Rodbell lecture features systems medicine pioneer Leroy Hood
By Robin Arnette
Leroy Hood, M.D., Ph.D., has spent his entire career thinking about and creating technologies that have changed the way researchers decipher the fundamental principles of biology. His current endeavor, called P4 medicine, uses a systems approach to studying disease and its counterpart, wellness. Hood addressed the four P’s of his approach to medicine — predictive, preventive, personalized, and participatory — during his 2015 Dr. Martin Rodbell Lecture Series seminar March 10.
NIEHS and National Toxicology Program (NTP) Director Linda Birnbaum, Ph.D., introduced Hood to the audience, which included Barbara Rodbell, the widow of the late Nobel Laureate Martin Rodbell, Ph.D. NTP toxicologists Warren Casey, Ph.D., and Kristine Witt, cohosted the presentation.
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Systems medicine seeks to quantify wellness
As president and cofounder of the Institute for Systems Biology (ISB), a nonprofit biomedical research organization in Seattle, Hood thought that if he and his team could track wellness and watch its transition into disease, they could see the first mechanisms of illness. That would help them understand how to put people back onto a path to wellness.
"This wellness endeavor will create a whole new industry that will be separate from what I call the disease industry, which is the current health care industry," Hood said. "I predict that in 10-15 years, the wellness industry will far exceed the market captured by the disease industry."
According to Hood, there are three major principles behind this goal, which he calls P4 medicine or systems medicine. First, every individual patient’s personal and health information will be used to create a data set, and then scientists will use computational tools to create a profile for each individual. Hood’s team has already successfully modeled data for 100 people. His goal now is to conduct a long-term study of 100,000 people (see sidebar).
Second, using this approach, researchers can identify biological networks, which are the information channels that govern development, normal body functions, and aging. Hood said that when these channels become altered, they lead to disease.
Third, data collection should be as global as possible, to capture the unknown elements of particular diseases. Hood said this would allow the ISB team to look at the dynamics of the system and see how they change across time and place.
Early P4 studies
Hood went on to explain some of his early P4 studies. To understand the dynamics of neurodegenerative conditions caused by prions, or misfolded proteins, Hood collaborated with George Carlson, Ph.D., of the McLaughlin Research Institute in Great Falls, Montana. The team found 300 genes potentially involved in neurodegeneration. Further analyses uncovered two major findings. First, these genes turned on four processes in sequential order — accumulation and replication of prions, activation of microglia, degeneration of synapses, and death of neuronal cells. Second, the biomarkers for these processes could be detected in the blood. A biomarker is a molecule, detected in the body, that is a sign of a particular process.
In another example, Hood explained that pulmonary oncologists see thousands of patients that have nodules in their lungs. Many patients elect to undergo surgery to remove the nodules, but 40-50 percent of the patients have benign growths.
Using the systems approach, Hood and his team identified 471 molecules relevant to lung cancer, and additional computer modeling narrowed it down to 13. These 13 proteins were then used as a biomarker panel, allowing the researchers to rule out benign nodules in patients with 90 percent accuracy. "We prevented more than a third of the unnecessary surgeries, saving the healthcare system about $3.5 billion a year," Hood said.
Human disease exhibits enormous biological complexity, and it seems that P4 may be another of the paradigm changes that Hood will impart to the world.