How We Die_ Reflections On Life's Final Chapter Part 7

The origin of karkinos karkinos and and karkinoma karkinoma was based, as were so many Greek medical terms, on simple observation and touch. As Galen, the foremost interpreter and codifier of Greek medicine, put it in the second century was based, as were so many Greek medical terms, on simple observation and touch. As Galen, the foremost interpreter and codifier of Greek medicine, put it in the second century A.D A.D., the appearance of this creeping, infiltrating stony ma.s.s, ulcerated at its center, which he so often saw in the b.r.e.a.s.t.s of women, is "just like a crab's legs extending outward from every part of its body." And it is not only the legs that are digging farther and deeper into the flesh of its victim-the center, too, is eroding its way directly through her.

The likeness is to an insidious, groping parasite, attached by sharp-clawed tentacles to the decaying surface of its imperiled prey. The clawing extremities ceaselessly extend the periphery of their malign grip, while the loathsome core of the burrowing beast eats silently away at life, able to digest only what it has first decomposed. The process is noiseless; it has no recognizable instant of beginning and it ends only when the despoiler has consumed the final remnants of its host's vital forces.

Until after the middle of the nineteenth century, cancer was thought to do its killing by stealth. Its lurking force lay under the cover of hushed darkness, its first sting felt only when murderous infiltration had strangled too much normal tissue to restore the overwhelmed defenses of its host. The perpetrator regurgitated as malignant gangrene the life it had noiselessly chewed up.

We know better now, because we have come to recognize a different personality when our old enemy is seen through the microscope of contemporary science. Cancer, far from being a clandestine foe, is in fact berserk with the malicious exuberance of killing. The disease pursues a continuous, uninhibited, circ.u.mferential, barn-burning expedition of destructiveness, in which it heeds no rules, follows no commands, and explodes all resistance in a homicidal riot of devastation. Its cells behave like the members of a barbarian horde run amok-leaderless and undirected, but with a single-minded purpose: to plunder everything within reach. This is what medical scientists mean when they use the word autonomy autonomy. The form and rate of multiplication of the murderous cells violate every rule of decorum within the living animal whose vital nutrients nourish it only to be destroyed by this enlarging atrocity that has sprung newborn from its own protoplasm. In this sense, cancer is not a parasite. Galen was wrong to call it praeter naturam praeter naturam, "outside of nature." Its first cells are the b.a.s.t.a.r.d offspring of unsuspecting parents who ultimately reject them because they are ugly, deformed, and unruly. In the community of living tissues, the uncontrolled mob of misfits that is cancer behaves like a gang of perpetually wilding adolescents. They are the juvenile delinquents of cellular society.

Cancer is best viewed as a disease of altered maturation; it is the result of a multistage process of growth and development having gone awry. Under ordinary conditions, normal cells are constantly being replenished as they die, not only by the reproduction of their younger survivors but also by an actively reproducing group of progenitors called stem cells. Stem cells are very immature forms with enormous potential to create new tissue. In order for the progeny of the stem cells to progress to normal maturity, they must pa.s.s through a series of steps. As they get closer to full maturity, they lose their ability to proliferate rapidly in proportion to the increase in their ability to perform the functions for which they are intended as grown-ups. A fully mature cell of the intestinal lining, for example, absorbs nutriments from the cavity of the gut a lot more efficiently than it reproduces; a fully mature thyroid cell is at its best when it secretes hormone, but it is much less inclined to reproduce than it was while younger. The a.n.a.logy with the social behavior of a whole organism, like us, is inescapable.

A tumor cell is one that has somewhere along the way been stopped in its capacity to differentiate differentiate, which is the term used by scientists for the process by which cells go through the steps that enable them to reach healthy adulthood. The clump of immature abnormal cells that results from the blocking of differentiation is called a neoplasm, derived from the Greek word for a new growth or formation. In modern times, the word neoplasm is used synonymously with tumor tumor. Those tumors whose cells have been blocked closest to the attainment of the mature state are the least dangerous and are therefore called benign. A benign tumor has retained relatively little of its potential for uncontrolled reproduction-it is well differentiated; under the microscope, it looks a lot like the adult it was close to becoming. It grows slowly, does not invade surrounding tissues or travel to other parts of the body, is often surrounded by a distinct fibrous capsule, and almost never has the capacity to kill its host.

A malignant neoplasm-what we call cancer-is a different creature entirely. Some influence or combination of influences, whether genetic, environmental, or otherwise, has acted as the triggering mechanism to interfere so early in the pathway of maturation that the progress of the cells has been stopped at a stage when they still have an infinite capacity to reproduce. Normal stem cells keep trying to produce normal offspring, but their development continues to be arrested. They do not attain a sufficient level of adulthood to do the work they were meant for or to look more than just a little like the grown-up forms they were intended to be. Cancer cells are fixed at an age where they are still too young to have learned the rules of the society in which they live. As with so many immature individuals of all living kinds, everything they do is excessive and uncoordinated with the needs or constraints of their neighbors.

Being not completely grown-up, a cancer cell does not engage in some of the more complicated metabolic activities of mature nonmalignant tissue. A cancer cell of the intestine, for example, doesn't help out in digestion as its adult counterpart does; a cancer cell of the lung is uninvolved in the process of respiration; the same is true of almost all other malignancies. Malignant cells concentrate their energies on reproduction rather than in partaking in the missions a tissue must carry out in order for the life of the organism to go on. The b.a.s.t.a.r.d offspring of their hyperactive (albeit as.e.xual) "fornicating" are without the resources to do anything but cause trouble and burden the hardworking community around them. Like their progenitors, they are reproductive but not productive. As individuals, they victimize a sedate, conforming society.

Cancer cells do not even have the decency to die when they should. All nature recognizes that death is the final step in the process of normal maturation. Malignant cells don't reach that point-their longevity is not finite. What is true of Dr. Hayflick's fibroblasts does not apply to the cellular population of a malignant growth. Cancer cells cultivated in the laboratory exhibit an unlimited capacity to grow and generate new tumors. In the words of my research colleagues, they are "immortalized." The combination of delayed death and uncontrolled birth are malignancy's greatest violations of the natural order of things. These two factors in combination are the main reasons a cancer, unlike normal tissue, continues to enlarge throughout its lifetime.

