Using supercomputers to find vaccines against malaria, AIDS and TB

Flickr, ghinson

Scientists in Seattle hope to pioneer a more “rational” approach to vaccine development, exploiting powerful computers to better identify immune system targets and reduce the huge burden (and cost) of clinical testing.

“I intend to focus first on malaria vaccines,” said Alan Aderem, an internationally recognized immunologist who will soon be taking the helm of Seattle BioMed. Aderem co-authored a paper in this week’s edition of Nature in which he outlines a new strategy aimed at discovering vaccines against HIV, TB and malaria.

Arguably, the ways in which researchers test and develop vaccines against disease today haven’t changed that much since the 18-century British physician Edward Jenner injected a young man with cowpox to see if it would protect him from smallpox. It did and, so the story goes, vaccines and the science of immunology were born.

Scientists certainly have more sophisticated tools and methods today, but testing a vaccine is still often a “shot in the dark” because of our incomplete understanding of how the immune response works.

What Aderem, his team at Seattle BioMed and collaborators at the neighboring Institute for Systems Biology (which Aderem co-founded with Lee Hood) want to do is exploit the power of computers to more precisely monitor what happens in the immune system when a virus or vaccine gets introduced.

Alan Aderem
ISB

“What we are trying to do is identify the networks involved,’ said Aderem.

Rather than try to find some single cell or immune response to fashion a vaccine around, he said their goal is to recognize first that the immune response often involves many players. Using powerful computational analysis, he said their approach is to initially identify the complex pattern, or network, in the respones.

“Once you know this, you can go in with much smaller, more targeted trials and within a fairly short time period identify the agents of immunogenicity,” said Aderem.

Sounds good in theory, but then so did the idea of “nuclear energy that’s too cheap to meter” and the ongoing promise made by Hood and others that mapping the entire human genome will transform clinical medicine.

Lee Hood
ISB

Hood is perhaps one of the world’s leading advocates claiming these new high-tech tools will revolutionize medicine, these days dubbing it P4 medicine. But as the director of the National Human Genome Research Institute noted in another Nature paper recently, the clinical benefits are all still largely a promise.

The question is if systems biology will truly be able to help develop cheap, effective vaccines for use in poor countries. Or will it remain, like much of genomics and P4 medicine, an expensive high-tech promise that appears still a distant glimmering on the horizon?

Here’s a post I did a year ago, exploring this question in greater detail, when Aderem, Hood and others at ISB held a forum on the promise of systems biology for global health.

On the cost issue, Aderem said this high-tech approach to vaccine development is almost certain to cost less than today’s methods of developing vaccines.

“Vaccine trials today are impossibly expensive,” said Aderem.

This, he said, is because researchers are still basically just following Jenner’s approach — trying something without really knowing fully why it works. Such an approach requires a massive amount of volunteers because of the need to achieve statistical power (i.e., a clear, demonstrative difference between those who get the vaccine and those who didn’t).

Others criticize the systems biology approach for suffering from an inherent flaw – presuming that doing this massive data collection and manipulation will produce a “pattern” or network of signals that will lead to a vaccine target. Some say this is high-tech “magical thinking” that is no more rational than Jenner’s empirical approach.

Aderem said such criticism is unwarranted. They are not saying the computers are expected to come up with all the biological insights. Rather, he says, they are just more powerful tools to assist the researcher who begins with an insight or hypothesis.

Clearly, Aderem says, the current approach to vaccine development has run up against some serious obstacles when it comes to HIV, malaria and TB. Computers, systems biology and technology in general will never replace a scientist’s insight, he says, but it’s time to start using the tools of the 21st century to move vaccine development completely out of the 18th.

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Tom Paulson

Tom Paulson is founder and lead journalist at Humanosphere. Prior to operating this online news site, he reported on science,  medicine, health policy, aid and development for the Seattle Post-Intelligencer. Contact him at tom[at]humanosphere.org or follow him on Twitter @tompaulson.