Authors: Sherwin B Nuland
How We Die (29 page)
There has never been a disease as devastating as AIDS. My basis for making that statement is less the explosive nature of its appearance and global spread than the appalling pathophysiology of the pestilence. Medical science has never before confronted a microbe that destroys the very cells of the immune system whose job it is to coordinate the body’s resistance to it; immunity against a swarming score of secondary invaders is defeated before it has had a chance to mount a defense.
Even the inception of AIDS seems to have been unique. There is now sufficient epidemiological evidence to speculate about the possible origins of the outbreak, and the pathways by which it has achieved its present oppressive hold. The virus is thought by some researchers to have been endemic in a different form among certain Central African primates in which it was not a pathogen and therefore caused no disease. Possibly, the blood of an infected animal may have come into contact with a skin or membrane wound of one or more inhabitants of a local village, who then gradually spread it to others in their immediate surroundings. Basing their work on mathematical models, the proponents of this theory estimate that the first primate-to-human transmission may have taken place as long as a hundred years ago. Because of the sparsity of interactions among communities, the disease spread slowly from its hypothetical village of origin. When cultural patterns began to change after the middle of the twentieth century and people traveled more and more from place to place and became more urbanized, the spread of infection rapidly accelerated. Once a large pool of infected people had come into existence, patterns of international travel carried the virus all over the world. AIDS is a jet-propelled pestilence.
Long before it made its presence manifest by the occurrence of so much as a single identifiable case of AIDS, the virus was being spread among thousands of unsuspecting people. The very first inkling of the new disease came in the form of two brief articles in the June and July 1981 issues of the
Morbidity and Mortality Weekly Report
issued by the Centers for Disease Control (CDC). The articles described the occurrence of two previously extremely rare diseases in a total of forty-one young homosexual men in New York City and California. One of the diseases was PCP, and the other was Kaposi’s sarcoma (KS).
Pneumocystis carinii
is not known to cause sickness in people whose immune system is intact. Virtually every one of the cases of PCP reported before this time had occurred in patients with immunity suppressed for the purposes of organ transplantation, or by chemotherapy or starvation, although there were also a few instances on record of congenital immune deficiency. The KS seen in these gay men was of a variety much more aggressive than had heretofore ever been encountered. Of the forty-one patients, those few whose blood was evaluated for T lymphocytes—one of the mainstays of the body’s immune system—were found to have conspicuously decreased numbers. Some as-yet-unknown factor had destroyed large numbers of these cells and thereby severely compromised these young men’s immunity.
Morbidity and Mortality Weekly Report
issued by the Centers for Disease Control (CDC). The articles described the occurrence of two previously extremely rare diseases in a total of forty-one young homosexual men in New York City and California. One of the diseases was PCP, and the other was Kaposi’s sarcoma (KS).
Pneumocystis carinii
is not known to cause sickness in people whose immune system is intact. Virtually every one of the cases of PCP reported before this time had occurred in patients with immunity suppressed for the purposes of organ transplantation, or by chemotherapy or starvation, although there were also a few instances on record of congenital immune deficiency. The KS seen in these gay men was of a variety much more aggressive than had heretofore ever been encountered. Of the forty-one patients, those few whose blood was evaluated for T lymphocytes—one of the mainstays of the body’s immune system—were found to have conspicuously decreased numbers. Some as-yet-unknown factor had destroyed large numbers of these cells and thereby severely compromised these young men’s immunity.
Within a few months, there were several more publications telling of similar cases of what was being given the name gay-related immunodeficiency syndrome, or GRID. At medical meetings, in letters, and over the telephone, infectious disease experts were telling one another about similar patients they were seeing. By December, a deceptively laconic statement in the editorial pages of the
New England Journal of Medicine
had outlined the dimensions of the problem and, in a sensitive and almost prescient way, laid out the framework of the research that needed to be done, as well as the social implications that would have to be addressed:
New England Journal of Medicine
had outlined the dimensions of the problem and, in a sensitive and almost prescient way, laid out the framework of the research that needed to be done, as well as the social implications that would have to be addressed:
This development poses a puzzle that must be solved. Its solution is likely to be interesting and important to many people. Scientists (and the merely curious) will ask, Why this group? What does this tell us about immunity and the genesis of tumors? Students of public health issues will want to put this outbreak into social perspective. Gay associations, which are often active and well informed on pertinent health issues, will want to take measures to educate and protect their members. Humanitarians will simply want to prevent unnecessary death and suffering.
