What discovery did Fleming make? Who discovered penicillin? How are infectious diseases treated?

Penicillium chrysogenium (notatum) is a member of the genus Penicillium. "Record holder" for the production of penicillin

The very idea of ​​using other microorganisms (or what they synthesize) to fight microorganisms has been around in medicine for a very long time.
In the microbial community itself, some microbes constantly suppress others and are in such a dynamic balance.

As early as 1897, long before the discovery of penicillin, Ernest Duchene used mold in an experiment to treat typhus in guinea pigs.

Penicillium roqueforti - "noble mold". Used to make Roquefort cheese and gives it a distinctive flavor

What do you think guinea pigs, blue cheese and tap water have in common?

The question is rather complicated. It would seem: nothing in common. But if you were a French medical student of the late 19th century, then these subjects would be your scientific reagents.
These reagents were used by the brilliant Ernest Duchen to discover antibiotics, almost 35 years before Alexander Fleming discovered penicillin.

So the history of anti-bitics did not begin with Fleming, no. Fleming was not the first to notice the antibacterial properties of mold. Mold was used to heal wounds by the ancient Egyptians. And, although in ancient Egypt there was no scientific support for many medical actions, one should not forget about the remarkable powers of observation of the ancient healers.

Ernest Duchen

It was he who first described the antibacterial properties of penicillin. Very little is known about his life. Born in Paris, he studied at the military medical school in Lyon, where he entered at the age of twenty.
Duchenne was simply fascinated by microbes. Still would! The discovery of pathogenic properties in microbes, the works of Louis Pasteur, simply turned the worldview of physicians of that time. Ernest Duchen decided to write his dissertation under the guidance of Professor of Microbiology Gabriel Roux. Gabriel Roux was then in charge of the laboratory responsible for the quality of the water supply in Lyon. Duchenne's dissertation was devoted to the following observation: tap water never got moldy, but mold could grow well in distilled water. The first suggestion was that bacteria prevent mold from growing in tap water.

Ernest grew Penicillum glaucum. This mold is used to make Gorgonzola and Stilton cheeses. He placed it in containers with tap and boiled water. Then he added typhoid fever and E. coli - the mold quickly died. It turned out that the bacteria in the water kill the mold. Duchenne began to set different conditions: temperature, acidity of the environment, but the mold did not always die. Sometimes the fungus won.
Again, the question arose: can mold somehow “respond” to bacteria? Can she fight them? In an experiment on guinea pigs, a decrease in the virulence of bacteria was found. Moreover, by injecting the mold, Duchene was able to cure the animal. A similar experiment will be conducted by Alexander Fleming, who is often called the discoverer of penicillin.

Much has been written about how Fleming discovered penicillin. So why is Duchenne not remembered as the discoverer of penicillin? There are several reasons for this. Well, first of all, he was researching Penicillum glausum, as opposed to another type of mold, Penicillum notanum. Mold, which actually synthesizes this penicillin. Later it was found that Penicillum glausum produces another, weaker antibiotic - patulin (by the way, it is toxic and works in high concentrations, therefore it is not used). Probably, if it were not for the health of the young scientist, as well as a short life path (he died of tuberculosis in 1912, having lost his wife long before that from the same tuberculosis), the discovery of penicillin would have belonged to him.

Alexander Fleming

But a fact is a fact. Alexander Fleming was the inventor and discoverer of penicillin. The date of discovery of the most famous antibiotic is September 3, 1928 (Birthday of penicillin). Fleming by that time was already widely known, had a reputation as a brilliant researcher.
Mankind still owes the discovery of penicillin to this Scottish biochemist. After the First World War, in which the "father of penicillin" served as a military doctor, Fleming could not accept the fact that a large number of soldiers died from infectious complications. In 1918 he returned from the war to work in the bacteriological laboratory of St. Mary's Hospital, where he had worked before (and where he would work until his death). In 1922, an incident occurred that, of course, looked more like a fable, but nevertheless, six years ahead of the discovery of penicillin. Fleming, who had a cold, accidentally sneezed on a Petri dish where there were bacterial colonies. A few days later he found stunted growth of bacteria (Micrococcus lysodeikticus) in some places. This is how lysozyme (muramidase) was discovered. This hydrolytic enzyme breaks down the walls of bacteria, that is, it has bactericidal properties. A lot of it in the secretions of nasal mucus, saliva (why animals can lick their wounds), lacrimal fluid. There is a lot of it in breast milk (moreover, it is noticeably more than in cow's milk and when feeding, its concentration does not decrease over time, but increases). Of course, when penicillin is discovered, interest in lysozyme will noticeably drop, until the discovery of chicken protein lysozyme.

As Alexander Fleming himself later noted, chance helped the discovery of penicillin. Working in the laboratory and studying the enzyme lysozyme, Fleming did not differ in order in the workplace (although scientists have their own order!). As is often the case with geniuses (remember at least Einstein's desktop), the scientist's laboratory was a real mess. Fleming, returning after a month of absence, noticed that mold fungi had appeared on one cup with staphylococcus cultures. The fungal colony dissolved the inoculated culture. The mold belonged to the genus Penicillaceae, which is why the isolated substance was later called penicillin.

The name penicillin is translated as "writing brush", a similar similarity is visible under a microscope.

Howard Flory

And although Alexander Fleming is remembered when it comes to the discovery of penicillin, other scientists, in particular the pharmacologist Govrad Walter Flory, have taken practical advantage of this discovery. In 1938, Florey, working with Ernest Cheyne and Norman Heatley at the University of Oxford, England, began experimenting with the antibacterial properties of the fungus Penicillium notatum. Fleming wrote about the properties of the fungus to suppress bacterial growth in his writings.
The first patient to be prescribed penicillin was Albert Alexander, a London police officer. A serious infection that affected part of the face, the periorbital region of the eye, the scalp, began with a small prick of a rose thorn. Flory and Cheyne gave the patient penicillin, and during the first day there was a good trend. However, it was not possible to determine the optimal dose of the drug (it was not known even then) and the infectious process nevertheless led to the death of the patient. The experiments continued, the drug was administered to seriously ill children with impressive effects. It is now believed that the work of Flory and Cheyne saved more than 80 million people.

Ernest Chain

And now it is worth saying about the previously mentioned biochemist Ernest Boris Cheyne. Born into a Jewish family and living in Germany, he was forced to emigrate to England when Hitler came to power. As co-recipient of the future Nobel Prize for the discovery of penicillin, Cheyne was for that part of the work in which he showed the structure of penicillin and successfully isolated the active substance. To isolate penicillin, for one therapeutic dose, it was necessary to process about 500 liters of nutrient broth with mold!
Cheyne wrote: “The difficulties Fleming encountered only spurred my interest in Fleming's discovery of penicillin. I told Flory that we would find a way to at least partially purify penicillin, despite its instability.
In 1938, Cheyne and his colleague Norman Heatley quickly came to the conclusion that penicillin, unlike lysozyme, is not an enzyme, but a small molecule of organic origin.
The small size of the molecule has encouraged researchers: it will be easy to decipher the molecular structure and synthesize it. The fact that it will be easy, scientists were wrong ...
It was found that the composition of penicillin includes a complex of structures, which were later called beta-lactams.


