Penicillin discovery story for children. The Incredible Discovery of Penicillin by Alexander Fleming

The facts from the history of the discovery of penicillin are striking in their drama. The Soviet school of microbiology, headed by Professor Yermolyeva, discovered a unique penicillin

On September 3rd, the world celebrates the birthday of penicillin. This medicine was discovered by Alexander Fleming. In the entire history of mankind, there was no other medicine that would save so many human lives. "Penicillin did more than 25 divisions to win World War II!" These were the words that Fleming, Cheyne, and Flory were awarded with the Nobel Prize in Biology and Medicine. prepared a selection of interesting facts about this amazing medicine.

Fact #1

The slovenliness of the Scottish microbiologist Alexander Fleming led to the discovery of penicillin. When he returned to his laboratory on September 3, 1928, after being absent for a whole month, he noticed a petri dish, inside of which a patch of mold had formed. The scientist noticed that all microbial colonies disappeared around the mold. This phenomenon interested Fleming, and he conducted a study of the contents of the cup. The mold belonged to the genus Penicillaceae, and the scientist called the substance that killed the microbes penicillin.

Fleming published a report on his new discovery in 1929 in a British journal that was devoted to experimental pathology. In the same year, he was still doing research and soon discovered that it was difficult to work with penicillin, its production was extremely laborious and it was impossible to isolate it in its pure form. In addition, the mold extract turned out to be unstable, quickly removed from the tissues, and it was not possible to create the required concentration for the complete destruction of bacteria.

Fact #3

Fleming continued in the hospital his experiments on the topical application of penicillin, using mold extract externally to treat inflammatory foci. The results were quite favorable, but by no means miraculous, since at the right time the drug lost its activity. In 1931, speaking at the Royal Dental Clinic, he again described penicillin as a promising drug. In 1932, Fleming published the results of his experiments in the treatment of infected wounds in the journal Pathology and Bacteriology.

Fact #4

In mid-1939, the young English professor Howard Walter Flory, head of the Department of Pathology at Oxford University, and the biochemist Ernest Cheyne, at the request of Fleming, tried to obtain pure penicillin. Only after two years of disappointment and defeat did they manage to obtain a few grams of the brown powder.

When England declared war on Germany on September 3, 1939, the Oxford Group, fearing German occupation, decided to save the miraculous mold at all costs. Cheyne and Flory smuggled their drug into the United States for analysis by soaking the brown liquid in the lining of their jackets and pockets. It was enough for one of them to survive so that the preserved mold spores would allow them to resume work. Only in the middle of 1940 was it possible to obtain penicillin in the amount necessary for research.

Fact #6

The first injections of the new agent were made to a person on February 12, 1941. One of the London police officers cut himself with a razor while shaving. Blood poisoning developed. The first injection of penicillin was given to a dying patient. The patient's condition immediately improved. But there was too little penicillin, its supply quickly dried up. The disease returned and the patient died. Despite this, science triumphed, as it was convincingly proven that penicillin works wonderfully against blood poisoning. A few months later, scientists managed to accumulate such an amount of penicillin, which could be more than enough to save a human life. The lucky one was a fifteen-year-old boy who had a blood poisoning that could not be cured. He was the first person whose life was saved by penicillin.

In 1941, the USSR asked the Allies for a sample of the drug. However, there was no answer. Then in 1942, under the leadership of the head of the All-Union Institute of Experimental Medicine Zinaida Vissarionovna Yermolyeva, domestic penicillin was obtained from the mold collected from the walls of the bomb shelter under the most difficult conditions. The Soviet drug was called "penicillin-crustosin". Its production was started in 1944 at the enterprises of the chemical and pharmaceutical industry by the method of surface cultivation of the fungus.

In 1943, penicillin was first mass-produced in Peoria, Illinois, at the Hiram Walker plant. Once upon a time, whiskey was “brewed” here with great skill, and the winery had excellent fermentation equipment. But it soon became clear that these premises were too small for increasing the production of the drug, which required the expansion of the business.

