UC Davis Magazine

One Medicine

Continued from previous page. Feldman

"It takes some luck to be studying a disease process that affects humans and animals and to find researchers working in the same area," said Ed Feldman, an authority on veterinary endocrinology. "You have to have a lot of dominoes line up just so."

Nearly a decade ago Feldman spent a year's sabbatic leave at the University of Miami with a team of medical researchers studying diabetes mellitus in dogs, a disease characterized by inadequate production of insulin to balance blood sugar levels. The researchers were transplanting the insulin-producing "islet cells" from the pancreas into the liver. It had been found that, even when displaced from the pancreas, the islet cells could continue to produce insulin.

As a result of that research project, Feldman was contacted a year later by medical researcher Patrick Soon-Shiong from Southern California, who had developed a technique for encapsulating islet cells from the pancreas in a semi-permeable membrane. The membrane allowed sugar from the blood to pass through, enabling the cells to meter the body's sugar level and adjust insulin production accordingly.

The holes in the membrane were so small that antibodies could not enter and destroy the transplanted cells. But most importantly, the semi-permeable membrane eliminated the need for patients to receive immuno-suppressive drugs, usually given to prevent rejection of the transplant.

Soon-Shiong proposed that Feldman create a colony of 20 to 30 diabetic dogs by removing their pancreases. The researchers would then test the efficacy of the membrane technology by transplanting encapsulated islet cells into the diabetic dogs.

Feldman was not enthusiastic about the proposal; maintaining a colony of diabetic dogs would be expensive and labor-intensive. Furthermore, he found little satisfaction in inducing diabetes in healthy dogs, when he spent many clinical hours treating canine patients with naturally occurring
diabetes.

He turned down the medical researchers' proposal and their money, suggesting instead that the transplants be performed on diabetic dogs that were patients at the UC Davis veterinary hospital.

At first Soon-Shiong and colleagues balked at the idea, but a week later they called back, interested in pursuing Feldman's suggestion. In 1990, with the cooperation of 20 clients and their dogs in the Davis area, the project began.

The procedure was fairly straightforward. A half-inch incision was made in each dog's abdomen. The encapsulated islet cells, suspended in a liquid, were poured through a tube inserted through the incision. The slightly sticky islet cells would then adhere to the tissue on the inside of the abdomen. There they would be near the dog's blood supply and able to "read" the animal's blood-sugar level and produce the necessary insulin.

Feldman and colleagues determined the project would be a success if the transplanted dogs showed some improvement for four to six weeks. They were delighted to find the dogs required no insulin for three to four months and a few of the dogs actually continued to be normal for nine months.

"It was kind of like a miracle," said Feldman. "We thought the transplanted islet cells would die relatively soon, but we found that the cells continued to function in the dogs' abdomens for a couple of years."

As a result of the study, federal approval was soon given to try the procedure in humans.

"The problem with the procedure in humans is that the transplanted islet cells were taken from cadavers, and there just aren't enough dead people of the right age, right health and the right religion to be organ donors," said Feldman wryly.

Instead, researchers transplanted pig islet cells into humans. For years, pig pancre-ases were the source of all insulin produced for treating diabetes in people. Today, insulin is produced using recombinant DNA technologies.

"But cross-species transplants, known as xenografts, take a whole new level of federal approval," said Feldman. At first his physician collaborators proposed performing experimental pig-to-dog islet cell transplants. Instead, they decided to take the research to New Zealand, where less stringent regulations permitted studies with human subjects. Those studies were carried out so successfully that Feldman anticipates the procedures will gain federal approval in the United States within just a few years.

Theoretically, islet cell transplantation may one day replace daily insulin shots for most diabetics, Feldman said. Patients would simply go to the doctor's office every three to six months for an injection of islet cells into the abdomen.

"This was a great learning experience not only for me but also for other veterinary faculty members and students," said Feldman of the research project. "To have it turn out the way it did is pretty remarkable. There is potential for this work to touch thousands of peoples' lives and really give them hope."

Pedersen with kittens Such successful collaboration between the human and veterinary medical communities should not be surprising, says Niels Pedersen, director of the Center for Companion Animal Health at UC Davis. A veteran researcher in the UC Davis School of Veterinary Medicine, Pedersen developed the first vaccine for leukemia in cats, identified the AIDS-like feline immunodeficiency virus in cats and is active in AIDS-related research. His studies have taken him across the veterinary/human medicine boundary so many times that he no longer recognizes it as such.

"The concept most of us have is that there is only one medicine," said Pedersen. "After all, the mouse has all of the same genes as the human and as the cat. That's why we don't look at a line dividing veterinary and human medicine."

For that reason, Pedersen encourages in young veterinary researchers not only a love for animals but a love for biology.

"If they are lovers of biology, they will take advantage of the smorgasbord of research opportunities out there," he said.

While there can be pitfalls to collaborative work, ranging from egos to money issues to transportation and communication problems, experience has taught Pedersen that such partnerships generally yield both lifelong colleagues and friends.

"You have to go into these collaborations thinking that you'll give as much as you can," he said. "As with Christmas gifts, you usually receive much more than you give."

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