Knowing no rules, cancer is amoral. Knowing no purpose other than to destroy life, cancer is immoral. A cl.u.s.ter of malignant cells is a disorganized autonomous mob of maladjusted adolescents, raging against the society from which it sprang. It is a street gang intent on mayhem. If we cannot help its members grow up, anything we can do to arrest them, remove them from our midst, or induce their demise-anything that accomplishes one of those aims-is praiseworthy.

There comes a point at which home turf is not enough-offshoots of the gang take wing, invade other communities, and, emboldened by their unresisted depredations, wreak havoc on the entire commonwealth of the body. But in the end, there is no victory for cancer. When it kills its victim, it kills itself. A cancer is born with a death wish.

Cancer is, in every possible sense, a nonconformist. But, unlike some nonconformist individuals about whom there is much to admire, the nonconforming malignant cell has not a single redeeming feature. It does everything it can not only to disa.s.sociate itself from but even to destroy the community of cells that has given it life. As though to make certain that it is not confused with the conformist adult members of its original family, the cancer cell retains an immature and different appearance and even shape. This characteristic of malignant growth is called anaplasia, from the Greek term meaning "without form." The anaplastic cell gives birth to anaplastic offspring.

But try as it may, only an unusual cancer is composed of cells that have changed their appearance completely enough to become unrecognizable as members of their own original tribe. Except in extreme cases, a careful look down the barrel of a microscope at a bit of the diseased tissue will suffice to reveal its ancestral lineage. Thus, a bowel cancer can be identified as what it is because it still has some characteristic features that betray its intestinal origin. Even far away from home, as when the bloodstream has carried its cells to the liver, the cancer's face, almost no matter the degree of anaplasia, will usually give it away. Even cancer, that remorseless renegade that ran away to join the biological equivalent of Murder, Inc., retains some dimly recognizable traits of its old family and its old obligations.

The twin characteristics of autonomy and anaplasia define the modern understanding of cancer. Whether they are to be thought of as "ugly, deformed, and unruly" or more academically as "anaplastic" and "autonomous," the cells of a cancer are wicked in ways far beyond what is implied by the scientific connotation of the word malignant. Malevolent malignant. Malevolent, in fact, says it better, because it bears the implication of an element of ill will.

The deformity and ugliness of the individual cancer cell are most manifest in the irregularities of its distorted shape. Whereas the appearance of a normal cell in normal tissue differs hardly at all from that of its normal neighbors, the forms and dimensions of the individuals in a cancer's cellular population are usually neither uniform nor orderly. They may bulge, flatten, elongate, round themselves out, or in some other way demonstrate that each is created as though with a mind of its own-it is an independent agent. Cancer is a state in which a breakdown has occurred in the communication and mutual interdependence between cells. That sequence of events noted above has taken place, in which the genetic characteristics of the malignant cell become altered, and everything else about the disease follows from that fact. Some of the environmental, lifestyle, and other causes of the alterations are known, some are being studied, and some are no doubt still unsuspected.

Though chaotic in appearance and inconsistent in size, the community of malignant cells is not necessarily always anarchic. In a few forms of cancer, in fact, all individuals are found to choose a specific uniform shape that suits a shared element in their willfulness. Such malignancies exist as though to demonstrate an obstinate refusal to conform to the accustomed disharmony expected of them; their cells reproduce myriads of virtually identical selves, like so many millions upon millions of little poisonous apples, boringly similar to one another but quite different from their tissue of origin. Even the predictability of malignancy's unpredictability is unpredictable.

The central structure of the cancer cell, its nucleus, is larger and more prominent than that of mature relatives and is often as misshapen as the cell itself. Its dominance over the protoplasm surrounding it is intensified by the enhanced avidity with which it takes up standard laboratory stains, a characteristic that gives it a darkened, ominous look. The evil-eye nucleus reveals its disordered independence in yet another way: Instead of dividing neatly into two symmetrical halves during the process of reproduction known as mitosis, the chromosomes (the components of the nucleus that carry the DNA) align themselves in bizarre patterns, attempting with varying degrees of success to multiply, figuratively head over heels, without any element of precision or accountability. The rate of mitosis of some cancers is so rapid that a quick look through the microscope will catch many times the number of cells in the act of trying to reproduce as are found in mature normal tissue, and every one of them seems to be doing it in its own haphazard way. Small wonder that the surviving offspring are ill-suited to their surroundings in the ordered, consistent tissue of the organs of which they were originally meant to be a part. So pugnaciously "other" are the new ma.s.ses of cells, in fact, that they not only invade but also push their law-abiding grown-up neighbors out of the way as they infiltrate and preempt surrounding territory.

In a word, cancer is asocial. Having escaped the constraints that govern nonmalignant cells, the newly formed tissues pursue uncontrolled and domineering relations.h.i.+ps with their host organs and cannot be made to restrict their encroaching margins to the foci that gave them birth. Unrestrained and patternless growth enables a cancer to force its way into nearby vital structures to engulf them, prevent their functioning, and choke off their vitality. By this means, and by destroying the organs from whose stem cells they are made, the ma.s.ses of cancer cells kill the gradually sickening person after feasting on the nutrients that were to have sustained him.

Although it begins as a microscopic phenomenon, the process of malignant growth, once properly established, inevitably continues until it can be seen with the naked eye or felt with the exploring hand. For a while, the growing ma.s.s may remain too small or confined to produce symptoms, but in time, the cancer's victim will sense that something untoward is happening to him. By that point, the malignancy may have grown so large that it is beyond cure. Particularly in certain solid organs, a cancer may reach considerable size before it makes its host aware of its presence. It was for this reason, of course, that the disease achieved its legendary reputation as a noiseless killer.

A kidney, for example, may be found to harbor a perfectly huge growth when it first reveals its advanced state of disease by spilling visible blood into the urine or causing a dull ache in the flank. If an operation is done at that point, the surgeon's efforts will be defeated by the wide extent of involvement of surrounding tissues. The otherwise-symmetrical brown smoothness of the organ will be found to have been eaten away in one large area by an ugly, lobulated protrusion of coa.r.s.e gray hardness that has forced its way through to the surface, invaded the adjacent fat, and drawn all nearby tissues into it, the misbegotten whole forming one great puckered grotesquerie of bunched-up aggression. Of all the diseases they treat, cancer is the one that surgeons have given the specific designation of "The Enemy."