The need for penicillin grew every day. It was important to increase not only the amount of the drug, but also its activity. An interesting test of antibiotics took place in January 1944, when Professor Flory arrived in Moscow with a group of foreign scientists. He brought his penicillin and decided to compare it with the Russian one. Our preparation turned out to be more active than the foreign one: 28 units against 20 in 1 ml. Then Professor Flory and the American scientist Sanders proposed to conduct clinical trials to evaluate the effect of the drug on patients. And again, our domestic penicillin won.

Fact #10

At the request of Professor Flory to provide Russian penicillin for further research, he was deliberately given an American strain, allegedly as his sample. Returning to America, Flory examined the material received and was disappointed. In his report, he wrote "Soviet mold turned out to be not crustosum, but notatum, like Fleming's. The Russians did not discover anything new." But Soviet scientists just "wiped their noses" to their American colleagues, but it was not easy to establish a large-scale production of this drug in a destroyed country.

Inventor Story by: Alexander Fleming
Country: Great Britain
Time of invention: September 3, 1928

Antibiotics are one of the most remarkable inventions of the 20th century in the field of medicine. Modern people are far from always aware of how much they owe to these medicinal preparations.

Mankind in general very quickly gets used to the amazing achievements of its science, and sometimes it takes some effort to imagine life as it was, for example, before the invention, radio or.

Just as quickly, a huge family of various antibiotics entered our lives, the first of which was penicillin.
Today it seems surprising to us that back in the 30s of the 20th century, tens of thousands of people died every year from dysentery, that pneumonia in many cases ended in death, that sepsis was a real scourge of all surgical patients, who died in large numbers from blood poisoning, that typhoid was considered the most dangerous and intractable disease, and pneumonic plague inevitably led the patient to death.

All these terrible diseases (and many others, previously incurable, such as tuberculosis) were defeated by antibiotics.

Even more striking is the effect of these drugs on military medicine. It is hard to believe, but in previous wars, most soldiers died not from bullets and shrapnel, but from purulent infections caused by wounds.

It is known that in the space around us there are myriads of microscopic organisms of microbes, among which there are many dangerous pathogens. Under normal conditions, our skin prevents them from penetrating organism.

But during the injury, dirt entered the open wounds along with millions of putrefactive bacteria (cocci). They began to multiply with tremendous speed, penetrated deep into the tissues, and after a few hours no surgeon could save a person: the wound festered, the temperature rose, sepsis or gangrene began.

A person died not so much from the wound itself, but from wound complications. Medicine was powerless before them. At best, the doctor managed to amputate the affected organ and thus stopped the spread of the disease.

To deal with wound complications, it was necessary to learn how to paralyze the microbes that cause these complications, to learn how to neutralize the cocci that got into the wound. But how can this be achieved? It turned out that it is possible to fight against microorganisms directly with their help, since some microorganisms in the course of their life activity emit substances capable of destroying other microorganisms.

The idea of ​​using microbes to fight germs dates back to the 19th century. Thus, Louis Pasteur discovered that anthrax bacilli are killed by some other microbes. But it is clear that the solution of this problem required a lot of work - it is not easy to understand the life and relationships of microorganisms, it is even more difficult to comprehend which of them are at enmity with each other and how one microbe defeats another.

However, the most difficult thing was to imagine that the formidable enemy of the coccus has long been and is well known to man, that he has been living side by side with him for thousands of years, every now and then reminding myself. It turned out to be an ordinary mold - an insignificant fungus, which in the form of spores is always present in the air and readily grows on everything old and damp, whether it be a cellar wall or a piece.

However, the bactericidal properties of mold were known as early as the 19th century. In the 60s of the last century, a dispute arose between two Russian doctors - Alexei Polotebnov and Vyacheslav Manassein. Polotebnov argued that mold is the ancestor of all microbes, that is, that all microbes come from it. Manassein argued that this was not true.

