By Joan P. Capuzzi Giresi
Photography by Jim Graham
was pure accident that led Dr. Ellen Heber-Katz to make a 90-degree turn
in her research focus. The year was 1994 and, in her investigations on
T-cells and their role in autoimmunity, the Wistar Institute researcher
was working with a special strain of mouse prone to developing the autoimmune
disease lupus. As part of an experiment, Heber-Katz separated the small
white critters into two batches, demarcating them by punching ballpoint-sized
holes into the ears of one of the groups. A few weeks later, she was confounded
to find that all of the holes had mysteriously closed, leaving behind
no hint of their former existence, not even a scar.
I saw there were no ear holes, she recalls, I didnt know who was who.
lemon or scientific serendipity? The future holds the answers. Heber-Katz,
who is also an adjunct professor in the pathology and laboratory medicine
department at Penns School of Medicine, now devotes about 80 percent
of her time to mapping the gene loci that confer these unique regeneration
properties and analyzing their patterns of expression. She hopes that
her research on the healer mouseas it was coined at Wistarwhich exhibited
full replacement of its epidermis, dermis and cartilage in three to four
weeks following ear puncture, could be a boon to burn victims and might
contribute to research on stem cells, wound healing, and cartilage and
nerve regrowth. But thats still a long way off. For now, Heber-Katz says,
the leading question on her mind is, Why are these mice able to do this
and other mice are not?
queries like this are what have kept the Wistar Institute at the forefront
of scientific research through the years. Major accomplishments by Wistar
investigators include the identification of a number of cancer-causing
genes, the development of the TALL-104 cellsa promising immunotherapy
currently in clinical testing against several forms of cancer, and the
discovery of interleukin-12 (IL-12)a messenger protein important in facilitating
immune response to infection. Among the first research institutions to
develop monoclonal antibodies, which can detect and destroy foreign invaders,
including cancer cells, Wistar has been responsible for a host of other
noted creations. These include the Wistar ratthe first standardized laboratory
animalfrom which over half of todays laboratory rats are thought to
be descended, and vaccines against rabies and rubella.
Frank J. Rauscher III
complexity of the work being done at Wistar is rivaled only by its pure
simplicity. Wistar is wholly devoted to basic research, says Dr. Frank
J. Rauscher III, professor and deputy director of the Institutes cancer
center. Basic research at Wistar runs the gamut, from the study of the
fruit-fly genome and the remarkable immune systems of insects to investigations
of the molecular mechanisms of cancer. The pursuit of the latter occupies
the bulk of the lab space and brain power at Wistar today.
other hallmark of Wistar-style scientific exploration is that it is hypothesis
driven. Ninety-eight percent of our experiments dont work, Wistar professor
Ellen PurČ confides. At a drug company, if an experiment doesnt work,
it stops there. At Wistar, a failed hypothesis goes on to a new hypothesis
and new experimentation. Hence the unwritten guiding principle at Wistar:
Go where the science leads. For Heber-Katz, this progressive approach
allowed her to rapidly shift direction in her research from autoimmunity
to cellular regeneration.
a different way, Rauscher has also followed where the seductive and meandering
trail of science has led. In the mid-1990s, he was studying the intricacies
of zinc- and RING-finger proteins, genetic proteins that modulate gene
function. At the time, a group of scientists in Utah discovered the BRCA1
gene, which, when mutated, renders a womans chances of developing early-onset
breast or ovarian cancer over 80 percent. When Rauscher realized that
the protein coded for by this gene was a member of the protein family
hed been studying, he became elated and headed into the directors office.
Look, I said to him, I think I can make an impact here, but I need
some basic support.
was granted, and Rauscher and his team went on to discover the gene BAP1,
which has the dual function of regulating BRCA1 levels and controlling
its activities. Rauscher hopes eventually to identify drug receptors on
oncogenesthe genes that activate the uncontrolled cell growth of cancer.
He says that the discovery of BAP1 makes it possible to genetically test
for its presence and then potentially use it as a target for cancer-fighting