Thomas Starzl
Surgeon who performed the first successful liver transplant and led research into anti-rejection drugs
THOMAS STARZL, who has died aged 90, was an American surgeon who, after years of pioneering experiments with immunosuppressive drugs, performed the world’s first successful liver transplant in 1967. Beginning with kidney transplants at the University of Colorado in Denver, Starzl battled to overcome the problem of rejection by treating patients with azathioprine, a powerful immunosuppressant. In 1963 he attempted a liver transplant on a three-year-old boy, Bennie Solis, who had been born with incomplete bile ducts leading to organ failure. But Bennie suffered a haemorrhage on the operating table, and none of Starzl’s next four patients survived more than a few weeks. Attempts to manage bleeding during the operation with doses of fibrinogen, a protein that helps to form blood clots, led to fatal complications.
There followed an informal moratorium on human liver transplantation, during which time Starzl dedicated himself to research that he hoped would transform the chances of a successful operation. He led the first clinical trials of antilymphocyte globulin (ALG), an infusion of antibodies that boosted survival rates, and developed preservative solutions that kept donor organs viable for several hours outside the body.
Meanwhile, he made great strides forward with kidney operations, resecting and transplanting organs from cadavers, living volunteers and – on six occasions – baboons. Though all the recipients of the baboon organs died within four months, and the subsequent moral backlash stalled further attempts at xenotransplantation (the transferral of organs between species), by the end of the decade Starzl was pre-eminent in his field.
Encouraged by his progress, the Denver team resumed the liver transplant programme in 1967, and the following year Starzl presented the results to the American Surgical Association. Of the seven critically ill children who had received a donor liver, all had survived the surgery. It was enough to suggest that, given the right combination of post-operative care and anti-rejection drugs, the general prognosis could improve.
Then, at the end of the 1970s, came the medical breakthrough Starzl had been holding out for. Hearing of experiments with a new and far more powerful Swiss-produced drug, cyclosporine, Starzl thought he could counter its significant side-effects by combining it with steroids. The results in his kidney patients were overwhelmingly positive. Over the next decade transplant surgery was transformed from a last-ditch experimental treatment into a clinical service. By the end of the 20th century Starzl was the most-cited researcher in clinical medicine, having published more than 500 articles in the decade between 1981 and 1990.
All the same liver transplantation carried significant risks, and the work took a toll on Starzl. He hated the physical act of surgery and was often besieged by anxiety beforehand. His first marriage broke down and his own health suffered, leading to ulcers, a 60-a-day smoking habit, and a heart condition for which he underwent bypass surgery in 1990.
Even in retirement the breakthroughs of his career haunted him almost as much as the setbacks. One of his dearest possessions was a portrait of two-year-old Julie Rodriguez, who at the time of her death on August 26 1968 had survived more than 13 months with a donor liver – then longer than anyone else in medical history.
Thomas Earl Starzl was born on March 11 1926 in Le Mans, Iowa, the second son of Czechoslovakian and Irish immigrants. His father, Roman, ran a local newspaper; before marrying, his mother Anna had been a surgical nurse. Later, Starzl would cite her example as pivotal in his decision to study medicine. A summer job sorting type at his father’s publishing house honed the manual dexterity essential for surgery.
He received his diploma during his service in the US Navy and, following demobilisation, graduated with a degree in Biology from Westminster College in Fulton, Missouri. By this time his mother was in the final stages of breast cancer, and Starzl returned home to care for her until her death in the summer of 1947. Despite his grief, he performed brilliantly in examinations at the Northwestern University Medical School, Chicago, graduating with a master’s degree in anatomy in 1950 and an MD two years later.
An extra year conducting research under the influential neuroscientist Horace Magoun led Starzl to work on a system for tracking the electrical impulses of the brain in response to stimuli. The studies, which earned Starzl a PhD in neurophysiology, were highly influential, and continued to receive citations in neurological articles decades down the line.
After completing his internship at the Johns Hopkins Hospital in Baltimore – a “purgatory” from which he was happy to escape – Starzl took a position at the Jackson Memorial Hospital in Miami.
With growing confidence in his ability, he began experimenting on dogs in an empty garage next to the hospital, where he developed a new method of removing the liver altogether. In order to prevent the transplant organ from being damaged after it had been disconnected from its original blood supply, he injected the blood vessels with cold liquids. The innovation was to prove critical to successful procedures on humans.
In 1981, having resigned from the chairmanship of Colorado’s surgery department, Starzl moved to Pittsburgh, where he continued his research into cyclosporine and began investigating samples of a new and still more potent drug from Japan, known as tacrolimus or FK-506. Appointed professor of surgery at the University of Pittsburgh and chief of transplantation services at the Presbyterian University Hospital, in 1985 he set up the Pittsburgh Transplantation Institute, later renamed the Thomas E Starzl Transplantation Institute.
But the lack of donor organs remained a problem, and a series of articles in The Pittsburgh Press during the mid-1980s accused Starzl’s team of giving priority to wealthy foreign nationals over American patients on the waiting lists.
Despite concern in the transplant community, Starzl forged ahead with his experiments. Early trials of FK-506 proved so encouraging that he abandoned his customary public reserve. He had lighted upon “a miraculous drug”, he rejoiced, and the press headlines reflected his excitement. In October 1989 The Lancet published his team’s findings: FK-506 was 50 to 100 times more powerful than cyclosporine.
Following his retirement from clinical practice in 1991, Starzl turned his attention to the study of the biological processes by which the human immune system accepts or rejects a donor organ. By compiling observations from 35 years of case studies, he and his colleagues found that a few patients who had stopped taking their immunosuppressive drugs had not experienced rejection.
In all these patients the white blood cells from the donor organ had migrated into the recipient’s blood and surrounding tissues, allowing the two cell systems to coexist without triggering an immune system response.
The pinpointing of this phenomenon, known as microchimerism, raised profound implications for the future of organ transplantation. If the process could be enhanced in all transplant patients, Starzl believed, the need for drug therapies – with their severe sideeffects – could be curtailed. Even xenotransplantation might, he hoped, become possible, through modification of those genes in the nonhuman donor which are involved with the rejection process.
Yet, at the turn of the century, the goal that Starzl first set himself with his baboon-to-human transplants in the 1960s remained elusive. Two attempts, in 1992 and 1993, to transplant baboon livers into men who had been rejected for conventional treatment ended in failure.
Characteristically, Starzl was optimistic. “With persistence, the field of human-to-human transplantation has proved highly successful,” ran his introduction to a 1997 paper. “It is possible that xenotransplantation may not be universally successful until further technologic advances occur; yet cautious exploration appears warranted.”
For his achievements in the medical field, Starzl was awarded the National Medal of Science by George W Bush in 2004. In 2012 he received the Lasker-Debakey Clinical Medical Research Award in tandem with the British surgeon Sir Roy Calne, who had performed Europe’s first liver transplant in 1968 and the world’s first liver, heart, and lung transplant in 1987.
Thomas Starzl married, in 1954, Barbara Brothers, with whom he had three children, two of whom predeceased him. The marriage was dissolved in 1976 and he married, secondly, in 1981, Joy Conger, a research technician. She survives him with his son from the previous marriage.
Thomas Starzl, born March 11 1926, died March 4 2017