Although the editorialist, Dr. David Durack of Duke University, could not have known it, some 100,000 people worldwide were already infected.
By this time, more than a dozen forms of microbes had been identified from the tissues of diseased young men, and most of them were ones that thrive only in conditions of severely compromised immunity. The part of the immune response affected had been found to be the one dependent on T lymphocytes, and this was supported by the great depletion in numbers of certain of those cells (T4, or CD4, cells) in the blood. Because the depressed immunity provides an opportunity for usually rather benign germs to cause serious trouble, the resultant diseases are called opportunistic infections. When Dr. Durack’s editorial appeared, it had already been recognized that “the death rate is fearfully high” and “the only patients . . . who were not homosexual were drug users.” The disease was renamed acquired immunodeficiency syndrome, or AIDS.
As noted earlier, the appearance of AIDS, as though from no-where, was a blow to those members of the public health establishment who had by the mid- to late 1970s convinced themselves that the threat of bacterial and viral disease had become a thing of the past. The present and future challenges to medical science, many were certain, would lie in the conquest of the chronic debilitating conditions such as cancer, heart disease, dementia, stroke, and arthritis. Today, barely a decade and a half later, medicine’s purported triumph over infectious disease has become an illusion, while the microbes themselves are winning unforeseen victories. The 1980s brought two new sources of fear—the emergence of drug-resistant strains of bacteria and the advent of AIDS. Both problems will be with us for a long time to come. Dr. Gerald Friedland, the international authority who directs the
AIDS
unit at Yale, expresses the situation in somber terms that foretell an unending menace: “AIDS is now with us for the duration of human history.”
AIDS
unit at Yale, expresses the situation in somber terms that foretell an unending menace: “AIDS is now with us for the duration of human history.”
The protests of some AIDS activists notwithstanding, the amount of information that has since then been gathered about the human immunodeficiency virus and the progress made in mounting a defense against its onslaughts are nothing less than an astonishment.
Astonishment
, in fact, is precisely the word used in describing the rapidity of progress by the time of the pandemic’s seventh year. In 1988, Lewis Thomas, among whose other outstanding accomplishments has been his role as a pioneer of immunology, wrote this:
Astonishment
, in fact, is precisely the word used in describing the rapidity of progress by the time of the pandemic’s seventh year. In 1988, Lewis Thomas, among whose other outstanding accomplishments has been his role as a pioneer of immunology, wrote this:
In a long lifetime of looking at biomedical research, I have never seen anything to touch the progress that has already been made in laboratories working on the AIDS virus. Considering that the disease was recognized only seven years ago, and that its agent, HIV, is one of the most complex and baffling organisms on earth, the achievement is an astonishment.
Thomas went on to point out that even at that relatively early time, scientists already knew “more about HIV’s structure, molecular composition, behavior and target cells than about those of any other virus in the world.”
Not only in the laboratory but in the realm of treatment as well, encouraging signs have appeared that patients are today living longer, their symptom-free periods are expanding, and the level of their comfort is improving. These changes are keeping pace with increased knowledge about routes of worldwide spread, public health measures, and the social and behavioral changes that will be necessary if we are to achieve optimum control over the pandemic.
Much of the progress has been made through the active collaboration of universities, government, and the pharmaceutical industry. Such a troika is a welcome phenomenon in American biomedicine, and its existence owes much to the forceful campaigns conducted by AIDS advocacy groups, at first almost exclusively those within the gay community. Patient pressure groups are a relatively new factor in the equation of biomedical research, but an increasingly powerful one. Due as much to the efforts of the AIDS lobby as to the demands of the doctors, approximately 10 percent of the $9 billion budget of the National Institutes of Health now goes to the study of HIV. The U.S. Food and Drug Administration has been kept under constant fire to relax the strict standards it has painstakingly developed in evaluating experimental drugs. In some ways, this has been to the good; conditional approval has been granted for therapeutic agents that have demonstrated sufficient effectiveness under laboratory conditions. The inherent danger of easing hard-won safeguards, however, must be borne in mind—even in times of plague.
