But biology does not readjust to accommodate the false theories of scientists, and by the mid-1990s the inconsistencies in The Social Theory started to become more generally recognised. In 1994 the editor of the prestigious New England Journal of Medicine enquired: ‘What should the public believe? They substitute margarine for butter, only to learn that margarine may be worse for the arteries. They are told to eat oat bran to lower the cholesterol only to learn it is useless. They substitute saccharin for sugar only to hear that some research has found an association with bladder cancer, while others do not.’51 A year later Science, in an article entitled ‘Epidemiology Faces its Limits’, observed ‘the search for subtle links between diet, lifestyle or the environment and disease is an unending source of fear – but yields little certainty’. The public had been exposed to a ‘mind-numbing array of potential disease-causing agents from hairdryers to coffee . . . the pendulum swings back and forth resulting in an “epidemic of anxiety”’.52
There is a view that it has all been in a good cause. Bacon and eggs may not cause heart attacks or cancer but the cult of a ‘healthy lifestyle’ is a good thing as it encourages people to become fit. Health concerns about the environment may have been exaggerated but have led to much stricter regulation against pollution, which again must be deemed a good thing.
But these alleged benefits must be set against a large debit account. The Social Theory is synonymous with victim-blaming because its logic requires that patients have only themselves to blame for persisting with their unhealthy habits and not heeding helpful advice. It has made people much more, rather than less, concerned about their health and an infinite variety of hidden dangers in their lives. The reality that now most people live out their natural lifespans to succumb from complex diseases determined by ageing is transformed into the illusion that illness is ubiquitous, and its causes lie in the way that people lead their lives, and thus can be readily prevented. The Social Theory simultaneously manages to overemphasise the role of illness in people’s lives while at the same time trivialising it. It generates the myth that the practice of medicine is futile, because the allegedly important factors in health are outside its control. Its apparently inexhaustible range of contradictory hazards of everyday life undermines the authority of medicine as a source of reliable knowledge, for if, as has been claimed, baked beans prevent cancer and children are to be discouraged from chewing plastic ducks lest their chemicals be carcinogenic, then anything goes. It has wasted hundreds of millions of pounds in futile research and health education programmes while justifying the imposition of costly regulations to reduce yet further the minuscule levels of pollution in air and water. And to cap it all, it does not work. Its promise of preventing tens of thousands of deaths a year has not been fulfilled.
3
THE UNSOLVED PROBLEM: THE
MYSTERIES OF BIOLOGY REVISITED
The two great projects of the last two decades – The New Genetics and The Social Theory – constitute the fall of modern medicine. Their scientific bases – molecular biology and epidemiology respectively – could not have been more diverse, yet they shared the same aspiration. They sought to replace the chance discovery of new drugs and the empiricism of technological innovation by a new ‘third’ way – the elucidation of the causes of disease that would lead either to rational forms of treatment or the prevention of common illnesses. The lure of The New Genetics lies in its reductionism, the explanation of the phenomena of disease at the most fundamental level of the gene and its products. The allure of The Social Theory is its simple, readily understandable explanation of disease, which offered the prospect that it could be simply prevented.
The main reason why these two projects have failed is that the causes of common diseases are neither genetic nor social, but are either age-determined or biological and (for the most part) unknown. The time has come to switch from contemplating the past, to gaze into the crystal ball to see how near, or far, medicine might be from identifying these unknown biological causes of disease. We start by reiterating the nature of this, the great unsolved problem of contemporary medicine.
