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.
