How We Die_ Reflections On Life's Final Chapter Part 6

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 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 h.o.m.os.e.xual men in New York City and California. One of the diseases was PCP, and the other was Kaposi's sarcoma (KS). 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 h.o.m.os.e.xual men in New York City and California. One of the diseases was PCP, and the other was Kaposi's sarcoma (KS). Pneumocystis carinii 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. 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 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: 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 a.s.sociations, 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 h.o.m.os.e.xual 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 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." 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 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 Inst.i.tutes 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 nonh.o.m.os.e.xual 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 hepat.i.tis 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 s.e.xual contact with one man, and these nine in turn to forty others who had been diagnosed in ten different cities. The finding established the s.e.xual 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 Inst.i.tute, 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.

It is no easy matter to explain or understand the mechanism by which the many opportunistic invaders lay waste the body of an adult or child with AIDS. Such a baffling array of problems is faced by the HIV-infected and their caregivers that one cannot but contemplate with a sense of awestruck grat.i.tude that so much has already been accomplished. When a doctor of my generation makes hospital rounds with an AIDS team of physicians and nurses, all he can do is figuratively gasp at how much these skilled clinicians know and what a large proportion of it has been learned in so short a time. Every patient on the unit carries a mult.i.tude of infections and sometimes one or two cancers; each is receiving four to ten or even more medications, without any certainty of predictable response or toxicity-Ishmael Garcia was on fourteen. Daily, and sometimes more often, new decisions must be made about everyone being treated (my hospital's relatively small AIDS area has forty beds, and they are always full).

As if the immensity of the clinical challenges were not enough, distraught families wait nearby for answers, and for consolation as well; there are reports for the staff to fill out, charts to review, tests to order, students to teach, conferences to attend, and an ever-burgeoning new literature to read and often to contribute to. And always, the most important charge is to care for those dreadfully stricken brothers and sisters of all of us, the sickest of whom are wasted, feverish, swollen, and anemic, their eyes seeking some rea.s.surance and the unspoken promise of relief from their torment, which too often will come only with death. No matter the perseverance and moral strength so many patients muster in the face of lethal certainty, the pitiless process by which they die is dispiriting anew with every reenactment.

IX.

The Life of a Virus and the Death of a Man THE DISCOVERIES THAT were being so rapidly made about the life cycle of the virus provided the background against which to seek points where it might be vulnerable to attack. Viewed simply, a virus is nothing more than a tiny particle of genetic material enclosed within the envelope of protein and fatty materials. Viruses are the smallest known living things, and they carry very little genetic information. Because they can't exist without the help of more complex structures, they must live within cells. Since a virus cannot reproduce (in the case of a virus, scientists prefer the term were being so rapidly made about the life cycle of the virus provided the background against which to seek points where it might be vulnerable to attack. Viewed simply, a virus is nothing more than a tiny particle of genetic material enclosed within the envelope of protein and fatty materials. Viruses are the smallest known living things, and they carry very little genetic information. Because they can't exist without the help of more complex structures, they must live within cells. Since a virus cannot reproduce (in the case of a virus, scientists prefer the term replicate replicate) on its own, like a bacterium, for example, it must get itself inside a cell and take control of the cell's genetic machinery by becoming integrated into it. HIV accomplishes this by a method that is the reverse of the ordinary process by which genetic information is transmitted; for that reason, it is called a retrovirus.

The genetic material of cells is composed of the strands of molecules called deoxyribonucleic acid (DNA); DNA is the repository of genetic information. Under ordinary conditions of reproduction, DNA is copied, or "transcribed," into other molecular strands called ribonucleic acid (RNA), which functions as a template to direct the production of the new cell's proteins. In a retrovirus, however, the genetic material is RNA. The retrovirus also carries an enzyme called reverse transcriptase, which, once the virus enters the host cell, transcribes the RNA into DNA, which is then translated in the usual proper sequence into proteins.

The series of events that takes place when a lymphocyte is infected by HIV is roughly as follows: The virus binds to structures called CD4 receptors on the membrane surrounding the cell; at those points, it sheds its envelope as it is taken into the cell, where its RNA is transcribed to DNA. The DNA then migrates into the lymphocyte's nucleus and inserts itself into the cell's own DNA. For the rest of that lymphocyte's lifetime and the lifetime of its progeny, it remains infected with the virus.

From this point on, every time an infected cell divides, the viral DNA is duplicated along with the cell's own genes and remains as a latent infection. For unknown reasons, at some point the viral DNA dictates the production of new viral RNA and viral proteins; in this way, new viruses are manufactured. They bud off from the lymphocyte's cell membrane, are set free, and then go on to infect more cells. If the process is fast enough, it can kill the lymphocyte that harbors it, which is destroyed as the virus particles burst out. Yet another method of lymphocyte destruction makes use of the fact that certain structures on the surface of the newly budded virus can bind to still-uninfected T cells, with the result that large numbers of the cells fuse together into clumps called syncytia. Because syncytia can no longer function in immunity, the clumping proves to be a very effective way of inactivating many lymphocytes at once.