Cheyne suggested the possibility of the existence of such a structure earlier, but the issue was resolved only in 1949.

When, using X-ray crystallography, Dorothy Hodgkin determined the arrangement of atoms in the crystal lattice of penicillin. It was after 1949, after determining the exact molecular structure of penicillin, that it became possible to mass-produce the drug cheaply.
By the way, Dorothy Hodgkin also received the Nobel Prize for the study of the crystal lattice in x-rays, in 1964. This outstanding woman laid the foundations of the method by which it became possible to study the structure of DNA (the program "Human Genome").

Cheyne and Flory used a new lyophilization technique to obtain penicillin in a concentrated form. The penicillin solution was frozen, and then, at low temperature and low pressure, the water was expelled, leaving valuable material.

Penicillium chrysogenium (notatum): how they found the most "penicillin" fungus

Since the beginning of World War II, the need for penicillin has increased dramatically. The need for such a drug was obvious.
In 1940, a group of scientists at Oxford University (led by Flory and Chain) took Fleming's penicillin out of stock and began to look for ways to produce it in large quantities.
Since the bombing of London began and the risk of occupation arose, the scientists went to negotiate in New York (the probability of a German landing was so great that Cheyne even soaked his jacket with healing mold, explaining to his colleagues: in which case, save this jacket first of all).
In New York, the arriving scientists were greeted without much enthusiasm: the production of penicillin rarely exceeded 4 action units per 1 milliliter of nutrient medium. This is very little: on a bottle of penicillin, for example, it says "1,000,000 units." For one dose of the drug, 250 liters of broth had to be processed.
The goal was immediately outlined: to find the most “yielding” fungus. First, the scientists went to Peoria (Illinois), where there was a research laboratory for studying the metabolism of mold. Laboratory staff amassed a significant collection, but only a few mold strains could produce penicillin.
We began to connect friends: to send samples of soil, mold grains, fruits and vegetables. They hired one woman to go around shops, bakeries, cheese dairies, looking for new samples of blue-green mold. Her name was Miss Mary Hunt, nicknamed "Moldy Mary" for her good work.
The course of history was changed by the cantatula melon, on which a blue-green fungus settled. This mold produced 250 units of penicillin per milliliter of growth medium. One of the strains that mutated from it began to produce 50,000 units! All penicillin-producing strains today are descendants of the same mold that was found in 1943. It was the fungus Penicillium chrysogenium, formerly known as Penicillium notatum.
From that moment, the era of industrial production of penicillin began.

When Fleming, Florey and Chain were awarded the Nobel Prize in Physiology or Medicine in 1945, Fleming said: “They say I invented penicillin. But man could not invent it - this substance was created by nature. I didn't invent penicillin, I just drew people's attention to it and gave it a name.".

Fleming, Cheyne and Flory at the Nobel Prize

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Humanity has passed a difficult and thorny path along the path of its development. Over the past millennia, thousands of great discoveries and outstanding inventions have been made in various areas of human life. One of these greatest discoveries, which made a real revolution in medicine, was invention of penicillin the world's first antibiotic. At the beginning of the 20th century, mankind has completely mastered such inventions as the telegraph, telephone, radio, automobile, airplane, and dreams of space exploration. And along with this, thousands of people around the world continued to die from typhus, dysentery, pneumonic plague and even pneumonia, and sepsis became a death sentence. The idea of ​​fighting microbes with the help of microbes themselves was put forward in the 19th century. So, as a result of the research carried out by Louis Pasteur, it was found that anthrax bacilli die under the influence of certain microbes. A recently discovered dissertation by medical student Ernest Duchesne indicates that as early as 1897 he used mold (the penicillin contained there) to fight bacteria that infect the human body. He performed his experiments on guinea pigs for the treatment of typhus. Unfortunately, the opening was not completed due to the sudden death of E. Duchesne.

Officially, the British bacteriologist Alexander Fleming is considered the inventor of the first antibiotic (penicillin), and the date of its discovery is September 3, 1928. While studying staphylococci, the scientist noticed that after a month mold fungi formed on one of the plates with cultures, destroying the colonies of staphylococci placed there earlier. The mushrooms grown on a plate with staphylococci, Fleming attributed to the genus Penicillaceae, the isolated substance was called penicillin. Further studies have shown that in addition to staphylococcus, penicillin also affects pathogens that cause scarlet fever, diphtheria, pneumonia and meningitis. Unfortunately, against paratyphoid and typhoid fever, the remedy he had isolated turned out to be powerless. In 1929, the scientist published a report on his discovery in the English Journal of Experimental Pathology. Further studies showed that the production of penicillin is slow, the scientist could not purify and extract the active substance. Until 1939, Fleming failed to develop an effective culture, the new drug was very unstable. Fleming worked on its improvement until 1942.

In 1940, the biochemist E.B. actively tried to purify and isolate penicillin. Chain and bacteriologist H.W. Flory, already in 1941, enough penicillin was accumulated for an effective dose. A 15-year-old with blood poisoning was the first to be saved thanks to the antibiotic he received. For the discovery of penicillin, E. Chain, A. Fleming and W. X. Flory received the Nobel Prize for three in 1945. All three refused patents for the invention of penicillin, believing that a tool that could save humanity should not become a source of profit. This is the only time that no one has ever claimed copyright for an invention of this magnitude. Thanks to penicillin and the victory over dangerous infectious diseases, medicine has managed to extend a person's life by 30-35 years.

During the Second World War, the production of penicillin on an industrial scale was established in the United States, which saved the lives of tens of thousands of wounded soldiers. After the war, the antibiotic production method improved significantly, since 1952 it has found practical application on a global scale. With the help of penicillin, such previously fatal diseases as osteomyelitis, syphilis, pneumonia, puerperal fever were cured, the development of infections after injuries and burns was excluded. Antibacterial drugs were soon isolated. Antibiotics have become a panacea for all diseases for several decades. In the Soviet Union, a great merit in the creation of a number of antibiotics belongs to the outstanding microbiologist ZV Ermolyeva. She is the first Russian scientist to investigate interferon as an antiviral agent. According to Professor W. X. Flory himself, penicillin, which Z. V. Ermolyeva received, was 1.4 times more effective than the Anglo-American. The first portions of penicillin were obtained by Yermolyeva in 1942. Soon, thanks to her, the mass production of the Soviet antibiotic was established.

The world famous inventor of antibiotics is the Scottish scientist Alexander Fleming, who is credited with the discovery of penicillins from molds. It was a new turn in the development of medicine. For such a grandiose discovery, the inventor of penicillin even received the Nobel Prize. The scientist reached the truth by research, saved not a single generation of people from death. The ingenious invention of antibiotics made it possible to exterminate the pathogenic flora of the body without serious health consequences.

What are antibiotics

Many decades have passed since the appearance of the first antibiotic, but medical workers all over the world and ordinary people are well aware of this discovery. Antibiotics themselves are a separate pharmacological group with synthetic components, the purpose of which is to disrupt the integrity of the membranes of pathogenic pathogens, stop their further activity, quietly remove them from the body, and prevent general intoxication. The first antibiotics and antiseptics appeared in the 40s of the last century, since that time their range has grown significantly.

