'Evidence-based' medicine, move over

Personalized approach tailors therapy based on genes, metabolism, environment

“Personalized medicine” is the mantra of modern medical science, a popular phrase coined to describe an impending world in which patients are treated based upon their individual genetic makeup.

But seven years after the first human genome was mapped, the idea remains more rhetoric than reality. There has been measurable progress, to be sure. Scientists and celebrities have had their genomes sequenced. Consumers can now purchase at-home genetics tests that purport to identify disease risk, such as one’s chances of getting cancer.

Dr. Gary Firestein

On the other hand, a recent Food and Drug Administration investigation found the claims of many at-home tests to be unfounded, their results dubious at best. We asked Dr. Gary S. Firestein, dean of translational medicine at the University of California San Diego’s School of Medicine and director of the Clinical and Translational Research Institute, to survey the situation and separate the hope of personalized medicine from the hype.

Q: How does “personalized medicine” differ from the treatment patients receive today?

A: Currently, we try to treat patients with “evidenced-based” medicine, i.e. using information based on clinical trials to give the best results. There are many problems with this approach. The main issue is that groups of patients selected for a clinical trial might have completely different characteristics from a person who needs therapy in the doctor’s office that day. For example, in rheumatoid arthritis there have been major advances in treatment, but of the new “biologic” drugs, only about half of the patients tested have a good response. We don’t know why and because we have no way to predict who will respond to what drug, doctors must test them one at a time until they find the right treatment for each patient by trial and error. In “personalized” medicine, the idea is that we evaluate each person as a unique individual and specifically tailor their therapy to their genes, metabolism and environmental exposures. We would predict in advance what “type” of rheumatoid arthritis a patient has, and use that to decide the best treatment from the start.

Q: The promise of personalized medicine is huge, but we’re clearly not there yet. Is it a question of science or something else?

A: We are only beginning to scratch the surface on personalized medicine because the technology for evaluating or stratifying individuals is expensive and not well-developed. The amount of information that will be collected and analyzed is enormous compared with our current capabilities. Deciphering a person’s genes is only a small part of the puzzle. Genes are important and will provide valuable clues to disease susceptibility in some cases, but there are many other ingredients in the mix, including the environment, the proteins expressed, how DNA is modified in cells, how metabolic pathways are altered. Many of these seem to be independent of our genes. Also, some genes are important only in specific subpopulations of people, such as Asians or people of Western European descent. A separate complete analysis of each group is needed before we truly understand the importance of a gene in a single person.


