Who discovered penicillin first. The history of the discovery of penicillin - biographies of researchers, mass production and consequences for medicine

It is known that back in the XV-XVI centuries. In folk medicine, green mold was used to treat festering wounds. For example, Alena Arzamasskaya, an associate of Stepan Razin, and the Russian Joan of Arc, knew how to treat with it. Attempts to apply mold directly to the wound surface yielded, 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 a substance from human tissue that had the ability to quite actively dissolve certain types of microbes. This discovery was made almost by accident while trying to isolate bacteria that cause the common cold. Professor A. Wright, under whose leadership A. Fleming continued his research work, named the new substance lysozyme (lysis - 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 antibacterial drugs that are effective and, at the same time, as harmless as possible to humans. It must be said that back in 1908, he conducted experiments with a drug called “salvarsan,” which the laboratory of Professor A. Wright was among the first in Europe to receive for comprehensive research. 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 would kill pathogens but be safe for the patient, the so-called magic bullet. Salvarsan was a fairly effective anti-syphilitic drug, but had toxic side effects 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.

Is everything brilliant discovered by chance?

First mention of antibacterial therapy?

It is interesting that in the Bible we find an incredibly precise indication of the properties of the semi-shrub plant - hyssop. Here is a fragment of Psalm 50, which, by the way, A. Fleming also remembered: “Purge 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 incredible accidents and coincidences that preceded the great discovery. The root cause was, oddly enough, A. Fleming’s sloppiness. 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 the studied cultures for several weeks, and as a result, his workplace was littered with fifty cups. True, during the cleaning process he scrupulously examined each cup for fear of missing something important. And I didn’t miss it.

One fine day, he discovered fluffy mold in one of the cups, which suppressed the growth of the staphylococcus culture sown in this cup. It looked like this: the chains of staphylococci around the mold disappeared, and in place of the yellow cloudy mass, drops resembling dew were visible. Having removed 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 against many common pathogenic bacteria.”

It appears that the mold spores were brought in through a window from a laboratory where mold samples taken from the homes of patients suffering from bronchial asthma, to obtain desensitizing extracts. The scientist left the cup on the table and went on vacation. The London weather played a role: colder temperatures favored the growth of mold, and subsequent warming favored the growth of bacteria. If at least one event had occurred from a chain of random coincidences, who knows when humanity would have learned about penicillin. The mold that infected the staphylococcal culture was a fairly rare species sort of Penicillium -P. Notatum , which was first found on rotted hyssop (a subshrub containing essential oil and used as a spice);

Advantages of a new invention

Further research revealed that, fortunately, even in large doses, penicillin is non-toxic to experimental animals and is capable of killing very resistant pathogens. There were no biochemists at St. Mary's Hospital, and as a result, penicillin could not be isolated into an injectable form. This work was carried out at Oxford by H. W. Flory and E. B. Cheyne only in 1938. Penicillin would have sunk into oblivion if A. Fleming had not previously discovered lysozyme (this is where 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 provided a whole range 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 bacilli of the diphtheria group. 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 has been obtained, but how to use it?

Similar to 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 discovered that during the preparation of vaccines, penicillin protects cultures from staphylococcus. This was a small but significant achievement, and A. Fleming made extensive use of it, weekly ordering the production of large batches of penicillium-based broth. He shared samples of culture Penicillium with colleagues in other laboratories, but, oddly enough, A. Fleming did not take such an obvious step, which was taken 12 years later by H. W. Flory and was to establish whether experimental mice would be saved from a fatal infection if treat them with injections of penicillin broth. Looking ahead, let's say that these mice were extremely lucky. A. Fleming only prescribed the broth to several patients for external use. However, the results were very, very contradictory. The solution was not only difficult to purify in large quantities, but also proved unstable. In addition, A. Fleming never mentioned penicillin in any of the 27 articles or lectures he published in 1930-1940, even when they talked about 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 came to a conclusion about the safety of penicillin, both for humans and animals.

