Alexander Fleming, Chain, Florey and the healing power of penicillin

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Alexander Fleming Biography, Discovery of Penicillin

A glass lid that slipped off a bowl, a researcher who became curious about what he saw and another researcher who ten years later read a forgotten article about the event. These are some of the unlikely coincidences that together led to the discovery of the penicillin. The discovery has led to hundreds of millions of human lives being saved and at the same time provided an explanation for why cobwebs and fungi have been used to treat wounds for thousands of years.

One day in 1938, Dr. Ernst Boris Chain was reading in Radcliffe’s library in Oxford.

Chain (1906-1979) was a biochemist, but that day he read in a ten-year-old journal about diseases. Chain’s eyes fell on the crisp headline “The antibacterial effect of penicillin cultures, especially with regard to their use in isolating B epidemics,” and he began to read.

When Chain had left, he was overjoyed. Here was the missing link he was looking for in vain – a description of a substance that killed bacteria.

The article was written by Dr. Alexander Fleming (1881-1955). It gave Chain the key to how the miracle drug penicillin was made, a drug that has saved hundreds of millions of lives and cured patients who were previously helplessly lost.

Alexander Fleming was born in 1881 on a Scottish farm. Fleming’s father died early, and his mother had to fight hard to provide food for the day for her eight children. Every school day, Fleming went to school, 6 kilometers there and 6 kilometers back. The mother understood that the son was talented, and at the age of 14 he was sent to a technical school in London. Alexander soon realized that it was medicine he wanted to study.

The bacteria and their enemies

Alexander Fleming took a job in an office, worked there for four years and saved as much as possible. Then he received a small inheritance, which together with the savings made it possible to pay for a medical education.

St. Mary’s Hospital in London received paying students, and Fleming applied here. When Fleming graduated with high marks, he was offered a place as an assistant to Sir Almroth Wright. He researched how bacteria were destroyed by their natural enemies.

When animals die, the bacteria immediately begin their destructive work, and a body that has been dead for a while is full of bacteria. Since all living things sooner or later return to becoming earth, the earth should not really consist of anything but bacteria. But why is it not so? The answer turned out to be that different microorganisms live off each other. A war of all against all is waged uninterrupted on a microscopic scale.

– Life hinders life, Louis Pasteur had said, when he described his discovery that different bacteria can fight each other.

Maybe it was possible to find an organism that attacked bacteria?

Doctors tried to use the new knowledge through various experiments. Often they preferred themselves to subjects rather than patients. At St. Mary’s Hospital, two doctors who tested new methods on themselves died. Fleming himself became very ill when he subjected himself to a similar experiment.

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Bullets caused sore fever

In 1914, World War I broke out and Fleming and Wright traveled to France to try to help the thousands of soldiers who were at risk of dying from wound fever. Fleming discovered that one of the most common causes of wound fever was that soldiers were wounded by bullets and shrapnel that had passed through their bacteria-filled uniforms and taken bacteria with them into the body. There, the bacteria multiplied rapidly and even made small wounds dangerous through infections.

After the war, Fleming returned to work. He discovered that human tears contained a substance that killed bacteria. However, the substance, which was named lysozyme, was too weak. Fleming had nevertheless made an important discovery – it was possible to find substances that attacked bacteria.

In 1928, the coincidence that would save so many human lives occurred. Fleming had prepared a series of glass bowls with cultures of staphylococcal bacteria. Staphylococcus causes pimples, boils and inflammation, among other things. Fleming placed the bowls on the workbench to travel on vacation. This was the end of July.

Zone without bacteria

During the holidays, Fleming was appointed professor and returned to his laboratory. He started sorting his crops and was just about to wash them away when he saw something strange. On a bowl the lid had slipped off and in it a lump of mold had formed on a plate. This was not unusual, but what caught Fleming’s interest was that the staphylococcal bacteria did not appear raw on the mold. A clear zone around the mold was completely free of bacteria!

This was a fantastic coincidence. Apparently some mold had landed on the bacteria at the right moment. In addition, the weather was perfect. A cold week was followed by strong heat. In the cold, mold grows faster than bacteria. In the test, the mold could only grow strong enough during the cold week to be able to affect the bacteria. Had it been hot all the time, the mold would have been engulfed by the bacteria.

– It was clear that something unusual was happening, Fleming himself said and continued:

– This interested me much more than the experiments with staphylococci, so I ended them immediately. Now I am glad that I have been particularly interested in antiseptics and that a few years earlier I had come across a similar antiseptic in nature: lysozyme. Without this previous experience, I would probably have thrown out the dish, which many other bacteriologists must have done before …

Instead of throwing out the contaminated bowl, Fleming did new research. There are thousands of different types of mold and thousands of different types of bacteria. The chance that this mold ended up in the right place at the right moment was as small as winning the highest prize.

Mold penicillin

What had fallen into the bowl was a trace of the mold fungus penicillium notatum, and when Fleming had found out, he continued his experiments.

It turned out that even if the mold was diluted 500-800 times, the growth of the bacteria was hindered. The fungus was thus two to three times more effective than the phenol that Joseph Lister used in his attempts to eradicate bacteria.

Penicillin also had few side effects and attacked a number of different diseases.

But it was one thing to kill bacteria in a glass bowl, quite another to eradicate staphylococci that have taken root in a patient’s body. The penicillin Fleming had was weak and gave no results in patients. Fleming could not produce enough pure penicillin but got stuck. His discovery was forgotten for ten years until the day Dr. Ernst Boris Chain read Fleming’s article.

Chain and Florey

Chain worked with biochemist Howard Walter Florey (1898-1968) to find a natural enemy of bacteria, but the results were poor. Chain was about to give up and engage in something else when he found the article.

