The Discovery of Penicillin

Through a Laboratory Window

The autumn of 1928 was damp, unusually damp even for London. The laboratory of St. Mary’s Hospital was ventilated by one slightly open window through which dead leaves and dust were blown in.

Dr. Alexander Fleming, the hospital’s bacteriologist, was writing an article on the behaviour of staphylococci, bacilli which cause various illnesses in human beings and animals.

A friend had called at the laboratory. As the two men talked, Dr. Fleming washed out some culture plates that had been spoiled by moulds coming from the air. Fine cultures of staphylococci were constantly being spoiled by moulds. Since such things happened from time to time and he was calm by nature, they did not bother him. He took one of the plates and turned the tap. As he did so he glanced at the plate and then turned off the water.

“That’s funny…” he said, and showed the plate to his friend. On the outer edges of the culture plate the colonies of bacteria were still flourishing, but round the part which was covered by the mould, the staphylococci had disappeared. It had secreted a substance which had killed the staphylococci.

The doctor grew more of the mould, which was a species of the genus penicillium, and then produced from it a small quantity of the substance which the mould secreted. He named it “penicillin” and began to make it work.

For years Alexander Fleming had been looking for substance which could kill dangerous bacteria. He knew as much about the subject as any man alive, yet nothing in his experience could do what this mould could do that had come in through his window and planted itself on his culture plate.

Dr. Fleming’s Experiments with Penicillin

Staphylococci, he soon found, were not the only members of the microbe world that penicillin attacked. It could also prevent the growth of streptococci and pneumococci, two of the most common man-killers. But it did not kill all the microbes that caused illness in human beings. It did not work according to any known rules.

Was penicillin dangerous? That, of course, was the big question. Lots of chemical antiseptics also killed bacteria in a test-tube, but they were dangerous to the human body. Dr. Fleming took two healthy rabbits. Into one he injected twenty cubic centimeters of penicillin solution, and into the other twenty cubic centimeters of ordinary solution. He found that penicillin was not toxic – at least to rabbits.

The main problem to be solved now was whether penicillin would kill microbes in the human body as it did in a test-tube.

“We tried a little in clinical work,” Fleming wrote, “but not much. When we went to hospitals and asked the surgeons if they had any septic cases we could try it on, they always said that they had none.”

In one way the cautious surgeons were right, for Fleming made no secret of the fact that he had hardly enough mould from which to prepare the penicillin and to concentrate it. Fleming was a bacteriologist, not a biologist or a chemist. He hoped that someone somewhere might be able to solve the problem of production, so he wrote a report on his laboratory experiments and presented it at a medical meeting. But there were many papers, no one paid special attention to Fleming’s, and it was forgotten.

The years passed. In the laboratory penicillin was used as a quick way to distinguish between various types of bacteria because of its indifference to some and its antagonism to others. For ten years Alexander Fleming kept a small store of it in a corner of the laboratory.

Dr. Fleming’s Hopes Realized

In 1935 the production of the sulpha drugs caused a great stir in the world of medicine, and – as often happens – the power of these important chemicals was very much exaggerated. Some years later a friend recalled a conversation about this with Fleming.

“You know, Mac,” Fleming said, “I have something much better – but not one will listen to me. I cannot find a chemist who will extract it for me.”

“What’s the name of it?”

“I named it ‘penicillin’”.

“I’ve never heard of it.”

Few people outside Fleming’s laboratory ever had.

In Oxford at this time two biochemists named Florey and Chain were doing research on “bacterial antagonisms”. They studied hundreds of old medical journals and finally found articles about three “antagonistic” substances that seemed promising. One of these three articles was Fleming’s original paper on penicillin.

The two men decided that of the three substances Fleming’s solution of penicillium mould had the greatest possibilities.

This was in 1937. By the next year it had become clear that England and perhaps the whole world would soon be at war. Before long hospitals might be full of wounded men. Of all the problems that war would present to medical researchers, none was more important than a way to check infection.

Florey and Chain soon found that Alexander Fleming had not exaggerated in his report on penicillin. A young chemist named Heatley joined the team. After working for some time the three men obtained a higher concentration of penicillin than had yet been possible. From this they produced the first penicillin salt.

In 1940, when England was already under heavy attack, they made their first decisive experiment. Florey injected large doses of the deadliest strain of streptococci he could get into fifty mice. He left twenty-five untreated. The other twenty-five were given penicillin injections at three intervals for forty-five hours. Of the untreated mice, all twenty-five died within sixteen hours. Of the penicillin-treated mice, twenty-four out of the twenty–five lived.

