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Rigging the roulette wheel to slow the spread of viruses

When animals sound a warning

Under the umbrella of a Yale center, ecologists and epidemiologists try to understand the not-always-felicitous interactions among humans, their environment and disease.

By Rhea Hirshman
Illustrations by Einat Peled

The native birds of Hawaii are vanishing. Of more than 100 species actively breeding on the islands when Capt. James Cook landed there in 1778, barely half remain and many of those are endangered. Having evolved in island isolation, with no mammalian predators, the birds were easy targets for alien rats—escapees from ships—which preyed on their eggs and their young. At the same time, bird habitats have been degraded by a range of human activities that date back more than 200 years, when cattle introduced to provide food for European settlers began to chew their way through the foliage.

But even though human activity has been damaging the Hawaiian bird population for centuries, the beginning of the population’s drastic decline can be traced more precisely to 1826, when the encroachers were not bulldozers flattening delicate ecosystems or pesticides spread for agribusiness (those threats came later), but mosquitoes brought by a whaling ship from Mexico. Two weeks after the ship left, after taking on water and washing out its casks, locals were complaining to missionaries about a new kind of fly that flew at night and buzzed.

“There had been no mosquitoes in Hawaii before then,” says Stephen C. Stearns, Ph.D., “and these mosquitoes could transmit malaria.” Not only did avian malaria decimate the native bird population, Stearns notes, “but when humans brought yellow fever to Hawaii, the mosquitoes were there to transmit the human disease as well.”

The interplay among human behavior, human health and disease, animal behavior and health and the ecology of the planet is the foundation of the activities of the new Center for EcoEpidemiology, which was established as part of the Yale Institute for Biospheric Studies and began operation on July 1 last year. Stearns, the Edward P. Bass Professor of Ecology and Evolutionary Biology and chair of ecology and evolutionary biology, is one of more than a dozen Yale faculty affiliated with the center. A specialist in the life history consequences of infections and disease, co-author of a widely used textbook on evolution and the founding editor of the Journal of Evolutionary Biology, Stearns calls the center “an important cross-disciplinary effort to both understand and anticipate the consequences of humanity’s interacting with the environment.”

Faculty from the School of Medicine (departments of Internal Medicine and Epidemiology and Public Health), the School of Forestry and Environmental Studies (FES), the Graduate School of Arts and Sciences and Yale’s Department of Ecology and Evolutionary Biology are among those participating in center activities. The center’s director, Durland Fish, Ph.D., notes that—through fostering the creation of new undergraduate and graduate courses, hosting seminars and symposia, coordinating Yale’s existing cross-disciplinary curricula and helping to develop an interdisciplinary doctoral program in epidemiology and ecology/environmental science—it will be addressing two main themes.

“The first,” Fish says, “is how do we integrate environmental and ecological sciences into infectious disease epidemiology? The focus in combating diseases has traditionally been to concentrate on individual humans or discrete groups of humans—for instance, by developing diagnostic techniques or vaccines. But many important human pathogens, whether transmitted human to human, animal to human or vector to human, originate in the environment. The risks of incurring or transmitting infection have everything to do with what happens in the environment.” Fish adds, “I view infectious diseases as environmental threats—measurable and predictable. So we want to look at how to get the ecological sciences as equal participants in understanding and combating infectious diseases.”

A professor of epidemiology (microbial diseases) at the School of Public Health (EPH) and principal investigator of the Centers for Disease Control and Prevention’s Fellowship Training Program in vector-borne diseases, Fish notes that he had experienced a “lack of communication between ecology and epidemiology” throughout his career. “I studied the ecology—the abundance and distribution—of insect-borne pathogens. There wasn’t much support for this kind of work, because in the 1960s we thought we had conquered all kinds of infectious diseases with drugs and vaccines.”

However, Fish points out, diseases thought to be controlled or eliminated have re-emerged, while “new” infections including Lyme disease and West Nile virus have also surfaced. Suburbs that encroach on once-natural areas bring humans in closer contact with deer and the deer ticks that carry Lyme disease. In parts of Central and South America, a decade-long pandemic of dengue fever is attributable to an increase in the number of items such as tires and cans—used as containers or left as garbage—that hold the standing water that becomes a breeding ground for mosquitoes. In these and a wide range of other instances, zoonotic diseases— those caused by infectious agents that can be transmitted between (or are shared by) animals and humans—have everything to do with environmental disturbance, human population growth and the speed with which people, animals, plants and materials are transported around the world.