To substantiate his arguments, he began to investigate green molds (in Latin, penicillium glaucum). He sowed the mold on a nutrient medium and noted with amazement: where the mold fungus grew, bacteria never developed. From this, Manassein concluded that the mold prevents the growth of microorganisms.

Later, Polotebnov observed the same: the liquid in which the mold appeared always remained transparent, therefore, did not contain bacteria. Polotebnov realized that as a researcher he was wrong in his conclusions. However, as a doctor, he decided to immediately investigate this unusual property of such an easily accessible substance as mold.

The attempt was successful: the ulcers, covered with an emulsion that contained mold, quickly healed. Polotebnov made an interesting experiment: he covered deep skin ulcers of patients with a mixture of mold and bacteria and did not observe any complications in them. In one of his articles in 1872, he recommended treating wounds and deep abscesses in the same way. Unfortunately, Polotebnov's experiments did not attract attention, although many people died from post-wound complications in all surgical clinics at that time.

Again, the remarkable properties of mold were discovered half a century later by the Scot Alexander Fleming. From his youth, Fleming dreamed of finding a substance that could destroy pathogenic bacteria, and stubbornly engaged in microbiology.

Fleming's laboratory was housed in a small room in the pathology department of one of London's major hospitals. This room was always stuffy, crowded and disorderly. To escape the stuffiness, Fleming kept the window open all the time. Together with another doctor, Fleming was engaged in research on staphylococci.

But, without finishing his work, this doctor left the department. The old cups of microbial colonies still stood on the shelves of the laboratory - Fleming always considered cleaning his room a waste of time.

One day, deciding to write an article about staphylococci, Fleming looked into these cups and found that many of the cultures that were there were covered with mold. This, however, was not surprising - apparently, mold spores had entered the laboratory through the window. Something else was surprising: when Fleming began to explore culture, in many there was not a trace of staphylococci in the cups - there was only mold and transparent, dew-like drops.

Has ordinary mold destroyed all disease-causing microbes? Fleming immediately decided to test his guess and put some mold in a test tube of nutrient broth. When the fungus developed, he settled in the same different bacteria and put it in a thermostat. After examining the nutrient medium, Fleming found that light and transparent spots formed between the mold and colonies of bacteria - the mold, as it were, hampered the microbes, preventing them from growing around it.

Then Fleming decided to make a larger experiment: he transplanted the fungus into a large vessel and began to observe its development. Soon the surface of the vessel was covered with "" - a fungus that had grown and huddled in cramped quarters. "Felt" changed its color several times: first it was white, then green, then black. The nutritious broth also changed color - from transparent it turned into yellow.

“Obviously, the mold releases some substances into the environment,” Fleming thought, and decided to check whether they have properties that are harmful to bacteria. New experience showed that the yellow liquid destroys the same microorganisms that the mold itself destroyed. Moreover, the liquid had an extremely high activity - Fleming diluted it twenty times, and the solution still remained detrimental to pathogenic bacteria.

Fleming realized that he was on the verge of an important discovery. He abandoned all business, stopped other studies. The mold fungus penicillium notatum is now entirely engulfed his attention. For further experiments, Fleming needed gallons of mold broth - he studied on which day of growth, at what and on what nutrient medium, the action of the mysterious yellow substance would be most effective in killing microbes.

At the same time, it turned out that the mold itself, as well as the yellow broth, turned out to be harmless to animals. Fleming injected them into the vein of a rabbit, into the abdominal cavity of a white mouse, washed the skin with broth and even buried it in the eyes - no unpleasant phenomena were observed. In a test tube, a diluted yellow substance - a product secreted by mold - retarded the growth of staphylococci, but did not disrupt the functions of blood leukocytes. Fleming named this substance penicillin.

Since then, he has constantly thought about an important question: how to isolate the active ingredient from a filtered mold broth? Alas, it turned out to be extremely difficult. Meanwhile, it was clear that introducing into the human blood an unpurified broth, which contained a foreign protein, was certainly dangerous.

Fleming's young associates, doctors like him, not chemists, made many attempts solve this problem. Working in artisanal conditions, they spent a lot of time and energy but achieved nothing. Each time after the purification undertaken, penicillin decomposed and lost its healing properties.

