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The story of penicillin

The story of penicillin(1)


image of penicillin bottle

penicillin. It can be said that humankind has changed completely before and after getting this medicine. It wasn't long ago that I got this. Prior to that, a number of illnesses that once infected had no choice but to pray for recovery, but after the advent of penicillin, they were easily cured. The evaluation of "the greatest invention of the century" is not an exaggeration at all.


So far, I've mentioned the Ebiswords that some drugs have saved historical celebrities. However, the number of lives saved by penicillin is at least millions. Perhaps some readers of this would not be in the world without penicillin.

From the Meiji era to the prewar period, the average life expectancy of Japanese people has been in the age range. Child mortality was high, and it was not uncommon to die in your thirties. He is now over 70 years old. This is due to factors such as improved nutrition and hygiene. The spread of antibiotics such as penicillin also plays a major role.


This "miracle medicine" can now be obtained at a nearby pharmacy for a few hundred yen. There is not much difference between people a year ago and us today.


Wear similar clothes, eat similar things, cry, laugh, and speak in the same way. However, when it comes to infectious diseases, the two are completely different worlds.


The birth of penicillin, which has brought about such a great change in the world, is surrounded by many legends and myths. The first protagonist was Alexander Fleming, a bacteriologist who worked at St Mary's Hospital in London.

It's from a runny nose

In the latter half of the 4th century, a disinfectant was discovered by British surgeon Joseph Lister, and it was very effective in preventing infectious diseases. However, the disinfectant phenol he used was either ineffective against bacteria that had invaded the body, or even exacerbated the symptoms. That's because phenol destroys the white blood cells that fight it first, rather than the bacteria.


Therefore, there has been a demand for a substance that does not act on the cells of the human body and kills only bacteria.

In 1922 Fleming was his own runny nose. Find this convenient substance from a surprising place. He found that a drop of his diluted runny nose in a culture of bacterial growth killed the bacteria and cleared them within minutes.


How did he discover such a strange thing? When he happened to have a runny nose on a petri dish that was culturing bacteria.

When I looked it up the next day, I heard that the bacteria had stopped growing only around the runny nose. However, there is no certainty that this discovery was really such a dramatic one, and it may be the creation of a posterity biographer. Anyway, Fleming found that this bactericidal component was also contained in tears, saliva, serum, etc., and presumed that the component was an enzyme. He names this bactericidal component "lysozyme" with the meaning of "degrading enzyme".


However, lysozyme was not something that could be a cure for the disease, contrary to his expectations. Lysozyme was powerless against the highly pathogenic typhoid, streptococcus, and pneumococcus, only killing a few harmless bacteria. This is not surprising when you think about it, and if the human body has such a powerful antibacterial agent, no one will get an infection. Fleming also reported the discovery of lysozyme at academia, but few were interested in the story of a runny nose killing harmless bacteria.

However, the discovery of lysozyme will have great significance after this. It was Fleming's own eyes that he knew of the existence of antibacterial substances and what the bacteria would look like with them. Originally, Fleming was a person who loved experimental operations such as culturing bacteria and found joy in observing them so much that he said, "I am playing with bacteria." The phenomenon of "antibacterial action" was firmly burned into his mind.


The story of penicillin(2)


Cultivating fungi in a Petri dish


Good luck

One morning in September 1928, six years after the discovery of Lysozyme, Fleming was once again lucky. He was culturing the staphylococcus in a petri dish to observe a variant of the staphylococcus. When the liquid collected from the lesion is smeared on the surface of the "agar medium", which is a solution containing nutrients solidified with agar, the bacteria grow in a few hours and become a round mass of visible size. Form (colony). One colony grows from one bacterium, and if it is collected, pure culture of a specific bacterium becomes possible.


However, with this method, pollution has been a problem both now and in the past. Bacteria are everywhere, so it's not uncommon for bacteria from somewhere to invade and multiply, overwhelming the cells in culture.


It happened at this time as well. Penicillium spores jumped from somewhere into one of the petri dishes Fleming was trying to cultivate staphylococci, and were breeding. However, he notices that there are no staphylococci around the penicillium. Fleming's mind passed through the memory of the discovery of Lysozyme.

He instinctively thought that this might be because Penicillium made some kind of antibacterial substance. "If I hadn't had the experience of lysozyme, I wouldn't have realized the value of this discovery and would have thrown away the medium," he later recalled.


When I asked a mold expert to identify it, I found that this Penicillium belongs to the genus Penicillium. Fleming takes its name from here and names the antibacterial substance "penicillin". Fleming himself never expected that this would eventually save millions of lives.

The petri dish, where he first discovered penicillin, was treated to prevent the growth of other fungi and is now on display at the British Museum. Fleming's laboratory has also been recreated in St Mary's Hospital at that time, and has been handed down to the present day.

The discovery of penicillin would have been due to Fleming's excellent eye, but it's a bit unbelievable that a researcher happens to be blessed with an antibacterial substance twice. ..


Fortunately, Fleming had been away from his lab for a long time on a family trip from the end of July after finishing staphylococcal culture. Without this period, Penicillium spores might not have jumped into the petri dish and propagated well.


The mold discovered by Fleming was a rare type of penicillium, and had outstanding penicillin production capacity. Almost the only researcher who knew the reality of the antibacterial phenomenon and its value-in fact, Fleming showed the petri dish to the members of the institute from one end, but who was interested in this strange mold? It's a miraculous probability that he jumped into the place where he didn't seem to be there.

