Viewpoint: Medical Education in the Post- Genomic Era

VOLUME 10, NUMBER 9

JORDAN J. COHEN, M.D., PRESIDENT

JUNE 2001

Viewpoint: Medical Education in the Post-Genomic Era

By Bruce Korf, M.D., Ph.D.

By Bruce Korf, M.D., Ph.D.Medical Director, Partners Center for Human Genetics Associate Professor of Neurology, Harvard Medical School

We are beginning the 21st century with a gift that will be of key importance in the study of human biology, that will lead to fundamental changes in the practice of medicine, and that will necessitate a shift in emphasis in medical education. The sequencing of the human genome is the culmination of a century of effort that began with the "rediscovery" of Mendel's laws and the realization of their importance to human disease during the first decade. The structure of DNA was known by mid-century, and the ability to isolate and sequence genes was developed during the past 25 years. Genetics emerged as a medical specialty during the 1950s and 1960s, with the development of methods of chromosomal analysis, newborn screening programs for inborn errors of metabolism, and prenatal diagnosis.

For most of the past five decades medical genetics has focused on the study of rare disorders, important to the individuals and families who have to deal with them but of marginal interest to most medical practitioners. Although it has been recognized that genes contribute to the pathogenesis of common disorders, such as cancer, cardiovascular disease, and diabetes, the tools of genetics were not up to the task of sorting out which genes contribute and how. Now, with a catalog of all human genes and over a million genetic markers in hand, we have a critical resource with which to begin the task.

How will physicians use genetics in their clinical practice? The announcement of the working draft of the genome has been accompanied by inevitable hype, simplistic notions of genetic determinism, and concerns about the ethical use of this new knowledge. It is not clear whether genetic testing will be used to determine risk of common, complex disorders or whether effective interventions will be available to reduce risk. Similarly, the notion that we will have the ability to choose the characteristics of our offspring or to fix "defective" genes at will requires extrapolation of knowledge far beyond current capability. Nevertheless, genetics will catalyze profound changes in the practice of medicine in the immediately foreseeable future that will place major demands on the system of medical education.

First, physicians need to learn to use family history as a screening test. Although most common disorders may require the combined action of multiple genetic and environmental factors, in some families a single major gene contributes overwhelmingly to risk. For example, long QT syndrome or cardiomyopathy can result from gene mutations that are transmitted as dominant traits. Similarly, in about 7 percent of breast cancer cases there is a single dominant gene that conveys a lifetime risk of 60 percent to 80 percent. Most complex disorders have single-gene versions, which, though individually rare, will become increasingly important in the aggregate. Family history helps identify those individuals who are at high risk and who may benefit from testing and from prevention, surveillance, or treatment strategies.

Second, the therapeutic armamentarium will vastly increase as the pathophysiology of disease is understood, largely due to the study of genetic mechanisms. Identification of genes that underlie rare single-gene disorders, or even of genes that make minor contributions to risk, reveals the cellular pathways that are required for normal function and the mechanisms by which these may be perturbed. The components of these pathways become targets for development of new pharmaceutical agents that more precisely attack the disease mechanism and reduce the likelihood of side effects. In some instances, genetic tests will be used to determine which drug is best suited to treat a particular patient based on the genetic factors that contribute to that individual's disorder and the person's genetically determined rate of drug metabolism.

Third, physicians will need to understand how genes flow through populations and how this affects indi-vidual risk. There are many examples of populations in which the risk of a specific genetic disorder is sufficiently increased to warrant screening. Successful programs have been in place for screening the Ashkenazi Jewish population for Tay-Sachs disease and several other disorders, and individuals of African, Mediterranean, and Southeast Asian ancestry for globin disorders. Moreover, one of the greatest gifts of the genome project may be the recognition that common notions of "race" have no biological basis.

Application of the tools of genetics in medical practice will require that physicians acquire new knowledge and skills, including recognition of the patterns of genetic transmission in a family and the ability to appropriately order and interpret genetic tests. Physicians will need to critically evaluate proposals for population screening for genetic disorders and the results of studies on the outcomes of interventions for individuals at risk.

Most important, physicians will need to know how, when, and where to go for up-to-date information. Genetics has come of age along with information technology; indeed, genetics is the information technology of the organism. The roles and interactions of more than 30,000 genes and 100,000 proteins exceed human ability to sort and retrieve information. Knowledge of databases and decision-support tools is becoming essential in medical practice.

Genetics is a major driver in the effort to increase the scientific basis for the practice of medicine. Patients will increasingly expect that their medical questions have answers, and that their doctors will be able to find these answers. The need for physicians to listen to their patients and to guide them through complex decision-making processes has never been greater. Physicians will learn to focus on the patient as an individual who is a product of evolution, who has a familial genetic legacy, who has undergone a process of development, and who has a unique history of environmental interaction.