SCIENCE

On the leading edge

Canadians are at the forefront of diabetes research

BARBARA WICKENS October 31 1994
SCIENCE

On the leading edge

Canadians are at the forefront of diabetes research

BARBARA WICKENS October 31 1994

On the leading edge

SCIENCE

Canadians are at the forefront of diabetes research

Searching for the gene that causes a particular disease can be compared to looking for the proverbial needle in a haystack. The scientist’s task is exponentially more complicated when more than one gene is implicated. But earlier this month, a University of Calgary research team led by medical geneticist Dr. Leigh Field announced that they had found the location of two genes that produce susceptibility to Type 1 diabetes—in effect, two needles in the haystack. In 20 previous years of research, scientists had found only two other

genes believed to trigger the deadly disease, in which the body’s own immune system destroys crucial insulin-producing cells in the pancreas. But using recent scientific advances, researchers worldwide have raced to identify more of the genes that put individuals at high risk of developing the disease, also known as juvenile diabetes. In all, five genes have so far been located.

“We have probably found most of the major genes that cause juvenile diabetes,” Field told Maclean’s, “although one or two more might be found.” Field’s work is part of intensifying scientific research into juvenile diabetes, a disease that affects about 100,000 Canadians. To live, such diabetics require daily injections of insulin, a hormone that the

body needs to derive energy from food. (Juvenile diabetes differs from the more common Type 2 diabetes, in which the pancreas usually produces insulin, but, for some unknown reason, the body cannot use it effectively.) Type 1 usually strikes children under age 20, putting them at risk of serious long-term complications, including kidney failure, heart disease, blindness and nerve damage. Other groups of scientists, including ones in the United States, France and England, have also been hot on the trail of the genes that predispose people to juvenile diabetes. About onethird of those with the predisposition develop the disease; medical researchers are looking for the factors that trigger it in those people

and not in the remaining two-thirds. Investigators elsewhere are looking for ways to prevent the disease from developing, while still others are searching for treatments to lessen the severity of the complications. “This is a very exciting time in diabetes research,” says Kenneth Färber, executive director of the Juvenile Diabetes Foundation International, a New York City-based charitable organization that funds research around the world. “There is a lot of very good work going on.”

Much of the leading-edge research is being conducted in Canada. In fact, ever since a Toronto team led by Dr. Frederick Banting discovered insulin in 1921, Canadian scientists have been at the forefront of research into the causes of diabetes and the hunt for its prevention, treatment and cure. Today, the government—through the Ottawa-based Medical Research Council of Canada—and such nonprofit organizations as the Canadian Diabetes Association grant nearly $10 million annually to diabetes research. They fund, among other things, exploration into the role that viruses may play in triggering the onset of diabetes, and research into how and why kidney failure develops in about 25 per cent of diabetics within 15 years of the onset of the disease.

In addition, the Juvenile Diabetes Foundation International allocates more than $2 million of its $25-million annual global budget to work in Canada. Färber says that in addition to that amount, the organization agreed to provide $1.4 million annually for the next five years to the University of Alberta in Edmonton to fund further research into transplants. In 1990, doctors there were the first to transplant insulin-producing cells into a vein leading to a woman’s liver, which enabled her to stop taking her daily insulin injections.

Färber also says that Field’s discoveries, by helping to identify those at risk of developing diabetes, dovetail with other research into prevention of the disease. In one wideranging clinical trial, hospitals throughout Canada are testing the effectiveness of the drug nicotinamide in preventing Type 1 diabetes in relatives of diabetics. In another large multi-centre trial in the United States, researchers are trying to determine whether taking very low doses of insulin before clinical onset of diabetes can prevent an individual from developing a full-blown case of the

disease. Field adds that it should eventually be possible to develop a simple blood test to identify those with the predisposition to diabetes. “There could be a general screening of all newborns,” she says. Field’s findings, which were published in the British medical journal Nature Genetics, also have implications for genetics research in general. Scientists have already located the single gene that causes cystic fibrosis, for instance, as well as the one that leads to Huntington’s disease. But most of the 4,000 diseases with a known hereditary tendency, such as heart disease and some types of cancer, are caused by several genes acting in combination—and finding them has proven a far more difficult task. But by simultaneously finding two

genes implicated in diabetes—the first of the major diseases to yield such information— Field has shown that it is possible. Instead of screening all the body’s estimated 50,000 genes, Field and her team screened 250 families with two or more diabetic children for so-called marker genes—distinctive inherited patterns of genetic components. A marker that is consistently inherited along with the disease shows the approximate region where the gene linked to the disease will be found. Locating the genes that cause diabetes and other diseases is the vital first step towards the eventual goal: finding cures.

BARBARA WICKENS