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The Life of Sir Alexander Fleming
Chapter IV - Fleming and Wright

It is not the marble halls which make for intellectual grandeur - it it the spirit and brain of the worker, Fleming

The introduction of Fleming, a circumspect young Scot, to this talkative and brilliant group conjures up before the mind's eye a curious picture. Far from being inferior to the other members of it, he arrived laden with diplomas and medals, a student already covered with glory, and possessing incontestable references. But his gift of silence appeared to be inexhaustible. 'He could', says Freeman, 'be more eloquently silent than any man I have ever known. He seldom or never gave himself away. In the stress of the moment I sometimes called him a blithering idiot, or used some equally opprobrious epithet. In reply, Fleming would merely look at me with his barely noticeable Gioconda-like smile, and I think he had the best of the exchange.* The lab. equipment was rudimentary: an incubator, a sterilizer, some Petri dishes, a number of test-tubes and a microscope. Fleming was trained in doing most things with a few rubber teats and capillary tubes, and making most of the gear he needed. At tea-time, whether at night or during the day, he joined the 'family' in the small room which was known as the library, a courtesy title, for it contained no books. Wright, massive and shaggy in his armchair, played the part of a Victorian father from behind his table, while the others crowded together on a settee, or sat on the floor round him* His disciples appeared to look upon him as some immense natural phenomenon. When Dr Robert Debry, a Frenchman, visited St Mary's, he was astonished to see Fleming, solemn-faced and dexterous, go up to Wright while the latter was holding forth and, without a word, prick the august finger so as to get a drop of blood which he needed for control purposes, while Wright went on talking without paying the least attention to this rite.

More often than not these meetings took the form of a long monologue by Wright who sat leaning forward in his chair, slightly terrifying but quite fascinating in his role of feudal lord and unquestioned ruler. No matter what the subject, he was perfectly capable of quoting fluently and at length from Kant, Sophocles, Dante, Rabelais, Goethe and even Mademoiselle de Maupin. When important visitors, like Balfour, happened to turn up, it was Wright who answered their questions, or sometimes Freeman. Fleming, as a rule, said nothing. At first he had been amazed at Wright's tremendous vitality and universal knowledge. But he had the precious, if somewhat embarrassing, gift of seeing the weak point in any argument, and driving straight forward. He very soon realized that the Chiefs glittering oratorical performances were not always constructed on irrefutable premisses. When the midnight tea became an orgy of metaphysical discussion, he would listen for a long time in silence, and then, with a single word, cause the whole laboriously constructed system to collapse noiselessly, 'Why?' he would say, with assumed innocence, at which there would be a general exchange of glances. For he was perfectly right: why?

Wright valued Fleming for the perfection of his work and his sure judgment. But his silences were in the nature of a challenge, and he enjoyed pulling his leg. Assuming that the young Scot, who never spoke about religion, must be a Covenanter and a Believer, the Old Man would try to provoke some show of emotion on that impassive countenance by indulging in blasphemous outbursts, such, for instance, as putting together two verses from the Gospels in such a way as to produce an absurd or scandalous sentence. Or he would say: 'Fleming, how could the star of Bethlehem be over one house? The apparent distance of the stars is such that the same star appears to be over all the houses in a village. Isn't that so?' But Fleming never rose to the bait. He knew what his behaviour was supposed to be in the lab.: that of a taciturn Scot, and he conscientiously played up to it.

Wright had a taste for quoting at length from the poets. Often, after a long piece of declamation, he would turn to Fleming, who had his beautiful blue eyes fixed on him, and say: 'What's that?' In the early days, Fleming, as a good Scot, had replied 'Burns' — on principle. Then, having a methodical mind, he established the fact that the Old Man chiefly quoted from three great works, the Bible, Milton's Paradise Lost and the plays of Shakespeare* From that moment, whenever Wright jumped on him with the question — 'What's that?', he regularly answered, *Paradise Lostand one time in three the attribution was correct*

After long days of work, Fleming enjoyed this atmosphere of gay badinage. He did not like people to take serious matters too seriously. He loved having a bit of a game, even where work was concerned. Himself given to teasing, he did not in the least mind being teased in return. But m games, as in everything else, he liked to be top-dog. Calmly, imperturbably, he would study the rules until he had completely mastered them* The really splendid game in the lab. was not conversation but research, and there Fleming triumphed. Though Wright was skilful in technical performance, in spite of his podgy fingers, Fleming, or, as he was affectionately called, 'Little Flem', was even more deft and ingenious. In his hands glass was made to serve the need of the moment. It was pure joy to watch him construct, with incredible rapidity and improvising as he went along, some complicated piece of apparatus. In the truest meaning of the word he was an artist, and his colleagues instinctively spoke of his work in terms of art. 'That experiment of Flem's,' someone would say, 'was a perfect little work of art.' In this way, and without any effort, he retained that contact with nature which is so precious a possession for those who question her, and which the abstract thinker is too apt to lose.

