Organ Transplant Pioneer Talks About Risks and Rewards Sir Roy Calne is a pioneer of organ transplants - the surgeon who in the 1950s found ways to stop the human immune system from rejecting implanted hearts, livers and kidneys. In 1968 he performed Europe's first liver transplant, and in 1987 the world's first transplant of a liver, heart and lung. This fall, along with Dr. Thomas E. Starzl of the University of Pittsburgh, he received a 2012 Lasker Award for "the development of liver transplantation, which has restored normal life to thousands of patients with end-stage liver disease." We spoke for two hours immediately before the awards ceremony. An edited and condensed version of the interview follows. When you were studying medicine in early-1950s Britain, what was the prevailing attitude toward organ transplantation? It didn't exist! While a medical student, I recall being presented with a young patient with kidney failure. I was told to make him as comfortable as possible because he would die in two weeks. This troubled me. Some of our patients were very young, very deserving. Aside from their kidney disease, there was nothing else wrong with them. I wondered then if it might be possible to do organ transplants, because kidneys are fairly simple in terms of their plumbing. I thought in gardening terms. Might it not be possible to do an organ graft, replacing a malfunctioning organ with a healthy one? I was told, "No, that's impossible." Well, I've always tended to dislike being told that something can't be done. I've always had a somewhat rebellious nature. Just ask my wife. When did you first think it might be a real possibility? Around 1957. I was teaching anatomy at Oxford. I attended a lecture there by the great biologist Sir Peter Medawar, who showed slides of successful skin grafts between white mice and black mice. Though he insisted that there was "no clinical application whatsoever," I wondered, "Why couldn't we do something like that with kidneys?" Afterwards, I began to devote myself to the two main obstacles to transplantation. One was surgical and the other immunological. In America, at that time, Tom Starzl, then at Colorado, and Francis Moore at Harvard were separately working on the surgical techniques. But I was in Britain, and there was no one there who could teach me. And so I worked out the surgical problem for myself. I taught myself how to transplant kidneys in dogs. Once I'd done that, the big problem was to find some way to prevent the immune system from rejecting the transplanted organs. I sought some way to make the immune system temporarily malleable, as it is in the fetus. If you performed the transplant during a period of plasticity, the hope was that you could avoid rejection. In those days, the only described method for doing that was X-ray irradiation, shutting down the immune system by destroying it. Well, that didn't work. It just made the dogs desperately ill and it didn't stop rejection. That led me to wonder if there wasn't some other method of immunosuppression we could consider - a drug perhaps? How long did it take you to find something effective? The first sign that we might have something came in 1959, when we tried the anti-leukemia drug 6-mercaptopurine with dogs who'd had kidney grafts. Some lived quite a long time. And this was a big step. It changed something that had been total failure to a partial success. Even Peter Medawar thought we were on to something. But cyclosporine was the real watershed. We tested it in my laboratory at the University of Cambridge during the mid-1970s. By 1977, it had moved the success rate from 50 percent to 80 percent. That really changed attitudes. Before cyclosporine, you had only 10 centers around the world doing organ transplants. Afterwards, it was 1,000. And now we had a whole new problem: not enough donor organs to meet demand. Is there any solution to the shortage of donor organs? I think an "opt out" program would work better than what you currently have in the United States. They are doing this in Spain, and it has worked very well. It offers the option for people to say "no" to have their organs used after death. If they don't take it, this is regarded as permission. This changes the atmosphere and the perception. Are you intrigued by the ethical questions your discoveries have brought? Well, one of the reasons we have them is that the results are so good. If we hadn't had successes, we wouldn't have ethical concerns. Still, it's one thing to transplant organs from deceased donors and another to pressure people to donate while alive. My profession has been very cavalier about taking organs from live donors - especially livers. Sometimes adults are willing to donate half their livers because of tremendous pressure from their families. With half a liver, there's a definite mortality rate, probably around 1 percent, maybe 2 percent, for the donor. I've seen tremendous disruption in families where a wife said, "My husband wants to give half his liver to his brother, but he's the breadwinner in our family and I don't want him to do it." What about the growth of "transplant tourism," where patients from wealthy countries travel to poorer ones to find organs? That's terrible - verges on the criminal, really. We've heard stories where a well-respected surgeon is asked to go to a third world country, and he gets there and the recipient has cirrhosis and the donor is his "cousin." In fact, the donor is probably some poor peasant who is apparently being paid for it. One hears of disasters where the surgeon has to work in countries with poor facilities and both the donor and the recipient have died. The surgeon returns home to this horrible news. These kinds of events can occur in countries where power is abused. We can just imagine what would have happened in Nazi Germany if organ transplantation had existed in the 1930s. You did a lot of your early experiments on dogs and pigs. What do animal rights activists think of your work? They once sent me a bomb. I was suspicious and phoned up the army - who blew it up. This was right around the time cyclosporine was first being used. A BBC director did a program on a child who'd been saved with it. And after that, I had no more trouble with animal rights. Not because they loved me. But that they thought it wouldn't do them any good if they killed someone treating children. The Lasker prize, which you and Tom Starzl just won, is often called the Pre-Nobel. Were the Lasker judges saying to Stockholm, "Hey, isn't it time you honored this world-changing discovery?" Well, I don't know how they work in Stockholm. If you look at the amount of good that resulted from organ transplantation it fits very much into what Alfred Nobel wanted the prize to be used for. I get a lot of satisfaction a different way. I have a patient and it's been 38 years since his transplant. He's just come back from a 150-mile trek bicycling through the mountains. That's my reward.