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Pioneer without peer

Sunday, June 11, 2000

By Anita Srikameswaran, Post-Gazette Staff Writer

The Starzl Story
First Of Two Articles

 
  Dr. Thomas Starzl (Darrell Sapp, Post-Gazette)

The hard-driving surgeon has made life-saving transplants seem almost commonplace

Dr. Thomas Starzl took the podium one evening last summer and delivered what may have been his shortest speech ever. It came at the end of a dinner at the Westin William Penn, Downtown, that had featured brief, heartfelt tributes from guests, and a videotape in which colleagues, former students and family members told tales about the man who is arguably the most important surgeon and researcher in the world in the field of human organ transplantation.

By the time he got up to speak, the scientist and physician who performed the first human liver transplant had been warmly roasted.

He was celebrated not just for his superhuman precision in the operating room, his brilliant, questing mind, and his indomitable will, but also for his love of doughnuts, his terror-inspiring driving and his penchant for phoning people in the middle of the night.

For once, Starzl seemed at a loss for words.

"On occasions like this it would be best for me to say as little as possible," he began in quiet, clear tones that hid his strong emotions. "I won't start anything I can't finish."

Then he added ruefully, "I wish I had behaved a little better," drawing laughter from the audience.

Starzl may have been referring to his reputation for being curt and demanding during his years in the operating room, all in the pursuit of saving some of the sickest patients ever to undergo surgery.

Or he may have been talking about his disregard of social conventions, which included calling friends at midnight with an idea he couldn't get off his mind and driving on the sidewalk to get where he wanted to go.

It is easy to allow Thomas Starzl, 74, some idiosyncrasies.

His contributions have enormously advanced medical knowledge and surgical technique, and he can claim as much credit as anyone for making organ transplantation a routine procedure that has rescued an untold number of people from certain death.

One way the research community assesses a scientist's impact is by counting citations -- the number of times his or her work is referred to in the research papers of others.

In May 1999, the Institute for Scientific Information announced that Starzl's work had been cited more than that of any other researcher in the world -- 26,456 times between 1981 and June 1998, or about 4,000 more times than the next-ranked researcher.

After such monumental achievements, Starzl seems to long for a change of pace. He wants to become an emeritus professor and stop drawing a salary from the University of Pittsburgh, whose medical school owes a large part of its stature to his presence there for the past 20 years.

He would like to spend more time in Texas, where his wife's family lives, play with his dogs, and catch up on all the movies he missed during decades of operating and conducting lab experiments night and day.

But there are research papers still to be written and new concepts to be shared with the scientific community.

"I'm really trying to not work, but I haven't got around to that yet," Starzl said.

 
   

Part Two: Life after surgery

 
 

Growing up in Iowa

Starzl's story begins in the small Midwestern town of Le Mars, Iowa, which has a Web site that bills it as the Ice Cream Capital of the World but doesn't mention its illustrious son.

The second of four children, Thomas Earl Starzl was born March 11, 1926. He grew up in a house that was less than 50 feet across the street from a Carnegie public library and two blocks from the Royal Movie Theater. He considers those lucky breaks.

In his youth, Starzl preferred the study of Latin to any other school subject. He played the cornet, entertaining residents of Le Mars with weekly concerts in the town park.

His father, Roman Frederick Starzl, owned and ran the local newspaper, the Globe Post, which he bought with earnings acquired during a secret career as a science-fiction writer for magazines such as Amazing Stories.

Roman Starzl occasionally used his wife's maiden name as a pseudonym when he wrote. Anna Laura Starzl, nee Fitzgerald, a nurse, died of breast cancer in 1947. Thomas Starzl had just graduated from Westminster College in Fulton, Mo., after being discharged from the Navy.

To ease her pain in the final days of her life, Starzl gave his mother morphine injections, which in those days required dissolving a morphine tablet and heating the liquid before drawing it into the syringe. He was with her as she drew her last breaths, and for a long time afterward he wondered if he could have held off her death by preparing the injections more quickly.

"When she was gone, there was no family anymore," Starzl wrote in his 1992 autobiography, "The Puzzle People."

At one time, he had thought of becoming a priest. But for 29 years after his mother's funeral Mass, he never went to church.

In the fall of 1947, he entered Northwestern University Medical School, where he began a long friendship with professor and neurosurgeon Dr. Loyal Davis, father of former first lady Nancy Reagan. Starzl made ends meet by taking a job as a proofreader and later as a copy editor of medical stories at the Chicago Tribune.

Starzl spent an extra year at medical school, using the additional time to complete a doctorate in neurophysiology, in 1952. He wrote a seminal paper describing a technique to record the electrical responses of deep brain structures to sensory stimuli such as a flash of light or a loud sound. The paper is still cited today.