Useful properties of mold

From the increased activity of pathogenic bacteria, antibiotics that were developed from mold fungi help well. The therapeutic effect of antibacterial drugs in the body is systemic, all this is due to the beneficial properties of mold. The discoverer Fleming managed to isolate penicillin by laboratory method, the benefits of such a unique composition are presented below:

• green mold inhibits bacteria resistant to other drugs;
• the usefulness of mold is evident in the treatment of typhoid fever;
• mold destroys such painful bacteria as staphylococci, streptococci.

Medicine before the invention of penicillin

In the Middle Ages, mankind knew about the colossal benefits of moldy bread and a separate type of mushroom. Such medicinal components were actively used to disinfect purulent wounds of combatants, to exclude blood poisoning after surgery. Before the scientific discovery of antibiotics, there was still a lot of time, so the doctors drew a positive aspect of penicillins from the surrounding nature, determined through numerous experiments. They tested the effectiveness of new funds on wounded soldiers, women in a state of puerperal fever.

How are infectious diseases treated?

Without knowing the world of antibiotics, people lived according to the principle: “Only the strongest survive”, according to the principle of natural selection. Women died of sepsis during childbirth, and fighters from blood poisoning and suppuration of open wounds. At that time, they could not find a remedy for effective cleansing of wounds and exclusion of infection, therefore, healers and healers more often used local antiseptics. Later, in 1867, a British surgeon determined the infectious causes of suppuration and the benefits of carbolic acid. Then it was the main treatment of purulent wounds, without the participation of antibiotics.

Who Invented Penicillin

There are several conflicting answers to the main question, who discovered penicillin, but it is officially believed that the creator of penicillin is the Scottish professor Alexander Fleming. Since childhood, the future inventor dreamed of finding a unique medicine, so he entered a medical school based at St. Mary's Hospital, from which he graduated in 1901. A colossal role in the discovery of penicillin was played by Almroth Wright, the inventor of the typhoid vaccine. Fleming was fortunate enough to collaborate with him in 1902.

A young microbiologist studied at the Kilmarnock Academy, then moved to London. Already in the status of a certified scientist, Flemming discovered the existence of penicillium notatum. The scientific discovery was patented, the scientist after the end of the Second World War in 1945 even received the Nobel Prize. Prior to this, Fleming's work has been repeatedly awarded prizes and valuable awards. People began taking antibiotics for experimental purposes in 1932, and before that, studies were carried out mainly on laboratory mice.

Developments of European scientists

The founder of bacteriology and immunology is the French microbiologist Louis Pasteur, who in the nineteenth century described in detail the detrimental effect of soil bacteria on tuberculosis pathogens. The world-famous scientist proved by laboratory methods that some microorganisms - bacteria can be exterminated by others - mold fungi. The beginning of scientific discoveries was laid, the prospects were grandiose.

The famous Italian Bartolomeo Gosio in 1896 in his laboratory invented mycophenolic acid, which became known as one of the first antibiotics. Three years later, the German doctors Emmerich and Lov discovered pyocenase, a synthetic substance that can reduce the pathogenic activity of pathogens of diphtheria, typhoid and cholera, and demonstrate a stable chemical reaction against the vital activity of microbes in a nutrient medium. Therefore, disputes in science on the topic of who invented antibiotics do not subside at the present time.

Who invented penicillin in Russia

Two Russian professors - Polotebnov and Manassein argued about the origin of mold. The first professor argued that all microbes came from the mold, and the second was categorically against it. Manassein began to investigate green mold and found that colonies of pathogenic flora were completely absent near its localization. The second scientist began to study the antibacterial properties of such a natural composition. Such an absurd accident in the future will become a true salvation for all mankind.

Russian scientist Ivan Mechnikov studied the action of acidophilus bacteria with fermented milk products, which have a beneficial effect on systemic digestion. Zinaida Yermolyeva generally stood at the origins of microbiology, became the founder of the famous antiseptic lysozyme, and is known in history as “Mistress Penicillin”. Fleming realized his discoveries in England, in parallel, domestic scientists worked on the development of penicillin. American scientists also did not sit in vain.

US inventor of penicillin

American researcher Zelman Waksman was simultaneously developing antibiotics, but in the United States. In 1943, he succeeded in obtaining a broad-spectrum synthetic component called streptomycin, effective against tuberculosis and plague. later, its industrial production was established in order to destroy the harmful bacterial flora from a practical position.

Timeline of discoveries

The creation of antibiotics was gradual, while using the colossal experience of generations, proven general scientific facts. In order for antibiotic therapy in modern medicine to be so successful, many scientists "had a hand in it." Alexander Fleming is officially considered the inventor of antibiotics, but other legendary figures also helped patients. Here's what you need to know:

• 1896 - B. Gozio created mycophenolic acid against anthrax;
• 1899 - R. Emmerich and O. Low discovered a local antiseptic based on pyocenase;
• 1928 - A. Fleming discovered an antibiotic;
• 1939 - D. Gerhard received the Nobel Prize in Physiology or Medicine for the antibacterial effect of prontosil;
• 1939 - N. A. Krasilnikov and A. I. Korenyako became the inventors of the antibiotic mycetin, R. Dubos discovered tyrothricin;
• 1940 - E. B. Chain and G. Flory proved the existence of a stable extract of penicillin;
• 1942 - Z. Waksman proposed the creation of the medical term "antibiotic".

History of the discovery of antibiotics

The inventor decided to become a doctor, following the example of his older brother Thomas, who received a diploma in England and worked as an ophthalmologist. Many interesting and fateful events happened in his life, which allowed him to make this grandiose discovery, provided an opportunity to productively destroy pathogenic flora, and ensure the death of entire colonies of bacteria.

Research by Alexander Fleming

The discovery of European scientists was preceded by an unusual story that happened in 1922. Having caught a cold, the inventor of antibiotics did not wear a mask while working and accidentally sneezed into a Petri dish. After some time, he suddenly discovered that harmful microbes had died at the site of saliva. It was a significant step in the fight against pathogenic infections, the ability to cure a dangerous disease. The scientific work was devoted to the result of such a laboratory study.

The next fateful coincidence in the work of the inventor took place six years later, when in 1928 the scientist left for a month to rest with his family, having previously made inoculations of staphylococcus in a nutrient medium from agar-agar. Upon his return, he discovered that the mold was fenced off from staphylococci with a clear liquid that was not viable for bacteria.

Preparation of the active substance and clinical studies

Considering the experience and achievements of the inventor of antibiotics, microbiologists Howard Flory and Ernst Cheyne at Oxford decided to go further and began to obtain a drug suitable for mass use. Laboratory studies were carried out for 2 years, as a result of which the pure active substance was determined. The inventor of antibiotics himself tested it in the society of scientists.

With this innovation, Flory and Chain treated several complicated cases of progressive sepsis and pneumonia. Later, penicillins developed in the laboratory began to successfully treat such terrible diagnoses as osteomyelitis, gas gangrene, puerperal fever, staphylococcal septicemia, syphilis, syphilis, and other invasive infections.

What year was penicillin invented?

The official date for the nationwide recognition of the antibiotic is 1928. However, this kind of synthetic substances have been identified before - at the internal level. The inventor of antibiotics is Alexander Fleming, but European, domestic scientists could compete for this honorary title. The Scot managed to glorify his name in history, thanks to this scientific discovery.