Wright, a scholastic, believed that pure reason or, at least, his own, could discover the laws which govern phenomena. 'Actually, he had a far greater intellectual affinity with St Thomas Aquinas than with Bacon', with Descartes than with Claude Bernard. He believed, of course, in the experimental method: he had carried out innumerable and 'beautiful* experiments, and had owed to them everything he knew, but when Nature gave him a negative answer, it was only after a tough struggle that he could bring himself to accept it. 'The positive spirit', says Alain, 'is a prey to the passions ... The reply given by things to our demands and our hopes is not always sufficiently definite to clear our minds of fantasies.' Though Wright, wisely and with perfect sincerity, preached self-criticism, he was not impartial where the choice and interpretation of his results were concerned. Words held an irresistible attraction for him. There were days when his dialectic, thickly sown with terms taken from the Greek, and of his own invention ('cataphylaxis', 'epiphylaxis', 'ecphylaxis'), led his audience beyond the borders of the real.

Fleming admired his master's genius, was full of praise for his integrity, and knew that, if Wright sometimes made a mistake, it was in perfect good faith. But ever since the days of his youth he had made it a strict rule that he would never cling obstinately to a preconceived idea if experience proved it to be wrong. His friend, Professor Pannett, writes: 'He never liked talking, but when he did make up his mind to express a judgment in words, you could be perfectly certain that it would be in the highest degree intelligent. Fleming's edged mind and clarity of thought are beyond dispute.' When Wright, carried away by his own eloquence, pressed a theoretical conclusion too far, Fleming was always courageous enough to say, quite calmly: 'That won't work, sir.' Wright would repeat his argument even more forcibly. Fleming would listen without interrupting him and then, quite simply, say again: 'That won't work, sir.' And it didn't.

Though often, with one sharp monosyllable, he would deflate a too audacious pilot-balloon, he felt, nevertheless, that Wright's passionate enthusiasm was a useful source of inspiration. The young Scot might seem cold and collected, but the indomitable, delightful and sometimes savage Irishman had awakened in him a spirit of unlimited loyalty. To contradict Wright to his face was one thing, and Fleming occasionally ventured to do it, but to argue against the Old Man's ideas outside the lab. was quite another, and that he never did. He knew perfectly well that some of Wright's theories were controversial, but he tried his best to find a solid experimental basis for the Chief's more hazardous hypotheses. Wright, because of his unbounded self-confidence and excessive outspokenness, had made a number of enemies in the world of science. Some there were who attacked his technical methods: Fleming, on the other hand, attempted with infinite patience, to perfect them. If Wright believed in a theory which others held to be debatable, he would return to it again and again, and prove to those of little faith that the Old Man had been justified.

He learned much from Wright and it was a stroke of luck for him to have been trained by such a master, but it was also a stroke of luck for Wright to have at his elbow so fiercely impartial and absolutely loyal a worker. This he knew. Though he had a tendency, like many great masters, to think of the mental processes of his disciples as his own personal possession, and to include the results of their work in his 'papers', he often quoted Fleming by name, and realized, many times over, how much he owed to him.

The essential qualities of the young research-worker were a powerful gift of observation, thanks to which no important detail ever escaped him; a piercing insight into the causes implied by this or that established effect; and a high degree of skill in cutting through the tangled minutiae of any problem and revealing the main lines along which inquiry should move. These qualities he used generously in defence of the opsonic index against a deal of sniping. It was said that thousands of 'counts' would be necessary before a reliable estimate could be arrived at, and that, even if the method were correct, it would be utterly impracticable* 'No,' replied Fleming, 'an experienced and intelligent bacteriologist does not need to count as many cells as a beginner.* In his hands everything became easy. Two examples, chosen from the work of the laboratory, seemed to justify the confidence felt by the team in this famous and much-debated method.

