LIVING DYING

( By Dr Manu L Kothari and Dr Lopa A Mehta )

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The Trans-Technique Aspects of Disease and Death

This is the century, we are told, in which innovation
and scientific-technological advance - progress in other
words - should be able to produce anything within the
limits of what is physically possible in principle. We
have only to want it sufficiently and to pay the price
and we can have it. If rocks from the moon can be
brought to Houston, why should we not be able to
apply molecular biology, cytology, and the rest, to cure
what is now incurable?

Mac Farlane Burnet

The technological triumphs in medicine this century outweigh and outclass the aggregate achievements of the entire human past; yet modern man has been denied the elixir, the cure for his disease and death. An objective survey of medicine’s failures reveals that it is not that the technology per se is ineffective - it does what it is designed to do - but that what technology solves is trivial, and what is just cannot touch is crucial, being beyond any technique - extant, evolving, or envisaged. Most of human diseasing and death is trans-technique.

What is technique, and what is trans-technique? Technique in medicine is whatever a doctor does to a patient, be it diagnosing, treating or prognosing. It admits of the simplest to the superlatively sophisticated. Trans-technique aspects of disease and death are those innate, ordinary, day-to-day features of human diseasing and dying that technique can in no way modify to a patient’s advantage. Before we detail the principles that underlie the trans- technique- ness, a survey of the state of the medical art at the end of this century is in order.

‘Need your doctor be so useless?’

The above title of a book by the Canadian physician A. Malleson is symptomatic of the current state of modern medicine - confronted with congenital malformations, cancer, coronary artery disease, peripheral artery disease, stroke, high blood pressure, or diabetes.

‘It is a sobering thought that after several decades of research, a number of international conferences and many other meetings, seminars and symposia, the problem of human malformations remains essentially unchanged.’ Having introduced a symposium with these words, McKeown proceeds to chastise modern medicine further on human malformations - etiology unknown, rate unchanged, relative contribution to infant mortality greatly increased.

Best cancer, as a paradigm, typifies the colossal failure of cancer research: It is a subcutaneaous (under-the-skin, superficial) cancer - the natural history of which has been studied for the past 200 years at least, easily amenable to examination by the patient herself, and more so by the doctor, subjected to varied forms of grading, staging, radiography, hormonal therapy, minimal to most radical surgery, and cocktails of chemotherapy -that has stubbornly refused to yield at all, in any way from the time a group of Scottish physicians published a memorandum on its nature in 1802. Indeed, Atkins of England pointed out that the recent studies on breast cancer have made such tremendous progress that, today, no one knows how to treat it.

Coronary artery disease, generally manifest as heart attack, has been attacked by doctors through electronic wizardry enshrined in the ICCU’s and through a work of surgical excellence called the coronary bypass. Of no avail. The ICCU’s, wryly described as ‘pressure cookers’ have proved counter- productive, with the patient having a greater chance of dying there than outside. McIntosh, a past president of the American College of Cardiology commented on coronary bypass that ‘there is no convincing evidence that the procedure prevents or postpones premature death.’ Datey, a leading Indian cardiologist stated: ‘The five year end results of heart patients with conservative medical treatment and bypass surgery are the same.’

About peripheral artery diseases, Jaffe has observed: ‘Despite an extraordinary investment in research resources we are still far from understanding the pathologic mechanisms responsible for peripheral vascular diseases. As a consequence, all treatment, medical and surgical, must be directed towards abatement of symptoms and prevention of complications, rather than against the diseases themselves. It must be clear, therefore, that our therapeutic armamentarium is limited severely.’ Stroke, medically labelled as cerebrovascular disease, has remained impervious to all modes of medical management, maintaining its pristine behaviour the world-over, exercising closely comparable 5-year-survival rates and ‘funeral-rates’, prompting an epidemiologist to suggest that we had better accept it as but a form of ageing, being as unsolvable and as irreversible as ageing itself.

