Each of us carries 10 to 15 "mistakes" in our personal genetic code. Though most of us are blissfully ignorant of our genetic flaws, these typos in our DNA may determine whether we have children, develop colon cancer, or end up with Alzheimer's.
Most genetic mistakes land in unimportant places--the genome is a large document after all--but occasionally they occur in a region that, either individually or in combination with other factors, has been shown to cause a genetic disease. As our knowledge of the human genome expands, more and more of these genetic defects are discovered. For practically each one, a new genetic test has been created. Someone has to interpret the results of these tests, predicting which genetic changes are harmless and which are bad news. And the people who do this work constitute a relatively new and growing class of science-trained professionals: clinical molecular geneticists.
Clinical molecular geneticists have a Ph.D. in genetics or a related discipline and have completed at least 24 months of postdoctoral training in an accredited clinical-molecular genetics program. Almost 40 such programs exist at locations across the country (complete listing of programs ). Trainees spend 6 months rotating through molecular diagnostic facilities and the rest of their time taking courses in medical genetics and doing research. Training exists for similar specialties in clinical biochemical genetics and clinical cytogenetics. Once training is complete, fellows--for almost all molecular-genetics trainees are supported by institutional fellowships-- are eligible to take an exam given every two years by the American Board of Medical Genetics.
A job for life
Those "boarded" in clinical molecular genetics are part of an elite few who are qualified to run a molecular diagnostics facility in any scientific sector, be it academia, government, or industry.
"If you want to have a safe job--a job for life--then clinical molecular genetics is it, no doubt about it," says Maximilian Muenke, who has been directing a medical genetics training program for more than a decade. One of the greatest joys of a career in diagnostics comes from what it lacks--a need to locate grant, loans, and other sources of support for research and research training. Funding for research in diagnostic labs at universities such as Johns Hopkins in Baltimore, Maryland, or the University of North Carolina at Chapel Hill comes in large part from the services they offer, including prenatal diagnosis, carrier testing, and diagnostic testing.
Suzanne Hart directs the Clinical Molecular Genetics Program at the National Institutes of Health (NIH) in Bethesda, Maryland. "Often as a Ph.D. in an academic setting, your value is based on how much funding you bring in," says Hart. "For me, being in molecular diagnostics and offering genetic services meant I had other value besides the number of grants I had." The research might end up on the backburner as new cases come in, but sometimes a new study may emerge from the tests you are doing. Hart says, "You might see a certain phenomenon and decide to explore it. Or your research could lead to a new molecular test."
That new test could eventually spin off into a new company, as it did for Sherri Bale, president of GeneDx, a molecular diagnostics laboratory in Gaithersburg, Maryland. Bale, who spent 16 years at NIH studying hereditary skin disorders, decided to take the leap into the world of diagnostics because she thought it was the way to help the most people. "The cure or gene therapy is of course the ultimate goal, but we we're not going for the ultimate goal, but for something that could be achieved," says Bale. "It was hard to talk to the families and say this is something we're trying for, but it might not happen in ten years. With diagnostics, you can help someone in an immediate way." Commercial labs come in many different flavors, from a national lab that screens as many as 500 samples a day for a single disorder, to the smaller "boutique" labs like GeneDx, which test for rare diseases.
Almost 600 diagnostic laboratories are listed on the GeneTests Web site , a listing of molecular genetic testing accessed by physicians and researchers around the world. Those laboratories test for genetic factors implicated in more than 1000 diseases, ten times the number listed in the laboratory directory when it was established in 1993.
Although new tests don't translate into new jobs directly and immediately, that does appear to be a trend. "I know there are jobs out there; molecular diagnostics is growing like crazy," Bale says. But Hart, who has directed diagnostic facilities at Wake Forest University in Winston-Salem, North Carolina, and the University of Pittsburgh, cautions that this does not mean that you can find a position anywhere you might wish to work. "You can't go to some small town and expect your board certification to mean anything," says Hart. "But if you're in a place with a hospital or an academic institution, you'll be able to find a job."
Not for shrinking violets
If you are shy--or if you just prefer the bench to interacting with others--molecular diagnostics might not be the best fit. Along with the growth in the field has come competition, meaning that a certain degree of marketing goes into running a diagnostic lab. Clinical molecular geneticists go to meetings just like any other scientist, but they spend some of their time convincing physicians to send them their samples. Bale, who enjoys the marketing aspect, has only one complaint about her job. "Dealing with insurance companies. Trying to teach them about genetics, and why these tests should be reimbursed on behalf of the patient."
Clinical molecular genetics can also involve interaction with the patients themselves. While at the University of Pittsburgh, Hart started a clinic for patients with Prader-Willi syndrome, an uncommon inherited disorder leading to life-threatening obesity. "People might call you because your lab tests for something that appears to run in their family. Or if you are doing a research study, a doctor may call and see if you can look at a patient of theirs to see if they have features of that disease." Some cases do not entail any interaction--a sample comes in, a test is run, and the results are reported. But in many cases, the opportunity exists to learn more about, or possibly even meet, the patient at the other end of the sample.
Either way, that patient always has to be kept in mind when performing a diagnostic test; the result has to be translated into a real risk for disease that not only has implications for the patient but also for all the family members that share the same DNA. So above all else, molecular geneticists must possess an eye for detail. Bale jokes that the personality best suited for molecular diagnostics is one with obsessive-compulsive disorder, explaining, "You have to be vigilant and very careful. Everyone here is a little bit psychotic, and we're successful because of it." Apparently a sense of humor is also a job qualification.
Marla Vacek is a postdoctoral fellow in clinical molecular genetics at the National Human Genome Research Institute.