Medicine’s post-war success, built on the chance discovery of drugs and technological innovation, concealed the fact that its impressive achievements had been won without the necessity to understand the nature or causation of disease. And now, fifty years on, medicine still knows the cause of only a fraction of the diseases in the textbooks: the bacterial and viral infections, those resulting from a defect in a single gene (like cystic fibrosis); occupational diseases; the causative role of tobacco in lung cancer; and those primarily determined by ageing: arthritis, cataracts, the majority of cases of cancer and the circulatory disorders. But everything else – all the neurological diseases such as multiple sclerosis, and all the rheumatological diseases such as rheumatoid arthritis, all the dermatological diseases like psoriasis, and all the gut disorders like Crohn’s disease, and so on – their causes, quite simply, are not known. Contemporary medicine is thus in a situation directly analogous to that of the mid-nineteenth century, dominated by numerous presumed ‘infectious’ diseases but of unknown cause – anthrax, gonorrhoea, typhoid fever, suppuration, cholera, diphtheria, tetanus, pneumonia, meningitis, food poisoning, gas gangrene, plague, botulism, dysentery, paratyphoid, syphilis and whooping cough. Then, in less than two decades, Robert Koch and his colleagues, armed only with their microscopes and a few simple stains, discovered the precise bacteria responsible for each and every one. Similarly, it has to be presumed that some types of as yet elusive biological agents must explain why one person gets multiple sclerosis, another rheumatoid arthritis and a third schizophrenia. But what are they?
The probability that these unknown biological agents must be some form of infectious organism emerges quite clearly from examining the evidence of causation of two very different illnesses – multiple sclerosis and childhood leukaemia. Multiple sclerosis is an episodic illness where the fatty sheath that insulates the nerves becomes inflamed, causing acute episodes of weakness and inco-ordination followed by partial (or sometimes complete) recovery. It is much commoner among northern Europeans than other racial groups, affecting 1 in 1,000 people in Britain between the ages of twenty and forty. Why? There is, as always, a genetic element. The risk of MS rises to one in fifty for those who have an affected sibling and one in two for those with an affected identical twin. In well over 90 per cent of cases, however, MS just comes ‘out of the blue’, so the genetic component presumably increases susceptibility to whatever causes MS but cannot be the determining factor. For the proponents of The Social Theory, its relatively high incidence among Western nations points to a ‘dietary cause’. By now it has become quite unnecessary to bother to refute such speculation (though it will come as no surprise that the diet of those unfortunate enough to have MS is no different from anyone else’s), so it is possible to turn immediately to considering the evidence that MS has a biological cause.1
The pattern of MS over the last fifty years conforms to that of an infectious disease: its incidence has increased ten-fold in Britain over the last fifty years, while simultaneously (as happens with infections) becoming less severe over time. MS was a much more aggressive and rapidly progressive disease in the past, with the average period from its onset to debilitating paralysis and death being a mere eight years. Nowadays MS is almost compatible with a normal lifespan and most survive at least twenty-five years with the disease.2
But the most persuasive evidence comes from several ‘epidemics’ of the disease, of which the best described was in the Danish Faroe Islands in the North Atlantic, related both in time and exposure to the islands’ occupation by 7,000 British troops during the war. Prior to 1943 there was not a single recorded case of MS on the Faroe Islands. Then, between 1943 and 1949, sixteen cases were diagnosed in a population of less than 30,000 and a further sixteen followed over the subsequent twenty years. Twenty-five of the thirty-two cases had never left the islands. ‘There is no question
the British troops introduced multiple sclerosis into the Faroe Islands during their occupation,’ observed Dr John F. Kurtzke of Georgetown University School of Medicine in Washington in 1986. ‘We also conclude that affected Faroese later [transmitted] the illness to other Faroese. It seems inescapable that a transmissible agent is the cause of MS. We think it is a single, specific, widespread systemic infection which in only a small proportion of those affected ever involves the central nervous system.’3
