2 Americans Win Nobel for Medicine

Two American scientists who discovered a cellular “switch” that is crucial to vision, smell and the functioning of hundreds of other processes throughout the body, were named Monday to receive the 1994 Nobel Prize for medicine or physiology.

Alfred G. Gilman, 53, of the University of Texas Southwestern Medical Center in Dallas and Martin Rodbell, 68, of the National Institute of Environmental Health Sciences in North Carolina shared the prize for their discovery of “G proteins,” which turn biological processes inside cells on and off in response to signals from other cells.

Defects in G proteins have been implicated in a variety of diseases, from cancer to alcoholism, and the Karolinska Institutet, which announced the award Monday, predicted that Gilman and Rodbell’s discoveries could eventually lead to a cure for these and other diseases.

Gilman has won a number of major awards for his work, and researchers have long expected at least one of the pair to receive the Nobel. “It would have been a major surprise if it were never awarded,” said biologist Ray Deshaies of Caltech.

Their discoveries, products of two decades of work, have been “paramount” in helping scientists understand diseases that affect tens of millions of people, said Bertil Fredholm of the Karolinska Institutet.

Rodbell and Gilman’s findings represent “a breakthrough so fundamental to medical science that G protein research has become one of today’s hottest fields,” said Dr. William Neaves, dean of the Southwestern Medical School.

In that sense, the award was “a little bit surprising in that . . . Nobels are often given in a field where all the work is finished,” said biologist Melvin Simon of Caltech. “This is a field that hasn’t matured yet. We have a lot more to learn.”

Ironically, Rodbell retired from the health sciences institute in May because he did not have enough funds to continue research for the entire year. His type of basic research, he said, is no longer widely welcomed in the mission-oriented world of federal science.

“The world ain’t the same,” he said at a news conference in suburban Washington, where he was visiting family. “Now everything is targeted, bottom line, how to make a buck. . . . The attention of the Congress and the executive branch always has been toward the end goal. They are not as willing to take a chance now on people like me in exploring the unknown.”

The pair will share an award estimated at $930,000.

Gilman, who became interested in science working in his father’s laboratory at Albert Einstein University at age 10, said: “I’m awestruck. I’m more excited than I’ve ever been.”

He pointed out that G proteins play a critical role in the adrenaline response, and noted that when he heard about the award early Monday morning, “this very pathway was being activated as my heart was going about 150 beats a minute.”

In fact, Rodbell and Gilman made their initial discovery working with the adrenaline pathway. The question before scientists in the 1950s was how, when adrenaline is released into the bloodstream to produce the classic “fight or flight” response, does it produce its effect on individual cells in the body.

The adrenaline binds to receptors on the surface of cells in much the same way that the radio signal from a remote control is captured by the antenna of a garage door opener. The two scientists discovered that inside the cellular membrane, right next to that receptor, sits a protein, which they named the G protein because it binds to a molecule called guanosine triphosphate.

When adrenaline binds to the receptor, it switches on the G protein, which then triggers a cascade of reactions within the cell in the same manner that a simple switch in the garage door opener transmits the signal that starts the motor that opens the door. After a very short period, the G protein shuts itself off, and the cell returns to normal.

Other scientists have subsequently found that G proteins work throughout the body. When light strikes a pigment in the eye, the pigment switches on the G protein, which triggers the visual pathway. When an odor molecule binds in the nose, it switches on a G protein that activates the process by which a smell is recognized. When an endorphin molecule binds to receptors on brain cells, it switches on a G protein that produces the “high” sensation when one is elated.

G proteins have assumed critical importance in recent years as researchers have discovered that several of them are produced by oncogenes, genes that cause cancer. G proteins produced from these genes trigger cell growth and replication in response to a hormone in their environment. But occasionally when the gene mutates, in response to a carcinogen perhaps, the G protein loses the ability to turn itself off. The affected cells thus continue to replicate, producing a tumor.

Many researchers believe that if they can find a way to mimic the normal activity of such G proteins, they can halt tumor growth.

“I think it’s a fairly safe bet that future G protein research will identify more problems that can be linked with malfunctioning of this mechanism,” Gilman said. Such knowledge, he said, could lead to treatments for a variety of such problems.

The Prize Winners

Two Americans won the Nobel Prize in medicine for shedding light on how cells communicate and how failures in that communication can cause disease.

* THE FINDINGS: The scientists determined how a certain group of proteins can help transmit and modulate signals in cells, much like a biological switchboard. They found that once a cell has received chemical signals by means of surface proteins called receptors, G proteins transmit and modify these signals within a cell to produce the cell’s response. Too many or too few G proteins can lead to disease.

* SOME EXAMPLES: In cholera, toxin from cholera bacteria keeps G proteins switched on like a stuck green light. That prevents salt and water from being absorbed from the intestines, which can lead to dehydration and death. Disturbances in the G proteins also can explain symptoms in tumor diseases, alcoholism and even whooping cough.

* POSSIBLE RESULTS: Knowledge about the communication process inside cells should help in designing better drugs for treatment of certain diseases.

SOURCE: The Associated Press