Oriented to Thoracic Transplant Recipients -- September 2000

SICKEST TO GET TRANSPLANTS FIRST

Some question wisdom of making urgency, not location, priority

By John Tuohy - USA TODAY, 8/29/00

After years of polarizing debate, the nation's organ-transplant system is being revamped to give the sickest patients first crack at donated livers and kidneys.

The new policy aims to end a controversial system that resulted in gravely ill patients getting passed over for livers because they weren't on the right waiting list at the right time.

Proponents of the plan claim it will save lives of hundreds of the sickest patients every year by making medical urgency, rather than location, the priority. Opponents, including many doctors, say it will discourage donations, waste organs on people whose bodies are too far gone to accept them and put small hospitals out of the transplant business.

`'One of the biggest complaints we've had from people on waiting lists is that these boundaries and separate lists prevent organs from going to people who need them most,'' says Jon Nelson of the Department of Health and Human Services, which oversees the organ transplant program and writes the rules. ''That just doesn't seem fair to many people.''

Here's how the new system, which applies mainly to livers, will work:

When a donated liver becomes available, it will be offered to the sickest people in an area of at least 9 million people before `'less urgent'' patients get a chance at it. That replaces the current scheme, in which everyone in a (usually) much smaller area is offered the liver first. And with liver recipients, the term urgent is no overstatement. The sickest patients, Status 1, have less than a week to live.

There are still many critics of the new plan, including the non-profit organization that has run the transplant program since its inception in 1986, the United Network for Organ Sharing.

Though UNOS fought against the changes, it must abide by them if it hopes to renew its contract for a fourth time when it expires in November.

`'We still believe they (the changes) are not appropriate, but we realize this is a contract, and we will be in compliance with all the provisions,'' says Mark Rosenker of UNOS. `'There is really no more debate left, just nuance. We'll do what we have to do.''

UNOS has competition for the contract this time around from a new non-profit company that could capitalize on any residual acrimony between UNOS and the government. The Center for Support of the Transplant Community claims it can do the job better and save more lives. The organization has ties to the University of Pittsburgh Medical Center, a frequent critic of the way UNOS has run the transplant program.

The new rules went into effect March 16. They won't be fully applied until after the new contract is awarded Nov. 1, but UNOS has already started to make some of the changes.

Resistance to the new policy persists, however. There is a bill pending in the House of Representatives that would strike down the rules, although that seems unlikely to succeed, because the Senate favors them. Several states have passed local laws to try to supersede the new rules and at least one state, Wisconsin, is suing the federal government to block them.

Shifting priorities

About 14 people die each day waiting for transplants of the liver, kidney, heart, lungs or pancreas because the demand for them far outpaces donations. Last year, when 21,692 transplants were done, 6,012 of the 60,000 people awaiting organs died. This year, the waiting lists have already grown 15%, to 71,105.

With organs being so scarce, an allocation policy of `'sickest first'' might seem most logical. But for reasons both practical and political, the transplant program has never been run that way.

Instead, it has been a system of local control, with limited sharing of organs between geographic areas. UNOS officials contend that this system gets the maximum benefit from each organ: Livers can only stay healthy for 12 hours once they are removed, so the range during which they can be transported is limited. People are more willing to donate organs if they know the organ is going to someone in the community. Giving livers to people with the best chance of living afterward is the most responsible way to allocate. `'Given the limited supply of organs, there is an ethical obligation to make the best use of them, put them where they do the most good,'' says Walter Graham, UNOS executive director. `'On the one hand, how do you make the best use of the limited resource? But on the other, how can you say no to someone who is at death's door?''

There are 63 local organ banks, called Organ Procurement Organizations, that keep waiting lists. But because the populations the OPO serve varies widely - from 1.1 million in southwest Florida to 12 million in New York City - the length of the waiting lists also varies.

For example, in September 1999, the number of people waiting for a liver in the two OPOs that serve Arizona was 116, while in the two OPOs that serve Illinois there were 1,250.

The possible result: a Status 1 patient, days away from death in Peoria, could have less chance of receiving an organ than someone with a life expectancy of years in Tempe.

When studies began to illustrate the disparity in the early 1990s, polls showed that the public favored changes in the system. After years of hearings, HHS completed its new policy guidelines in 1998, which it called the Final Rule. Congressmen who opposed it voted to delay implementation two years.

Local opposition

One powerful argument for maintaining the local allocation process, advocates say, is that it encourages donors. People like to know that their organs will stay in the community and possibly go to help a neighbor after they die.

Even though donors give their consent by filling out their donor cards, organ bank officials always like to get consent from family members at the hospital before taking organs.

`'It just makes it a lot easier for them if they can say to the family that some goodwill come from the death because the organ will go to save a person at the hospital down the street or in the next town,'' says Joel Newman of UNOS.