Launch into mass production

Since the discovery was officially recognized during the Second World War, it was very difficult to establish production. However, everyone understood that millions of lives could be saved with his participation. Therefore, in 1943, in the conditions of hostilities, a leading American company took up the serial production of antibiotics. In this way, it was possible not only to reduce mortality rates, but also to increase the life expectancy of the civilian population.

Application during World War II

Such a scientific discovery was especially appropriate during the period of hostilities, since thousands of people died from festering wounds and large-scale blood poisoning. These were the first experiments on humans that produced a sustained therapeutic effect. After the end of the war, the production of such antibiotics not only continued, but also increased significantly in volume.

Significance of the invention of antibiotics

Modern society to this day should be grateful that scientists of their time managed to come up with antibiotics effective against infections and brought their developments to life. Adults and children can safely use such a pharmacological appointment, cure a number of dangerous diseases, avoid potential complications, and death. The inventor of antibiotics is not forgotten at the present time.

Positive points

Thanks to antibiotics, death from pneumonia and childbed fever has become a rarity. In addition, there is a positive trend in such dangerous diseases as typhoid fever and tuberculosis. With the help of modern antibiotics, it is possible to exterminate the pathogenic flora of the body, cure dangerous diagnoses at an early stage of infection, and exclude global blood poisoning. The infant mortality rate has also noticeably decreased; women die during childbirth much less frequently than in the Middle Ages.

Negative aspects

The inventor of antibiotics then did not know that over time, pathogenic microorganisms will adapt to the antibiotic environment and cease to die under the influence of penicillin. In addition, there is no cure for all pathogens, the inventor of such a development has not yet appeared, although modern scientists have been striving for this for years, decades.

Gene mutations and the problem of bacterial resistance

Pathogenic microorganisms by their nature turned out to be the so-called "inventors", because under the influence of broad-spectrum antibiotic drugs they are able to gradually mutate, acquiring increased resistance to synthetic substances. The issue of bacterial resistance for modern pharmacology is particularly acute.

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It is known that in the XV-XVI centuries. in folk medicine, green mold was used to treat festering wounds. She, for example, was able to treat Alena Arzamasskaya, an associate of Stepan Razin, the Russian Joan of Arc. Attempts to apply mold directly to the wound surface gave, oddly enough, good results.

Penicillin should not be considered the only merit of A. Fleming; back in 1922, he made his first important discovery - he isolated from human tissues a substance that has the ability to quite actively dissolve certain types of microbes. The discovery was made almost by accident while trying to isolate the bacteria that cause the common cold. Professor A. Wright, under whose leadership A. Fleming continued his research work, called the new substance lysozyme (lysis is the destruction of microorganisms). True, it turned out that lysozyme is ineffective in the fight against the most dangerous pathogenic microbes, although it successfully destroys relatively less dangerous microorganisms.

Thus, the use of lysozyme in medical practice did not have very broad prospects. This prompted A. Fleming to further search for effective and, at the same time, as harmless to humans as possible antibacterial drugs. It must be said that back in 1908, he conducted experiments with a drug called "salvarsan", which the laboratory of Professor A. Wright received for comprehensive research among the first in Europe. This drug was created by the talented German scientist P. Ehrlich (Nobel Prize jointly with I. I. Mechnikov, 1908). He was looking for a drug that is deadly for pathogens, but safe for the patient, the so-called magic bullet. Salvarsan was a fairly effective anti-syphilitic agent, but it had a toxic side effect on the body. These were only the first small steps towards the creation of modern antimicrobial and chemotherapeutic drugs.

Based on the doctrine of antibiosis (suppression of some microorganisms by others), the foundations of which were laid by L. Pasteur and our great compatriot I. I. Mechnikov, A. Fleming in 1929 established that the therapeutic effect of green mold is due to a special substance secreted by it in environment.

Everything ingenious is discovered by chance?

First mention of antibiotic therapy?

It is interesting that in the Bible we find an incredibly accurate indication of the properties of a semi-shrub plant - hyssop. Here is a fragment of Psalm 50, which, by the way, A. Fleming also remembered: “Sprinkle me with hyssop, and I will be clean; wash me and I will be whiter than snow.”

Let's try to recreate the chain of almost unbelievable accidents and coincidences that preceded the great discovery. The root cause was, oddly enough, the slovenliness of A. Fleming. Absent-mindedness is characteristic of many scientists, but it does not always lead to such positive results. So, A. Fleming did not clean the cups from under the studied cultures for several weeks, as a result, his workplace turned out to be littered with fifty cups. True, in the process of cleaning, he scrupulously examined each cup for fear of missing something important. And didn't miss it.

One fine day, he discovered a fluffy mold in one of the cups, which suppressed the growth of the culture of staphylococci sown in this cup. It looked like this: the chains of staphylococci around the mold disappeared, and drops resembling dew could be seen in place of the yellow cloudy mass. After removing the mold, A. Fleming saw that "the broth on which the mold had grown acquired a distinct ability to inhibit the growth of microorganisms, as well as bactericidal and bacteriological properties in relation to many common pathogenic bacteria."

The mold spores appear to have been brought in through a window from a laboratory where mold samples taken from the homes of asthmatic patients were cultivated to produce desensitizing extracts. The scientist left the cup on the table and went to rest. The London weather played its part: a cold snap favored the growth of mold, and the subsequent warming favored the growth of bacteria. If at least one event fell out of the chain of random coincidences, who knows when humanity would have learned about penicillin. The mold that infected the culture of staphylococci belonged to a rather rare species of the genus Penicillium -P. Notatum , which was first found on rotten hyssop (a semi-shrub plant containing essential oil and used as a spice);

Advantages of the new invention

Further research has shown that, fortunately, even at high doses, penicillin is non-toxic to experimental animals and is capable of killing highly resistant pathogens. There were no biochemists at St. Mary's Hospital, and as a result, it was not possible to isolate penicillin in an injectable form. This work was carried out in Oxford by X. W. Flory and E. B. Chain only in 1938. Penicillin would have sunk into oblivion if A. Fleming had not previously discovered lysozyme (here it really came in handy!). It was this discovery that prompted Oxford scientists to study the medicinal properties of penicillin, as a result of which the drug was isolated in its pure form in the form of benzylpenicillin and tested clinically. Already the very first studies of A. Fleming gave a number of invaluable information about penicillin. He wrote that it is “an effective antibacterial substance that has a pronounced effect on pyogenic (i.e., causing the formation of pus) cocci and diphtheria bacilli. Penicillin, even in large doses, is not toxic to animals. It can be assumed that it will be an effective antiseptic when applied externally to areas affected by microbes sensitive to penicillin, or when administered internally.

The medicine is received, but how to apply it?

Like the Pasteur Institute in Paris, the vaccination department at St. Mary's Hospital, where A. Fleming worked, existed and received funding for research through the sale of vaccines. The scientist found that during the preparation of vaccines, penicillin protects cultures from staphylococcus aureus. This was a small but significant achievement, and A. Fleming made extensive use of it, giving weekly instructions to make large batches of penicillium-based broth. He shared culture Penicillium with colleagues in other laboratories, but, oddly enough, A. Fleming did not take such an obvious step, which 12 years later was taken by X. W. Flory and was to establish whether experimental mice would be saved from a deadly infection if treat them with injections of penicillin broth. Looking ahead, these mice are exceptionally lucky. A. Fleming only prescribed the broth to several patients for external use. However, the results were very, very conflicting. The solution was not only difficult to purify in a significant volume, but also proved to be unstable. In addition, A. Fleming never mentioned penicillin in any of the 27 articles or lectures he published in 1930-1940, even when they dealt with substances that cause the death of bacteria. However, this did not prevent the scientist from receiving all the honors due to him and the Nobel Prize in Physiology or Medicine in 1945. It took a long time before scientists made a conclusion about the safety of penicillin, both for humans and for animals.