The visible structure and invasiveness of a cancer are only two of its many forms of unruliness. One of the most duplicitous of malignancy's misbehaviors is the way in which it seems to elude the defenses ordinarily mounted by the body against tissue it perceives as not belonging to it. Theoretically at least, cells that have become cancerous should be detectable as foreign or "other" by an intact immune system and then killed, much as is a virus. This actually does happen to an extent; some researchers believe that our tissues are continually making cancers, which are just as continually being destroyed by this kind of mechanism. Clinical malignancies would then develop in those rare instances when the surveillance system fails. An example of support for such a thesis is to be found in the prevalence in people with AIDS of tumors such as lymphoma and Kaposi's sarcoma. Overall, the incidence of malignancies in immunocompromised individuals is some two hundred times that found in the general population, and for Kaposi's the figure is more than twice what it is for the average tumor. One of the most promising fields of today's biomedical research is the study of tumor immunity with a view toward strengthening the body's responses to the antigens that cancers may produce. Although there have been some promising results, the target cells continue, for the most part, to outwit the scientists.

Normal cells require a complex mixture of nutrients and growth factors in order to continue functioning and retain viability. Throughout all tissues of the body, they are bathed in a life-giving nutrient soup called extracellular fluid, which is constantly being restored and cleansed by exchanging substances with circulating blood. The blood's plasma, in fact, amounts to one-fifth of the body's extracellular fluid; most of the other four-fifths lies between the cells, and is called interst.i.tial. The interst.i.tial fluid accounts for approximately 15 percent of body weight; if you weigh 150 pounds, your tissues are soaking in 22 pints of the salty stuff. The nineteenth-century French physiologist Claude Bernard introduced the term milieu interieur milieu interieur to name and describe the function of this internal environment in which cells live within us. It is as though the earliest groups of prehistoric cells, when they first began to form complex organisms in the marine depths from which they drew sustenance, brought some of the sea into and around themselves so that they might continue to be nourished by it. Among the unique features of malignant tissues is their reduced dependence on the nutritional and growth factors in the extracellular fluid. Their lessened need for sustenance from the surroundings enables them to grow and invade even those areas beyond optimal supply lines. to name and describe the function of this internal environment in which cells live within us. It is as though the earliest groups of prehistoric cells, when they first began to form complex organisms in the marine depths from which they drew sustenance, brought some of the sea into and around themselves so that they might continue to be nourished by it. Among the unique features of malignant tissues is their reduced dependence on the nutritional and growth factors in the extracellular fluid. Their lessened need for sustenance from the surroundings enables them to grow and invade even those areas beyond optimal supply lines.

No matter that each cellular unit can get along with less, the helter-skelter increase in population soon acc.u.mulates so many malignant cells that the requirements of the aggregate tend to outstrip whatever supplies are available. As a result, a total tumor ma.s.s will often develop an increased demand for nutrition, even though each individual within it may require less than a normal amount of it. If growth is rapid enough, blood supply after a time will be insufficient to restore used-up nutrients, especially because new vessels usually do not appear rapidly enough to keep pace with the needs of the whole expanding tumor.

The result is that a portion of an enlarging tumor may die, literally of malnutrition and oxygen lack. It is for this reason that cancers tend to ulcerate and bleed, sometimes producing thick, slimy deposits of necrotic tissue (from the Greek nekrosis nekrosis, meaning "becoming dead") within their centers or at the periphery. Until mastectomy became a common operation less than a hundred years ago, the most dreaded complication of breast malignancy was not death but the fetid running sores it produced as a hapless woman's chest wall was digested away. This is precisely why the ancients referred to karkinoma karkinoma as the "stinking death." as the "stinking death."

In the late eighteenth century, Giovanni Morgagni, the author of a landmark text of pathological anatomy, said of the cancer he saw in his patients and at their autopsies that it was "a very filthy disease." Even in relatively recent times, when much more was known, malignant tumors continued to be viewed as repugnant sources of self-loathing and decay, a humiliating abomination to be concealed behind euphemisms and lies. Many are the stories of women with breast cancer who withdrew from friends, secluded themselves at home, and lived their final months as recluses, sometimes even from their own families. As recently as the period of my training, just over thirty years ago, I saw a few such women who had finally been prevailed upon to come to the clinic because their situations had become intolerable. Of the several reasons we still hesitate to utter the word cancer cancer in the presence of a patient or family a.s.saulted by it, the residual heritage of its odious connections is the one most difficult for our generation to expunge. in the presence of a patient or family a.s.saulted by it, the residual heritage of its odious connections is the one most difficult for our generation to expunge.

Not enough that a rapidly growing cancer may so infiltrate a solid organ like the liver or kidney that insufficient tissue remains to perform the organ's functions effectively; not enough that it may obstruct a hollow structure like the intestinal tract and make adequate nourishment impossible; not enough that even a small ma.s.s of it can destroy a vital center without which life functions cannot go on, as some brain tumors do; not enough that it erodes small blood vessels or ulcerates sufficiently to result gradually in severe anemia, as it often does in the stomach or colon; not enough that its very bulk sometimes interferes with the drainage of bacteria-laden effluents and induces pneumonia and respiratory insufficiency, which are common causes of death in lung cancer; not enough that a malignancy has several ways by which it can starve its host into malnutrition-a cancer has still other ways to kill. Those just mentioned refer, after all, only to potentially lethal consequences of encroachment by the primary tumor itself, without its ever having left the organ where it first arose. These are the kinds of damage cancer does in its own neighborhood. But it has an additional way of killing that takes it out of the category of localized disease and permits it to attack a wide a.s.sortment of tissues far from its origin. That mechanism has been given the name metastasis metastasis.

Meta is a Greek preposition meaning "beyond" or "away from," and is a Greek preposition meaning "beyond" or "away from," and stasis stasis connotes "position" or "placing." Introduced as early as the Hippocratic writings to indicate a change away from one form of fever to another, connotes "position" or "placing." Introduced as early as the Hippocratic writings to indicate a change away from one form of fever to another, metastasis metastasis later came to be applied specifically to migration of bits of tumor. In modern times, this one word, later came to be applied specifically to migration of bits of tumor. In modern times, this one word, metastasis metastasis, has come to articulate the defining feature of malignancy-cancer is a neoplasm that has the potential to go beyond its home and travel to some other place. A metastasis is, in effect, a transplant of a sample of the primary tumor to another structure or even a distant part of the body.

