Immunology/infectious diseases: Lifesaving opportunities on a shifting battlefront

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Today’s microbe hunters face an onslaught of illness, from aids and antibiotic-resistant bacteria to mad cow disease and SARS. On top of those threats, bioterrorism also poses unexpected challenges for scientists in research and technology. As described here, only new recruits to disease fighting can reinforce the attack on emerging public health issues.

Mother Nature keeps throwing new challenges at infectious disease fighters. If Ebola virus didn’t keep epidemiologists busy enough, surely bovine spongiform encephalopathy (mad cow) and severe acute respiratory syndrome (SARS) would. In addition, bioterrorists released sarin in the Tokyo subway in 1995 and put Bacillus anthracis in the U.S. mail in 2001. This spring ricin turned up in a U.S. Senate office. Both natural viruses and agents of bioterrorism put an unprecedented urgency behind research in immunology and infectious diseases.

When asked about the impact of bioterrorism and emerging infectious diseases, Thomas Kindt, director of intramural research at the National Institute of Allergy and Infectious Diseases, says, “It has had a deep impact in our program. It allowed us to accelerate a number of planned programs.” These threats released more money, which allowed Kindt to finance the building of biosafety level 3 and 4 facilities for his research teams. “This is a very enabling thing,” Kindt says.

Future fights

Despite the ongoing battles against disease and attacks, experts in this field see even more work ahead. “Our population is aging,” says Ramesh K. Akkina, professor in the department of microbiology, immunology, and pathology at Colorado State University. Consequently, he sees more need for regenerative medicine and transplantations in the future, and those operations will demand more research on graft rejection and tolerance.

As a higher percentage of people move toward old age, autoimmune diseases will also rise. “As the Baby Boomers get older and people start living longer,” points out Akkina, “more autoimmune diseases will come to the surface.” J. Donald Capra, president of the Oklahoma Medical Research Foundation, agrees. Now out of medical school 40 years, Capra says, “I have seen new approaches to treating many diseases, but there has been significantly less progress in treating autoimmune diseases.”

New technologies, too, will drive further research. Akkina points to embryonic stem cells as an appealing field of research in the future. “Things are progressing rapidly,” he says, “and we may eventually be transplanting stem cells for many diseases, including diabetes. There, too, you must deal with foreign-cell rejection.”

Overall, the field of immunology remains in its infancy, according to some scientists. Mike Arbige, senior vice president of research and development at Genencor International, says, “We are learning things every day.” Down the road, he expects the first wave of antibody response to attract plenty of research attention. “If you can understand how to control and manipulate the body’s initial response to foreign proteins and invading organisms,” he says, “that’s where the magic can emerge.” This angle of research includes the stimulation, control, and biochemistry of inflammation, which is the first line of defense against infection, plus the genetics of the antibody response, T-cell immunity—including antigen presentation, thymic selection, and receptor signaling—and autoimmunity.

Putting together the pieces

Many future successes in prevention and treatment may arise from a holistic approach to research. “In the old days,” says Akkina, “the pathogen was an entity and the host was an entity. Now, we can look at the interactions between the host and the pathogen in more detail.” In looking at diseases today, a scientist can examine the clinical symptoms, study the susceptible cells, develop cytokine profiles, and even note the transcription of perturbed genes. Akkina says, “We can assess the complete picture now, instead of each piece.”

Kindt also sees great power in putting together techniques. He says, “Immunology embraces the findings from all of the other disciplines—especially cellular biology and genomic sciences—and we try to paint a complete picture of the immune system.” In addition, Kindt points out that the global picture can actually trigger more directed research. He says that he and his colleagues now target specific diseases where they search for precise processes and then attempt to intervene. That well-aimed approach, though, still must speak to many objectives. “We want to develop health products,” Kindt says, “and that includes diagnostics, therapeutics, and preventative measures, which are mainly vaccines.”

When it comes to pharmaceuticals, proteins make up many of the new drugs. Some of them, though, can create adverse effects. Using a technology developed by Genencor called the i-mune assay, Arbige says, “One can take any protein and identify the epitopes, or pieces of that protein, that kick off the first steps of the immunity response. Protein engineering would then allow you to modify those sections of the protein to make it safe.”

All in the atmosphere

For younger scientists looking for a career in the fields of immunology or infectious diseases, the experts interviewed here send along some perhaps unexpected advice. First, Kindt reminds job candidates to look at the overall atmosphere of a potential institution. “Find an atmosphere that will contribute to your success,” he says. “If I come to this job, will I have the resources that I need?”

For Arbige, he wants to work in a company that focuses on unmet medical needs. Moreover, he emphasizes the need for focus. “Is a company focused or just dabbling?” he asks. “You should find a company with good technology, strong intellectual property bases, and a winning strategy.”

Others also mentioned the value of the right feel in a job. Akkina says, “Find the right research atmosphere. Find a place with highly qualified people who are well versed in your area of interest and with high energy levels. You will want to interact with valuable colleagues.”

The right feel, though, may not be so obvious. So, Kindt encourages young scientists to also look for what he calls “the intangible.” To him, the intangible is not the atmosphere that can be seen at a potential institution, but rather the atmosphere that the candidate must feel. “Whenever I look at a job,” Kindt says, “I try to project myself into that desk with these people. Does it feel good?” Like an athlete practicing mental imagery, scientists can do the same. In essence, a job candidate needs some imagination to really test out a place. But Kindt can tell anyone what a good job feels like. “As a young scientist,” he recalls, “I bounded out of bed and wanted to get an experiment moving. I wanted to go to the incubator and see what grew.” For any job candidate, if the intangible test generates an out-of-bed-bounding image, he says, take that job!

Getting real

Granted, not everyone will find the job with exactly the right feel. Still, it never hurts to try out a job, even if it’s only in the mind’s eye. Likewise, it never hurts to ask questions on a job visit. Many applicants may come up with the same questions. How much will I be paid? How much startup money will I get? Capra encourages a different question.

“I’ve interviewed hundreds of job candidates,” he says, “and no one ever asked me what I consider to be an extraordinarily important question: Will there be someone at this institution who will mentor me?” After graduate school and a postdoc or two, maybe a young job candidate wants freedom, not mentoring. But Capra advocates a mentor. With support of a Centers of Biomedical Research Excellence (COBRE) grant from the NIH’s National Center for Research Resources, Capra instituted a mentoring program at the Oklahoma Medical Research Foundation. He gives every new faculty member a senior-faculty mentor, and he asserts that this program works wonderfully. Capra says, “All of the people whom we mentored in the first five years got RO-1 grants and at least one paper in a top journal.”

In addition to those powerful results, Capra encourages young scientists to look between the east and west coasts. “We have spectacular jobs available,” he says. At the time of this reporting, Capra needed a developmental biologist, an immunologist, and a crystallographer. Maybe there’s a Midwest or Great Plains or southern or mountain mentor—or other immunity-related job opportunity—in your future.

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