In the end, Fleming realized that this task was not up to him and that its solution should be left to others. In February 1929, he made a report to the London Medical Research Club about an unusually strong antibacterial agent he had found. This message didn't get any attention.

However, Fleming was a stubborn Scot. He wrote a long article detailing his experiments and published it in a scientific journal. At all congresses and medical conventions, he somehow made a reminder of his discovery. Gradually about penicillin became known not only in England, but also in America.

Finally, in 1939, two English scientists - Howard Florey, professor of pathology at one of the Oxford institutes, and Ernst Chain, a biochemist who fled Germany from Nazi persecution - paid close attention to penicillin.

Chain and Flory were looking for a topic to work with. The difficulty of the task of isolating purified penicillin attracted them. There was a strain (a culture of microbes isolated from certain sources) sent there by Fleming at Oxford University. With him, they began to experiment.

In order to turn penicillin into a drug, it had to be associated with some substance soluble in water, but in such a way that, when purified, it would not lose its amazing properties. For a long time, this task seemed unsolvable - penicillin quickly collapsed in an acidic environment (therefore, by the way, it could not be taken orally) and did not last long in an alkaline environment, it easily passed into the ether, but if it was not put on ice, it also collapsed in it .

Only after many experiments, the liquid secreted by the fungus and containing aminopenicillic acid was filtered in a complicated way and dissolved in a special organic solvent, in which potassium salts, which are highly soluble in water, did not dissolve. After exposure to potassium acetate, white crystals of the potassium salt of penicillin precipitated. After many manipulations, Chain received a slimy mass, which he finally managed to turn into a brown powder.

The very first experiments with it had an amazing effect: even a small granule of penicillin, diluted in a ratio of one per million, had a powerful bactericidal property - deadly cocci placed in this medium died in a few minutes. At the same time, the drug injected into the vein not only did not kill her, but had no effect on the animal at all.

Several other scientists joined Cheyne's experiments. The action of penicillin has been comprehensively studied in white mice. They were infected with staphylococci and streptococci in doses more than lethal. Half of them were injected with penicillin, and all of these mice survived. The rest died after a few. It was soon discovered that penicillin destroys not only cocci, but also the causative agents of gangrene.

In 1942, penicillin was tested on a patient who was dying of meningitis. He recovered very soon. The news of this made a great impression. However, it was not possible to establish the production of a new drug in warring England. Flory went to the USA, and here in 1943 in the city of Peoria, the laboratory of Dr. Coghill first began the industrial production of penicillin. In 1945, Fleming, Flory and Chain were awarded the Nobel Prize for their outstanding discoveries.

In the USSR, penicillin from the mold penicillium crustosum (this fungus was taken from the wall of one of the Moscow bomb shelters) was received in 1942 by Professor Zinaida Ermolyeva. There was a war. The hospitals were overflowing with the wounded with purulent lesions caused by staphylococci and streptococci, complicating already severe wounds.

The treatment was difficult. Many wounded died from purulent infection. In 1944, after much research, Yermolyeva went to the front to test the effect of her drug. Before the operation, Yermolyeva gave all the wounded an intramuscular injection of penicillin. After that, most of the fighters' wounds healed without any complications and suppuration, without fever.

Penicillin seemed like a real miracle to seasoned field surgeons. He cured even the most seriously ill patients who were already ill with blood poisoning or pneumonia. In the same year, factory production of penicillin was established in the USSR.

In the future, the family of antibiotics began to expand rapidly. As early as 1942, Gause isolated gramicidin, and in 1944 Waksman, an American of Ukrainian origin, received streptomycin. The era of antibiotics has begun which in subsequent years saved the lives of millions of people.

It is curious that penicillin remained unpatented. Those who discovered and created it refused to receive patents - they believed that a substance that could bring such benefits to humanity should not serve as a source of income. This is probably the only discovery of this magnitude for which no one has claimed copyright.

