FEATURE STORY — Mar./Apr. 2006

Living in a microbial world

Whether it’s anthrax or HIV, researchers in UIC’s Section of Infectious Diseases are studying what makes microbes tick

By Rick Asa

To infectious disease experts, this is a microbial world and humans are just living in it. “There is this endless evolution going on in the interaction between man and microbes,” says Dr. James Cook, professor and head of the Section of Infectious Diseases at the UIC College of Medicine. “What happens is that occasionally we get infatuated with one thing or another because of an outbreak. But the truth is, it’s going on all the time.” In her best-selling book, The Coming Plague, Laurie Garrett quotes Nobel laureate Joshua Lederberg from a speech he gave at the Irvington Institute for Medical Research: “We have beaten out virtually every other species to the point where we may now talk about protecting our former predators, but we’re not alone at the top of the food chain.”

As Garrett documents in her book, beginning in the early 1940s, antibiotics began to pummel bacterial diseases, and scourges such as Staphylococcus and tuberculosis moved from “extremely dangerous” to “easily managed minor infections.” Some predicted that, by the 21st century, virtually every infectious disease would be under lock and key. By the 1960s, polio prevalence rates had plummeted, and by the mid-1970s, cases of Variola major (smallpox) were eliminated worldwide. Scientists began to believe that this linear course of disease eradication would continue.

But in 1976, there was the frightening and mysterious outbreak of what would become known as Legionnaire’s Disease, and by 1983, acquired immune deficiency syndrome (AIDS) had been formally identified. In the late 1980s, tuberculosis made a comeback with drug-resistant forms that laughed at antibiotics. And tuberculosis formed a partnership with human immunodeficiency virus (HIV) in Asia and Africa that made the whole worse than the sum of its parts.

In 2003, severe acute respiratory syndrome (SARS) made its presence known in Asia and spread to Toronto. The worldwide panic that quickly ensued drove home the point that infectious diseases, far from being gone, were devising new ways to prey on humans.

This past fall and winter, scientists, government health experts and media from around the world had their collective eyes peeled for a widespread outbreak of avian influenza.
“It’s amazing how [infectious disease experts] can go from being very boring to very important when something like SARS comes along,” remarks Cook. “It’s important to keep our balance, though, rather than constantly letting ourselves be buffeted by fear and trends. There is no way we are ever going to completely outsmart microbes. Anybody who expects that we’re going to live in a sterile world is not paying attention. Microbes are as much a part of our culture as is religion or race or ethnicity.

“We carry millions of organisms around inside of us,” continues Cook. “For example, we have to have bacteria in our guts or we can’t clot blood. It’s a love-hate relationship that will never end.”

SARS could have been much worse, Cook explains, but it was identified genetically within weeks. Its quick identification was due, in part, to organizations, such as U.S. Centers for Disease Control and Prevention and the World Health Organization, which have established comprehensive surveillance outposts to monitor influenza, including the emergence of strains that have the potential to develop into pandemics like the devastating Spanish Flu that killed millions worldwide from 1917-18.

Understanding infectious diseases

Dr. James Cook, professor and head of the Section of Infectious Diseases at the UIC College of Medicine

Yet, for all the attention that killer viruses such as HIV and SARS attract, the world of infectious disease study is broader and deeper than most people realize. Several UIC faculty members, for example, have expertise in lesser known—but sometimes equally lethal—infections.

Dr. Peter Williamson, assistant professor of medicine, is one of them. He treats patients with complicated fungal infections, and has conducted extensive research into these primitive, one-celled parasites. In immunosuppressed patients, for example, exposure to normally harmless fungi can be deadly. The spores of white bread mold, for instance, can be inhaled by most people without problems. But if a transplant patient inhales them and develops progressive fungal infection, he or she has about a 5 percent chance of surviving, explains Williamson.

Dr. Richard Novak, associate professor of medicine, is a noted HIV clinician and researcher. Novak heads the ID Section’s HIV program, which includes an on-site clinic and several community-based satellites that have become a national model for HIV case management. Novak also has been key to National Institutes of Health-sponsored clinical trials of HIV preventive vaccines, and is involved in several anti-viral drug trials for HIV-infected persons. He and Mahmood Ghassemi, PHD ’95 com, research assistant professor of medicine, have focused for many years on how other infections may enhance HIV virus replication and worsen the disease.

Finding the levers

Cook, who joined UIC in 2002, is a clinician and a basic researcher. He has extensive experience in treating and consulting on cases in which patients have drug-resistant mycobacterial infections, such as those caused by tuberculosis and related non-TB mycobacteria. Previously, Cook held three appointments as professor of medicine, microbiology and immunology at the University of Colorado Health Sciences Center in Denver.

For more than 25 years, Cook has been conducting basic research, with a focus on how viruses interact with mammalian cells and how host innate immune responses defend against infection and neoplasia. His expertise in host innate immunity is being applied in one phase of a project, funded by a $15.7 million NIH grant, which has a multidisciplinary team of UIC researchers investigating novel drugs that will control the spread of anthrax in the event of bioterrorism. Specifically, Cook is analyzing the role of the macrophage (one type of innate immune defender cell) in responding to anthrax bacterium and associated toxin that induces the anthrax-related shock syndrome and leads to death. It appears to be the cascading “cytokine storm” in an anthrax victim’s body during the innate immune response that kills him or her, not the anthrax bacteria itself. (Cytokines are the regulatory proteins released by cells of the immune system. In cytokine storm, the immune system essentially overproduces cytokines, creating a toxic situation in the victim.)

The foundation of Cook’s virology is that viruses are little bundles of genetic information, which can invade a host cell and begin, as he puts it, “pulling levers” to turn certain mechanisms off and others on. Viruses know how to make a cell hospitable to their invasion and replication. Cook and other basic researchers are trying to determine how viruses do that and how the levers can be manipulated, for example, to make resistant cancer cells susceptible to chemotherapy. The basic mechanisms of this cellular control were the basis of the multi-year NIH grant that Cook received when he moved to UIC.

“In a medical center like this,” Cook says, “we’re…able to form groups and think about long-term commitments. We have to be focused on teaching and research that is [both] durable and responsive.”

Cook notes that the anthrax drug program is an example of how one of those eternally occurring infectious disease “events” prompted UIC and other universities to develop a “research reaction,” which provides an “opportunity to move into a new area of investigation,” Cook explains. “The ongoing evolution of problems associated with this co-evolution between us and microbes [won’t be] solved quickly, so people have to have sustained interest, maybe over the course of their lifetimes. We don’t pretend to be in private practice. We try to provide something qualitatively different that complements what clinicians do in the community.

“It all seems pretty arcane to the average person, but all our goals are very much the same, and that’s to understand the basic mechanism by which microbes cause disease, so we can be more effective at interfering with them,” continues Cook. “With SARS, for example, we want to be able to name it, quickly contain it, and then be able to respond to it on a cyclical basis, as with a vaccine. People want to know that their fear of the problem can be reduced because those of us struggling to understand infectious agents are doing our job.”