The Rochester Review, University of Rochester, Rochester, New York, USA
By Christopher DiFrancesco
Tim Mosmann is among the hottest scientists in his field. Credited with one of the most important discoveries in modern immunology, this Nobel nominee has joined the Rochester faculty to lead a new research effort in immunology and vaccine development.His center is one of six components of the new University of Rochester Institute of Biomedical Sciences whose research building is nearing completion on the Medical Center campus.
Imagine getting a shot in the arm that will keep you safe from cancer. Eating a banana that will protect you forever against diabetes. Or sticking a patch like a Band-Aid on your kid's arm to prevent ear infections.
A new generation of wonder vaccines--sometimes in exotic guises--is being developed in laboratories around the world. And it's thanks in good measure to one of Rochester's newest scientists.
"These are exciting times in vaccine development," declares immunologist Tim Mosmann. Advances in basic science over the past two decades are leading to what he calls "a renaissance" in the field.
One of the biggest advances fueling this rebirth has come from Mosmann himself. While working as a senior scientist at the DNAX Research Institute in Palo Alto, he made a fundamental discovery about the way the immune system responds to various types of infections.
As harmful pathogens such as bacteria, viruses, and parasites enter the body, the immune system must identify the invader, choose how best to respond, and then marshal the agents that will participate in the defense.
Mosmann's discovery was that there are two types of helper T-cells--the master cells that give orders to all other cells involved in an immune response--and that each of these types is responsible for coordinating specific responses.
One type of helper T-cells (called Th1 cells), he found, regulates two kinds of defensive actions: During an infection, they urgently signal the immune system to begin producing "killer" cells that destroy invading pathogens. They also send signals that dispatch infection-fighting fluid, cells, and proteins to the area under attack. Ever had an infected cut on your finger? The swelling, redness, and warmth you felt was--in immunological parlance--an inflammatory response. It happened because your Th1 cells ordered it.
The other set of helper T-cells (called Th2 cells) regulates two other types of immune responses: allergic reactions, for one, and--as a safeguard for the future--the production of antibodies enabling the body to mount an even more rapid and intense response the next time that particular pathogen comes visiting.
Mosmann's discovery of Th1 and Th2 cells--and their respective roles in orchestrating the ways our immune system responds to infections--was a major step toward helping scientists harness its power and enlist it to fight a variety of diseases, from cancer to asthma.
"Tim's work in this area stands as one of the most fundamental discoveries in immunology in the past several decades," says Arthur Kornberg '41M (MD), a Nobel laureate and founding chair of the department of biochemistry at Stanford University. "He is a terrific immunologist whose work has provided us with an understanding of those major phenomena."
Kornberg, as it happens, enjoys a special familiarity with Mosmann's work. As one of three science advisors to the DNAX Research Institute, he early spotted the younger scientist's talents and helped recruit him in 1982. Eight years later--after Mosmann's landmark T-cell research had brought international acclaim both to himself and the institute--he left DNAX to take an appointment as chair of immunology at the University of Alberta. Not a decade later, however, the two scientists' paths would cross again--this time as Mosmann was being recruited to Rochester by Medical Center CEO Jay Stein.
Stein approached Mosmann last spring about leading a vigorous new research effort aimed at unlocking the labyrinthine secrets of the immune system--with the ultimate goal of using that knowledge to find ways of developing new vaccines and to make existing ones more effective.
"I was immediately intrigued," says Mosmann. "The Medical Center offers so many of the ingredients necessary to develop a world-class research program in this field."
High among those ingredients, he says: "one of academia's most impressive track records in vaccine development."
The first vaccine against human papillomavirus, believed to cause nearly all cases of cervical cancer, was developed and has entered its first human trials at the Medical Center, Mosmann points out. The University is also one of six sites in the nation currently testing potential AIDS vaccines.
Perhaps even more impressive, during the mid-1980s when their future colleague was teasing apart the subtle differences between groups of T-cells in his Palo Alto lab, researchers at Rochester were developing a vaccine against Haemophilus influenza type b ("Hib" for short), the deadly bacterium responsible for nearly all cases of bacterial meningitis in children.