Who was the first to invent penicillin?

And what was happening in the laboratories of our country at that time? Did domestic scientists sit idly by? Of course it isn't. Many have read V. A. Kaverin's trilogy "The Open Book", but not everyone knows that the main character, Dr. Tatyana Vlasenkova, had a prototype - Zinaida Vissarionovna Ermolyeva (1898-1974), an outstanding microbiologist, creator of a number of domestic antibiotics . In addition, 3. V. Ermolyeva was the first of domestic scientists to begin studying interferon as an antiviral agent. A full member of the Academy of Medical Sciences, she made a huge contribution to Russian science. The choice of profession 3. V. Ermolyeva was influenced by the story of the death of her favorite composer. It is known that P. I. Tchaikovsky died after contracting cholera. After graduating from the university, 3. V. Ermolyeva was left as an assistant at the Department of Microbiology; at the same time she was in charge of the bacteriological department of the North Caucasian bacteriological institute. When in 1922 an epidemic of cholera broke out in Rostov-on-Don, she, ignoring the mortal danger, studied this disease, as they say, on the spot. Later, she conducted a dangerous experiment with self-infection, which resulted in a significant scientific discovery.

During the Great Patriotic War, watching the wounded, 3. V. Ermolyeva saw that many of them did not die directly from wounds, but from blood poisoning. By that time, research in her laboratory, completely independent of the British, showed that some molds retard the growth of bacteria. 3. V. Ermolyeva, of course, knew that in 1929 A. Fleming obtained penicillin from the mold, but he could not isolate it in its pure form, since the drug turned out to be very unstable. She also knew that for a long time our compatriots at the level of traditional medicine, healers noticed the healing properties of mold. But at the same time, unlike A. Fleming, 3. V. Ermolyeva did not indulge in happy accidents. In 1943, W. X. Flory and E. Cheyne were able to establish the production of penicillin on an industrial scale, but for this they had to organize production in the USA. 3. V. Ermolyeva, who at that time was at the head of the All-Union Institute of Experimental Medicine, set herself the goal of obtaining penicillin exclusively from domestic raw materials. We must pay tribute to her perseverance - in 1942 the first portions of Soviet penicillin were received. The greatest and indisputable merit of 3. V. Ermolyeva was that she not only received penicillin, but also managed to establish mass production of the first domestic antibiotic. At the same time, it should be taken into account that the Great Patriotic War was going on, there was an acute shortage of the simplest and most necessary things. At the same time, the need for penicillin grew. And 3. V. Ermolyeva did the impossible: she managed to provide not only the quantity, but also the quality, or rather, the strength of the drug.

How many wounded owe her their lives cannot even be estimated. The creation of Soviet penicillin became a kind of impetus for the creation of a number of other antibiotics: the first domestic samples of streptomycin, tetracycline, levomycetin and ecmolin, the first antibiotic of animal origin isolated from sturgeon milk. Relatively recently, a message appeared, the reliability of which is still difficult to vouch for. Here it is: penicillin was discovered even before A. Fleming by a certain medical student Ernest Augustin Duchesne, who in his dissertation work described in detail the surprisingly effective drug discovered by him to combat various bacteria that adversely affect the human body. E. Duchenne could not complete his scientific discovery due to a transient illness that led to death. However, A. Fleming had no idea about the young researcher's discovery. And only quite recently in Leon (France) the dissertation of E. Duchesne was accidentally found.

By the way, no one has been granted a patent for the invention of penicillin. A. Fleming, E. Chain and W. X. Flory, who received one Nobel Prize for three for his discovery, flatly refused to receive patents. They considered that a substance that has every chance to save all of humanity should not be a source of profit, a gold mine. This scientific breakthrough is the only one of such magnitude that no one has ever claimed copyright.

It is worth mentioning that, having defeated many common and dangerous infectious diseases, penicillin extended human life by an average of 30-35 years!

Beginning of the era of antibiotics

So, in medicine, a new era has begun - the era of antibiotics. "Like cures like" - this principle has been known to doctors since ancient times. So why not fight some microorganisms with the help of others? The effect exceeded the wildest expectations; in addition, the discovery of penicillin marked the beginning of the search for new antibiotics and sources of their production. Penicillins at the time of discovery were characterized by high chemotherapeutic activity and a wide spectrum of action, which brought them closer to ideal drugs. The action of penicillins is aimed at certain "targets" in the cells of microorganisms that are absent in animal cells.

Reference. Penicillins belong to a large class of gamma-lactam antibiotics. This includes cephalosporins, carbapenems and monobactams. Common in the structure of these antibiotics is the presence of a ß-lactam ring, ß-lactam antibiotics form the basis of modern chemotherapy for bacterial infections.

Antibiotics Attack - Bacteria Defend Bacteria Attack Antibiotics Defend

Penicillins have a bactericidal property, that is, they have a detrimental effect on bacteria. The main object of action is the penicillin-binding proteins of bacteria, which are the enzymes of the final stage of the synthesis of the bacterial cell wall. Blocking the synthesis of peptidoglycan by an antibiotic leads to a disruption in the synthesis of the cell wall and, ultimately, to the death of the bacterium. In the process of evolution, microbes have learned to defend themselves. They secrete a special substance that destroys the antibiotic. This is also an enzyme that bears the terrifying name of ß-lactamase, which destroys the ß-lactam ring of the antibiotic. But science does not stand still, new antibiotics have appeared containing so-called inhibitors (ß-lactamase - clavulanic acid, clavulanate, sulbactam and tazobactam). Such antibiotics are called penicillinase-protected and.

General features of antibacterial drugs

Antibiotics are substances that selectively suppress the vital activity of microorganisms. Under the "selective influence" is meant activity exclusively in the relationship of microorganisms while maintaining the viability of the host cells and the impact not on everything, but only on certain genera and types of microorganisms. For example, fusidic acid has high activity against staphylococci, including methicillin-resistant ones, but has no effect on GABHS pneumococci. Selectivity is closely related to the idea of ​​the vastness of the spectrum of activity of antibacterial drugs. However, from today's standpoint, the division of antibiotics into broad-spectrum and narrow-spectrum drugs seems conditional and is subject to serious criticism, for the most part due to the lack of criteria for such a division. It is wrong to say that broad-spectrum drugs are more reliable and effective.

