Significant Scots - Sir Alexander Fleming

The greatest derangement of the mind is to believe things because one wants to believe them and not because one has seen that they are. bossuet

'A barrowful will do, to begin with.'
'A barrowful of what?' thought Alice, lewis Carroll, Alice in Wonderland

ONE day in 1912, young Dr James, paying a visit to St Mary's after the completion of his studies, saw a sturdy, bronzedsoldier, in the field uniform of the London Scottish standing at the top of the steps. It was Fleming. He was just back from the annual camp and James was staggered to learn that a doctor of his quality, a learned bacteriologist, should be willing to go into training as a simple private. "At that time', says James, T had no military experience. The idea of sharing a tent with six or seven other men filled me with horror ... I ventured to ask him how he managed to keep his equipment so spotless, his rifle and boots so clean in spite of the rain and mud. He gave me an icy-blue and rather terrifying look, and replied with his habitual brevity: "By bloody hard work!"

'My former meetings with Fleming had left me with a lively sense of admiration. Finding my hero transformed into a soldier gave me something to think about. I had been taught by my Nonconformist upbringing to think of war as a crime. I believed that no one went into the Army unless he had something to reproach himself with, and that all officers were more or less like the immoral Cavaliers who had taken up arms in the Civil War against the Puritans. The realization that one of my most highly esteemed seniors, with a remarkable record of work, was prepared to risk his life as a soldier of the King, made me revise my views about the possibility of a war.

Actually, war did not break out until two years later. Fleming had left the London Scottish in April 1914, because the training periods did not fit in with his work at the hospital.

A month or two after the beginning of the war Wright was given the rank of colonel and sent to France to establish a laboratory and research centre at Boulogne-sur-Mer. He took with him Douglas as a captain, Parry Morgan, and Fleming who sported the two stars of a lieutenant in the R.A.M.C. Colebrook joined them later. Freeman went first to Russia to prepare vaccines against the cholera and then proceeded to the laboratory at Boulogne. This was officially attached to the hospital established by the English Army in the Casino. To begin with, the bacteriologists were accommodated in an appalling basement through which a drain-pipe ran, so that the whole place stank. Every morning at six o'clock a sapper sergeant poured some cresol into the pipes, but the sickening stench persisted.

Sir Almroth reacted in no uncertain manner (he could be most effectively brutal on occasion), and got the fencing-school on the top floor allotted to the research staff. Naturally it contained none of the equipment needed by a laboratory — no benches, no running-water and no gas. The ingenious Fleming did yeoman service. Bunsen-burners were kept going on methylated spirit, and the incubators were heated with paraffin stoves. For such work as demanded the use of glass, he contrived a very effective blow-pipe out of rubber tubes and a pair of bellows mounted on a petrol-tin. He said, later, that he had never had a better laboratory.

In war as in peace, nothing could disturb his habitual composure. 'My first impression of Lieutenant Fleming^', says his former orderly sergeant, 'was of a short, pale officer who never said more than he had to, but carried on calmly and efficiently with his work. When Captain Douglas went sick, Captain Fleming (he was promoted by that time) took over the command. Captain Douglas had always been chaffing and swearing when he talked to me about service matters. The first time I gave Captain Fleming some papers requiring his signature, he was busy with his microscope. I waited respectfully until he could give me his attention. At last, he raised his head, took a pencil and, without asking me for a word of explanation, signed the vouchers. On such occasions as I had to make a report to him, I got the feeling that he wasn't interested, though he was — much more than I thought. He took the whole thing in, solved the problem on the spot, and ended up with: "Right, Sergeant, carry on."

Throughout the war the amount of work done by the Department was tremendous and enormously beneficial. The question was no longer one merely of vaccines, though Wright (like Vincent in France) had fought tooth and nail to get anti-typhoid vaccination made compulsory in the Army. It saved thousands of lives, but the wounded brought other problems, most of them urgent and distressing. Wright and his assistants on their way to the laboratory had, every morning, to go through the wards, where they could see for themselves the terrible effects of explosives more powerful than those used in any previous war, and the infections set up in open wounds by earth and scraps of clothing. The surgeons despairingly drew the attention of the bacteriologists to innumerable cases of septicaemia, tetanus and, especially, gangrene. Every day convoys of wounded men arrived with splintered bones, torn muscles and severed blood-vessels. Within a very short space of time the patient's face would become ashen in colour, his pulse would weaken and his breathing diminish almost to nothing. This was the effect of gas-gangrene and meant certain death.