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. By "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. - have 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 earlier there were diseases that were more characteristic of a particular region, then at the moment even the boundaries of climatic zones that are 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. No less famous 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 experimental 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 shown 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.

Do you love neatness? It is believed that the order on the table is the order in the head. Fleming, discoverer of penicillin, did not really like to clean his laboratory table, which fortunately helped him in 1928 make one of the most important discoveries of the 20th century in medicine.

Enzyme lysozyme in saliva, he also discovered by accident: one day Fleming sneezed into a Petri dish (bacteria are grown in a nutrient medium in it) and a few days later discovered that in places where drops of saliva fell, the bacteria were destroyed. Fleming underestimated his discovery of penicillin and at first used the bactericidal properties of mold to paint pictures...

Scottish bacteriologist Alexander Fleming Born August 6, 1881 in Ayrshire in the family of farmer Hugh Fleming and his wife Grace.

When the boy was seven years old, his father died, and his mother had to manage the farm herself. She scrupulously calculated expenses and incomes, trying to carve out at least some funds for the education of her children. And this diligent and economical woman succeeded. Alexander attended first rural school located nearby, and later - kilmarnock academy. He early learned to carefully observe nature.

At the age of thirteen, Alexander followed his older brothers to London, where he worked as a clerk, attended classes at the Polytechnic Institute, and in 1900 joined London Scottish Regiment. Fleming enjoyed military life and earned a reputation as a top-notch marksman and water polo player. But by that time the Boer War had already ended, and Fleming did not have a chance to serve in overseas countries.

A year later, he received an inheritance of £250, which amounted to almost $1,200 - a considerable amount in those days. On the advice of his older brother, he applied for a national competition for admission to medical school. In the exams, Fleming received the highest scores and became a scholarship holder. medical school at St. Mary's Hospital. Alexander studied surgery and, having passed his examinations in 1906, became Fellow of the Royal College of Surgeons. Working in the pathology laboratory of Professor Almroth Wright at St. Mary's Hospital, he received his BSc and MSc degrees from the University of London in 1908.

After the entry of Britain into the First World War, Fleming served as a captain in the medical corps of the Royal Army, and participated in hostilities in France. In 1915 he married Sarah Marion McElroy, an Irish nurse. They had a son.

Working in the wound research laboratory, Fleming showed that the antiseptic carbolic acid (phenol), then widely used to treat open wounds, kills white blood cells that form a protective barrier in the body, which ultimately helps bacteria survive in tissues.

In 1922 after unsuccessful attempts to isolate the causative agent of colds, Fleming purely accidentally discovered lysozyme(the name was invented by Professor Wright) - an enzyme that kills some bacteria and does not harm healthy tissues. Unfortunately, the prospects for medical use of lysozyme turned out to be rather limited, since it was quite effective against non-causative bacteria, and completely ineffective against disease-causing organisms. This discovery prompted Fleming to look for other antibacterial drugs that would be harmless to the human body.

Next fluke - Fleming's discovery of penicillin in 1928- was the result of confluence a series of circumstances so incredible that they are almost unbelievable. Unlike his meticulous colleagues who cleaned bacterial culture dishes after they were done, Fleming did not throw away cultures for 2-3 weeks until his laboratory bench was cluttered with 40-50 dishes. Then he began to clean, looking through the cultures one by one, so as not to miss anything interesting. In one of the cups he found mold, which, to his surprise, inhibited the sown culture of bacteria. After separating the mold, he found that the “broth” on which the mold had grown acquired a pronounced ability to inhibit the growth of microorganisms, and also had bactericidal and bacteriological properties.

Fleming examines the crops in a petri dish.

Fleming's slovenliness and his observation were two factors in a whole series of accidents that contributed to the discovery. The mold, which turned out to be infected culture, belonged to a very rare species. It was probably brought in from a laboratory where mold samples were grown from the homes of patients with bronchial asthma in order to make desensitizing extracts from them. Fleming left the cup that later became famous on the laboratory table and went to rest. Coming to London cooling created favorable mold growth conditions, and the subsequent warming — for bacteria. As it turned out later, the famous discovery was due to the coincidence of these circumstances.