Allan Brownstein of the National Liver Foundation says he doesn't agree organs should stay local, but says he understands that point of view. ''These places work very hard at organ donations and think, why should they go elsewhere?'' he says.

That's the thinking behind laws in more than a half-dozen states that ban organs from crossing state lines. In Wisconsin, Gov. Tommy Thompson went a step further: He sued the government to prevent the law from being enforced.

`'We feel that (HHS) is exceeding its constitutional powers by passing this law,'' says the governor's spokesman Tony Jewell. `'Wisconsin's donor rate is double the national rate, so we feel like we are getting penalized for doing a good job if our organs go elsewhere.''

Other people oppose giving organs to the sickest people because they often reject them and need another transplant, which wastes the organ. A study by the Institute of Medicine found that the sickest patients reject organs 11% of the time, compared with rejection rates of 2% to 5% for less sick patients.

But the government says the moral thing to do is to give organs to the sickest patients. Especially when it is impossible to predict who will reject a liver and who won't.

Robert Gibbons, a University of Illinois at Chicago researcher, who was part of the IOM study, is a strong advocate of the sickest-first policy. He and his colleagues did a follow-up study that found that 298 less severely ill patients were transplanted over more critically ill patients in 1998. At the same time, the number of the most critically ill patients nationwide increased by 731.

"'I call for broader sharing. I know they can do better,'' he says.

But Graham says any system will have shortcomings, and he repeats a well-worn truism in the transplant community: `'Until we have enough organs,'' he says, `'no system is fair.''

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Historic Transplant: 1 Donor, 4 Recipients

By Larry Tye ­ Globe Staff

Talk about split-second timing. A hundred doctors, nurses, and other staff members at Brigham and Woman's Hospital last week managed to quickly track down four patients anxiously awaiting new organs, to harvest and fly back to Boston a heart, two lungs, and a kidney from a donor who had just died, and to simultaneously stage four implant operations within the four-hour window during which the excised organs remain viable.

The quadruple-recipient donation, the first of its kind in New England and maybe in the world, yielded precisely the results that doctors and hospital administrators hoped for: All four recipients were doing "great" last night. And while that sort of symphony of surgical movement is a novelty now, doctors say it worked so well that it will soon be standard operating procedure.

"It's the first grand slam transplant," Dr. David Sugarbaker, Brighams chief of thoracic surgery, said at a press conference yesterday announcing the results. "I think this is the future. The idea is to maximize the organ donations."

Maureen Perry of Tauton, whose husband received a new heart, was even more effusive, "It's amazing that the donor's family rose above their pain to reach out and help somebody else... They've given something very precious to these people," she said, adding that as soon as her husband recovers he plans to take her dancing and go fishing with his grandchildren.

Despite decades of efforts to enroll people, organ donations still are rare enough that there is a list of several hundred would- be recipients at Brigham alone, with thousands more across the region hoping for hearts, livers, and other organs. The result is that every time a donor emerges, physicians labor to make maximum use of available body parts.

The first quadruple transplant was performed at the Mayo Clinic in 1996, but in that case all four organs went to a single recipient. The Brigham operations involved considerably less stress to any one patient but more to the hospital as a whole, requiring it to assemble four separate operative teams on a moment's notice, at a time of the year when medical professionals and recipients tend to be on vacation.

The first call that a donor had surfaced came Thursday at about 10 p.m. That setoff a chain of carefully scripted events, starting with Brigham staff members activating beepers for the four patients at the top of their respective recipient lists. Other beepers were set off and phones rung for the 100 or so surgeons, anesthesiologists, OR nurses, admitting officials and all the rest of the personnel who handle heart, lung, and kidney transplants. Luckily all were easily summoned to the hospital.

Even as the four transplant teams and their patients were assembling at Brigham, another medical unit was heading to the facility where the donor had died. Brigham officials would not identify the other hospital, but they did say it took a jet to get the harvest team there and back in time.

The organs were removed from the donor shortly after 7 Friday morning. Two hours later they were back in Boston and the four operations were underway. "They all came out at the same time and went back in at the same time," said Sugarbaker. "The plane had to fly into Logan. Thank God there were no delays."

Brigham has a tradition of being on the cutting edge when it comes to organ transplant. In 1954 it performed the world's first successful human organ transplant, involving the exchange of a kidney between identical twins. In 1984 it conducted the first heart transplant in New England. And in 1990 it was the first Bay State hospital to perform a lung transplant; later that year it was one of the first in the nation to complete a double lung transplant. Brigham showed in 1995 and again in 1998 that it could do three simultaneous transplants, involving two lungs and a heart. Doing four at once "was the same experience," said Dr. Scott Swenson, head of Brigham's lung transplant program. "It's like a general going into battle. Everyone knows their job, they know who's called for, for what, and when. And we're in a groove right now because this is our ninth transplant since July 1."