High blood pressure, medically called essential hypertension or essential high blood pressure, has remained as elusive entity for it has yet to be defined, satisfactorily for the doctor or rewardingly for the patient. Pickering, one time Regius professor of medicine at Oxford, showed that the ‘so-called essential hypertension’ is incapable of being defined except arbitrarily, the definition varying from day to day, doctor to doctor, and place to place. Doctors cannot decide whether or not what they call high blood pressure or hypertension is something natural to the patient, being ‘a disease in its own right;’ and no wonder, they hold the appellation essential, as essential to their hypertensive thinking. As is the definition, so too are the diagnosis, treatment, and prognosis of essential hypertension - arbitrary, erratic and anxiety-making.

Talking of diabetes, Boyd, an eminent pathologist and author, lamented that the more we know about it the less we seem to understand it. This continuing counterproductiveness stems from the fact that (a) diabetes - more completely called diabetes mellitus - has never been clearly defined, (b) the disturbance of glucose metabolism that doctors emphasize and treat represent only the tip of the iceberg of the disturbed metabolism of the patient, and (c) neither insulin nor any other ‘antidiabetic’ agent alters the course of the disease or the accompanying, inevitable arterial damage. It is chastizing to note that 60 years after the epochal discovery of insulin and its (first) usage on Leonard Thompson, we know more about the inherent limitations of insulin therapy than about its presumed ability to ‘cure’ diabetes.

All told, the most sophisticated medical manoeuvers or machines don’t seem to make a major difference, and ‘advances in diagnosis and treatment do not necessarily translate into increased survival.’ Most of the tools a doctor used twenty-five years ago fitted into a small black bag; today the technologically- armed physician owns or has access to $250,000 worth of equipment: whenever one tries to link the development of new technology with a coincidental improvement in healing, the answer is always the same: Nil. Medical recourse to computers has had the GIGO snag: Garbage In, Garbage Out.

Where has medical technology gone wrong? A dispassionate, epistemological evaluation of medicine’s technological gains reveals them to be imagery; accessible, analytic, associative, and amplificatory. The more the physicistic science and the physicianly art interact, the greater is the variety of means by which medical imagery can be obtained. Yet, to take but one example, X-rays, xeroradiography and computerized-tomgraphic (CT) scan,ultrasonography and nuclear-magnetic-resonance (NMR) imaging have left a cancer where it was - diagnosed a little too late. The ability to cannulate the pancreatic duct or artery towards the diagnosis and treatment of pancreatic cancer, or to get into the skull to treat the brain cancer, is an accessible advance that leave the cancer’s autonomy untouched. Increasingly refined biochemical techniques allow many a substance to be measured with pico-precision (pico = 1/10 12), thus analytically telling us a lot about heart attack, diabetes mellitus or rheumatoid arthritis, but without the liberty to predictably and / or favourably alter the course of the disease. Epidemiology connect the husband’s cigar to the wife’s cancer, coffee to cardiovascular disease, and refined sugar to peptic ulcer - an associative exercise that makes more anxiety than sense. The electron microscope amplifies the size of a T-lymphocyte any number of times only to amplify our ignorance of the cell to the same magnitude. In modern medicine, technology glisters, but is, often, not gold.

A number of diverse medical men have admitted that ninety per cent of the bad things that happen to man’s body are beyond the ken of modern medicine. Armed with technical might, the doctor can, with the healing power of nature providentially at the patient’s beck and call, revert acute physiological crises to healthy states, set fractures, fix retinae, deliver babies facing a narrow birth canal, remove lumps and cataracts, replace a valve or a joint, correct mechanical defects such as cleft palate or hernia, all this comprising the ten per cent of man’s maladies that medicine can manage. The rest is trans-technique. Let us see how, and why.

Four principles account for the trans-technique nature of diseases. These are cellularity, systemicity, uniqueness and heredity. An integrated appreciation of these principles will help us understand medicine’s limits, no matter what its technical might.

Cellularity

There are features of a mammalian cell that make disease and death trans-technique in more ways than one. It is a fitting paradox that what advanced cytological techniques have revealed about the cell has driven home the truth that a cell’s behaviour, in health or disease, can hardly be trifled with. The microsize of human body cells accounts for the fact that before a scan discovers a cancerous lump measuring one cubic millimeter and weighing one milligram - the smallest tumor mass that one could ever hope to detect clinically - the cancer is already a million cells strong and several years old. Early diagnosis of cancer is, thus, only a myth. The same considerations apply to the disease of coronary (or any other ) arteries, the underlying atheromatous process being held by some as cancerous in origin. Any attempt at flooding the body with anti- abnormal cell-agents (radiation, chemicals) fails because of the selfsameness of all body cells, rendering selective destruction of undesired cells impossible. Supposing that a highly specific drug is developed and administered, the target cell can easily recall its microbial past to readjust its genetic machinery - that is, mutate - to knock out the drug, since the mutative repertoire of a human cell borders on 256 followed by 2.4 billion zeros.

