University Of Wisconsin Getting Money To Study Cross-Species Transplants

Drug Research On Baboons, Pigs Could Lead To Putting Animal Organs In People

By Marilynn Marchione

of the Journal Sentinel staff

University of Wisconsin-Madison officials have reached an agreement with a drug company to do cross-species research aimed at enabling animal-to-human organ transplants someday.

The UW System Board of Regents was to vote today on the agreement with a subsidiary of Switzerland-based Novartis AG. The subsidiary will pay for research on drugs to prevent rejection of pig kidneys that will be transplanted into baboons. A committee of the regents approved the contract Thursday.

University officials stressed that none of the work will involve transplanting animal organs, or grafts, as they are called medically, into people. Putting one species' tissue into another species is known as xenotransplantation.

"No human xenografts are even considered as part of this research," said Hans Sollinger, who heads UW's transplant program.

Novartis long has been a leader in transplant research. One of its predecessor companies developed the breakthrough anti-rejection drug cyclosporine, and one of its subsidiaries, Imutran of Cambridge, England, has been breeding pigs engineered to carry genes that inhibit rapid rejection of foreign organs.

Imutran will pay UW up to $1.3 million for the first year of research, Sollinger said.

"It's a large grant. It's wonderful," he said.

Imutran is close to reaching agreement with several other U.S. transplant centers on similar grants, the company said.

"These experiments are very difficult to do, so we are pooling our data," Sollinger said.

The work at UW will start in about six months and is expected to involve 10 baboons that will get different doses of a combination of immune-suppressing drugs, including some experimental drugs not yet on the market, Novartis spokesman Geoffrey Cook said.

"Basically, they're testing what's the best combination of immune-suppressing agents to protect the transgenic organ after transplant," he said.

Baboons were chosen because they're the most similar animal to humans for transplants, and research with pig organs is furthest along because of the genetic alterations that have been achieved in that species, Cook said. The longest that a primate has survived with a pig kidney has been 70 days, he said.

Pig kidneys are "technically the simplest" xenotransplant to perform, Sollinger said.

"Our challenge is not a surgical technique but immunological suppression" to keep the organ from being rejected, he said.

The work should have potential human applications because "any time you cross a species," extreme rejection risk must be overcome, Sollinger said.

"It is really not that different if you transplant a pig kidney into a monkey or a dog or a sheep," he said.

UW has been a pioneer of transplantation both in general and in research with animals. In 1996, the UW Medical School used two pig livers to keep a 17-year-old girl alive for two days until a human liver could be found. At the time, only about 20 such operations had been attempted in the nation.

But transplants of animal organs to humans have been put on hold by federal officials until more is known about safety and potential risks. The main fear is that xenotransplantation could spread animal diseases to humans, a medical phenomenon known as zoonosis. The most well-known zoonosis of our times is AIDS, which scientists say came from chimpanzees.

There appears to be some basis for the worry. A 35-year-old HIV patient who received a baboon liver in 1992 and died two months later of liver disease recently was discovered to have acquired a baboon version of cytomegalovirus, or CMV, from the transplant.

A number of medical centers nationwide are proceeding with experiments putting tissues or cells from animals into humans, such as using pig cells to treat Parkinson's disease.

In Wisconsin, Infigen Inc., a private biotechnology company that is a unit of ABS Global Inc. of DeForest, has been working on technology that it hopes will aid transplants of animal organs to humans.

The company creates transgenic pigs by modifying pig cells' DNA to increase their compatibility with humans.

Appeared in the Milwaukee Journal Sentinel on March 10, 2000.

Copyright © Copyright 2000 Milwaukee Journal Sentinel.