The second theme of the center, Fish says, is “getting the tools of human medical science into the hands of those studying disease ecology and environmental health.” He notes, for instance, that David K. Skelly, Ph.D., another faculty member affiliated with the center, is using ultrasound technology originally developed as a diagnostic tool for humans to study parasitic cysts in frogs. Amphibians, he notes, have been central to the development of biological knowledge and have become icons for environmental decline.

“We can learn a lot about human health by looking at nonhuman systems, and the development of the field of ecoepidemiology is a recognition of that,” says Skelly, a professor of ecology at FES and of ecology and evolutionary biology, and a 2003 recipient of a Guggenheim fellowship to write a book on amphibians aimed at the general public. “Animals and plants can be sentinels—whether we’re dealing with risks that are infectious or chemical. What sorts of environmental conditions are conducive to disease? How does the exposure of a frog in a pond to infection or toxins or pollutants translate into possible human exposure, and what are the effects of that exposure? Our message as scientists should not be only about risks to humans. But if we are modifying our environment so that reptiles are becoming hermaphrodites, we have to ask if there is a relationship to the decrease we’re seeing in human male sperm counts.”

While Skelly uses tools of biomedical science in his work as an ecologist, he talks in turn about the relevance of ecological tools and methods to medical research. “As an ecologist, I know that the emerging field of disease ecology shows us a discernible relationship between infectious agents and species distribution and abundance.” Skelly says that the tools of ecology, including field experimentation (going out into the environment where infection happens, modifying some part of the natural world and comparing it to a control location), “are now spreading into the biomedical world—medical researchers are building models and testing them in nature, taking the study of disease outside the laboratory and looking at the environmental contexts of disease and infection.”

Using Lyme disease as an example of changing perspectives on managing infection, Skelly asks, “Can we decrease Lyme disease risk by intervening with nonhuman hosts?”

Fish, who has worked on Lyme disease “since the beginning,” also talks about taking a different approach. “An ecological perspective to preventing Lyme or any other vector-borne disease involves thinking about how populations are regulated by nature and how we can work within the natural environment to reduce the presence of disease vectors.”

He points out that in the case of Lyme disease, reforestation of the Northeast has caused changes in the population density and distribution of the white-tailed deer and, correspondingly, its natural parasite, the deer tick. These changes have caused a Lyme disease epidemic as humans have increasingly come into contact with ticks infected with Lyme disease bacteria. “We did an experiment—using the vaccine originally developed for humans, we vaccinated mice in the woods outside of New Haven. Over the next several years, we found fewer infected ticks. While human vaccination turned out not to be an effective defense against Lyme disease, this research path is promising.” The point, Fish emphasizes, “is that there is a range of options for us to work with.”

From his discipline, Stearns also notes the importance of looking at “ecological context,” which he describes as standard evolutionary thinking. “Every organism ‘wants’ to survive,” he says. “We can’t really understand the development of virulence or resistance or the emergence of diseases like Ebola or SARS or AIDS unless we look at that ecological context, one that humanity has often affected.”

To illustrate his point, Stearns tells what he calls a cautionary medical tale—the consequences of the spread of a cattle disease (rinderpest) into Africa. Rinderpest first evolved in Eurasia, entering Africa either with General Charles Gordon’s attempt to lift the siege of Khartoum in 1885 or with the Italian invasion of Ethiopia in 1895. In Africa rinderpest encountered a continent with no evolutionary experience of—or immunity to—the disease. “The rinderpest virus spread rapidly all the way south through Africa, reducing native herds of hoofed animals down to about 1 percent of their former levels,” says Stearns. “Lions, whose prey were dying off, began eating people.

“In true ecological fashion,” Stearns says, the effects of these events on the human population were significant. Without the grazing animals, bushes grew up along creeks and river beds—and created ideal environments for tsetse flies. “So when people tried to move back after the virus had gone through,” Stearns continues, “they encountered sleeping sickness.” Now, decades later, those areas that experienced a high incidence of sleeping sickness are the national parks of Africa, because giraffes and antelopes and many other wild animals are not affected by sleeping sickness, which kills both cattle and humans.

