”All triumphs in medicine are the forgotten sorrows of past days. . . .”
-Thomas E. Starzl
A balky heart from a four-pack-a-day habit may have forced him to turn in his scalpel, but at 66, Tom Starzl keeps shoving medical science over ethical cliffs into brave new worlds. His fabled hands are stilled now, but not his obstinacy and sense of mission.
To the father of liver transplantation, the final frontier, the so-called xenograft or cross-species transplant-swapping animal parts for human parts-offers the only solution to the shortage of donor organs available to repair and rebuild people and save lives.
”This is the only hope for the field,” Starzl states flatly.
”Each day, three potential organ recipients are dying waiting-at the moment, 28,000 Americans are in limbo. Some 2,136 are waiting for livers, most of the others for kidneys.
”But we`re stalled by our own success. We`ve got to turn to animals, or we`ll never advance.”
Where Starzl sees hope, his critics see horror. The conflict exploded recently when his team at the University of Pittsburgh Medical Center struggled to stitch a baboon liver into a dying human being and make it govern the man`s biochemistry. Starzl ended up being pilloried by medical ethicists, other doctors, AIDS activists-even animal rightists who were defending baboons.
Fellow transplant surgeons cheered, however. The Starzl juggernaut has been rolling over the status quo for 30 years.
Starzl`s mentor was Dr. Loyal Davis, a neurosurgeon and chairman of surgery at Northwestern University for 32 years, and the stepfather of former first lady Nancy Reagan.
It was in Northwestern`s surgical research unit at 303 E. Chicago Ave. that Starzl, in 1959, conducted the experiments on stray dogs that enabled him to perfect the toughest, bloodiest, most intricate transplant of all, involving ”that enormous and silent reddish-brown organ,” as he calls the liver.
Had Chicago not been so conservative, it could have become the transplant capital of the world, Starzl says. ”But the medical climate was too conventional. I knew I had to get out, so I headed for the relative wilds of the University of Colorado.”
For reasons he never questioned, Starzl`s subconscious seemed to point to the liver, an organ that defied surgeons for centuries. Each minute, half of the body`s blood passes through the liver, and surgeons who touch it risk high-pressure, jet-stream hemorrhages that can quickly kill a patient.
A virtual stewpot of churning chemicals, the liver stretches across the top of the abdomen, the spleen to one side, the ribs encircling it, providing a roof for the stomach, and the small and large intestines.
The liver processes blood and blood proteins. It metabolizes iron. It converts sugar to starch and then back again, as needed by the body. It detoxifies toxins. It produces greenish-yellow bile to help the small intestine absorb fat.
If the passageway is blocked by cancer, infection or cirrhosis, the bile dams up and flows backward into the blood, causing jaundice-the abnormal yellowing of the whites of the eyes, the skin and the urine. Lose your liver and you`ll die in a day.
Here was an organ worth challenging, Starzl decided. He performed the first liver transplant in 1963, in Denver, took the heat when it failed, and two years later did the first successful one.
After clashing with superiors at various institutions, he settled down in 1981 to build the world`s busiest body shop in the hilly Oakland section of Pittsburgh. Since his arrival, the center has performed more than 6,400 organ transplants. Currently, every 12 hours on average, a vital organ from a person who no longer needs it gets stitched into a stranger who desperately does.
Starzl`s liver wards are filled with deathly ill patients with bloated bellies, spindly arms and legs, deeply yellow eyes and skin; shared misery that makes them eerily look alike. The procession of children, like Stormie Jones, Bennie Solis and David Yomtoob to name but a few, never ceases.
`Brutality` of surgery
Hiding out from the frenzy of his own empire, Starzl works from a secret office hideaway above a nearby Pizza Hut. His two dogs are constantly with him, he listens to classical music and churns out scientific papers. Between 1981 and 1990, Starzl and his team published 503 articles in journals, the most of any American scientist, according to experts who keep track of such matters.
His restless urge to write is genetic, apparently. Born into a newspaper family in LeMars, Iowa, Starzl is a scholar of Latin who considered becoming a priest before graduating from Westminster College in Fulton, Mo.
He came late to surgery after abandoning other specialities (”until I was 33,” he says, ”I felt like a missile looking for a trajectory”), only to discover that he was brilliantly suited for the operating room in all ways but temperament.
”I wasn`t emotionally equipped to be a surgeon or deal with its brutality,” he reveals in his newly published memoirs, ”The Puzzle People:
Memoirs of a Transplant Surgeon” (University of Pittsburgh Press).
