A Systems Approach to Global Health

What could systems biology do for global health?

Answering that question was the goal of a two-day conference held Sunday and Monday at Seattle’s Institute for Systems Biology. Obviously, the institute would like to argue that its approach (still somewhat broadly, vaguely, defined) is of value to global health since there is now big money in this arena.

The challenge for high-tech medicine is that global health solutions, in general, need to be cheap since most of the real problems are in communities where people live on $1 or $2 a day. Even coming up with a drug or vaccine that costs $20 per dose is often too expensive to be practical. But based on some of the presentations, there may be value in using high-powered computation to sort through the massive biological databases (of genes and proteins and such) to help solve some problems of the developing world.

Emory University’s Bali Pulendran described sophisticated techniques that can be used to figure out how vaccines actually work. As Pulendran noted, yellow fever vaccine is one of the most effective vaccines in use but nobody had known exactly how it works (which is the case for most vaccines). He and his colleagues used a systems biology approach to identify some 100 genes associated with a strong immune response, which led to finding the key proteins triggered to prompt immunity (report). Pulendran says this approach could be used to improve the effectiveness of vaccines.

Alan Aderem, co-founder and director of ISB, talked about how his team applied a systems approach to figuring out what went wrong in an HIV vaccine study known as the STEP trial. Done mostly in Africa, the study was halted when it became clear those getting the vaccine were also more likely to get infected with HIV. It turned out that people who had strong immunity to a particular cold virus, known as adenovirus 5 (Ad5), were made more susceptible to HIV by the vaccine. Nobody yet truly understands why. Aderem and his colleagues applied a systems approach to identify some critical players in the immune response that he claims ((I couldn’t quite follow it all) showed how people with a strong reaction to Ad5 may have had a diminished protective response to HIV.

The problem here is that both of these examples, though impressive in analytical power, are retrospective. These systems biologists are applying their fancy analytical tools to try to figure out in more detail what the vaccines are doing – after-the-fact. Aderem acknowledged that nothing in his approach would have allowed scientists to predict beforehand that people with high immunity to this cold virus would react negatively to the experimental HIV vaccine. But that is the goal, he said.

Lee Hood, president and co-founder of ISB, contends that systems biology is the future of medicine. Hood talks a lot about something he calls “P4” medicine – predictive, preventive, personal and participatory. But Hood’s vision of the future is based on the assumption that the cost of computing and the cost of managing every individual’s entire genomic blueprint will go down so fast we will all be getting our genomes done at the doctor’s office. He’s great with the scientific vision thing, and with buzzwords, but I’m not so sure about his economic trending predictions. At the meeting, Hood said Bill Gates once asked him what he can do today, now, to help improve the health of poor people around the world. Hood, in characteristic fashion, answered that “Tomorrow is now today.” Whatever that may mean, systems biology does appear to have potential for assisting with some large-scale (and well-funded) western science efforts aimed at tackling tough analytical questions in global health. It seems unlikely it could produce many tools or techniques that will offer help directly to people in poor countries.

Tom

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