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Cancerology: Science or non-science?- (a plea for cancerrealism) ML Kothari, Lopa A MehtaDepartment of Anatomy, Seth G.S. Medical College, Bombay-400 012, India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 722608
Cancerology is, by all counts, a non-science, which may be defined as a so-called scientific pursuit in the teeth of obvious proofs to the contrary. Not one facet of current cancerology-etiology, diagnosis, therapy, prevention, and its latest fad, immunology enjoys any clear, rational basis. No wonder that the outcome of the whole gargantuan effort is "precisely nil", with possibly more people living on, than dying of, cancer. The pathway to the logically acceptable and comprehensible science is simple-to give cancer its due place in biology, to give the cancer cell its rightful place of but a form of cytodifferentiation, and to give the cancer therapist the supremely relevant role of a palliator. To talk of cancer cure is to deny - the cytosomatic reality that cancer is one's own flesh and blood. Being a part of one's self, cancer need not always be treated. I f a therapist has the right and obligation to diagnose, treat, and prognose upon a cancer patient, he has, hitherto unrecognized, equal right and obligation, not to do one or all of these. Cancerrealism offered in this article can guide a therapist to this often necessary path of inaction.
Cancer, paranoically personified, is continuing to have the last laugh, after 'being attacked on all possible fronts, Bier's [14] summing up many decades ago" There is a tremendous literature on cancer, but what we know for sure about ii can be printed on a calling card."-found itself fully revindicated recently whey. Burnet [28] declared that the outcome of the entire cancer research has been "precisely Breast cancer as a paradigm typifies the colossal cancerologic failure. A subcutaneous cancer, the natural history of which has been studied for centuries, [60] most amenable to self; clinical examination, -graphies, staging, grading, -ectomies, hormonization, dehormonization and the most varied therapeutic combinations, has stubbornly refused to yield even a wee bit in the last 70 years; [81] it has, in fact, gone worse. [125] Yet research establishments refuse to prune their anticancer claims, for "It just doesn't pay to rock the boat." [81] Cui bono? The lay-the media-do not lag behind. A promethean prophesy, a book, No More Dying[117]α envisions drugs to cure or prevent cancer, heralding the emergence of the eternally non-dying Homo longevus. Cancer research is based not on science, but on non-science, an epistemologic revelation that explains the cancerous proliferation-"now more people live on cancer than die of cancer" [7] -of research, [41] in the teeth of the writings on the wall. Putting it in Ardrey's [6] style, the whole cancer fiasco represents "the disastrous consequences of applying utter logic to a false premise." The many false premises on which the cancer edifice rests need analyses, as follows.
Bertrand Russell [167] delvered, in 1918, a devastating judgment against causalism: "All philosophers, of every school, imagine that causation is one of the fundamental axioms or postulates of science, yet, oddly enough, in advanced sciences, ... the word `cause' never occurs. The Law of Causality, I believe, like much that passes among philosophers, is a relic of a bygone age, surviving like the monarchy, only because it is erroneously supposed to do no harm." The gains of cancerologic causalism have been nil; the harm done is global phobia of "cancerogenesis" should people eat, drink, breathe, or copulate. The medical finger accuses- almost everything as cancerogenic [141] and having accused, moves on to accuse still more. [58] Such anxiety-making-the curious preoccupation of the medical profession's-reaches its apogee when PUFA, which is supposed to prevent heart attack, is declared as causing malignant melanoma. [79],[122],[143] Editorially, Ingelfinger [101] rightly described cancerophobia as a social disease as serious as cancer, and morally far more devastating. Cancerogenism [30],[56] -the obsession that a -gen causes cancer-has not for once satisfied the fundamental tenet [71] of causalism: an invariant relationship of events in which the cause must precede its effect and the effect must follow its cause. "It is this sense of must which distinguishes causal connection from coincidence." [71] Any -genie postulate that A causes B, must in the same breath, explain why A occurs without, and refuses to occur despite, B. The causalism of modern medicine is incapable of complying with the foregoing, be it coronary, or cancer. Further, causality cannot jump gaps in time; the effect must immediately follow the cause. [71] The concept of "latency" [105],[141] that allows as many as 12 to 56 years between the exposure to the postulated cause and the occurrence of cancer is, because of the irreconcilable temporal gap, clearly against the causalism of cancerogenism. The current epidemic of epidemiologic studies [46] on cancer was triggered by a search for Mr. Cause that never was, a wild-goose chase powered by the application of utter logic to a nonexistent premise. The noble aim behind the cause-hunt is the prevention-promise. [56] "Since so little is known about the origin and development of neoplasia, it is not surprising that many cancers can be neither prevented nor cured." [66] What if much is known? Reviewing a book ambitiously titled The Prevention of Cancer, Jellife [103] concluded that, although the various authors provide an excellent analysis of the large amount of data related to the causation of different cancers, no reasonable means are provided anywhere for prevention. "For example," Jellife [103] remarked, "after twelve erudite pages on breast cancer, the reader can discover no practical alternative to prophylactic bilateral mastectomy at an early age." Harvey Cushing [50] exclaimed that, like many other catchwords, prevention can be overworked: "There is only one ultimate and effectual preventive for the maladies to which flesh is heir, and that is death." A la Koestler, [110] scientismic perversity reaches its climax when patients are purportedly "cured" by the very agents known as causing cancer-irradiation, chemicals, and hormones. Viruses and immunity had hitherto escaped this cancerologic diabolism of what causes, cuss cancer. However, viruses have been mooted as curative [198] while immunity, [34] our last hope against cancer, has been incriminated [159] as cancerogenic and cancerotrophic. Diagnostic procedures (mammography, [9],[23],[141],[142] right now) are not exempt from the cancerogenic edge. All that is done to cure cancer, manages to cause cancer. The truth in all probability, is tha: cancer is causeless. Cancer, the primeval broth of pre-life that spawned organized life, [51],[95] is a property of all living systems" [52],[200] ab aeterno, being but a way of cytodifferentiation that is part of the normal cellular repertoire. [157] It is an integral part of the human biologic trajectory, a bioevent that can't be caused. In this light, cancerogens have been rightly held as agents that are "accelerators of some process that is inherent in the animals." [47],[175],[184] Neologistically, cancerogens, not excluding the recently notorious polyvinyls, should be called cancer-preponers [113] The invention of the new science of ecogenetics [149] is the last-ditch effort of the causalists to somehow incriminate our milieu for what programmedly is, in Shakespearean words, "an illfated thing, Sir, but my own."
