THE VIRGINIAN-PILOT
Copyright (c) 1994, Landmark Communications, Inc.
DATE: Tuesday, October 11, 1994 TAG: 9410110305
SECTION: FRONT PAGE: A2 EDITION: FINAL
SOURCE: BY MARIE JOYCE, STAFF WRITER
LENGTH: Long : 102 lines
Now, Alfred G. Gilman's former colleagues at the University of Virginia find it hard to separate hindsight from memory. They can't say if they realized, 17 years ago, that Gilman's work would open new doors in medicine.
But even back then, they knew he was onto something big.
Gilman is one of two Americans awarded the Nobel Prize in medicine yesterday. The work that earned him that honor started at U.Va.
Gilman, 53, is now chairman of the department of pharmacology at the University of Texas. He shares the $930,000 prize with Martin Rodbell of the National Institute of Environmental Health Sciences in North Carolina.
Their work showed how cells process information from outside messengers. Their discoveries, which were made separately, led to many more scientific advances and helped improve scientists' understanding of many diseases, including cholera and some types of cancer.
``It's a fundamental way your body works and thus is very important,'' said James Garrison, chairman of the department of pharmacology at U.Va.
Gilman wasn't available for comment yesterday.
Theodore Rall, professor emeritus of pharmacology at U.Va., remembers vividly a day in 1977 when Gilman burst into his office at Jordan Hall.
He had an idea.
Gilman was usually pretty low-key. But this day he paced from one end of the room to the other, almost literally bouncing off the walls. He grabbed a piece of chalk and scribbled test results on Rall's blackboard.
Rall leaned back in his chair and kept silent.
They'd known each other for years. Rall, 12 years older, had been Gilman's doctoral adviser at Case Western Reserve University in Cleveland in the 1960s. They often bounced ideas off each other.
At U.Va., Gilman was trying to find out how cells receive and respond to messages from outside the cell membrane.
This is what scientists knew at the time: Stimuli - for instance, hormones floating around the bloodstream - attach themselves to receptor proteins on the outside of cells.
This leads to the production of a substance inside the cells called cyclic AMP, an internal messenger that prods the cells to do whatever they do - create steroids or glucose or proteins, for instance.
But there was a missing link. That's what Rodbell had been the first to recognize. Scientists didn't know what substance in the cell received the outside message and created the cyclic AMP.
But Gilman thought he knew how to find it.
``When he left, he thanked me for my input,'' Rall recalled, then burst into laughter. ``I didn't say a word.''
Gilman went on to isolate the first G-protein - the missing link in the chain. After he was recruited by the University of Texas' Southwestern Medical Center in 1981, he did more work showing that the first protein was just part of a larger family.
Since then, about 20 G-proteins have been discovered by Gilman and others.
It's not the kind of work that leads to the immediate creation of new drugs, said Garrison. It's really an advancement in basic knowledge about cell function.
It has greatly improved scientists' understanding of certain diseases, he said.
Cholera, for instance, makes a toxin that attacks a type of G-protein molecule in cells of the intestines. In effect, the cells are permanently switched on.
These overstimulated cells do too much of what they're supposed to do - secrete water. Water pours into the intestines, leading to terrible diarrhea, then dehydration.
The G-protein also plays a role in certain types of cancers, such as pituitary tumors, which form when the cyclic AMP causes cells to reproduce out of control.
While Gilman was at U.Va., he was gregarious and eager to talk about his work, colleagues recalled. His voice carried weight in faculty meetings because his abilities were well-respected.
He was a serious scientist, with few outside interests besides his family and his garden, they said. But he had a sense of humor and wasn't above playing a practical joke.
Once, Gilman was introducing a scholarly lecture by Rall. The introduction included a few slides.
Suddenly, up popped a picture of Rall as a very young Army recruit. He had gone about 36 hours without sleep when the picture was taken, and he looked pretty dazed. The lecture hall exploded with laughter.
Rall said he's always been impressed by Gilman's precise, focused mind.
Even as a student, Gilman could look at a scientific problem and ``somehow identify the crucial point or question in an unknown sea of various questions someone could ask about something,'' said Rall. ``That's something you can't teach people.
``My claim to fame was I got out of his way,'' he added with a laugh.
Gilman's background couldn't have been more suited to his work.
His father, Alfred Gilman, was a Yale University professor who helped compile the ``Blue Bible'' - the seminal textbook for pharmacologists.
When the younger Gilman was a boy, he helped his mother type pages for the book, Rall said. As an adult, he took over his father's editorial job for several years.
Gilman got his undergraduate degree from Yale, then entered a competitive Case Western program that allowed him to earn a medical degree and a doctorate in pharmacology at the same time.
``There are some people in the world who manage to do 10 or 15 times the average human,'' Garrison said. ``He was one of those people.'' by CNB