Beyond the Heart

Just two months ago, when Dr. Christiaan Barnard remarked that he would not hesitate to remove a still-beating heart for transplantation if the donor had suffered indisputable "brain death," the suggestion still seemed shocking to many surgeons. Since then, heart transplants have become increasingly common and the criteria of brain death generally agreed upon. Thus, gathering last week in Manhattan, most of the world's transplant surgeons accepted the idea of a beating-heart transplant with Barnardian aplomb.

Concurring completely was Houston's Dr. Denton A. Cooley, who has seven recipients surviving. The only note of caution was sounded by Mississippi's Dr. James D. Hardy,*who said that it might take a while to persuade certain segments of the public that the procedure is morally permissible.

Lung Failures. With some 2,000 kidney, 30 liver and more than 40 heart grafts now logged in surgery's annals, the second international congress of the Transplantation Society turned its attention to two main problems: how to extend the variety of transplantable organs, and how to improve the survival chances of all grafts of whatever kind.

Most candidates for heart transplants have been ill so long that they have suffered deterioration of many other vital organs, notably the lungs. So, Stanford University's Dr. Norman E. Shumway Jr. suggested, it would be a good thing to transplant at least one lung, or a large part of it, along with a heart. Nine transplants of lungs, or lobes of lungs, have failed. The tenth, performed a fortnight ago by Dr. Arthur Beall of Dr. Michael DeBakey's team in Houston, was doing well last week.

Since the pancreas manufactures insulin essential for the utilization of sugar and other carbohydrates, the patients most likely to need a transplanted pancreas are victims of the severe juvenile form of diabetes. The pancreas, said Minneapolis' Dr. Richard C. Lillehei, is so inaccessible that it is the only major organ that is harder to get out of the donor than to put into the recipient. He has made three grafts of an entire pancreas, with the patient surviving 41 months in the most successful case. Be cause all three died of infection rather than rejection of the graft, Lillehei declared confidently: "We know enough to justify going ahead, and in a few years pancreas transplants may be as common as kidney transplants."

Transplantation of the cartilage that surrounds the bone in joints would offer hope to vast numbers of victims of arthritis and other joint diseases. And, said Glasgow's Dr. Thomas Gibson, there would be no rejection problem, because cartilage is bloodless. But cartilage by itself is not enough. In animals, joints have been reconstructed successfully with cartilage left adhering to a delicately sculptured layer of bone, though Gibson is not yet ready to try that approach in man.

When the transplant experts tackled the rejection problem, they quickly agreed that all early drugs designed to suppress the body's immune reaction to foreign protein were bad. Since they blocked off the production of disease-fighting antibodies indiscriminately, said London's Sir Peter Medawar, they left the transplant patient easy prey to infectious crises caused by the commonest microbes that healthy people carry around all the time.

All the most noted transplant teams have now turned to antilymphocyte serum or globulin (TIME July 26). It is made by injecting human white blood cells into animals (usually horses), which make antibody against them. When this antibody, extracted from the animal's serum, is injected into a transplant patient, it interferes with the ability of his own white cells to make antibody against his graft.

The trouble with ALG, as it is abbreviated, is that transplant patients apparently can never be weaned of it, and some cannot tolerate it for more than a few weeks or months. They develop severe allergic reactions to it. Besides, said Medawar, "ALG is conceptually an archaic substance. Injecting horse-serum derivatives into human beings violates our sense of the fitness of things." It was Medawar's work in the early 1950s, which explained why some skin grafts in mice are rejected and others not, that laid the foundation for all today's transplant surgery. And now the transplant researchers are returning to work with the lowly mouse and guinea pig, to find a more satisfactory answer to the problem of rejection.

Different Shapes. The target of all medications that suppress organ rejections is what the experts call "the transplant antigens," protein molecules that are too small to be seen even with the electron microscope. Apparently they sit on the outside of the body's cells, ready to trigger an antibody reaction and rejection phenomenon if the cells are transplanted, as part of a kidney or heart, into another person.

Worse, the antigens come in many different shapes and compositions even among individuals of the same species. Result: the chance that any two people (except identical twins) will have the same "antigenic constitution" is virtually nil. Transplanters have tried to get around that by matching donor organs with recipients whose antigen patterns seem fairly similar, but these resemblances are not close enough to exclude the rejection mechanism.

Detested Strep. Before this can be circumvented completely, the transplant antigens must be better understood both chemically and biologically. Then perhaps they can be manipulated so that a recipient will get an injection to switch off his rejection mechanism before he gets his transplant. The most encouraging news of progress toward this goal came from British investigators, who reported that some mouse antigens appear remarkably similar to man's and might therefore serve as a source of raw material. More surprisingly, New York University's Dr. Felix T. Rapaport reported that a similar antigen can be extracted from some of the common streptococci. These are the microbes that cause "strep throats," scarlet fever, rheumatic fever, and a severe form of kidney disease.

Rapaport would only say that his experimental results indicated a line for further research. But the implication for future treatment was clear, although the method by which the antigen would be treated or administered to protect a graft was not. If it happens that the detested streptococci are eventually "farmed" as a wholesale source of raw material for a transplant vaccine, that will be no more surprising than the transplant successes already achieved.

*Who performed the first transplant of a heart into a human patient in 1964, using a chimpanzee as the donor, and also the first lung transplant.

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