Weighing risks of pig transplants

By Kitta MacPherson and Edward R. Silverman
STAFF WRITER

It could be a science fiction fantasy, replete with a Light and Dark Side.

Scientists find a way to implant animal organs in humans, forever doing away with the problem of persistent donor shortages.

A band of Cassandras warns, however, that such transplants risk the creation of a super infectious agent, aping the way the AIDS virus was created.

This is no futuristic fairy tale. A small, but growing band of scientists, industrialists and entrepreneurs, many based in New Jersey, are pioneering the field of animal-to-human organ surgery known as “xenotransplantation.” And they’re quickly closing in on the human experiments that will, once and for all, prove what this technology can do. They will be inserting pig parts in people.

At the same time, in a quiet, behind-the-scenes battle being mediated by the Food and Drug Administration, these xeno-scientists are combating fears held even by some of their own colleagues that, in trying to save thousands of individuals who would otherwise certainly die, they will be endangering many more, perhaps all of society. The fear is that, by transplanting a foreign species into a human, scientists could transmit a virus that could bloom and spread among people.

Minimizing the risk, therefore, is essential. So as early as May, the FDA is expected to release long-awaited guidelines that will shape the field — and affect the lives of millions of people around the globe — for years to come.

“The science is very exciting,” conceded Jay Fishman, a practicing physician and research scientist who heads up the transplantation department at Massachusetts General Hospital in Boston and counts himself as one of the “worriers” in the debate. “It’s at the point where researchers have reached their Holy Grail. But since many of these are corporate entities who are not necessarily driven by service to mankind, we have to be very circumspect about the role they are playing in ethical decisions.”

Organs in demand

Certainly, there’s a need for more organs. As of March 4, there were 54,403 patients waiting for a transplant in the U.S., according to the United Network for Organ Sharing, a non-profit group that oversees the national organ exchange network. And two years ago, 3,916 people died waiting for a transplant. With the numbers expected to grow, the promise offered by xenotransplantation takes on a greater sense of urgency.

True to any new scientific endeavor, this controversial field includes a wide variety of players, from some of the biggest health care companies running laboratories with the most expensive research equipment in the world to hard-bitten entrepreneurs operating out of briefcases as they juggle the intricate demands of reconciling cutting-edge science, public policy and profits.

Among them is Novartis AG, the huge Swiss pharmaceuticals manufacturer that has U.S. offices in East Hanover and Summit. A leader in xenotransplantation research, Novartis also dominates the $1 billion global market for cyclosporine, a so-called immunosuppressant drug used to combat organ rejection. With interests in both research and post-operative treatments, Novartis stands to reap huge profits if the technology eventually boosts the number of transplantations performed each year.

“Right now, the market is only limited by the number of organs available for transplantation,” said Sergio Traversa, a securities analyst with Mehta Partners, an investment firm that specializes in health care, who calculates the market for the drugs is growing by 10 percent annually. “Xenotransplantation is going to be a big change. But without it, the market for immunosuppressant drugs is pretty limited.”

 

A medical harvest

At the other extreme is Ari Marshall, an aviation consultant originally from Turkey who several years ago struck a deal to commercialize xenotransplantation technology being developed in Bulgaria. Working out of a Woodbridge condominium a stone’s throw from the town’s sprawling shopping mall, he works a telephone, fax and computer in a furious attempt to interest scientific leaders and pharmaceutical executives in his rural Bulgarian pig farm and the experimental operations he has scheduled for next month.

“Nobody else is doing this,” says Marshall, as he holds aloft test tubes containing freeze-dried arteries and veins taken from his specially bred Bulgarian pigs. “There are no live cells. It’s virus-free. We freeze-dry the tissue and apply a solution before the operation. We want to do this with a person soon and invite Western experts to watch. It was already being done under the Communist regime, but there were no records.”

Even with the wider debate, there is controversy over technique. And While few experts say they have heard of Marshall or his company, Cryobiogenics Corp., his approach to extracting pig parts for later use in humans prompts, by turns, doubt, amazement and curiosity. His efforts also take on an air of mystery, however, because his company’s work is being conducted in Eastern Europe, out of the purview of the FDA and the widely accepted standards governing clinical research.