These sensational results were published on August 24, 1940, in The Lancet. Alexander Fleming, like most doctors in England, glanced through each issue of this weekly medical journal to see what was new and interesting. It is hard even to imagine the emotions he felt while reading the report from Oxford.

Very soon he was knocking on the door of Florey and Chain’s laboratory. He was Alexander Fleming, he explained to the astonished scientists, and he had come to see what penicillin looked like in a pure state. The two men were hardly able to speak. They had thought that Alexander Fleming was dead.

Fleming sent Florey a strain of the penicillium mould descended from his original colony. The Oxford men now began preparing a supply for their first tests of penicillin on human beings, but Florey began the experiments with a heavy heart. The scientists had discovered there was a great problem with the magical substance. The body does not retain penicillin. It is thrown out almost as quickly as it can be injected. The amount necessary to keep twenty-five mice alive had almost used up the laboratory supply. Could they now produce the amount large enough to treat one man? What did they hope to prove by being able to treat one man, when men in that year were dying by the thousands and being wounded by the tens of thousands?

The first trials

In February 1941, a London policeman cut his face while shaving. It was a common enough accident, but as it happened in this case, a terrible one. Two weeks later the man was dying; his body was invaded by an army of staphylococci.

The case was almost made to order for the purpose of Florey and his colleagues. Every bit of penicillin in the laboratory was taken to the hospital where the policemen was lying. The dying man was given a dose of penicillin injected into the blood stream every three hours. Five days passed. It seemed to Florey that they would never end. Within two days a slight drop in temperature was noted on the third day the horrible swellings on the policeman’s face began to disappear. The next day his temperature was almost normal, but by the fifth day all the penicillin was gone.

In the laboratory great efforts were made to produce some more. The efforts came too late. Before the treatment could be resumed the infection again flared up. The policeman died.

By some standards the first trial of penicillin had failed, since the patient was dead. But those who had followed the case were now more convinced than ever of penicillin’s effectiveness. They worked day and night to produce more of it.

In the Oxford laboratory the telephone rang early one morning. “Florey? Fletcher here. I have a case that I think you might want to look at. Fifteen-year-old boy. Streptococci infection. Sulphas cannot do a thing for it. He’ll die in less than two days, unless…”

This time it happened. The boy did not die. Again the supply of penicillin was gone, but this time there had been just enough. “Now,” Florey thought, “we have to have more of it,” and they began to look for a way to put penicillin into production on a large scale.

England was too busy with the necessities of war to start a new industry. The drug had to be produced somewhere abroad.

A solution is found

In 1941 Howard Florey and Norman Heatley were invited to the United States. They carried with them a sample of the mould descended from Alexander Fleming’s original visitor that had come through the window. Florey and Heatley were taken to a research laboratory in Peoria, Illinois, where the American scientists decided to find some new fast way to grow the mould which gave penicillin. They began to look for a better solution in which to grow it. One day, when one of the scientists was checking his cultures, he found that one of them was producing two hundred units of penicillin to every cubic centimeter – 200,000 to a litre instead of the 1,000 to a litre that had been produced in the Oxford laboratory. They had found a way to make the mould grow fast.

The great difficulty was now solved. Drug manufacturers who had said: “Sorry, not interested”, were now eager to produce large quantities of penicillin. They were ready to spend money, because they saw profits in the future. All over the United States chemists, bacteriologists, engineers, government officials, military officials, and medical research men were sitting up late at night over their notebooks and their test-tubes.

During the first five months of commercial production 400 million units of penicillin were produced and the figure reached 9,194 million units a month. Later the figures became astronomical.

Alexander Fleming wrote: “There are thousands of different moulds and there are thousands of different bacteria, and that chance which put that mould in the right spot at the right time was like winning the Irish sweepstake.”

It may be added that there are also thousands of bacteriologists. Very likely other penicillium moulds had settled on other culture plates on other laboratories and had not been noticed. “In the field of observation,” Louis Pasteur once said, “chance helps the mind that is prepared.” It was one of the happiest accidents in history that the mould spoiled a culture belonging to Alexander Fleming.

3) Give the English equivalents to the following: человечество всегда будет благодарно, диссертация, наглядные пособия, зайти (заглянуть), стеклянные чашки (лабораторная посуда для культивирования микроорганизмов), по крайней мере, больной (поражённый какой-либо инфекцией), израсходовать, сделать по заказу, разгореться (вспыхнуть с новой силой), наладить производство в широких масштабах, выиграть пари на ирландских скачках (выигрыш выплачивается только один и может быть очень большим), весьма вероятно.

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