In no two human beings, twins not excluded, do the cells of one see eye-to-eye with those of the other person. Each cell, then, in a human being, has an irrepressible individuality that brooks no foreign cell around nor is likely to be tolerated as friend in an alien body. This is an age of transplants, performed because they are technically easy, although biologically baseless. Following any organ / cell transplant, the donor cells and guest cells wage a relentless war for which the patient (the recipient) pays a great price. There is nothing on the medical horizon that can mitigate the biological impotence of organ transplantation.

Systemicity

The human body is an integrated whole that starts as a single cell, and builds up a cytogalaxy that behaves as a single, concerted unit whose seemingly disparate parts form, grow, and decay in unison. Systemicity of a disease implies its presence in wide areas of the body. Cancer, for example, has been correctly declared a disease of the whole organism. Arteriosclerosis or the hardening- and-blocking of the body’s arteries involves all the areas of the body. Diabetes (mellitus) affects all blood vessels and all parts of the metabolic machinery of the individual. All diseases of ageing involve the whole body; they thus exhibit systemicity.

The systemicity of a disease rules out its being either diagnosed early or removed or destroyed completely. A cancer thus does not lend itself to complete destruction by surgery, radiation, chemotherapy, or immunotherapy. Even if we were to nab the last cancer cell, the next normal cell would foil attempts by turning cancerous, through a process named neocanceration or recruitment. The sole curative triumph against gestational choriocarcinoma ( a cancer arising from fetal tissue during pregnancy) is entirely due to the fact that such an eventuality of neocanceration is ruled out by the absence of the normal progenitor cells that comprise the discarded fetal part of the placenta. An arterial bypass takes care of the block that the operator sees or has access to, but what of the arteries beyond, or before, or elsewhere? This explains why a patient with heart disease fails to benefit from the much-vaunted coronary artery bypass. As for diabetes, antidiabetic agents touch the proverbial tip of the metabolic iceberg, affecting in no way the overall, arterial disease and fat and protein metabolic disorders, that are now accepted as integral parts of the diabetic process.

Uniqueness

Variability, it is said, is the only invariable law of biology, a natural propensity that unfailingly varies one cancer from another, one heart attack from the next. If the uniqueness of every individual is an unsolved problem of biology, then the uniqueness of every disease is the unsolved and unsolvable problem of medicine. There are as many different diseases as patients. Even ‘identical’ twins differ in their individual disease patterns. The presumed identicality of the genotype in such twins is unable to circumvent this code of individuality.

Cancer, indisputably traceable to precisely pinpointable and culturable cancer cells, provides a remarkable example of the unprecedented, unparalled and unrepeatable nature of a disease. Naturally occurring cancers are extremely diverse even when they carry the same diagnostic label. No two cases of coronary artery disease, stroke, cancer, diabetes, arthritis, or auto-immune disease are identical either in their presentation or in their progress. The behavioral uniqueness of a disease, with its unpredictability, forms the basis for unexpected successes and equally unexpected failures, given the same treatment. Cancers have been classified into ‘good’ and ‘bad’, the good ones curable by any treatment, the bad ones by none - a retroactive judgment applicable to any other disease and fully justifying the Chinese proverb that a therapy works in a patient destined to survive.

This proverb smacks of irreverence for the celebrated and seemingly learned art of prognosing, now backed up by technology. Among diagnosis, prognosis and treatment, prognosis is the most difficult to evaluate. The accurate prediction of things to come is baffling, perplexing, and problematic. The reason is two-fold: (a) In most diseases, what the doctors can prognosticate about is based on group statistics that obviously have no bearing on an individual case. (b) Even when, at an individual level, the doctor has fully at hand the reports of some test, ECG (EKG), X-ray. or scan, and thus ‘justifiably’ bases his prognosis on the evident benignity or otherwise of the lesion, such a correlation has not proved trustworthy or fruitful. Patients with reassuring investigations and prognosis have died, and those with a prognosis of doom have survived. All technological marvels, computers not excluded, deal with the appearances and assumed correlations of a human being’s disease; none, as yet, knows or can know of the behavioral uniqueness of such a biological entity. Of diagnosis, treatment, and prognosis, the last is the most trans-technique.

