A New Dynamic

A New Dynamic With an eye toward host-pathogen interactions, can a Penn State center predict and prevent the next pandemic? By Brendan Borrell ARTICLE EXTRAS 1 "Our vision really is to have a systems approach to disease," says Hudson. "Issues that go from intracellular interactions between viruses and cells right the way through to pandemics, something we call the protein-to-pandemic link." Pathogens don't just interact, they evolve. In the 1960s, optimistic researchers had declared victory over infectious disease. It was time to move on to heart disease, cancer, and psychiatric disorders. That bubble burst in 1981 with the recognition of HIV. The disease had leapt from nonhuman primates to humans and continued to evolve and diversify in ways scientists still don't understand. Bryan Grenfell began his career on this first wave of disappointment. He worked with Roy Anderson, an early pioneer of disease ecology at Imperial College London, to build mathematical models of the population dynamics of the brown stomach worm, a parasite of cattle. Over the years, his models became more complex as he added a spatial dimension and started crunching a measles dataset that spans fifty years. He spends most of his days in front of two 24-inch Apple monitors, on which he can scrutinize the output from enormous simulations piped in from a campus facility where a 10-teraflop computer bank crunches his data. View an 2 Ronald Ross, one of the first to use mathematical models in epidemiology, first introduced the concept of R0 in 1897. If R0 is low (less than one), then it may be possible to wipe out the disease, but as it increases eradication becomes increasingly unlikely. Still, the work of mathematicians was neglected by public health officials for the better part of the century. As May puts it, epidemiologists in Africa were deemed about as useful as CAT scanners, seen as overkill in a continent lacking basic human services. Halfdan Mahler, head of the World Health Organization from 1948 to 1990, dreamed of barefoot doctors in every village. Hudson grows animated as the group discusses the paper, which demonstrates that Ross was only partly right. The basic reproductive number is remarkably heterogeneous: It can vary anywhere between 1 and 3,000. The students complain that the paper is impractical, and one student suggests that it really just comes down to finding breeding mosquitoes and wiping them out on a case-by-case basis. Hudson wonders out loud: "Do we really need science to address these questions or is it just common sense?" He talks about a privately run park he visited in South Africa in which operators dumped animals of different types into fenced-in tobacco fields. "To begin with, of course, they bought too many leopards and cheetahs and they ate all the gazelles and things. Then, they all started dying off, and the elephants increased quite dramatically and they suddenly discovered they were knee-deep in elephant [dung]," he says. "The only thing they needed to introduce was dung beetles. Then, everything went off. We didn't need ecology to tell them how to do it. They just put it all in the same pot and stirred it up." His comments hint at the challenges CIDD will face as they attempt to scale up from proteins to pandemics. Uncertainties at the small scale become magnified in the ecological realm, and the true currency of disease ecology is not a measurable parameter like R0, but rather, stochasticity and heterogeneity. Research of the type that CIDD is promoting may never conquer infectious disease, but it might assist in controlling it. Later that afternoon Hudson is heading to a late meeting. He's been scheming for a way to hire three new faculty members from the United Kingdom and Australia, and he counts on his fingers the number of E-mails he has to send to gain support from the administration. Bjørnstad, on his way to the Allen Street Grill, asks Hudson to join him, but to no avail. Hudson has two more meetings planned that night at his house. With a grin, he adds that he likes talking about enormous gobs of money. He's been doing that quite a bit lately. Recently he claimed space in a proposed biology building that will bring together CIDD faculty currently dispersed on campus. Allen Street Grill is one of several pubs crammed onto the corner directly across from campus. In the wood-paneled room upstairs, Bjørnstad greets Grenfell and Stephan Schuster. Grenfell and Bjørnstad recently improved the measles model by including a "gravity" term, which factors in both the distance and size of cities in propagating an epidemic. Schuster, another CIDD member, has just developed a program, MEGAN, which can be used in performing a metagenomic analysis on a slab of beef, taking advantage of the shotgun approach to classify every microbe contained within. In his spare time, he's been sequencing the woolly mammoth. As drinks are poured, the conversation eventually shifts from work to a recent announcement of a futures market for avian influenza. The Robert Wood Johnson Foundation put up roughly $250,000 to create a trading market in which authorities might wager on their predictions for pandemic scenarios. In a bar full of experts, even lighthearted prophesy takes on a foreboding air. Postdoc Jamie Lloyd-Smith remarks, "I'm bullish about bird flu." References 1. A Dobson et al., "Sacred cows and sympathetic squirrels: the importance of biological diversity to human health," PLoS Med, 3(6): e231, 2006. 2. D.L. Smith et al., "Revisiting the basic reproductive number for malaria and its implications for malaria control," PLoS Biol, 5(3): e42, 2007.

A New Dynamic

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	A New Dynamic With an eye toward host-pathogen interactions, can a Penn State center predict and prevent the next pandemic? By Brendan Borrell