Cancer's ability to metastasize is both its hallmark and its most menacing characteristic. If a malignant tumor did not have the ability to travel, surgeons would be able to cure all but those that involve vital structures, which cannot be removed without compromising life. In order to travel, the tumor must erode through the wall of a blood vessel or lymph channel, and then some of its cells must become detached and pa.s.s into the flowing stream. Either individually or clumped into an embolus, the cells are then carried to some other tissue, where they implant and grow. Determined by the route of blood or lymph flow as well as other still-unclear factors, various cancers have a predilection to be deposited in certain specific organs. For example, a breast cancer is most likely to metastasize to bone marrow, lungs, liver, and, of course, the lymph nodes in the armpit, or axilla. A cancer of the prostate commonly travels to bone. Bones, in fact, along with the liver and kidney, are the most common sites for metastatic deposits, regardless of the malignancy's organ of origin.

In order to take root in a distant location, tumor cells need to be hardy enough to resist destruction while on their journey. The simple mechanical dangers of traveling through the jolting circulation complicate the possibility of being killed by the host's immune system during the course of the pa.s.sage. If they survive the voyage, the cells must then establish a new home and be provided a reliable source of nutrition. This means a priori a priori that the transplanted bit of cancer cannot create a viable colony on the newly reached distant sh.o.r.e unless it is capable of stimulating the growth of tiny new blood vessels to supply its needs. that the transplanted bit of cancer cannot create a viable colony on the newly reached distant sh.o.r.e unless it is capable of stimulating the growth of tiny new blood vessels to supply its needs.

So difficult is it to satisfy all of these requirements that very few of the migrating cells ever do manage to colonize some far-flung site. When tumor cells are experimentally injected into mice, only one-tenth of 1 percent survive beyond twenty-four hours; it is estimated that only one of each 100,000 cells entering the bloodstream lives to reach another organ, and a far smaller proportion successfully implant themselves. Were it not for obstacles such as these, ma.s.sive numbers of metastases would appear as soon as a cancer becomes sufficiently large to shed many cells into the circulation.

By the twin forces of local invasion and distant metastasis, a cancer gradually interferes with the functioning of the various tissues of the body. Tubular organs are obstructed, metabolic processes are inhibited, blood vessels are eroded sufficiently to cause minor and sometimes major bleeding, vital centers are destroyed, and delicate biochemical balances are deranged. In time, a point is reached at which life can no longer be sustained.

In addition, there are less direct ways for cancer to take its toll on those in whom its growth is unchecked, and they are usually the result of the debilitation, poor nutrition, and susceptibility to infection that come with the malignant process. Nutritional depletion is so common that a term has been devised to designate its effects: cancer cachexia cancer cachexia. Cachexia is derived from two Greek words meaning "bad condition," which is exactly the situation in which advanced cancer patients find themselves. It is characterized by weakness, poor appet.i.te, alterations in metabolism, and wasting of muscle and other tissues.

Actually, cancer cachexia is sometimes present even in people whose disease is still localized and relatively small, so it is clear that factors account for it other than a tumor's gobbling up of its host's resources. Though a tumor is capable of depriving its host of some essential nutrients, the concept of parasitizing may be, in fact, a simplistic way of looking at far more complicated causes of its ability to deplete resources. Changes in taste perception, for example, and local tumor effects such as obstruction and swallowing problems sometimes contribute to inadequate intake, as do chemotherapy and X-ray treatment. Numerous studies of people with malignancies reveal various kinds of abnormalities in the utilization of carbohydrates, fats, and proteins, the causes of which are uncertain. Some tumors even seem capable of increasing a patient's expenditure of energy, thereby contributing to the inability to maintain weight. To add to the problem, certain malignancies and even some of the host's own white blood cells (monocytes) have been shown to release a substance appropriately given the name cachectin, which decreases appet.i.te by direct action on the brain's feeding center. Cachectin is not the only such agent. It is likely that tumors of all sorts are capable of secreting various hormonelike substances which produce generalized effects on nutrition, immunity, and other vital functions that until recently were attributed to the parasitizing effects of the growth itself.

Malnutrition causes problems far beyond weight loss and exhaustion. The healthy body adapts to ordinary starvation by using fats as its main energy source, but this process is not effective in cancer, with the result that protein must be utilized. Not only does this and the lessened food intake cause muscle wasting; the decreased protein levels contribute to the dysfunction of organs and enzyme systems, and may significantly affect the immune response. There is evidence that one of the substances released by tumor cells further depresses immunity. Although this may, at least theoretically, enhance cancer growth, that untoward effect seems much less important than the fact that depressed immunocompetence, especially when magnified by chemotherapy and radiation, increases susceptibility to infection.

Pneumonia and abscesses, along with urinary and other infections, are frequently the immediate causes of death of cancer patients, and sepsis is their common terminal event. The profound weakness of severe cachexia does not permit effective coughing and respiration, increasing the chances of pneumonia and the inhalation of vomitus. The final hours are sometimes accompanied by those deep, gurgling respirations that are one of the forms of the death rattle, quite distinct from the agonal bark of a James McCarty.

Near the end, a decreased volume of circulating blood and extracellular fluid not infrequently leads to a gradual decrease in blood pressure. Even if this does not proceed to shock, it may cause organs such as the liver or kidney to fail because of chronic lack of sufficient nutrients and oxygen, although they are not directly involved with tumor. Since many people with cancer are in an older age group, the various forms of depletion often induce stroke, myocardial infarction, or heart failure. Of course, the presence of a generalized disease of metabolism, like diabetes, complicates the problems enormously.

Thus far, only those cancers have been mentioned that begin as tumors originally localized to a specific organ or tissue. A smaller group of malignant diseases have a more generalized distribution from the very beginning, or arise in multiple sites of a particular kind of tissue, specifically the blood and lymph systems. Leukemia, for example, is a cancer of the tissues responsible for the production of white blood cells, and lymphoma is a malignancy of lymph glands and similar structures. Patients with leukemia and lymphoma are particularly p.r.o.ne to infection, and it is a leading cause of death in those malignancies. One of the common forms of lymphoma is Hodgkin's disease.

I cannot mention Hodgkin's disease without calling attention to a remarkable accomplishment that is in many ways exemplary of the biomedical achievements of the last third of the twentieth century. Thirty years ago, virtually every patient with Hodgkin's disease died of it, unless claimed by something else in the several-year interval between diagnosis and the terminal phase. Since then, improved understanding of the way in which the disease distributes itself in the lymph glands, and its responsiveness to appropriate programs of chemotherapy and supervoltage X-ray, have resulted in five-year disease-free survival of approximately 70 percent, which is as high as 95 percent for patients whose disease is discovered when its extent is still limited; recurrence rates after this period are low and decrease with each year. Not only Hodgkin's disease but lymphomas in general are now among the most curable of all cancers.