”I`ve always had an intense fear of failing the patients who had placed their health or life in my hands.
”As my skills improved, the anxieties worsened. Even for simple operations, I would review books to make sure no mistakes would be made or old lessons forgotten. Then, sick with apprehension, I would go to the operating room, almost unable to function until the case began.”
Only other transplant surgeons can know what it was like, working all night in desperate fury, hands buried deep in his patient, trying to control bleeding that would stop only if he could sew in the liver that makes blood clot.
Despite hating what he was doing, Starzl performed thousands of operations-more than 3,600 liver transplants alone-culminating in his virtuoso showpiece, the first human heart-liver-kidney transplant in December 1989 on a 26-year-old woman.
As a doctor who has seen people return from the last minutes of life to complete health after transplantation, Starzl has little patience with anyone who would stand in the way.
His longest survivor, a woman named Kim Hudson, is 23 years post-transplant; among his starting group of 206 liver-transplant patients, 43 are alive.
Starzl single-handedly made liver transplantation common practice-20,000 have been performed with a 74.4 percent overall survival rate.
A new age
The historic operation last June 28 at the University of Pittsburgh Medical Center could have changed medicine forever. At the least, it presaged the dawning of a new age.
Masked and gowned in blue pajamas (but not scrubbed), Starzl coached in twin operating rooms nearly bursting with specialists. For 11 hours, he shouted orders, guiding and goading nearly a dozen of his proteges (”the best technical surgeons in the world, in my opinion”) as they transplanted a liver from a 15-year-old male baboon into a dying, 35-year-old human being.
The man was at death`s door from hepatitis B virus that had scarred, shrunk and ravaged his liver and made him ineligible for a human organ because the virus would attack it too. Baboons don`t get hepatitis B, so the patient seemed a good candidate for the first primate-to-human liver transplant. It was his only chance.
Although other baboon organs had been transplanted into people in at least 33 operations since 1905, all had failed dismally. In 1963, Starzl, a virtual upstart out West who was tearing up his fledgling field from his haven at the University of Colorado, sewed six baboon kidneys into humans, only to stand helplessly by as, within a few days, the blood vessels to the organs choked, blackened and died from overwhelming rejection.
But 29 years later, he had a secret weapon: the Japanese experimental drug FK-506, which the University of Pittsburgh has used in more than 1,250 transplants since 1989. It has awesome power, perhaps even more than cyclosporine, the Swiss anti-rejection miracle that in the early 1980s made organ transplants feasible.
”FK allows us to transplant intestines and other visceral organs with a survival rate better than 90 percent,” Starzl explains. ”Our animal work showed it could control xenograph rejection in animals.
”But don`t misunderstand,” he cautions. ”These animal-human transplants are terra incognita. With this, we`re back where we were with kidneys in the early 1960s.”
At first, Starzl`s baboon liver seemed to like its new home.
Although the baboon weighed only 53 pounds and the recipient 170, a remarkable adaptation was about to occur. Two days after surgery, the man was breathing on his own, sitting in a chair and watching TV.
By July 3 he was eating food, with the new liver obligingly controlling his digestion. A liver biopsy on July 10 showed no signs of rejection. Remarkably, the animal organ already had grown one-third larger than its original 1.3 pounds. Unlike kidneys, which can be stashed in many body cavities, transplanted livers must go in their natural place, and they ordinarily must fit. At least roughly.
”We can cut them down, though,” says Starzl, ”or if too small, they will regenerate to exactly the right size. Nature has curious wisdom: She knows precisely when to stop.”
On July 18, the patient had trouble breathing. A change in blood chemistry indicated a minor rejection episode, common in the first weeks after liver transplantation. The episode was quelled with steroids.
Ten days later, by July 28, there were no further signs of rejection. Tests showed that the donor organ had grown to the size of an adult human liver, about 4 pounds. It was now the largest organ in the man`s body. He was moved from the intensive care unit to a regular room.
”He`s doing so good, it`s scary,” Starzl had confided at the time in a telephone interview, the hope evident in his voice.
Slow decline
On Aug. 25, he was back in intensive care, where doctors anxiously were monitoring an unexplained fever.
On Aug. 29, the patient developed a serious blood infection after an invasive diagnostic X-ray test called a cholangiogram. He was placed on a respirator to help him breathe and treated with antibiotics.
Two days later, he was still sick, though another liver biopsy (he endured five after surgery) showed no indication of rejection. But the next day, he was sicker. He couldn`t whip the infection, and now his liver showed signs of deteriorating function. Yet more antibiotics seemed to stabilize his condition.