Who was the first to invent penicillin?

What was happening in the laboratories of our country at this time? Have domestic scientists really been sitting with their hands folded? Of course this is not true. Many have read V. A. Kaverin’s “Open Book” trilogy, 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, Z. V. Ermolyeva was the first Russian scientist 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 of 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, Z. V. Ermolyeva was left as an assistant at the department of microbiology; at the same time she headed the bacteriological department of the North Caucasus Bacteriological Institute. When a cholera epidemic broke out in Rostov-on-Don in 1922, 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, observing the wounded, Z. V. Ermolyeva saw that many of them were dying not directly from their wounds, but from blood poisoning. By that time, research from her laboratory, completely independent of the British, had shown that some molds inhibit the growth of bacteria. 3. V. Ermolyeva, of course, knew that in 1929 A. Fleming obtained penicillin from mold, but could not isolate it in its pure form, because the drug turned out to be very unstable. She also knew that our compatriots had long ago noticed witchcraft at the level of traditional medicine medicinal properties mold. But at the same time, unlike A. Fleming, fate did not indulge Z. V. Ermolyev with happy accidents. In 1943, W. H. Florey and E. Chain were able to launch the production of penicillin in industrial scale, however, to do this they had to organize production in the USA. 3. V. Ermolyeva, who at that time was 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 obtained. The greatest and indisputable merit of Z. V. Ermolyeva was that she not only obtained penicillin, but also managed to establish mass production of the first domestic antibiotic. It should be taken into account that the Great Patriotic War, there was an acute shortage of the simplest and most necessary things. At the same time, the need for penicillin was growing. And 3. V. Ermolyeva did the impossible: she managed to ensure not only quantity, but also quality, or rather, the strength of the drug.

How many wounded people owe their lives to her cannot even be roughly calculated. 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, chloramphenicol and ecmolin - the first antibiotic of animal origin isolated from milk sturgeon fish. A message appeared relatively recently, the authenticity of which is still difficult to vouch for. Here it is: penicillin was discovered even before A. Fleming by a certain medical student Ernest Augustine Duchenne, who in his dissertation work described in detail the surprisingly effective drug he discovered for combating various bacteria that have a detrimental effect on the human body. E. Duchenne was unable to complete his scientific discovery due to a transient illness that resulted in death. However, A. Fleming had no idea about the young researcher’s discovery. And only quite recently in Leon (France) the dissertation of E. Duchenne was accidentally found.

By the way, a patent for the invention of penicillin has not been issued to anyone. A. Fleming, E. Chain and W. H. Florey, who received one Nobel Prize between them for its discovery, flatly refused to receive patents. They considered that a substance that has every chance of saving all of humanity should not be a source of profit, a gold mine. This scientific breakthrough is the only one of this magnitude for which 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!

The beginning of the era of antibiotics

So, a new era has begun in medicine - 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 our wildest expectations; In addition, the discovery of penicillin marked the beginning of the search for new antibiotics and sources of their production. At the time of their discovery, penicillins 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 microbial cells that are absent in animal cells.

Reference. Penicillins belong to a broad class of gamma-lactam antibiotics. This also includes cephalosporins, carbapenems and monobactams. What is 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 bactericidal properties, that is, they have a detrimental effect on bacteria. The main target of action is the penicillin-binding proteins of bacteria, which are enzymes of the final stage of bacterial cell wall synthesis. Blocking peptidoglycan synthesis by an antibiotic leads to disruption of cell wall synthesis 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 with the intimidating 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.

General features of antibacterial drugs

Antibiotics are substances that selectively suppress the activity of microorganisms. By “selective influence” we mean activity exclusively in the interaction of microorganisms while maintaining the viability of host cells and the effect not on all, 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. Closely related to selectivity is the idea of ​​the broad spectrum of activity of antibacterial drugs. However, from the standpoint today The division of antibiotics into broad-spectrum and narrow-spectrum drugs seems arbitrary and is subject to serious criticism, largely due to the lack of criteria for such a division. The assumption that broad-spectrum drugs are more reliable and effective is incorrect.