One of the workers in the lab., John Wells, who was on holiday in the country, wrote to say that he was suffering from influenza. Wright replied, telling him not to come back until he had completely recovered. Two months later, Wells wrote again: T really must get back to work: this influenza seems to be interminable.' He returned and crawled about the laboratory, depressed, feverish and obviously a very sick man. One day, Fleming, who had taken a sample of his blood, showed Freeman two glass slides, and said: 'Would you mind counting these two films?' He had marked them 'A' and 'B', but gave no further explanation. Freeman, after making a careful count, said: 'Blood "B" has twice as much lesseffect upon the microbe as blood "A" ...'

'That tallies with my own finding,' replied Fleming: ' "B" is the control sample; "A" comes from Wells. The microbe is that of "glanders" ...John Wells is suffering from the "glanders" ... Do you remember that young woman whose pony died? ... Wells, on that occasion, handled a culture and probably did not take sufficient precautions ... The pony must have had the "glanders", and John Wells caught the infection Six weeks later the diagnosis was confirmed, and John Wells died from the 'glanders' which, at that time, was incurable.

The other case was that of Dr May, a robust and red-faced Irishman who rejoiced in the nickname of 'Maisie'. Like the others, he had contributed some of his blood to build up a reserve of normal blood for control purposes. Someone put the question: 'Does this total mixture really and truly represent the average blood of the lab. workers?' The opsonic index of the mixture was compared with that of the individual donors. May noticed that his blood differed markedly from that of any of the others. Wright said to him: 'We won't take any more of your blood. You are not normal.' 'Maisie' continued to measure his opsonic index and established the fact that it was diverging more and more from the norm. Wright told him: 'I'm afraid you'll have to leave the lab. You are suffering from a suppressed form of tuberculosis.' 'Maisie' laughed, for he did not feel ill, but, nevertheless, accepted a less exacting post in South Africa. When this became known in the medical world, many pathologists said: 'Wright really is completely mad! He's got in his laboratory a chap who's the very picture of health and, just because this man's opsonic index varies from the norm, he has calmly announced that he is tubercular. Never heard anything so ridiculous!' ... May, however, had not been in Africa two months before the doctors found Koch bacillus in his sputum. The diagnosis by opsonic index had anticipated the clinical diagnosis by several weeks.

It looked, therefore, as though this immense labour had not been in vain. But it condemned Wright's disciples to spend whole nights in the lab. The students of St Mary's knew that if they left a party round about two in the morning, they could always look in for a final mug of beer on Fleming, who at that hour would invariably be found bending over his microscope. They liked nothing better than to find him there — at once unperturbed and welcoming — wearing his neat bow tie and ready to listen to anything they might have to say, while the eternal cigarette dangling from his lips, even when he was speaking, made it more than usually difficult to hear what he was saying.

Another of Fleming's qualities was the masterly manner in which he organized his expositions. From the very first his papers had been noted for the clarity of his scientific style. Wright, whose taste in literature was exacting and reliable, could not help recognizing that Fleming in his precise and sober way wrote well. cMy colleague, Dr Alexander Fleming, has given in the treatise which is prefaced by these remarks of mine an admirable summing-up of the results obtained by the Inoculation Department of St Mary's Hospital ...' Wright had moved on from preventive to therapeutic vaccination, and it is now necessary to give some account of the flow of ideas which had carried him forward in this direction.

To immunize means, when there is any threat of infectious illness, to give to the blood the means of fighting against a possible attack. Jenner's inoculations as well as Pasteur's had been preventive. But Pasteur had also successfully treated those already infected with rabies. How had that been possible? Because rabies in the human being does not develop until some time after the bite has been inflicted by the mad dog. An injection of the virus in an attenuated dose, given during the period of incubation, stimulates the production of antibodies and with them the human system can fight the invasion before it is established; this is still, therefore, a sort of preventive inoculation.

Wright took it as his starting-point. Why, he asked, should one not go farther? Up till then the 'immunizers' had held the view that the invaded body was one and indivisible. But was this view correct? Observation had been recorded of numerous cases of local infections which had not become generalized. A patient might suffer from tuberculosis of the knee without the rest of his body being attacked. To what did this point? To this — that the local natural defences, and they alone, had been carried by the enemy; that the microbial forces had won a bridge-head but nothing more. The general defence mechanism had not been put on the alert.

