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Immunology: Attacking a Moving Target

This Advertising Feature has been commissioned, edited, and produced by the Science/AAAS Custom Publishing Office

Modern immunology plays a fundamental role in many aspects of biology, from biochemistry to virology. Today’s uncertain world also pulls immunologists into the war on bioterrorism. So in both basic research and applications, immunology keeps growing.

The concept of defense runs through the minds of most Americans on a daily basis since September 11, 2001. Although they wonder about conventional military defense, people also worry about strategies to resist illicit uses of more modern weapons, including anthrax and smallpox. These concerns push immunology—the biological system of defense—to the forefront of today’s basic research and applied technology.

Today’s immunology spreads across many biological disciplines. Sankar Ghosh, professor of immunobiology at Yale University, explores the regulation of gene expression in developing and differentiating lymphocytes. He said that the most exciting arenas of immunology today include new strategies for vaccines and studies of regulatory T lymphocytes and the innate immune response, which is essentially the most general form of attacking pathogens. In addition, he said, “The broader questions in gene regulation and signal transduction are also fundamental to immunity.”

David McKean, cancer center immunology and immunotherapy program leader at the Mayo Clinic, takes a translational perspective on immunology. He said, “Immunology has a major impact in every aspect of medicine.” At Mayo, some immunologists work on basic research and others lean more toward the clinical applications of immunotherapy. “Immunology is rapidly evolving, so there are lots of opportunities in basic research and applications,” McKean said.

Fast-paced changes in immunology appear in pharmaceuticals, too. For instance, Ribapharm—a research and development organization that focuses on antiviral and anticancer drugs—licensed its antiviral drug ribavirin to Schering-Plough for use in combination with its Intron A or Peg-Intron to treat chronic hepatitis C in adults with compensated liver disease. Zhi Hong, Ribapharm’s vice president of drug discovery, said, “From the pharmaceutical industry point of view, I see immunotherapy as the most exciting aspect of immunology.” Immunotherapy includes three main categories: therapeutic cytokines or chemokines, which are potent immunomodulators; cell therapies, such as harvesting dendritic cells, modifying them to fight cancer, and then replacing them in a patient’s body; and therapeutic monoclonal antibodies. “There are a lot of commercial activities in this area,” Hong said.


Battling Bioterrorism

With the anthrax scare following September 11, Americans grew wary of bioterrorism. According to Charles Hackett, chief of the molecular and structural immunology section in the Division of Allergy, Immunology, and Transplantation at the National Institute of Allergy and Infectious Diseases, “Immunology is essential to developing vaccines and immunity based therapies. We deal with highly virulent infections, and we don’t have the ability to test things multiple times in natural settings, so understanding immunology helps.” So far, Hackett sees enormous progress in innate immunity, which he calls the “first line of defense.” But he added, “We need to improve the memory responses of T and B cells to make longer-lasting vaccines.”

Immunology related to bioterrorism demands work with humans. Hackett said, “Studies of human immunology are usually not the first choice for research in basic immunology, but it is very important now to understand how humans differ from animal models.” For example, bioterrorists aim many agents at the mucosal surfaces, including the lungs and gastrointestinal tract. So Hackett said, “We are therefore encouraging looking at human responses on the level of mucosal immunity.” He added that many immunologists involved in fighting bioterrorism also study bacterial and viral immunology and explore infectious diseases.

To examine lots of pathogens and potential antidotes to them, immunologists explore bioterrorism with high throughput techniques. “Microarrays are becoming practical tools,” Hackett said. “As you look for methods to discern complex immune responses in human cells, more and more people look at what genes are turned on with infections or vaccination procedures.”

Although bioterrorism spawned a very specific subdiscipline in immunology, this field demands a broad perspective. To get into this field, Hackett said, “Study fundamental aspects of immunology. That knowledge will be applicable to emerging challenges, because we don’t know what agents will emerge in the future.”

Converging Conclusions

The breadth required to battle bioterrorism mirrors the integration occurring in other branches of immunology. Not long ago, some immunologists specialized in cancer. Others studied inflammation, and so on. Now, Hong said, “The disease boundaries are disappearing, because different diseases are interrelated.” For example, Hong pointed out that inflammatory bowel diseases are associated with colon cancer. Instead of simply thinking of a disease, immunologists explore mechanisms. “The therapeutic areas,” Hong said, “are merging at the molecular levels and transforming into metabolic disorders or cellular dysfunction.” He added, “The same target that causes cancer could also cause inflammation.”

This blurring of boundaries sends good news for job hunters. Now, immunology crosses paths with many other fields. Hong said, “The job opportunities are getting better and better.”

To be ready for ongoing changes, however, a graduate student in immunology should prepare for unexpected opportunities and challenges. Hong said, “I’m fundamentally against students at the graduate level being highly specialized.” Instead, he believes that graduate students should develop versatility. It worked for him. Hong did graduate work in parasitology and a postdoc on antifungal and antibacterial studies. Then, he started his industrial career by working on antivirals, and now he is turning to anticancer agents. “There are a lot of crossovers between fields,” he said. “It keeps your job fun.”

Go for the Gold

With all of the interest in developing new therapeutics, new vaccines, and strategies for fighting bioterrorism, immunology poses many serious questions for scientists. As Ghosh’s students head off to postdoctoral positions or jobs, he tells them: “Don’t be afraid to ask the difficult questions, because those questions are the ones whose answers will be important, too.” Ghosh recognizes that this can be easier to say than to do. Nevertheless, he believes that answering the difficult questions leads to the most fruitful career.

Other considerations also face job seekers. To feel at home, a scientist needs the right environment. “Be in an environment that challenges you to be productive,” McKean said. “This is a great field to be in right now because the potential for applications is tremendous.” He also indicated the value of staying adaptable. “Be able to move in different directions as things change,” he said.

Sometimes, experimental obstacles wear away a scientist’s optimism. “In the biosciences, a graduate program can turn into a long cycle,” Hong said. “Graduate students can get frustrated when a project doesn’t work very well.” Everyone in science knows that disappointment. Still, Hong offered this simple advice: “Stay positive. Be alert. If you have fun and enjoy your life, that will influence your career in positive ways.”

In seemingly every detail, these experts describe immunology as one of science’s ever-expanding frontiers. They also recommend that budding immunologists follow four rules: study widely, change with the times, tackle the toughest questions, and keep your chin up—no matter what. In the end, those in immunology will answer fundamental questions about disease, save hundreds of thousands of lives, and, they hope, put a major crimp in the arsenal of bioterrorism.

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