Swanson said both his lung patients were doing "extremely well" last night. Doctors treating the heart and kidney patients were equally upbeat.

And it was not just the four Brigham patients who benefited from the unidentified donor. Doctors also were able to harvest and use, or save for future use, another kidney, along with a liver, skin, corneas, and bone and cartilage.

"At least a dozen patients could benefit altogether," said Sugarbaker.

Contributed by Tx Mary Robinson, Boston

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An Advanced Study of the Insect Repellant Qualities of Cyclosporine

By Don S. Marshall A.C.(Almost Certifiable), UpBeat Medical Center

Background: As the initial drug of choice in organ transplantation, cyclosporine continues to be in common use by transplant recipients. There have been side effects, mainly negative, such as a propensity of the patient to develop various types of cancer due to lowered immunity. However, one side effect of positive ilk was noted early on by transplant recipients; that was the apparent ability of the compound to repel insects from the body of the person into which the material was systemically induced. This property has been confirmed not only with other users, such as those taking the product for severe arthritis, but also in comparison with non-users standing in the same field so to speak.

It has also been learned that those patients who have had their cyclosporine dosage reduced at the on-set of cancer, often no longer are availed of the insect protection they formerly had. [One day we will also study why the cyclosporine dosage is so often reduced after the on-set of cancer, yet still continues to provide anti-rejection protection. Ergo, why not reduce it before the on-set SOP?]

We set out to learn whether it was a combination of being systemic in the human body that set up the repellant situation, or perhaps would the mere presence of the "raw" chemical itself produce the same "go away" result.

Method: The UpBeat Medical Center was fortunate to have on its staff a patient who fit the required criterion for our study perfectly. This patient had been on a level of cyclosporine for approximately 9 years, when the onset of laryngeal cancer indicated the dosage should be cut by 50%. One of the effects immediately noted by the patient, who's abode is about 2 feet above mean high water in the Virginia swamps, was that he was no longer immune to mosquito bites. After a good deal of persuasion that he should donate his surface skin to the scientific cause the study began.

Initially to determine whether all repellant effect had indeed dissipated our subject was sent into the swamp (Actually where he lives merely cracking the front door would have been good enough!) and asked to stand quietly for 5 minutes. [See Illus. 1] There were two problems that developed right away: 1. Our technician, the patient's principal caregiver and wife, refused to leave the house to observe. 2. The patient was nearly removed from the site by hoards of mosquitoes about his body. He fled in seeming fear after only two minutes, which we clocked from our car.

For the second and final exposure, in an effort to determine potential toxicity of the chemical alone, we pinpricked a recently expired gel-cap of Sandimmune and daubed just a bit on a tissue. We then wiped this tissue gently on two approximately 2 x 2-inch areas on the patient's right forearm.

Results: The patient withstood the swarm for approximately 1 minute and 50 seconds. Our technician, nee wife, nee caregiver, dashed from the house with all deliberate speed and hastily documented the feat. Then as a technician she said, "Sir, may I respectfully request that I be allowed to withdraw from this project?" As a wife and caregiver she screamed, "Your really are an idiot! I'm being eaten alive! I'm going in the house and wipe the blood off! Later the camera was retrieved and it was found she did indeed get the required picture. By actual count of the patient, because no one else would even approach him, he had 4 immediate "perches" on the left arm, 2 on the back of neck, and zero, as in none, on his right arm!

Conclusion: Cyclosporine does indeed have insect repellent properties. If taken in large enough quantities internally this function will become apparent. The patient's caregivers and nurses early on in transplantation noted that this level of dosage also produced a rather pungent body odor in the patient that was eventually traced to the olive oil carrier. If however, the patient's dose falls below a level in PPM yet to be determined, all insect effect is lost. In that instance the only potential retrieval of the benefit would be to either sneak more cyclo. on the sly, or take some of those old bottles of the stuff you still have lying around and dab it on like perfume in critical areas.

Further Result: The technician/wife is now under observation for West Nile virus and from her hospital bed keeps mumbling," My God, let's hope there aren't any others out there as stupid as he is, who might actually try it!"

Illustration 1 ­ Patient shows scientific tech- nique in swamp. It was found if the IQ of the patient is low enough, very little training is required.

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PVCS

To those of us who sought eye care after reading last month's UpBeat, we offer our apologies. It is indeed a mystery how most of the copy got italicized. Somewhere in this great cyber age a an actual human must have punched the wrong button and we launched a newsletter that by the time I had finished caused me to seek help in getting my eyeballs untwisted. Later I did find that a couple of glasses of medicinal lite wine assisted the vision quite a bit.