Glemser, [75] from his globe-trotting survey of cancer research and treatment, gathered, from the scientists themselves, that radiotherapy is obsolete, chemotherapy is an absolute farce, and that surgery ought to be dispensed with, sooner the better. The reasons are not far to seek: If even the doubtfully helpful [147] mammograph threatens to cause "as many cancers as it is picking up" [9],[23],[141],[142] by increasing the natural risk of breast cancer, by one-one-one-one mechanism (one mammogram gives one rad to one breast to increase the risk by one per cent), [23] then sure enough any form of therapeutic radiation's would increase the risk of iatral (so-called iatrogenic) [25] cancer much more. Chemotherapy is another story: Karnofsky, [106] lately of the SKI, in his chapter on experimental chemotherapy gave the directive that "if an agent has certain biologic effects such as carcinogenic, mutagenic, or bone-marrow depressant activity, it merits testing for chemotherapeutic activity." Each agent used against cancer, was "cancerogenic" to start with, a farce that has not changed from nitrogen mustard to adriamycin. [135] The situation is similar to that in Anthony Burgess's A Clockwork Orange: [27] "Our subject is, you see, impelled towards the good by, paradoxically, being impelled towards evil." The too-generously funded cancer chemotherapy research programs provide an "anticancer" drug which, by a semantic alchemy, turns anti-psoriasis when used by a dermatologist, anti-immunity when employed by a Barnard, and anti-rheumatoid-arthritis when given by an internist. Cancer chemotherapeutic agents prove to be anti-everything, including the patient. (Cf. "The aggressive chemotherapeutic approach used ... is often lethal to the patient with LRE." [127] ) The chemicals provide cent per cent failure against autochthonous [74],[183] cancer and, sometimes, cent per cent success against the so-called transplanted cancer [74] which is not a cancer at all but a borrowed mass of mitotically active cells. The singular, and outstanding, success of cancer chemotherapy against gestational choriocarcinoma is a function of the transplanted (fetus to mother) nature of the cancer, rather than any special qualities of the drugs. As back as 1947, Woglom [206] described the quest for cancer drug as much difficult as finding an agent that will dissolve away the left ear and yet leave the right ear unmolested; "So slight is the difference between the cancer cell and its normal ancestor." [206] Haddows [84] has compared the search to the biological equivalent of squaring a circle. Regardless, cancer chemotherapy continues to be defined as "essentially the science of discovering exploitable difference between malignant cells and normal cells." [183] Farce, in science, seems to have its own reasons. Surgery's dispensability stems from the closely comparable successes of measures ranging from tylectomy (which tantamounts to nil-ectomy), for breast cancer on the one hand, and supraradical mastectomy on the other. "Each of these diverse treatments has its fervent advocates," the BMJ [60] editorialized, "and yet despite a plethora of reports there is little evidence on which to recommend the `best buy' for the patient." Radicalism is however the preferred course, either because it is approved by the majority of breast surgeons," [188] or because it is more dollarogenic. [49] Be as it may, cases for which nothing is done, fare no worse. [17],[104],[209] The we-must-operate/ treat diehards insist so on the ground that not enough is known about untreated cases. "On the contrary, if one bothers to scan the literature, there are ample articles on just this subject." [186] If it is Dowian do and be damned, and do not and be damned, then why do anything at all? Why not allow many a woman to die with her own breasts on? All other measures-hormones, immunotherapy, Isselsism, thermotherapy, and all other nostra-are used faut de mieux, when the three bulwarks of surgery, radiation and chemotherapy have failed, or are prima facie useless. Malleson's diatribe Need Your Doctor Be So Useless? [132] could be paraphrased to read Need Your Cancerologist Be So Useless? Notwithstanding the foregoing, cancerology reeks with treatment, nay, overtreatment, probably because, it is better to believe in therapeutic nonsense, than openly to admit therapeutic bankruptcy." [8] What happens when a doctor-a cancerologist-is at the receiving end of such therapeutic nonsense? He doesn't want it, for he can't trust it. Solzhenitsyn portrays this poignantly in Cancer Ward. [179] Erik Erikson's [63] invocation Doasyouwouldbedoneby does not strike a responsive chord in the heart of medical therapists, for they know too well of the therapeutic non-sense. A word about controlled clinical trials, the most important condition for which namely, that even cancer must be left untreated to serve as control [166] "('-is' rarely obtained. [166] The failure of such trials visa-vis many problems including cancer therapy is too well-known, [65] and large-scale international trials only serve to highlight their futility. [39] Foulds, [70] as it were, ruled out the scope of controller trials when he generalized that "no two tumours are exactly alike." Connors and Ball [42] enlarged on this by declaring that this behavioral unlikeness reigned amongst "morphologically similar tumors' as also amongst "tumors obtained by the same means and in the same pure line of animal." How come controlled trials, when no two humans, nay, no two cancers, nay, no two cancers in the same human, may, no two clones in the same cancer are exactly similar to each other
