Web Exclusives:Features

June 5, 2002:

Faculty File:
Lupus link
Martin Weigert discovers point where immunity breaks down

The work Martin Weigert is doing in Schultz Laboratory could lead to better lives for millions of Americans suffering from lupus, an autoimmune disease that U.S. health experts say is causing an increasing number of deaths.

Weigert, the Henry Hillman Professor of Life Sciences in the Department of Molecular Biology, and his collaborators at the University of Pennsylvania and the University of Tennessee, have discovered what could be a primary cause of the disease. They have found a point at which the immune system's mechanism for making disease-fighting antibodies breaks down and allows antibodies to attack the body's own DNA, an identifying characteristic of lupus.

As many as 4 million Americans have lupus, a disease with symptoms that range in severity from mild rashes to organ failure. According to a study released on May 2 by the Centers for Disease Control, the number of deaths due to lupus has risen from 879 in 1979 to 1,406 in 1998. During that 20-year period, 22,861 people died from the disease.

Weigert's research could lead to new treatments that may be ready for testing in three years. He is already developing peptides, small protein fragments, which are designed to block the disease in mice, and could lead to similar treatments for humans. Currently, lupus treatments call for immuno-supression, which compromises the entire immune system, and gene therapy similar to that undergone by cancer patients, says Weigert.

Weigert has been studying immunology for nearly 40 years and pioneered the use of genetically altered mice in researching how certain cells are regulated and the impact on autoimmune disease. This year, his 10th at Princeton after working at the Institute for Cancer Research in Philadelphia, Weigert again taught his popular freshman seminar on immune systems and an advanced immunology course for graduate students.

The freshman seminar Why Immune Systems Fail: Autoimmunity, Influenza Pandemics and HIV uses a computer simulation software called ImmSim that Weigert helped developed. Instead of simply reading about viruses and immune cells, students get to work with a virtual lab animal, directing ImmSim to "inject" doses of viruses and watching the reaction unfold as armies of immune cells emerge and fight the invader. Ultimately, they see whether the virtual animal lives or dies.

Weigert says most of the students who take the class do not have much of a foundation in immunology. The simulation program goes a long to teaching them the "players" in the continuous battles that go on in immune systems.

"It has the advantage over the usual textbook in biology because, as they run ImmSim schemes, they become aware of quantitative aspects of the immune system and the dynamics of the immune system," says Weigert. "Textbooks don't worry about how many viruses one is typically infected with when sneezed upon and how likely it is that a virus will come across a lymphocyte that bears a receptor directed against that virus. And how long in turn it takes those lymphocytes to divide and begin to secrete protective antibodies, while at the same time other viruses, or the same kind of virus is going on, infecting cells, multiplying, causing the initial stages of the flu."

For his efforts in the treatment of lupus, the National Lupus Foundation has provided funding for Weigert's research through its Philadelphia chapter since his days at the Penn Medical Center. "It's been a joy and a privilege to be associated with them. They're some of the most dedicated and sophisticated groups of patients I've been familiar with," says Weigert.

Goldie Simon, president emeritus of the Philadelphia area Lupus Foundation, describes Weigert as a "brilliant and caring" person. "I knew that by touching him and his expertise we'd be able learn much," says Simon, who lost a daughter to lupus.

By A.D.