PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. Excerpts from “Ethical Issues in Pharmacogenetics” by Carol Isaacson Barash, Ph.D. Drugs can be developed for individuals. Pharmacogenetics is the study of how genes influence an individual's response to drugs. Though the field would seem to be brand new, it is really half a century old. In the 1950's, scientists first identified deficiencies in enzymes that explained adverse reactions to drugs and that they could be inherited. The Human Genome Project has enabled us to identify the molecular composition of the enzymes in question so that we can study correlations between genotypic (gene trait) and phenotypic (physical trait) variability. These advances will increasingly enable us to detect individuals who are likely to experience adverse reactions to medicines without having to use potentially dangerous methods of trial and error. In coming years, we are likely to learn that particular single nucleotide polymorphisms (SNPs) are associated with sensitivities or resistances to chemical compounds in the environment. Scientists are now rushing to not only identify common SNPs, but to determine what drug effects can be correlated to them. Pharmacogenomics is a recent offshoot of pharmacogenetics. Its scope is broader; for example, it attempts to understand not only the molecular composition of genetic variants associated with drug response but also the behavior of those variants, including how those genes affect drug receptor sites. "Good" or "Bad" Allocation of Scarce Resources? Many believe that pharmacogenomics, like other new fields spawned by the Human Genome Project, represent a misallocation of resources. Rather than embark on learning how genes indicate a predisposition to disease and developing cures and enhancements, or experimenting with ways to change the human germ cell, global efforts should be spent on solving more urgent problems facing humanity, such as global famine or accessibility to potable water. Others contend that pharmacogenomics, in particular, offers enormous potential for clinical benefits to patients as well as economic benefits for health care delivery. The arguments in favor include: * In the U.S. alone, adverse drug reactions are thought to KILL about 100,000 hospitalized patients annually. It is believed that many of these reactions are due to genetic variants and thus many of these deaths can be avoided by testing people for adverse drug response before giving them drugs. The science and technology for such tests, however, are in their infancy. * Another 2.2 million incur serious, but non-fatal, reactions. Physicians, in view of their Hippocratic oath, are obligated to do no harm. Can this obligation be fulfilled when the information available to physicians about how particular medicines will fare in their patients is so meager? At present, physicians, generally have no way of knowing in advance whether the drug they prescribe will or will not cause an adverse effect in their patients. * This situation is further compounded by the fact that most adverse drug reactions result from the fact that medicines are "a one-size-fits-all." In other words, although medicines are taken in different dosages depending on symptoms, patient age, weight and other clinical factors, these criteria may not be adequate to ensure that a particular medicine will be safe and effective for a particular individual. Until recently, there has been no alternative to either developing or prescribing medicines. Pharmacogenomics promises to take the guesswork out of developing and prescribing safe and effective drugs. What is a fair distribution of burdens and benefits in developing the field of pharmacogenomics? Monies and people (as research subjects and as researchers) will develop the field to the point that customized medicine will be possible. Who will benefit? * The availability of this new technology may be costly initially, and thus accessible only to those wealthy enough to pay for both the test and the designer drug best suited to them. Yet, the cost will likely diminish so as to become affordable to most. However, will lower costs influence a person to submit to the required genetic testing, thus creating threats, if not violations, to one's autonomy (the basic tenet of bioethics)? * Researchers who have investments in companies competing in their field may be in a conflict of interest if they are conducting research for such a company. Substantial concerns about conflicts of interest as both a threat to quality research as well as to the well being of research subjects have abounded for decades. * A recent study found that policies governing conflicts of interests at major medical institutions varied considerably in both disclosure requirements and the nature of permitted academic-industry relationship, thereby opening a door to the possibility that an interest in financial gain could overpower an interest in either achieving valid research or protecting the well-being of subjects. * Further, there are several examples in the history of medical research where the patient population standing to benefit from advances (i.e., people who have donated their time, bodies, and hearts to research, though compensated per standard National Institute of Health [NIH] terms), did not receive the anticipated medical benefits because new therapies were unaffordable, when they became commercially available, or not covered by insurers. Will individualized medicine be used ethically? Knowing if a person will respond to a drug in ways that are safe and effective for that individual will enable patients to avoid medications that are dangerous or ineffective for them. This is not to say that genes are the only key to cures. Environment plays a role, too. Dietary and lifestyle behaviors are likely to still affect the safety and efficacy of medicines for particular individuals. As well, variation in drug response is not limited to micro polymorphisms. Environmental factors also play a role (such as sun exposure, drug/drug interaction, drug/food interaction). However, scientists are poised to uncover why the metabolism of particular individuals absorbs and dispels pharmaceuticals in a particular manner. Conclusion In spite of our best efforts to anticipate and resolve ethical quandaries arising from the application of new genetic technologies, it is likely that unexpected conflicts will arise. In the absence of guidance about what constitutes high and low stakes, ethically defensible decision making requires acknowledgement of the competing interests and a broad enough scope of concern to analyze how an apparent low risk can become a real high risk and vice versa. Pharmacogenetics will permit gene profiling to answer questions about medicine responses, as well as enable researchers to design better and safer medicines. The science and its applications are real today and will be increasingly common in coming years. While the likelihood that individuals will be shut out from health insurance because they do not respond to a single drug or because a particular drug formula is toxic to them is extremely low, as would be employment exclusions (in hiring, promoting or job responsibilities), the issues underscore the importance of debating more widely the ethical use of pharmacogenetics. In the U.S., 45 million people lack any health insurance, and thus are at the mercy of hospitals' budgets for unrecoverable expenditures. Further, these individuals, and the many more millions of people with health insurance, have no access to sophisticated medical care due to limits imposed by insurers, especially for-profit managed care organizations and self-insured employers. Whether customized medicine will be available to all remains a large unknown. If history is a hint to how this new field will be used, we ought to act now to ensure that the benefits are available to ALL. ### © 2001, BioScience Productions, Inc., an education resource of the American Institute of Biological Sciences. Excerpted with kind permission. Full text of the article is available at http://www.actionbioscience.org/genomic/barash.html. Dr. Carol Isaacson Barash is the founder and principal of Genetics, Ethics & Policy Consulting (GEPC), which specializes in optimizing the integration of genomics into 21st- century health care delivery. Prior to establishing GEPC, Dr. Barash was director of a study on genetic discrimination funded by the Department of Energy. She is a trained philosopher with over twenty years experience in health care. ### << Previous Next >> [ View All Perspectives ] |
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