The unique reality of medical practice is that, be it Paul Dudley White (Cardiologist to American Presidents) and his 103 year old patient Charles Thierry, or James Herriot and the dog Jock, it is a one-to-one encounter where the uniqueness of the individual, his disease, his very biological trajectory is unpredictable, unalterable, and overwhelmingly important. For modern medicine, the most chastizing part of an individual’s biological trajectory is its refusal to provide any quantitative correlation- ship between the earliness or lateness of a disease on the one hand, and the probability of the disease and / or death on the other. The healthy do not necessarily survive; the diseased do not necessarily die. Norman Cousins’ dig at medical experts who don’t really know enough’ in his Anatomy of an Illness must be viewed from the standpoint that the experts never know anywhere near enough, not because they do not way to, but because what they wish to know and what patients expect them to be knowledgeable about truly lies in the realm of the unknown, or, more accurately, unknowable.

Herdity

Herdity could well be described, at the very outset, as a corporate programme subserved by individual performance. Cellularity, systemicity and uniqueness are features innate to an individual; heredity is a force that the human herd exerts on the individual. The relationship between the individual and the herd is a remarkable biological feature that more than vindicates John Donne’s statement that ‘no man is an island of itself: every man is a part of the main.’

Mankind was, and is, a single inclusive population and is endowed with a single corporate genotype,a single gene pcol. Appropriate to this is the concept of an individual as one who extends, in time as in space, beyond the frontiers of his body, and who is linked to the past and to the future, regardless of the ephemerality of his present. Add to this the conceptual framework of quantum physics that reveals a basic oneness of the universe in which, at a deep and fundamental level, the seemingly separate parts of the universe are connected in an intimate and immediate way, in a complicated web of relations between the various parts of the whole. We are now poised to view an individual’s body, his disease, his cancer - each unfailingly unique - as a spatiotemporal manifestation of a cosmic order. I am what I am, and allowed to be so, for I know who all others were, are, and will be so as not to duplicate them, and they in turn know of me so as not to make a duplicate of me or of my disease at any time.

Climbing down from cosmic considerations to clinical, beside reality allows us to appreciate the role of herdity in distribution of disease in any given group. As general statistics go, the incidence of, say, acute lymphatic leukemia is 1 in 33,000, of cleft palate or neural tube defect is 1 in less than 1,000, of cancer 1 in 5, of blood vessel disease 1 in 2, at random, country after country, year after year. A surveyor of the statistical figures on the occurrence of cancer is struck by their unexpected constancy, for a given region, year after year, decade after decade. A high incidence of cancer in one part of the body is consistently balanced for a given country or a population, by a low incidence of cancer at another site, to permit the reassuring generalization that cancer occurs everywhere in the world, in excess nowhere. The age-specific mortality rates from cardvascular disease, year after year, decade after decade, and in country after country fit quite closely the same line. There is a fundamental natural benevolence in the global impartiality with which disease and death treat mankind. The prevalence of diabetes mellitus is more or less constant for all countries. Cancer, stroke, diabetes, hypertension, heart attack and so on are an integral part of humanity, of human heredity. This remarkable herd-certainty and individual probability of pathological events is a function of a corporate herd program that finds expression at the level of an individual who has crossed a critical genetic threshold. Herdity, thus, is a reciprocal relationship between an individual and his herd, what geneticists have been describing as polygenic inheritance.

The evolution of the concept of polygenic inheritance has brought a shift in genetic thinking, from heredity to herdity, for polygenic inheritance is necessarily a statistical concept that concerns not the individual but population aggregates. Polygenic inheritance has been invoked to explain a wide variety of diseases, ranging from congenital malformations to cancer, porphyria to peptic ulcer. This means that most diseases do not have a cause. Causeless diseases cannot be prevented; they are an integral part of man’s growth; in terms of both cause and course they are trans-technique. Herdity is trans-technique.

