Tailoring Medical Treatment to the Individual

Physicians should one day be able to pinpoint differences among patients at the molecular level and use that information to truly individualize treatment. Getting to that point, however, will require a monumental effort.

Which of an oncologist’s lung cancer patients will respond favorably to a new treatment, and which will see no improvement at all from the same drug? Of all the patients an internist sees with high cholesterol, who are the ones most at risk of developing heart disease?

While physicians have long been able to use diagnostic tests or facts gleaned from a patient’s family history to get at such questions, the answers still sometimes elude them.

That’s why the evolving field of personalized medicine, in which a strategy for prevention, diagnosis, or treatment of a disease would be tailored to a patient’s unique genetic makeup, holds such promise. And with the help of researchers who are extracting and harnessing ever more information from the human genome, physicians should one day be able to pinpoint differences among patients at the molecular level and use that information to truly individualize treatment.

Getting to that point, however, will require a monumental effort.

“Diabetes, heart disease, and many cancers are generally caused not by just one gene, but rather by the combined effect of many genes. How they do so is a crucial problem to understand in order to develop better diagnostics and therapeutic strategies for patients,” says Kevin P. White, the James and Karen Frank Family Professor in Human Genetics, Ecology & Evolution, and the College.

White, who investigates how networks of genes and proteins control development and disease, is hard at work on efforts to unlock that understanding.

Not long after joining the University in 2006, he and one of his research teams won a $9-million grant from the National Human Genome Research Institute to identify all regulatory elements—the DNA sequences that control when and where specific genes get turned on or off—in the genome of the fruit fly (Drosophila melanogaster).

“The fruit fly genome is the ideal model for this study because it shares the structure and many features of the human genome,” White says. “Beginning with Drosophila allows us to test our predictions in live animals, the only way to experimentally validate our computational methods.”

That sort of groundbreaking work adds to the significant work being done by Chicago’s other computational and genomics teams; its theoretical genetics researchers, led by T. Conrad Gilliam, the Marjorie I. and Bernard A. Mitchell Professor and Chair of Human Genetics; and scientists at Argonne National Laboratory, whose high-end computing architecture allows for the extraction of crucial biomedical information.

Those combined capabilities helped convince White that Chicago was the ideal place to establish a research and academic program focusing on genomics, the study of the entire DNA sequence of an organism’s genome, and systems biology, the study of protein networks, cells, tissues, entire organisms, and other biological systems as integrated “wholes.”

“Conrad and I are working together to realize a vision that plays to the unique strengths of the University and Argonne for the development of personalized medicine and also to obtain support for the infrastructures underlying that vision,” says White, who also directs the Institute for Genomics and Systems Biology, a joint program of the University and Argonne.

To make that happen, building bridges among many diverse disciplines is essential, and Chicago, with its single campus unifying undergraduate, graduate, and medical training and research, has a clear head start.

“Chicago has an institution-wide commitment to interdisciplinary research that is going to be key to the development of our genomes-to-medicine concept,” White says.

That emphasis on collaboration makes it possible for White’s group to work with the Department of Pathology, for instance, to collect large numbers of clinical specimens, particularly of cancers from patients who undergo surgery at the University of Chicago Medical Center. Together, the teams are developing diagnostics for predicting outcomes and informing the treatment of cancer patients. Among their recent discoveries: a new biomarker for breast cancer that predicts metastasis and what is believed to be the first molecular marker for the most common kind of kidney cancer.

Personalized medicine will be driven by research at “the interface between genetics, clinical medicine, and the computational sciences,” says Gilliam, a specialist in identifying and characterizing heritable mutations that affect the nervous system.

“There are still important problems to solve at this interface, but Chicago has a lot going for it. With the arrival of leading genome scientist Kevin White, we are able to generate massive data sets that measure hundreds of thousands of individual molecular events in each of potentially thousands of hospital patients. With our combined strength in computational science and theoretical genetics, we are one of very few institutes nationwide who can manage and analyze these data in a sufficiently sophisticated manner to make sense of them.”

Argonne—which the University manages for the U.S. Department of Energy—“provides a great home for doing big science,” says White. At the same time, Chicago’s computation experts are leading the way in understanding the implications of the new technological capacity for processing huge amounts of information.

White hopes to set up a state-of-the-art gene expression processing facility at Argonne to handle projects involving tens of thousands of specimens, including blood and tissue samples. Using DNA chips, scientists will be able to determine the whole repertoire of which genes are turned on or off, up or down, throughout the entire genome under different conditions.

Also contributing to such big thinking is Chicago’s involvement (along with Northwestern University and the University of Illinois at Chicago) in the Chicago Biomedical Consortium, whose goal is to bridge institutional boundaries to transform research at the frontiers of biomedicine.

But scientific challenges, though crucial to the task, are not the only ones to overcome in the quest for realizing the true possibilities of personalized medicine. There are ethical, legal, and social issues to tackle as well.

“How we practice medicine, treat people, and insure people will resonate through our economy,” says Gilliam.

And the strength of Chicago thinking, he says, could make it a leader in creating new policy paradigms that respond to this revolution.

“We have people in the Graduate School of Business already thinking about how personalized medicine will have a dramatic impact on the insurance industry, and in ways that are not always intuitive,” Gilliam says. Chicago’s MacLean Center for Clinical Medical Ethics, the nation’s leading center for the teaching and study of clinical ethics, will be a key player as well.

“We have the opportunity to bring together all the brainpower at Chicago—not just in medicine, but in business, law, and ethics—and become national policy leaders.”