We are duty bound to note the passing of heart recipient Cal Stoll of Minneapolis. The former head football coach at the University of Minnesota turned his energies in full to transplant recipients and organ donation after his heart transplant 13 years ago. His motivational off the cuff talks were fascinating. Cal completed his "pay back" in full with extra credit.

Dear Don,

Thought perhaps you might be interested in this for "Upbeat" since we always enjoy publication and felt your readers would find the program enlightening.

NTAF is Subject of PBS Documentary
Kirby Foundation Underwrites Program

National Transplant Assistance Fund (NTAF) has been selected as a documentary subject for the PBS television series called, "The Visionaries." Check local listings for dates and times or see the web pages of NTAF (www.transplantfund.org) and The Visionaries (www.visionaries.org).

A $100,000 grant was awarded by F.M. Kirby Foundation to finance production of the program that focuses on the mission and the people of the National Transplant Assistance Fund. This television series, currently being seen throughout the country, features non-profit organizations doing extraordinary work.

Recognizing NTAF's outstanding fundraising efforts on behalf of transplant patients throughout the United States, the 30-minute program will examine the transplant process and the financial challenges faced by the recipients.

The program will highlight a patient's initial contact with National Transplant Assistance Fund, show how the organization helps identify uninsured expenses of transplant and establishes a network of friends and family willing to help with fundraising to cover the transplant-related expenses.

Dr. Jack Kolff, a cardio-thoracic surgeon, and NTAF director, Patricia Kolff, were selected by the producers as "visionaries." The couple envisioned a way to help patients to achieve transplant who otherwise could not afford the procedure and created the organization to carry out this vision.

NTAF, located in Bryn Mawr, Pa., was established in 1983 for just such a purpose and over the past 17 years has helped raise over $16 million through grass-roots fund-raising campaigns.

Submitted by: Sidney Constien - National Transplant Assistance

Our local Rescue Squad puts up weekly notices regarding health and safety ­ mostly. This week's is, "A balanced diet is a chocolate cookie in each hand."

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Exercise Aids Transplant Patients

By Ira Dreyfuss - Associated Press Writer

WASHINGTON (AP 8/27/00) - Exercise is good for your organs, even if the organs originally were someone else's.

"It's beneficial for a lot of reasons - to play basketball, or go back to work, or just live your life," said NBA All-Star forward Sean Elliott, who has a kidney transplanted from his brother, Noel.

Elliott had developed a progressive disease, focal segmental glomerular sclerosis, which reduces the kidneys' ability to filter the body's waste products. "I started retaining a ton of water," he said. "I lost my appetite. I became fatigued and started lying in bed a lot."

On Aug. 16, 1999, Elliott had the transplant that let him start rebuilding his career and his life. "A month out of surgery, I felt great - but extremely out of shape for me. It took me seven months to make it back to playing the game of basketball."

Elliott is the first professional athlete to return to a sport after receiving an organ transplant. But his return to exercise after a transplant is not unusual. Doctors commonly recommend physical activity for patients with transplants.

A study in The New England Journal of Medicine in January 1999 found that heart transplant patients who did aerobic training gained greater endurance after six months, compared with patients who did not take part in the exercise program. Researchers at the University of California at Los Angeles concluded "exercise training increases the capacity for physical work."

Other studies have found similar benefits for patients with other transplants. For instance, an Austrian study published in 1998 in the American College of Chest Physicians' journal, Chest, found that stationary bike training improved the performance of lung transplant recipients.

Transplantees these days are not only encouraged to exercise, they are encouraged to compete. They even have their own version of the Olympics, the World Transplant Games, open to people with a functioning organ transplant.

Leading up to the world games, which will be held in 2001, were this year's U.S. games, organized by the National Kidney Foundation. They were held in June at Disney's Wide World of Sports Complex in Orlando, Fla., with Elliott as the official leading celebrity.

Nonetheless, transplantees have special needs in exercise. Chief among them is a greater need to stay hydrated. The requirement is partly a response to the drugs the patients take to suppress their immune systems, so their own bodies don't reject the donated organs, said Dr. Sharon Hunt, a heart transplant cardiologist at Stanford University. "They all have a mild compromise in kidney function," she said.

"I drink about a gallon of water a day, at least," Elliott said.

Heart transplant patients may never reach the exercise ability of similar people who have their own hearts, although the difference might not be noticeable except to an elite athlete, Hunt said. "They can't quite run the same marathon, but I'm guessing 80 percent," she said.

Transplanted hearts don't function quite the same to exercise, Hunt said. They don't immediately respond to stress by beating faster, because nerve connections needed to do this are not there, she said. Instead, the heart responds initially by contracting harder to pump blood, and starts to beat faster after a few minutes in response to higher levels of the hormone adrenaline, she said.