Today, the recurring theme in writings medical [13],[73],[190] or lay [23] is the war cry Diagnose And Treat Early (DATE). DATE has been tirelessly advanced as the cure-all promise against cancer; the motto takes for granted that treatment applied sufficiently early is or should be successful treatment. While the outcome of DATE program has remained ill-defined, it has certainly bred a widespread I/wedid-not-seek-DATE neurosis among cancer patients and their relatives. The iatral nature of this neurosis is dependent upon statements such as these: "In no other disease does the patient himself bear so large a share of responsibility. . In no other disease does the patient alone influence the outcome to a great degree." [32] The title to the foregoing text is dramatic: THE BIG IF. The ending is no less incriminative: THE RESPONSIBILITY IS YOURS. The author [32] heightens the impact by figures: "Ninety thousand American lives are lost needlessly every year. These are the deaths which early diagnosis could have prevented-and can prevent," The DATE concept, as has been presented to the public and patients so far, puts the therapist in an enviable and inculpable position. Should the therapy fail-and it must, so often-it is only the patient who has to admit mea culpa, mea culpa. The patient has no escape, for he/ she has been categorically told: "The choice is yours-and wholly yours." (Cameron) . [32] The medical naivete, [190] that the earliness of a cancer is synonymous with its curability, is laid bare the moment a definition of the elusive earliness is asked for. Cytokinetic studies, apart from dispelling the myth of faster multiplicability of cancer cells, [11],[183] have revealed, (a) that it takes years before a cancer marches from inception to detectability and (b) prior to being detected, a tumor enjoys a formidable number of cancer cells. "Unfortunately, gross or microscopic tumor cell identification in man or animals is probably, at best, limited to between 1 million and 1 billion tumor cells." [172] An average cancer cell, like an average normal mammalian cell, has a diameter of around 10 microns [120] and gives rise, through 20 exponential doublings, to around 2,500,000 cells comprising a lesion only a millimeter in diameter, [59],[129],[196] a size smaller than "an `o' on this page." [23] Cheatle [35] declared, in 1927, that the appearance of a lump in the breast meant advanced cancer beyond the hope of cure. Cytokinetic studies have done the disservice of proving that this is so even when it is a microlump, undiagnosable by any -graph. "Early diagnosis of breast cancer operates on a fast track these days and better results in survival statistics are appearing." [73] This robust optimism has to be tempered by a global survey revealing the worsening of breast cancer mortality. [125] We can continue to hope, but the DATE drive, damned by so many cancer-realities, has failed. As Macdonald [129] puts it for breast, the fixed rates of incidence, mortality, and survival following diagnosis-"that discouraging and almost parallel line " [164] -allow only one conclusion that early diagnosis, small size of the primary lesion, long meticulous or extended surgery, with or without adjuvant radiotherapy have not been of any value in our battle against a biologic complex formed by mammary carcinoma; even metastasis and recurrence of breast cancer have not been found to be influenced by earliness or lateness of treatment. All the inconvenient data [130] from the various DATE programs can allow the generalization that no cancer, that can be labeled-microscopically, endoscopically, or clinically-as a cancer, is an "early" cancer and that the so-called earliness of a cancer is no guarantee for a late death, nor the lateness a passport for early demise. Moertel, [145] citing Palmer, convincingly drives home the DATE debacle: "It might be hoped that earlier diagnosis could brighten the surgical picture, but even this road seems blocked. In a group of sixteen cases in which esophageal cancer was diagnosed prior to the development of symptoms while the patient was under active medical surveillance, Palmer could demonstrate no improvement in survival."