As noted earlier, the cell attacked by HIV is the T lymphocyte, a white blood cell that has a major role in the body's immune response. Specifically, it is a subset of the T cells called CD4, or T4, lymphocytes (yet another name is the helper T cell) that is victimized. So dominant is the CD4 cell in the overall functioning of the immune system, it has been called its "quarterback."

HIV can thus affect CD4 cells in various ways. It can replicate in them, can lie dormant for long periods of time, and can also kill or inactivate them. It is the enormous depletion of CD4 lymphocytes gradually occurring over time that is the major factor in preventing a patient's immune system from mounting an effective defense against various forms of infections by bacteria, yeasts, fungi, and other microorganisms.

HIV attacks another type of white blood cell as well, called the monocyte, of which as many as 40 percent have the CD4 receptor in their membrane, and can thus take on the virus. Yet one more refuge is the macrophage (literally, the "big eater"), among whose functions is the ingestion and destruction of infectious cellular debris. Unlike the CD4 lymphocyte, neither the macrophage nor the monocyte is destroyed by HIV; they seem to be used as reservoirs and safe houses in which the microbe may lie dormant for long periods of time.

All of the foregoing is but a sketchy outline of the way in which the immune system is gradually laid waste by HIV. Although some have protested the use of military a.n.a.logies to portray the pathophysiology of disease, AIDS lends itself particularly well to such descriptive comparisons. The process, in fact, is not unlike a gradual buildup of forces, during the later stages of which a prolonged artillery and air bombardment destroys a country's defenses in preparation for a ma.s.sive land invasion carried out by a large coalition of belligerents, allied together to accomplish total annihilation. The army of microbes that kills the victim of AIDS after HIV has knocked off his CD4 cells includes many different kinds of divisions, and every one of them has its own target and its own lethal mechanism of attack. The most conservative epidemiologists predict that by the year 2000, there will be 20 to 40 million sero-positive people on our planet who are under siege or already invaded. Forty to eighty thousand Americans are becoming newly infected each year, and the same number die.

As far as has yet been determined, there are only three ways in which infection can take place: via s.e.xual contact, an exchange of blood (as with a contaminated needle, syringe, or blood products), or transmission from an infected mother to her child in the uterus, at the time of delivery, or even in the breast milk postnatally. HIV has been isolated in the laboratory from blood, s.e.m.e.n, v.a.g.i.n.al secretions, saliva, breast milk, tears, urine, and spinal fluid, but only blood, s.e.m.e.n and breast milk have ever been found to transmit the disease. Since 1985, the banked blood supply has been so carefully screened that the possibility of contracting HIV from transfusion is remote. In the United States and most developed nations, the overwhelming majority of those infected by the s.e.xual route are gay or bis.e.xual men, but in Africa and Haiti, the great predominance is among heteros.e.xuals. Although the number of heteros.e.xually transmitted cases remains low in the West, it is gradually rising, as is the number of infected infants. Approximately one-third of the Americans who become infected each year are intravenous drug abusers, and at least an equal number are gay men. The remainder, most of whom are black and Hispanic women, acquire the disease heteros.e.xually, and their seropositivity explains why two thousand babies are born infected each year.

AIDS is a disease of low contagion. HIV is a very fragile virus-it is not easy to become infected with it. Simple household bleach in a 1:10 dilution kills the virus efficiently, as do alcohol, hydrogen peroxide, and Lysol. Within twenty minutes of being poured on a tabletop and allowed to dry, virus-laden fluid is no longer infective. One need not fear any of the four bugbears (or bug-bearers) so often avoided by the germ-shy: insects, toilet seats, eating utensils, and kissing. Although there are certainly cases thought to have been transmitted by a single s.e.xual encounter, seropositivity usually requires a very high dose of virus or repeated episodes of contact. In the United States, the risk of seropositivity via a chance heteros.e.xual intimacy is real but very small. As rea.s.suring as it may be to contemplate the difficulties that must be overcome by the virus in order to infect us, the sense of security disappears in the face of the grim fact that once infected, we are likely to die. That consideration alone justifies the precautions urged on us by public health authorities.

The virus often shows its hand very soon after entering a new host. Within a month or less, rapid replication causes its concentration in the blood to become extremely high, and it stays that way for about two to four weeks. Although many newly infected people remain without symptoms, others during this period develop low-grade fevers, swollen glands, muscle aches, a rash, and sometimes central nervous system symptoms such as headaches. Because these symptoms are not specific and may also be accompanied by a general sense of fatigue, they are often erroneously attributed to flu or mononucleosis. As this brief syndrome is ending, the first antibodies against HIV begin to appear in the blood; a blood test will detect them, and the patient is henceforth sero-positive. Although the short symptomatic period ends, the virus continues to replicate.

