Faculty File: Lupus
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
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
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
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.