SHAKESPEARE'S SECRETARY

Associate Professor of Chemistry Laura Furge delivered the College's annual Honors Day Lecture in November. Her talk was titled "Cancer in America and Beyond." Furge returned to her teaching post last fall after a sabbatical doing cancer research at the Van Andel Research Institute in Grand Rapids. Well, not exactly just Grand Rapids. Furge was part of an international research team headed by cancer scientist Bin Teh, who maintains labs in Michigan and Singapore. Countries represented by scientists on the team included China, England, Malaysia, Japan, France, Brazil, Taiwan, Singapore, and the U.S.

This fact is instructive, according to Furge, underscoring the importance to science students of a liberal arts undergraduate experience that includes meaningful study abroad.

In her talk Furge explored changes in the factors that influence life expectancy in countries throughout the world, which ranges from 32 to 82 years. Humankind's progress against infectious diseases has been the most significant factor in a general increase in life expectancy. A somewhat ironic measure of success in this area has been the increase in mortality rates due to degenerative diseases like heart disease and cancer.

Furge spoke to an audience that was as liberal arts-ish as it was large. Nearly every department in the College was represented. Seeing faculty from English, art, biology, political science, sociology, physics, math, and economics attend a chemistry lecture seems the very elixir of the meaning of liberal arts. That the chemist can speak to such an audience so that its members comprehend the subject shows that (in true Margaret Meade fashion) she has mastered her subject matter well enough to step from the lab.

In deference to the varied level of scientific literacy of her audience, Furge used a metaphor to illuminate the molecular basis of cancer, which usually arises from "copying" errors during cell division. The instructions for correct division are included in a cell's DNA, arranged in chromosomes.

"Every time a cell divides is like asking an administrative assistant to re-key Shakespeare's entire opus - plays, sonnets, and long poems - without making a single typo," explained Furge. The vast amounts of genetic information contained in DNA mean a vast potential for tiny transcription errors to occur - tiny errors that may express in unregulated cell proliferation.

Live long enough and likelihood of cancer increases. After all, aging isn't so much a matter of years as it is increased cell divisions - in other words more chances for Shakespeare's beleaguered transcriptionist to make a typo when re-keying his entire oeuvre.

Eleven million new cases of cancer are diagnosed each year, said Furge. Each year seven million people die of the disease. Furge shared graphs of cancer incidence - they resemble tornado funnel clouds - and explained their use in the determination of cancer risk factors (there are more than just aging).

At the bottom of the funnel is a baseline rate of incidence for a specific cancer. For example, the baseline rate for stomach cancer is 3 people in 100,000 in some countries, but it ranges (think of a tornado's widening ascending gyre) up to 62 people per 100,000 in other countries. With that data in hand, scientists have a map to explore and begin to understand risk factors for specific cancers.

"In the early 20th century lung cancer was so rare that professors would make special efforts to point out cases to their medical students noting that they were unlikely to see the disease again," said Furge. Obviously
Furge spoke to an audience that was as liberal arts-ish as it was large. Nearly every department in the College was represented.
new risk factors - most notably smoking - changed the incidence.

Cancer risk factors include life style choices (such as smoking and diet), environmental exposures, infection, and combinations of the above. Cancer incidence can be affected by prevention and vaccination. Treatment is often a matter of surgery, radiation, or chemotherapy (the use of powerful medicines). Oftentimes these medicines poison healthy cells along with cancer cells.

That's where Furge's sabbatical research comes in. She worked in the area of targeted drug design: building molecules that hone in on a specific genetic mutation (think "typo") and thus confine the medicine's deadly effect to cancer cells alone.

Her research focused on kidney cancer, unique among cancers for its refractoriness to all cancer medicines. Because of that characteristic, medicinal scientists have explored treatment strategies other than direct attack on kidney cancer cells. One of those is starvation. Kidney cancer is associated with a mutation of a molecule called vascular endothelial growth factor (VEGF). The mutation causes VEGF to bind with a receptor, the result of which is the growth of new blood vessels that feed the tumor. A medicine has been developed that effectively treats the cancer by blocking VEGF's binding, but the medicine stops working after six months. No one knows why.

During her sabbatical Furge explored whether resistance to the medicine occurs because of changes in the way the body processes (or metabolizes) it. The hope is to attenuate whatever factors cause the resistance, thus prolonging the medicine's effectiveness and the lives of patients with this particular cancer.

Photo: Members of Laura Furge's international cancer research team.

by Jim VanSweden

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