The changed outlook for people with lymphoma is only one example of extraordinary progress in treating cancer. Another is childhood leukemia. Four out of five children with this disease have a form of it called acute lymphoblastic leukemia, previously fatal in every case; today, the five-year rate of continuous remission of acute lymphoblastic leukemia is 60 percent, and most of these youngsters will be cured. Although there have thus far been only a few other success stories of the sheer magnitude of these two, the general trend in the campaign against cancer is favorable enough to justify cautious optimism. Basic research, new ways of interpreting the clinical phenomena of disease, innovative applications of pharmacology and the physical sciences, and the willingness of informed patients to enroll in large-scale trials of promising treatments are among the reasons for the vast changes over the past few decades.

In the year I was born, 1930, only one in five people diagnosed with cancer survived five years. By the 1940s, the figure was one in four. The effect of modern biomedicine's research capacity began to make itself felt in the 1960s, when the proportion of survivors reached one in three. At the present time, 40 percent of all cancer patients are alive five years after diagnosis; making proper statistical allowances for those who die of some unrelated cause, such as heart disease or stroke, 50 percent survive at least that long. It is well known that those who reach the five-year milestone free of disease face greatly decreased odds of eventual recurrence of their malignancy. Virtually all of the progress has been made possible by a combination of earlier diagnosis and the improved treatment resulting from the factors listed in the preceding paragraph. Improved treatment and the possibility of success of the constantly appearing innovative approaches to advanced disease bring hope to today's cancer patient. Paradoxically, and sometimes tragically, that kind of hope is the very thing that has led to some of the most error-fraught dilemmas that patients and their doctors are compelled to face today.

My clinical career encompa.s.ses a period during which a realistic expectation first began to be felt in the scientific community that malignant disease would prove amenable to treatment based on an understanding of cellular biology rather than the ages-old oversimplifications of surgery. As more was learned about the cancer cell, new and increasingly effective ways were developed to combat its unchecked ravages. With the optimism born of therapeutic successes came a determined c.o.c.kiness that sometimes goes beyond reason; it finds expression in the philosophy that treatment must be pursued until futility can be proven, or at least proven to the satisfaction of the physician.

The boundaries of medical futility, however, have never been clear, and it may be too much to expect that they ever will be. It is perhaps for this reason that there has arisen the conviction among doctors-more than a mere conviction, it is nowadays felt by many to be a responsibility-that should error occur in the treatment of a patient, it must always be on the side of doing more rather than less. Doing more is likely to serve the doctor's needs rather than the patient's. The very success of his esoteric therapeutics too often leads the physician to believe he can do what is beyond his doing and save those who, left to their own unhindered judgment, would choose not to be subjected to his saving.

XI.

Hope and the Cancer Patient A YOUNG DOCTOR YOUNG DOCTOR learns no more important lesson than the admonition that he must never allow his patients to lose hope, even when they are obviously dying. Implicit in that oft-repeated counsel is the inference that a patient's source of hope is the doctor himself, and the resources he commands; thus, only a doctor has the power to offer hope, to withhold it, or even to take it away. There is a great deal of truth in such an a.s.sumption, but it is not the whole story. Beyond the medical establishment-and beyond even the capability of one's own physician, no matter his beneficence-is the power that rightfully belongs to the patient and those who love him. In this chapter and the next, I will write of people with terminal cancer, some of their kinds of hope, and how I have seen them enhanced or enfeebled-and sometimes destroyed altogether. learns no more important lesson than the admonition that he must never allow his patients to lose hope, even when they are obviously dying. Implicit in that oft-repeated counsel is the inference that a patient's source of hope is the doctor himself, and the resources he commands; thus, only a doctor has the power to offer hope, to withhold it, or even to take it away. There is a great deal of truth in such an a.s.sumption, but it is not the whole story. Beyond the medical establishment-and beyond even the capability of one's own physician, no matter his beneficence-is the power that rightfully belongs to the patient and those who love him. In this chapter and the next, I will write of people with terminal cancer, some of their kinds of hope, and how I have seen them enhanced or enfeebled-and sometimes destroyed altogether.

Hope is an abstract word. In fact, it is more than just a word; hope is an abstruse concept, meaning different things to each of us during different times and circ.u.mstances of our lives. Even politicians know its hold on the human mind, and the mind of the electorate. is an abstract word. In fact, it is more than just a word; hope is an abstruse concept, meaning different things to each of us during different times and circ.u.mstances of our lives. Even politicians know its hold on the human mind, and the mind of the electorate.

Scanning my Webster's Unabridged Webster's Unabridged, I find five separate interpretations of the meaning of the noun hope hope, and that doesn't include the synonyms. The meanings listed range from "the highest degree of well-founded expectation" to expectation that is "at least slight." In a separate entry is to be found an example of usage for hope hope as an intransitive verb, and herein may lie the crux of the matter for many patients suffering with terminal cancer: as an intransitive verb, and herein may lie the crux of the matter for many patients suffering with terminal cancer: "to hope against hope," "to hope against hope," which the lexicographers describe as "having hope though it seems to be baseless." A physician has no greater obligation than to be sure that no hope is baseless if he has given his patient reason to believe in it. which the lexicographers describe as "having hope though it seems to be baseless." A physician has no greater obligation than to be sure that no hope is baseless if he has given his patient reason to believe in it.

When the Oxford English Dictionary Oxford English Dictionary is consulted, there are no fewer than sixty examples ill.u.s.trating the different uses of the noun. Truly, hope springs eternal, if not necessarily in the human breast, at least in the human propensity for making a word mean "just what I choose it to mean-neither more nor less," as Lewis Carroll's Humpty Dumpty scornfully proclaimed to Alice. The meaning that hope brings is perhaps best expressed by Samuel Johnson: "Hope," wrote England's greatest authority on words, "is itself a species of happiness, and perhaps the chief happiness which this world affords." is consulted, there are no fewer than sixty examples ill.u.s.trating the different uses of the noun. Truly, hope springs eternal, if not necessarily in the human breast, at least in the human propensity for making a word mean "just what I choose it to mean-neither more nor less," as Lewis Carroll's Humpty Dumpty scornfully proclaimed to Alice. The meaning that hope brings is perhaps best expressed by Samuel Johnson: "Hope," wrote England's greatest authority on words, "is itself a species of happiness, and perhaps the chief happiness which this world affords."