More typical is Nextran Inc. The fledgling biotech company, based in Princeton, is owned by Baxter Corp., one of the largest suppliers of medical devices and blood products. Like Cryobiogenics, Nextran breeds special pigs, but its farm is in Ohio. Nextran has achieved a high degree of visibility through its research into making pig organs palatable to the human body.

 

In the hands of the FDA

Sooner, not later, each of these companies and the nearly dozen others pioneering this field will have to answer to the FDA. The agency recently asked the firms to halt their clinical trials, the necessary round of medical studies conducted before a drug or device can be approved.

Nonetheless, research is proceeding at a rapid pace and regulators expect to devise guidelines spelling out safety procedures and monitoring efforts without inhibiting the experiments under way. The biggest fear among some scientists is that a so-called porcine endogenous retrovirus — a virus that is normally found in pigs — could be passed along to humans and prove fatal.

The argument against xenotransplantation goes like this: each individual whose life may be saved with a pig organ could, nonetheless, jeopardize untold numbers of other people if a previously unknown virus is created then transferred among the population. That is how AIDS and the fearsome Ebola virus spread.

With AIDS, scientists believe that a monkey passed the virus to a human, probably through a bite, transferring what had principally been a latent virus to a new medium. No one knows what the host organism for Ebola is, it could possibly pass to humans through insects or rodents like other hemorrhagic fevers, but it causes death in most humans infected with the deadly pathogen.

Science fiction has explored these ideas for decades. Organ transplantation and transferring genetic material between animals and humans has appeared in H.G. Wells’ “The Island of Dr. Moreau” and more recently, in Robin Cook’s current medical thriller “Chromosome 6.” Now, though, the possibility that a virus hiding deep inside an anonymous pig will contaminate the human race has put even experts on notice.

“Right now, there’s a big yellow sign up that says caution,” acknowledged Amy Patterson, the FDA’s deputy director of the division of cellular and gene therapies. “Infectious diseases don’t carry passports. But we have to balance this against the recognition that this technology can save lives.”

 

Success with an old idea

Researchers began experimenting with organ transplantation in the 18th century. Over the years, a veritable zookeeper’s roster of animals — sheep, goats, rabbits, pigs, cows, chimpanzees — were experimented on in China, Russia and other corners of the world.

Transferring human organs into other humans, a fantastically complex business, was attempted successfully by the mid-20th century. And now, transplants of kidneys, livers, hearts, pancreases and lungs are considered an integral part of medical treatment.

In the last 20 years, key breakthroughs occurred, such as the development of drugs that suppress the human immune system and, therefore, thwart organ rejection. This allowed for a larger number of organ transplants and a longer survival rate for transplant recipients. Most notable was Jean Borel’s discovery of cyclosporine, culled from a soil fungus in the mid-1970s. The drug was approved for commercial use in 1983.

Until now, the best-known case of xenotransplantation may have been Baby Fae, an infant born with a heart defect that within a month would kill her. In 1984, physicians operated on the 2-week-old baby, replacing her heart with one from a young baboon. Three weeks later, Baby Fae died. Her immune system had done what it was designed to do, successfully waging war on the foreign organ.

Now, though, researchers believe they have a much clearer idea as to why the human body fiercely rejects organs from other animals. And they’ve figured out various ways to circumvent that destructive process. The future, as they see it, is in pigpens.

Pigs are easy to raise, they mature quickly, produce large litters, and have organs that are comparable in size to humans. And since they’re widely raised for food, using their organs for xenotransplantation would likely raise fewer ethical concerns among most Americans, as opposed to using organs from non-human primates, such as chimpanzees and baboons.

“Biologically, pigs are perfect,” said Marvin Miller, Nextran’s chief executive. “And we believe we can justify using them on an ethical basis, too.”

But even if xenotransplantation can save lives, it’s not clear whether the procedure will save money. Nextran, for instance, says the cost of one of its pig organs will eventually carry the same price tag as an organ donated by a human — between $12,000 and $18,000. As is typical in the widening debate over the technology, even discussion of its economic benefits produces little agreement.

“At this point, it’s hard to say if anything could be saved,&qot; said Roger Evans, an economist at the Mayo Clinic’s health services evaluation division. “We don’t freeze the cost of dying by doing a transplant. If we become more effective in our ability to save lives, we increase health care costs, because those people will live longer and eventually die of something else. We’re not at the point where technology has developed to be able to make any claims. It’s going to cause a whole social dilemma.”