Very likely, the brief mononucleosislike syndrome is caused by the first response of the body's immune system to the alarm set off by the ma.s.sive number of new virus particles that have by then been produced. The body is initially successful, and the number of virus-particles in the blood drops dramatically to low levels. What seems to have happened at this point is a retreat by the remaining microbes into CD4 lymphocytes, lymph nodes, bone marrow, the central nervous system, and spleen, where they lie dormant for years or replicate so slowly that the total low concentration in the blood remains stable. Actually, only 2 to 4 percent of the body's CD4 cells are in the blood. Most likely, those in the lymph nodes, spleen, and marrow are being gradually destroyed during the long dormant period, but the destruction is not reflected in the blood until the end of this time, when the CD4 counts, having remained constant till then, begin to drop dramatically, allowing the multiple secondary infections that characterize AIDS to ensue. At that point, the amount of virus in the blood rises again. The reason for the prolonged period of relative inactivity is unknown, but it does suggest that the body's immune system may be playing some role in mitigating the infection, at least that part of it which is restricted to the blood itself. When the immune system has sufficiently deteriorated, the amount of virus in the lymphocytes and free in the blood increases markedly.

This sequence of events may explain why most HIV-positive people develop swollen lymph glands in the neck and armpits during the early two-to-four-week period of symptoms, which do not recede at the end of it. When that period is over, patients continue to feel well for an average of three to five years or even ten years, by the end of which time examination of the blood will usually reveal that the number of CD4 cells has declined considerably, from a normal count of 800 to 1,200 per cubic millimeter to below 400. This means that 80 to 90 percent of these lymphocytes have been destroyed. On an average of eighteen months later, standard skin tests for allergy begin to show that the immune system is becoming impaired. The CD4 count continues to drop, but patients at this stage of disease still may not have begun to show evidence of clinical illness. In the meantime, the level of virus in the blood is rising and the swollen lymph nodes are slowly being destroyed.

When the CD4 cell count falls below 300, the majority of patients will develop the fungal infections of the tongue or oral cavity called thrush, which presents itself as white patches in those areas. Other infections that may begin to appear when the count is below 200 are herpes around the mouth, a.n.u.s, and genitals, as well as a severe v.a.g.i.n.al infection with the same fungus that caused the thrush. A characteristic finding is a condition called oral hairy leukoplakia (from the Greek leukos leukos-meaning "white," and plakoeis plakoeis-meaning "flat") a group of fuzzy-looking vertical white patches standing upright like corrugations along the lateral margins of the tongue. These lesions are due to a virus-induced thickening of the surface layers.

Within a year or two of this time, many patients are beginning to develop opportunistic infections in areas beyond the skin and body openings. By then, the CD4 cell count has usually fallen well below 200 and is dropping rapidly. The entire syndrome of immune deficiency begins to make itself evident as diseases appear that are caused by microbes ordinarily living in perfectly healthy people whose normal physiological defenses prevent trouble. The stage has now been reached at which serious pathology can be caused by any organism that requires intact immunity to combat it. Although people with AIDS are highly susceptible to well-known diseases such as tuberculosis and bacterial pneumonia, they are also set upon by a group of otherwise-unusual sicknesses due to a variety of parasites, fungi, yeasts, viruses, and even bacteria that physicians rarely encountered before the advent of HIV. For some of these organisms, there was no effective treatment until the late 1980s, when the efforts of university laboratories and the pharmaceutical industry were finally rewarded with the development of a group of drugs that have shown varying degrees of clinical success.

Every variety of microbial invader attacking the shattered defenses of the immune-compromised person with AIDS is equipped with its own unique a.s.sault weapons and directs its onslaughts against specific objectives. With little remaining CD4 cell resistance to bar their way, the individual divisions and regiments of opportunistic killers devastate the territory that comprises the patient's tissues. Sometimes by exhausting a person's energy and small supply of reserve firepower, and sometimes by knocking out a central structure like the brain, the heart, or the lungs, the swarming bits of infection will have their way. Though the pestilential offensives may be slowed or halted for a while by one or another of the newer pharmaceutical agents, they will always in time resume, if not in one form, then in another. A skirmish may be won here and there, or a battle prevented by timely use of prophylactic drugs, and some months of stability thereby achieved-but the eventual outcome of the struggle is preordained. The determined microbial aggressors will accept nothing less than the unconditional surrender that comes only with the death of their involuntary host.

Although AIDS patients may die of any of a number of pathological processes, a relatively small group of microbes is involved in the vast majority of deaths. Foremost among these is Pneumocystis carinii Pneumocystis carinii, the first one to be identified at the very outset of the worldwide pestilence. The figures are now declining because of prophylactic medication, but until fairly recently, more than 80 percent of patients had at least one experience of PCP, and many died during an episode, either from the respiratory insufficiency itself or from problems a.s.sociated with it. Depending on the severity of the onslaught, an individual episode used to kill between 10 and 50 percent of its victims before effective means had been found to combat it. It remains a significant factor in the death of nearly half of all AIDS sufferers, but the percentage continues to decrease.

The symptoms of PCP are essentially those experienced by Ishmael Garcia as his breathing became progressively compromised until he sought treatment. Occasionally, the organism may be found in other parts of the body than the lungs, and in autopsies of patients who die of this infection it is sometimes disseminated throughout virtually every major organ, most particularly the brain, heart, and kidneys.

