New Specialties for Physician-Scientists

MD/PhD students have long selected internal medicine for their clinical specialty. This was particularly true when I was an MD/PhD student, from 1976-83. Medicine played a dominant role in studies of disease pathophysiology--far more than the narrower clinical specialties--and this was reflected in all 4 years of my medical school curriculum. Accordingly, I and other MD/PhD students encountered the largest number of role models, physician-scientists, on medical rotations. Medicine was also unique for its breadth: It encompasses numerous organ systems and, therefore, diverse physiologic and pathologic processes.

Over the last 2 decades, however, much has changed that has enabled several other clinical disciplines to catch up to internal medicine. Increasingly, young scientists--and their more senior colleagues--are recognizing that outstanding research opportunities exist in other clinical specialties. The clinical neurosciences, for example--psychiatry and neurology--are being redefined by direct clinical research as well as state-of-the-art basic research with direct clinical applications.

Increasingly accurate animal models are now driving research, at the molecular and cellular levels, aimed at understanding the pathophysiologic mechanisms involved in many psychiatric and neurologic disorders. In drug addiction--my field--rodents will self-administer and addict themselves to the same drugs that humans self-administer and addict themselves to, which makes it possible to identify the neural circuits in the brain, and the molecular changes within those circuits caused by drug exposure, that underlie states of addiction. In Huntington's disease, mice carrying the pathologic genetic variant of the huntingtin gene are being used to understand how this genetic lesion causes degeneration of striatal neurons and to develop novel treatments for the illness. Similar examples could be given for many other disorders, including depression, schizophrenia, Parkinson's disease, Alzheimer's disease, Rett syndrome (an autismlike disorder), obesity, and multiple sclerosis.

Basic neuroscience research in psychiatry and neurology is also making exciting use of the latest tools for manipulating genes in vivo. Viral-mediated gene transfer now enables investigators to overexpress or knock out a gene of interest within highly localized regions of brain. Similarly, it is possible to generate genetic mutant mice in which the genetic mutation of interest (a knocked-out, overexpressed, or mutated endogenous gene) is induced selectively within particular brain regions in adult animals. These tools, coupled with animal models of disease and with the latest methodologies in genomics and proteomics, are leading to vast amounts of information about the nervous system under normal and pathologic conditions.

Translational--bench to bedside--research remains a particular challenge in the clinical neurosciences, in large part due to the inaccessibility of the brain. The brain is, after all, encased within the skull, and brain biopsies are not feasible for the vast majority of patients with psychiatric and neurologic disease. Then again, such obstacles often provide uniquely strong opportunities for major advances.

Genetics is a major domain where opportunities in clinical neuroscience are ripe. Most common psychiatric and neurologic disorders are highly genetic; 40% to 80% of these disorders are known to have genetic components. Indeed, psychiatric and neurological disorders are at least as genetically determined, and in many cases more so, than common diseases of other organ systems. The genetics of brain disorders are complex, in that multiple genes interact with a host of nongenetic factors to determine an individual's risk. But this is no less true of many common medical conditions.

Given the high inheritance of brain diseases, it is not surprising that tremendous advances are being made. The genetic basis of Huntington's disease, Rett syndrome, and of familial forms of Parkinson's and Alzheimer's diseases and amyotrophic lateral sclerosis are now established. The genetic basis of many epilepsies are similarly known. The identification of these genetic defects has fed back to create ever more realistic animal models of the diseases, as mentioned earlier for Huntington's disease. In addition, investigators are homing in on genomic regions that contain risk loci for many other disorders, such as depression, bipolar disorder, schizophrenia, and autism. The next decade or two will witness the discovery of numerous psychiatric and neurologic disease genes, and such discoveries will revolutionize the practice of these disciplines. No doubt, many of these discoveries will be made by physician-scientists!

The other major opportunity for translational research in clinical neuroscience is brain imaging. Recent advances allow neuroscientists to study levels of neurotransmitters or their receptors in specific brain regions via PET (positron emission tomography), SPECT (single photon emission computerized tomography), and MRS (magnetic resonance spectroscopy). In addition, fMRI (functional magnetic resonance imaging) allows the delineation of detailed neural circuits in the brain involved in complex human behavior. MD/PhD psychiatrists and neurologists have opportunities not only to apply these techniques to studies of their patients, but also to develop improved imaging methodologies.

This is a time of unparalleled opportunities in areas as diverse as radionuclide biology, computer science, and computational and cognitive neuroscience. Increasingly, investigators are also combining brain imaging with studies of human brain samples at autopsy. Application of genomic and proteomic techniques to the tissue is providing powerful insight into the molecular lesions underlying a wide variety of brain disorders.

Rich opportunities are also available in treatment, or so-called interventions, research. There is an all-too-common prejudice that psychiatrists and neurologists lack effective treatments for the disorders they're charged with treating. The facts show otherwise. Treatment of a range of common, chronic, and potentially fatal psychiatric and neurologic disorders (e.g., depression, schizophrenia, epilepsy) compares very favorably with the treatment of similarly common, chronic, and potentially fatal medical syndromes (e.g., chronic obstructive pulmonary disease, diabetes, congestive failure, solid organ cancers). Just as was commonplace a generation ago in internal medicine, the broad advances in psychiatric and neurologic neuroscience are driving the development of fundamentally new and exciting treatments for many brain diseases.

If I haven't convinced you of the tremendous scientific opportunities that await you as an MD/PhD psychiatrist or neurologist, there are practical reasons for choices of these specialties as well. Both fields require 4 years of residency training, during which time a typical MD/PhD student, at the right training program, can spend one and a half years doing research. As a result, it is commonplace for MD/PhD psychiatrists or neurologists to obtain fully independent, tenure-track assistant professorships--at the top universities in the country--within 4 or 5 years of their graduation from medical school. By contrast, MD/PhDs in internal medicine typically must devote 3 years to a general residency, followed by another 3 to 5 years of fellowship training, prior to their first faculty appointments.

Once they become faculty members, MD/PhD psychiatrists and neurologists have ample opportunities to obtain NIH funding for their basic or clinical research. The National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Neurological Disorders and Stroke, National Institute of Alcohol Abuse and Alcoholism, National Aging on Institute, and other NIH institutes and centers support disease-oriented basic and clinical research tailor-made for MD/PhDs. In fact, some of these so-called "brain institutes" lead the NIH in providing career awards for physician-scientists.

Today's medical schools are very different than the medical schools of 25 to 30 years ago. Medical school curricula are being revised to reflect the explosive pace of discoveries in the clinical neurosciences and other nontraditional specialties. MD/PhD students now encounter, during the basic-science years and during their clinical rotations, an increasing number of outstanding role models who embody the career-making opportunities available in psychiatry and neurology. And an increasing number of psychiatry and neurology department chairs, like myself, are MD/PhDs!

These same changes are occurring in several other medical specialties; clinical neuroscience is just one of several more specialized clinical disciplines that offer viable alternatives to internal medicine for exciting careers in state-of-the-art research. Dermatology, ophthalmology, anesthesiology, pathology, and several other specialties each offer abundant opportunities for important basic research with clear and important clinical potential.

Dr. Nestler is the Lou and Ellen McGinley Distinguished Professor and Chair of the Department of Psychiatry at the University of Texas Southwestern Medical Center at Dallas (5323 Harry Hines Blvd., Dallas TX 75390-9070, tel 214-648-1111, fax 214-648-4947, e-mail

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