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The discovery of penicillin
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2007-9-26
It was a September morning in 1928, when Fleming, the bacteriologist of St. Mary's Hospital in London came to his lab as usual. On rows of shelves in the lab, dozens of glass culture dishes stood in apple-pie order, each of them with a label reading respectively: streptococcus, staphylococcus, bacillus anthracis, colibacillus and so on. These were all virulent bacteria, which were collected by Fleming for the purpose of conquering them, to turn them into the avirulent ones. That ball-shape bacterium under the microscope, which was widely found, greatly harmful and terribly easy to cause infection and fester, was the one he especially desired to defeat. It is the bacterium that was making big troubles, he thought. Fleming had already been trying various kinds of bactericides in order to find out an ideal one to defeat it, but all failed.
That morning, he came to the shelves, checking the changes in the culture dishes one by one. Suddenly, he frowned when close to one of the dishes, mumbling to himself, "en, what's the matter? How could it be?" It was the culture dish labeled as staphylococcus, where some mould grew into a very small bunch of bluish-green fungi upon the culture medium. "It has been contaminated by other fungi. Don't use it any more, I will cast it away," said his assistant coming hurriedly. Fleming didn't hand the dish to the assistant immediately; instead, he observed it carefully for a while. To his surprise, the cultured staphylococcus surrounding the bluish-green fungi extinguished, only leaving a small space around the mould in the dish. Was that secretion of the bluish-green fungi killing the staphylococcus? Thinking about this, Fleming excitedly put it under the microscope for observation. He found that staphylococcus surrounding the bluish-green fungi died out completely, leaving only a slight trace. Promptly, he decided to culture the bluish-green fungi with culture medium.
Days later, the bluish-green fungi reproduced vigorously. So Fleming conducted an experiment, in which a thread that had been dipped into staphylococcus solution was placed in the culture dish containing the bluish-green fungi. Hours later, staphylococci were wiped out altogether. Then he put the threads which had been respectively dipped into streptococcus diphtheria solution, streptococcus pneumoniae solution, streptococcus solution, and bacillus anthracis solution, noticing that bacteria attached to the threads all died. However, colibacillus and salmonella typhi could still be alive and propagate in the culture dish.
In order to test how strong the bluish-green fungi could be in killing staphylococcus, Fleming diluted the culture solution with water as much as twice volume of the culture solution, followed by three times volume and finally 800 times volume. Each time, the eliminating capacity of the solution for staphylococcus, and streptococcus pneumoniae remained. It must be the most powerful bactericide that had ever discovered in the human history. But would it be harmful to animals too? To find out the answer, Fleming carefully injected it into the veins of rabbits, anxiously observing their reactions. The rabbits turned out to keep a whole skin, no any abnormal reactions taking place. This proved that the culture solution of the bluish-green fungi is nontoxic.
Fleming put his findings into a paper and published it in Jun. 1929. In the paper, he called the bactericide secreted by the fungi as penicillin. People came in flood to congratulate. A British grandee even suggested him apply the patent right to produce penicillin, so that he could make a fortune from it. However, after consideration, Fleming wrote to the grandee, gently refusing his suggestion. "I can't bear to hurt the lives of innumerous people unconsciously for the fame and wealth of myself and my family" he wrote.
It seemed accidental that Fleming had discovered penicillin. But it's virtually the inevitable result of his carefulness in observation. However, the disappointment was that penicillin couldn't be applied to practical clinics immediately as its content in the culture solution was too small, far from adequate to provide therapy. For clinical treatment, hundreds or even thousands of milliliters of the solution would be needed for a single patient to be injected only once. That was unpractical. Given this obstacle, Fleming had to suspend the culture and study of penicillin at that time. Nevertheless, his discovery paved the way for the study and research of the future scientists.
When time ran into 1940s, Howard Florey, the Australian pathologist who was in charge of pathological study in Oxford University, carefully read Fleming's paper on penicillin and developed a deep interest in the bactericide that could kill a variety of pathogens. But he was very clear about that abstraction of the substance required the joint efforts of many scientists from other disciplines. Florey quickly set up a lab, after he gathered some biologists, biochemists and pathologists, among which Ernst B. Chain, the German biochemists, was obviously his major and most right-hand assistant.
Under the leadership of Florey, the team conducted the research work strenuously. Every day these experts had to confect scores of tons of culture solution, pour it into culture dishes and inoculate penicillium into them. After penicilliums had sufficiently reproduced, they put them into large pots and sent them to Chain for abstraction. This was a heavy and arduous work, for culture solution in a large pot could only produce an amount of penicillin as small as a needlepoint. Several months' efforts brought Chain just a spoonful of penicillin. Dissolving it in water, it was quite effective in killing staphylococcus. Even though diluted with water of 2 million times volume, it still had eliminating capacity. In an experiment, 50 mice chosen by the research team were similarly injected the lethal amount of staphylococcus. Then penicillin was injected into only 25 of them. Result showed that mice without the injection of penicillin all died, while those with the injection were all alive except one.
Later, with even more strenuous efforts, the team started to abstract an amount enough to save one patient. And they did save one. The clinical case testified the unparallel effect of the bactericide, suggesting Florey that penicillin could be widely applied to practical clinics, provided that facilities were improved to realize mass production. For the research team, However, this was something impossible at that moment. In addition, London was then under Germany's frequent bombing, and mass production could not be safe.
In Jun. 1941, regardless of the objection of Chain, Florey, with the sample of penicillin, went to America, a country free from the flames of war. He worked in cooperation with American scientists in short order and finally confected culture solution with corn juice and built a set of facilities suitable to operate at 24¡æ.With all these, they were able to produce penicillin of high purity in a large scale and quickly put it into wide application to clinics. From that on, death rate resulted from epidemic diseases dropped dramatically, as innumerous people's lives had been saved by penicillin.
In recognition of their outstanding contribution to the discovery and application of penicillin, Fleming, Florey and Chain were together awarded the Nobel Prize in Physiology or Medicine in 1845.
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Organizer:
Beijing Municipal Association for Science & Technology
Undertaker: Beijing Science & Technology
Consulting Center,
Information Center of Beijing Municipal Association for
Science & Technology |
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