February 2010
Feature Story

Anne Ford

Pathologists Mark Boguski, MD, PhD, and Jeffrey Saffitz, MD, PhD, have never had to lace up ice skates to go to work. But when the two sat down several months ago to brainstorm ways to incorporate personal genomics into the pathology residency program at Beth Israel Deaconess Medical Center, Boston, their conversation was influenced by a quotation attributed to legendary hockey player Wayne Gretzky: “A good hockey player plays where the puck is. A great hockey player plays where the puck is going to be.”

And where the puck is going to be, Dr. Saffitz says, is the sequencing of individual genetic information as everyday medical practice. “As we come to recognize more and more the genetic basis for chronic disease, as we begin to understand more about the genetics of cancer, and as more drugs become available that are targeted at a specific mutation, then it will become absolutely obligatory to do this kind of genetic analysis on many patients in many different settings. It’s not a question of if; it’s a question of when,” he says. And if pathologists don’t take the lead in helping clinicians interpret that analysis, “then we’re going to be losers. There’s no doubt.” Dr. Saffitz is chief of the Department of Pathology at Beth Israel Deaconess and Mallinckrodt professor of pathology at Harvard Medical School. Dr. Boguski came to Beth Israel Deaconess less than two years ago from Novartis, where he was vice president of research. He is associate professor of pathology at Harvard Medical School.

Last fall, Beth Israel Deaconess’ pathology residency program became what could be the first in the country to offer training in personalized genomics. The training includes lectures on current genotyping platforms, next-generation sequencing, genetic counseling, and the like, as well as the chance for residents to undergo genetic testing themselves. Dr. Saffitz hopes the training will not only introduce Beth Israel Deaconess’ pathology residents to the world of personal genomics, but also spur pathology residency programs at other institutions to include similar material. “Our goal is within two years to have every pathology residency program in the country incorporating something similar to what we’re doing—and having pathology as a discipline make a very bold and clear statement that we will do this in the future,” he says.

Beth Israel Deaconess’ effort was inspired at least in part by Dr. Boguski’s decision some time ago to have genetic testing performed on himself by three direct-to-consumer companies. “I’m the type of person who learns by doing,” he says. “I decided that rather than criticize this [direct-to-consumer testing] from the point of view of not having done it, I really did owe it to myself to see what was being offered to patients and how they might interpret this data, react to it, et cetera.” He was primarily curious to find out whether and to what extent the companies’ interpretation of his results varied. “What I learned is that the basic data was uniform across all three companies, but there were significant differences in the risks they associated with these results,” he says.

The experience convinced him that it was important for pathology residents to understand how these companies calculate and express the risks of disease to consumers, as well as “the scientific methods and experimental designs by which genetic associations are discovered and reported in the literature,” he explains. “We want them to understand how the probability statistics are calculated. Each resident picks a disease, and then they have to go off and learn about it in the literature and say whether they think the evidence is strong and what the experimental design was. The purpose of this exercise is giving them the critical skills to evaluate the literature, so when a patient or one of their professional colleagues comes to them and says, ‘What does this mean?,’ they’ll know all the caveats.”

Other molecular genomics experts agree. “Doing the test is one thing, but the interpretation is what’s critical,” says Gail H. Vance, MD, professor of medical and molecular genetics, director of the genetic testing laboratories, and director of the Indiana Familial Cancer Program at Indiana University School of Medicine, Indianapolis. “As technology advances, there’s going to be more and more automated molecular testing, and it’s not going to be doing the testing that’s critical; it’s going to be interpreting the testing,” she says.

One potentially controversial aspect of the personal-genomics training at Beth Israel Deaconess: the chance for residents to undergo genetic testing themselves. Drs. Boguski and Saffitz stress that they put the idea at the outset before the institution’s internal review board, which okayed it, and that the testing is strictly optional. “Conceptually, it’s no different from practicing physical exams on your lab partner in medical school or doing your own blood type,” Dr. Boguski says. “What the testing did for me was demystify the whole process, and I think we should do that for the residents. Everyone thinks they’re going to find out something terrible about themselves hidden in their genetics that they didn’t know before. I tell the residents, ‘Listen, if you know your family medical history pretty well, these tests are probably not going to tell you anything you didn’t already know.’” What did Dr. Boguski learn from his own genotype that he didn’t already know? “That I’m a slow caffeine metabolizer.”

Still, he and Dr. Saffitz worried how the residents would react to the opportunity. “Anything unknown is a little bit scary,” he says. As it turned out, about two-thirds of the residents decided to undergo the testing. “I think there’s a generational thing going on here,” he speculates. “People of my generation and beyond have certain expectations about privacy, and the generation that puts everything about itself on Facebook has a different point of view here. I think that spills over into knowing your own genome.” It helps, too, that the residents’ genetic test results remain private: “What they learn, we may never know, because it’s between them and their data set,” Dr. Boguski explains.

Of the several companies that offer direct-to-consumer genetic tests, Drs. Boguski and Saffitz elected to use Navigenics to test the residents’ specimens. “The reason we picked Navigenics is that they cover the fewest genes,” Dr. Boguski says. “They only cover ones for which there’s very, very strong evidence in the literature of an association” and for which the results are medically actionable. In addition, Navigenics offers genetic counseling to consumers who are concerned about their test results. (Dr. Boguski emphasizes that while Navigenics did give Beth Israel Deaconess a reduced price for the testing, “we did pay for the kits, to make sure there wasn’t any perceived conflict of interest or favoritism.”)

So how has the first round of personal genomics training gone for Beth Israel Deaconess’ pathology residents? Well, it isn’t over yet. The training is taking place in two parts—a series of lectures that were held last fall, and a series of followup sessions that will take place soon, once all the residents who elected to undergo the genetic testing have their results.

In the meantime, Drs. Boguski and Saffitz are working to spread the word about the training in hopes of spurring other pathology residency programs to create a similar course in their own institutions. “We have been invited to write a special article for the American Journal of Clinical Pathology, which we are now putting the final touches on,” Dr. Saffitz says. Provisionally titled “A Call to Action,” the paper will be an appeal to the academic pathology community to make personal genomics training an obligatory component of residency training in pathology. “We’re also working with the Association of Pathology ­Chairs’ program directors section. We’ve requested the opportunity to present our training program at their annual meeting this summer, where we hope to discuss program details with pathology department chairs and pathology residency program directors and urge them to adopt something similar,” he says.

In addition, the materials from Beth Israel Deaconess’ course, including lectures, are available to anyone at www.genomicmedicineinitiative.org. “It’s fair to say we’ve taken the lead on this, but we don’t want to be the only ones doing this,” Dr. Saffitz says. “We don’t want to be at all proprietary about it.”

On the contrary, he hopes that spreading the word about the training as widely as possible will help convince pathologists everywhere that personal genomics can and should fall into their purview. “If you need to make a diagnosis, and to make that diagnosis you have to look at a slide under a microscope and use pattern-recognition skills, well, we’re in very safe territory there,” he says. “But if to make the diagnosis and guide the clinical physician in managing a patient you need to analyze some genetic sequence information, you don’t have to necessarily be a pathologist to do that—you can be in almost any field. I think we have an opportunity now to say, ‘Look, this is basically pathology. This is clinical laboratory diagnostic activity. A sequence file is just like a tube of blood.’ We have to be at the forefront, and we have to be leading the charge.”