Artificial Pancreas Is Implanted in Diabetic : Medicine: Experiment is first in U.S. If successful, procedure may eliminate the need for insulin shots.


Physicians at St. Vincent Medical Center announced Thursday that they have begun the first U.S. human trials of an artificial pancreas that they hope will someday free diabetics from the need for insulin injections.

The artificial pancreas was implanted last week in the abdomen of 38-year-old Steven Craig of Lake Isabella, who has been diabetic for more than 30 years and has been unable to work for seven years because of complications of the disease. It is the first of 20 such implants the hospital is planning during the next two years.

Dr. Patrick Soon-Shiong of St. Vincent and USC implanted insulin-secreting islet cells from cadavers. The cells were encapsulated in a porous membrane that keeps them safe from attack by Craig’s immune system.


Soon-Shiong hopes that the implanted cells will permit Craig to forgo his daily insulin shots and prevent progression of his symptoms but noted that it will be months before doctors can assess the implant’s value. “This is the very first step on a long, exciting but unexplored road,” he said.

If the device is shown to be safe and effective, the researchers hope to use pigs as islet donors, which would theoretically provide enough cells to treat all 1.4 million insulin-dependent diabetics in the United States.

“This is really exciting,” said biochemist Joan Harmon of the National Institute of Diabetes and Digestive Disease. “We’ve been waiting for this for years.”

But officials of the American Diabetes Assn. cautioned diabetics not to get high hopes about the procedure. “It’s nice and it’s exciting, but that doesn’t mean it is going to work,” said physiologist Richard Kahn, the group’s chief scientific and medical officer. “Come back in six months. If the patient still (does not need insulin injections) . . . then we have something.”

Insulin-dependent or Type 1 diabetes occurs when the body’s immune system destroys islet cells in the pancreas. Insulin is normally released by the pancreas when the level of sugars in the bloodstream rises after eating. The insulin enables body cells to use the sugars for energy.

If the body does not receive insulin, it must use stored carbohydrates for energy. The buildup of toxic byproducts from that process eventually leads to coma and death.

Diabetes is treated with insulin obtained from cows or pigs or with human insulin produced by the biotechnology industry. But because insulin is injected periodically, the levels of blood sugar go through wide variations. Many researchers believe that these concentration swings cause the long-term complications of diabetes, including kidney malfunction, nerve damage in the limbs and blindness.

Pancreas transplants have been relatively successful in treating diabetes, and transplants of isolated islets have shown recent promise. But there are not sufficient donors to treat even a small fraction of diabetics, and recipients have to receive immunosuppressive drugs for the rest of their lives to prevent rejection of the grafts.

Researchers have speculated for at least 25 years that such immune attacks could be foiled by enclosing the islets in a porous membrane that would let in nutrients that nourish the cells and permit insulin to be released into the body. At the same time, the membrane would shield the implanted islet cells from attacks by the immune system. Such an approach would permit the use of islets from unrelated donors--or from animals--without the need for immunosuppression.

But the idea, conceptually simple, has proved immensely difficult in practice. Plastic implants in dogs and other large animals have quickly become overgrown with the recipient’s cells, cutting off the supply of nutrients and killing the implanted cells within two to four weeks.

The procedure has been attempted in humans at least three times--twice in Italy and once in France. None of the three patients were freed from their insulin dependence, said Dr. David Sharp of Washington University in St. Louis, and the implanted cells died when the capsules became clogged.

Soon-Shiong developed a membrane material based on alginic acid, a polymer isolated from seaweed that is used as a thickener in ice cream. A similar membrane was used in the Italian experiments, but Soon-Shiong said that he discovered an impurity in those preparations that caused the membrane to be clogged.

Membranes prepared without the impurity cured diabetes in dogs and survived for at least two years without becoming clogged, he said. A report of those results will appear next month in the Proceedings of the National Academy of Sciences.

For his first patient, Soon-Shiong chose Craig, a former mechanic and sheriff’s aide in Riverside County and Costa Mesa who developed diabetes at age 8. Craig’s kidneys failed in 1988 and one was replaced by a donated organ from his brother eight months later.

Craig has been unemployed for seven years because of nerve damage in his legs and failing eyesight. Doctors do not know if the procedure will alleviate any of those symptoms.

In the 30-minute transplant, performed May 6, Soon-Shiong and his colleagues cut a small slit in Craig’s abdomen and poured in eight ounces of encapsulated islets--about 680,000--that had been isolated from cadavers. The capsules become attached to a flap of tissue, called the omentum, just below the skin.

Two days later, Craig ate his first breakfast in 30 years without an accompanying insulin injection. “The experience was terrific,” he said at a news conference.

Although the implanted cells are producing insulin, Craig’s physicians are still giving him small quantities of insulin, about 20% of his requirement before the surgery, so that the cells are not overly stressed. Soon-Shiong said he hopes to wean Craig from insulin over the next three weeks.

Soon-Shiong has permission from the U.S. Food and Drug Administration to perform 19 more implants. He hopes to do the next one in July, and about one per month thereafter.

All recipients will be St. Vincent diabetic patients who have had a kidney transplant and are receiving immunosuppressive drugs--assuring in the first phase of the trial that the capsules will not be rejected. If the first phase is successful, he said, he will try the procedure in patients who are not receiving immunosuppressive drugs.

New Procedure to Fight Diabetes

Type 1, or juvenile, diabetes is the most severe form of the the disease, affecting more than a million Americans. Those diabetics are treated with insulin injections, but there are side effects, and effectiveness varies. Now surgeons at St. Vincent Medical Center have implanted encapsulated human islets in a Lake Isabella man, the first human trials of this approach in the United States.

HOW A NORMAL PANCREAS FUNCTION * Tiny cell clusters, called islets of Langerhans secret insulin, which enables the body to use and store sugars in the blood. The body typically has about 1 million islets, making up only 2% of the mass of the pancreas. The other 98% secrete digestive enzymes. * Islets comprise four types of cells. The most common type, beta cells, secrete insulin. The others secrete hormones that regulate insulin use. * Diabetes results when the body attacks and destroys beta cells. Without insulin, the body can no longer properly use and store sugars from food.

HOW THE NEW GRAFT WORKS * Islets are separated from the pancreas and encapsulated in a porous membrane that allows nutrients in and insulin and wastes out, while shielding the cells from attack by the immune system. * About 680,000 encapsulated islets--about eight ounces worth, the equivalent of half a pancreas--are infused into the abdominal cavity through a small slit. The procedure takes about 30 minutes. Physicians hope the islets will survive indefinitely. * Because the islets are encapsulated, the patient should not require immunosuppressive drugs.