Fleming's initial research provided a number of important insights into penicillin. He wrote that it is " an effective antibacterial substance ... that has a pronounced effect on pyogenic 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 orally". Knowing this, however, Fleming did not take the obvious next step, which 12 years later was taken by Howard W. Flory to see if mice would be saved from a lethal infection if they were treated with injections of penicillin broth. Fleming appointed his several patients for outdoor use. However, the results have been inconsistent. The solution turned out unstable and was difficult to clean up if it was a large amount.

Like the Pasteur Institute in Paris, the vaccination department at St. Mary's where Fleming worked was supported by the sale of vaccines. Fleming discovered that during the preparation of vaccines penicillin helps protect crops from staph. This was a technical achievement, and the scientist widely used it, giving weekly orders to produce large batches of broth. He shared culture samples of penicillin with colleagues in other laboratories, but never mentioned penicillin in any of the 27 articles and lectures published by him in 1930-1940, even if it was about substances that cause the death of bacteria.

And Alexander Fleming also used penicillin in his picturesque delights. He was a member of the association of artists and even was considered an avant-garde with a special creative style. André Maurois, in his novel The Life of Alexander Fleming, argues that the bacteriologist was attracted not so much by "pure art" itself as by a good billiards and a cozy artist's cafe. Fleming liked to communicate and even collected mold for experiments from the shoes of his eminent friends, painters and graphic artists.

The paintings, oriental ornaments and outlandish patterns of the brush of the painter Fleming attracted the attention of the art world primarily because they were painted not in oil or watercolor, but in multi-colored strains of microbes sown on agar-agar, spilled on cardboard.

An avant-garde artist and a great original, Fleming skillfully combined the bright colors of vibrant colors. However, brainless microbes could not even imagine what a great cause they were participating in, and therefore they often violated the creative plan of the creator of paintings, creeping into the territory of neighbors and violating the original purity of colors.

Fleming found a way out: he became separate microbial colored spots from each other in narrow strips carried out with a brush previously immersed in a solution of penicillin.

Just as the creative heritage of the artist Fleming has sunk into oblivion, so penicillin itself was almost forgotten if it were not for the discovery of lysozyme by Fleming. It was this discovery that led Flory and Ernst B. Chain to study the therapeutic properties of penicillin, as a result of which the drug was isolated and subjected to clinical trials.

Nobel Prize in Physiology or Medicine 1945 was awarded jointly to Fleming, Cheyne and Flory "for the discovery of penicillin and its curative effects in various infectious diseases." In the Nobel Lecture, Fleming noted that "the phenomenal success of penicillin has led to intensive study of the antibacterial properties of molds and other lower members of the plant kingdom. Only a few of them have such properties.

In the remaining 10 years of his life, the scientist was awarded 25 honorary degrees, 26 medals, 18 prizes, 30 awards and honorary membership in 89 academies of sciences and scientific societies.

On March 11, 1955, Alexander Fleming died of a myocardial infarction. He was buried in St. Paul's Cathedral in London - next to the most revered Britons. In Greece, where the scientist visited, national mourning was declared on the day of his death. And in Barcelona, ​​Spain, all the flower girls of the city poured out bunches of flowers from their baskets to a memorial plaque with the name of the great bacteriologist and physician Alexander Fleming.

Fleming kept a cup with an overgrown mold fungus until the end of his life.

According to the magazine "Repetitor".

Mass production of penicillin was established during World War II (1942 - USSR, 1943 - USA). At first there was general rejoicing - the most severe infections were quickly cured. It seemed that the microbes had come to an end. But the bacteria also wanted to live and began to develop and pass on antibiotic resistance to each other. There is an uphill battle going on right now between bacteria and the pharmaceutical industry, and I think people are losing it.

Conventional penicillin is produced mostly in vials of 500,000 IU (action units) and 1,000,000 IU.