The path leading to nowhere

Gentlemen, microbes will have the last word!
Louis Pasteur

All microscopic enemies of the human race have been declared a life-and-death war. It is still being carried out with varying success, but some diseases have already receded, it seems, forever, such as smallpox. But this leaves smallpox of camels, cows, and also smallpox of monkeys. However, with smallpox, not everything is so simple. From the mid 1980s. cases of smallpox are not recorded. In this regard, children have not been vaccinated against smallpox for quite a long time. Thus, the number of people resistant to the variola virus is decreasing every year in the human population. This virus hasn't gone anywhere. It can be preserved on the bones of people who died from smallpox (far from all the corpses were burned, some and there was no one to burn) for an arbitrarily long time. And someday, an unvaccinated person, for example, an archaeologist, will meet with a virus. L. Pasteur was right. Many previously fatal diseases - dysentery, cholera, purulent infections, pneumonia, etc. - receded into the background. However, glanders, which have not been observed for almost 100 years, seem to have returned. In a number of countries, outbreaks of poliomyelitis are observed after decades that have passed without this formidable disease. New threats have been added, in particular bird flu. The bird flu virus is already killing predatory mammals. Open borders have made it impossible to fight germs in a single state. If previously there were diseases that were more characteristic of any region, then at the moment even the boundaries of climatic zones more characteristic of a particular type of pathology are blurred. Of course, specific infections of the tropical zone do not yet threaten the inhabitants of the Far North, but, for example, sexual infections, AIDS, hepatitis B, C, as a result of the process of universal globalization, have become a truly global threat. Malaria has spread from hot countries all the way to the Arctic Circle.
The cause of classical infectious diseases are pathogenic microorganisms represented by bacteria (such as bacilli, cocci, spirochetes, rickettsia), viruses of a number of families (herpesviruses, adenoviruses, papovaviruses, parvoviruses, orthomyxoviruses, paramyxoviruses, retroviruses, bunyaviruses, togaviruses, coronaviruses, picornaviruses, arenoviruses and rhabdoviruses), fungi (oomycetes, ascomycetes, actinomycetes, basidiomycetes, deuteromycetes) and protozoa (flagellates, sarcodes, sporozoans, ciliaries). In addition to pathogenic microorganisms, there is a large group of opportunistic microbes that can provoke the development of so-called opportunistic infections - a pathological process in people with various immunodeficiencies. Since the possibility of obtaining antibiotic drugs from microorganisms has been clearly proven, the discovery of new drugs has become a matter of time. It usually turns out that time does not work for doctors and microbiologists, but, on the contrary, for representatives of pathogenic microflora. However, at first there was even reason for optimism.

Chronology of the emergence of antibiotics

In 1939, gramicidin was isolated, then in chronological order - streptomycin (in 1942), chlortstracycline (in 1945), levomycetin (in 1947), and by 1950 more than 100 antibiotics had already been described. It should be noted that in the 1950-1960s. this caused premature euphoria in medical circles. In 1969, a very optimistic report was presented to the US Congress, containing such bold statements as "the book of infectious diseases will be closed."

One of the biggest mistakes of mankind is an attempt to overtake the natural evolutionary process, because man is only a part of this process. The search for new antibiotics is a very long, painstaking process that requires serious funding. Many antibiotics have been isolated from microorganisms that live in the soil. It turned out that mortal enemies of a number of pathogenic microorganisms for humans live in the soil - the causative agents of typhus, cholera, dysentery, tuberculosis, etc. Streptomycin, which has been used to treat tuberculosis to date, was also isolated from soil microorganisms. In order to select the right strain, 3. Waksman (the discoverer of streptomycin) studied over 500 cultures for 3 years before he found the right one - one that releases more streptomycin into the environment than other cultures. In the course of scientific research, many thousands of cultures of microorganisms are carefully studied and rejected. And only single copies are used for further study. However, this does not mean that all of them will later become a source for obtaining new drugs. The extremely low productivity of cultures, the technical complexity of the isolation and subsequent purification of medicinal substances put additional often insurmountable barriers to new drugs. And new antibiotics are as necessary as air. Who could have imagined that the viability of microbes would become such a serious problem? In addition, more and more new pathogens of infectious diseases were identified, and the spectrum of activity of existing drugs became insufficient to effectively combat them. Microorganisms very quickly adapted and became immune to the action of seemingly already proven drugs. It was quite possible to foresee the emergence of drug resistance in microbes, and it was not at all necessary to be a talented science fiction writer for this. Rather, the role of brilliant visionaries was to be played by skeptics from the scientific community. But if someone predicted something like this, then his voice was not heard, his opinion was not taken into account. But a similar situation was already observed with the introduction of the insecticide DDT in the 1940s. At first, the flies, against which such a massive attack was made, almost completely disappeared, but then they bred in huge numbers, and the new generation of flies was resistant to DDT, which indicates the genetic fixation of this trait. As for microorganisms, A. Fleming discovered that successive generations of staphylococci developed cell walls with a structure resistant to penicillin. Academician S. Schwartz warned more than 30 years ago about the state of affairs that could develop with such a vector of events. He said: “No matter what happens on the upper floors of nature, no matter what cataclysms shake the biosphere ... the highest efficiency of energy use at the level of cells and tissues guarantees life to organisms that will restore life on all its floors in the form that corresponds to new environmental conditions". Some bacteria can reject antibiotics as they invade or neutralize them. For this reason, in parallel with the search for new types of natural antibiotics, in-depth work was carried out to analyze the structure of already known substances, in order to then, based on these data, modify them, creating new, much more effective and safe drugs. A new stage in the evolution of antibiotics, undoubtedly, was the invention and introduction into medical practice of semi-synthetic drugs similar in structure or type of action to natural antibiotics. In 1957, for the first time, it was possible to isolate phenoxymethylpenicillin, resistant to the action of hydrochloric acid of gastric juice, which can be taken in tablet form. Penicillins of natural origin were completely ineffective when taken orally, as they lost their activity in the acidic environment of the stomach. Later, a method was invented for the production of semi-synthetic penicillins. For this purpose, the penicillin molecule was “cut” by the action of the penicillinase enzyme and, using one of the parts, new compounds were synthesized. Using this technique, it was possible to create drugs with a much broader spectrum of antimicrobial action (amoxicillin, ampicillin, carbenicillin) than the original penicillin. An equally well-known antibiotic, cephalosporin, first isolated in 1945 from wastewater on the island of Sardinia, became the ancestor of a new group of semi-synthetic antibiotics - cephalosporins, which have a powerful antibacterial effect and are almost harmless to humans. There are already more than 100 different cephalosporins. Some of them can destroy both gram-positive and gram-negative microorganisms, others act on resistant strains of bacteria. It is clear that any antibiotic has its specific selective effect on strictly defined types of microorganisms. Due to this selective action, a significant part of antibiotics is able to nullify many types of pathogenic microorganisms, acting in concentrations that are harmless or almost harmless to the body. It is this type of antibiotic preparations that is extremely often and widely used to treat a variety of infectious diseases. The main sources that are used to obtain antibiotics are microorganisms with a habitat in soil and water, where they continuously interact, entering into a variety of relationships that can be neutral, antagonistic or mutually beneficial. A striking example is putrefactive bacteria, which create good conditions for the normal functioning of nitrifying bacteria. However, the relationships between microorganisms are often antagonistic, that is, directed against each other. This is quite understandable, since only in this way in nature could the ecological balance of a huge number of biological forms be initially maintained. The Russian scientist I. I. Mechnikov, far ahead of his time, was the first to propose the practical application of antagonism between bacteria. He advised to suppress the vital activity of putrefactive bacteria, which constantly live in the human intestine, at the expense of beneficial lactic acid bacteria; waste products released by putrefactive microbes, according to the scientist, shorten a person's life. There are various types of antagonism (counteraction) of microbes.

