Big answers from small creatures

A graduate student tracks the spread of viruses from bats to humans in Madagascar

By Cara Brook

IT IS SPRINGTIME in the Makira-Masoala peninsula of northeastern Madagascar, and the lychee trees are in full fruit. I sit crouched with my research team in camping chairs as dusk settles, our eyes intent on Rousettus madagascariensis, one of three species of endemic Malagasy fruit bat. The fox-faced bats flit deftly amongst the leafy branches, dodging our nets as they search out juicy pink fruits for their evening meal.

Our quiet vigil is interrupted by the arrival of a whistling gray-haired man from the nearby village who carries a net strung on a pole in one hand and a garish yellow plastic fuel can in the other. With a nod to us, he strides up to a neighboring tree and expertly scoops five of the feasting bats, pins the net to the ground with a bare hand, and coaxes the bats one-by-one into his yellow can. Mission accomplished, he straightens up with a wink and turns back home, rattling his can of bats in time to his whistle as he walks.

“Handeha hihinina andrehy izy?” I ask my Malagasy colleagues in astonishment. Is he going to eat the bats? Laughing at my horror, they nod in affirmation.

Bats as reservoirs

I study zoonotic diseases, infections that transmit from wildlife to humans, as a graduate student in Princeton’s Department of Ecology and Evolutionary Biology. Bats are native reservoir hosts — meaning they host viruses without getting sick — for a number of the world’s most dangerous human diseases, including rabies, Ebola and SARS. I want to understand how bats host these viruses without getting sick and what factors contribute to the viruses’ spillover to human populations.

A lot of my work involves building mathematical models to understand disease. When I started graduate school, I barely understood what a “model” was. Four years later, I recognize that a model is simply a representation of reality — it can be physical, like a model of the solar system; experimental, like a mouse that a scientist infects to monitor disease progression; or mathematical, like the equations we use to describe disease transmission in my field of disease ecology.

The goal is to build simple models that still adequately represent reality. One of my professors, Bryan Grenfell, once told me, “If you apply a complex model to a complex system, then you have two things that you don’t understand.” If we can understand our models, then we can learn by observing the differences between these models and the more complex reality.

In disease ecology, our simple models are mathematical equations that class all potential disease hosts — bats, in my research — into three categories: (1) susceptible to infection; (2) currently infected; or (3) recovered from infection and now immune. We use our equations to predict how the proportion of hosts within each category changes over time, and then we collect data to determine whether our predictions match reality.

Remote corners

One of the ideas we are testing is whether bats are fundamentally different from other mammals in their capacity for resisting or tolerating viral infections. I build models depicting the spread of infected cells within individual bats and explore the physiological processes that might allow a bat cell to host a replicating virus without experiencing the cellular damage that causes the host to feel sick.

In the lab, I grow layers of bat cells, infect them with virus, and monitor cell-to-cell viral spread. Then I compare these data with what is predicted in my models. If the data match the model, then maybe the mechanism for disease mitigation that I chose for my model also is the one used in real life.

At a population level, bat-virus transmission, including spillover, peaks in the winter, and we want to know why. I build population-level transmission models that incorporate different seasonal pathways to cause winter infections, then I try to match those models to data. Collecting field data is hard — I spend years trekking to remote corners of Madagascar, mastering obscure Malagasy dialects, and rigging complex pulley systems out of nets, fishing lines and carabiners.

At the end of it all, like the man in Makira- Masoala, I catch a few bats. Instead of cooking them for dinner, however, I use fine-gauge needles, cryogenic vials and sterile swabs to collect their blood and other bodily fluids before I let them go. I haul the fluids in vats of liquid nitrogen to the laboratories of the Pasteur Institute of Madagascar in the capital city of Antananarivo. From there, samples are shipped to collaborators in London, Berlin, New York and Washington, D.C., while others remain in-country. My collaborators and I perform a variety of tests on these transported fluids to ascertain whether the bats were susceptible, infected or recovered from infection at the time of sampling.

When all is said and done, the results are sometimes difficult to interpret. Science is a gradual process, and the goal is to always narrow the window of possible hypotheses at least a little bit.

For me, science is a recognition of, as John Steinbeck put it, “how man is related to the whole thing.” I’m still trying to understand how humans fit into the zoonotic cycle of disease. I’m nearing the end of my Ph.D., but I have enough questions to keep me going for a lifetime.

Cara Brook is a fifth-year doctoral student. Her advisers are Andrew Dobson, professor of ecology and evolutionary biology; Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Ecology and Evolutionary Biology and Public Affairs; Andrea Graham, associate professor of ecology and evolutionary biology; and C. Jessica Metcalf, assistant professor of ecology and evolutionary biology and public affairs. Brook’s research is funded by the National Science Foundation, the National Geographic Society and PIVOT, a Madagascar-based health care nongovernmental society.