All of the definitions of hope have one thing in common: They deal with the expectation of a good that is yet to be, a perception of a future condition in which a desired goal will be achieved. In a very perceptive pa.s.sage in his book The Nature of Suffering The Nature of Suffering, the medical humanist Eric Ca.s.sell writes with great sensitivity of the meaning of hope in times of serious illness: "Intense unhappiness results from a loss of that future-the future of the individual person, of children, and of other loved ones. It is in this dimension of existence that hope dwells. Hope is one of the necessary traits of a successful life."

I would argue that of the many kinds of hope a doctor can help his patient find at the very end of life, the one that encompa.s.ses all the rest is the belief that one final success may yet be achieved whose promise vanquishes the immediacy of suffering and sorrow. Too often, physicians misunderstand the ingredients of hope, thinking it refers only to cure or remission. They feel it necessary to transmit to a cancer-ridden patient, by inference if not by actual statement, the erroneous message that it is still possible to attain months or years of symptom-free life. When an otherwise totally honest and beneficent physician is asked why he does this, his answer is likely to be some variation of, "Because I didn't want to take away his only hope." This is done with the best of intentions, but the h.e.l.l whose access road is paved with those good intentions becomes too often the h.e.l.l of suffering through which a misled person must pa.s.s before he succ.u.mbs to inevitable death.

Sometimes it is really to maintain his own hope that the doctor deludes himself into a course of action whose odds of success seem too small to justify embarking on it. Rather than seeking ways to help his patient face the reality that life must soon come to an end, he indulges a very sick person and himself in a form of medical "doing something" to deny the hovering presence of death. This is one of the ways in which his profession manifests the entire society's current refusal to admit the existence of death's power, and perhaps even death itself. In such situations, the doctor resorts to a usually ineffective delaying action that utilizes what has been called by a leading physician of the generation just past, William Bean of the University of Iowa, "the busy paraphernalia of scientific medicine, keeping a vague shadow of life flickering when all hope is gone. This may lead to the most extravagant and ridiculous maneuvers aimed at keeping extant certain representative traces of life, while final and complete death is temporarily frustrated or thwarted."

Dr. Bean was referring here not just to the respirators and other end-of-life artificialities but to the whole gamut of stratagems whereby we attempt to turn our eyes away from the fact that nature always wins. This is the baseless hope that contradicts expectation; it was the kind of "hope against hope" to which I succ.u.mbed a few years ago when my own brother was diagnosed with widely metastatic intestinal cancer.

Harvey Nuland was a healthy sixty-two-year-old man who occasionally visited a doctor when he was concerned about some specific symptom, but otherwise was not inclined to undergo medical surveillance. He carried ten to fifteen extra pounds on his compact frame, but he was hardly obese. His work as an executive partner in a large New York accounting firm was a source of enormous gratification for him, although it demanded long hours and great responsibility-perhaps because because it demanded long hours and great responsibility. The focus of my brother's life was not his work, however. Harvey's happiness was invested in his family. He had not married until his late thirties and did not become a father until he was past forty. That, and the disjointed nature of our lives as he and I were growing up, may have been the reasons that the closeness of his family became the paramount fact of his life, almost as though it had been sanctified by having come as such a late blessing. it demanded long hours and great responsibility. The focus of my brother's life was not his work, however. Harvey's happiness was invested in his family. He had not married until his late thirties and did not become a father until he was past forty. That, and the disjointed nature of our lives as he and I were growing up, may have been the reasons that the closeness of his family became the paramount fact of his life, almost as though it had been sanctified by having come as such a late blessing.

One morning in November of 1989, Harvey phoned to tell me that he had been having bowel irregularities and pain for a few weeks, and the previous afternoon had been found by his doctor to have a ma.s.s on the right side of his abdomen. There were to be definitive X rays later in the day, and he wanted me to be aware of what was going on. He tried to speak matter-of-factly, but we had been through far too much together for me to be fooled. Neither was he taken in by some rea.s.suring words I managed to come up with. Even this most guileless of men was not to be sweet-talked out of his anxiety. We saw through each other, as brothers usually do, but only I knew just how bad his diagnosis was likely to be. A painful ma.s.s in a sixty-two-year-old man with bowel problems and a family history of intestinal cancer will almost certainly prove to be due to a partially obstructing malignant tumor-and one that is probably too far advanced for effective treatment.

The X rays confirmed my fears, and Harvey was admitted to a large university medical center. He chose it because his work had brought him into contact with a senior member of its gastroenterology staff. The surgeon I had recommended was away at a national meeting, and it was felt that impending completeness of the obstruction demanded urgent intervention. Accordingly, the operation was done by a man not personally known to me but highly praised by the gastroenterologist. Harvey was found to have a very large intestinal cancer that had invaded the tissues around his right colon and virtually all the draining lymph nodes. The tumor had deposited clumps of itself on numerous surfaces and tissues within the abdominal cavity, metastasized to at least half a dozen sites in the liver, and bathed the whole murderous outburst in a bellyful of fluid loaded with malignant cells-the findings could not have been worse. All of this had followed on a mere few weeks of symptoms.

Somehow, the surgical team managed to remove the part of the bowel in which the tumor had originated, so that Harvey's obstruction was circ.u.mvented. Ma.s.ses of cancer had to be left behind-in numerous tissues and in the liver. As Harvey recovered from the operation's a.s.sault, I grappled with the twin issues of truthfulness and treatment. The decisions were mine to make, because it was clear that my brother would do as I recommended. But how was I to be objective in trying to make clinical judgments for my own blood? And yet, I could not avoid my responsibility by pleading the emotionality of a kid brother who knew that his first childhood friend was going to die. To do that would have const.i.tuted a kind of abandonment not only of Harvey but also of his wife, Loretta, and their two college-age children.

There was no likelihood of guidance, or even understanding, from Harvey's doctors, who had by then shown themselves to be untouchably aloof and self-absorbed. They seemed too distanced from the truth of their own emotions to have any sense of ours. As I watched them strutting importantly from room to room on their cursory rounds, I would find myself feeling almost grateful for the tragedies in my life that had helped me to be unlike them. Decades of observing the highly trained university specialists who are my colleagues had persuaded me of the sensitivity of most and the isolation of the relatively few. In this place, the few seemed to be in charge of setting the scene.