The path leading to nowhere

Gentlemen, the last word will be behind germs!
Louis Pasteur

To all microscopic enemies human race war has been declared for life and death. It is being carried out so far with varying success, but some diseases have already receded, it seems, forever, for example smallpox. But at the same time, camel and cow pox, as well as monkey pox, remain. However, with smallpox, not everything is so simple. Since the mid-1980s. cases of smallpox are not recorded. In this regard, children have not been vaccinated against smallpox for quite some time. Thus, the number of people resistant to the smallpox virus in the human population decreases every year. But this virus has not gone away. It can be preserved on the bones of people who died from smallpox (not all the corpses were burned, some of them there was no one to burn) for an arbitrarily long time. And someday there will definitely be a meeting between an unvaccinated person, for example an archaeologist, and a virus. L. Pasteur was right. Many previously fatal diseases have faded into the background - dysentery, cholera, purulent infections, pneumonia, etc. However, glanders, which had not been observed for almost 100 years, seems to have returned. A number of countries are experiencing outbreaks of polio after decades without this terrible disease. New threats have been added, in particular bird flu. People are already dying from the bird flu virus carnivorous mammals. Open borders have made it impossible to fight germs in a single state. If previously there were diseases more typical of a particular region, now even the boundaries are blurred climatic zones, more characteristic of a particular type of pathology. Of course, specific infections of the tropical zone do not yet threaten the inhabitants of the Far North, but, for example, sexually transmitted infections, AIDS, hepatitis B, C as a result of the process of general globalization have become truly global threat. Malaria spread from hot countries all the way to the Arctic Circle.
The cause of classical infectious diseases is 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, sarcoids, sporozoans, ciliates). In addition to pathogenic microorganisms, there are large group 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 was clearly proven, the discovery of new drugs became 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 a reason for optimism.

