Dialogue: More research vital before pig cells put into humans

The risks of transplanting live animal cells into people include the possibility of introducing new strains of viruses into mankind, particularly retroviruses, writes BOB BOYD*.

There must be greater public debate before there is any New Zealand-based research that involves transplanting living animal cells into humans.

There are a number of unanswered questions around the ethics of arranging to conduct this type of research overseas when the same or a similar research application has been declined here.

The issue has come to a head with publicity about an appeal against a declined application for researchers to implant live pig pancreas cells into humans and an announcement that the same company, Diatranz Ltd, was arranging to conduct clinical research using the same cells in the Cook Islands.

It is time more voices were added to the debate about risks the public could face from a treatment designed for an individual.

This form of research is different from any other research because the benefit, if any, is potentially for a small number of individuals, but the risk is borne by the entire community.

It is ironic that the research proposals from Diatranz up to now have been to carry out clinical trials of the treatment of Type I diabetes, which usually presents first in young people as a lack of insulin production.

Now the company has altered the protocol to treat Type II diabetes, which presents at an older age and is often associated with resistance to the insulin already circulating in the body. Presumably this is because Type II is predominant in the Cook Islands and trial subjects would be easier to recruit.

World authorities do not share the Diatranz view, echoed by some diabetics and parents of diabetics, that the risk of spreading infection from this procedure is "a fantasy". Unfortunately, the risks include the possibility of introducing new strains of viruses into humans, particularly retroviruses.

At this stage we don't know how many, or which, infectious agents are potentially transmissible by xenotransplantation, nor can we rule out the introduction of new human diseases from agents such as retroviruses which cause infection in animals. The best-known example of a retrovirus is HIV/Aids.

This concern was the reason the Health Ministry asked Dr Bob Elliott, of Diatranz, to halt the clinical trial in the mid-1990s after a small number of young people with diabetes had received living pig pancreas cells.

Dr Elliott has apparently stuck to the approved protocol, checking on the subjects after the trial and has reported to the ministry that he has been unable to find any evidence of virus infection arising from pigs.

While the risks might be considered small, they are considered real by most experts around the world. Since the risk of the pig retrovirus was recognised, there have been bans on this form of research in many countries, which are only now starting to be lifted.

In the few countries where clinical trials of xenotransplantation are proceeding, there are rigorous guidelines on who should be included in the trial, the way patients and their close family and contacts are monitored, their progress recorded, and the amount of information which should be supplied about the trial.

The types of constraints placed on participants include: not having children, or being of childbearing age; notifying health authorities of any sexual partners they have; always practising safe sex; permitting health authorities to closely monitor their families and any sexual contacts they may have for the rest of their lives; and not giving blood or donating any organs or tissue.

These severe restrictions are considered necessary to limit the harm to individuals and establish systems to try to limit the spread of any new disease transmitted by xenotransplantation.

These restrictions would be negotiated as part of the ethical consent for the research and would be managed by the researchers.

The US Food and Drug Administration, one of the few regulatory agencies permitting xenotransplantation trials in a limited set of closely monitored patients, has undertaken extensive public consultation and has just announced that it should have consulted the public more, and will do so before trials are extended.

A letter to Diatranz from the Director-General of Health last year stated that, in addition to the lack of adequate definition of the risk of retrovirus infection, there was a series of deficiencies in the application and more information was needed.

This included: the efficacy of the islet cell transplants in the pre-clinical (mice and rabbit) studies; details of the manufacturing process and validation of the process; the information to be provided to the trial subjects and their families and contacts; and why the proposed study departs from the internationally published guidelines in areas such as who should be included in the trial, screening tests of animal handlers, medical contacts, patients and their families.

The advice to the Director-General from the Health Research Council was that in addition to ensuring the safety of the procedure it would be inappropriate for her to approve a clinical trial of xenotransplantation until the appropriate infrastructure was in place (for continuing regulatory oversight) and public consultation on the potential risks and benefits of xenotransplantation had taken place.

Unfortunately, medical science does not have a good track record of being able to predict risks.

The spread of BSE disease from cows to humans was considered no more than a minuscule risk during the "mad-cow" crisis in Britain. There is good reason to be cautious and to ensure that there is general public acceptance of the risks.

There needs to be substantially more informed debate than there has been, and it should involve wider views than those who stand to benefit if the research leads to future benefits for diabetics.

The proposed amendment to the Medicines Act before Parliament does not call for a ban on innovations in treatment, but puts an onus on the Minister of Health that she must be satisfied that these issues have been adequately addressed before the go-ahead is given.

* Dr Bob Boyd is safety and regulation chief adviser at the Ministry of Health.

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