• AT 1945 it was possible to cure gonorrhea with one (!) intramuscular injection of penicillin in 300 thousand units.
• AT 1970 for this it was necessary course of injections for 3 million units.
• As of 1998, 78% of gonococci were resistant to antibiotics of the penicillin group. Penicillin is no longer used to treat gonorrhea.

Hence the conclusions:

1. need to be treated with antibiotics strictly according to indications. The common cold does not require antibiotics, because they are powerless against viruses.
2. cannot be treated according to the old schemes. Bacterial resistance is constantly growing. You may not cure the infection, but at the same time destroy the balance of normal microflora. As a result, "wrong" bacteria and fungi will breed.

Until 1989, no cases of vancomycin-resistant Enterococcus infection were detected in the United States. In 2002, many cases of a new form of enterococcus (called S. aureus) were noted, in the fight against which vancomycin was ineffective. In 2003, S. aureus (Staphylococcus aureus) appeared for the first time, on which vancomycin had no effect. In 2004, S. aureus also developed resistance to more powerful antibiotics.

Here's some more food for thought. Antibiotics are freely sold in Belarusian and Russian pharmacies (prescription only in the USA). What is more from over-the-counter sales - harm or benefit?

Opening penicillin owned by Alexander Fleming. When he died, he was buried in St. Paul's Cathedral in London - next to the most revered Britons. In Greece, where the scientist visited, national mourning was declared on the day of his death. And in Spanish Barcelona, ​​all the flower girls of the city poured armfuls of flowers from their baskets to a memorial plaque with his name.

Scottish bacteriologist Alexander Fleming (1881-1955) was born in Ayrshire to farmer Hugh Fleming and his second wife, Grace (Morton) Fleming.

Alexander attended a small rural school located nearby, and later Kilmarnock Academy, early learned to carefully observe nature. At the age of 13, he followed his older brothers to London, where he worked as a clerk, attended classes at the Regent Street Polytechnic Institute, and in 1900 joined the London Scottish Regiment.

On the advice of his older brother, he applied for a national competition for admission to medical school. In the exams, Fleming received the highest scores and became a fellow of the medical school at St. Mary. Alexander studied surgery and, having passed the exams, in 1906 became a member of the Royal College of Surgeons. Staying to work in the pathology laboratory of Professor Almroth Wright at St. Mary, he received his Master's and Bachelor of Science degrees from the University of London in 1908.

At that time, doctors and bacteriologists believed that further progress would be associated with attempts to change, strengthen or supplement the properties of the immune system. The discovery in 1910 of salvarsan by Paul Ehrlich only confirmed these assumptions. Ehrlich was busy looking for what he called the "magic bullet", meaning by this a means that would destroy the bacteria that entered the body without harming the tissues of the patient's body and even interacting with them.

Wright's lab was one of the first to receive salvarsan samples for testing. In 1908, Fleming began experimenting with the drug, also using it in private medical practice to treat syphilis. Well aware of all the problems associated with salvarsan, he nevertheless believed in the possibilities of chemotherapy. For several years, however, the results of the studies were such that they could hardly confirm his assumptions.

From the corridor, through the half-open door into a small, cramped laboratory, one could see Dr. Alexander Fleming, bustling around in a cramped, crowded room. Here he rearranges Petri dishes from place to place, ... carefully examines them and sorts them according to some signs known to him alone. He needs to write a chapter on streptococci for a bacteriology textbook. To do this, he needs to conduct a series of experiments on numerous colonies of these microbes. He fills the Petri dishes with agar-agar, which, as it cools, forms a smooth film on the bottom of the dishes; on it he plants a culture of bacteria. In this excellent nutrient medium, at the right temperature, the bacteria develop and form large colonies that look like branched amber clumps.

In Fleming's laboratory, mold was his worst enemy. Common greenish-gray mold, which comes from nowhere in the damp corners of poorly ventilated rooms, covers stale food products if they are not stored well. Mold is nothing more than a microscopic fungus that arises from even smaller germs, thousands of which are floating in the air. As soon as the embryos fall into a favorable environment for them, they begin to grow very quickly.