We now turn to the second example, acute leukaemia in childhood, where the malignant proliferation of white blood cells infiltrates the brain, the bone marrow and other organs and which, prior to 1971, was incurable. There is already one well-known cause of leukaemia, radiation, as revealed by the increased incidence among survivors from Hiroshima and Nagasaki, so when in the early 1980s a cluster of cases was identified in Seascale near the nuclear reprocessing plant of Sellafield in west Cumbria, it was only logical to presume the radioactive discharges from Sellafield must be responsible. This assumption, as observed earlier, proved to be incorrect, as it would have required levels of radiation 400 times greater to have caused the cases of leukaemia. There had to be another explanation. The ‘clustering’ of cases of leukaemia that occurred in Seascale is a well-recognised phenomenon, having been first thoroughly documented back in 1963 with an ‘outbreak’ in eight children from the suburban community in the town of Niles in Illinois. ‘Seven of the eight children were from Roman Catholic families and each attended or had older siblings who attended the Parochial Grade School in the parish. The eight cases occurred in a typical time pattern and were accompanied by the parallel appearance of a “rheumatic-like” illness amongst other children attending the school.’4
This clustering pattern was no more than suggestive of an infectious cause (and could indeed have occurred by chance) until Dr Leo Kinlen of Oxford University conducted an extended and inspired series of studies. He noted how, as with MS in the Faroe Islanders, the cluster of leukaemia cases in Seascale occurred in a previously isolated and small community exposed to the influx of a large group of outsiders, the construction workers involved in the massive civil-engineering project of constructing the Sellafield plant. If leukaemia, like MS, was related to an isolated population’s exposure to some infectious agent ‘from outside’ to which they had no natural immunity, then, speculated Dr Kinlen, there should be similar clusters of leukaemia around other major civil-engineering sites in remote areas and in other situations where there was large-scale ‘mixing’ of populations – around military camps and the building of new towns in rural areas.
And so it has turned out. The excess number of cases is not great, but is certainly present wherever Dr Kinlen has looked: ‘The magnitude and consistency of the increases of childhood leukaemia found in population-mixing studies effectively rules out the operation of chance. Overall the findings point strongly to the transmission of some unidentified, possibly viral, infection and provides the most likely explanation for the Sellafield cases.’5
It is not usual to think of diseases such as MS or leukaemia as being ‘infectious’ illnesses, but, unlikely as it may seem, the pattern of their occurrence is strongly suggestive of some contagious biological agent that passes from one person to another, either damaging the insulating material around the nerves or stimulating the massive overproduction of white blood cells. It seems likely, on reflection, that the same must apply to all the other hundreds of illnesses that appear ‘out of the blue’ and are not determined by ageing – like rheumatoid arthritis, Crohn’s, schizophrenia or diabetes – but where, like multiple sclerosis and leukaemia, the putative biological agent remains unknown. It is, of course, not possible to predict where the biological explanations for these illnesses will come from, or indeed what form they will take (or indeed whether they will ever be elucidated), but there would seem to be three possible ways in which they might be found.
Firstly, the cause might be a bacterium or virus that has been overlooked or has proved difficult to isolate. Here, Dr Barry Marshall’s discovery in 1984 of helicobacter as the cause of peptic ulcer is the classic example, and it is interesting to note how the same organism has subsequently been implicated in other gut disorders, including stomach cancer and tumours of the small intestine.6 There are other examples ranging from the mundane, like dandruff (now known to be caused by a fungus, Pityrosporum ovale),7 to the exotic, such as tick-born Lyme disease (caused by an organism similar to that which causes syphilis).8 And, rather more circuitously, rheumatoid arthritis is now believed by some rheumatologists to be induced by the bacterium proteus.9