Timeline of the emergence of antibiotics

In 1939, gramicidin was isolated, then chronological order- streptomycin (in 1942), chlorotstracycline (in 1945), chloramphenicol (in 1947), and by 1950 more than 100 antibiotics had already been described. It should be noted that in 1950-1960. this caused premature euphoria in medical circles. In 1969, a highly 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 humanity is the attempt to overtake the natural evolutionary process, since 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 whose habitat is soil. It turned out that the soil contains deadly enemies of a number of human pathogenic microorganisms - the causative agents of typhus, cholera, dysentery, tuberculosis, etc. Streptomycin, which has been used to treat tuberculosis to this day, was also isolated from soil microorganisms. In order to select the desired strain, 3. Waksman (discoverer of streptomycin) studied over 500 crops for 3 years before finding a suitable one - one that releases more streptomycin into the environment than other crops. During scientific research, many thousands of microorganism cultures are carefully studied and rejected. And only single copies are used for subsequent study. However, this does not mean that all of them will later become a source for new drugs. The extremely low productivity of crops and the technical complexity of the isolation and subsequent purification of medicinal substances pose additional, often insurmountable barriers to new drugs. And new antibiotics are needed like air. Who could have predicted that microbial viability would become such a serious problem? In addition, more and more new pathogens of infectious diseases were being identified,” and the spectrum of activity of existing drugs became insufficient for effective fight with 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 absolutely not necessary to be a talented science fiction writer to do this. Rather, the role of brilliant visionaries was to be played by skeptics from scientific circles. But if someone predicted something like that, 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 launched almost completely disappeared, but then they multiplied in huge numbers, and the new generation of flies was resistant to DDT, which indicates the genetic consolidation of this trait. As for microorganisms, A. Fleming discovered that subsequent generations of staphylococci formed cell walls with a structure resistant to penicillin. Academician S. Schwartz warned about the state of affairs that could arise with this vector of events more than 30 years ago. He said: “No matter what happens on the upper floors of nature, no matter what cataclysms shake the biosphere... highest efficiency the use of energy at the level of cells and tissues guarantees the life of organisms, which will restore life on all its levels in a form that corresponds to the new environmental conditions.” Some bacteria can reject or neutralize antibiotics as they invade. 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 this 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, which was resistant to of hydrochloric acid gastric juice, which can be taken in tablet form. Penicillins natural origin were completely ineffective when taken orally, since they lost their activity in the acidic environment of the stomach. Later, a method for producing semi-synthetic penicillins was invented. For this purpose, the penicillin molecule was “cut” through the action of the enzyme penicillinase and, using one of the parts, new compounds were synthesized. Using this technique, it was possible to create drugs with a significantly wider spectrum of antimicrobial action (amoxicillin, ampicillin, carbenicillin) than the original penicillin. An equally well-known antibiotic, cephalosporin, was first isolated in 1945 from Wastewater on the island of Sardinia, became the founder new group semisynthetic 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 a certain selective effect on strictly certain types microorganisms. Due to this selective action, a significant part of antibiotics is capable of eliminating many types of pathogenic microorganisms, acting in concentrations that are harmless or almost harmless to the body. It is this type of antibiotic drugs 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 that live in soil and water, where they continuously interact, entering into various relationships with each other, which can be neutral, antagonistic or mutually beneficial. A striking example putrefactive bacteria that create good conditions for the normal functioning of nitrifying bacteria. However, often the relationships between microorganisms are antagonistic, that is, directed against each other. This is quite understandable, since only in this way could nature initially maintain the ecological balance of a huge number of biological forms. The Russian scientist I.I. Mechnikov, far ahead of his time, was the first to propose the practical use of antagonism between bacteria. He advised suppressing the activity of putrefactive bacteria, which constantly live in the human intestines, at the expense of beneficial lactic acid bacteria; The waste products released by putrefactive microbes, according to the scientist, shorten human 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 a direction that is optimally suitable 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 their production of various antibiotic chemicals. These substances are capable of either suppressing the growth and reproduction of other microorganisms (bacteriostatic effect) or destroying them (bactericidal effect). Bacteriostatic agents include antibiotics such as erythromycin, tetracyclines, and aminoglycosides. Bactericidal drugs cause the death of microorganisms; the body can only cope with the elimination of their waste products. These are penicillin antibiotics, cephalosporins, carbapenems, etc. Some antibiotics that act bacteriostatically destroy microorganisms if used in high concentrations (aminoglycosides, chloramphenicol). But you should not get carried away with increasing the dose, since with increasing concentration the likelihood of a toxic effect on human cells increases sharply.

History of the discovery of bacteriophages.

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

Bacteriophages were discovered independently by F. Twort, together with A. Londe and F. d'Herel, as filterable, transmitted agents of destruction of bacterial cells. Initially, they were believed to be the key to the control of bacterial infections, however, early studies were largely inconsistent. Bacteriophages have been isolated that can infect most prokaryotic groups of organisms; and they are readily isolated from soil, water, sewage and, as might be expected, from most environments colonized by bacteria. In 1940-1950 research papers on the study of the structure and physiology of host-phage interactions, carried out by G. Delbrück, 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 the whole a number of new branches of the industry based on biotechnology. Bacteriophages, like other viruses, carry their genetic information in the form of DNA or RNA. Most bacteriophages have tails, the tips of which 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 reads it to form new phagocapsular material to create new phage particles. The number of phages produced during a single infection cycle (yield size) varies between 50 and 200 new phage particles. Resistance to bacteriophage can develop due to loss or changes in receptor molecules on the surface of the host cell. Bacteria also have special mechanisms that protect them from invasion by foreign DNA. Host DNA is modified by methylation at specific points in the DNA sequence; this creates protection from degradation by host-specific restriction endonucleases. Bacteriophages are divided into 2 groups: virulent and temperate. Virulent phages cause a lytic infection, resulting in the destruction of host cells and producing clear spots (plaques) on colonies of susceptible bacteria. 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 an issue 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 suppressing 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 combating viruses using bacteriophages were developed. Enteral and purulent-septic diseases initiated by opportunistic pathogens, including surgical infections, infectious diseases of children in 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 antibacterial therapy. The fatal outcome for these infections reaches 30-60%. The factor of ineffectiveness of therapy is high frequency resistance of pathogens to antibiotics and chemotherapeutic drugs, reaching 39.9-96.9%, as well as suppression of the immune system as the effect of these drugs on the patient’s body, reactions toxic properties and allergic in nature with side effects, manifested in intestinal disorders against the background of dysbiosis, and a similar disorder of the upper respiratory tract during the treatment of scleroma and ozena. The problem of intestinal dysbiosis in children is especially relevant. early age. The long-term results of such treatment in children are immunosuppression, chronic septic conditions, nutritional disorders, and developmental deficiencies.