Virchow cited by Ewing, [64] declared that no man, even under torture, could say exactly what cancer is. Yet, while cancerology continues to ail from the spinelessness of definition lessness vis-a-vis cancer, [116],[181] it has chosen to establish the burgeoning science of precancer, that boasts of the ability to doubtlessly diagnose [37] precancer-earlier-than- early cancer-and to grade [173] it from 0 to 10, unmindful of the fact that the microscopic grading of even a fait accompli cancer which may be "cytologically indistinguish able" [93],[115] from the parental normal tissue-depends so often on the barometric pressure and the bowel one of the pathologist. [148] What is carcinoma in situ below the umbilicus, becomes with equal, characteristic equivocation minimal can cer above it. To wit, listen to Hutter, [98] concluding a conference on minimal breast cancer. "The great aspiration for the future is to have the pathologists identify any lesion which is significant threat to the future health of the patient so that it can be treated ...I have carefully chosen my words to avoid specifying whether the significant lesion is actually cancer or what the preferred treatment should be. Nevertheless, if we can consistently identify an obligate precursor to metastasizing cancer we can establish a cure rate of 100 per cent." The rank uncertainty of what is precancer, breeds, what Park and Lee [156] called long ago, pragmatism that thrives on "probably not cancer but safer away" [156] type of diagnostic and therapeutic approach. As early as 1923, Bloodgood, [16] from his experiences with breast cancer, at the Johns Hopkins over 33 years in retrospect, wrote of "Benign Lumps Diagnosed Cancer or Suspicious of Cancer." He remarked that such pragmatism increased the cure-rates. Sheep-slaughter presented as wolf-slaughter has managed to create the mysterious "paradox of increasing incidence and decreasing mortality" [46] of two most sought-after precancers-cervical [46] and mammary. [22] Bloodgood's [16] highly objective generalization is as relevant today: "As this element of error has been present in my own investigations for years, I feel justified in the conclusion that it is present in all statistical studies throughout the world." The precancer pragmatism reminds one of Voltairs: Si cancer n'existait pas, it faudrait l'inventer. Such cancerous invention explains the sudden four-fold leap in cancer rates for the year 1975, [141] the demoralizing cancerophobia, [101] and the fright, confusion, and panic'' [23],[130] that plagues womankind. It also accounts for 690,000 hysterectomies performed in the USA in 1973, [26] (a number equivalent to the global publications on cancer per year), [176] many of these carried out "unnecessarily," and as such useless towards preventing cancer . [26] It is a measure of sanity that the worth of Pap smear More Details is being questioned, [13],[90] and it may not be too long before precancerology dies a natural death, like many an advance in modern medicine. [174] The poor public response to cytologic screening [193] could be looked upon as an evidence of, what Comfort [38] calls, "the astounding resilience of human common sense against the anxiety makers." May be, that is what makes more and more people-60 million Americans [141] -smoke dsepite the Surgeon General's warning on every cancer stick.
Wilcox, [202] writing on "The last surviving cancer cell: The chances of killing it" generalized that "a minimum requirement for a cure is the elimination of the last cell." The presupposition here is, as it is in DATE drives, that canceration of normal body cells is a kind of once-and-for-all affair so that the demon can be completely exorcised, provided the multidisciplinary exorcists arrive in time. The cytokinetic concept of "clonogenic cells," [177],[182] advanced to explain the failure of chemotherapeutic exorcism also suffers from the illusion of canceration as a once-and-for-all process. What foils the exorcists, however, is not the last cancer cell but the neighbouring normal cell waiting to turn cancerous. Le roi est mort, vive le roi-so the heralds proclaimed the death of one French king and the coming to the throne of the other. The body playing host to a cancer, on removal or destruction of the latter, proclaims Le cancer est mort, vine le cancer, by asking some normal cells to turn cancerous, be it stomach, lung, bowel, or brain. Canceration is a fundamental prerogative of every normal, divisible cell. A cell that turns cancerous afresh could be said to neo-cancerate. [113] The human body's propensity for neo-canceration rules out the possibility of any therapeutic-surgical, radiational, chemotherapeutic, or immunologic-triumph against the hypothetic "last" cancer/clonogenic cell, and, therefore, against cancer. It may be emphasized that neo-canceration is not equivalent to "cell recruitment, " [66] which presupposes the ability of a cancer cell to seduce a normal cell into cancer. hood. Neo-canceration is canceration once more, independent of the cancer that already exists or that has been treated. Even if the DATEists manage to grab a cancer before it has jumped the fencemetastasized-neo-canceration is a force that may thwart their curative aims. An exception to the above cellular scare is presented by gestational choriocarcinoma. This cancer, being a transplant from the fetal tissues to the mother, has no would-be-choriocarcinomatous normal progenitor cells in the mother so that a chemotherapeutic agent administered in the right dosage at the right time manages to achieve a total cell kill, thus accounting for its much celebrated cure.