Dr. Osamu Shimomura, who won the 2008 Nobel Prize in Chemistry for the discovery of GFP (Green Fluorescent Protein), mentioned that this research was a result of various lucks, and this discovery seems to be a heavenly guide. I even wonder if Heaven used me as a human being to give humanity. " Looking at the history of the discovery of penicillin, it is tempting to wonder if this substance was also a benefit that Heaven had given to humankind through Fleming. To that extent, the discovery of penicillin is a combination of good luck and chance.


The story of penicillin(3)


An image depicting the flow of atoms


Fleming continued his research on penicillin and found that the substance did not destroy white blood cells and was essentially harmless to animals. In fact, he tried to use penicillin as a medicine, but this didn't work very well. Benicillin was chemically unstable and difficult to remove purely or store for long periods of time.


It turned out long after that the source of the antibacterial activity of penicillin was its molecular structure, especially the part he called lactam. This is a square cyclic structure consisting of three carbon atoms and one nitrogen atom. Lactam is an extremely rare structure, and it was never expected that such a compound would exist naturally.


In carbon, etc., the most stable state is a hexagonal shape with six atoms forming a ring. Lactam forcibly twists this into a square, so if something happens, the ring will pop and open immediately. In other words, it is chemically reactive.

Bacteria protect their bodies from the outside world by wearing strong armor called cell walls. When penicillin attaches to the enzyme that makes up this cell wall, the lactam part opens and binds, causing the enzyme to lose its function. Since higher animals such as humans do not have a cell wall, penicillin basically has no effect on the human body. This is the mechanism of penicillin's antibacterial activity, and the high reactivity of lactam is inseparable from its antibacterial activity.


However, high reactivity also means that penicillin is unstable and difficult to handle. Fleming, who is proficient in the handling of bacteria, is not specialized in the handling of compounds, and it was difficult to concentrate and purify penicillin.


Fleming himself thought that it would be difficult to apply penicillin to medicine, so he focused on using it as an experimental reagent in biology.

In the field of infectious disease treatment, penicillin was applied to medicine with the advent of sulfa drugs in the mid-1930s (although there were salvarsans developed by Ehrlich and Qin, side effects were also strong. Effective diseases were also limited to syphilis at that time).

It has been shown that there is definitely a "solution" to the previously unanswered question of whether chemicals can cure illness. Then, find a better "solution".


Fleming's penicillin treatise was spotted by Howard Florey of Oxford University and Ernst Chain. As the study progressed, the potential of penicillin excited them. The following year, in 1939, he decided to abandon other projects and pour his never-rich research funding into a bottle of Benicillin.


They gradually improved the extraction operation with organic solvents and acid or alkaline aqueous solutions, and established a technique for concentrating without damaging unstable penicillin molecules. In 1940, they get about 100 milligrams of precious penicillin powder. Flories thought it was almost pure, but later found that the powder was about 0.1% pure, that is, only 0.1 milligrams of real penicillin was contained. .. You can see how difficult it was to purify penicillin.


Animal experiments were successful in 1940, and clinical trials in humans began the following year, saving the lives of people infected with staphylococci and streptococci. Then, in 1941, the Pacific War broke out, and the world was once again involved in a huge war. Drug development to prevent infectious diseases of injured soldiers has become one of the nation's most important issues.


In 1942, penicillin research was designated as a "state secret" in the United States and the United Kingdom. The total amount of research funds invested after this is said to be 24 million dollars, which is second only to the "Manhattan Project" that developed the atomic bomb as a scientific research during the war. When mass production became possible in this way, the use of benicillin began to increase in general, and the fame of "miracle medicine" increased day by day.


In June 1944, the Normandy landing operation, also known as the "largest operation in history," was carried out, and penicillin unfortunately demonstrated its true value. The wounded injured recovered safely, thanks to penicillin, with almost no gas gangrene or sepsis. The common sense of the battlefield until then changed completely, and Fleming will be celebrated as a hero. In 1945, Fleming, Flory, and Chain were jointly awarded the Nobel Prize in Physiology or Medicine. Within just a few years of mass production research, penicillin changed the history of the world.

Penicillin has various episodes because it is a drug that has had a great impact on the world. Let me introduce some.


First, there is a theory that Ieyasu Tokugawa was the first person in the world to save his life. During the battle between Komaki and Nagakute, Ieyasu probably had a bacterium like Staphylococcus aureus from his wound, causing a large swelling on his back. Seeing the condition getting worse day by day, one of his vassals headed to Kasamori Inari and brought back a dumpling that was said to be "effective for swollen things." He smeared the penicillium dumplings on his back, and a plethora of pus spewed out and the swelling healed. This was due to the penicillin contained in Penicillium.


This is not a completely impossible story in theory, but it is unlikely that the penicillium that grew a little on the dumplings made penicillium enough to annihilate the bacteria that nested in Ieyasu's body. Ieyasu's penicillin legend will only be "interesting as a story."

Churchill's story

One of the "myths" about penicillin is that Fleming saved the life of British Prime Minister Winston Churchill twice. Churchill was rescued by a young Fleming who happened to pass by when he was drowning in a swamp when he was a boy. This allowed Churchill's father to help Fleming with his tuition, which made him a doctor. Churchill suffered from pneumonia in 1943, but was killed by the penicillin discovered by Fleming.

But in reality, Churchill is seven years older than Fleming, and Fleming's youth cannot help the Churchill boy or receive tuition assistance. Also, as mentioned in the previous chapter, it was actually sulfa drugs, not penicillin, that treated Churchill's pneumonia.

The story seems to have been first mentioned in Sbeach by Treasury Secretary Vinson when Fleming received the award in the United States. Fleming couldn't have been denied that it was "random" because it was the words of a high-ranking government official in a sunny seat. In this way, this overkill anecdote has spread all over the world, and even now, it can be seen as a "real story of emotion" on the Internet.

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