Matchmaker, Find Me a Match

By Christine Gorman

With flying fingers, fine sutures and a potent arsenal of drugs, surgical teams have become so successful at transplanting organs that the demand for viable tissue has far outstripped supply. In 1967, the first person ever to feel the beat of another man's heart in his own chest survived for just 18 days after the operation. Today, more than eight out of 10 heart recipients live at least a year with their borrowed organs. For kidney transplants, first-year survival tops 90%. As success rates soar, doctors attempt ever more variations on the transplant theme: installing a new pancreas, lobes of a live donor's lungs, even several organs at once. But rising hopes mean more people will be disappointed. Some 23,000 Americans desperately await replacement organs this year; if current shortages continue, more than 2,000 of them will die before a donor is found.

The present golden age of transplants occurred only after researchers began tackling one of medicine's greatest puzzles: How do you sneak a foreign organ past the body's immune system, which is dedicated to the proposition that all alien tissue is dangerous and should be destroyed? On the one hand, doctors try to disable the body's defenses just enough so that they will not reject the transplant. Here the trick is not to go overboard and completely cripple the immune system, leaving the body open to attack by deadly viruses and bacteria. On the other hand, they try to cajole the body's defenders into accepting the graft as one of its own.

In 1980, a single drug, derived from a Scandinavian soil sample, provided a stunning breakthrough in the effort to tame the immune system. Cyclosporine targets the killer T cells -- the cellular commandos that seek out alien tissues after other defenders have marked them for elimination. Within a few years of the drug's introduction, first-year survival rates for kidney recipients jumped from 50% to over 80%. Only a handful of drugs have had such an impact on the history of medicine.

But cyclosporine is not perfect. It damages the kidneys and leaves the body more vulnerable to cancer. Doctors try to minimize these problems by using the lowest possible dose of the medication and supplementing it with other drugs that suppress the immune system, including steroids. Two experimental drugs, FK-506 and rapamycin, may be many times more powerful than cyclosporine but have yet to prove more effective in clinical trials.

If everybody had an identical twin from which to harvest organs, such drugs would be unnecessary. Failing that, doctors try, where possible, to find the closest approximation of a twin: a good genetic match. In a feat every bit as heroic as cracking the Enigma code during World War II, immunologists have determined just what makes for a good tissue match. Research dating from the 1960s shows that the immune system has developed its own set of molecular passwords, called human leukocyte antigens, that identify every nerve, every capillary, every organ as either friend or foe. If a cell displays the right HLA molecules on its surface, the T cells will leave it alone. If not, it gets zapped.

Six pairs of genes contain the code for the HLA proteins, half inherited from a person's mother and half from the father. Since each one of these genes may come in as many as 25 different varieties, there are countless different possible HLA combinations. The chance that two unrelated people will have the same HLA combination is less than 1 in 100,000. But the odds of a complete match between two siblings are about 1 in 4.

For patients in need of bone marrow transplants, such as Anissa Ayala, a good match is absolutely essential, and close relatives are frequently tapped. The reason: marrow recipients face a unique threat known as graft-vs.-host disease. In a Trojan Horse ploy, transplanted marrow can quickly turn against its new body. If the match is poor, the marrow, which manufactures many of the components of the immune system, will recognize its adopted home as foreign and mount a massive attack against virtually every tissue. This sort of rejection crisis is harder to control than the rejection of a transplanted heart or kidney, and is, in many cases, fatal.

The body is more accepting of other kinds of transplants. Tissue typing is not used to match heart, lung or liver transplants. One reason is that no one has yet found a way to preserve these organs long enough after removal to complete an HLA test. Generally, doctors simply check that donor and recipient blood types are compatible and then depend on lifelong drug therapy to prevent rejection. Eventually, surgeons confidently predict, more and more powerful drugs will allow them to ignore HLA matches for organ transplants altogether.

This seemingly cavalier attitude toward tissue typing concerns many immunologists, who worry about the side effects of suppressing the immune system for years or even decades. Patients seem to do better when the organs are well matched. Though less than 1 in 10 kidney recipients gets a fully compatible organ, at least one study shows that those who do are 20% more likely to survive five years than other recipients. But better matching will require the technology to store organs long enough for them to be flown to a person with the right tissue type.

Another critical need is a bigger pool of donors from which to draw matches. Over 2 million people die each year in the U.S., but only about 25,000 of them are suitable sources for organs. The principle requirements for this select group: good health and sudden death as in a traffic accident or stroke. Of those who are eligible, only one-sixth actually give up their organs. Though a 1988 federal policy requires hospitals to inform families of potential donors about making "a gift of life," physicians are often reluctant to approach grieving families about carving up their loved ones. Many people are repelled by the idea of parting with organs after death.

Blacks and Asians donate organs less often than whites, perhaps because they < are less comfortable with the medical establishment. Because it can be difficult to find a good match between races, this has led to a chronic shortage of organs for minorities. Congress has allocated $20 million over the next year to help address this shortfall. Some transplant experts have suggested giving tax breaks to the estates of people who agree in advance to donate their organs at their death.

In the meantime, the shortage of donors forces doctors to make wrenching decisions about who lives and who dies. Though medical considerations are paramount, subjective judgments often come into play. Can an uneducated patient handle the sometimes complex follow-up care required after surgery? Should a relative be approached and asked to give up a piece of himself? Should an alcoholic be granted a new liver? Such dilemmas can be far more complex than any challenge posed by the immune system.

With reporting by Barbara Dolan/Chicago and Andrew Purvis/New York.