TWO FROM US SHARE NOBEL PRIZE IN MEDICINE
'G PROTEINS' SEEN KEY TO CELL LINKS

Author: By Usha Lee McFarling, Globe Staff

Date: Tuesday, October 11, 1994
Page: 5
Section: NATIONAL/FOREIGN

Alfred G. Gilman, of the University of Texas Southwestern Medical Center in Dallas, and Martin Rodbell, of the National Institute of Environmental Health Sciences in North Carolina, won the prize for work they conducted independently in the past three decades to discover the "G proteins" that act as the switchboard of the body's communication pathway.

"This very pathway was being activated as my heart was going about 150 beats a minute," Gilman, 53, told reporters in Dallas of his reaction to the news. Gilman and Rodbell, 68, will share the prize's $930,000 award.

Rodbell, at a press conference in Maryland, criticized the commercialization of science. "The tenor is changed, the world ain't the same, everything is targeted, everything is bottom line, how to make a buck," he said, adding that it is crucial to "capture knowledge for its own sake and for humanity."

The realm the Nobel winners studied is the complex relay of cell communication, by which information from the outsides of cells is conveyed to the cells' interior machinery by a series of agents.

G proteins, the most crucial of those agents, have been described as ''biological traffic lights." Lying inside the cell, they can respond to signals from outside the cell -- light, smell, neurotransmitters and hormones -- and translate them into a frenzy of cellular action inside.

While G proteins are little known to the general public, research on them has been one of the hottest biological pursuits of the past decade.

"G proteins are one of the keys to all functions in every cell of the body," Reuters quoted Gosta Gahrton, a professor of medicine at the Karolinska Institute in Stockholm and a member of the prize panel that awarded the prize, as saying.

The proteins are implicated in a growing list of cellular activities -- from mating in yeast to thinking in humans. They permit sight and smell by converting light and scent into messages that can be taken to the brain.

When G proteins do not work, they can lead to symptoms of such diseases as diabetes, alcoholism, cholera and whooping cough. The proteins, which have been called "ubiquitous, influential, and enigmatic," will be the target of medical treatments, the Nobel institute predicted.

At least 17 of the proteins have been discovered. They are called G proteins because they bind to guanine nucleotides, a major component of the genetic molecules DNA and RNA.

Rodbell and his co-workers at the National Institutes of Health determined that guanine nucleotides were involved in cell communication -- a finding that led to the discovery of G proteins. His work in the 1960s and '70s also described how messages like light are converted inside cells, and showed that cells have different components that receive, transport and amplify outside messages.

Rodbell retired in May. He holds the title of scientist emeritus at the National Institutes of Health. Gilman chairs the pharmacology department at the University of Texas Southwestern Medical Center in Dallas and won biology's coveted Lasker award in 1989. Gilman is the fourth UT Southwestern faculty member to win the Nobel Prize.

Gilman and colleages, while working at the University of Virginia in Charlottesville in the 1970s, looked for the chemicals that made up the substances Rodbell described. In 1980, they discovered G proteins.

The field did not blossom until 1984, when the first genes for G proteins were cloned. Since then, more scientists began working with the proteins, and some pharmaceutical companies are now trying to develop drugs targeting G proteins.

In a 1992 Scientific American article on G proteins that Gilman co-wrote with Maurine E. Linder, he predicted that scientists would evenutally diagram the cellular players involved in communication and be able to predict how those cells will operate in response to different combinations of signals.

"For those who would hope to develop drug therapies," the authors said, ''such discoveries would be like giving a thief a wiring diagram to the alarm system at a bank."

The medicine award is the first Nobel prize to be awarded annually. The economics prize will be announced today, and those for chemistry and physics tomorrow. The Nobel Peace Prize is to be awarded Friday, and the literature award will be conferred later this month.

CHOLERA -- Toxin from cholera bacteria keeps one type of G-protein switched on. This prevents salt and water from being absorbed from the intestines, causing dehydration and death.

WHOOPING COUGH -- Whooping cough bacteria keep one type of G-protein from being activated.

DIABETES -- Some symptoms may be due to faulty signaling through G-proteins.

MCFARL;10/10 NIGRO ;10/12,11:49 NOBEL11