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Rewriting Life

Surgical Frontiersman

Transplant pioneer Thomas Starzl.

At 79, thomas starzl doesn’t have much left to prove. In July 1967, the surgeon was the first to perform a successful human liver transplantation; since then he has been instrumental in making the liver the United States’ second-most-commonly transplanted organ. “He led the field of transplantation into the modern era,” says J. Richard Thistlethwaite, a transplant surgeon at the University of Chicago.

Despite his accomplishments and acclaim, though, Starzl still goes to work each day at the nation’s most active organ transplantation center, a University of Pittsburgh fa­cility that happens to be named after him. He and others in the field, it turns out, are still struggling with the same basic challenge they’ve faced since Starzl’s pioneering surgeries: preventing patients’ immune systems from attacking and destroying new organs. That a field’s founder is still doing battle with some of its oldest demons more than 40 years later is instructive. It reminds us that the birth of a new technology is not a discrete event, and that emerging technologies bring not only hope and new possibilities but also their own collections of emerging problems. That may be frustrating, but it’s what drives many innovators and keeps them coming back to the office long after they really need to. “I’m pretending to be retired,” says Starzl.

By the time Starzl began dabbling in liver transplantation in the late 1950s, doctors in Boston had already done the first kidney transplant. But because they had no form of drug treatment to prevent the immune system from rejecting an organ it recognized as foreign, they were limited to trans­planting organs between twins. Most didn’t think that transplanting organs between ge­netically dissimilar people was possible. But that didn’t stop Starzl from trying.

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Toiling alone in a hospital lab, Starzl, then 32 and a surgical fellow at Northwestern University, began by transplanting livers between dogs. At the outset, he didn’t realize how bloody and difficult the procedure would be. All of the dogs died. Even so, he never thought of giving up. “I’m not sure I wasn’t considered insane at the time,” says Starzl. “It seemed a total fantasy.”

But after gutting it out for nine years, and switching briefly to kidneys (which proved much easier to transplant), Starzl finally perfected his surgical technique and hit upon a combination of immune-suppressing drugs that kept transplant recipients, at least in the short term, from rejecting their new livers. Today, more than 5,000 Americans get new livers, and a new chance at life, every year. Immune-suppression treatments, many of them devised by Starzl, opened the door to other organ transplants as well and continue to improve. One-year survival rates for liver and kidney transplant recipients are now in the 85 to 95 percent range, up from less than 50 percent a few decades ago.

In developing immune-suppression therapies, though, Starzl and his colleagues traded one set of problems for another. Transplant patients on long-term suppressive regimens face higher-than-normal risks of infection, heart disease, diabetes, and kidney damage. And though immune-suppressing drugs effectively block acute rejection, many transplant recipients still suffer “chronic rejection,” meaning that over time, their new organs begin to fail. All together, 20 to 30 percent of liver and kidney transplant recipients die within five years of their surgeries.

Starzl and other transplant researchers have therefore devoted themselves to finding more-sophisticated ways of training the immune system to accept new organs over the long term so that they can wean their patients off of the harsh antirejection drugs. One intriguing lead: a small number of transplant patients are “tolerant” of their new organs; they can stop taking the drugs, and their organs do just fine. Starzl’s theory, a controversial one, is that a transplanted organ “sends its own army of cells out” into the recipient’s body, and that in some cases, the peaceful coexistence of donor and recipient cells trains the immune system to accept the transplant. ­Giving patients immune-suppressing drugs before transplant surgery, Starzl argues, can help foster this coexistence; he’s published evidence that such pretreatment reduces patients’ need for immune-suppression therapy after surgery.

Even if Starzl is able to solve the problem of chronic rejection, though, that will do little to address another huge issue looming over transplant medicine: organ shortage. The next Starzl will likely be a pioneer in engineered “bioartificial” organs (see Saving Lives with Living Machines,” July/August 2003) or animal-to-human organ transplantation. And those technologies, of course, are almost certain to introduce a whole new set of challenges.

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