Like patients with other types of pneumonia, those who die with PCP are asphyxiated by the infected lung's inability to be aerated. As wider areas of tissue become involved, more and more alveoli are destroyed, and a point is reached where arterial oxygen levels cannot be raised in spite of every available means of forcing the gas into the soggy and plugged tissues. The lack of oxygen and the buildup of carbon dioxide damage the brain and finally stop the heart. Sometimes destruction of tissue has been so severe that cavities have been created in the areas of disintegration, very much as in tuberculosis.

The lung is the organ most commonly a.s.saulted by AIDS. Virtually every one of the opportunists, as well as the tumors, looks to the lung as a target. On hospital rounds I have attended, tuberculosis, pus-forming bacteria, the herpeslike cytomegalic virus (CMV), and toxoplasmosis are among the most common problems discussed. Except for the last, they all seek out a home in the respiratory tissue. The incidence of tuberculosis in AIDS patients is some five hundred times what it is in the general population.

Toxoplasmosis is a disease that was at one time so rare that I had difficulty remembering just what it was when I first encountered it in an early AIDS patient. In little more than a decade, it has become a major belligerent in the HIV invasion, and I will never again have to search my memory about its details, so devastating are the things I have seen it do to defenseless people. The organism itself is a protozoan commonly found infecting birds, as well as cats and other small mammals. Most commonly, it is transmitted to humans in inadequately cooked meat or is ingested when food is contaminated with animal feces. Toxoplasma Toxoplasma lives harmlessly in anywhere from 20 to 70 percent of Americans, its frequency depending on the social and economic group tested. In an immunodeficient patient, however, it manifests itself by fever, pneumonia, enlargement of the liver or spleen, rash, meningitis, encephalitis, and sometimes involvement of the heart or other muscles. Its most common focus of attack in AIDS is the central nervous system, where it can cause fever, headache, neurological deficits, seizures, and mental changes ranging from confusion to deep coma. On CT scans, the infected areas of the brain sometimes so much resemble the lesions of lymphoma that they are differentiated only with difficulty. This was the diagnostic dilemma that caused so much uncertainty in the care of Ishmael Garcia. lives harmlessly in anywhere from 20 to 70 percent of Americans, its frequency depending on the social and economic group tested. In an immunodeficient patient, however, it manifests itself by fever, pneumonia, enlargement of the liver or spleen, rash, meningitis, encephalitis, and sometimes involvement of the heart or other muscles. Its most common focus of attack in AIDS is the central nervous system, where it can cause fever, headache, neurological deficits, seizures, and mental changes ranging from confusion to deep coma. On CT scans, the infected areas of the brain sometimes so much resemble the lesions of lymphoma that they are differentiated only with difficulty. This was the diagnostic dilemma that caused so much uncertainty in the care of Ishmael Garcia.

It is a rare AIDS patient whose nervous system escapes the pillaging of the disease. Even in the early period of HIV infection, some few people go through a transient period of neurological disabilities, which may sometimes appear even before AIDS itself has supervened; fortunately, this particularly distressing complication is far less common in early than in late stages of HIV disease, when it is more severe and called the AIDS dementia complex. Its eventual effects on cognition, motor function, and behavior can be devastating, but most frequently present initially as simple forgetfulness and loss of concentration. After a while, apathy and withdrawal become common symptoms, while some smaller number of patients complain of headaches or develop seizures. Should these findings not pa.s.s off when they occur early in HIV infection, they slowly worsen. In that case or in those far more common patients whose symptoms appear in the AIDS period, intellectual function often declines and difficulty with balance or muscular coordination appears. In the most advanced stages of the complex, patients are severely demented and show little response to their surroundings; they may be paraplegic and suffer tremors or occasional convulsions. These complications exist without any relationship to those processes caused by cerebral toxoplasmosis, lymphoma of the brain, or other opportunistic neurological disabilities such as meningitis caused by the yeastlike fungus cryptococcus. AIDS dementia complex is thought to be due to the virus itself, but its exact cause is unknown, and the cerebral atrophy seen on CT scan and biopsy is unrelated to any other factor. Of the many neurological problems a.s.sociated with AIDS, this one and toxoplasmosis are the most common. Fortunately, the beneficial effects of AZT have resulted in some decline in its frequency.

Two cousins of the tuberculosis germ share the distinction of being the bacteria most frequently disseminated throughout the body of people with AIDS. Mycobacterium avium Mycobacterium avium and and Mycobacterium intracellulare Mycobacterium intracellulare (MAI), jointly called the (MAI), jointly called the Mycobacterium avium Mycobacterium avium complex (MAC), are present in about half of AIDS patients when they die, having caused a wide variety of symptoms during life. MAI is now a more frequent cause of death than PCP. Fever, night sweats, weight loss, fatigue, diarrhea, anemia, pain, and jaundice are often attributable to these marauding twins. Although the complex rarely causes death on its own, its wasting effects are major contributors to the general debilitation and malnourishment that further weaken defenses against other invaders. complex (MAC), are present in about half of AIDS patients when they die, having caused a wide variety of symptoms during life. MAI is now a more frequent cause of death than PCP. Fever, night sweats, weight loss, fatigue, diarrhea, anemia, pain, and jaundice are often attributable to these marauding twins. Although the complex rarely causes death on its own, its wasting effects are major contributors to the general debilitation and malnourishment that further weaken defenses against other invaders.