Could the garrison be mobilized? Yes, said Wright, by means of auto-inoculations. It would be enough, in cases of local infection, carefully to determine the microbes responsible, to prepare from them dead cultures (auto-vaccines), to inject these into the patient, and then study his opsonic index to ascertain the effect of the treatment. Beyond this first area of research Wright could already see vast fields waiting to be explored by vaccine therapy — e.g. blood poisonings and certain secondary infections which often accompany cancer. An enthusiastic inquirer with a fixed idea can find it everywhere.

There can be no doubt that Fleming, like his colleagues, had a firm belief in vaccine therapy. Indeed, numerous cures brought about by its use were on record at St Mary's. This new conception made a great stir. Bacteriologists from all over the world came to study auto-vaccines and the opsonic index under Wright's direction. It was not easy to find accommodation for them in the two wretched rooms which were all the Department at its disposal; far too little for half a dozen foreign scientists in addition to Wright's six or seven assistants. Patients, attracted by favourable rumour, arrived in a steady flow. It was necessary to take blood-samples, to identify the microbes, to prepare the vaccines, and to keep a watch on the blood of the sufferers by making a count of the number of microbes absorbed by the leucocytes. It was gruelling work, and there was a shortage of everything, of money as well as space.

In 1907 the hospital authorities, who lacked the funds necessary to equip the upper floors of a recently constructed block (the Clarence Wing), offered them to Wright if he would undertake to obtain a subsidy. Wright had rich and powerful admirers. He rallied to his aid Lord Iveagh, Arthur James Balfour, Lord Fletcher Moulton and Sir Max Bonn. Between them they rapidly collected the sum needed. In addition, as soon as the laboratories were equipped, arrangements were made with a large firm of pharmaceutical chemists, Parke Davis & Co., to supply them with vaccines, serums and antitoxins for distribution. From that moment, the Department had permanent resources, but these were used to expand the laboratories, and the research-workers continued to be paid about what sweepers would earn today. In 1909, the constitution of the Inoculation Department was definitely established at a meeting held at the House of Commons under the chairmanship of Balfour. The Department now became entirely independent. Its administration was vested in a committee which met only when Wright thought it necessary to call it together. Wright and two other members constituted a quorum. In this way was the benevolent tyranny of the Old Man legitimized.

Few women ever came to the laboratory except when Wright had prepared what his friend Ehrlich called a Damenprogramme. On these occasions, Lady Horner, Mrs Bernard Shaw and other privileged females were put au fait with the latest discoveries by means of a number of spectacular demonstrations. Wright affected a profound contempt for the intelligence of women, and many of the 'midnight teas' were devoted to his diatribes against the sex. 'The continual over-estimation of the feminine intelligence', said Wright, 'is very largely due to conjugal infatuation. Everyone must have noticed that wives who love their husbands adopt their ideas ... I once heard a mother say of her daughter, "she is so devoted to her husband that if he turned Mohammedan tomorrow, she would follow suit"...'

He maintained that the passions are almost always engendered by bacterial toxins. His taste for Greek words led him to explain the need felt by so many men and women to press against one another, to clasp their arms round the beloved object, and to lean his (or her) head on her (or his) shoulder, as a stereotropic instinct, in other words, the desire to find something solid to lean on. He had written a whole book against Votes for Women which, at that time, were being violently demanded by the Suffragettes, and had collected all the most wounding things that the most famous authors had said about the 'second sex', from Michelet's 'A man loves God: a woman loves a man', to Meredith's expect that Woman will be the last thing civilized by Man' and Dr Johnson's remark that 'there is always something a woman will prefer to the truth.'

The man who would pursue a great design and work without intermission should, according to Wright, live completely separated from women, a rule which he applied rigorously in his own case, for he kept his family in the country while he himself lived in London. The laboratory was his home. 'Before making a decision on any subject, a man should always have numerous conversations with those who are expert in it' was another of his sayings. And so it was that he surrounded himself with disciples. Some of them, like Freeman, stimulated him and led him on to make his most brilliant repartees: others, like Fleming, gave him their sureness of judgment, technical skill and sturdy good sense, though at times they might be silently rebellious.

Fleming had quickly fitted into this new world which he had entered quite by chance. The work demanded more of human nature than human nature could give. Every morning the young men had to make the rounds of the wards, for Wright still clung to the view that research-workers should also be practising doctors. The afternoon began with a 'consultation' at which those cases regarded by the old-fashioned doctors as hopeless were examined. Samples of blood were taken and labelled. Fleming was always anxious to get these preliminaries over quickly, for he was in a hurry to get back to the laboratory and prepare his slides. After dinner these innumerable specimens were studied. The workers used their own blood for control purposes. 'We were', says Colebrook, 'so many human pincushions.5 All this was not without danger.

