Circumventing Immunity

The main barrier to the transplantation of organs from one human being to another is the immune mechanism by which the body defends itself against invasion by foreign substances. The surgical techniques have been perfected for years, and in the case of kidneys at least, the supply of organs has been sufficient for a total of 1,200 transplants. But some 500 of these have failed, in nearly every case because the immune reaction led to rejection of the transplant. Now new ways are being explored to bypass the barrier; last week specialists in surgery and immunology from all over the U.S. met at Duke University to hear about them.

Cadavers Are Best. The ideal way to get around the rejection reaction is to find an organ donor with the same immunity pattern as the recipient. This happens with any certainty only in the case of identical twins. For patients not so fortunate as to have an identical twin, the conferees agreed, the best source for a donated kidney is a brother or sister, with the mother next. The one-year survival rate for kidneys from close relatives, reported Dr. Joseph E. Murray of Boston's Peter Bent Brigham Hospital, is now 70%. For the patients themselves, it is 80%. The difference is due to the fact that some patients survive the failure of an initial transplant with the help of the artificial kidney or a second transplant.

For kidneys removed from cadavers, the corresponding survival figures are 55% and 65%. Astonishingly, the chances of a successful transplant from an unrelated living donor are less than half as good as those for kidneys from unrelated cadavers. Just why, no one knows; perhaps a dying man's kidney loses some of its power to trigger the rejection mechanism.

In treating patients with transplants, doctors have been teetering on a precarious seesaw. They must use drugs enough to suppress the immune mechanism and spare the kidney, but not in such strong dosages as to let the patient die from any passing infection. The drugs used, mainly azathioprine (Imuran) and prednisone, are so highly potent that by themselves they can seriously weaken or help to kill a patient. A major factor in boosting the cure rate in the past two years, said Dr. Murray, has been a steady reduction in the dosage of azathioprine. The researchers gathered at Duke were seeking new and gentler ways of avoiding the rejection reaction by manipulating the immune mechanism itself. Among the most promising approaches currently being investigated:

. LYMPH DRAINAGE. Many of the powerful antibodies against foreign protein are carried by lymphocytes, white blood cells circulating principally in the lymphatic system. Dr. Murray reported on a method in which a plastic tube is inserted in the thoracic lymph duct just above the collarbone. The lymph drains out by gravity into a plastic bag. With good drainage, up to 32 billion cells are removed daily, for as long as four months. They are separated from the lymph fluid by centrifuge, and the fluid is reinfused into the patient through an arm vein. With a well-drained lymph system, said Dr. Murray, rejection crises are only half as common as formerly.

. ANTILYMPHOCYTE TREATMENT. One way to depress white-cell and antibody activity is to introduce antibody against the lymphocytes themselves. So thymus glands, spleens and lymph nodes are removed from human cadavers, and the extract is injected into horses. The horses' rejection mechanism goes to work and makes particles active against the human lymphocytes. The horses are later bled, antilymphocyte serum is extracted, and may be further refined to a globulin fraction. At the University of Colorado, a team headed by Dr. Thomas Starzl has performed 19 successful transplants since last June; given antilymphocyte globulin, the patients have got along well on sharply reduced doses of azathioprine and prednisone.

. ANTIGEN OVERLOADING. Though there are at least two major types of antibody represented by billions of particles, they can be either confused or exhausted if the invading particles of foreign antigen (antibody-triggering substances) are numerous enough. In the medical equivalent of a massive military diversion, doctors try to overload the immune mechanism temporarily by flooding it with antigen particles. By coincidence, an antigen sufficiently similar to the human type is in some streptococci. So these bacteria, usually rated as harmful, are being mass-produced in a program backed by the National Institute of Allergy and Infectious Diseases. The antigen, chemically removed from its microscopic bacterial source, is being distributed to investigating doctors.

For wide application, said Dr. Kenneth Sell, organ transplantation will have to depend on organ banks, similar to the tissue bank he now maintains for the U.S. Navy at Bethesda, Md. So far, no one has devised a way to freeze a whole organ and get it to work after thawing it out. But another visionary suggestion is for a "living bank," in which organs from human cadavers might be implanted in baboons and stored in the animals until needed for transplants.

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