These are just a few of the manifestations of AIDS. Lengthening the list serves only to name some of the other common problems that beset patients, but it cannot even approach the complete inventory of suffering: the blindness of the retinitis resulting from CMV or Toxoplasma Toxoplasma infection; the ma.s.sive diarrhea that can have any of five or six causes, or sometimes none that are identifiable; the meningitis or occasional pneumonia of cryptococcosis; the thrush or swallowing difficulties of candidiasis, and perhaps the slimy wet ooze of its skin lesions; the discomfort of herpes around the a.n.u.s; the fungal pneumonia or bloodstream seeding of histoplasma; the bacteria typical and atypical; the more than a score of creeping, crawling things with names like infection; the ma.s.sive diarrhea that can have any of five or six causes, or sometimes none that are identifiable; the meningitis or occasional pneumonia of cryptococcosis; the thrush or swallowing difficulties of candidiasis, and perhaps the slimy wet ooze of its skin lesions; the discomfort of herpes around the a.n.u.s; the fungal pneumonia or bloodstream seeding of histoplasma; the bacteria typical and atypical; the more than a score of creeping, crawling things with names like Aspergillus, Strongyloides, Cryptosporidium, Coccidioides, Nocardia Aspergillus, Strongyloides, Cryptosporidium, Coccidioides, Nocardia-their time has come and they act like looters after a natural disaster, which is exactly what they are. Though they pose no danger to people with normal immunity, every one of them is a bane to those with a depleted store of CD4 lymphocytes.

The heart, kidney, liver, pancreas, and gastrointestinal tract are affected in numerous ways by AIDS, as are the tissues less commonly thought of as specific organs, such as the skin, blood, and even the bones. Rashes, sinusitis, clotting abnormalities, pancreat.i.tis, nausea, vomiting, draining sores and noxious discharges, visual disturbances, pain, gastrointestinal ulceration and bleeding, arthritis, v.a.g.i.n.al infections, sore throat, osteomyelitis, infection of heart muscle and valves, kidney and liver abscesses-there are many others. Not enough that this disease depletes and dispirits, many patients feel humiliated by the details of their ordeal.

Kidney and liver function are often affected; there may be conduction or valvular abnormalities of the heart; the digestive tract betrays its owner in any number of ways; the adrenal and pituitary glands sometimes lose their power. When bacterial infection is no longer controllable, the familiar picture of sepsis supervenes. All the while, malnutrition and anemia are further weakening the body's ability to slow down the processes of destruction. The malnutrition is often aggravated by huge protein losses through the damaged kidneys, resulting from a rapidly progressive condition of uncertain cause, called HIV-a.s.sociated nephropathy (kidney disease). The nephropathy may go on to terminal uremia within three to four months of onset.

Even without direct involvement by infection, the heart in AIDS patients occasionally becomes enlarged and may fail, or it may develop a rhythm irregularity leading to sudden death. The liver, too, is susceptible to attack, not only because of AIDS itself but because so many patients are concomitantly infected with the hepat.i.tis B virus. CMV, MAI, tuberculosis, and several of the fungi have a predilection for the liver. The hapless organ is not only battered by the disease but by attempts to treat it, as drug toxicity affects its performance in many ways. The liver is found to be abnormal in some way or other in 85 percent of autopsied patients.

The entire length of the gastrointestinal tract is a vast twisting tunnel of opportunity for the various predators of AIDS. From the herpes and that wide a.s.sortment of ulcerations and infections around and in the mouth to the running sores and problems of continence at the a.n.u.s, the torment of the final months may be magnified by the involvement of so many structures that it inhibits eating, interferes with digestion, and produces uncontrollable watery diarrhea that not only is a source of constantly recurring distress but also makes it difficult to maintain proper hygiene of the raw areas around the a.n.u.s and r.e.c.t.u.m. To imagine extracting a sc.r.a.p of dignity from this kind of death is beyond the comprehension of most of us. And yet the indignity itself sometimes brings out moments of n.o.bility that overcome for a while the reality of anguish-arising from sources so deep, they can only be marveled at, for they surpa.s.s understanding.

An intact immune system is needed not only to resist infection but to inhibit growth of tumors as well. In the absence of an effective defense, certain kinds of malignant processes find a favorable environment in which to make their appearance. HIV has been particularly conducive to one form of cancer previously so rare that I had seen exactly one case, in an elderly Russian immigrant, since my graduation from medical school almost forty years ago. The incidence of this malignancy, Kaposi's sarcoma, has been magnified by a factor of well over a thousand-from 0.2 percent of the general population to more than 20 percent of Americans with AIDS. It is by far the most common tumor seen with this disease, and for as-yet-uncertain reasons, it afflicts a greater percentage of h.o.m.os.e.xual men (40 to 45 percent) than IV drug abusers (2 to 3 percent) or hemophiliacs (1 percent). These figures reflect only the people in whom the diagnosis is made during life. When autopsies are done, the frequency of KS triples or quadruples, making its presence somewhere in the bodies of gay men even more common.