With this burden on my shoulders, I made a series of mistakes. That I made them with what seemed like the best of intentions does not mitigate how I feel about them in retrospect. I became convinced that telling my brother the absolute truth would "take away his only hope." I did exactly what I have warned others against.

Harvey had very blue eyes. So do I and so do all four of my children. Our blue eyes are an inheritance from my mother. Every time I visited my brother during the first of those three long postoperative weeks in the hospital, his pupils were constricted to pinpoints by morphine or some other narcotic, necessitated by the unremitting pain of his ribs-to-pubis incision. Although very near-sighted, he rarely wore his gla.s.ses during that time, and I saw in those wondrously blue eyes a look that had not been there since we were two kids playing stickball in the Bronx in the few hours free from our after-school jobs. Sickness had somehow restored to Harvey his innocence of early adolescence, and his trust. He seemed a boy again, this big brother to whom I had so often in my life turned for counsel and help. And I, in my vibrant health, remained a grown man. I resolved during those postoperative days that I would protect my brother from the anguish suffered by those who know there is no hope for cure. In retrospect, I now realize that I was trying to protect myself as well.

I knew of no form of chemo- or immunotherapy that might deter so advanced a cancer from its course. In New Haven, I "discussed the case" (a euphemism for what I really did, which was to sc.r.a.pe the brains of oncologists in my search for a miracle) with colleagues. Several times, I tried to talk things over with Harvey's doctors, which I found an exercise in frustration and a lesson in medical arrogance. I heard about an experimental new treatment using an unusual combination of two agents in a way never tried before. One of the drugs, 5-fluorouracil, interferes with the metabolic processes of cancer cells, and the other, interferon, exerts ant.i.tumor effects in ways not yet completely understood. The 5-fluorouracilinterferon program had decreased tumor bulk in eleven of nineteen patients in the only group of any size that had yet been tested, but it had cured no one. The small number of treated patients had suffered an a.s.sortment of major toxic side effects, and there was even one chemotherapy-induced death.

I sought out the doctor at Harvey's hospital who had experience with the drug combination. I let my instincts as a brother overwhelm my judgment as a surgeon who has spent his career treating people with lethal disease. What could have made me believe that a unique medical coincidence had somehow occurred to solve what my rational mind knew was insoluble? Could I really have thought that a potential cure or even a reasonable palliative had somehow magically appeared just at the moment when my brother was found to have a cancer I knew to be beyond any treatment? Looking back on it, I'm not sure what I thought-I seem only to have been motivated by my inability to tell Harvey the truth of his prognosis.

I could not face my brother and speak the words that should have been said; I couldn't tolerate the immediate burden of hurting him, and so I exchanged the possibility of the comfort that may come with an unhampered death for the misconceived "hope" I thought I was giving him.

I had looked into those boyishly trusting blue eyes and seen my brother asking me for deliverance. I knew I was not able to give it, but I knew also that I could not bring myself to deprive him of the hope that I would somehow find a way. I told him about the cancer in his colon and the metastases in his liver but chose not to reveal the extent of the deposits elsewhere or the significance of the fluid. At no time did I ever consider sharing with him what I knew to be the virtually certain prognosis that he would not survive till summer. In every way, I had returned to the misconceived paternalistic dictum of the professors who taught me a generation ago: "Share your optimisms and keep your pessimisms to yourself."

In all of this, I took my cues from Harvey's eyes and his words. No one who has treated cancer patients will ever discount the power of the subconscious mechanism we call denial, which is both friend and enemy of a person seriously ill. Denial protects while it hinders, and softens for a moment what it eventually makes more difficult. As much as I applaud Elisabeth Kubler-Ross's attempt to categorize a sequence of responses to the diagnosis of mortal illness, every experienced clinician knows that some patients never, at least overtly, progress beyond denial; many others retain large elements of it right to the end, in spite of every effort that might be made by a physician to clarify each issue as it arises. Explanations of the forcefulness of denial's influence are themselves often denied. Harvey Nuland had a first-cla.s.s mind and two perfectly good ears, not to mention the keen degree of insight common in those accustomed to adversity, and yet-again and again-I was to be taken aback by the magnitude of his denial, until near his last days. There was something in him that refused the evidence of his senses. The clamor of his wish to live drowned out the pleadings of his wish to know.

Denial is one of two factors that immeasurably complicate our best intentions when, as physicians or the beloved of a dying person, we seek to enlist him as a full partic.i.p.ant in choices that must be made in the days remaining. Few dying people with a clear understanding of the inevitability of their disease process are willing to suffer through heroic and debilitating attempts to fight off an end that seems close. It is in the "clear understanding of their disease process," however, that reason and logic sometimes founder, and denial is a major element that stands in the way. Denial is a significant factor, for example, in the surprising frequency with which dying people refuse to confront the nearness of circ.u.mstances they antic.i.p.ated when, while still healthy, they signed advance directives prohibiting major resuscitative efforts. When the chips are down, almost no one wants his life to end, and one good way for the conscious mind to avoid it is for the unconscious mind to deny that it is about to happen.

The other hindrance to full partic.i.p.ation is the refusal of many patients to exercise their right to independent thought and self-determination-in other words, their control. The psychoa.n.a.lyst and legal scholar Jay Katz has used the term psychological autonomy psychological autonomy to denote this right of independence. Many a patient worn down by the ravages of illness or overwhelmed by the immediacies of a dire situation will be unwilling or emotionally unable to use his autonomy. The need to be cared for and to be relieved of responsibilities is not easily dealt with under such circ.u.mstances, and it may lead to wrong decisions. But the problem may be lessened if both patient and caregivers reflect on it together. When this is done, a dying man will sometimes decide that he wants to partic.i.p.ate much more actively than he thought he could. If he does not, this, too, must be respected. to denote this right of independence. Many a patient worn down by the ravages of illness or overwhelmed by the immediacies of a dire situation will be unwilling or emotionally unable to use his autonomy. The need to be cared for and to be relieved of responsibilities is not easily dealt with under such circ.u.mstances, and it may lead to wrong decisions. But the problem may be lessened if both patient and caregivers reflect on it together. When this is done, a dying man will sometimes decide that he wants to partic.i.p.ate much more actively than he thought he could. If he does not, this, too, must be respected.