Surveying the field of tumor immunology, a science-writer 73 hit upon the generalization that immunology is now so advanced that one immunologist cannot comprehend what another is talking about. Medical obfuscation [48],[102] never had it so good. Tumor immunity hasn't been defined, and is unlikely to be in view of such learned editorial doublespeak: "This article illustrates that under proper circumstances, tumor immunity can stimulate tumor growth." [61] Yet, today's most dominating form of cancer research is tumor immunity, [44] threatening to usurp the top place enjoyed by the disproportionately overfunded" [28],[29],[151] tumor virology, already declared as "a major disappointment." [28],[29] Tumor virology presses on regardless, rejuvenating itself by virologic obfuscation-"misevolution" of protovirusesls [187] or virogene colliding with oncogene [94] -keeping alive thus the unending promise of immunologic bullets against "specific tumor proteins" [160] and the ultimate bonanza of a vaccine program. [62],[138] While the obfuscatory going is good, anticancer going is otherwise. Burnet, [28],[29] writing on cancer antigens, stated that "Nothing of value for either prevention or cure has come from the laboratories," adding that lab-oratorial immunology, bred from inbred strains, has had nothing to do with human cancer. Tumor immunity ambitiously aims at diagnosis, treatment, prevention and prognosis of cancer and precancer [13],[22],[37],[41],[77],[89],[163] ,[168] but a review [137] of a book on tumor immunity's "Scientific Basis and Current Status" ends up with unsuccess, disappointment, frustration, and difculties, the latest one being that a circulating cancer antigen may in fact protect the parent tumor. The typical double-speak of cancerology reaches one of its high, when the talks of the prevention of cancer by tumor immunity, get matched by the promotion [22],[68] of the use of potent "oncogenic" [87] immunosuppressors as prophylactic against recurrence of cancer. Tumor immunity itself does not seem to have decided on which side of the tumor it is. The betrayal by antibodies is a thing of the past; now even the cell mediated immunity is turning a leading suspect in the initiation and promotion of cancer. [159],[168] May be it is decided by "Immunostaging as a guideline to immunotherapy." [2] May be it depends on immunity's moods: It is antitumor if it is malignant melanoma, lung or colon carcinoma, but blatantly protumor if it is carcinoma cervix or bladder. [88],[168] Immunity may, however, betray to enhance malignant melanoma. [153] Oettgen and Hellstrom, [154] writing a chapter in the current Bible, Cancer Medicine, raise enough anticancer hopes before and after the few lines that follow: "Thus, it is not simply a matter of deciding whether 'immunity' inhibits or fosters cancer. Only if means can be devised to shift the balance between inhibitory and enhancing immunologic forces in either direction can we hope to find a clearer answer." BCG immunotherapy of cancer, apart from "frequent complications [136],[139],[153],[180] assumes, in the light of the foregoing a procancer edge. [18] A la Peter Principle, BCG immunisation has reached its level of incompetence and is paving way for a wormicidal drug-levamisole-that has proved to be an "immunostimulant" with its own unpredictable efficacy and side reactions. [136] Let us face it: The cancerous proliferation of highly fundogenic tumor immunology is a comic verification of the principle of applying utter logic to a false premise. No autochthonous cancer has believed in being non-self. [114] It is for everyone, to borrow words from Mr. Doolittle in My Fair Lady, "Me own flesh and blood." For gastric carcinoma, for example, the suture line takes even when the knife runs "actually through the cancer" [131] amply proving the self nature of cancer cells. The elaborate studies on "How Lymphocytes Kill Tumor Cells "[4] in culture has little to do with the selfsameness of cancer cells and lymphocytes in the same individual.
Were hindsight to help, we would realize that the unmitigated failure [28],[29],[40],[185],[189] of cancer research can be attributed to the fact that cancer is, by its very nature, unresearchable. Burnet's [29] candor that the contribution of lab-science to medicine has come to an end is not even applicable to cancerology, for the contribution has never begun. Huxley [99] generalized that each cancer is a species, being like the human owner, unhelpably unique. [29] The individualistic character of every autochthonous cancer [70],[99] animal or human, coupled with the unique biologic trajectory of the individual, rules out any structural or behavioral comparison, prediction of therapeutic outcome, or disease-death correlation. The little emphasized benignancy [195] of malignancy-that cancer does not always kill-questions the very raison detre of cancer therapy. In fact, Hardin Jones [104] went to the extent of concluding that treatment, more often than not, shortens the lifespan of a cancer patient. A biologic, non-anthropocentric approach to cancer reveals it as is no error, but an integral part of cellular/organismal behavior, that will not yield to "the basic-science route to a medical nirvana" [82] regardless of the fact that such "research is still the lifeline of medicine." [111] Non-medical sciences have started admitting the trans-science [121] nature of problems. Cancer is trans-science and trans-two-billion-dollar-NCI-budget. The "light-at-the-end-of-the-tunnel" thesis [81] of Vietnam war days is only relevant to the point that there is certainly dark at the end of the cancerous tunnel. The use of transplantable cancer, because of the sheer incapability of using autochthonous animal cancer, [74] is an intellectual compromise that has spawned 1ittle good. Any immunologic/therapeutic data obtained using cancer transplants cannot be extrapolated for the simple reason that it is cancer only when it is autochthonous and with the owner; otherwise it is a borrowed mass of mitotically capable cells that, multiplying in a test tube or a biotube, can only prove that MOPP, [165] POMP [170] or TRAMPCOL [86] are "terribly toxic drugs" [86] that form "the blind artillery which cuts down its men with the same pleasure as it does the enemy's, "[179] making hitherto unknown in fections "now the major cause of death in patients with leukemia." [96] It is a sad comment on the perversity of lab-science that cancer transplantation and organ transplantation were born as twins in the womb of inbred mice, [97] and that cytotoxic agents prove friendly for graft-survival and inimical to cancer-survival, purely because of their cytotoxicity against the mitotically capable lymphocytes on the one hand and the cancer cell-lines on the other. All that the transplantable L 1210, B 18 melanoma, osteogenie sarcoma HE 17304 and so on have done at The Cancer Chemotherapy National Service Centre (CCNSC) [78] (now, Drug Research and. Development) [78] and elsewhere is to show, animal after animal, and year after year, the naggingly prototypal -tidal efficacy of the "drugs" against dividing cells. The dependence of all forms of life on the cardinal biologic phenomenon of