After obtaining his medical degree, Starzl trained in surgery at Johns Hopkins Hospital in Baltimore and Jackson Memorial Hospital in Miami. At both places, he conducted lab and animal research, showing a keen interest in liver biology.

In a makeshift lab in a garage across from Memorial's emergency room in Miami, Starzl figured out how to remove a dog's liver and keep the animal alive for as long as 24 hours, a key step toward transplantation's success in humans, because it would become the first half of a liver transplant operation. And, Starzl realized, a donor liver could then be sewn into the vacant space in the dog's belly.

In 1958, he returned to Northwestern to train as a thoracic surgeon, and joined the faculty the next year. Federal and private research grants allowed him to spend significant time in the lab, where he performed liver transplants in dogs. The transplants worked for about a week before the organs were rejected.

In the years that followed, he met and joined a small band of physicians who were determined to make organ transplantation successful and reliable. Few believed that was possible with the liver, because the complex organ bled profusely when operated upon.

Starzl joined the faculty at the University of Colorado in 1962, and that is where his career in human organ transplants blossomed. Within three months of his arrival, he had performed Denver's first kidney transplant.

On March 1, 1963, Starzl and his team attempted the first human liver transplant on 3-year-old Bennie Solis.

The boy had biliary atresia, in which the liver lacks its normal network of bile ducts needed for the elimination of wastes. There was no treatment for the condition then.

The operation could not be completed. The boy's blood would not clot and he bled to death. Four subsequent liver transplant patients in Denver were treated with clot-promoting drugs and survived their operations, but died soon afterward because clots lodged in their lungs and produced abscesses and other damage.

Starzl and liver transplant pioneers elsewhere decided to halt their trials and go back to the laboratory.

 
  Dr. Thomas Starzl and Ophelia -- He is acutely aware of the contribution made by one species -- dogs. (Darrell Sapp, Post-Gazette)

Could he do it again?

Looking back on those early transplant years, Starzl is acutely aware of the contribution made by one species -- dogs.

And that is a painful thought for him today because of his deep love for those animals, particularly his constant companion, a pretty mutt named Ophelia.

"It really bothers me in many respects to realize what a tremendous price was paid by dogs to allow transplantation," Starzl said. He operated on hundreds of them over the years to perfect his surgical techniques, and most of the dogs were euthanized afterward. "I couldn't do that again, I think."

Starzl and Ophelia get up before 6 a.m. so they can be the first at the park to play Frisbee to their hearts' content.

After a pit stop at home, Ophelia accompanies her smitten owner to his Oakland office, where he works from 9 a.m. until 6 p.m. When Starzl leaves for his midmorning coffee and doughnut fix, or his bagel at lunch, she trails him to the exit, where he reassures her of his imminent return.

As he works, she lies near his feet or on them, occasionally sleeping but always ready to leap up and bark greetings to visitors as they climb the stairs to Starzl's office. She and her owner enjoy another romp in the park before heading home.

Starzl is intrigued by Ophelia and her loyal and loving nature.

"Dogs give you something you could never ask another human being to give you, nor would you be willing to accept it," he mused. "That is, total existence in the shadow of a human. If you treat a dog right, you have a companion who is devoted, whose sole reason for being is to be with you. That's extraordinary."

And he noted, with his typical wry touch, "If you treat a dog badly, you have a nuisance that's shedding hair."

Another animal that paved the way for transplantation was the horse.

In the mid-1960s, scientists devised a way to destroy the immune cells known as lymphocytes, which attack transplanted tissue. They injected lymphocytes into horses, which made proteins called gamma globulins that hunted and destroyed the human cells. The gamma globulins were then extracted from the animals and injected into transplant recipients to suppress their immune systems.

In the summer of 1966, Starzl and the Denver team began trials of what they called antilymphoid globulin (ALG) on kidney transplant patients, adding it to a regimen that already included the immunosuppressive drug Imuran and steroids.

A pioneer patient

Burl Osborne, director of publishing for media company Belo and publisher of the Dallas Morning News, was the third person in the world to get the experimental treatment.

At the time, he was 27 and ran the Spokane, Wash., office of The Associated Press. Osborne's kidneys had been inflamed and dysfunctional since childhood. He was one of a handful of people lucky enough to get dialysis treatments, then a rare procedure. His heart had once stopped and he had constant problems with fluid buildup in his lungs.

The dialysis "was not really agreeing with me well," Osborne said. "I reached the conclusion that I'd rather risk a transplant. I thought, 'Really there's not too much hope, so why don't I do this?' "

Kidney transplants weren't routine procedures then, in part because of the high risk of organ rejection that scientists were trying to circumvent with preparations such as ALG.