“The interactions between predators, prey, pathogens, vectors and vegetation reshaped the human ecology of a continent for a century,” Stearns says. “No one could have predicted this when some sick cows came along with an invading army into northern Africa.”

Looking beyond the immediate and the obvious and paying attention to the possibility of the unpredictable are central to the interdisciplinary mission of the Center for EcoEpidemiology. The overall goal is to develop an innovative curriculum among the participating schools and departments to provide training that cannot be obtained at any other American academic institution. “I’m also hoping to see more emphasis on prevention in a much more global way. We want all sorts of new ideas to emerge,” says Fish, “and there is a lot of excitement about what we’re doing. When the creation of the center was announced I was inundated with e-mails and phone calls from people wanting to be involved or to know more.”

A listing of just some of the topics under consideration for the center’s fall seminars—the impact of global warming on infectious disease, biodiversity, environmental change, wildlife as sentinels for environmental hazards, health implications of fossil fuel use, potential bioterrorism threats to the environment—illustrates the range of interests of participants and the possibilities that the center holds. Stearns envisions the center as “a place to train a new generation of graduate students to observe the world in new ways and come up with syntheses that my generation was not trained to be able to see.” Skelly adds, “We want to train people who are oblivious to disciplinary boundaries. Once faculty and students from different disciplines start talking to each other, there’s no telling what can happen.”

For more information about the Yale Institute for Biospheric Studies Center for EcoEpidemiology, and a list of upcoming events and courses, check the center’s website at http://www.biology.yale.edu/oib/resources/yibs.htm. YM

Rhea Hirshman is a freelance writer in New Haven.

Rigging the roulette wheel to slow the spread of viruses

Avian flu virus is not new. All the influenza strains that affect people have avian origins—including the virus that caused the 1918 - 1919 influenza pandemic, according to Durland Fish, Ph.D., professor of epidemiology. That outbreak killed at least half a million people in the United States and more than 30 million worldwide. As with such other “emerging” diseases as Ebola hemorrhagic fever, Lyme disease and severe acute respiratory syndrome, or SARS, what is “new” about avian flu is a heightened awareness of the role of other species in the development of this human health hazard, says Fish. That makes it a perfect case study for the new center Fish directs, the Center for EcoEpidemiology, part of the Yale Institute for Biospheric Studies. The center’s purpose is to bring together experts in ecology and epidemiology in areas where their studies intersect.

Fish highlighted one such intersection in a talk at a conference on campus last May, “Ethical Aspects of Avian Influenza Pandemic Preparedness, Part 1: Vaccines,” when he discussed the necessity of focusing more resources on understanding how the virus evolves and functions in wildlife populations so that we can keep it from developing into a strain transmissible to humans.

Of the numerous strains of the influenza virus, of most concern is the H5N1 strain. “A common scenario is that avian viruses in wild-bird populations are transmitted to domestic birds or sometimes to pigs. New strains can evolve when animals are in proximity to each other,” Fish says. This process is known as “recombining.” Although humans have developed some immunity to various influenza genotypes through exposure, they would be highly susceptible to the new strain were it to become widespread in the human population.

What could make that happen? Fish says that we do not know why some strains jump the species barrier to humans and others do not. “We do know,” he says, “that the H5N1 strain recombined in domestic animals and is now back in the wildlife population. We saw the first human cases in the late 1990s. When several people in Southeast Asia died of a previously unknown influenza virus, the virus was studied and we now know it as H5N1.”

A pandemic occurs when a virus introduced into the human population through another species moves from person to person. Rather than relying on the wholesale destruction of infected and susceptible bird populations, or pouring resources into developing a human vaccine (he notes the impracticality of vaccinating billions of people quickly), Fish suggests other ways to keep a pandemic at bay.

“The first,” he says, “is to vaccinate carrier species against viral genotypes with pandemic potential by developing oral vaccines that can be distributed to wild birds through feed.” Another approach would involve the introduction of a variation of the virus that produces a milder form of the infection but still maintains itself in appropriate bird populations, thus rendering the birds immune to pandemic genotypes.

Fish would like to see greater cooperation between the disciplines of ecology and epidemiology. “We should preserve wildlife, while at the same time figuring out how to keep it from being a threat. If we can buy time and learn more about the evolution of viruses in nature, we can rig the roulette wheel rather than just waiting for it to turn.”

—R.H.