Firm Sees Trials of
Pig Organ Transplants Soon
By Kathy Fieweger
CHICAGO (Reuters) - It's a scenario recurring thousands of times each year: Patients lie critically ill, waiting for a kidney, heart or liver. Minutes, days, weeks tick by but no organ arrives in time to thwart death.
There are simply not enough organs for everyone.
Two companies are hoping to solve this unending problem and one, Baxter International Inc., appears ready to take the next step.
The firm's Nextran subsidiary, located in Princeton, New Jersey, concluded trials in late 1999 in which specially engineered pig livers were used as filters outside the body to perform human liver functions, Baxter spokeswoman Deborah Spak told Reuters.
``The results were very encouraging,'' she said. ``There were several patients who bridged.'' That is, they stayed alive on the pig liver apparatus until a human organ was available.
Spak said this so-called ``ex vivo'' trial involved a handful of patients, but the researchers have enough data to publish results in a major scientific journal within a few months.
Next Step Is 'In Vivo' Trials
The next step after that is to ask the U.S. Food and Drug Administration for permission to perform ``in vivo'' trials -- where the organ is actually transplanted inside the body. Spak said she anticipates this submission in the next 18 months.
Baxter chief executive Harry Kraemer said in a recent interview he is pleased with Nextran's progress. Whether it is first in its quest to transplant an organ is not critical, Kraemer said, but just that it be one of the leaders.
Nextran's long-term goal is not to have its genetically engineered pig organs supplant human transplants, which will always be preferred. Instead, it hopes to provide a viable alternative when no human organ is available -- a sad and all-too-common event for those on transplant lists.
``The whole reason that we're doing this stuff that may seem so crazy to people is that there are just not enough organs to go around and the number of people who are waiting and dying is absolutely staggering,'' said Dr. Marlon Levy, a transplant surgeon at Baylor University Medical Center in Dallas.
Levy performed the two ``ex vivo'' liver trials that have taken place at Baylor and said both patients -- who were literally on death's doorstep -- are doing quite well. ``This is, on our part, an act of desperation to try to solve the crisis in organ availability,'' he said.
Critical Shortage
According to data from the United Network for Organ Sharing, there is a critical shortage.
As of January 2000, more than 67,000 patients in the United States were on its waiting list for organs: nearly 44,000 for kidneys; another 4,000 for hearts; 3,600 for lungs.
Thousands of people die waiting. Another 100,000 never even qualify to get on the list in the first place.
Baxter sees this need as a logical fit with its own leading position in kidney dialysis. In the mid 1990s, the company began to study xenotransplantation -- or transplant of organs between species -- as a possible alternative.
``If we're successful, the way we look at it is: What would medicine be like if there were an unlimited supply of organs available? That's clearly our goal,'' said Nextran chief executive Marvin Miller in an interview. ``If we reach it or not, that remains to be seen. We hope we will.''
According to Miller, there would be 125,000 organ transplants yearly in the United States if everyone who could benefit actually got one. In 1998 only 21,000 people were lucky enough -- most of them were kidney recipients. Furthermore, Baxter says, the demand for transplants increases 15 percent each year while the supply of organs is static.
Pig Kidney, Heart Transplants Foreseen
Research into using animals for transplant purposes is not new but started as far back as the late 1960s. In the early 1990s, worldwide attention focused on two patients in Pittsburgh, Pennsylvania, who received baboon livers but eventually died. Use of pig tissue heart valves is common today, but unlike organs, the pig cells are killed first.
Dr. Goran Klintmalm, another Baylor transplant surgeon, said critical new information was learned in each attempt of animal-to-human transplantation. Only now are specially engineered animals being studied, a whole new realm.
Unlike the ``ex vivo'' trials, Nextran's trials of fully transplanted organs will involve hearts and kidneys, he said. That is because if the transgenic kidneys or hearts do not work, doctors can turn to other alternatives like kidney dialysis or a heart device called a left-ventricular assist device to keep patients alive. For livers, there is simply no alternative.
Also, the liver acts like a biochemical factory performing numerous complex functions that may be hard to replicate. But doctors said what has been learned about rejection in livers can readily be applied to other organ systems.
Biggest Challenges Involve Immune System
While some people question the ethics of breeding animals for this type of use, the chief obstacles are immunological in nature, according to John Logan, vice president of research and development and Nextran.
First is preventing what Logan said is called hyperacute rejection -- the process by which foreign tissue is turned into a pulpy mess almost immediately by a human's immune system.
Nextran is engineering pig organs to express a human gene that prevents this rapid rejection. Even with the transgenic organs, however, patients still need to take special immunosuppressive drugs every day for the rest of their lives.
Researchers are also very concerned with a certain virus contained by most if not all pigs -- the porcine endogenous retroviruses (PERV). They pose no threat to pigs and at least so far, seem not to infect humans who have undergone pig tissue transplants. But concerns linger.
``The results so far cause us to be cautiously optimistic,'' Levy said. ``Two or three years ago, everybody was ready to bring these trials to a screeching halt because of the concern that PERV viruses could infect human cells in a tissue culture. Now, just a short two years later, we've got data on my two patients that show no PERV infectability in serial sampling over time.''
In addition, Levy pointed to a recent study conducted by Imutran, the unit of Swiss pharmaceutical giant Novartis AG, and the only other major company studying xenotransplatation of whole organs. Imutran studied 160 people who had some form of pig tissue transplant and found no evidence of PERV infection.
To Dr. Klintmalm, tremendous progress has been made to date with the transgenic animals. ``Just the fact that we've tried is progress,'' he said. ``We have much, much more to do than we've done, but we've started.''


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