Other transplantees should have no such limitations on their performance, said Dr. Lew Teperman, director of transplantation at New York University. But the patients may have lingering problems from the disease that forced them to get the transplant, he said. For instance, former diabetics with a transplanted pancreas may have compromised hearts or blood vessels from the diabetes, he said.

However, people should not see transplant patients as any less able than people with all their original organs, said Corinne Carson, a 29-year-old Washington woman who received a liver transplant in 1994. In the season after the operation, Carson played basketball at Marymount University in suburban Virginia.

Carson tried out for the Women's National Basketball Association in 1997. But she didn't make the WNBA cut, and she suspects officials' perception of her health was a reason why. "I had a couple of coaches tell me that if I get on someone's team, you are going to raise insurance prices," she said. "They don't understand I have no restrictions."

Nonetheless, Carson is thinking about trying out again. "I can outplay the majority of girls out there, but I don't want my transplant held against me," she said. "I just want a fair tryout. If I make it, I make it. If I don't, I don't."

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And again the news from the barnyard ­ It's somewhat confusing this month. Apparently we now have "good" pigs and "bad" pigs. Only one thing is for sure, if they're cloned the Pope wants nothing to do with either! Ed.

Cloning Pioneers End Pig Research

LONDON (AP 8/13/00) - The creators of Dolly the Sheep are halting their research into genetically modifying pigs for human organ transplants, one of the scientists said Sunday.

The decision is motivated in part by fears that transplanting animal organs into people could unleash deadly new viruses among the human population.

California-based Geron Bio-Med, which owns exclusive rights to biotechnology developed by Edinburgh's Roslin Institute - where Dolly was created - has decided to cut funding for the work, said Ian Wilmut, leader of the team that created Dolly, the first clone made from an adult animal.

"I think the concern is mainly unknown viruses. That's the frightening thing," said Wilmut. "It's possible there could be viruses we don't know about that could be released into the human population."

Roslin scientists have been working for two years on experiments aimed at creating genetically altered pigs whose organs and cells could be successfully transplanted in humans - a process known as xenotransplantation.

In March, the Scottish company PPL Therapeutics successfully produced five cloned piglets.

Pigs are physiologically one of the closest animals to humans, and so of particular interest to scientists looking to fill a shortage of transplant organs.Other researchers continue to pursue work on genetically modified, or transgenic, pigs.

Biotech Firm Breeds Swine For Organ Transplants

By Laura Johannes - Staff Reporter of The Wall Street Journal

Scientists at a Boston biotechnology company say they have bred a line of miniature pigs that don't transmit potentially harmful viruses to human cells, advancing the prospects of using animal organs for human transplantation.

If confirmed by other scientists, the discovery - slated to be presented today by BioTransplant Inc. at a conference in Rome - would allay much of the concern about infection in xenotransplantation, or transplants across species. If other issues can be overcome, researchers have little doubt there will be a market for the miniature pigs' organs, including livers, kidneys and hearts. About 6,000 Americans died last year while waiting for human organs.

BioTransplant's work is likely to gain significant attention because its main reseacher, Clive Patience, is a member of a British academic team whose discovery in 1997 that pig viruses can infect human cells sounded a world-wide alarm. Dr. Patience, whom BioTransplant hired last year, said he had expected to disprove the company's preliminary findings that its pigs don't transmit viruses to humans. "I said I'd eat my hat if this turned out to be true," says Dr. Patience. He adds, "My colleagues are selecting the hat."

The transfer of animal organs into humans has been tried unsuccessfully for centuries - stymied mainly by the human body's stunningly efficient mechanism for eradicating invaders. The BioTransplant finding doesn't address that hurdle, but other barriers to cross-species transplants are falling. Last month, the journal Nature announced that pigs had become the fourth mammal to be cloned. The development, achieved by Britain's PPL Therapeutics PLC, raises the possibility of the creation of an unlimited supply of pigs with organs designed for use in humans.

In the past year, BioTransplant, collaborating with Novartis AG, has managed to keep pig hearts and kidneys functioning in baboons for as long as a month. And Baxter International Inc.'s Nextran unit has kept desperately ill patients alive for as long as 10 hours by filtering their blood through external pig livers - long enough to bridge the gap until a human organ arrived. Nextran says it could be ready to attempt a full-fledged pig-to-human transplant in as little as 18 months.

Attempts at full-organ xeno-transplanation yielded poor results in the early 1990s, and widespread caution about renewing the efforts remains. But Robert Michler, chief of transplantation at Ohio State University Medical Center, believes human trials ought to begin as soon as possible after half of the pig hearts transplanted into baboons last three months.

In the 1960s, researchers began transplanting human cadaver hearts into humans after such hearts had worked only 200 days in test animals. The first human heart recipient lived only 18 days. Today, half the humans who get heart transplants live 10 years, Dr. Michler says.

