R egardless of all the notoriety accorded to it, cancer presents itself as an integral part of biology - a spontaneous, intrinsic universal phenomenon found in both plant and animal kingdoms, not excluding insects. There is no reason to think that cancer is a disease which has been as it were, superimposed on life. On the contrary, cancer is certainly an integral factor in the evolutionary process, and has a his- tory as long as the type of life which it affects.' 17 It has been sug- gested that life, as we understand it today, emerged from the pur- poseless, incessantly proliferating cancerous mass called pre-life. 18 Stated below are features of cancer that accord it its rightful place in biology.
Cancer Cell and Normal Cell
1. Every normal cell in the body has the potentiality of turning can- cerous by the property of cell differentiation - 'a part of its reper- toire.' 19 Cell differentiation is the process by which a cell irrevers- ibly changes its character to turn into another type of cell. The same process by which an embryonic cell changes into a normal liver cell occurs when a normal liver cell turns into a cancerous one.
The human body is made up of a wide variety of cell types - skin, liver, muscle, retina, etc. Although all the cells of an individual have the same genetic content, they manage to develop, look, and behave differently, as distinct cell types, through the as yet ill-understood process called differentiation 253-255 - generally de- fined as the creation of new types of cells not present earlier. The formation of a cancer cell, from a normal cell of the body at any age, is once again the creation of a distinct, new cell type - one that looks and behaves differently despite having the same ge- netic content as all the other normal cells of the body. It is now generally agreed 253 that the formation of a cancer cell involves the same process of differentiation as gives rise to normal cells of the body. No wonder that the seemingly gross malfunctioning by cancer cells - such as the secretion of carcino-embryonic an- tigen (CEA) 256 , or ectopic hormones 257 is now being understood as mere quantitative variations 256,257 of normal cell function.
2. There is no consistent single, structural, immunological, or bio- chemical dividing line between a normal cell and its cancerous counterpart. Thus a cancer cell does not have any feature which is not observed in some normal body cell.
The above points can be rendered more clear by taking, say, leukemic cells as an example: 'Since the leukemic cells originate from transformation (cell differentiation) of normal hematopoietic cells, they retain many of the normal cells' properties, and their proliferative behaviour is in many ways similar.' 315 . More specifi- cally: 'Attempts to distinguish normal from leukemic cells bio- chemically have failed to demonstrate qualitative differences in virtually every instance.' 98 Cytokinetically, both leukemic and nor- mal cells demonstrate 'equivalent cell renewal activity.' 98,258. Nor can they be differentiated morphologically or immunologically. 98
3. The difference between a normal cell and a cancer cell lies in their behaviour. A cancer cell, unlike a normal cell which only divides to replace cell loss and maintain the constancy of cell number, divides by its own self-determined rhythm seemingly without the body's need. Unlike a normal cell, a cancer cell also migrates from its site of origin and colonizes at distant sites.
Cancer in an Individual
1. Each cancer, human or animal, is, to borrow Rene Dubos' phrase, unprecedented, unparalleled, and unrepeatable. The uniqueness of a cancer lies in its cells as also in the way the cells are arranged and behave. This very uniqueness 3,15,155,156 of every can- cer rules out the possibility of having any specific drug or vaccine as curative or preventive against cancer. Writing in The Lancet on 'Uniqueness of malignant tumours,' Spriggs and co-workers 239 concluded: 'It is impossible to, prove the negative - that identical carcinomas never occur - but the present tests confirm an im- pression, obtained from thousands of cases, that naturally occur- ring cancers are extremely diverse even when they carry the same diagnostic label.'
2. The course of a cancer is as unpredictable as that of the individual. Having formed, it may not grow; having grown, it may not dis-ease or trouble; having dis-eased, it may not kill. Many a cancer dies with its owner. Hence it is the cancer and not the therapy given, that determines the outcome in a human being or an animal .
3. Cancer in its occurrence exhibits a predictable certainly at the level of herd, but always remains a matter of chance or probabil- ity at an individual level. World over, the overall cancer occur- rence is one in five humans. 55 One in five is a matter of certainty; which one, is that of probability. This holds good even in ani- mals 21 specially inbred in laboratories for studying cancer-occur- rence generation after generation.
4. Cancer is neither hereditary nor familial. It is its very common- ness that makes it occasionally seem so. Willis 20 has generalized that most of the 'cancer families' exemplify only the laws of chance. Scheinfeld's 240 incisive comments on the problem - 'Thus, in grand- mother, mother and daughter, where all have breast cancers, each of their cancers may be entirely unrelated to the others ... The breast cancers in the three generations of women might be no more related than three cases of stomach trouble, one resulting from over-eating, another from drinking bad liquor, and the third due to stomach ulcers.' - made way back in 1939, has a resound- ing echo in the 'But so what?' reassurance from Frazer Roberts 241 : 'This is a very common condition.'