Fleming more than once, when lifting the lid of a Petri dish, was convinced with annoyance that cultures of streptococci were contaminated with mold. Indeed, in the laboratory it was enough to leave a Petri dish for several hours without a lid, as the entire nutrient layer was covered with mold. It cost Fleming a lot of work to fight against undesirable impurities on one or the other cup. Once, on one of the cups, Fleming saw a strange phenomenon and looked at it for a long time. As happened more than once, the cup was covered with mold, but unlike other cups, a small round bald patch formed around the colony of bacteria. There was an impression that the bacteria did not multiply around the mold, although on the rest of the surface of the agar-agar, at some distance from the mold, the bacteria grew, and quite strongly.

“Accident or regularity?” Fleming thought. To answer this question, Fleming placed a small amount of mold in a test tube with nutrient broth: he wanted above all to preserve the strange mold. "Then he did not think that this cup would be his most precious treasure and that in it he would find a solution to the problem to which he devoted his whole life. From a microscopic piece of mold, Fleming received a large colony. Then he placed part of this mold on the cups where he cultivated different bacteria.

It turned out that some types of bacteria get along well with mold, but streptococci and staphylococci did not develop in the presence of mold. Numerous previous experiments with the reproduction of harmful bacteria showed that some of them are capable of destroying others and do not allow their development in the general environment. This phenomenon was called "antibiosis" from the Greek "anti" - against and "bios" - life. Working on finding an effective antimicrobial agent, Fleming knew this very well. He had no doubt that on a cup with a mysterious mold, he met with phenomenon of antibiosis. He began to carefully study the mold. After some time, he even managed to isolate an antimicrobial substance from the mold. Since the mold with which he was dealing had the specific Latin name Penicilium notatum, he named the resulting substance penicillin. Thus, in 1929, in the laboratory of St. Mary's Hospital in London produced the well-known penicillin.

Preliminary tests of the substance on experimental animals showed that even when injected into the blood, it does not cause harm, and at the same time, in weak solutions, it perfectly suppresses streptococci and staphylococci. Fleming's assistant, Dr. Stuart Greddock, who fell ill with purulent inflammation of the so-called maxillary cavity, was the first person who decided to take a crush of penicillin. He was injected into the cavity with a small amount of extract from the mold, and after three hours it was possible to see that his state of health had improved significantly. It was clear that Fleming had won a major battle against bacteria. But mankind's war on microbes was not yet over: industrial methods for the production of penicillin had to be developed. Fleming worked on this problem for more than two years, but did not achieve success. This explains the fact that the first article reporting on the antimicrobial properties of penicillin was written by Fleming three years after the end of the experiments on its practical application.

The attempts of industrial production of penicillin carried out by other researchers were also unsuccessful. But in the middle of 1939, two scientists from Oxford: the physician Edward Howard Frey and the chemist J. Ernest Cheyne took up the matter. After two years of disappointment and defeat, they managed to obtain a few grams of brown powder, which could already be tested on 117 people. It was, although not quite pure, but of sufficient quality crystalline penicillin. The first injections of the new agent were made to a person on February 12, 1941. One of the London police officers cut himself with a razor while shaving. Blood poisoning developed. The first injection of penicillin was given to a dying patient. The patient's condition immediately improved. But there was too little penicillin, its supply quickly dried up. The disease returned and the patient died. Despite this, science triumphed, as it was convincingly proven that penicillin works wonderfully against blood poisoning. A few months later, scientists managed to accumulate such an amount of penicillin that could be more than enough to save a human life.

The lucky one was a fifteen-year-old boy who had a blood poisoning that could not be cured. He was the first person whose life was saved by penicillin. At this time, the whole world has been engulfed in the fire of war for three years. Thousands of the wounded died from blood poisoning and gangrene. A huge amount of penicillin was required. Frey went to the United States of America, where he managed to interest the government and large industrial concerns in the production of penicillin.