In 1992 and 1993, transplants of baboon livers into humans proved unsuccessful, either because the host rejected them or because the strong antirejection drugs killed the patients. Alarmingly, in at least one of the cases, a primate virus was transferred to a human recipient, who died of other causes. Amid an outcry that such transplants could unleash an AIDS-like epidemic, the Food and Drug Administration banned further primate-to-human transplants in 1996.

That left pigs. They are easy to breed. And given their widespread slaughter for meat, advocates figure few Americans would object to killing them for medical purposes. Pigs are physiologically close to humans, and their organs are of similar size.

Although infection from pigs is viewed as less likely than from baboons, pathogens known as porcine endogenous retroviruses, or PERVs, have raised concerns. As many as 50 different kinds of PERVs are present in each pig cell. They are harmless in pigs, but their effect in humans is unknown. In mice, similar viruses can cause leukemia.

PERVs aren't a problem in pig heart valves, which are routinely used in humans: The viruses are killed with chemicals used before transplant. And the FDA has approved the experimental transplant of carefully screened pig brain cells to humans with Parkinson's disease. The risk of infection in full-organ transplants, however, is higher, and use of the chemicals isn't possible because they would kill the organs.

In testing BioTransplant's swine, Dr. Patience mimicked the 1997 experiment that raised the initial alarm, taking cells from pigs and mixing them with human ones to see whether infection would occur. Unlike the earlier work, which used a type of full-size pigs, this time he found that in miniature swine, the viruses, while present, didn't infect the human cells. The smaller pigs have been specially bred by BioTransplant and Massachusetts General Hospital with an eye toward use in transplants. Although significantly in-bred, the pigs started out as a wild miniature breed.

BioTransplant says it doesn't know why the miniature pig cells didn't transmit the pathogens and is continuing research to find out. After generations of inbreeding, it could be that the pig viruses may have lost their power to infect.

Daniel R. Salomon, a scientist at the Scripps Research Institute, in La Jolla, Calif., and author of a report last month in Nature about the transmission of PERVs from pig pancreatic cells to mice, hailed BioTransplant's finding. But even if the research holds up to further testing, he cautions, the PERVs could mutate into a more infectious form after human transplant. And pigs may contain other, as yet unknown, pathogens, he says.

If scientists solve the PERV problem, they still must grapple with rejection by the human immune system, which generally turns foreign organs black and useless within hours. The red flag that alerts the human body to the invader's presence is a sugar called alpha galactosidase, the same one that sits on the outside of bacteria humans fight off daily.

Some companies, such as Alexion Pharmaceuticals Inc., of New Haven, Conn., are
developing stronger and smarter drugs to suppress the immune system. Britain's pig cloning PPL and other companies are working on making pigs that would lack the sugar. But this work could take as long as a year.

BioTransplant, in another gambit, is using full-size pigs genetically altered by Novartis to add a human protein that slows the defenses set off by the foreign sugar. It also is attaching pig thymuses to the transplanted organs - hoping that the gland, which functions to educate the immune system, will teach human host cells that the new organ is family.

These approaches have more than doubled the length of time BioTransplant can keep pig organs working in baboons, to 30 days compared with about 10 to 12 days a year ago, says Julia L. Greenstein, the company's chief scientific officer.

The next step is to breed miniature swine with the Novartis genetic modification. BioTransplant believes the pigs, which weigh about 250 pounds, or roughly a quarter the weight of a full-size pig, are also useful because they are closer to human dimensions.

Other companies plan to harvest organs from full-size pigs at the age of six to eight months old. What isn't known is "whether the organs will continue growing at a pig rate once they are transplanted into humans," says John Logan, Nexran's vice president of research, adding that preliminary evidence suggests they won't.

Even when corporate scientists say xenotransplantation is ready for human tests, critics will abound. Alix Fano founded an antixenotransplantation advocacy group called Campaign for Responsible Transplantation following Dr. Patience's 1997 work with pig viruses infecting human cells. She says she is skeptical of his latest work.

"It's amazing how scientists change their tune when biotechnology companies are paying their salary," she says.

Dr. Patience replies, "If anybody wants to look at the data, they are welcome."

Wall Street Journal ­ 8/28/00

Pope Offers Moral Medical Guides

By ELLEN KNICKMEYER - Associated Press Writer

ROME (AP 8/29/00) - Pope John Paul II sought Tuesday to lay down moral guidelines for medical research in the 21st century, endorsing organ donation and adult stem cell study but condemning human cloning and embryo experiments.

John Paul's address to an international conference of 5,000 transplant specialists appeared to be an attempt to set moral limits on such life-and-death issues as organ transplants and related research.

John Paul won applause from the transplant experts when he encouraged organ donation, calling it an "act of love."