cellular division [12] constitutes the most unabrogable obstacle to the present or future success of cytotoxic (chemical and/or radiational) [207] agents. The human body is dotted from head to foot with renewing cell populations many of which exhibit far more consistent and faster cellular proliferation than the fastest growing Walker carcinoma 60. [123] As and when a patient is exposed to the CRAB [183] aims of a cytotoxic agent, the damage to normal cell populations is a certainty while the damage to the cancerous cell population is only a probability. Cancer research has now entered the cell-surface, [150],[185] cell-enzyme [199] era , [150],[185] entailing a massive research effort that has provided an enormous catalogue of differences between normal and cancerous cells. The compromise here too, is no different. "These `in vivo' approaches are complicated by the fact that most tumor cells arise from unknown precursors, making comparisons with other cells difficult. Because of these problems and the limited availability of uniform cell populations, the main tools of the cancercell biologist have thus been model systems employing untransformed/transformed tissue-culture cell lines, frequently of rodent or avian origin." [150] Koestler's fourth Pillar of Unwisdom [109] could not be more relevant than to cancer lab-science, ever ready to reduce a complex phenomenon to simple quantifiable elements without worrying at all that the specific characteristics of the complex phenomenon--cancer-are lost in the process,
We can visualize a parallel-problem here: diabetes mellitus. [112] Boyd [20] concluded that "the more we know about diabetes, the less we seem to understand it;" the more we treat the patient, the less we seem to benefit the patient; [108],[204] the more we research on it, the more we replace certainties by uncertainties. [144] Nevertheless, eminent diabetologists [31] in "an exercise of mass delusion "[133] blatantly "propose as `truth' a concept that remains to be proved. [133] May be, this is the way modern medicine works. A 4-page color-ad on clofibrate [1] promotes lipidlowering therapy with an apologetic box that renders clofibrate a non-drug; but the color carries the show and doctors universally prescribe the drug notwithstanding the two columns, in small print, on its hazards. The burden of the foregoing is to draw attention to a malady that afflicts modern medicine-the connivance of the dividing line between what we know and what we know not. Holmes [92] while pointing out the "Border Lines of Knowledge in Some Provinces of Medical Science," observed that "The best part of our knowledge is that which teaches us where knowledge leaves off and ignorance begins." Finding or erecting such an epistemologic watershed, in cancerology, is not difficult provided we abjure non-science (which in the current context can best be defined as arrogance despite ignorance) in favor of science pregnant with the humility to accept ignorance. "Science," Holmes [92] declared, "is the topography of ignorance." Let us see where, in cancer, does knowledge leave off and ignorance begin. What follows should be perused with Arcadian humility, which the Homo sapiens (?), preparing now to be Homo longevus, [117]α appears in no mood to have. With the aid of his "optimistic ignorance" [79]α on cancer, he hopes to "square the circle", and boldly declares right away, that YOU CAN FIGHT CANCER AND WIN.[22]α A saner 1977 survey [189]α of the "Science and Technology of Medicine" leaves no scope for such Homohopes. The simple realities of cancer cancerrealism-that follow assure an easy change from the non-science to the science, of cancerology. Tumor = Lump: The Border Line The raison d'etre of cancer therapy is that the chief manifestation of cancer is mass-ive-a celluloma called a tumor or a lump. (Imperatively, the synonymy between cancer and tumor is avoidable obfuscation. [113],[116] ) A cancer clinician's knowledge begins with a tumor and ends with it. By a variety of lumpectomic and/ or lumpolytic measures, the neoplasm is made to disappear. The whole cycle of detection/destruction of lump is repeated with the reappearance of the tumor. Tumor = Lump, is thus the clinical border line between the blissful ignorance of what did happen and the unhelpabk uncertainty of what will. Vis-a-vis a patient, a cancerologist only knows of the tumor-how to diagnose/treat/retreat it in n-tuple ways. It is a sobering thought that cancerology is nothing more, or less, than lumpology. The logic of such curl summing up can be understood by considering, (a) the preclinical or pretumor phase, and (b) the clinical phase-the tumor and after. Canceration to Tumor: Preclinical Phase Let the setting of the story be the body of an eminent cancerologist-the pancreas [21] or the stomach [10] of Armand Trousseau, the great clinician of Hotel Dieu de Paris, the stomach [36],[113],[206] of William Mayo, Sir D. P. D. Wilkie, or Ernest Borges of Tata Memorial Centre, Bombay, the lung [54] of David Karnofsky, the kidney [100] of Harold Dorn the cancer-epidemiologist or the colon [126] of Leslie Foulds. Whether it be these luminaries or their patients, canceration-the inception of cancer-starts as a very small, silent event that tardily marches over several years to the stage of being detected, by a -graph, -scope or clinical/self examination, the starting point being a few cells in a single focus or in many foci as in leukemia. Before hitting the eye of the clinician or causing symptoms in the patient, each cancer takes a pretty long time-computed as ranging from 2½ years [43] for a rapidly lethal cancer as of the lung to as much as 17 years or more for such cancer as of the breast. [43],[128],[130] During this time, even the cancerologist-patient is blissfully unaware of the cancerous happening. Considering that the average duration of survival after the diagnosis of cancer is 3 years, [33] this preclinical silence of cancer speaks for the quiet, benignant behavior of cancer over a greater part of its stay in an individual. This is probably true of a number of pathologic processes: "Thus, the myocardial infarction, the cerebral infarction, or the gangrene of leg which terminates a patient's life may be seen as the final episode of a series which remain silent over a long period of the patient's life before they obtrude into his experience and finally terminate it." (Pickering). [158] While the