Meanwhile, though never abandoning these exacting labours, Fleming continued to read for his final medical examinations which he passed in 1908, coming out, as usual, top, and being awarded the Gold Medal of the University of London. Nor should it be forgotten that at this time, too, and without any preparation, he sat for and got his F.R.C.S. As though this were not enough, he wrote a thesis on 'Acute Bacterial Infections' for one of the prizes regularly offered by his own Faculty (St Mary's), and again headed the list, winning the Cheadle Medal. His success was announced in the St Mary's Hospital Gazette as follows: ' Mr Fleming, who recently was bracketed for the Gold Medal and who seems to have taken the Fellowship in his stride, is one of Sir Almroth Wright's most enthusiastic followers, and we see great distinction in store for him in the future.' The far-sighted author of this article was Zachary Cope, who later became Sir Zachary Cope and a great surgeon.

Fleming's thesis on bacterial infections and the means of fighting them constitutes, as it were, a prefiguration of the line of research which the author was to follow all through his life. In it he presents an inventory of the contents of the arsenal at that time available to the medical profession in its war against bacteria: surgery, where the centre of infection is accessible; antiseptics; general methods of increasing the patient's resistance; the use of products which have an effect upon certain specific bacteria (quinine for malaria; mercury for syphilis, etc.); ways of increasing the exudation of the blood-lymph into the infected tissues; and, naturally, serums and vaccines.

He gave the place of honour in his essay to Wright's vaccine therapy. The latter's enemies asked ironically: 'What is the point in adding dead microbes to a body which is already carrying on a battle against living ones?5 — and, with an air of triumph, brought up against him the phenomenon known as infectious endocarditis, where, the valves of the heart being contaminated, the microbes are continually shed into the general circulatory system. According to Wright's theory, this process should be a natural form of vaccination, and there should follow an increase in the resistance of the organism. In fact, nothing of the sort occurred. The blood did not produce antibodies.

Fleming, having come up against this obstacle, ventured to put forward an hypothesis. The intravenous route, he suggested, was not suited to the injection of a vaccine. But this theory still needed to be confirmed by experiment. Being unable and unwilling to use a patient for this purpose, he became his own guinea-pig and submitted to an intravenous injection of a staphylococcic vaccine. This was a rather courageous thing to do. Intravenous injections were held at that time to be dangerous, and no one could say with any certainty what the consequences might be. One Saturday he had a hundred and fifty million dead staphylococci injected into a vein. On the Sunday he had a feeling of nausea, a headache and a high temperature. Given such symptoms, it was reasonable to expect an increase of resistance in the blood. There was, however, none, whereas the same quantity of staphylococci administered hypodermically caused it to rise sharply. This seemed to justify the hypothesis that inoculation into the blood-stream, which occurs naturally in endocarditis, is a bad method, which produces the maximum toxic effect with the minimum of immunization. The results of the experiment had been what the young doctor had expected.

This thesis on the infections is important, providing us, as it does, at the very dawn of a life devoted to medicine, with a picture of the direction that life was to take. All through his working career, Fleming was to seek one thing, and one thing only: a means of fighting infections which at that time were looked upon as the most dangerous of all the scourges of the human race. For this line of research he felt himself to be well equipped. He was a born naturalist, and was fully conscious of his abilities. It would, therefore, be a great mistake to think of him as an embarrassed and discontented man living in a refined, literary circle much superior to anything to which he had been accustomed. For soured and querulous persons he felt nothing but contempt. 'Alec was always happy, and always on top of his work', writes one of his colleagues, Dr Hollis; 'there was never any sign in him of bitterness or fatigue ... His attitude to his research-work seemed to be a combination of humour and seriousness.' Here, too, is what Professor Cruickshank thinks: cHe tolerated, and was probably amused by, sophistication in life, and by the kind of intellectual philosophy in which Almroth Wright indulged. Although he took little part in argument, one gets the impression that, even in his early days, his opinion was greatly respected.' His own infrequency of speech did not at all depress him. He liked listening. It was one of his strong points. Wright's tremendous personality dominated the scene, but the tranquil Fleming, for ever at his side, was loved and esteemed.

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