Particularly impressive is the rapid series of early discoveries, beginning almost immediately upon the CDC alert. The fact that several cases of PCP in nonhomosexual IV drug abusers had been reported by the end of 1981 gave rise to the probability that the mode of spread of the new disease was similar to that of hepatitis B, a virus commonly found in that group. It was reasoned that the causative agent being sought must be a virus. This theory was given credence in 1982 by a CDC report that nine of the first group of nineteen patients in the Los Angeles area could be linked through sexual contact with one man, and these nine in turn to forty others who had been diagnosed in ten different cities. The finding established the sexual transmissibility and infectiousness of the disease with a degree of certainty beyond doubt.
By mid-1984, the human immunodeficiency virus had been isolated and demonstrated to be the causative agent of AIDS, and its methods of attacking the immune system were clarified. At the same time, the clinical ravages of the disease process had been characterized and a blood test developed. While this was being accomplished in the laboratory and clinic, studies by public health officials and epidemiologists had elucidated the general form and dimensions of the outbreak.
At first, there was considerable skepticism in the scientific community that any drug would ever be found with the capability of damaging the virus itself. Much of the concern grew out of what was becoming known about the characteristics of the microbe, especially the fact that it survives by integrating itself into the very genetic material (the DNA) of the lymphocytes it attacks. Not only that: HIV was found to have the ability to hide in various cells and tissues where it is not only protected but also difficult to find. Additionally, it fools the body’s antibody response by a remarkable bit of trickery: the outer envelope of a virus is made of protein and fatty materials, whereas a bacterium is surrounded primarily by carbohydrate. The body’s immune response is kicked off much more readily by protein than by carbohydrate. HIV, however, coats its protein envelope with carbohydrate, becoming, in a sense, a virus in bacterial clothing. This insidious masquerade succeeds in decreasing antibody production. As if all of this was not enough, HIV mutates extensively, allowing it to turn itself into a somewhat different strain of beast should the body’s antibody response or a new antiviral drug somehow manage to overcome the obstacles placed before it.
Given all of these challenges, plus the fact that HIV kills off the mainstay of the body’s defense by destroying the lymphocytes within which it lives, there was reason for discouragement. Almost in desperation, researchers began to carry out laboratory evaluations of a variety of drugs they thought might conceivably fight the evasive virus. In the face of the reality that HIV’s duplicity would prevent the early development of a vaccine to mobilize the body’s own immunity, scientists adopted the same approach to fighting AIDS that they had been using to combat bacterial infections: They began to search for pharmaceutical agents that function in the same way as antibiotics, by killing the infectious organism or preventing its reproduction without depending on the immune system as a first line of defense.
Some of the agents tested had been intended for other uses, found to have limited effectiveness, and been put back on the shelf. As more knowledge was gained of the specific characteristics of the virus (especially after HIV became available in a form that could be used in the laboratory, in 1984), it was possible to be more focused in the search for effective compounds. By the late spring of 1985, three hundred drugs had been tested at the National Cancer Institute, and fifteen of them were found to stop the reproduction of HIV in the test tube. The most promising of them was an agent first described as an anticancer drug in 1978, bearing the chemical designation of 3-azido, 3-deoxy-thymidine, or AZT (often called zidovudine). AZT was administered to the first patient on July 3, 1984, and large-scale clinical studies were begun at twelve medical centers in the United States. By September 1986, there was sufficient evidence to show that the drug could decrease the frequency of opportunistic infections and improve the quality of life of AIDS patients, at least until the virus mutates against it. It was the first effective therapy ever to have been found against the particular category of viruses in which HIV belongs, called retroviruses. Although the drug is very expensive and potentially toxic, it soon became the mainstay of treatment directed at HIV. The discovery of AZT’s effectiveness encouraged the search for other, similar agents. The first to be identified was dideoxyinosine (ddl, or didanosine), and work has continued.
The development of AZT is only one example of the furious efforts sometimes required to combat HIV at that early time. From the beginning, an amount of information has come forth that is sometimes staggering to nonspecialists.
There are ever-deeper insights into molecular biology, improved methods of surveillance and prevention, constant revision of statistical reporting, increased understanding of the pathology wreaked by opportunistic organisms, and, thankfully, new drugs against those infectious jackals and the viruses they follow after.
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