How was it to be dealt with? 'In this war,' said Sir Alfred Keogh, Head of the Army Medical Services, 'we have found ourselves back among the infections of the Middle Ages.' Since the time of Lister, surgeons had got into the habit of relying on antiseptic and, especially, aseptic treatment. Except in certain cases of road-accidents, the wounds with which they had had to deal were reasonably clean, and they had learned how not to infect them. Lister had introduced the system of passing smocks, gloves and instruments through an antiseptic preparation. Later, everything which had to come in contact with the patient was first sterilized by heat. It looked as though 'hospital sickness' had been conquered once and for all. But in the terrible.butchery of 1914, by the time the injured reached hospital, their wounds were already crawling with microbes. Any poor wretch who happened to have fallen in a field or on a road was bound to have picked up any number of deadly germs. Fleming, examining odds and ends of uniform, found in them microbes of every description. As to manure heaps, they were infested with germs.

What was to be done? Fleming made a careful study of recently infected wounds, and noticed a remarkable fact. Phagocytosis was more active in them than in wound infections observed m ordinary civil practice. The leucocytes had devoured, and killed, an enormous quantity of microbes. Why? In normal times/ he said, 'infections occur more or less spontaneously in individuals, who for some reason or other have become less resistant to the infecting agent. In civil practice also the bacteria have frequently an enhanced virulence, due to their passage from one individual to another. In war, on the contrary, a strong and healthy man when wounded finds himself suddenly and violently infected by microbes the virulence of which has been weakened as the result of living in unfavourable conditions. It is, therefore, only natural that phagocytosis should in these cases be greater. But why, then, in these conditions, should the infection in war-wounds be worse? Because the projectile has produced a very extensive destruction of tissues. Not only do dead tissues provide a good culture medium for microbes, they actually prevent the healthy phagocytes from reaching them. His first piece of advice, therefore, to the surgeons was: remove all necrotic tissues as soon as possible.

He had learned from his experience as a research-worker to have a solid respect for the natural defence-mechanisms of the human body. What happened in the case of a wound relieved of dead tissues and left to the processes of nature? The healthy leucocytes, penetrating the walls of the blood-vessels, attacked in strength, and cleansed the wound by absorbing the microbes. What was the cause of this ^'diapedesis', or migration, of the white corpuscles? To say that a 'positive chemotaxis' attracted the phagocytes to the toxins, was merely to stress, once again, the soporific effect of opium. But, whatever the cause might be, the effect was certain. What mattered, therefore, was to let the natural defences of the body have free access to the microbes.

The army doctors were lacking in neither courage nor devotion, but they were now finding themselves face to face with a new problem. In the absence of adequate direction, they stuffed wounds with antiseptics, often chosen in a rather haphazard manner. That was strictly in accordance with the instruction which they — and Fleming, too — had received as students. T remember', he said, 'that I used to be told to be most careful to use antiseptics in the dressing of wounds — carbolic acid, boric acid, peroxide of hydrogen. I could see for myself that these antiseptics did not kill all the microbes, but was told that they killed some, and that the results were better than if no antiseptics had been used at all. At that time I was in no position to argue.'

At Boulogne he could see that antiseptics were powerless, that microbes abounded, that the wounded were dying. Being nothing if not thorough, and suspicious of all a priori ideas, he devised a series of brilliant experiments for the purpose of bringing various antiseptic dilutions into contact with different forms of microbial infection. These showed that not only did the antiseptics do nothing to prevent gangrene, they seemed actually to promote its development.