In trying to do the right thing for Harvey, I became what he wanted me to be, and in so doing fulfilled both his fantasy of me and my own: the smart kid brother who had gone off to medical school and grown up to be the all-knowing and quite omnipotent medical seer. I could not deny him a form of hope that he seemed to need. I would marshal the forces of cutting-edge medicine and rescue him from the brink of death. This is every doctor's most pervasive near-conscious self-image, and my brother's eyes persuaded me to succ.u.mb to it. Had I been wiser, or consulted disinterested colleagues who knew me well, I might have understood that my way of giving Harvey the hope he asked for was not only a deception but, given what we knew about the toxicity of the experimental drugs, an almost certain source of added anguish for all of us.

Harvey required three further hospitalizations in the ten months of life that were left to him after his operation. He was admitted to monitor the initiation of the chemotherapy, and near the end he had to return when growing tumor deposits obstructed his intestine again, this time completely. The obstruction spontaneously opened just enough to let him take sufficient liquids by mouth to avoid reoperation, but not to maintain even the dwindling state of his previous nutrition. As difficult as was this last period in the hospital, it was the one before it that has left the most tormenting memories.

Harvey's son, Seth, had taken a year's leave of absence from school to work on a kibbutz in Israel, but came home to be his father's primary caregiver because Harvey insisted that his wife, Loretta, not give up her full-time job at a local community college. Seth phoned me one Friday evening to tell me that Harvey had been lying on a stretcher outside the hospital's emergency room for two days, suffering the effects of severe drug toxicity and pa.s.sing in and out of coma. He, his sister, Sara, and Loretta had been taking turns at his side, though he often did not know they were there. No bed was available on any floor in the entire building. The toxic effects of the drugs-nausea, diarrhea, depression of the bone marrow's ability to make white blood cells-were a problem from the start but had lately become increasingly unmanageable. Obviously, things were now out of control. The professor who was Harvey's oncologist had gone away for the weekend and his training fellows seemed uninterested or unable to do much beyond ordering an intravenous drip.

When I arrived at the hospital the next morning, I found every cubicle in the chaotic emergency room occupied. Crowded into the narrow corridor outside were at least seven stretchers, on which lay some of the sickest people I had ever seen packed into one small area, and almost all of them appeared to have AIDS or advanced malignancy. As I picked my way carefully through the narrow s.p.a.ces between patients and their anxious families and friends, I looked up and saw my nephew standing disconsolately next to a gurney on which lay his unconscious father. At the foot of the gurney sat my niece, hunched over and staring at the floor. She looked in my direction and tried to give me a wan smile, but tears began streaming down her face.

During all of those three days when Harvey was pa.s.sing in and out of stupor in that cluttered hospital corridor, his temperature had been ranging between 102 and 104 degrees. In spite of valiant efforts by the overwhelmed nurses attempting to provide at least a modic.u.m of care for everyone, and the help given Harvey by his wife and children, he had lain for long periods of time in the liquid diarrhea that periodically poured spontaneously out of him in response to the ravaging effect of the drugs on his intestinal tract. Even his periods of consciousness were not completely lucid, and most of the time he was uncertain of either his whereabouts or his condition.

I spoke to the harried resident physician who had been calling the admitting office over and over to try to place some of her sickest patients, and she agreed to make one more attempt, happy at the opportunity to use my medical connection to help at least one of them get into a real bed. An impressionable clerk must have been on duty, because the strategy worked-within two hours, Harvey was upstairs on one of the nursing floors. As we wheeled him toward the elevator, I sneaked a last guilty look in the direction of the s.p.a.ce alongside the one we were vacating, where an exhausted boy not much older than my nephew was hovering over a blanket-covered stretcher. He was speaking softly to his s.h.i.+vering friend, another young man close to death from AIDS.

Harvey paid a high price for the unfulfilled promise of hope. I had offered him the opportunity to try the impossible, though I knew the trying would be bought at the expense of major suffering. Where my own brother was concerned, I had forgotten, or at least forsaken, the lessons learned from decades of experience. Thirty years earlier, when there was no chemotherapy, Harvey would probably have died at about the same time that he eventually did, of the same cachexia, insufficiency of the liver, and chronic chemical imbalance, but his death would have been without the added devastation of futile treatment and the misguided concept of "hope" that I had been reluctant to deny him and his family, as well as myself. When I have explained the high frequency of dangerous toxicity of certain desperate forms of treatment whose likelihood of success is remote, some of my advanced cancer patients have wisely chosen to do nothing, and found their hope in other ways.

By the time Harvey recovered from this nearly lethal episode, his liver metastases, which had initially responded to the new treatment by a shrinkage of 50 percent, were once more enlarging. Because of this and the fact that the other areas of tumor had never stopped growing, it was clear that there was no longer any justification for the continuing chemotherapy. He returned home to die.

It was at this point that the local hospice was called in. I had been a board member of the Connecticut Hospice, and many of my terminally ill cancer patients had benefited from the care that these devoted nurses and doctors provide. Their goal is comfort, and their concept of comfort includes the totality of the life of patients and their families. The local hospice set to work immediately, showing Loretta how she could organize the household in ways that would minimize Harvey's distress. Seth was taught to administer medications for pain and nausea, and learned useful techniques to help his father get around the house.

One additional hospitalization became necessary when continued growth of the cancer finally obstructed the intestine. So many areas of small bowel were tethered into the encroaching tumor ma.s.s that no surgery was possible. Just when the situation seemed to have reached its conclusion, the gut spontaneously opened just enough so that Harvey could return home. This time, I asked my original choice of surgeon to take over, and I will ever be grateful to him for restoring to all of us a sense of commitment and kindness, as well as common sense.

Even with the frequent hospice visits and the selfless care given by Seth, who had by then become Harvey's constant companion and his nurse, the pain and increasing weakness were difficult to manage. The narrowness of the intestinal pa.s.sage prevented retention of any but a little nourishment; medication had to be given by suppository. Harvey had already lost a great deal of weight, but now his cachexia rapidly worsened.

When I visited, Harvey and I would sit together on the couch and try to keep each other's spirits up. A few times, when we were briefly alone, we talked about Loretta and the kids and how things would be after he was gone. Sometimes we spoke not of the future lost to him but of the long-ago past that seemed like yesterday, when we were boys in the Bronx speaking Yiddish to Bubbeh. Gone were the petty irritations and occasional conflicts that arise when two strong-willed brothers marry and their lives go off in different directions. It comforted me, in those last weeks, to remind Harvey of the several troubled times I had experienced deca