“It was pure luck,” Chain said afterwards. I am a biochemist, not a pathologist, and no chemist would come up with the idea of ​​reading a journal in pathology (pathology = the study of diseases) to help his chemical research. But in Oxford the two subjects are gathered under one roof, and that thought made me go through the magazines.

Chain and Florey took an evening walk in Oxford, and Chain persuaded Florey. They would examine the penicillin more closely.

Experiments on mice …

In 1939, World War II broke out . The researchers realized what help penicillin would be for wounded soldiers and increased their efforts. By May 1940, Florey and his assistant, Norman Heatley, had obtained a brown powder, the first penicillin salt. The salt contained only one percent penicillin – would that be enough?

Eight mice received a lethal dose of streptococcal bacteria. One hour later, four of the mice received penicillin. Late into the night, Florey and Heatley sat at the mice’s cages. In the morning, the four mice that did not receive penicillin died. The others survived.

Fleming found out the news eight weeks later, when he read the report on the experiment in the medical journal The Lancet at breakfast . He traveled straight to Oxford – without finishing his breakfast.

… And on people

Now the penicillin must be produced on a larger scale to be able to be used at the fronts. Heatley discovered that penicillin, the active ingredient in the mold, could be extracted at low temperatures with a solution of ether and acid.

A group of girls, students and nurses, were called to the university. Dressed in coats, gloves and earmuffs, the so-called penicillin girls worked in cold rooms rolling bottles of mold so that the ether could draw out the penicillin. In the winter, bottles were rolled in the snow on the laboratory roof. But the petition went too slowly.

In 1941, the first experiment was performed on a human – a policeman who was dying of blood poisoning. He received penicillin and steadily got better. But then the penicillin ran out, the police got worse again and died after a few weeks.

Adversity took Dr. Florey hard.

– No more attempts until we have enough penicillin, he decided.

A few weeks later, the doctors got another chance, when a 15-year-old boy with blood poisoning was taken to hospital. Penicillin was inserted, and this time the patient was saved.

Patent

Florey and Heatley realized that war-torn Britain could not invest enough resources. They traveled to the United States with samples of the mold.

They did not patent the petition themselves, as they considered that their discovery belonged to the public. In the United States, researchers were less careful. The patent was applied for, and the United Kingdom was subsequently forced to pay to use the manufacturing methods.

In 1943, Chain, who had stayed in the United Kingdom, was able to obtain one hundred percent pure penicillin, and in October of that year he was able to map its chemical composition.

In the United States, a program to develop penicillin had been launched, and in 1943, 500 people could be treated.

Nobel Prize in Medicine

By the end of World War II, thousands of people had already been given penicillin, which is still one of the most important drugs in the world today. About 30 percent of Sweden’s population is treated with penicillin for one year.

In 1945, Fleming, Florey and Chain received the Nobel Prize in Medicine. Fleming and Florey were knighted in Britain.

When Fleming later in Paris lectured on his discovery, he repeatedly emphasized the series of happy circumstances that led to the discovery. Had Fleming not inherited his small inheritance, he might never have had the opportunity to study medicine. Had the mold not ended up in his bowl and Chain would not have read his article, penicillin might have been undetected even today.

It has been known for thousands of years that fungi and herbs could be used to treat wounds, including in ancient Egypt , ancient Greece, and the Roman Empire . The reason why the treatment worked was often that bandages with fungi and herbs molded and the mold counteracted bacteria. But that bacteria caused diseases was unknown until the second half of the 19th century when Louis Pasteur mapped the connection. Before that, no one knew why fungi and herbs could soothe wounds.

In the Roman Empire, soldiers used cobwebs to heal wounds on horses. In Europe, wounds were treated with soaked bread mixed with cobwebs. Cobwebs often contain substances that have similar properties to penicillin. Sometimes even mold spores may have stuck to the sticky cobwebs.

Alexander Fleming died of a heart attack in 1955. He was buried in St. Paul’s Cathedral in London. Penicillin may have saved the lives of up to 200 million people. The discovery also prompted others to continue the work begun by the penicillin discoverers.

Other cures …

When penicillin was discovered, researchers soon began trying to find other remedies for the diseases that penicillin did not bite.

In 1943, the American Selman Waksman isolated streptomycin. It turned out to be effective against tuberculosis . Sixty years after Robert Koch found the bacillus, scientists had also found a cure for it. Yet another of humanity’s great torments could be fought.

Unlike penicillin, streptomycin is toxic and must be used with caution. In 1952, Waksman received the Nobel Prize in Medicine.

The next step was the discovery of a series of drugs called tetracyclines. These are today one of the most widely used drugs against infections.

At the same time as humans have been getting better and better remedies for infections, new bacterial strains have emerged that the old remedies do not bite on. New ones must be constantly researched.

In 1939, all cases of meningitis could be cured with antibiotics, as these medications are called. Twenty years later, only half of the cases could be cured with the antibiotics known in 1939.

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Tasks and questions

Questions to the text:

  1. When and where was Alexander Fleming born?
     
  2. What is the name of the substance in human tears that attacks bacteria?
     
  3. What is penicillin?
     
  4. Why did Fleming realize that penicillin could counteract bacteria?
     
  5. Why could not Fleming use his discovery to produce effective drugs?
     
  6. In what year could a patient be saved for life for the first time penicillin?
     
  7. How large a part of Sweden’s population is treated every year with this form of penicillin?
     
  8. How did you go about extracting the penicillin in pure form?
     
  9. Name some types of drugs other than penicillin and explain what diseases they are used for.
     
  10. Why do new drugs have to be developed all the time for various diseases?

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