On The Transplant Horizon: More Animal-human Grafts

Science & medicine

September 15, 1991|By Richard A. Knox Boston Globe

MINNEAPOLIS — Driven by concern over the growing shortage of human organs for transplantation, scientists are reviving the ancient dream of melding animals from different species - including humans - into real-life chimeras.

The mythical chimera was a bizarre beast combining a lion's body, goat's head and serpent's tail. The 1991 versions, described here recently at the First International Congress on Xenotransplantation, mix such disparate parts as a pig's heart in a baboon's body and a hamster's liver transplanted into a rat, with growing success.

And there are new human-animal chimeras, too, for the first time since 1984, when doctors at California's Loma Linda University transplanted a baboon heart into a 12-day-old infant known as Baby Fae, who died 20 days later.

The latest human xenografts, as they are known from the Greek root xeno, or ''foreign,'' are five Swedish diabetics who have received transplants of insulin-producing cells derived from up to 50 fetal pigs. The patients had received kidney transplants earlier, so they were already taking drugs to suppress their immune systems.

Two of the Swedish xenografts were performed too recently to evaluate, but the first three patients showed evidence of pig insulin in their urine for several months, indicating that the transplanted cells did survive, mature and start producing insulin. In no case so far has the xenograft rendered the patient free of the need to have insulin injections, but immunologists called the results promising.

More such human experiments with insulin-producing cells from animal pancreases, called islet cells, ''are around the corner, I'm sure,'' predicted transplant pioneer John Najarian, chief of surgery at the University of Minnesota. Researchers are devising a variety of strategies to protect the animal cells from being rejected, such as an approach one called ''islets in a baggie,'' in which the foreign cells are encased in a semipermeable membrane that allows insulin to seep out but keeps immune cells and antibodies at bay.

''There's almost no possibility that allograft (same-species) islets will be useful in man over the long haul from a numbers standpoint,'' explained Anthony Monaco of New England Deaconess Hospital, whose team is developing one such approach. ''There just aren't enough human pancreases around.''

Mindful of the Baby Fae experiment, which was widely criticized as premature, researchers say that further attempts to transplant solid organs such as livers, hearts and kidneys from animals to humans are more remote.

But many think recent interspecies transplants among animals suggest that animal-human organ grafts will eventually be possible - even from such genetically distant species as the pig. (There is apparent consensus among researchers that primates like chimps and baboons are too scarce or present too many ethical issues to consider them as organ donors for humans, although they will be indispensable in preclinical research.)

The first barrier to a successful xenograft is hyperacute rejection. All animals, including humans, carry in their blood an arsenal of antibodies primed to attack foreign tissue. When an organ from a disparate species is transplanted, these preformed antibodies attack it so vigorously that the xenograft quickly turns into a blackened, stony, massively clotted glob.

However, Guy Alexandre of Brussels and colleagues have averted hyperacute rejection in baboons that received pig kidneys by using a common method called plasmaphoresis to cleanse the baboons' blood of antibodies before the transplant.

If immediate rejection can be prevented the recipient of a xenograft can tolerate a foreign organ for at least some months.

One thing is obvious: After years of scientific obscurity and even scorn, xenotransplantation has suddenly become the cutting edge in immunology. Drug companies are pouring money into xenograft research, and government is interested. Senior scientists are reorienting their laboratories and junior researchers are staking their careers on xenotransplantation. ''The important point,'' observed Terry Strom of the Beth Israel Hospital in Boston, ''is there is a community large enough and interested enough to move this field forward. There are terrific leaders and plenty of worker bees.''

''Three years ago at a New York transplant meeting, people were laughing if you were doing xenografting,'' said Jean-Francois Borel, a Swiss immunologist who, by discovering the immune-suppressing drug cyclosporine-A in the 1970s, sparked the last transplant revolution. ''Now we have the First International Congress on Xenotransplantation, and it's astonishing how many people are here.''

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