All of them are associated with competition for oxygen and nutrients and are often accompanied by a change in the acid-base balance of the environment in the direction that is optimal for the life of one type of microorganism, but unfavorable for its competitor. At the same time, one of the most universal and effective mechanisms for the manifestation of microbial antagonism is the production of various antibiotic chemicals by them. These substances are capable of either inhibiting the growth and reproduction of other microorganisms (bacteriostatic action), or destroy them (bactericidal action). Bacteriostatic agents include antibiotics such as erythromycin, tetracyclines, aminoglycosides. Bactericidal drugs cause the death of microorganisms, the body can only cope with the excretion of their metabolic products. These are antibiotics of the penicillin series, cephalosporins, carbapenems, etc. Some antibiotics that act bacteriostatically destroy microorganisms if used in high concentrations (aminoglycosides, chloramphenicol). But one should not get carried away with increasing the dose, since with an increase in concentration, the likelihood of a toxic effect on human cells sharply increases.

The history of the discovery of bacteriophages.

Bacteriophages (phages) (from the Greek phages - “devour”) are viruses that selectively infect bacterial cells. Most often, they begin to multiply inside the bacteria, thus causing their destruction. One of the areas of application of bacteriophages is antibacterial therapy, an alternative to taking antibiotics. For example, bacteriophages are used: streptococcal, staphylococcal, klebsiella, polyvalent dysenteric, pyobacteriophage, coli, proteus and coliproteus, etc. Bacteriophages are also used in genetic engineering as vectors that transfer DNA segments, it is also possible to naturally transfer genes between bacteria through some phages (transduction ).

Bacteriophages were discovered independently by F. Twort, together with A. Lond and F. d ​​"Erel, as filterable transmitting agents for the destruction of bacterial cells. Initially, they were thought to be the key to controlling bacterial infections, but early studies were largely untenable. Bacteriophages were isolated , capable of infecting most prokaryotic groups of organisms, and are readily isolated from soil, water, sewage, and, as might be expected, from most bacterial colonized environments. phage, carried out by G. Delbruck, S. Luria, A. Dermanom, R. Hershey, I. Lwoff and others, laid the foundation for the development of molecular biology, which, in turn, became the foundation for a number of new branches of industry based on biotechnology Bacteriophages, like other viruses, carry their genetic information in the form of DNA or RNA. Most bacteriophages have tails whose tips are attached to specific receptors such as carbohydrate, protein, and lipopolysaccharide molecules on the surface of the host bacterium. The bacteriophage injects its nucleic acid into the host, where it uses the host's genetic machinery to replicate its genetic material and read it to form new phagocapsular material to create new phage particles. The number of phages produced during a single infection cycle (output size) varies between 50 and 200 new phage particles. Resistance to bacteriophage can develop through loss or changes in receptor molecules on the surface of the host cell. Bacteria also have special mechanisms that protect them from invading foreign DNA. The host DNA is modified by methylation at specific points in the DNA sequence; this creates protection against degradation by host-specific restriction endonucleases. Bacteriophages are divided into 2 groups: virulent and temperate. Virulent phages cause a lytic infection that destroys host cells and produces clear spots (plaques) on susceptible bacterial colonies. Temperate phages integrate their DNA through the host bacterium, producing a lysogenic infection, and the phage genome is passed on to all daughter cells during cell division."

Development of bacteriophage therapy.

Bacteriophage therapy (the use of bacterial viruses to treat bacterial infections) was a problem of great interest to scientists 60 years ago in their fight against bacterial infections. Discovery of penicillin and other antibiotics in the 1940s provided a more effective and multifaceted approach to the suppression of viral diseases and provoked the closure of work in this area. In Eastern Europe, however, research continued to be carried out and some methods of fighting viruses using bacteriophages were formed. Enteral and purulent-septic diseases initiated by opportunistic pathogens, including surgical infections, infectious diseases of children of the first year of life, diseases of the ear, throat, nose, lungs and pleura; chronic klebsiellosis of the upper respiratory tract - ozena and scleroma; urogenital pathology, gastroenterocolitis, are increasingly difficult to respond to traditional antibiotic therapy. The lethal outcome at the listed infections reaches 30-60%. The factor of therapy failure is the high frequency of resistance of pathogens to antibiotics and chemotherapeutic drugs, reaching 39.9-96.9%, as well as immune suppression as the effect of these drugs on the patient's body, toxic and allergic reactions with side effects, manifested in intestinal disorders. against the background of dysbacteriosis, and a similar disorder of the upper respiratory tract in the treatment of scleroma and ozena. The problem of intestinal dysbacteriosis in young children is especially relevant. The long-term results of such treatment in children are immunosuppression, chronic septic conditions, malnutrition, and developmental deficiencies.

You should know it!

Bacteriophages are viruses that selectively infect bacterial cells. Most often, they begin to multiply inside the bacteria, thus causing their destruction. One of the areas of application of bacteriophages is antibacterial therapy, an alternative to taking antibiotics.

Clinical studies have shown that the use of bacteriophages to treat indoor surfaces and individual objects, such as toilets, prevents the transmission of infections caused by Escherichia coli in children and adults. In veterinary medicine, it has been proven that escherichiosis in calves can be prevented by spraying droppings in calf pens with aqueous suspensions of bacteriophages. While quite significant success was shown in the early research phase, phage therapy failed to become an established practice. This was explained by the inability to select highly virulent phages, as well as the selection of phages with an excessively narrow strain specificity. Other points included the appearance of phage-resistant strains, the neutralization or elimination of phages by the protective functions of the immune system, and the exfoliation of endotoxins due to extensive massive bacterial cell destruction. The potential for phage-mediated horizontal translation of toxin genes is also a reason that may limit their use for the treatment of certain specific infections. According to the data provided by M. Slopes (1983 and 1984), the use of bacteriophage preparations in infectious diseases of the digestive system, inflammatory-purulent changes in the skin, circulatory system, respiratory system, musculoskeletal system, genitourinary system (more than 180 nosological units of diseases, caused by bacteria Klebsiella, Escherichiae, Proteus, Pseudomonas, Staphylococcus, Streptococcus, Serratia, Enterobacter) showed that bacteriophage preparations have the desired effect in 78.3-93.6% of cases and are often the only effective therapeutic agent.