There is a second and particularly fruitful method of identifying the putative but unknown agents of disease: the technique known as polymerase chain reaction (PCR), which can detect the genetic footprint of a virus in the cells it has infected. Thus, the droopy face of Bell’s palsy has long been presumed to result from a viral inflammation of the facial nerve. But which virus? In 1996 Dr Shingo Murakami, a Japanese virologist, with the help of PCR found traces of the genes of the herpes simplex virus (responsible for cold sores) in the fluid surrounding the facial nerve of patients with Bell’s palsy, but not in the fluid taken from patients with other forms of facial paralysis. Hence Bell’s palsy must be caused by the herpes virus.10 Similarly, another variant of the herpes virus has been incriminated, with the PCR technique, in the lethal cancer Kaposi’s sarcoma, particularly prevalent among AIDS patients,11 and the human wart virus has been incriminated in cancer of the cervix.12 Similarly again, the acute onset of diabetes in childhood is highly suspicious of an acute viral infection attacking the insulin-producing cells in the pancreas, but it was not until the advent of PCR that the precise virus – coxsackie B – was identified.13
Finally, it must be presumed that forms of biological agents as yet undreamed of hold the key to the understanding of some diseases, or as Hamlet tells Horatio: ‘There are more things in heaven and earth, than are dreamt of in your philosophy.’ The biological world, it cannot be stressed enough, is full of mysteries. We have encountered many along the way. Why do bacteria produce antibiotics? Why are plants medicinal factories? We do not, and probably cannot, answer these questions because, as Einstein once famously observed, nature is ‘damned weird’. And perhaps somewhere in this damned weirdness will be found the as yet unanswered explanations for the causes of disease. Two examples must suffice. Every living organism from amoeba to man shares the one common feature that the DNA of their genes makes the messenger RNA that codes for the construction of the proteins that make up their cells. Or at least that was the dogma until the discovery in 1970 of the one solitary exception to this rule, a retrovirus that takes RNA and turns it back into DNA. The discovery of this utterly unique biological organism proved to be enormously significant on two counts. The enzyme produced by the retrovirus – reverse transcriptase – was the crucial step that allowed the New Geneticists to identify the genes for haemoglobin and insulin. Then, in 1984, Robert Gallo of the National Cancer Institute discovered that one species of retrovirus – human immunodeficiency virus (HIV) – was responsible for the most lethal new infection to have emerged in the Western world over the last 100 years, AIDS, which again, utterly uniquely, wreaked its havoc by destroying the immune system of those infected.14
Again, the notion that a non-living organism, a protein, could cause a transmissible disease would until recently have been inconceivable – until, that is, Stanley Prusiner discovered a special type of protein, the prion. Prions, it subsequently emerged, could be transmitted from the brains of sheep to those of cattle to cause mad cow disease, and then to the brains of humans to cause the variant of the lethal dementing illness Creuzfeldt-Jakob disease. Prions are, in the words of Chief Medical Officer McCoy of the starship Enterprise, ‘life, but not as we know it’. Prusiner duly received the Nobel Prize for medicine in 1997 ‘for his pioneering discovery of an entirely new genre of disease-causing agent’.15
There is no precedent in th
e whole of biology for either retroviruses or prions, but that does not prevent them from having an enormous influence on human disease. Perhaps it is in such mysterious niches of the natural world that the last great intellectual problem facing medicine – the causes of disease – will be found. Or perhaps they never will be.
PART IV
The Rise and Fall:
Causes and Consequences
1
LEARNING FROM THE PAST
The pattern of the Rise and Fall identified in the Introduction is clear enough. For thirty years from the mid-1940s onwards, the combination of clinical science, fortuitous drug discovery and innovative technology – together with the human virtues of imagination, perseverance and hard work – impelled medicine forward. By the late 1970s, these dynamic forces had become exhausted, creating the intellectual vacuum that was filled by the two radical but ultimately unsuccessful approaches of The Social Theory and The New Genetics. Further, as promised in the Introduction, this pattern of a Rise and Fall helps to explain the paradox that, despite medicine’s staggering success, doctors are increasingly discontented and the public is increasingly neurotic about its health. It would be reasonable to infer that doctors’ discontents may be related to the fact that medicine is not quite as exciting as in the past, while increasing public neuroticism may be related to the anxiety-mongering of the proponents of The Social Theory. It is necessary, however, to dig a bit deeper than this.
The Rise and Fall of Modern Medicine Page 37