cancerous silence is kind to the patient, it rings the death knell for the DATE dogma, as was editorialized [59] over a decade ago, and almost concurrently echoed by Macdonald [130] when he declared that two-thirds of the life cycle of breast cancer is completed by the time "early" clinical discovery becomes possible. Furth and Kahn [72] could experimentally produce "leukemia" in a healthy mouse by transplanting a single "cancer" cell. This may drive home the point that a cancer to become generalized-undetectably to begin with-does not require more than the first few cancer cells. The clinican, then, is too late when the first few normal cells turn into the first few cancer cells. A mammographically detectable "tumor" has to be at least a cubic mm in size, and worth at least 1000,000 cells [119] before it could be detected; such a lump over the silent years has had on each day "twenty-four hours for metastasis to occur." [59] Let us, for once, admit cancerrealisatically that from canceration to tumor is from ignorance to tumor. Tumor and After Eureka, the tumor is found. This eureka-euphoria can last no longer than the time Archimedes was in the bathtub on that fateful day, for uncertainty plagues every move. The incurable individuality of each tumor and its owner makes unpredictable, (a) what the tumor will do to the patient, and (b) what the treatment will do to the tumor. Regarding the former, it may be, as for Mayo, Wilkie, Borges, Foulds and Dorn, "the discovery of a hard tumor, " [203] and an inexorable downhill course, despite all attempts at treatment. Left untreated, as stated earlier, the tumor may not bother, choosing to go to the grave with the patient. Treated, as for the pathologistauthor Boyd, [21] the tumor may nol reappear for a lifetime. In short, tumor treats the patient the way it likes in a predetermined fashion regardless of the therapist. Treatment, in fact, may ill-treat the tumor: Even after the most painstaking application of the criteria of operability, there are women in whom surgery manages to accelerate the evolution of breast cancer. [130] "Some patients with breast cancer in early, operable stages have very short survival after surgical intervention." [107] The authors [107] introduced the concept of acute evolutive onset (AEO) attending some cases of breast cancer as could be judged by clinical examination, mammography, skin thermometry, and provoked hyperglycemia test. Surgical intervention markedly precipitated distant spread in cases with AEO as compared with the control AEO group untreated by surgery. The authors [107] concluded that "surgical intervention must be excluded as the first therapeutic step, even in stage I breast cancer." We do not know how many other cancers have AEO so that this or that form of therapy may only serve to fan the fire of a smoldering early cancer. The foregoing uncertainties are . complicated by what treatment does to the patient, for all cytotoxic agents-chemical or radiational-are accelerators of aging, [3],[161] all with a "marrow-devastating" [86]"oncogenic" [87] potential. Tumorectomy (or -lysis), in a manner of speaking, is symptomectomy/signectomy, but not cancerectomy. Treated, the tumor is out, the cancer is not, much less cancerability of normal tissues. Over a century ago, Billroth [15] , aphorised that surgery removes a tumor, but not the patient's diathesis for cancer. "Unfortunately it must be admitted that all cancer surgery is in large measure palliative, given the occult spread of the disease before treatment in a high percentage of cases." [192] -an observation not denied by the most diehard DATEists." [13],[91] The much-celebrated victory over leukemia must contend with the fact that, although in complete remission the peripheral blood picture and the bone marrow are normal, 10 8 to 10 9 leukemic cells still remain, making relapse virtually inevitable. [201] Whither Cancer Treatment? Thus, all told, prior to the detection of and after the detection/treatment of a tumor, clinicians are essentially knownothings-a gnoseological bitter pill served sweet in Shelleyan style: We look before And after, a tumor And find that We know naught. Glemser's worldwide survey of Man Against Cancer [75] only revealed that the realistic title of his book could have been Man Helpless Against Cancer: Surgery is dispensable, radiotherapy obsolete, and chemotherapy a farce. Any talk of treating cancer tantamounts to Ecclesiastes' Vanitas vanitatnm: "Nothing is worth doing, no way is better than another." [205] The foregoing finality may smack of a deliberate offense-a Nietzschean "devaluation" [205] of all therapeutic values. But the reality is different, more about which, anon. "At the present time," Brooke [24] generalized in 1971, "cancer treatment appears to have reached a culmination, a peak beyond which we have not moved for several decades." This means that cancer therapy did reach its (whatever) zenith of perfection which has plateaued ever since then. But as none of the therapeutic measures against cancer has been, as yet, held as not rejectable, we are forced to conclude that cancer therapy reached its Peterian zenith of imperfection "several decades" ago, and all that we have been doing is to move in circles and call it as "'progress" and "recent advances" and so on. Such euphemismism may be justified on the geometric ground that all circular motions are made up of a series of motions in a straight line, and straight line motion is progress. Cancer therapy has, all along, betrayed the application of utter lumpolytic logic to the false premise of a cure. Watts [197] has described the peculiar and perhaps fatal fallacy of modern times: the confusion of symbol with reality. Such fallacy dominates cancerology so that what is diagnosed and treated is not cancer-"a disease of the whole organism" [162] -but its most evident manifestation, a lump or an -oma. The consoling cures obtained in "certain rare neoplasms" [183] such as gestational choriocarcinoma, neuroblastoma, retinoblastoma, Wilms' tumor or even "low-grade malignant bone tumor (s) ", [19],[134] are a function of the nature of the cancer, rather than any ingenuity of the hit-and-miss treatment. The cure of solar-plexus cancer-"the 19th neoplasm cured by chemotherapy' [140] -by MIRACI, makes the curable list impressively big enough, yet scientifically too hollow for cancerology to survive its current intellectual crisis.
