than harms to these very ill persons and won't influence the overall results of the study since he is one of many investigators contributing data to the study.
Dr. Mendit, after years of painstaking effort, has developed a surgical technique that holds great promise of curing hydrocephalus in infants. She has invented and patented an ingenious shunting device that relieves dangerously high cerebral pressure by conveying excess spinal fluid from the ventricles into the jugular vein. A biotechnology firm has agreed to provide financial support to test the device in a clinical population. Dr. Mendit will perform the surgery herself; she (like the babies' parents) is certain that her device will benefit the babies. Dr. Mendit has a long-standing relationship with the biotech firm, first as a consultant and later as a member of their board of directors, compensated by a small but accumulating number of shares in the company.
Ishood Dorite is a new postdoc in Dr. Sage's lab. Ishood is brilliant and has many ideas he would like to test in his quest to advance science and promote the public's health. Working in this lab on the cutting edge of molecular biology, identification of the genetic defect linked to Alzheimer's disease is almost a reality. Dr. Sage, Ishood's mentor, while reviewing a colleague's manuscript for the top journal in their field, realizes that information in the article will greatly assist Ishood, shortening his work by months, as it provides strategic methods for isolating the gene defect. He shows the article to Ishood, suggesting that it is best not to disclose this breach of confidentiality. Dr. Sage convinces Ishood that the raison d'tre they share as researchers is to advance science and, if this small assist helps, it should be accepted. Besides, everyone realizes that confidentiality is a flimsy concept no longer valid in this highly competitive environment. Ishood feels uncomfortable, but fears irritating his mentor or appearing naive and judgmental. He decides to do as he is told and get on with his science.
What's wrong with these scenarios? The ethical dilemmas seem dissimilar: the role of personal and collective responsibility in today's research environment; the growing interface between academe and industry that can induce conflict-of-interest issues over the protection and promotion of intellectual property; and the practical hazards of the mentor-trainee relationship faced by postdoctoral trainees. But they share a common subtext, the tension between "big" science that is, targeted research projects that involve many investigators, multiple research sites, and high levels of funding as opposed to "small" science, characterized by the individual investigator-initiated research study. "Big science" can work; the Huntington's Disease Collaborative Research Group, where researchers functioned as a collective, captured the gene for Huntington's last year. But how can the individual maintain autonomy and accountability for personal actions when there is diffusion of responsibility spawned by the scale of the project?
We are experiencing a new era in academic-industrial relationships. As government funding becomes ominously scarce and uncertain due to the escalating competition for grants, reduced compensation for overhead expenses, and federally mandated spending levels that barely meet inflation, industrial firms increasingly appear to fill the void. From this partnership emerge difficult questions, such as whether students can or should train in industry-sponsored labs; what obligation, if any, do academic scientists have to patent their inventions or products of their research efforts to raise capital for their institutions; concomitantly, should individuals or academic centers offer an exclusive license to one company to market these products or inventions? Particularly contentious is the question of what limits should be set on the amount of equity, level of consultant fees, or royalties researchers may receive before appearances of conflict of interest become manifest?
Academia is a market place, the rewards are there grants, advancement, tenure, respect of peers the list is long. The fierce pressures on researchers to succeed can be overwhelming and may tempt them to bend the acceptable standards. At times these standards may appear nebulous, and the demarcation between sloppy science and fraudulent practice may not be immediately clear. The many conflicts that pose personal gain against societal benefit call for sustained vigilance in maintaining standards for responsible conduct.
Given the complexity and acceleration of the scientific enterprise, it is crucial that we confront the implications of the latest technological advances. Ethics can be seen as a discipline to assist in defining and improving the making of hard choices. In science or medicine the question is "what can be done?" In ethics, however, the question is "what should be done?" Even while the technological imperative exhorts us to use the latest advances available, we should consider the consequences, long term and short term, of our decisions. Preventive ethics, analogous to preventive medicine, can avert or mitigate the harmful outcomes of ill- considered endeavors. I do not advocate a voluntary moratorium on all research which raises ethical dilemmas. Rather, we should examine potential hazards and define reasonable guidelines that promote standards of safety. We need to allow ethics to catch up to technology. Why not take as a model the multi-billion dollar Human Genome Project? There, three percent of the designated funding is set aside for ethical studies of issues stemming from this monumental project.
Research involving the brain and nervous system provokes some of our most exquisite ethical dilemmas. Here are a few issues that scientists, ethicists, and indeed society must grapple with; should we:
The opportunity to study the ethical values and principles of science, not currently required across the field, should be integral and requisite in professional training and practice at all levels. A recent Newsweek poll found that 76 percent of adults surveyed agree that "the United States is in a moral and spiritual decline;" concern is voiced that science, representing a microcosm of society, may also reflect this decline. Yet given the financial and psychic temptations, it is remarkable how few cases of misconduct occur, though sometimes highly publicized, among the 22,000 studies funded by the federal government (a total of 14 cases were resolved by the federal Office of Research Integrity last year).
Still, at a time when we are on the cusp of some of the most exciting and beneficial scientific breakthroughs, researchers need to demonstrate to the public that trust in the scientific enterprise is their best investment. Scientific advancement profoundly influences our culture and society, from the manner in which we are born to the last breath we take.
Dr. Fischbach, Co-Director, Program in the Practice of Scientific Investigation, Harvard Medical School, organized "Issues in the Conduct of Research: What is Happening to American Science?" at HMS in June. The symposium brought together leaders in ethics and science from around the country, including the ethicist, Sissela Bok, author of the bestselling Lying (1978) and Secrets (1982), and Harold Varmus, Director of the National Institutes of Health.