In 1990 the Hib vaccine was approved by the Food and Drug Administration and recommended for universal use in children--the first vaccine to receive such approval in more than 20 years.
Epidemiologists at the Centers for Disease Control and Prevention recently announced that use of the vaccine has cut the incidence of Hib infection in children under 5 by a stunning 99 percent--from about 20,000 cases a year to only 81 in 1997.
The Hib vaccine's development "put Rochester on the map in the field of vaccines," says Jay Stein. "We want to capitalize on it by making a long-term investment in basic research that will yield similar successes for us in the future."
Mosmann's charge is to establish the Center for Vaccine Biology and Immunology, one of six research centers that will comprise the University's new medical research institute.
Accordingly, he is busy this spring recruiting the 10 scientists and some 40 technicians and other support personnel who will occupy the top floor of a new research building nearing completion at the corner of Elmwood Avenue and Lattimore Road on the Medical Center Campus.
(Other components of the new Institute of Biomedical Sciences to be housed there will focus on aging and developmental biology; cancer biology; cardiovascular research; human genetics and molecular pediatric disease; and oral biology.)
Research in the Center for Vaccine Biology and Immunology will be similar to the work that vaulted its new chief to international acclaim a decade ago and earned him several nominations for the Nobel Prize.
Rather than setting out to develop new vaccines, Mosmann says, his center will pursue basic research aimed at understanding how the immune system works--in particular, how it organizes the myriad activities that accompany the body's battles against infections.
The repertoire of defenses is vast--as it must be to fend off marauders as diverse as bacteria (such as those that cause ear infections and strep throat), parasites (such as malaria), and viruses (such as HIV).
Finding ways to harness this arsenal of disease fighters--which viciously attack invading pathogens but carefully spare the body's own cells and tissues--is Mosmann's goal for the new center. "If we can learn to regulate aspects of the body's immune response," he says, "we can make progress toward treating or preventing a variety of diseases."
By manipulating the immune system, he notes, researchers are finding ways to cause it to attack and destroy cancer cells. "Cancer vaccines are promising because with cancer you're dealing with a slow-growing disease. This may make it possible to develop vaccines that are administered after the patient has been diagnosed. It would be similar to the way we administer vaccines against rabies--we give you the vaccine after you've been exposed to the infected animal."
Learning to modify the immune system could also offer hope to people who suffer from diseases such as asthma, allergies, and rheumatoid arthritis--disorders in which the body mounts an immune response that is either too powerful or not needed at all. By learning more about how the immune system manages itself, researchers may be able to devise ways to curb these inappropriate responses.
One of Mosmann's discoveries is being applied in this effort. While studying the ways that the Th1 and Th2 master cells regulate various functions of the immune system, he identified a protein, Interleukin-10, that is secreted by Th1 cells. Its role, he found, is to damp down the immune system's inflammatory response. Researchers are now testing Interleukin-10 to see if it can help in reducing inflammation in patients with rheumatoid arthritis and other diseases.
While the ability to put the brakes on certain immune responses may prove useful in treating some diseases, the opposite may be true also.
If researchers could learn to boost the body's immune system--rev it up, so to speak--they could help it fight diseases such as malaria and AIDS that typically win the battles in our blood.
Even with an arsenal of new vaccines already in the pipeline, Mosmann says that our greatest successes will arise from knowledge that has yet to be learned.
"The vaccines of the future will emerge as a direct result of basic research--of scientists gaining a clearer understanding of how the immune system works at the basic, molecular level," he says.
From his perspective as one of our era's top immunologists, what does Mosmann expect in the world of vaccines 20 years from now?
"That's a tough question. If you had asked that 20 years ago, many people would have told you that by the year 2000 we would have vaccines for tuberculosis and malaria. But we don't. And 20 years ago no one had even heard of AIDS.
"There are a lot of unknowns," he muses. "That's what makes it fun. That's why we do science."
Christopher DiFrancesco is director of communications for research at the University Medical Center.
Copyright 1999, University of Rochester