But if his stance against embryo research were followed, "all these people with serious diseases would have no hope," said one supporter of the research, Dr. Robert Goldstein of the New York-based Juvenile Diabetes Foundation.

Underscoring how important he considered the issue, the 80-year-old pontiff left his summer retreat at Castel Gandolfo outside Rome to address the International Congress of the Transplantation Society.

But the address went beyond being a booster speech for organ donations.

John Paul spelled out the church's position on transplant-related matters, condemning the sale of organs, insisting on informed consent on both sides of the exchange and singling out the complete end of brain activity as an acceptable way to determine that death has occurred.

Calling organ donation "a genuine act of love," he said, "Accordingly, any procedure which tends to commercialize human organs or to consider them as items of exchange or trade must be considered morally unacceptable."

The decision on who should be first in line to receive organs can be based only on medical factors, John Paul said - not on age, sex, race, religion, social standing, usefulness to society or any other standard.

He left the door open for cross-species transplants.

The pope's support for organ donation was likely to have an impact on his 1 billion-strong flock of Roman Catholics. Traditionally, many Catholics have been adverse to both organ transplants and cremation for reasons having to do with keeping the body intact for resurrection.

John Paul also spoke out against cloning and related embryo research, a rapidly developing field in the four years since Dolly the lamb first struggled to its cloned hooves.

The pope renewed his opposition to both techniques just weeks after Britain moved toward allowing limited human cloning for research and the United States approved federal funding for research on human embryo stem cells.

The British and U.S. actions both grew out of scientific excitement about the promise of research on embryonic stem cells - parent cells that go on to form most types of cells and tissues.

Researchers hope the cells can some day be used to grow cells, tissues or whole organs - offering hope for scores of diseases from diabetes to Alzheimer's.

Experts say one of the most promising areas for the research is in Parkinson's - a neurological ailment of which the pope himself shows symptoms. The Vatican no longer denies he has it, although it has never confirmed it.

In the church's view, cloning is irreconcilable with its position that sex between married couples is the only acceptable way to create human life.

"Methods that fail to respect the dignity and value of the person must always be avoided," John Paul told the medical workers.

"I am thinking in particular of attempts at human cloning with a view to obtaining organs for transplants: These techniques, insofar as they involve the manipulation and destruction of human embryos, are not morally acceptable, even when their proposed goal is good in itself."

John Paul ruled out use of embryonic cells as well, pointing scientists in the direction of adult stem cells as the acceptable route for research.

Adult stem cells already have been the object of research for up to 25 years now, with minimal results, said Goldstein, speaking by telephone from New York.

In all this time, "there's no indication, none whatsoever, that adult stem cells have the same effect as embryonic," Goldstein said.

"For those people, where they have no other hope, this offers remarkable hope and promise," he said.

The British and U.S. moves have prompted the Italian government to consider a public referendum on whether Italy should follow their lead.

"All points of view merit appreciation and a calm and open discussion, without preconceptions or dogma," Italian Health Minister Umberto Veronesi said after the pontiff's speech.

One Italian scientist, Dr. Severino Antinori of Rome, says he needs only approval from a national bioethics committee - which includes religious representatives, including a Roman Catholic cardinal - to start working on a fertility treatment for humans.

In Italy, "the religious groups are blocking it," Antinori said. "That is very dangerous in the world."

Heart Transplants "Only Benefit Sickest Patients"

LONDON (Reuters 9/1/00) - Heart transplants prolong the lives of only the sickest patients and should be given to people with the highest risk of dying, doctors said Friday.

A study of 889 German heart patients, published in The British Medical Journal, showed that less seriously ill patients would not benefit from a transplant.

"Patients with a predictive low or medium risk have no reduction in mortality risk associated with transplantation; they should be managed with organ saving approaches rather than transplantation," Professor Mario Deng said in the study.

Deng, an associate professor at Columbia University College of Physicians and Surgeons in New York, and his German colleagues assessed the risk of death of all patients on the heart transplant waiting list in Germany in 1997.

Patients were divided into those at low, medium and high risk of dying.

As with lungs and kidneys, the demand for donor hearts exceeds supply so there are not enough hearts available for patients who need them.

Deng added that the findings of the study suggest that only the sickest patients should be included on heart transplant waiting lists.

In a editorial on the research, Sharon Hunt of Stanford University in California said it supported the idea of organ allocation systems which are used in the United States and have recently been introduced in Britain.

"The findings will probably be an impetus to continue development of schemes for organ allocation that give donor hearts to those most likely to derive survival benefits from them," she said.

"Testing... Testing." Immune Drugs Make U.S.
Hand Transplant A Success

BOSTON (Reuters8/17/00) - A year after the world's second hand transplant, the patient's new hand can sense temperature, pressure and pain, and he can use it to write, turn the pages of a newspaper, throw a baseball and tie shoe laces, according to a report in Thursday's New England Journal of Medicine.

