23 May 1999 – THE SUNDAY TELEGRAPH
The unsolved mystery of modern medicine
As a student Dr James Le Fanu was in awe of the post-war discovery of antibiotics and cortisone, which had removed the spectre of many serious illnesses. In this preview of his controversial new book, he argues that these breakthroughs, far from being the work of scientific genius, were simply ‘gifts of nature’ which defy rational explanation.
ALTHOUGH I could scarcely have appreciated it at the time, I was born – on April 19, 1950 – in the middle of the revolution that convulsed medicine in the post-war years. In 1941 Howard Florey and Ernst Chain had cured the first patient with penicillin. Cortisone, the “magic cure” of several hundred previously intractable illnesses, was but a year old. In September 1950, when I was just five months old, tuberculosis – “the captain of the armies of death” – was finally defeated, and two months after that came the first definitive proof that smoking caused lung cancer.
But this, as it turned out, was merely the beginning. As I grew from childhood into adolescence through the 1950s and 1960s, every year brought more astonishing breakthroughs: open-heart surgery, in which the heart was stopped for several hours to permit surgeons to repair complex defects; drugs to suppress the immune system, which allowed first kidney and then liver and heart transplants; drugs for every major type of mental illness; vaccines against crippling infections such as polio; new operations to replace arthritic hips and clouded cataracts; the cure of leukaemia and other childhood cancers.
Together, this multitude of discoveries over a period of three decades must rank as one of the most sustained epochs of human endeavour of all time. It was more than enough to encourage a young man to chose medicine as a career. By the time I qualified in the mid-1970s, this Golden Age, at least in retrospect, was drawing to a close. But even now, after 25 years in medical practice, it strikes me as an extraordinary phenomenon that has never been properly explained.
What initiated and sustained the rise of modern medicine? What can it tell us about the nature of scientific solutions? The alchemy of modern chemistry was vital, particularly the expertise with which research scientists could synthesise thousands of chemical compounds in the search for new drugs. The urgency of conflict was, as always, a great spur to innovation: during the war surgeons learned how to remove bullets from beating hearts, which would be crucial for later developments in open-heart surgery; and the search for antidotes to mustard gas would lead, 25 years later, to a cure for leukaemia.
The architects of the post-war therapeutic revolution had great moral courage, which enabled them to persevere when their research stretched over decades, as with transplantation or open-heart surgery. But they were otherwise quite ordinary men and women. Intelligent and clear-sighted, certainly, but not geniuses. This brings us to the great mystery of modern medicine, for no amount of intelligence or courage could, by itself, have initiated the torrent of discovery that characterised these years. There had to be some other vital factor – and indeed there was.
Several of the most important advances, including antibiotics such as penicillin and cortisone, remain to this day biological mysteries that lie beyond the realms of rational explanation. In an earlier age they would have been attributed to the inscrutable power of God’s creation, but now they are probably best described as “gifts of nature”.
ON February 12, 1941, a 43-year-old Oxford policeman, Albert Alexander, became the first person to be treated with penicillin. Two months earlier a rose bush had scratched his face, a trivial enough injury, but the scratch had turned septic and soon his face was covered with abscesses. Pus was draining from an infection deep in the bone of his right arm, and he was coughing up copious amounts of phlegm from cavities in his lungs. He was, as his doctor Charles Fletcher recalled, “in great pain, desperately and pathetically ill”.
Penicillin was started every three hours, all Mr Alexander’s urine was collected, and each morning Dr Fletcher took it over to the laboratory on his bicycle so that the antibiotic residues could be extracted to be used again. There, he would be greeted by Howard Florey and Ernst Chain, who were keen to hear of Mr Alexander’s progress. “On the first day I was able to report that for the first time throughout his illness Mr Alexander was beginning to feel better,“ Dr Fletcher recalled. "Four days later there was a striking improvement… He was vastly better, with a normal temperature and eating well, and there was obvious resolution of the abscesses on his face."
By the fifth day, however, the supply of penicillin was exhausted and inevitably the patient’s condition deteriorated again. His death a month later is a stark reminder of the transitional moment between human susceptibility to the malevolence of bacteria and the ability to defeat them.
When more supplies of penicillin became available several other patients were treated, including a 48-year-old labourer with a vast carbuncle on his back, which vanished “leaving no scar”, and a 14-year-old boy extremely ill with an infection of the bone – osteomyelitis – and blood poisoning. “It is difficult to convey the excitement of witnessing the amazing powers of penicillin,” Charles Fletcher observed. During the next few years antibiotics would close down all but a handful of the infectious disease hospitals – the “chambers of horrors” in which Albert Alexander and tens of thousands like him – “desperately and pathetically ill” from the ravages of tuberculosis or typhoid fever, meningitis or septicaemia – had spent their last days.
Penicillin, and the penicillium fungus from which it was derived, was not unique in possessing these “amazing powers”, for several other micro-organisms, retrieved from the most unlikely places (including a chicken’s throat and the dung of a Japanese monkey), were also found to produce these antibiotic chemicals with the capacity to destroy the full range of bacteria that cause infectious disease in humans. And the more these antibiotics were studied, the more “amazing” they seemed to be.