In 1879, Moritz Kaposi, a professor of dermatology at the University of Vienna Medical School, described an ent.i.ty he called "multiple pigment sarcoma," consisting of a group of reddish brown or bluish red nodules that originates on the hands and feet and advances along the extremities until reaching the trunk and head. In time, stated his report, the lesions enlarge, ulcerate, and spread to the internal organs. "Fever, b.l.o.o.d.y diarrhea, haemoptysis [coughing of blood] and marasmus set in at this stage, and are followed by death. At the autopsy, similar nodules are found in large numbers in the lungs, liver, spleen, heart and intestinal tract."

Sarcoma is derived from the Greek is derived from the Greek sark sark, meaning "flesh," and oma oma, meaning "tumor." These growths originate in the same kinds of cells that give rise to connective tissue, muscle, and bone. In spite of Kaposi's admonition about his disease that "the prognosis is unfavorable... and fatal termination could not be prevented by extirpation, local or general, or the administration of a.r.s.enic [a favored treatment for cancer at the time]," physicians for a century underestimated the danger of this unusual malignancy.

Because the progression of KS was known to be slow, requiring "three to eight years or more," subsequent textbooks most commonly employed the word indolent indolent to describe its course. Thus was conveyed an erroneous message about the basically lethal nature of the malignancy, even though some authorities continued to write of its deadly manifestations, such as ma.s.sive intestinal bleeding. The word to describe its course. Thus was conveyed an erroneous message about the basically lethal nature of the malignancy, even though some authorities continued to write of its deadly manifestations, such as ma.s.sive intestinal bleeding. The word indolent indolent, in fact, appears in the original 1981 reports in British and American medical journals of outbreaks of Kaposi's sarcoma among gay men. So alarmed, however, were the authors of those reports by the sudden raging aggressiveness of a disease traditionally regarded as lethargic that the American article saw fit to remind its readers that the course had sometimes been known to be "fulminant, with extensive visceral involvement"; the paper published in England made the same case and gave it immediacy by pointing out that "half our patients were dead within 20 months of diagnosis." Clearly, this was a new form of KS, suddenly far more worrisome than even Kaposi had warned.

Decades before KS became a.s.sociated in physicians' minds with HIV infection, it was being recognized too often for coincidence as an accompaniment of various forms of the lymphatic cancer called lymphoma. Today, KS and lymphoma, not necessarily concomitant, are the two leading malignancies that prey on people with AIDS. Except for reasons of immunodeficiency, the relationship between the two has not yet been clarified. AIDS-related lymphoma, which most often involves the central nervous system, gastrointestinal tract, liver, and bone marrow, is no less aggressive than KS.

Unlike any other pestilence previously known to humankind, HIV does not limit its array of deadly options. There are only so many ways for a pancreatic cancer, for example, to kill; when a heart fails, or a kidney, very specific events take place; a deadly stroke takes aim at a single focus in the brain, starting its victim down a well-marked road to deterioration. Not so with HIV-it offers seemingly endless choices as one organ system and then another is set upon by a wide a.s.sortment of microbes and cancers. At autopsy, the only consistently predictable finding is a severe depletion of the lymphatic tissue that is part of the immune system. At the dissecting table, even members of the AIDS care team are often surprised by unexpected areas of involvement and the degree to which the tissues of their patient have been laid waste.

Respiratory failure, sepsis, destruction of brain tissue by tumor or infection-these are the more common immediate causes of death; some patients bleed into the brain, or the lung, or even the gastrointestinal tract, and some succ.u.mb to widespread tuberculosis or sarcoma; organs fail, tissues bleed, infection is everywhere. And invariably, there is malnutrition. No matter the magnitude of methods activated to fight it, starvation cannot be prevented. A care unit for terminal AIDS patients is peopled by emaciated, wraithlike men and women whose shrunken eyes look dully out from cavernous sockets, their faces often without expression, their bodies wizened with the shriveled frailty of prematurely advanced age. Most are beyond courage. The virus has robbed them of their youth, and it is about to rob them of the rest of their lives.

Autopsy pathologists distinguish between two separate designations for the cause of death: They refer to the proximate cause of death and the immediate cause of death (officially known by the acronyms PCOD and ICOD). For all of these young people, the PCOD will be AIDS-the specific ICOD seems hardly to matter. The quant.i.ty of suffering is the same for all, even though the quality varies. I talked about these matters not long ago with Dr. Peter Selwyn, one of the several Yale professors whose single-minded devotion to the care of AIDS patients has animated the efforts of many of the residents and students at our school. Despite his authoritative contributions to current understanding of HIV infection, he is a reticent man who expresses large concepts with few words. He said simply, "My patients die, I think, when their time comes." It seemed an incongruous statement, floating there in the company of the biomedical complexities still hanging in the air from our long discussion of molecular biology and bedside management. And yet it made sense. At the end, he said, so many things go wrong that there comes a time when the depleted forces of gasping life just seem to give out. Death comes with sepsis and organ failure and starvation and with the final departure of the spirit, all at once. Selwyn has seen it many times, and he knows.