The operation was performed on Jan. 24, 1999, at the Jewish Hospital of Louisville in Kentucky on a 38-year-old man who received a transplanted left hand from a 58-year-old male cadaver. The transplant recipient was a paramedic who had lost his own left hand in a fireworks accident at the age of 24.

In their report on the surgery, a team led by Dr. Jon Jones said the results "show that early success at hand transplantation can be achieved with the use of currently available immuno-suppressive drugs," which prevent the body from rejecting the new appendage.

One year after the transplant, the recipient was able to throw a baseball, swing a lightweight bat, turn pages of a newspaper, tie his shoelace, write and pick up checkers or poker chips, according to the Jones team. He was unable to perform any of these activities with a prosthesis before the operation.

The man also could experience the sensations of temperature, pressure and pain. In one sense, the operation is not new. Surgeons have been taking severed limbs and reattaching them since 1964.

But using limbs from a cadaver represents an extra medical challenge because the body's immune system identifies the new hand as foreign and tries to attack it. That is where the powerful drugs that suppress the immune system come into play.

In this case, there were three episodes of rejection, each of which were overcome using a variety of drugs, most of which pose potentially serious risks.

Surgeon Dr. James Herndon of Harvard Medical School, in an editorial in the Journal, said that because the drugs can produce life-threatening side effects and hand transplant surgery will not save someone's life, its use should be limited until better anti-rejection medicines are developed.

"I suggest that the ideal candidate is a patient who is already taking immunosuppressive drugs for a life-threatening problem who loses a hand," he said. "Other candidates would be patients who have lost both hands, especially if they are blind."

The world's first hand transplant from a cadaver was performed in September 1998 in France.

Women Denied Heart Transplant

By Burt Herman - Associated Press Writer

BERLIN (AP 8/22/00) - A German hospital drew harsh criticism Tuesday for admitting it denied a heart transplant to a Turkish resident because she didn't speak German.

The Heart and Diabetes Center of North Rhine-Westphalia said denying the transplant for 56-year-old Fatma Elaldi was standard procedure when a patient is unable to understand a doctor's instructions or communicate with hospital staff after the complicated surgery.

Still, the issue touches a nerve in Germany, coping with a wave of anti-foreigner violence and always sensitive about how it deals with its 2 million Turks, the largest minority group in the country.

The clinic's decision was criticized by other medical groups in Germany and government officials, as well as Turkish community groups.

"The arguments of the clinic don't convince me," said Safter Cinar, a board member of the Turkish Council of Berlin and Brandenburg. "I don't want to say racist, but it's a problematic thing. Medicine has the obligation to care for the health of the people and this cannot depend on German knowledge."

Elaldi, who has lived in the western city of Neuwied for 21 years, has suffered heart trouble since birth and received a pacemaker last year. At the time, doctors told her she wouldn't be able to survive long without a new heart. After five days of examination at the clinic this year, specialists planned to place her on the transplant waiting list.

But in February she was notified by letter that she wasn't a candidate, citing her "lack of knowledge of the language" as one of the main reasons. Her daughter, Bektas, who speaks German and had offered to serve as a translator, called the decision "insanity."

Elaldi eventually was placed on a waiting list for a transplant at a Muenster hospital, according to Dr. Yasar Bilgin, chairman of the Turkish-German Medical Foundation. He also said language knowledge wasn't a reason to deny a transplant - citing German patients who go to the United States for operations without speaking English.

A spokeswoman for the medical center in the town of Bad Oeynhausen, Petra Mellwig, stood by the decision Tuesday - saying the hospital has found that 50 percent of its patients without sufficient language knowledge die soon after transplants. She said two other hospitals in Germany also refused to operate on her.

Mellwig stressed the doctors' decision had nothing to do with Elaldi being a foreigner. She said drug or alcohol addicts are also turned down as transplant candidates for the few available organs because they are seen as risk cases in complying with medical instructions.

She said the offer from Elaldi's daughter to translate wasn't enough. "Are they there 24 hours a day caring for the patient?" she asked.

But the hospital later said that, in light of the "public discussion," it would review its criteria to see whether "possibilities can be found in similar cases that would lead to an improvement in the chances of success."

About 500 hearts are available each year for transplants in Germany, but the demand is for more than twice that. About 20 percent of patients on waiting lists die before they are able to receive the transplant.

The health minister in North Rhine-Westphalia, Birgit Fischer, called Monday on the clinic to seek more practical solutions for the problem rather than denying operations - such as using relatives to translate or Turkish-speaking doctors.

"Every person has the right to adequate medical care. And we as doctors have the duty to help," Alfred Moehrle, president of the Hesse state doctors' association, said Tuesday.

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