You should know it!

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

Clinical researches showed that the use of bacteriophages to treat the surfaces of rooms 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 the droppings in calf pens with aqueous suspensions of bacteriophages. While early research has shown significant success, phage therapy has 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 overly narrow strain specificity. Other points included the emergence of phage-resistant strains, the neutralization or clearance of phages by the protective functions of the immune system, and the release 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 data provided by M. Slopes (1983 and 1984), the use of bacteriophage preparations in infectious diseases digestive system, inflammatory and 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 treatment.

Over the past 2 decades, several experimental studies have been undertaken to re-evaluate the use of bacteriophage-based therapeutic techniques for the treatment of infectious diseases in humans and animals. Recently, the results of these studies have 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 such as diarrhea in calves. It has been proven that both prevention and treatment are possible if phage titers are used that are much lower than the number of target organisms, which is an indication of the proliferation of bacteriophages in vivo. They showed that intramuscular injection of 106 units of E. Coli led to the death of 10 experimental mice, while simultaneous injection into the other paw of 104 phages selected against the K1 capsule antigen gave complete protection.
Bacteriophage therapy has a number of advantages in comparison with antibiotic therapy. For example, it is effective against drug-resistant organisms and can be used as an alternative therapy for patients with allergies to antibiotics. It can be used prophylactically to control the spread of an infectious disease where the source is identified on early stage, or where outbreaks occur within relatively closed organizations such as schools or nursing homes. Bacteriophages are highly specific to target organisms and have no effect on organisms that are not targets of attack. They are self-replicating and self-limiting; when a target organism is present, they self-replicate until all target bacteria are infected and destroyed. Bacteriophages mutate naturally to combat host resistance mutations; in addition, they can be deliberately mutated in the laboratory. In Russia and the CIS countries, bacteriophage preparations are used to treat purulent-septic and enteral diseases of various localizations caused by opportunistic bacteria of the genera Escherichia, Proteus^ Pseudomonas, Enterobacter, Staphylococcus, Streptococcus, and serve as substitutes for antibiotics. They are not inferior and even surpass the latter in effectiveness, without causing side 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 peritonsillar ulcers, inflammation of the sinuses, as well as purulent-septic infections, intensive care patients, surgical diseases, cystitis, pyelonephritis, cholecystitis, gastroenterocolitis, paraproctitis, intestinal dysbiosis, inflammatory diseases and sepsis of newborns. With the widespread development of antibiotic resistance in pathogenic bacteria, the need for new antibiotics and alternative technologies for the control of microbial infections is becoming increasingly important. Bacteriophages likely have yet to fulfill their role in the treatment of infectious diseases, either when used independently or in combination with antibiotic therapy.

Hundreds human lives saved during the use of antibiotics in medical practice. The discovery of penicillin made it possible to easily save people from diseases that until the beginning of the 20th century were considered incurable.