The idea of herdity governs all the phenomena in relation to disease and death in a herd. The herd determines who will get what and when, in whom the disease will be slow, in whom fast, and so on. This would explain why the commonness of prostatic cancer beyond the age of 50 is paradoxically matched by the uncommonness of its malignant behaviour and how persons with bad coronary angiograms survive those with good ones.

The most compelling evidence in favor of herdity is, in general, the programmed, herd mortality that, as a physiological function, is seen in man, in animals, and in drosophila. Gompertz saw this as a constant increment in mortality beyond the third quinquennium of human life, doubling every 8 years, a phenomenon no medical advance has been able to stem. John Knowles, as president of the Rockefeller Foundation, wrote in 1977 on ‘The responsibility of an individual ‘ charging the latter’s ‘personal misbehaviour and environmental conditions’ for over ninety-nine percent of illnesses. Knowles’ faith in reasoned behaviour did not prevent the pancreatic cancer that killed him in 1979. He was but one of the 19,000 that develop pancreatic cancer and die from it in the United States every year. Knowles died at 52, some do at an earlier age, others at a later age, all a part of herd distribution, of herdity.

Summing up

Lester Brown, of the Worldwatch Institute, has divided recent history into two distinct technological periods - the period 1940 to 1970 of unrestrained optimism, the second, thereafter, of utter disillusionment, of the crumbling of a seemingly shatter-proof faith in technology. It is time that medical men understand the reason behind this stalemate, and turn the situation to the benefit of their patients and to their own enlightenment.

Cellularity, systemicity, uniqueness and herdity can be realized as the suchness, of diseasing and dying. The evolution of the trans-technique concept explains technology’s failures and limits, exercises restraints on this age of inflated expectations, encourages us to be radical enough to abjure straight-line solutions and many a technological trap - to wit, the tyranny of mass-screening, debilitating therapies, or kill-joy preventionism.

An editorial in The New England Journal of Medicine entitled ‘The toss-up’ bears eloquent testimony to the rationale of the above. It is common experience that, on a given case, the proposed diagnostic or therapeutic thrust ranges from extreme conservatism to surgical ultra-radicalism. After attributing such divergence in medical thinking to the idiosyncracies of the physicians, the authors propose: ‘Perhaps all these factors are involved in clinical controversies, but we propose that one explanation has not been sufficiently recognized: that it simply makes no difference which choice is made. We suggest that some dramatic controversies represent "toss-ups" - clinical situations in which the consequences of divergent choices are, on the average, virtually identical.’ The identicality of the consequences, no matter what the investigations and what the therapy, is a result of the basic fact that the problem being tackled is beyond the limits of technology.

Scientis est potentia: knowledge is power. The knowledge that a lot in medical practice is beyond medical technique can, as a concept, propel us towards discerning inaction in medicine. Munsif, an eminent Bombay surgeon, was fond of stating that ‘a good surgeon is one who knows when not to operate.’ What a medical man needs to learn, in today’s technicalized scene is when not to act, an intellectual and a therapeutic revolution that can safely rest on the concept of trans-technique.

The well-informed physician and patient of tomorrow will accept ‘doing nothing’ as an integral part of the relevant investigations, diagnosis, and treatment. No treatment can often be the right treatment, a proposition that is consistent with a revised connotation of ‘cure’, the most cherished word in medicine. The word ‘cure’ comes from curatio ‘I take care’. Jackson, Oliver Wendell Holmes’ teacher, never talked of curing a patient except in the true sense of ‘taking care’. Jackson felt that doctors, by the misuse of the word ‘cure; arrogated to themselves greater powers than were their due. Modern medicine is in need of humility, and must restore ‘cure’ to its pristine and most pertinent meaning: with a concerned physician around, no disease, no death, is incurable. A drug to ease, a procedure to palliate, a word of cheer, the graceful stoicism to hold the dying patient’s hand - all this and more falls within the curative competence of a compassionate clinician. Regardless of the trans- science and the trans-technique aspects of disease and death, the art of medicine and the Dear and Glorious Physician, will be there forever.

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