The New York Times - July 24, 1983
Harold M. Schmeck Jr.

AIDS does not seem to be an old, hitherto unnoticed malady, but it is not unprecedented. It stands among a class of disorders, though it is clearly among the most deadly and widespread.

As with other immune deficiencies, the fatal effects of AIDS reflect weaknesses in the body's normal defenses, rather than the attack of a specific disease process. AIDS victims often die from overwhelming infection caused by microbes that would pose trivial problems to a person whose immune system is at full strength.

One of the presumed functions of a healthy immunological defense system is to maintain surveillance against the appearance of cancer cells and to eliminate those that arise. This self-defense appears to be compromised in AIDS patients, a number of whom have developed an otherwise rare, and potentially fatal cancer called Kaposi's sarcoma. Scientists have noted that other kinds of immune deficiencies also carry a heightened risk of some forms of cancer. For reasons not entirely clear, it is a selective risk likely to involve cancers of the blood and lymphatic system that are relatively uncommon in the general population.

Because the human immunological defense system is so complex and its effects so manifold, immune deficiency disorders comprise a broad spectrum of conditions varying in severity and cause. Most such disorders are rare; some are so mild as to pass virtually unnoticed by the patient, while others are so severe as to threaten life.

At the most serious extreme are youngsters whose disorders are hereditary and, so far, uncorrectable, such as 12-year-old David in Houston who has never felt a breeze against his skin or the touch of his mother's hand. He suffers from a rare genetic disorder called severe combined immunodeficiency, which involves weaknesses at many points of the immune system. Because he has virtually no defenses against disease, the boy (whose full name is being kept confidential) must remain isolated from the outside world. Since birth he has lived in a plastic tent almost as thoroughly sealed as a spaceship. When he emerges, he must wear the equivalent of a spacesuit. Without these artificial barriers he would soon die of infection.

Further along the spectrum are reversible immune deficiencies. Patients who are given transplanted organs, for example, receive regular doses of drugs that deliberately suppress specific aspects of the immune defenses. It is a necessary risk; without these drugs, a patient's immune mechanisms would identify the transplanted organ as foreign and attack and destroy it. When drug use is stopped, the immune defenses ordinarly regain their normal strength.

Several virus infections seem to depress the immune system, which rebounds when the infection ends. But it is also true that an inborn immune deficiency invites viral infections, making it sometimes unclear whether the viral infection is the cause or result of the immune deficiency. Cancer can present scientists with a similar chicken-egg dilemma: In the final analysis, they are often unsure whether the malignancy suppressed the immune system, or the immune deficiency set the stage for the malignant growth, or perhaps both processes were at work. There is no evidence, however, that the treatments used on the viruses or cancers suffered by AIDS victims have any effect on the inexorable progress of AIDS itself.

Immune deficiencies can result from severe malnutrition and from the effects of kidney disease. Doctors have frequently observed that the effectiveness of the body's immune defense system wanes with age. None of these acquired immune deficiencies is as profound as AIDS.

Among the pure and probably inborn forms of immunodeficiency, one of the most common and least severe is the selective lack of one type of disease fighting substance in the blood, an antibody called immunoglobulin A. The incidence of this deficiency is thought to range from 1 in 1,000 to 1 in 500 people of European ancestry, according to Dr. Max D. Cooper, director of the cellular immunobiology unit of the Tumor Institute at the University of Alabama in Birmingham. Its effects -more infections than normal, for example - are often so mild as to pass unremarked by victims.

Many immune deficiencies involve the suppression or short supply of one or more types of antibodies, proteins whose prime role is protecting the body against invading germs. The various classes of antibodies circulating in the blood are the major weapons of "humoral immunity" - the type of immunity produced by a vaccination or by a natural infection with a virus or bacterium.

Searching for Treatments

The design specifications for each antibody are laid down by immunologically active white blood cells called B lymphocytes, which originate in the bone marrow. In general, antibodies are made by B cell offspring called plasma cells. Dr. Cooper noted that acquired immune deficiencies, particularly among adults, usually involve failures of one or another part of the B cell system.

AIDS falls into another category of immune deficiency diseases involving defects in "cell-mediated immunity" - the kind of immunity that prompts the body's rejection of transplants. The main agents in this process are another type of white blood cell called T lymphocytes, or T cells, which also originate in the bone marrow, but which in their early development are processed in the thymus gland, near the throat. Whatever causes AIDS, Dr. Cooper said, seems to wipe out most of the T cells. No one, as yet, has found any way of restoring their functions in AIDS patients.

All manner of treatments have been tried against AIDS including bone marrow transplantation, which, medical experts hoped, would reconstitute a patient's defective immune defenses. None has produced a notable success.

One recent treatment strategy involves a white blood cell product, interleukin 2. Several weeks ago, researchers at the National Institutes of Health began preliminary experiments on four AIDS patients to determine if interleukin 2 is safe and effective, and at what levels - if any - it might benefit an AIDS victim's weakened immune system. They have already reported that in test-tube experiments using blood from AIDS patients, the naturally occurring substance seemed to restore the infection-fighting capacity.

AIDS was first thought to be limited to promiscuous homosexual men and to addicts who took drugs by injection. Recently, however, cases have been found among heterosexuals who are not drug-abusers, including people from Haiti and parts of Africa, hemophiliacs and at least a few other patients who seem to have acquired AIDS through transfusions of blood and blood products. The existence of this last group of victims has strengthened the conviction that something transmissible, probably a virus, plays a key causal role and has set many scientists on the culprit's trail. It is a complex process made more difficult by the AIDS victims' susceptibility to viral infections. The logical candidates must have a long latent period between invasion of the body and the first detectable effects. They also should exhibit a special tendency to attack T cells or their precursors.

Some experts believe a likely prospect is a new-found virus, HTLV for human T cell leukemia virus, which has been associated with certain cancers arising in the blood-forming system, notably among the Japanese. The lack of reported AIDS cases in Japan, however, might argue against that link. Other specialists think the menace may be a still undiscovered virus related to HTLV acting alone or in combination with contributing factors. "Only when the putative agent of AIDS is identified," Dr. Fauci said, "can we fully embark on appropriate steps to limit its scope."

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