Osborne recalled his first impressions of Starzl, then 40 years old: Frenetic. Intense. Very smart. Photographic memory. Very matter-of-fact. Tireless.

Starzl, he said, had leadership qualities that persuaded people to attempt the seemingly impossible.

"He made believers out of the people he worked with, even though many times they didn't know where he was headed," Osborne said. "So many times, he was able to get there."

The newspaperman got to know the surgeon better after transferring to the Denver office of The Associated Press in 1967. Curiosity led him to follow the ups and downs of the fledgling liver transplant program, which had been resumed because of hard-won improvements in anti-rejection therapy and methods to preserve donor organs outside the body.

"They'd do one, and everybody would be euphoric," Osborne recalled. "And then they'd have the inevitable failures. [The team] would be in just a deep, deep funk."

He wondered in those days about Starzl's family life, because the doctor was around whether Osborne dropped in at his office at 8 a.m. or midnight.

In fact, Starzl was living a schedule that eventually would wreck his first marriage.

In 1954, he had married Barbara June Brothers, then of Hartville, Ohio, and they had three children: Tim, Rebecca and Tom. They divorced 23 years later because "her rival, Mistress Surgery, had been too strong," Starzl wrote in "The Puzzle People."

His daughter, Rebecca Starzl of Tucson, Ariz., has long since come to terms with her father, warts and all.

"He would have made a wonderful father if he hadn't turned into a superstar surgeon," she said. "When we were kids, he was completely immersed in his work."

In the turmoil of her parents' divorce and her entry into college, Rebecca severed communication with her father, a situation that lasted a decade. She did it because of her rebellious nature and a need to be someone other than "Dr. Starzl's daughter," she said.

Back then, "I'd rather eat macaroni and cheese all week than let him give me $5 for a used textbook," Rebecca Starzl said, laughing. "I was very angry at him for a long time. But [the estrangement] was a good thing for both of us."

She reopened talks more than 15 years ago, telling her father that she would not be overpowered or intimidated by him. Somewhat to her surprise, Tom Starzl, who respects people who stand on their own feet, had no problem with that. Since then, she has relished being introduced by him as his "favorite daughter."

Starzl also enjoys good relationships with his sons and is a proud grandfather to Tim's son, Ravi.

Rebecca Starzl has marveled watching her father "work the room" at countless banquets and tributes, aided by his powerful memory. He remembers not only the names of patients and their surgeries, but the names and occupations of their family members and the towns they call home.

Starzl is not only good at charming people, he seems to enjoy it.

The same cannot be said of another of his skills.

Never liked surgery

Starzl has never been too crazy about performing surgery, although many have described him as one of the best surgeons of the 20th century.

"I remember him telling me operating, to him, was a means to achieve an end," said Dr. John Fung, executive director of the Thomas E. Starzl Transplantation Institute. "Surgery being the means and the end being trying to understand the puzzle" of anatomy, immunology and physiology.

Fung, who already had a doctorate in immunology, was doing surgical training in Rochester, N.Y., in 1984 when he met the man he now considers his mentor. Scheduled to perform a hip replacement at the same time Starzl was to give a talk, Fung paid another resident $25 to do the operation. After the lecture, the two had a short conversation and the younger man was invited to Pittsburgh to train in transplantation.

Fung soon learned that Starzl was a different man inside the operating room. He never raised his voice, but was very curt. If a surgical assistant pulled too hard and broke a suture thread while tying a knot, Starzl threw him out of the room.

"If he really didn't like the way you operated, he'd tell you to go away and he'd bring someone else in," Fung recalled. "And then he wouldn't forget. He'd send you off to the dog lab and you'd have to work your way back up the ladder."

Outside the operating room, he said, "You always had to be looking out for Starzl. He always knew what was going on." If a trainee faked knowing a patient's lab results or the latest research findings, he was doomed. "If you tried to [fool] him, he'd kill you."

Ego-withering as it sounds, Starzl's methods forced his students to perform beyond their expectations, a fact that many of them recognized only after they were out on their own. In surgery, Starzl's combination of technical mastery and artistry created magic, Fung said.

"It was just awe-inspiring watching this guy operate," he said. "He was never what you'd call a fast surgeon. He was very slick. He would never really do the same thing twice, but at the same time, there were no wasted movements."

Dr. Byers Shaw, now chief of surgery at the University of Nebraska Medical Center, had no intention of participating in liver transplants when he arrived in Pittsburgh in 1981. He wanted the renowned surgeon to teach him to do kidney transplants.

"I kept hearing about this guy named Tom Starzl, who was basically a very intense individual doing crazy things," Shaw said. The idea of transplanting a liver struck him not only as nearly impossible, but also as "a terrible thing to do to somebody right before he died."