I am a hundred miles away from the hospital. This is one of those unexpected afternoons in mid-autumn when everything under nature's cloudless blue sky has become exactly the way it should be, but almost never is. The summer just pa.s.sed was rainy, and perhaps for that reason the hills surrounding my friend's farm have taken on those heartbursting effusions of color that are almost more than my city-bred soul can comprehend or contain. Nature is being kind without knowing it, as nature can be cruel without knowing it. At such an instant, it seems as though no other day will ever attain the impossible splendor of this one. Already, I feel a nostalgia for today even as I live it. I am obsessed with an urge to memorize the image of every tree because I know its blazing flourish will begin to fade as soon as tomorrow, and never appear precisely like this again. When a thing is beautiful and good, it should be seen so clearly, and held so snugly, that no one will ever forget how it looks and how it feels.

I am sitting in the sunny kitchen of John Seidman's farmhouse, built a century ago in the midst of twenty acres of fertile land, near the town of Lomontville in upper New York State. In an upstairs bedroom, ten years ago, John's best friend, David Rounds, died in his arms at the end of a long and difficult illness. John and David were more than best friends; they shared a love that was meant to endure. But cancer determined otherwise. David was taken from John, and from those others of us who also loved him in our variety of ways, at a time when the future seemed secure and certain for both of them. David had won a Tony Award for Best Supporting Actor on Broadway only two years before, and John's stage career was showing increasing promise, In that farmhouse, grief was a long time in pa.s.sing before life resumed its proper rhythms.

I have known John Seidman for almost twenty years, and Sarah, my wife, shared a house with him and David long before that. He has been so close a friend to my family that my two youngest children call him Uncle. And yet there is a large part of his life that he and I have never discussed and about which I know almost nothing. On this splendorous day just before the fleeting grandeur of autumn disappears, the two of us are sitting together and we are talking about death-and AIDS.

Death has become much too familiar to John. It is as though the loss of David was the prelude to a succession of sorrows, during which friends, colleagues in the theater, and even mere acquaintances sickened, withered, and died. In the past decade, John has repeated with one after another the cycle of discovery of seropositivity, disease progression, watchful caregiving, descent to terminal illness, and death-again and again. In his early forties, he is one of tragedy's witnesses. There have been many others, and more than a few are now dead. The young men, and the few young women, who have companioned one another to the grave have been taken in the most productive years of their lives-what might have been and what should have been is lost. The vigor, the talent, and undoubtedly the genius of a generation are diminished, and so is our society.

We talk about John's friend Kent Griswold, who died in 1990 with toxoplasmosis and a trio of the common acronyms: CMV, MAI, and several bouts of PCP. Could there, I wanted to know, be any dignity in such a death? Can anything be salvaged of what once was, to bring a sense of himself to a man near his final hour, when he has been through so much? John thought a long time before answering, not because he had never considered the question before but because he wanted to be sure I would understand. The search for the elusive dignity, he said, may become irrelevant to the person who is dying-he has already carried out his struggle, and so often near the end, those around him can detect no recognizable conscious thought. Dignity is something, said John, that the survivors s.n.a.t.c.h-it is in their minds that it exists, if it exists at all: Those of us left behind search for dignity in order not to think ill of ourselves. We try to atone for our dying friend's inability to achieve a measure of dignity, perhaps by forcing it on him. It's our one possible victory over the awful process of this kind of death. With a disease like AIDS, we need to deal with the sadness that comes with seeing a beloved friend lose his particularity, his uniqueness. Toward the end, he becomes just like the last person you saw go through this. You feel the sadness of seeing someone lose his individuality and become a clinical model.

How much of the "good death" is for the person dying and how much for the person helping him? They're obviously related to one another, but the question is how. To me, the concept of a good death is generally not something that can be managed very well for the one who is dying. A "good death" is only a relative thing, and what it really means is decreasing the mess. There isn't much you can manage beyond trying to keep things neat and keep things painless-keeping someone from being alone. But leading up to those final moments, I think even the importance of one's not being alone is something we infer.

In retrospect, and in a way this sounds brutal, my own experience is that the only means we have of knowing if we have helped someone to a better death is whether or not we feel regret, or whether there is anything we feel sorry about or have left undone. If we can truly say that we missed no opportunity to do what we could, we've done the best job that's possible. But even that, as an absolute achievement, only has absolute value to oneself. What you're left with at the end is a situation that makes no one happy. The fact is that you've lost someone. There's no way to feel good about it.