5. A cancer is for the owner, a part of his or her own flesh and blood. It cannot be attacked with impunity without damaging other nor- mal tissues. All anticancer agents treat cancer cells in the same manner as they treat all normal cells. This inseparableness of cancer from normal tissues has rendered cancer radiotherapy 'obsolete' 22 and cancer chemotherapy 'an absolute farce' 22 . In the laboratory cancer chemotherapy produces 100% success be- cause the so-called cancer is a transplanted mass of cells that never belonged to the test animal. 6 In the laboratory and by the bedside, chemotherapy is a 100% failure if the cancer is autoch- thonous, i.e. the one that arose by itself in the individual. 23
Cancer in a Herd
1. The type of cancer that occurs is species specific - of the kidneys in frogs, of the nasal sinuses in dogs, of the eyes in Hereford cattle, breasts in bitches, as leukemia in Scottish terriers, and as melanoma of the skin in grey horses. 30,31
2. A predominant involvement of a particular organ or system is seen in the different races of man too, as exemplified by the very high incidence of stomach cancer in the Japanese who, as a compen- sation, have the lowest incidence of leukemia in the whole world. 32 This varying prevalence is not dependent on the environment. It is the racial or the ethnic genetic constitution which governs the type of cancer in a given population. The high incidence of stom- ach cancer is as much a Japanese feature as are the stub nose and the slit eyes.
However, the total incidence of cancer, in a herd, is determined by the genetic constitution of mankind irrespective of racial and geographic variations. Thus the aggregate incidence of cancer remains the same world over. Smithers 165 has generalized that although the anatomic distribution of cancers in different parts of the world is extremely varied, the overall death-rate from cancers at all sites is remarkably constant for humans the world over.
3. The environmentalistic claim 242,243 that migrants readily develop a cancer profile typical of the host community made regardless of the 'manifestly inadequate' 244 data and the many difficulties as- sociated with the study of migrants, 244,293 fails to find support epi- demiologically. 245 Japanese migrants in the USA maintain the high rates of stomach cancer typical of Japan, as also the characteristics low rates of breast and cervical cancers, and of leukemias.
Cancer as a Senescent Process
1. Cancer is a manifestation of aging, like hardening of arteries, development of cataract, etc. 'Most spontaneous tumours in ani- mals, as in man, occur in middle-aged or elderly animals.' 20 In children, too cancer is but a form of senescence. (See Chapter 11).
2. As is typical of biologic processes, cancer in its many facets ex- hibits gaussian (normal/continuous/bell-shaped) distribution, as may be evinced from, say, the age-incidence of a particular can- cer in a human population. 6,20 This must also be true for its other facets such as growth rate, invasiveness, site of origin, size of cells, etc. 6
Cancer and Death
1. The fatal bite of the cancerous crab often lies in its spread. The spread of a cancer occurs throughout the length and breadth of the body, but usually manifests itself, apart from the original seatof occurrence, at four sites - lung, liver, bones, and brain. No place in the body is, however, exempt from this process. The spread of cancer fools the clinician, frustrates the surgeon, and frightens the patient. The when, where, and how much to spread is determined by the inherent nature of a cancer. Treatment of cancer can precipitate its spread.
2. Cancer apparently serves the natural function 24 of herd mortality, which simply means increasing mortality with increasing age. 'The age-specific mortality rate for cancer increases with age in much the same way that the overall rate does.' 25 To put it simply, the increase in mortality rate with age in cancer is similar to the increase in mortality rate with age in general.
The nature of the link between cancer and death is debatable as may be realized from the computation that, were cancer elimi- nated altogether from mankind, it would just add a little more than a year to the human life span. 26 Animals would fare no better, in the futuramic World Without Cancer . 27
3. Death is a natural function, not dependent on the presence or absence of a particular disease. 28 It would seem death does what it wants to, and gives the pre-death disease a bad name. Zumoff and co-workers 29 analyzed the mortality statistics for series of patients with diverse diseases - liver cirrhosis, metastatic breast cancer, chronic leukemia and heart attack. 'It was found that the four diseases analyzed shared an unexpected relationship of mortality rate to duration of disease: the basic mortality rate remained constant during the course of disease; prognosis was neither better nor worse for the patient late in the disease than for the patient early in the disease.' The workers 29 concluded that all the above diseases shared a common alteration of 'the undefined physiological systems' that govern susceptibility to aging and dying.
4. The causes of death in human cancer, Jones 11 surmised have less to do with the extent of cancer growth than with some other explanation of the metabolic state in cancer. Jones 11 emphasized that 'only a fraction of cancer follow-up suggests that death is due to recurrence of the cancer in an advanced state.' Jones 11 pointed out that the death rate from intercurrent disease, in can- cer, is as great as the rate of death from cancer itself. He specu- lated that there may be a general metabolic basis of cancer as a disease, a phenomenon that may explain why our intense search for cancer cures has been very poorly rewarded. '... the popula- tion that shows cancer may be already aged from the standpoint
THE OTHER FACE OF CANCER
of intact metabolic function, so that cancer is only one of the manifestations that occurs in the diseased population.' 11
Summarizing the biologic features of cancer, one could say that cancer cell is an altered normal cell; that in an individual, cancer ex- hibits self-determined uniqueness; that at the level of a herd, while the cancer types vary, the total quantum does not, the world over; that cancer is an evident part of overall vertebrate aging and senescence; and that in relation to death, cancer is NOT the villain of the piece, as portrayed.
Were cancer to have ears and a tongue, it would listen to all our wailings and then apologetically declare its helplessness because of its being rooted in the very thing called life. Thanatologists have, rightly, started preaching from public rostra that death is an inevitable, and an indis- pensable necessity. Can it not occur to us that this is true for cancer also and that cancer is not a problem but a solution to the problem of dying? Sir George Pickering, 33 Regius Professor of Medicine at Ox- ford, summed this up well: 'Aging as a preparation for death is a con- cept so fundamental that it needs emphasizing before we consider the diseases of old age. After all, it is these diseases which kill and make way for the new life. Without them none of us would be living as we are today.' And so it is, with cancer. Cancer will be with us till eternity; let it be.