LONDON - The U.K. government has published guidelines that open the way for the first clinical trials of animal to human organ transplants.

Following a consultation exercise last year, Minister of Health Frank Dobson reported details of a regulatory framework, including procedures for submitting applications for clinical trials, which signals the go-ahead for development of xenotransplantation in the U.K.

Applications are to be scrutinized by the U.K. Xenotransplantation Interim Regulatory Authority (XIRA), which will advise government ministers on a case-by-case basis.

Dobson said, “Trials in xenotransplantation will only be allowed to take place if and when we are fully satisfied that the risks associated with such procedures are acceptable, taking account of all the available evidence at the time.“

Imutran Ltd., of Cambridge, U.K., which has bred transgenic pigs that it claims overcome the problem of hyperacute rejection, welcomed the announcement as an important step forward in the development of the technology.

“The company is pleased that there are now formal guidelines in the U.K. to help ensure the safe and appropriate introduction of xenotransplantation into clinical practice,“ Imutran officials said.

Corine Saville, Imutran's chief operating officer, said the company's first application will be to link a patient up to a transgenic pig liver outside the body to perform liver function while a human donor is sought. The next stage will involve transplants of solid organs, probably hearts or kidneys.

“The company will only submit an application to proceed to clinical trials when we are confident that the scientific and safety issues have been addressed,“ Saville said, adding the company, a subsidiary of Novartis AG, of Basel, Switzerland, is awaiting results of a study of approximately 160 patients who received living pig tissue such as skin, islet cells or spleen or liver perfusion over the past 10 to 15 years.

These patients are being examined to establish whether there has been transmission of any retrovirus from pig tissue to human cells, and if so, whether there is evidence of any harm. Results of the study are expected in late 1998.

Guidelines Target Animals, Spread Of Infection

The Department of Health guidelines covered other measures to regulate the development of xenotransplants, including the following:

* Ensure all hospitals comply with the procedures for applying to carry out trials of xenotransplantation.

* Give XIRA an explicit duty to consider the welfare of animals when scrutinizing clinical trial applications.

* Create a national code of practice governing the welfare of xenotransplantation source animals and hygiene regulations to control their breeding environment.

* Monitor patients who receive animal tissue according to national surveillance procedures being prepared by XIRA.

* Authorize evaluation by the government's Advisory Committee on Dangerous Pathogens of xenotransplantation therapy's infection risks.

* Limit the types of animals bred as xenotransplant donors, banning use of chimpanzees, gorillas and orangutans. (The government said, “We also take the view that there should be a strong presumption against the use of any other primates as sources for xenotransplantation.“)

Dobson commented, “Xenotransplantation is a subject which raises many different views from many different interests. There are patients and patient groups who are looking to xenotransplantation - and other developments - to provide therapies they need. There are members of the scientific and medical communities and of the general public concerned about the risk to public health from infections transmitted from animals. And there are also concerns about the implications for animal welfare.

“A clear finding from the consultation exercise was that the regulation of xenotransplantation should have statutory backing,“ he noted. “This has the support of those who are concerned about possible risks of infection and of the [companies], which want a clear regulatory structure to enable them to take their work forward in a responsible manner.“

XIRA is not a statutory body, but Dobson said by appointing it to oversee the development of xenotransplantation, the government was ready to legislate “to prevent undesirable activities, if that becomes necessary.“ *