The medical researchers are closing in day by day, like detectives on the trail of an elusive criminal. Five years ago, they followed their suspect into a microscopic world, to part of a single chromosome.

Six months ago, while looking for more clues, they walked across the culprit's neighborhood, gene by gene.

Now the search is door to door, say researchers at the Coriell Institute for Research in Camden who are hunting for the gene on Chromosme 6 that protects people from developing diabetes.

They're also trying to determine how an altered form of this gene makes people more susceptible to the disease.

"We know we're in the right place," said Coriell president David P. Beck, "but the level of detail is extremely fine. We could find what we're looking for tomorrow or three years from now."

If scientists can pinpoint either the "susceptibily" gene that seems to cause diabetes or the "protective" gene that prevents it, they'll try to develop gene therapies, or drugs to head off the onset of the disease - two huge hurdles, but goals for the future.

About two dozen facilities around the world - including Harvard, the University of Pennsylvannia and research sites in England and France - are searching for the gene, or genes responsible for diabetes.

Only Coriell and a couple of other institutions are concentrating the search on a protective gene, Beck said.

"Technology has moved to the point where we can hope to understand diabetes," said Beck.

Here we are thousands of years later and we have insulin - a halfway technology. It doesn't do anything but treat the symptoms."

Sophisticated lab equipment, computers, powerful microscopes and DNA analysis units now allow scientists to dissect and study parts of the human genome. "A program like this is timely," according to Beck. "It's hot, it's right on target."

Coriell researcher Marie L. Hoover, who is heading up the diabetes work at the institute, is conviced she will find the protective gene - and when she dose, "the biggest questions will be: "What does it do and how does it work?"

Diabetes is one of the most common genetic maladies - the leading cause of kidney transplants, the leading cause of blindness in people ages 30 to 65, and the fourth leading cause of death by disease.

About seven million Americans have it. Six million others probably have it - and go undiagnosed.

The disease prevents the body from producing its own insulin or utilizing its insulin, which is necessary for regulating the level of glucose in blood. Glucose is produced by the digestive system for sugars and starches, and is distributed to muscles and organs.

"The complications of diabetes are very, very devastating," said HOOVER. "If you can stop the disease, that's what you want to do-not just treat it."

There are two major forms of diabetes: insulin-dependent Type I., and non- insulin-dependent Type II. Type I usually occurs in childhood or adolescence and causes a lifelong dependence on external sources of insulin. Type II comes later in life and may often be controlled by diet and exercise.

Hoover has focused her work on Type I. She has said scientists became interested in studying Chromosome 6 in 1972 when, during the matching process for kidney transplants, they found that patients with diabetes shared certain genetic characteristics.

Five years ago, while looking at the chromosome further, Hoover and other researchers found what they believed might be a protective gene. Seventy-four of 203 people without diabetes had it. Only six of 266 people with the disease also had it.

Hoover looked at the chromosome of those six people in more detail last spring, expecting "to show that the gene was not protective, how could it be, since some diabetics had it too?"

To her surprise, a closer look at the chemical subunits of DNA showed that the diabetics did not have the protective gene. Out of 266 diabetics, none had it. Sixty-nine of two hundred and three people without the disease had the gene.

"Zero says there's got to be something," said Hoover. Then, pointing to a graphic representation of Chromosome 6, she said, "There has to be something along here...something along here."

Scientists have been attacking diabetes on many fronts, trying to find a trigger that sets the body against itself.

Researchers at Children's Hospital of Philadelphia (CHOP), the University of Flordia and other institutions are checking the relatives of Type I diabetics for the antibodies typically found in the blood before the onset of the disease.

The antibodies can signal the immune system's attack on the insulin-producing Beta cells in the pancreas. If scientists could prevent that immune system response, they could head off diabetes.

Lester Baker, director of CHOP's Diabetes Centre for Children, said experimental evidence suggests that giving insulin injections to people at a high risk for diabetes has the potential to halt, slow or delay the progression of diabetes.

Giving patients compounds such as insulin and the enzyme glutamate decaroxylase - in pill form - also can help. University of Florida researchers have found that these compounds occur naturally in the body and apparently become targets of the immune response that causes Type I. The pills can cause the immune system to tolerate the insulin's presence and prevent the disease.

Baker said the research project began about six months ago and will involve thousands of patients across the country over the next five years.

Earlier research, dating back 20 years, focused on suppressing the immune system with the same drugs used by transplant patients to prevent organ rejection.

That approach was abandoned because permanently suppressing the body's defences could lead to other serious health problems.

Genetic work offers another area of investigation. Much of the research thus far has concentrated on finding a susceptibility gene on Chromosome 6- a gene that leaves people more likely to get diabetes.

If someone inherits a copy of the gene from each parent, the risk for the disease is high. A susceptibility gene from one parent and a neutral gene from the other makes the risk low. The pairing of a protective gene and a susceptibility gene makes the chance of getting diabetes nil.

Richard Spielman, professor of genetics at the University of Pennsylvania School of Medicine, said some evidence suggests that genes for diabetes susceptibility also exist on other chromosomes, including Chromosome 11.

What's more, he said, the correlation between the genes and the onset of the disease isn't perfect. "You can have the same genes as someone with diabetes, like an identical twin of a diabetic, but never develop Type I diabetes."

Spielman and other researchers are now "systematically looking at all the chromosomes to find places in addition to Chromosomes 6 and 11, where there might be genes that contribute to susceptibility and resistance."

While many types of research continue simultaneously, Hoover and other scientists continue to look to Chromosome 6.

Somewhere on this human blueprint resembling a pricing bar-code is a gene or genes that encode for protein molecules on the surface of cells. It makes them recognizable to the immune system.

In people without diabetes, the cells of the immune system "see" the Beta cells in the pancreas as part of the body.

"The surface of the Beta cell is labeled," daid Beck. "So the cells of the immune system say, 'You're OK.' "

In diabetics, the Beta cells are not recognizable.

"The name badge has somehow been smudged," said Beck. "The cells of the immune system think they're foreign and attack."

"We're chromosome-walking, looking at big chunks." "If this was history, it would be like looking at the years 1812 and 1850, but not knowing what happened in between. Once we find the overlapping pieces, we find the steps in between."

"NOBODY BUT GOD CAN TELL WHAT THE RIGHT PATH IS."