2 Americans Win Nobel Prize for Medical Discovery

Times Medical Writer

An American biochemist and an Italian-American neurobiologist were named co-winners of the 1986 Nobel Prize in medicine Monday for discovering proteins, known as growth factors, that play a key role in regulating cell and organ development in animals and humans.

In awarding the prize to Stanley Cohen, 63, of the Vanderbilt University Medical Center, and Rita Levi-Montalcini, 77, of the Institute of Cell Biology in Rome, the Nobel Assembly of Stockholm's Karolinska Institute said their research "may increase our understanding of many disease states," such as Alzheimer's disease and cancer.

The study of such growth factors has increased understanding of one

of the enduring mysteries of life: how individual cells develop into complex organ systems.

And the awards are all the more poignant because of the personal obstacles each researcher has had to overcome.

Levi-Montalcini, a Jew, carried out experiments in her bedroom while hiding from the Nazis during World War II, after being forced to quit her university post in Turin, where she grew up.

Erling Norrby, professor at Sweden's Karolinska Institute, which awards the medicine prize, said she "made a laboratory out of her bedroom, sharpened the knives herself and once in a while the eggs she used became scrambled eggs after the experiment."

The results of her clandestine research in developmental biology were published in Swiss medical journals and came to the attention of Viktor Hamburger of the Washington University in St. Louis. Hamburger, who studied the nervous system of chick embryos, invited her to join his laboratory in 1947.

It was at Washington University that Levi-Montalcini met Cohen, and the two worked together for seven years in the 1950s. She retired from the university in 1977 and returned to Italy.

Polio Victim

Cohen suffered from polio as a child and continues to walk with a limp.

"It feels good to get world recognition for something you've been working on for 30 years," Cohen said in a telephone interview from Nashville. "When we started, we were following a little trail of interesting observations. We had no expectation it would open up a whole field of research."

In Turin, Levi-Montalcini told the United Press International: "Twenty minutes ago I received a call from Stockholm and I was very, very surprised because I came back from there only yesterday. I gave a talk at a neuroscience meeting in Stockholm and everyone was very kind to me but there was no mention of a Nobel prize."

The collaboration between Levi-Montalcini and Cohen began in 1953 when she asked him to help her isolate a nerve growth factor that she had found in mouse tumor cells.

Cell Maturation

The two researchers subsequently isolated and purified more potent nerve growth factors from snake venom and the salivary gland of mice. That lent credence to their belief that such factors play a crucial role in the maturation of nerve cells.

In 1962, while studying nerve growth factor from mice, Cohen accidentally detected another growth factor that stimulates cells to divide.

He discovered that extracts of the gland, when injected into newborn mice, caused their eyelids to open sooner than usual. Subsequently, he purified mouse "epidermal growth factor" and, in 1975, isolated its human counterpart.

Initially, such research received skeptical reviews, and some even suggested that growth factors didn't exist or were of trivial importance.

But in the last decade, the role of these growth factors has become increasingly accepted. Scientists have studied these two growth factors, and more than a dozen others, to learn how cells communicate with each other. Such research has led to better understanding of the molecular basis for cancer and degenerative diseases of the brain.

Structural Relationship

It has also been discovered that growth factors are structurally related to other important hormones, such as insulin.

In the early 1980s, British scientists, studying animal tumor viruses, discovered a structural relationship between another growth factor and proteins involved in the development of some cancers, a finding that has stimulated additional interest in the field.

Growth factors have now been found in a variety of human tumor cells as well, according to Harry Haigler, a former student of Cohen's and now an assistant professor at the UC Irvine Medical Center.

Levi-Montalcini, who is popularly known in Italy as "signora of the cells," holds joint Italian and American citizenship. She is the fourth woman to win the Nobel Prize in medicine since it was first awarded in 1901. She never married and lives with her sister, who is an artist.

Friend's Appraisal

"She is a very tough lady, all steel from one end to the other," said Ralph A. Bradshaw, chairman of the department of biological chemistry at the UC Irvine Medical Center, who is a friend and colleague of both Levi-Montalcini and Cohen. "She did a lot of this research at a time when women had a hard time succeeding in science."

Cohen, described by colleagues as a modest, soft-spoken man who smokes a corncob pipe and paces for hours while trying to solve research problems, is married and has three children.

"Stanley does science the way you are taught to do it in the textbooks," Bradshaw said. "Most of his seminal observations would have been missed by somebody else who wasn't as careful."

The two laureates, who last month also won Lasker basic medical research awards, will share a record prize of 2 million Swedish kroner, or about $290,000.

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