Of course, in certain cases of superficial infection there was an advantage to be gained in using solutions sufficiently concentrated to destroy the bacilli. True, they also destroyed some of the cells of the body but, since this process took place on the surface, the surgeon could then remove the dead tissues. But cases of superficial infection were rare. Modern explosives produce deep wounds which are more than just simple cavities. Scraps of underclothing and other dirty objects, driven inwards by the explosion, penetrate deeply into the tissues. The injuries with which Fleming had to deal presented multiple anfractuosities, corners and crannies which might be compared to the configuration of the Norwegian fjords, and infection broke through the walls of these. Such antiseptics as were then in use were powerless to get at the tissues. Was it possible to sterilize these ragged recesses? In order to find the answer to that question, he hit on the idea of modelling an artificial wound in glass. After first making the closed end of a test-tube red-hot, he drew out, on the inside, several hollow excrescences to represent the anfractuosities of the wound. Next, he filled the tube with a serum previously infected with faecal matter. The general result gave a diagrammatic, but sufficiently exact, picture of a war-wound.

He then put the tube into an incubator and left it there for the night. Next morning the serum, invaded by microbes, had a muddy appearance and stank. The tube was then emptied of the serum and refilled with an antiseptic solution strong enough to kill the microbes. After certain intervals, not always the same, he emptied the tube and filled it again with non-infected serum. After incubation, this serum, which had begun by being sterile, was as muddy and stinking as the first. No matter how many times the operation was repeated, the result was the same. What did that prove? Obviously that, since the new serum had been originally free of contamination, microbes must still be lurking in the anfractuosities of the tube. From this he concluded that it was not possible to sterilize a war-wound with the then-known antiseptics.

Once more the question arose, what was to be done? Wright's answer was — leave the natural defences of the body to do their work, and help them. The leucocytes which flocked through the walls of the blood-vessels formed a pus the action of which was powerfully beneficial. Wright and Fleming had demonstrated by experiment that fresh pus destroys the colonies of microbes. To this bactericidal power of healthy leucocytes there is no limit, provided they are present in sufficient numbers. The best form of treatment, therefore, would be the one which would mobilize armies of leucocytes and cause the greatest possible quantity of fresh lymph to exude from the walls of the wound. Wright showed by laboratory tests that this action could be produced by using a high concentration of saline solution. Fleming confirmed these findings by experiments made on actual wounds.

The same cause explains the jsuccesses obtained in the field by the French physiologist, Carrel, who introduced the system of washing out wounds with Dakin's solution (hypochlorite of soda) which, like the high concentration of saline solution, stimulated an intense exudation of fresh lymph. Fleming, knowing that antiseptics rapidly lose their bactericidal properties when in contact with pus and tissues, wanted to see how long Dakin's solution remained active in a wound. He found that ten minutes after instillation, this antiseptic ceased to be dangerous to microbes. 'Yes/ was his conclusion, 'Dakin's solution gives good results, but, like the highly concentrated saline, only because it helps the natural defences. It's lucky', he added, with a touch of humour, 'that it loses its antiseptic action so quickly. In ten minutes it can't do much damage, and, after that, nature has two hours' rest in which to recuperate without being interrupted.'

Fleming's later discoveries have thrown his work during the war into the shade. But those qualified to judge (Dr Freeman, for instance) are of the opinion that he never conceived anything more perfect or more ingenious than those brilliant experiments by which he demonstrated the danger to human tissues of antiseptics when wrongly used.

Bernard Shaw, a frequent visitor to Boulogne, was cock-a-hoop. 'We are left in the hands of doctors who, having heard of microbes much as St Thomas Aquinas heard of angels, suddenly concluded that the whole art of healing could be summed up in the formula: Find the microbe and kill it ... The simplest way to kill most microbes is to throw them into an open street or river and let the sun shine on them ... But doctors instinctively avoid all facts that are reassuring, and eagerly swallow those that make it a marvel that anyone could possibly survive three days in an atmosphere consisting mainly of countless pathogenic germs. They conceive microbes as immortal until slain by a germicide administered by a duly qualified medical man ... In the first frenzy of microbe-killing, surgical instruments were dipped in carbolic oil, which was a great improvement on not dipping them in anything at all and simply using them dirty; but as microbes are so fond of carbolic oil that they swarm in it, it was not a success from the anti-microbe point of view Here Shaw did not understand, or pretended not to understand. The instruments were genuinely sterilized because in their case the strong concentrations were inoffensive. Lancets do not have vulnerable cells.