During the last 2 decades, some pilot studies have been carried out in order to re-evaluate the use of bacteriophage-based therapeutic methods for the treatment of infectious diseases in humans and animals. The results of these studies have recently been revised. D. Smith and associates published the results of a series of experiments on the treatment of systemic E. Coli infections in rodents and intestinal disorders in the form of diarrhea in calves. It has been proven that both prevention and treatment are possible using phage titers much lower than the number of target organisms, which is an indication of the growth of bacteriophages in vivo. They showed that intramuscular injection of 106 units of E. coli resulted in the death of 10 experimental mice, while simultaneous injection into the other leg of 104 phages selected against K1 antigen capsules gave complete protection.
Bacteriophage therapy in relation to antibiotic therapy has a number of advantages. For example, it is effective against drug-resistant organisms and can be used as an alternative therapy for patients who are allergic to antibiotics. It can be used prophylactically to control the spread of an infectious disease where the source is identified early, or where outbreaks occur within relatively closed institutions such as schools or nursing homes. Bacteriophages are highly specific for target organisms and have no effect on non-target organisms. They are self-replicating and self-limiting; when the target organism is present, they self-replicate until all of the target bacteria have been infected and destroyed. Bacteriophages mutate naturally to fight resistance mutations in the host; moreover, they can be deliberately mutated in the laboratory. In Russia and the CIS countries, bacteriophage preparations are used to treat purulent-septic and enteric diseases of various localization, excited by opportunistic bacteria of the genera Escherichia, Proteus, Pseudomonas, Enterobacter, Staphylococcus, Streptococcus, serve as substitutes for antibiotics. They are not inferior and even superior to the latter in terms of effectiveness, without causing adverse toxic and allergic reactions and without contraindications for use. Bacteriophage preparations are effective in the treatment of diseases caused by antibiotic-resistant strains of microorganisms, in particular in the treatment of paratonsillar ulcers, inflammation of the sinuses, as well as purulent-septic infections, intensive care patients, surgical diseases, cystitis, pyelonephritis, cholecystitis, gastroenterocolitis, paraproctitis, intestinal dysbacteriosis, inflammatory diseases and sepsis of newborns. With the widespread development of antibiotic resistance in pathogenic bacteria, the need for new antibiotics and alternative technologies to control microbial infections is becoming increasingly important. Bacteriophages likely have yet to fulfill their role in the treatment of infectious diseases, either alone or in combination with antibiotic therapy.

He wrote about how in the USSR almost all the great inventions of mankind, including a steam locomotive, an incandescent lamp, a balloon, a bicycle, etc., strove to be attributed to Russian inventors. But in fairness, it must be said that in some cases such statements pursued purely practical goals, an example of which is the story of penicillin.

On September 13, 1929, at a meeting of the Medical Research Club at the University of London, a modest microbiologist at St. Mary Alexander Fleming reported on the therapeutic properties of mold. This day is considered to be the birthday of penicillin, but few people paid attention to Fleming's report at that time. And there were good reasons for this. Mentions about the treatment of purulent diseases with mold were found in the writings of Avicenna (XI century) and Philip von Hohenheim, known as Paracelsus (XVI century), but the problem was how to isolate from the mold the substance due to which its miraculous properties are manifested.

Three times, at the request of Fleming, biochemists began to purify the substance from impurities, but unsuccessfully: the fragile molecule was destroyed, losing its properties. This problem was solved only in 1938 by a group of scientists at Oxford University, who received a $5,000 grant from the Rockefeller Foundation for research. This group was headed by Professor Howard Florey, but it is believed that its think tank was a talented biochemist, the grandson of the Mogilev tailor Ernst Chain. However, some experts believe that the success was achieved mainly due to the third member of the group, the remarkable designer Norman Heatley, who successfully used the latest lyophilization technologies for that time (evaporation through low temperatures). Convinced that the Oxford group had succeeded in purifying penicillin, Alexander Fleming exclaimed: “Yes, you have managed to process my substance! It was with such scientists-chemists that I dreamed of working in 1929.

But the story of penicillin did not end there. There was no way to establish mass production of medicine in England, which was bombarded daily. In the autumn of 1941, Flory and Heatley traveled to America, where they proposed the technology for the production of penicillin to the chairman of the US Medical Research Council, Alfred Richards. He immediately contacted President Roosevelt, who agreed to fund the program. The Americans approached the matter with their characteristic scope - the penicillin program in miniature resembled the "Manhattan Project" to create an atomic bomb. All work was strictly classified, leading scientists, designers and industrialists were involved in the case. As a result, the Americans managed to develop an effective deep fermentation technology. The first $200 million plant was built at an accelerated pace in less than a year. Following this, new factories were built in the USA and Canada. The production of penicillin grew by leaps and bounds: June 1943 - 0.4 billion units, September - 1.8 billion, December - 9.2 billion, March 1944 - 40 billion units. Already in March 1945, penicillin appeared in American pharmacies.

Only when sensational news about healings began to arrive from the United States, and after them the drug itself appeared, did they realize in England that the technology used for surface fermentation of mold not only did not provide enough penicillin, but in addition it turns out to be much more expensive than American. For the technology and equipment that the British asked to transfer to them, the Americans broke a lot of money. I had to put presumptuous overseas friends in their place. With the help of several publications in the press, the British proved to the whole world their priority in the invention of penicillin. For persuasiveness, smart reporters even added something. There is still a tale that the microbiologist Fleming was such a slob that he had
mold.

In the USSR, they also tried to borrow this technology from the Americans, but unsuccessfully. Deputy People's Commissar of Health of the USSR A.G. Natradze said: “We sent a delegation abroad to purchase a license for the production of penicillin by the deep method. They broke a very high price - $ 10 million. We consulted with the Minister of Foreign Trade A.I. Mikoyan and agreed to the purchase. Then they told us that they made a mistake in their calculations and that the price would be $20 million. We again discussed the issue with the government and decided to pay this price as well. Then they said that they would not sell us a license even for $30 million.”

What was left to do in these conditions? Follow the example of the British and prove their priority in the discovery of penicillin. First of all, they raised the archives and found out that back in 1871, Russian doctors Vyacheslav Manassein and Alexei Polotebnov pointed out the healing properties of mold. In addition, Soviet newspapers were full of reports of the outstanding successes of the young microbiologist Zinaida Yermolyeva, who managed to produce a domestic analogue of penicillin called crustosin, and, as expected, it turned out to be much better than the American one. It was not difficult to understand from these reports that the enemy spies had treacherously stole the secret of the production of crustosene, because American scientists who suffer from inhuman exploitation in their capitalist jungle would never have thought of it before. Later, Veniamin Kaverin (his brother, virologist Lev Zilber, was Yermolyeva's husband) published the novel Open Book, which tells how the main character, whose prototype was Yermolyeva, despite the resistance of enemies and bureaucrats, gave the people a miraculous medicine.

This was not true. Using the support of Rosalia Zemlyachka (the fury of the red terror, as Solzhenitsyn called her, studied for some time at the medical faculty of the University of Lyon, and therefore considered herself an unsurpassed connoisseur of medicine), Zinaida Yermolyeva, based on the fungus Penicillium crustosum, really established the production of crustosin, but the quality of domestic penicillin is significantly inferior to the American. In addition, Yermolyeva's penicillin was produced by surface fermentation in glass "mattresses". And although they were installed wherever possible, the volume of production of penicillin in the USSR at the beginning of 1944 was about 1000 times less than in the United States.

It ended up that the technology of deep fermentation bypassing the Americans was, as far as is known, privately purchased from Ernst Chain, after which the Research Institute of Epidemiology and Hygiene of the Red Army, whose director was N. Kopylov, mastered this technology and put it into production. In 1945, after testing domestic penicillin, a large team led by Kopylov was awarded the Stalin Prize. After that, all talk about the Russian-Soviet priority in the discovery of penicillin subsided - Vyacheslav Manassein and Alexei Polotebnov were once again forgotten, Zinaida Yermolyeva was removed from the post of director of the Penicillin Institute, and her magical crustozin, thanks to which the builders of communism could live forever, was thrown out to the landfill.