On Sept. 3, good news: the infection had subsided. The doctors continued to blame it on their cholangiogram, but didn`t rule out some kind of weird baboon rejection, even though the biopsy showed none of the typical signs.
Then on Sept. 6 at 9:45 p.m., the recipient had a stroke and died.
The medical team was crushed. But Starzl has announced many deaths.
”This heroic man almost made it, but fell short of the mark” he told reporters that night with the bravado of the surgeon who has given his best to no avail.
”No matter what kind of a transplant was given, he was a high risk. This was not a normal man. He was in the last days of his life.”
Starzl then shared what he viewed as the good news: ”The state of the liver after more than 70 days was really remarkably good; almost normal,” he declared.
”Everyone at the beginning of this race had an almost pathologic fear of rejection,” he pointed out. ”Because it had been seen in a virulent form in every other case ever done.
”But they didn`t see it here.”
Choices and chances
The next day, responding to rumors that the patient had AIDS, the doctors, with the family`s permission, confirmed that he had been infected by the virus that causes AIDS but had shown no symptoms.
Laboratory tests indicated that his immune system was fully competent. The medical center stands firm in its policy to not deny transplants to candidates who test positive for HIV but do not yet have AIDS.
The man and his family had asked for confidentiality.
Nonetheless, to many, the announcement raised new questions about the already-controversial experiment.
What could scientists tell about xenographic rejection in a human when the recipient already had an immune disease? Had the doctors preyed on the vulnerability of a doubly doomed man? Had he been able to give truly informed consent? Or was he basically just a human guinea pig with a baboon liver?
Ethicists fumed over the mania to prolong life at any cost.
Most transplant centers will not deal with patients who are HIV-positive. The official reason is that they do not want to put such patients on anti-rejection drugs, which suppress the immune system. What choice did Starzl`s patient really have? What chance for ultimate survival?
Choices and chances. To Starzl, that`s the point.
His patient was desperate. And vulnerable. No one else would try to help him, Starzl says.
”I think someone who`s dying of terminal organ failure, and who seeks care when he`s home and is rejected by his local and regional transplant programs has every reason to be desperate.”
The University of Pittsburgh was his last chance, in more ways than one. It is one of the few centers that will accept such patients, believing it would be unethical to not do so.
”On the other hand, it would have violated our credo to have given him a human liver,” Starzl says. ”He had a B-virus infection that would have destroyed it. We treat such people at our center. There were a number of B-virus patients on our waiting list. This man was the sickest.”
The shadow of AIDS
In the mid-1980s, when the AIDS epidemic surfaced, Starzl discovered that 25 of his organ-transplant recipients had been infected with HIV, 10 of them children.
”We`d have expected them to be killed off fast by immunosupression,” he says. ”Despite this, many of them were getting along quite well. So it was clear that if our objective is to treat with the best possible means people with HIV-and that meant they needed a kidney, heart or liver-they deserved to get the organ.”
In 1986, Starzl developed hepatitis. A chill ran through his staff. ”We all asked ourselves about the possibilities of HIV infection,” Starzl says.
”We`d been standing in the blood of those patients for hours. It was all over us and we`re always knicking ourselves during surgery.”
The team tested clear.
And as it happened, the death of Starzl`s patient had nothing to do with either HIV or rejection of the baboon liver.
”I`m sorry to say it was due to surgical error,” Starzl says. ”Somehow there was an obstruction of the bile duct (from the liver to the small intestine). The liver itself was in remarkably good condition.”
Such obstructions always have been the Achilles heel of liver transplantation. ”When the duct became blocked, the bile dammed up and formed a sludge that damaged the duct further,” Starzl says. ”Finally, it blew out and leaked bacteria into the bloodstream.”
”The bacteria made it to the patient`s brain and killed him.”
The baboon duct was smaller than a lead pencil. Starzl hoped the liver would grow quickly in the human body. But the bile duct grew in ways that no one could have predicted. Starzl knows what to do next time.
And there will be a next time, he insists.
”I don`t think we have any choice,” he says. ”It would be unethical to not go ahead.
”Our first patient`s course was great for two months. The guy was happy. He felt great. He wanted to go on talk shows and get the word around. All the things that brought him down occurred only in the last few days.
”We`re not experimenting on these patients,” Starzl says. ”I hope people will understand that. We`re really trying to treat them. We`re really trying to help.”