The one bond we do need to believe is absolutely unbreakable in death is love. If love is what we feel we're providing at those mysterious moments leading up to death, that, I suppose, is what makes a death "good," if anything really can. But it's such a subjective quality.

During his terminal weeks in the hospital, Kent was never alone. Whatever help they could or could not provide him at the final hours, there is no question that the constant presence of his friends eased him beyond what might have been achieved by the nursing staff, no matter the attentiveness of their care. It is impossible to observe h.o.m.os.e.xual AIDS patients without being struck by the way a circle of friends, not necessarily all gay, will almost predictably come together as a man's family and a.s.sume responsibility for what a wife or parents might otherwise do. Dr. Alvin Novick, one of the earliest of America's AIDS activists and among the most highly respected, has called this phenomenon of joined commitment "the caregiving surround." It is a communal act of love, but it is also something more. John describes it: AIDS is happening to people, especially in the case of gay men, who have created families by a conscious affinity-we have chosen the people who will be our family. Our sense of responsibility to each other isn't based on the usual social forms. In many cases, the traditional family has rejected us. So the affinitive family is much more important.

A lot of the greater community really do feel that what is happening to us should should happen to us-it's some kind of visitation on us for our sinful and abnormal ways. And so it's in our mutual interest not to leave someone alone with that judgment of society. Those of us who suffer from some kind of self-loathing may find it very easy to think of AIDS as a form of punishment, but even those of us who don't are aware that much of society does see it that way. To neglect our friends who have to deal with the disease themselves is somehow to abandon them to the judgment of the straight world. happen to us-it's some kind of visitation on us for our sinful and abnormal ways. And so it's in our mutual interest not to leave someone alone with that judgment of society. Those of us who suffer from some kind of self-loathing may find it very easy to think of AIDS as a form of punishment, but even those of us who don't are aware that much of society does see it that way. To neglect our friends who have to deal with the disease themselves is somehow to abandon them to the judgment of the straight world.

Kent's last few weeks, John tells me, were like those of so many other people with AIDS, and of so many people with any of the diseases that slowly eat away at life's ebbing strength. Following the long months during which he had been forced to fight off one unantic.i.p.ated problem after another, he seemed to undergo a suspension of any understanding that an incremental reduction of control was accompanying each new complication. As he stopped trying to comprehend, he also stopped struggling against the successive a.s.saults, as though it seemed now less important to resist-there was no longer any point to it. Or perhaps the effort required to grasp the significance of events simply sapped too much of his limited energy.

The details of a latest onslaught lost their urgency. There are those who would call such exhausted indifference acceptance, but the very word implies a welcoming. Perhaps it is rather the recognition of defeat, the involuntary acknowledgment that the time has come to quit fighting. Most of the dying, not only of AIDS but of any prolonged sickness, seem unaware that they have reached this stage. For some few, mental faculties remain so intact that they are able to consciously decide, but much more often the decision is made for them by a lapse into a degree of lessened sensibility or even coma. This is the phase of dying in which William Osler and Lewis Thomas seldom saw aught but serenity. For most of us, it will come much too late to give consolation to those who watch at the bedside.

While Kent had been less sick, he had sometimes spoken of his concern about how much physical pain he would be able to withstand, how uncomfortable his last weeks might be. He expressed a wish to find that critical moment when he could knowingly make up his own mind whether to continue the struggle. No one around him could tell for sure whether that wish was granted.

An influential friend had somehow gotten Kent a commodious private room in the hospital, and in that large s.p.a.ce he appeared daily to become smaller. He seemed almost hard to find. In John's words, "He dwindled further and further beneath the sheets." Even when he was at his strongest, Kent needed help to get to the bathroom, but the rest of the time he was completely bedridden. Never a large man, he seemed now to be disappearing. As John describes Kent's withering, I think again of Thomas Browne watching his dying friend go through the same process 350 years earlier: "He came to be almost half himself and left a great part behind him which he carried not to the grave."

Because of Kent's toxoplasmosis, he was losing cognition to the point where he was unable to comprehend what was going on around him. CMV retinitis blinded first one eye and then the other. He had by then wasted to such a degree that it was impossible to read his face or decipher his expressions-was he smiling, or was it a grimace that twisted the corners of his silent mouth? John says it so well: "A form of communication is lost when someone is so diminished." The dying man's whole body had grown very dark, especially his face.

Early on, Kent had made it clear that no aggressive treatment was to be used once it became evident that it would be futile. Guided by that, his "caregiving surround" consulted with the doctors, and together they tried to make correct decisions as each succeeding necessity arose. Finally, there were no longer any decisions to make. It had become so clear-there was nothing further to be done. It was just as Peter Selwyn says-Kent's time had come.

Kent was less and less conscious of any sort of discomfort. No longer was it important that he receive medical help of any kind. "It became our mission just to keep him surrounded, just to keep him connected, at least as much as he was capable of sensing any connection. The most important thing was that we didn't want him to be alone." At the end, Kent just slipped away. John now comes to the final part of the story.

I wasn't in New York when he died-I was up here at the farm for a few days. I got off a bus at the Port Authority and called in