But though Shaw may have been amused, the pundits were shocked. Wright who, with his customary quickness of mind and his passionate enthusiasm, had concentrated all his attention on this problem, the solution of which might save thousands of lives, increased the number of his lectures to English and French doctors. In 1915, he addressed the Royal Society of Medicine in London on two separate occasions. He did his best — and this, for him, meant a great effort — to keep his talks at a purely practical level, with his literary genius in abeyance. He did all he could not to be aggressive or ironical, his object being to convince without giving offence. In this he did not succeed. Self-satisfaction is so strong an emotion that it will deny the most obvious facts in the interest of a pride which is quick to take offence. The President of the Royal College of Surgeons, Sir William Watson Cheyne, who, having been a friend of Lister and spent his life in carbolic acid, was pleased to regard these new ideas on the surgical treatment of war-wounds as amounting to an attack upon his own honour and that of his master — quite wrongly, for Wright and Fleming had the greatest respect for Lister, but conditions were different. Consequently, Sir William thundered from the mountain-top of his authority.

This was, to say the least, unwise, for Wright, when touched on the raw, could be a ferocious controversialist. On September 16th, 1916, he published in the Lancet an admirably written reply which, in fact, amounted to a pamphlet. He lacked neither authority nor competence, since he and his assistants had had recent and extensive experience of war-wounds. Sir William Watson Cheyne had admitted that, when infection had been active for ten or twelve hours, the chance of doing much good with antiseptics was very small.

'But^', replied Wright, 'in war, a wounded man who has been left for a long time on the battlefield, then slowly transported in an ambulance, can rarely receive attention within those limits of time which you appear to think necessary for successful treatment. And once the proper moment for the use of antiseptics has gone by, what is your programme? So far as I can make out, you haven't any. You say, in effect: "I have opened the wound, I have inserted a drain, I have washed the affected parts of the body with a weak antiseptic solutibn, and I am not prepared to give further thought to the problem."

'For my own part,^' continued Wright (and here we are summarizing his argument), 'I take a diametrically opposite view. So far as the sterilization of war-wounds is concerned, I share with all those who have had the same experience in France as myself, the feeling that serious wounds inflicted in battle are never sterilized, and never can be, by the application of antiseptics. I have, therefore, strongly put forward the view that we must help the body, by physiological means, to combat bacterial infection. By stimulating a plentiful flow of lymph, we can aid the fluids in the blood to act upon the infected tissues. The more fresh serum we can produce, the more we can accelerate the migration of the leucocytes, the more we can assist in the destruction of the infecting microbes ... It seems to me that Sir William Watson Cheyne is blind to all these problems. He has not even caught a distant glimpse of the towers of that city in which we are seeking to arrive ..'

He then produced overwhelming arguments to show that his illustrious opponent seemed to have not the remotest idea what an experiment was. 'Let us consider what the necessary qualifications for a practical scientist are ...' Sir William had referred to a case of a gaping fracture sterilized by Lister. 'All that this passage in Sir William's text shows is that a muddled mind and deficient logic can draw false conclusions from a genuine clinical observation ...' One of the objections put forward to Sir William's contention had been that Sir Almroth Wright's physiological treatment must be effective since so many doctors had been using it at the front for some considerable time. 'I have nothing to do with the actions of men at the front' Sir William foolishly replied, 'to say nothing of the fact that a well-known piece of mechanism, known as discipline, operates in the field ...' In other words, since Wright was a colonel, his word must always be law in military circles. But so far was this from being true that Wright had asked the army surgeons, no matter what their rank, to think for themselves, and verify from their own experience the experiments carried out in the little laboratory at Boulogne, all of which were objective, simple and irrefutable.

