Xenotransplantation - How Bad Science and Big Business Put the World at Risk from Viral Pandemics

ISIS Sustainable Science Audit #2

Xenotransplantation:

How Bad Science and Big Business Put the World at Risk

from Viral Pandemics

by Mae-Wan Ho and Joe Cummins

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Summary

Xenotransplantation - the transplant of animal organs into human beings - is a multi-billion dollar business venture built on the

anticipated sale of patented techniques and organs, as well as drugs to overcome organ-rejection (1). It has received strong criticism

and opposition from scientists warning of the risks of new viruses crossing from animal organs to human subjects and from there to

infect the population at large. But regulators are adopting a permissive attitude for clinical trials to go ahead. Scientific reports of virus

crossing from pig to human cells (2) and of viral infections in humans subjects transplanted with baboon livers (3) are being ignored or

dismissed, while inconclusive, widely faulted papers are taken as evidence that no viruses are found in xenotransplant patients (4).

This audit exposes the shoddy science that puts the world at risk of viral pandemics for the sake of corporate profit, and concludes

that xenotranplantation should not be allowed to continue in any form. Instead, effort should be devoted to developing safer, more

sustainable and affordable alternatives that are already showing promise and will be more likely to benefit society as a whole in the

industrialized west as well as in the Third World.

Key words: transgenic pigs, hyperacute rejection, xenozoonosis, endogenous retroviruses, xenotropism, viral infections,

recombinant viruses, PERV, pig HEV, baboon endogenous virus, simian foamy virus.

A multi-billion dollar business venture

Xenotransplantation - the transplant of organs or tissues between species - has become a major issue within the past ten years.

Biotech companies are developing genetically engineered 'humanized' pigs to meet the demand for spare body parts in the

industrialized world. A multi-billion dollar market is anticipated from the sale of patented techniques and organs, as well as existing

and new drugs to overcome organ-rejection (1). Still at the experimental phase, it has received strong criticism and opposition from

mainstream scientists warning of the risks of new viruses crossing from animal donor organs to human subjects, and from there to

infect the population at large. But these warnings have done little to dampen the enthusiasm for continued research well into clinical

trials.

The world-leader in xenotransplant research is the UK biotech company Imutran based in Cambridge, now a subsidiary of Novartis.

Novartis already own the rights to Cyclosporine A, the main anti-rejection drug given to transplant patients to suppress the immune

system. Since acquiring Imutran, Novartis have pledged $1 billion for research in xenotransplantation, and thereby to dominate a

projected $11billion a year market for organs and associated immune-suppressive drugs.

An estimated 10 000 pigs and nearly five hundred primates have been in the UK, with very little accomplished. Xenotransplantation is

in crisis. At the bottom of the crisis lies some shoddy science that puts the world at risk of viral pandemics for the sake of profit. At

least one company, PPL, which produced Dolly the cloned sheep, is reported to be winding up xenotransplantation research, on the

possibility that pig virus could infect humans (5).

'Humanized' transgenic pigs as organ donors

Transgenic pigs, rather than our close relatives primates, were considered as organ donors because there are greater ethical

objections to using primates, many of which are endangered protected species (6). As pigs are already farmed for food, it was

thought that there would be less ethical concern, and that pigs could also be more easily controlled for viral infections and consistent

quality. Nevertheless, large numbers of primates are exploited and made to suffer as experimental transplant recipients; and primate to

human transplant clinical trials have been authorized in the United States.

The first hurdle in transplanting organs between distant species, as in the case of pig to human, is hyperacute rejection (HAR) of the

donor organ by the host. This reaction is swift and severe, and depends on naturally occurring, pre-existing antibodies. Naturally

occurring human anti-pig antibodies predominantly recognize the carbohydrate antigen galactose-alpha-(1,3)-galactose attached to

cell-surface proteins. Both IgM and IgG (different classes of immunoglobulins or antibodies) in the human blood contain antibodies

that bind this antigen; which may comprise up to 1% of the IgG. The enzyme for making the galactose-alpha-(1,3)-galactose exists in

all mammals except humans, old world monkeys and the great apes. The binding of these antibodies to the antigens triggers a cascade

of reactions - complement activation - that results in destruction of the donor organ and cells within minutes. Induced antibodies

against the foreign graft,