At the very outset, the indispensable role of cancer therapy must be underscored. Despite the accepted impotency of all therapies [Figure 1] against autochthonous cancer, one and all measures are useful when employed to ease a dis-eased cancer patient. Cancer is, as Foote [69] observed, "a mysterious plague that cries out not for philosophy but for a palliative." A cancer patient with esophageal/ colonic obstruction, symptomatic SOL in the brain, a massive ungainly jaw from Burkitt's tumor, fungating mass in the breast, or a large osteosarcoma of the humerus cannot be bored with the philosophy of whither cancer therapy, but must be eased immediately with an appropriate palliative measure. Cancer will be with mankind forever, being part, and progenitor of it. Cancer therapists will be needed to play their vital easing role as long as mankind survives. As a science, cancerology has been a do-goodistic crusade, devoid of biologic scholarship, [28],[178] that has anthropocentrically made an enemy out of a biophenomenon. Despite all its bizzare demeanors, cancer is contradictionlessly [171] comprehensible [113] as an intrinsic, age-dependent, senescent process. Its intrinsicality does not permit of cause/s, nor of its cure/control by any extrinsic agent; its age dependence permits it to subserve obligatory herd mortality; [104] its senescent nature allows it to be present and progress without being necessarily symptomatic or lethal, making it a la Dobzhansky, [55] a part of an organism's continuing development. We still know not whether cancer really kills a patient, or is merely an incidental manifestation of a larger thanatogenic reality. [104] At whatever age it occurs and whatever time it is diagnosed and treated, cancer-death-rate has characteristic constancy, [57],[104],[208] render ing the five/ten-year-cure rates mere fallacies of confounded countdowns. [124] On the basis of vast survival data of cancers treated and untreated, Waterhouse [195] , was inspired to suggest that the diagnosis of cancer should not necessarily deprive a person of the benefit of insurance. That cancer is not [152] the villian-of-the-piece can be appreciated even when compared with other diseases. ZumofT et al [208] analyzed the mortality statistics for series of patients with hepatic cirrhosis, metastatic breast cancer, chronic lymphatic leukemia, and myocardial infarction. "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" [208] . The authors [208] concluded that all the above diseases have a common alteration of "the undefined physiologic systems" that govern susceptibility to aging and dying, producing thereby an elevated and constant increase in this susceptibility. Cancerrealism can be a good guide in outlining the scope and limitations of the clinician, engaged in cancer diagnosis, treatment and prognosis. The appreciation, that rank ignorance and uncertainty rule the fore and aft of the crude dividing line of our tumorous knowledge, compells the formulation of and the adherence to a therapeutic [76],[113] dictum: Treat to ease the patient ill at ease, and to this end spare no measures, including those for the relief from pain, and anxiety. Cancerrealism does not permit of treating those who are at ease, at peace with their lumps. The need and the wisdom to treat the patient symptom/sign-far and no further leaves out radicalism, superradicalism and cytotoxic cocktailism, knowing that a cancer patient needs, above everything, joie de vivre which greatly depends on healthy bowel mucosa and cellular bone marrow. Such restraint is not rare; CML, CLL, breast and rectal cancer are examples [49],[80],[83],[146],[194] in point. The Hippocratic ideal of primum non nocere could not find a better place than in clinical cancerology. Dunphy [57] has recently underscored the hazards of prognosing; many a cancer manages to make a mockery of carefully considered clinical prognostications. The better course is "I do not know," the best course is to emphasize that No one knows, no matter how benign or malignant looking, localized or widely spread, early-treated or late-treated, ill-treated or well-treated, the cancer is. The needlessness [118] of treating asymptomatic cancer takes us a step backwards to the needlessness of diagnosing cancer, and more so precancer, thus avoiding diseasing an individual fully at ease. Diagnostic iatrality is a potent dis-easing force of modern medicine thriving on DATE drives. A Fischerism [67] very well describes the lethal potential of a diagnosis: "Do you ever ponder the advisability of not making a diagnosis and thereby avoiding a death sentence?" With the pronouncement of the diagnosis of cancer, the bird of fear-as Norman Mailer would describe-builds a nest in the patient's throat. Cancer-diagnosis inevitably induces [53] overwhelming anxiety, paralyzing fear, universal panic "akin to an animal response with witchcraft powers, "[53] not sparing even the physicians and surgeons "thoroughly acquainted with the facts of curability." [53] The antidote to this iatrality is the cancerrealistic restraint-not to diagnose a cancer that has, hitherto, not bothered the patient. Soma cue is currently available in this direction: "The benign behavior of an occult thyroid carcinoma (which cancer, when considered as a systemic process, is not occult?) makes the risk of not diagnosing one during life of no consequence." [169] The greatest service that a clinician can render, apart from diagnosing lumps and treating cancer, or giving poppy [5] for pain, is to teach a patient to live, zestfully and productively, with cancer. Such enlivening approach is consistent with the little emphasized benignancy of malignancy viz., that all cancers do not kill rapidly. A favorite theme of William Osler [155] was to live in daytight compartments. Osler did not direct his positivism to some cancer patients, for whom time is supposedly running out. He, like Kipling and Stevenson, pleaded that time is running out for everyone afflicted, as Cowley put it, with "an incurable disease" called life. And since everyone so incurably afflicted with a killer disease lives, there is no reason why the presence of another killer disease, e.g., cancer, should mar an individual's zest for living, her or his joie de vivre. And if the physician can teach the patient how to live with cancer, could he not as well teach how to die, with dignity, of cancer? If life should be regarded as essentially good, Ardrey [7] avers, then death must be revered as its foremost angel. Death has its own reasons a thing thanatologists are urging us to accept. [57],[117] If we accept death as natural, should we not also accept the bodily processes that lead to it? "After all," Pickering [158] emphasized, "it is these diseases which kill and make way for the new life." JBS Haldane [85] paid a tribute to his rectal cancer that killed him by the poem Cancer's a Funny Thing, the message being "cancer can be rather fun" provided one faces the tumor with a sufficient sense of humor. Tout comprendre cancer, c'est tout pardonner cancer, c'est tout pardonner mort. Let us accept cancer as a part of living, and a way of dying.
[Figure 1]
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