Penn State harnessing research muscle to fight infectious diseases

Andrew Read, director of the Center for Infectious Disease Dynamics and Evan Pugh Professor of Biology and Entomology at Penn State, assesses the impact of temperature fluctuations on mosquitos in the insectary at University Park. The insectary's environmental chambers allow researchers to conduct experiments involving temperature variations, insecticides, and behavioral assessments on insects. Image: Patrick Mansell

It’s easy to forget about the deadly diseases of the past when decades-old breakthroughs in science and medicine have kept them at bay for so long. Diseases like measles, mumps, whooping cough and polio tend to lose their shock value when they’re out of sight and mind — as they have been, by and large, since the mid-20th century.

However, time and again, the notion that infectious diseases are no longer a threat in the developed world has proven wrong. Sometimes it takes an epidemic like the Ebola outbreak of 2014 and 2015 to shine light on the fact that Mother Nature is still in control.

That truth is not lost on the scores of faculty members, research associates and post-docs who comprise Penn State’s Center for Infectious Disease Dynamics (CIDD). Housed within the Huck Institutes of the Life Sciences, CIDD spans five academic colleges and 15 departments to bring a cross-disciplinary approach to the study of infectious diseases.

“In the 1960s people thought, at least in the developed world, that there were going to be no more problems with infections,” said Andrew Read, Evan Pugh Professor of Biology and Entomology at Penn State and the director of CIDD. “That’s turned out to be horribly wrong; there is a lot of re-emergence happening and new pathogens coming along — things like SARS, HIV, MRSA and avian flu.”

The reasons why new diseases are emerging and old ones are coming back are many and complex, ranging from disrupted ecosystems and greater global interconnectivity to evolution-based drug resistance.

“Depending on your view, between 26,000 and 100,000 Americans will die of drug-resistant infections this year. Those infections would have easily been treated by drugs when I was doing my Ph.D.,” Read said. “So, in 25 years the game has changed, and the problem is just getting worse. To put that number in perspective, it’s in the ballpark of the number of Americans dying in car crashes each year. However, the car crash rate is going down, whereas the antibiotic resistance rate is going up.”

An interdisciplinary approach

To help tackle the complexities of infectious disease dynamics, Penn State has developed an interdisciplinary approach to disease research, bringing together a diverse team of theoreticians and empirical scientists — representing such disparate fields as molecular biology, mathematics, plant pathology, entomology, genomics, statistics, physics, population dynamics and more — under a single umbrella.

“The normal vertical structure of a university, with its various colleges and departments, doesn’t bring people together to bear on a single problem like infectious diseases, whereas the horizontal structure of a center does,” Read said.

To foster such collaboration, CIDD faculty members and graduate students meet every Thursday for a lively seminar series, and a standing lunch gathering on Mondays provides an opportunity for discussion and relationship building. There is also a vibrant CIDD Graduate Student Association that holds journal clubs and speaker lunches.

Once spread across campus, many CIDD-affiliated faculty members are now co-housed in the Millennium Science Complex, and the interactions forged out of proximity have produced new research projects that span departmental and college lines.

“There’s this mix of fundamental research and applied research, and then there’s a mix of approaches, from the molecular, to the whole organism, to the population, to the community level,” said Katriona Shea, Alumni Professor of Biology and a CIDD-affiliated faculty member. “People are working in all of these different ways, and every time we interact via seminars or the social interactions that go on in CIDD, other new and exciting ideas emerge.”

Shea has been conducting research on the use of adaptive management for disease control, which is a process for dealing with unknowns when faced with a new problem, and ascertaining what information is most crucial to finding a solution. Like Shea herself, adaptive management has its roots in wildlife management, but she soon saw its place in disease management as well — and has since applied it to research involving foot-and-mouth disease in livestock and Ebola in humans.

“So it’s kind of learning while doing, rather than just learning before or after an outbreak,” Shea said. “It’s been used in wildlife and conservation efforts, which was my background, and I realized it wasn’t really being used with diseases. So I went to Matt Ferrari and Ottar Bjornstad, both members of CIDD, and pitched to them that there were ways that adaptive management could really streamline disease management and potentially save lives.”

Tackling global problems

Since its founding in late 2003 by faculty members Bjornstad, Pete Hudson, Eric Harvill, Darla Lindberg and others, CIDD has quickly gained a global reputation for its ecological, rather than clinical, approach to the study of infectious diseases, which focuses on disease transmission at a population level over time.

“The ecology of transmission is heavily involved in what we do,” Read said. “In clinical microbiology, for example, they’re interested in what the agent is that’s making a person sick and how to kill it. We’re interested in that, too, but we’re also interested in how that agent gets from person to person. How does the resistance to a drug spread through a population? Can we use any of those population-level processes to reduce transmission, to reduce sickness?”

The work being performed by CIDD faculty members and researchers is as broad as it is critical. There are CIDD faculty members working to stop malaria transmission in villages in Africa, as well as developing new drugs and vaccines against malaria. Of particular note is the work being done by a team of researchers led by Matt Thomas, professor of entomology, which recently was awarded a $10.2 million grant from the Bill and Melinda Gates Foundation to develop novel approaches to block malaria transmission by controlling mosquitos’ access to homes in Africa.

Other Penn State researchers are interested in disease dynamics in developing world settings, particularly the impact of vaccination schedules for measles and meningitis in developing world countries.

“One of the most interesting things to happen in the last year is Matt Ferrari’s discovery that Ebola’s biggest effects are going to be on other diseases,” said Read. “Diseases like measles are going to kill more people than Ebola did because of the disruption that Ebola caused to the delivery of drugs and vaccines.”

Current CIDD research projects are also looking at Lyme disease transmission in wildlife, poultry viruses in Pennsylvania, the interaction between virus infections and pesticides in honeybees, the timing of measles outbreaks, and the re-emergence of whooping cough, just to name a few.

“We don’t have any bias with respect to the type of pathogen or the type of host, so plants, wildlife, farm animals, humans — everything’s covered. And there are people who work on viruses, bacteria, worms, protozoa, fungi, rusts — anything involving a host and pathogen,” said Read.

Now entering its 13th year in existence, CIDD has become a global leader in infectious disease research. The field of phylodynamics, for example, which studies a disease by reconstructing its evolutionary history — where it came from, where it’s going and how fast it’s spreading — was essentially created by CIDD.

With the full weight of Penn State’s research muscle being brought to bear on the problem of infectious diseases, CIDD’s contributions in the areas of vaccine and drug development, epidemic modeling and disease management — and the need for such solutions — only figure to grow.

“I’m not sure we can ever fully predict or even prevent disease outbreaks, but I think we might be able to improve our ability to deal with them when they happen — to minimize the misery,” Shea said. “There always will be unforeseen things happening, but the trick is if you can handle them efficiently and with state-of-the-art methods. We have a whole tool box of skills at our disposal in CIDD, and, together, they work far better than they might have worked individually.”