The organisms that make them are the simplest forms of life, no more than a single cell containing a nucleus and surrounded by a wall. Yet the chemical structure of their antibiotic products proved to be of such extraordinary complexity as to defy the efforts of thousands of research chemists to synthesise them. And later, when it became possible to investigate how the antibiotics worked, it was found that they kill bacteria in a bewildering variety of ways – by blowing holes in the cell wall, by interfering with their metabolism or preventing their replication by disrupting their genes.
So, although antibiotics are frequently portrayed as the star witness in the triumph of modern science, scientists could never have invented or created them. They are, rather, a “gift of nature”, and it was in trying to work out what their role in nature might be that the greatest surprise was to come.
The common perception, first proposed by Selman Waksman, who in 1943 discovered the antibiotic streptomycin which cured tuberculosis, is that antibiotics are “chemical warfare” weapons deployed by organisms such as the penicillium fungus to maximise their chances of survival by destroying bacteria that are competing for nutrients nearby.
After deservedly receiving the Nobel Prize in 1952, Waksman turned his attention to developing his “chemical warfare” theory further. He soon realised, however, that it could not possibly be correct: it should have been quite a straightforward matter to detect antibiotic chemicals in the soil in concentrations sufficient to destroy competing bacteria, but it could not be done. Waksman was forced to conclude that the ability of these few species of microbe to produce such staggeringly complex antibiotics was “a purely fortuitous phenomenon… there is no purposeness behind it”.
This verdict is so difficult to accept that it is tempting to assume Waksman must have been mistaken. But whatever purpose antibiotics may serve for the microbes that produce them (if indeed there is one), nearly 60 years after Albert Alexander received his first slug of penicillin we still do not know what it is. This is the mystery of mysteries of modern medicine.
It is a similar story with cortisone, the first account of whose use – in a 29-year-old woman, Mrs Gardner – sounds as miraculous now as it must have appeared back in 1949. Mrs Gardner was crippled with rheumatoid arthritis. “Many of her joints were swollen and tender,” her physician, Dr Philip Hench, of the Mayo Clinic, observed. "She could only walk with the greatest difficulty and was essentially confined to a wheelchair."
After three months in hospital she was still no better – until one of Dr Hench’s colleagues informed him that a chemist at the drug company Merck had finally, after great difficulty, managed to synthesise the hormone cortisone in sufficient amounts for therapeutic use. It arrived by post the following morning. “During the first day there was no change,” Dr Hench later recalled. Two days later, when she awoke she could roll over in her bed with ease. And the following day her muscular stiffness was entirely gone. By the end of the week she was able to shop down-town for three hours."
During the next few months Philip Hench treated several more patients as seriously afflicted as Mrs Gardner, and presented the results at a meeting of his fellow physicians in April 1949. One of those present described how: “the lights were turned down and a film started to flicker on the screen. First came the ‘before treatment’ pictures in which patients with characteristically deformed joints struggled to take a few steps. Suddenly an electrifying gasp swept through the audience as the ‘after treatment’ scenes appeared, and they saw the very same patients jauntily climbing steps, swinging their arms and legs and even doing a little jig. Before the film ended the watching physicians filled the hall with wave after wave of resonating applause.” No Nobel Prize has ever been awarded so quickly, and the following year Philip Hench travelled to Stockholm.
Cortisone, it subsequently became clear, was not the miracle cure for rheumatoid arthritis, as even a few months’ treatment at the high doses required caused devastating side effects. But during the next few years, it proved invaluable in many types of illness, including allergies, acute inflammatory conditions and devastating infections.
By the time I started practicising medicine in the mid-Seventies, cortisone and its derivatives, now known as steroids, had transformed the treatment of hundreds of disorders of the eye, the skin, the gut, the lungs and kidneys.
Steroids also transformed doctors’ perceptions of how medicine would advance. It had always been assumed that a basic understanding of the nature of the disease and how it might be influenced by drugs were essential requirements for therapeutic progress. And yet, as Philip Hench himself consistently emphasised, the cause of all the diseases that responded so dramatically to steroids was quite unknown – as indeed were the mechanisms by which the cortisone molecule had such an impressive effect. So now I, and every other doctor, can pole-vault over our lack of knowledge and address the only important question – "What will make this better?" – by writing a prescription for cortisone.
CORTISONE is thus also a "gift of nature"; scientists could never have created it from first principles. Even now, the reasons remain obscure as to why this naturally occurring hormone, secreted in minute quantities by the adrenal gland, should prove to be so beneficial when administered as a drug.
Now it is possible to see how the architects of the therapeutic revolution were able to achieve so much. Men such as Howard Florey and Philip Hench may not have been scientific geniuses, but they happened to be around at the crucial moment when the potential of these “gifts of nature” could be exploited without the need to create them in the first place – or even know how they worked.
It was inevitable that doctors and scientists would assume the credit for the rise in modern medicine without acknowledging the contribution of these natural miracles – so obscure in their origins, and so complex and powerful in their actions as to lie beyond human understanding. Not surprisingly, they came to believe their intellectual contribution to be greater than it was and, indeed, that they had the answer for everything. From the 1970s onwards these hubristic claims to knowledge not possessed would lead to the flourishing of false ideas. But that is the story of the Fall of Modern Medicine.
Copyright: Telegraph Group Ltd