Hopkins Medical School: Research is the Hallmark

June 06, 1993|By DAVID A BLAKE AND RACHEL WILDER

When the Johns Hopkins University School of Medicine opened its doors in 1893, it changed the way medicine was taught. It soon became what no medical college had ever been: a center of basic as well as applied science.

A century ago, American medical education was in a deplorable state. Students learned medical practice by rote. There were no laboratories in which to develop new treatments, no teaching at the bedside. Hopkins was the first American school to insist on rigorous premedical training, at both the bedside and at the laboratory bench.

Applying the basic sciences to human disease was a Hopkins hallmark from the start. The school was the first to give doctors the luxury of being paid to do research. And what that luxury spawned endures to this day: a long list of Hopkins "firsts" that helped revolutionize the practice of medicine over the course of the last century.

Today, that tradition continues. Hopkins basic scientists Daniel Nathans and Hamilton Smith, for example, paved the way for ever-more sophisticated genetic engineering when they found the body's own chemical scissors for cutting DNA. This discovery, for which they won the Nobel Prize in 1978, may one day allow physicians to remove, replace or repair genes before ++ they can cause such problems as cancer or diabetes.

Current research that combines the science of the brain, behavioral science and clinical neurology promises a profound understanding of ourselves and entirely new approaches to neurologic and behavioral disorders. In many specialties, the wave of the future will be to emphasize the prevention of illness, rather than treatment of end-stage disease.

Every decade, a very few studies emerge as milestones that move medicine forward. When, a century from now, our great-grandchildren look back on today's research, which advances will be considered the "greats" that completely changed our approach to disease?

Here are five of the most fertile research areas at Hopkins now -- all likely candidates for that future list of greats.

1. Phantom messengers in the brain.

The journal Science declared the gas nitric oxide "molecule of the year" in 1992, when research from neuroscientist Solomon Snyder's lab helped elevate the status of this gas from toxic molecule to crucial carrier of messages between brain cells. The gas was previously known to be a relaxer of blood vessels, but the discovery of nitric oxide's function in the brain established gases as an entirely new class of messengers within the body.

Dr. Snyder's studies on the basics of nitric oxide -- how it works, where it's found and how it can go awry -- may have implications for the treatment of stroke, Alzheimer's disease and Huntington's disease.

Recently, a second gas -- carbon monoxide -- was found to carry signals between nerve cells in the brain as well. And other research -- a collaboration between urologists and neuroscientists -- solved an age-old mystery by demonstrating that nitric oxide transmits nerve signals in the penis and is thus responsible for penile erection. This discovery one day may yield new treatments for impotence, which affects one in 10 American men.

2. Fighting cancer with the body's own "smart bombs."

Cancer researcher Drew Pardoll has stopped tumor growth in mice by genetically stimulating the animals' own immune systems. He discovered a way to manipulate the body's own natural defense systems so that they kill cancer cells and leave normal ones unharmed.

In the fall of 1991, Dr. Pardoll and his team were the first to show that gene therapy could cure an animal of an established tumor. Already, researchers at Hopkins are in the early stages of testing gene therapy on human cancers.

Dr. Pardoll's approach involves calling cancer-fighting chemicals into action from within the tumor cells. He genetically engineered tumor cells from mice to secrete large doses of a natural chemical called Interleukin-4, which destroys cancer cells.

Ordinarily, immune cells called T-cells produce IL-4, but for an as-yet-unknown reason, T-cells are not properly activated in cancer. Dr. Pardoll's genetic manipulation "turned on" the T-cells. Once activated, these cells function like smart bombs, killing the specific target but leaving little collateral damage.

3. Genes that can start or stop cancer.

In Bert Vogelstein's lab at the Johns Hopkins Oncology Center, researchers have laid bare the molecular genetics of colorectal cancer, the second most common form of cancer in the United States.

Last month, Dr. Vogelstein and researchers from the University of Helsinki in Finland announced the discovery of a the genetic basis for one of the most common forms of colon cancer. They estimate that one in every 200 people carries a mutant gene that leads to colon cancer, making it the most common inherited disease yet identified in humans.

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