No doubt, though Wright was an individualist and boasted that he had never taken orders from anyone, he considered that in so grave, so tragic, a situation, it was impossible to let every regimental medical officer go his own sweet way. In peace the practitioner works in a familiar and well-explored field. In wartime, on the other hand, he finds himself having to deal with unfamiliar problems, and forced to take decisions on the spot. It is essential, therefore, that his seniors and advisers shall make available to him the results of experiments carried out by others. Thus, for instance, Wright was totally opposed to the immediate evacuation of the wounded to England ... After an exhausting journey, he argued, they would be in no fit state to undergo operations which, carried out on the spot, would have a far better chance of being successful. 'We accumulate surgeons in France and wounded men in England ... It looks as though the problem, as set by the Army, is never to have the wolf, the lamb and the cabbage all together on the same side of the river ...' It was a matter of regret to him that the medical administration of the armies in the field, excellent though it was in dealing with the feeding and transportation of the wounded, seemed unable to shoulder the responsibility of solving such far more important problems as those affecting the improved treatment of the wounds themselves.

He, for his part, went to infinite trouble to make generally known what he thought to be the truth. At Boulogne he delivered a lecture: 'On the Proper Methods of Judging Different Types of Treatment'. 'Our task,' he said, 'is to find the truth and to convince others that it is the truth. The medical organization of our armies is such that it becomes necessary to persuade all the doctors who are working in the field. It is not enough to win over their superior officers because there can be no certainty that they will issue orders He was urgent in putting forward a suggestion that a 'Medical Intelligence and Investigation Department⁵ should be set up at the War Office. Its duty would be to study all the problems arising out of war conditions, not only as they concerned wounds, but other matters as well, such as epidemic jaundice, trench-fever and the causes of nervous break-down among air-pilots. Its decisions would be accepted by all. Since he had many friends in the world of politics, he went in person to London to put his point of view to the Secretary of State for War, Lord Derby, and to Arthur Balfour. But the opposition of the 'high-ups' in the Army Medical Service was violent. Sir Arthur Sloggett, the D.G.M.S., loudly denounced the scheme, said that Wright should stick to his laboratory work, and went so far as to demand his recall. He failed to get it, but Wright, too, failed to get what he wanted.

Dr James, at that time a battalion M.O., visited the Boulogne Casino on his way back from leave. There he saw Fleming and Colebrook. His first reaction, when he compared the almost academic calm of the laboratory with the din of battle, the dirt, the stench and the nervous tension in the forward aid-posts, was one of faint irritation. These back-area doctors, he thought, have too easy a life! Wright lived in a charming house on the Boulevard Daunou, where Lucienne, an excellent French cook, looked after his comfort. But it was not long before he noticed how much thinner Fleming had grown and how worn-out he looked. In conversation with him, he soon realized that these same 'back-area' doctors were working night and day, and that their only wish was to do everything they could to help the fighting men. Fleming, more eloquent than usual, explained to him the experiments he was conducting and the very precise ideas he had formed about what was necessary if that great enemy of the wounded, infection, was to be overcome. 'What we are looking for/ he said, ^cis some chemical substance which can be injected without danger into the blood stream for the purpose of destroying the bacilli of infection, as salvarsan destroys the spirochaetes.' They had not yet found such a substance, but the team had already collected a number of very important facts. These enabled them to avoid the more fatal mistakes and to help the organism of the wounded man in its curative work. James took back with him to his battalion several new, precise and sound ideas on the treatment of wounds.

There was no lack of visitors to the Casino. Bernard Shaw turned up on several occasions. Wright and he spent long nights in front of the fire discussing the relative importance of philosophy and medicine. One evening, when they were deep in argument, the chimney caught fire and the room was soon full of smoke. Lucienne and Freeman took turns in going into the street to see whether the roof was alight. Shaw and Wright, completely undisturbed, went on with their discussion.

The famous American brain-specialist, Harvey Cushing, stayed for a while with Wright. Though the two men were very different in temperament, they liked each other enormously. Though Cushing, like Fleming, had a matter-of-fact mind, he was greatly entertained by Wright's passionate tirades on women, the Catholic Church and intellectual integrity. While the talk was going on, on one occasion, the fire died down. Wright got it going again with the help of a newspaper and, since he had theories about everything under the sun, explained that, to keep the paper from catching fire, one must always on the first sign of combustion make a hole with a poker in such parts of the paper as had turned black. Cushing, much amused by this fire-surgery, called the method 'Wright's Punctures'.

