Where Science Leads, continued
these problems are universal
in the realm of scientific exploration. Researchers everywhere complain
about the obstacles they deal with to obtain funding for their work, says
Wistar professor Dr. Meenhard Herlyn. Since grants and scientific productivity
are tightly tethered, Herlyn explains, Wistars administration has learned
to cater to the research. The grants office, for example, formats and
prepares grant proposals for investigators so that they need only spend
their grant-writing time on the science and their budgetary needs. The
development office identifies donors who might want to underwrite specific
calls Wistar the best of all possible worlds for a researcher. The Institute
is relatively small and administratively streamlined. Investigators have
virtually no bureaucratic obligations or teaching responsibilities to
eat up their time. And they have access to all the assets Penn has to
offer, including libraries, seminars, patient samples and graduate students,
who come to work in their labs.
Wistar is a separate and independent entity, it has a strong history of
research collaboration with Penn. Some of the researchers at Wistar hold
joint appointments at the University and many Penn degree candidates do
much of their accreditation work at Wistar. As a result, theres no shortage
of comparisons between the two institutions. For example, Wistar,
unlike Penn, can be likened to a farmers market, where everyone has his
own stall. The institute, which boasts a 50 percent rate of Ph.D.s among
its 300 or so employees, is populated by independent labs with little
overlap in their specific fields of expertise. Yet Wistar fosters interdisciplinary
interaction that allows the scientists to share, and use, each others
knowledge. Ellen PurČ, who studies the inflammatory mechanisms behind
atherosclerosis, says her research benefits, for instance, from the interaction
she has with the molecular genetics group down the hall and the structural
biologist next door. By contrast, she says, Penn is so big that one needs
to really work at getting to know anothers research.
what Penn offers to Wistar is an enormous supply of M.D.s who are in the
trenches and can deliver patient samples for research purposes. An additional
benefit: the possibility for unique fusions of the clinical and the research
perspectives, says PurČ. She explains that a doctor might remark to her,
I have a patient that lacks the enzyme that results in this phenotype.
Can we think about this problem together? A place like Wistar-Penn
is fertile ground for such collaborations, she says. We need these two
types of people talking so that they can connect the dots.
her research on atherosclerosis and airway inflammation associated with
asthma, PurČ works closely with several physicians within the University
of Pennsylvania Health System, including pulmonary specialists and an
internist who specializes in lipid disorders. While both of these disease
processes share a common enemyinflammationPurČ foresees atherosclerosis
to be the domain in which she may have the most immediate clinical impact.
PurČ hopes to combat this battle in the vessels by identifying the genes
and molecular mechanisms that facilitate the atherosclerotic process.
She studies the receptors in the blood vessel that allow for the adhesion
of the inflammatory cells that comprise plaques, and she has uncovered
the role of a significant receptorthe CD44 moleculein the development
of plaques that may be more susceptible to rupture and clot formation
leading ultimately to heart attack or stroke.
mechanisms that underlie chronic inflammatory disease, which are also
key players in tumor metastasis, are potential targets for new drugs aimed
at preventing atherosclerosis and other inflammatory conditions, she says.
But this pathologic machinery cannot be manipulated until it is understood.
been a lot of discussion about getting all of this basic research to be
translated into human healthcare, PurČ adds. The conventional wisdom,
she continues, has been to get M.D.s to do science. And then everyone
said, Lets get people with combined degrees to do science. But neither
solution has worked completely. She believes that the therapies of tomorrow
will come from basic scientistsworking with research tools like lab mice
and test tubesin collaboration with their counterparts in the clinical
Thanos Halazonetis, assistant professor at Wistar, is busy mapping the
distinctions between tumor cells and normal cells, and defining certain
checkpoint genes that, when mutant, fail to assume their normal function
of inhibiting cells from entering into the spiraling growth patterns of
cancer. He laments the fact that basic science is given little popular
attention. The people think that their doctor will figure out better
ways to treat cancer. But thats not going to happen, he says. If the
public understands that laboratory research is important for the development
of new therapies, then so will the politicians. In his laboratory just
inside Wistars elegantly marbled, first-floor atrium, to the left of
the steep grand staircase, Halazonetis walks past a row of large beakers
filled with yellowish liquid. He stops for a moment to make a predictionthat
his exhaustive research on seemingly esoteric bits of DNA will materially
improve the way in which doctors treat patients within the next 20 years.
melanoma research lab,
by Meenhard Herlyn, is the institutes largest laboratory. It also comprises
the largest melanoma research group outside of the NIH. Like Halazonetis,
Herlyn hopes to advance clinical medicine through his bench work. Herlyn
describes a study conducted a few years ago in which seven world-class
pathologists were given 38 samples of lesions that represented either
melanoma or dysplasticabnormally-growingtissue. Shockingly, the doctors
disagreed on their diagnoses in 40 percent of the cases.
is striving to understand the early changes that take place in the growth
of melanomas, and to develop highly accurate molecular models that will
help pathologists to better diagnose them. He notes that the cure rate
for melanoma is about 100 percent when it is caught and treated early.
And by better defining the transcription factors that promote the proliferation
of melanoma cells, Herlyn hopes to pinpoint ways in which chemotherapy
and radiation could be rendered more effective in treating melanoma.
this research did not come soon enough to save Noreen ONeill, who died
last summer of metastatic melanoma. ONeill was president of the Foundation
for Melanoma Research, an organization that Herlyn cofounded with a group
of melanoma patients. Herlyn continues to be inspired by ONeills plight,
from which, he says, it became clearly obvious to me that therapy for
melanoma is very much in its infancy.
better characterize the behavior of melanoma cells, Herlyn, who has been
engaged in melanoma research since 1977, uses a mouse model to cultivate
the disease. He grafts human skin, which he obtains from surgeons at the
Hospital of the University of Pennsylvania, onto the backs of his mice.
He then injects them with growth factor and places them under ultraviolet
lights. After about three months, some 10 percent of the mice have melanoma
lesions, which are then harvested, grown in tissue culture, and analyzed
during their successive growth phases. Herlyn scrutinizes the abnormal
melanocytes to determine how they escape the control of the keratinocytes,
which are the normal cellular gatekeepers in this growth process. And
he also tries to ascertain which genes are the culprits in transforming
the melanocytes from normal to aberrant cells.
Louise Showe, an associate professor and core facility director at Wistar,
runs the microarrayer that Herlyn and some of the other cancer researchers
hope to soon rely on to better define the differences between normal and
cancerous cells. Showe, who last year received a five-year, $500,000-a-year
NCI grant to develop microarray technology at Wistar, produces arrays
that consist of spots, or probes, of DNA for 1,700 selected genes. RNA
is extracted from the cellsmelanoma cells, for examplethat are under
investigation. Copies of the RNA are then produced, each incorporating
a radioactive tag. Once brought into contact with the DNA probes, these
RNA targets bind to the probes that correspond to the genes that generated
them. The resulting DNA-RNA complexes are read radiographically to assess
which genes in the study sample are active, and how strongly they are