Center puts animal organs to human test

by Melanie Evans

It is an alluring prospect for surgeons: an ample supply of organs to end the loss of 3,000 patients who die each year while waiting for potential organs.
The possibility of harvesting pig hearts and livers — similar in size and far more available than their human counterparts — moved one step closer to reality in 1996 after the Food and Drug Administration issued preliminary guidelines for regulating the new technology.
A new center located on the St. Paul campus will land scientists from three colleges at the University in the middle of the national effort to move forward the new technology called xenotransplantation — the transfer of animal organs or cells to humans.
Announced last week, the Center for Excellence in XenoDiagnostics — composed of a service office and research laboratory — will begin tests for viruses and bacteria in animal tissue by fall.
If successful, the new center would be uniquely positioned as the only facility of its kind in the United States prepared to meet the growing demands from federal agencies, the medical industry and the scientific community for a testing site in the high-risk, potentially high-profit area of animal-to-human transplantation.
Despite the pressing medical need and support from business investors, the medical community and federal government remain hesitant to fully endorse the new process.

Safety first
Fear of unleashing new diseases, indigenous in animals but foreign to humans, has spurred calls from the United States and European governments and scientists to halt the process despite the potential benefits.
Retroviruses identified in pigs this summer, which demonstrated the capability to live in human cells, alarmed scientists and health officials worldwide. Retroviruses, like HIV, the virus that causes AIDS, readily mutate to adapt to new hosts.
The fear that these viruses may flare up in humans with fatal consequences resulted in a mix of international legislation, ranging from cautious support and demands for a stop on all such testing.
The Food and Drug Administration reacted by suspending all clinical trials in the United States in late 1997, though the organization continues to approve trials using animal transplants on a case-by-case basis.
The center will test for at least 20 different identified infectious agents, said Tom Molitor, clinical and population sciences professor who specializes in infectious diseases and immunology in swine.
The University has the technology, expertise and track record of putting together these high-profile molecular diagnostic tests, said Vivek Kapur, assistant professor of veterinary pathobiology and director of the advanced genetic analysis center.
“We seized the opportunity and decided to go ahead and form the center,” he said.
The concern surrounding infectious agents essentially halted industry and medical efforts to move ahead, said Dr. Larry Schook, the xenotransplantation center’s director and professor of veterinary pathology.
The center will work with federal agencies, universities, and businesses as they continue to develop policies for the new process, he said. Combined interest from the medical community, industry and the federal government has prevented a full-stoppage of research in the emerging area.
But not all physicians feel the same way. A London-based international group of doctors and lawyers announced their opposition to xenotransplantation March 20, citing concerns that animal implants could carry unknown and untreatable diseases.
Safety concerns prompted the United Kingdom to suspend animal-to-human tissue transplant trials in 1997. Sweden and Germany adopted a voluntary moratorium as well, according to Medical Industry Today journal.

Dire shortage
According to the United Network for Organ Sharing, about 55,000 people nationwide are registered on a waiting list for a transplant, and 10 people per day died in 1996 waiting for an organ transplant.
The dire shortage of organs prompted several federal initiatives to meet the needs of individuals waiting for transplants. In 1997, the Clinton administration launched an initiative to increase organ donors’ participation by 20 percent in a two-year time span.
On Thursday, Secretary of Health and Human Services Donna Shalala announced new federal guidelines for the National Organ Transplant Network, a private-sector system created in 1984 by federal legislation.
The secretary called on the group to develop new non-geographic-based criteria for distribution. Effective 90 days after Shalala’s announcement, the rule will dramatically change the method by which the scarce organs are distributed.
Outside of changing distribution policies and public relations campaigns to increase donor-awareness, patients’ hope lies in the progress of science.
Clinical trials for patients with diabetes, liver failure, Parkinson’s disease, and bone marrow transplants, have all begun using xenotransplantation, according to the FDA.

Technology Boost
In recent years, the variety of animal tissue types that can be transplanted to humans has mushroomed as researchers identified more compatible tissue and supporting technology continued to develop, Molitor said.
Breakthroughs like Dolly, the Scottish sheep cloned from an adult cell in 1996, could further scientists’ ability to understand and manipulate the way in which cells develop, eventually allowing researchers to genetically alter animal organs or grow human organs.
Scientists have known about agents that have the potential to cross-over from animal to human for a while, but the actual transplantation process is new, Molitor said.
Introducing animal organs to the already risky procedure of transplant surgery raises the stakes. The body’s immune system rejects foreign human tissue. Heavy doses of drugs are required to suppress this natural reaction.
An animal organ only makes the process more complex. A host of unknowns awaits doctors who must not only navigate the fragile surgery, but also be prepared for the possibility of unknown or latent viruses, docile in their natural host but deadly when introduced to humans.
Molitor said the team expects to have the first two tests within the next six months. The center will include services for all stages of xenotransplantation, from the identification of possible viruses to post-surgery follow-up of patients.

Big business
The team is capitalizing on the University’s resources with encouragement from local animal producers and medical device companies from the East and West coasts, Kapur said.
“Its a very hot issue right now,” he said.
University researchers met in Chicago at the end of March with industry giant Nextran, a division of Baxter Healthcare Corporation, which specializes in organ transplant technologies.
“They said ‘yesterday’ is when they wanted these tests,” Kapur said.
The center’s rapid development has forced the researchers to scramble for space to dedicate to laboratories. Space has been identified for the service facility, but the research and development will be spread out across the campus.
The Academic Health Center agreed to commit resources to support the project; however, the team is still working on outside sources of funding, Schook said.
A world-class research center attracts big business, and generates start-up companies and jobs, said James Woodman, executive director of MNBIO, a biotechnology trade association.
Minnesota’s legacy in medical innovation and medical devices, such as the pacemaker, secured its place as an attractive prospect for business investment. According to Medical Alley, a health care business trade association, Minnesota ranks 5th in the nation for the number of people employed in medical device manufacturing.
Understanding the genetic basis for disease could indirectly assist all the states’ animal producers as well, Woodman said.
“Minnesota life sciences companies are excited about the center; it further illustrates the University of Minnesota’s commitment to world class research,” he said.