Cushing was Surgeon-in-Chief of the American Hospital provided by the University of Harvard, which had recently been transferred to Boulogne. Another Harvard professor, Roger Lee, was the Head Physician. He knew Wright by reputation because of anti-typhoid vaccination. (During the Spanish-American war,

for every one man who died of wounds, a thousand succumbed to typhoid.) He had done some laboratory work on the opsonins and was delighted to learn that the famous Wright was under the same roof with him. He lost no time in paying him a visit and found him surrounded by Fleming, Freeman, Keith and Colebrook. 'I was at once attracted by Fleming,^' he says, 'though he hardly spoke.^' The attraction was mutual and the two men remained lifelong friends.

Among other visitors were Robert W. Bliss, the United States Ambassador in Paris, and several Frenchmen: Professor Pierre Duval, Jacques Calve and Dr Tuffier. Wright got along very well with the French, who shared his taste for general ideas. Freeman soon grew tired of Boulogne and went to work in Paris. On leaving, he said to Fleming: 'You know, Flem, we two ought to be playing a more active part.^' A grunt was the only answer he got. Fleming was thinking that the research-work at Boulogne might well save the lives of innumerable wounded men.

At the time of the First World War, the British had not, as had the French, the feeling that war is a quasi-religious ceremony, an act of sacrifice to be made with a becoming sense of gravity. They regarded it as a point of honour to relax occasionally, to seem to have time on their hands. A few miles behind the front the officers fished for trout and went sea-bathing. An eye-witness relates how one day Captain Fleming and another scientist — ^CI rather think it was Wright himself—feeling the need for exercise, had a wresding-match. Just as both of them were rolling on the floor, the door opened to admit a delegation of high-ranking French army doctors. The wrestiers jumped to their feet and at once embarked upon a learned scientific discussion. But I shall never forget the expression on the faces of those French medical generals.'

Nothing could well have been less in accordance with army conventions than the life led by this little group of scientists in uniform. So careless was Wright of his appearance that his orderly sergeant, Clayden, insisted on putting him through a dress-parade every morning, so as to make sure that he had got his belt on properly, etc. 'One day⁵, says Clayden, 'I noticed that the seat of his trousers was torn and that a piece of his shirt was showing. I didn't quite like to mention it, so I told Captain Fleming and said that he really ought to draw the Colonel's attention to it. His reply was: "Do it yourself." So I went straight up to Sir Almroth, stood to attention, clicked my heels (which always earned me a mocking smile from the Colonel), and said, " There's a hole in the seat of your pants, sir" He looked at me. "That's a nice way to talk, Sergeant, I must say! I suppose you think the nurses will be shocked. Well, what do you suggest I should do about it?" "I think, sir, the best thing would be for you to send your driver back to your billet for another pair." "What a brain!" he said. Captain Fleming and I had a good chuckle, and then everyone settled down to work.'

On Sundays Fleming and two of his colleagues (Thomson, an Irishman from Belfast, and Dr Keith, a Canadian) used to play golf at Wimereux. The links were situated on the sand-dunes which lie along the Channel coast. It meant a walk of a couple of miles or so northwards from Boulogne, but that didn't frighten the old foot-slogger of the London Scottish. Nevertheless, if an empty staff car happened to pass, the three musketeers would stop it. A somewhat self-important colonel regularly put in an appearance on the links. Fleming, a silent humorist, thought it great fun, when he was out of sight behind a dune, to drop the colonel's ball into the hole, and the colonel, thinking he had achieved the miraculous feat of holing out in one, was duly elated.

Fleming was far from being a brilliant player. As always, he wanted to improvise a secondary game within the game proper. To vary the proceedings, he adopted a number of non-regulation methods. He would, for instance, he on the ground and use a reversed putter as a billiard-cue, or turn his back to the hole, and putt between his legs. Sometimes the results were successful. The others accused him of cheating, but that didn't worry him.