Soon after Shaw's arrival, Starzl turned up on a hospital ward looking for assistants to help him with a liver transplant. He was about to pass Shaw over, but the young surgeon piped up suddenly and asked to be included.

"In five years of [surgical] training, I had never seen anything like the operation that I witnessed that night," Shaw said. "That was when I saw my first miracle."

Before the transplant, the recipient was clearly on the verge of death, the sickest patient Shaw had ever seen. Within days of the operation, the patient was up and walking.

"I suddenly understood why it was so important for [Starzl] to soldier through even when the rest of the world was criticizing him for doing something where the survival probabilities were so low," he said.

There were times during those intricate, bloody operations when it seemed there was no hope to save the patient before them.

"The only thing that kept the entire team going was his mean, nasty refusal to give up and his badgering the hell out of everybody else at the table until we were all ready to kill him," Shaw said.

This is how Starzl would castigate them, Shaw said: "Quit behaving this way. Quit acting like you're giving up. What the hell is wrong with you people? Isn't there anyone else interested in life but me?"

Starzl's tenacity made those operations succeed, Shaw said.

Rocky start in Pittsburgh

Starzl's arrival in Pittsburgh on New Year's Eve 1980 was met by critics who had little confidence in the viability of liver transplantation, or in the surgeon himself, as well as by supporters such as Dr. Henry Bahnson, who headed the university's surgery department. Some of the members of the Denver team came along, while others at that hospital were relieved to see the controversial surgeon go.

Newspaper accounts from that time say Starzl had done 175 liver transplants in Denver, with a survival rate of 30 percent to 50 percent. Pittsburgh's first four liver transplant patients died, drawing jeers from some.

But Starzl brought a powerful companion with him to Pittsburgh -- the anti-rejection drug cyclosporine.

After animal experiments showed that cyclosporine, extracted from a fungus, could suppress the immune system, it was tested in the late 1970s on kidney transplant patients in Great Britain by Cambridge University transplant surgeon Sir Roy Calne. The English group's work showed the drug had serious side effects, including damage to the transplanted kidney.

But early trials in Denver indicated that cyclosporine, combined with steroids, had the potential to improve survival rates and make organ transplants commonplace. Tests performed here confirmed it, and the jeers finally turned into cheers.

Soon, surgeons from around the world were flocking to Pittsburgh to learn from Starzl's transplant team, along with patients who first came for kidney operations, and then, at long last, reliable liver replacements.

Eventually, the widespread use of cyclosporine and the decision by many insurance companies to start covering the cost of transplantation led to a boom in organ transplant centers around the country.

As transplants became routine, waiting lists for the procedures grew, and the need for a systematic and fair method of distributing scarce donor organs intensified.

That's when Starzl's team was faced with its first big public relations crisis in Pittsburgh.

In the mid-1980s, reporters at The Pittsburgh Press investigated Starzl's kidney transplant program and said the team had flouted hospital guidelines by taking too many foreign transplant patients, and by putting wealthy Saudi Arabian nationals and other foreigners ahead of Americans on waiting lists. The stories also said what was then known as Presbyterian-University Hospital was charging the foreign patients higher fees and accepting gifts and research funds from them.

The allegations were volcanic.

Starzl and hospital officials insisted that the kidneys were given to patients based on need rather than monetary considerations.

The Rev. George Werner, who was then dean of Trinity Episcopal Church, Downtown, was one of those called in to deal with the fallout.

Werner recalled that "a potential scandal was brewing, so the board of directors at Presbyterian-University Hospital asked eight semifamous people to form a committee to oversee organ transplantation." He became vice chairman of the group.

A federal grand jury began hearings in 1985 to see if Presbyterian-University Hospital and Starzl had allowed kidney transplants to be performed "for valuable consideration," which would be a violation of the National Organ Transplant Act and grounds for prosecution.

Starzl, Werner and many others were called to testify in the years that followed. Their testimony was secret, which is usual in grand jury investigations. In 1989, a spokesman for the U.S. Justice Department announced that the matter had been closed and no charges would be brought, a decision that Starzl and others felt was a vindication of him and the program.

The Press went on to produce a series of stories in 1985 that examined what was happening with organ transplants around the world, and revealed that organs were being sold in some countries. It won the now-defunct newspaper a Pulitzer Prize and cast a spotlight on the need to develop a national consensus on how to rank people on transplant waiting lists.

The Pitt team, with input from the oversight committee, developed a point system for patients based on such factors as time spent on the list and how sick the patient was. That system became the national standard and remained so for several years. Starzl seemed to have weathered his first serious controversy in the public arena, although he still harbors some anger over the newspaper's stories.

But he would soon face other problems -- the physical toll that surgery and an intense lifestyle had taken on his body.



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