University confronts bioterrorism

By Jennifer Bussell

Treatments for anthrax and a better smallpox vaccine may be one step closer due to an innovative regional research effort. A consortium of researchers from 14 Midwestern research organizations led by the University has submitted a proposal to become one of five new Regional Centers for Excellence in Biodefense and Emerging Infectious Diseases Research (RCE). Using federal funds from the National Institutes of Health (NIH), the Midwestern RCE scientists will work in “collaboratories,” remarkably high-tech research groups that are bound not by space but by the common goals of participants.

“Biology is coming of age,” said Olaf Schneewind, the University professor who has coordinated the Midwestern RCE proposal. “It used to be principal investigator- and single scientist-driven, but investigating bigger questions that involve whole genomes–that can’t be done by one scientist.”

The RCE will bring together hundreds of scientists to tackle the problems posed by biological weapons and infectious disease. The kinds of questions these scientists will address–how the Ebola virus works, how to detect anthrax in the air, how to immunize a population against plague–require the dedication of many people and the highest technology available. Such resources are not available in a single institution or even a single state, and rather than try to provide hundreds of researchers’ salaries, the government has allocated funds for the creation of regional centers.

Following the anthrax attacks in the fall of 2001, facing the threat of bioterrorism became a national priority, and the NIH and NIAID (National Institute of Allergy and Infectious Diseases) set aside nearly $2 billion for biodefense research in 2003. A significant portion of that will go towards funding 4 to 5 RCEs in the 10 regions of the nation and National and Regional Biocontainment Laboratories (RBLs). For the past year, Schneewind, professor and chair of the Committee on Microbiology, and Bernard Roizman, professor of microbiology, have been determining how the University, U of C-operated Argonne National Laboratory, and other institutions in the Midwest can work together as one center.

“If you really wanted to bring together the best scientists, you’d have to hire them. By and large, universities can’t afford that. The idea is that you can connect them over distance,” Schneewind said.

The RCE will provide core projects such as administration, bioinformatics, and animal models of infection to scientists while managing funding for their biodefense research. Some researchers will provide materials such as mutant anthrax strains or data on protein structure to others. Peer review will serve a critical role in deciding which projects are funded and how funded projects are progressing.

Long-distance connections such as teleconferencing, e-mail, and webcasts will hopefully allow the scientists to exchange data and insights, but a critical part of the University’s proposal is a physical building where researchers can share time in the high-security animal testing facilities critical to infectious agent research.

The Howard T. Ricketts Laboratory for Infectious Disease Research has already been designed for a site at Argonne National Laboratories. It will be built a block away from the Advanced Photon Source, the world’s strongest source of x-rays and a critical tool for understanding the three-dimensional structure of disease-causing agents.

However, the building is a Regional Biocontainment Laboratory, a separate NIAID initiative requiring a separate grant application, and will not be built if funding does not come through. This, according to some, would leave the RCE without a critical intermediate between traditional collaborative science with its water-cooler serendipity and collaboration via videoconference.

“If there is good science that needs to be done…you hope that results in people actually coming to a facility like this because that’s the way things happen,” said Harvey Drucker, associate lab director of energy and environmental science and technology of Argonne. “You aren’t going to reproduce that via e-mail.”

The grant proposal is a specific strategy to tackle what are known as CDC category A-C agents–the deadliest infectious diseases in the world. The current state of knowledge about anthrax, botulism, hemorrhagic fevers like the Ebola virus, plague, smallpox, and tularemia would likely be inadequate in the event of an attack. By elucidating their mechanisms of infection and the body’s response, researchers hope to develop viable plans to protect Americans from potential terrorist attacks with these diseases.

Much of the research in the agenda is considered basic science that simply helps scientists understand these diseases, but the real goal of the RCE model is to translate that research into protection like vaccines for the American public as quickly and effectively as possible. “Our goal is to do a whole variety of research that will lead to new drugs and end up with better products to serve the needs of the country,” said Rona Hirschberg, senior program officer at NIAID, in a phone interview.

Although the RCE would not be directly involved in responding to a biological attack, its brain trust–the scientists and their expertise–would be immediately available to government authorities. In addition, part of the thrust of the RCE plan is to recruit and train future infectious disease researchers.

While the nearly $40 million the NIH has indicated it is willing to spend on the RCEs–which can request funding for up to five years–will be available this summer, the Midwestern RCE has been developed without the aid of a planning grant. Organizers believe the substantial resources, scientific talent, and commitment in their region and especially the Chicago area will lead to success. “We took a reasonable gamble,” Drucker said. “We said let’s go for it now and be early participants in this. That will increase our chances of getting the grant.”

The University created the Committee on Microbiology (CoM) in 2001 with the recruitment of Schneewind in preparation for biodefense research. The committee now includes 14 faculty members–with promised recruitment of 16 more–as well as a curriculum offering undergraduate and graduate degrees. The University has made a total commitment of $16.7 million towards the CoM, in addition to facilities improvements like renovations to the Cummings Life Sciences Center and construction of the Carlsson Biosafety Facility (CBF). The CBF provides 13,000 square feet of secure space in the sub-basement of the University hospitals for studying animal reactions to anthrax and plague.

“This is a vehicle for us to, well, you know, do the best,” Schneewind said. “Discovery in areas like is the very stuff that makes universities great.”

While University personnel recall visions of Chicago’s fame and success with the Manhattan Project and the first sustained nuclear chain reaction under the football bleachers, the RCE proposal is truly based on collaboration. The twelve other institutions like Northwestern University, the University of Illinois system, the University of Wisconsin, and Minnesota’s Mayo Clinic, as well as partners from the biotechnology industry, all figure prominently into the plan.

The NIH has had an unprecedented response to its call for American scientists to come together. “It’s creating a whole new spirit of cooperation,” Hirschberg said. “I think people are very excited about working together. And we haven’t even funded them yet.”