Keith, the Canadian, had become one of Fleming's great friends. He had done his medical studies at various American universities and, in the eyes of the English, he was a Tank. Fleming's practical mind was much to his taste, because it was so effective. 'We found this research group more than usually interesting,' says Keith, 'because it kept in constant touch with the doctors and surgeons who looked after the wounded. The exchange of views which went on between them turned out to be useful and exciting. At tea-time, Boulogne being the great supply port for the B.E.F., there was always a crowd of guests, and the talk grew animated. Though Fleming said little, he did a great deal to keep the conversation at a practical level with his felicitous and opportune remarks. His views on the work done by the others, though penetrating, were always mixed with the milk of human kindness. His breadth of outlook reminded me of the best of our American research-workers, and it played a great part in the birth of our friendship.'

In 1918, a special hospital (No. 8 Stationary) was established at Wimereux to deal with fractures of the femur involving deep laceration. It was decided that a special study should be made there of septicaemia and gas-gangrene. Tt was a proud moment for me', says Dr Porteous, ^cwhen I was sent to this hospital as a bacteriologist working under Fleming's orders. He was in charge of the laboratory, and we shared a hut. Our lab. was a wooden shed. The walls were covered with "pin-ups", pictures of phagocytes with, here and there, an illustration from La Vie ParisienneFleming was still busy with his study of antiseptics and the saline treatment of wounds. He did a great deal of work on the septicaemias caused by streptococci and, with Porteous, tried to establish the conditions which would make this form of infection less frequent. He also practised transfusion, brought the method to a fine point, and published his results in the Lancet Transfusion was not yet a familiar routine. The blood donors were volunteers, who were encouraged by the promise of extra leave. To keep himself physically fit, Fleming had laid out two golf-holes on a piece of grass behind the hut and the two friends played there at night, with candles in the holes, whenever wind and air-raids permitted.

The great 1918 epidemic of Spanish flu kept the doctors hard at it night and day. The unexpected rate at which the sufferers were dying was heartbreaking. The orderlies themselves went sick with it. Quite often Fleming and Porteous themselves had to carry corpses to the improvised cemetery. Gas-gangrene was still raging and the stench was appalling, flies became a positive scourge, until Fleming devised a method of 'bringing them down⁵ by spraying them with xylene out of a syringe. He studied the Pfeiffer bacillus which was said to be causing this notorious form of flu. To be sure, it was found in ninety per cent of those suffering from it, though in general this particular bacillus is not regarded as being very dangerous, Fleming wondered why it should suddenly have produced this deadly epidemic. He attempted to grapple with the problem and discovered that there were several variants of the Pfeiffer bacillus and that it was not always the same but one or other of those variants which was found in people suffering from Spanish flu. He concluded, therefore, that the illness was caused by some agent other than the Pfeiffer bacillus which, in itself, was only the germ of a secondary infection. He was right, but that did not do much to help the sufferers.

'The picture I have of him', says his sergeant, 'is that of a short R.A.M.C. officer carrying a tray loaded with pipettes, Plasticine, platinum wire and a spirit lamp, standing on a cold winter's morning, with ice an! snow everywhere, in a tent heated by a brazier, with me carrying out an autopsy on a table, while on another table another corpse lay awaiting its turn! We had six autopsies to do that morning! It was Christmas Day and from each of the bodies Captain Fleming took specimens.'

In spite of all their efforts, the hospital doctors never succeeded in protecting the wounded from gas-gangrene. Fleming was in despair. 'Surrounded by all those infected wounds,' he wrote, 'by men who were suffering and dying without our being able to do anything to help them, I was consumed by a desire to discover, after all this struggling and waiting, something which would kill those microbes, something like salvarsan In this way he was driven back again on to the problem with which he had been obsessed when he wrote his thesis on 'How to Overcome Infectious Diseases'. But by this time Foch, in a sequence of unexpected blows, had shattered the enemy front. The war ended in November 1918. In January 1919 Fleming was demobilized.