Medicine before the invention of penicillin

For many centuries, medicine was unable to save the lives of all sick people. The first step towards a breakthrough was the discovery of the fact about the nature of the origin of many ailments. It's about that most diseases arise from the destructive effects of microorganisms. Quite quickly, scientists realized that they could be destroyed with the help of other microorganisms that exhibit a “hostile attitude” towards pathogens.

In the course of their medical practice, several scientists came to this conclusion back in the 19th century. Among them was Louis Pasteur, who discovered that the action of certain types of microorganisms leads to the death of bacilli. But this information was not enough. It was necessary to find specific effective ways to solve the problem. All attempts by doctors to create a universal medicine ended in failure. And only pure chance and a brilliant guess helped the scientist who invented penicillin.

Useful properties of mold

It's hard to believe that the most common mold has bactericidal properties. But this is true. After all, this is not just a greenish-gray substance, but a microscopic fungus. It arises from even smaller embryos that float in the air. In conditions of poor air circulation and other factors, mold forms from them. Penicillin had not yet been discovered, but in the writings of Avicenna in the 11th century there are references to the treatment of purulent diseases with the help of mold.

Dispute between two scientists

In the 60s of the 19th century, Russian doctors Alexey Polotebnov and Vyacheslav Manassein seriously argued. The issue at issue was mold. Polotebnov believed that it is the ancestor of all microbes. Manassein insisted on the opposite point of view, and to prove his case, he conducted a series of studies.

He observed the growth of mold spores that he sowed into the growing medium. As a result, V. Manassein saw that the development of bacteria did not occur precisely at the sites of mold growth. His opinion has now been confirmed experimentally: mold does indeed block the growth of other microorganisms. His opponent admitted the fallacy of his statement. Moreover, Polotebnov himself began to closely study the antibacterial properties of mold. There is evidence that he even successfully used them in the treatment of poorly healing skin ulcers. Polotebnov devoted several chapters of his scientific work description of the properties of mold. There, the scientist recommended using these features in medicine, in particular, for the treatment of skin diseases. But this idea did not inspire other doctors and was unfairly forgotten.

Who invented penicillin

This merit belongs to the medical scientist Alexander Fleming. He was a professor in the laboratory of St. Mary of the city of London. Its main theme scientific activity- this is the growth and properties of staphylococci. He discovered penicillin by accident. Fleming was not famous for being particularly careful; quite the contrary. One day, after leaving unwashed cups with bacterial cultures on the work table, a few days later he noticed mold that had formed. He was interested in the fact that the bacteria in the space around the mold were destroyed.

Fleming gave the name to the substance secreted by mold. He called it penicillin. After conducting a large number of experiments, the Scientist became convinced that this substance could kill different types of pathogenic bacteria.

In what year was penicillin invented? In 1928, Alexander Fleming's powers of observation gave the world this miraculous substance at that time.

Production and Application

Fleming was unable to learn how to obtain penicillin, so at first practical medicine was not very interested in his discovery. Those who invented penicillin as a medical drug were Howard Florey and Chain Ernst. They, together with their colleagues, isolated pure penicillin and created the world's first antibiotic based on it.

In 1944, during World War II, scientists in the United States were able to industrially produce penicillin. Testing the drug took a little time. Almost immediately, penicillin was used by the Allied armed forces to treat the wounded. When the war ended, US civilians were also able to purchase the miracle drug.

Everyone who invented penicillin (Fleming, Flory, Chain) became owners Nobel Prize in medecine.

Penicillin: history of discovery in Russia

When the Great Patriotic War was still ongoing, J.V. Stalin made numerous attempts to purchase a license for the production of penicillin in Russia. But the United States behaved ambiguously. First, one sum was named, it must be said, astronomical. But later it was increased two more times, explaining these increases by incorrect initial calculations. As a result, the negotiations were unsuccessful.

There is no clear answer to the question of who invented penicillin in Russia. The search for methods for producing analogues was entrusted to microbiologist Zinaida Ermolyeva. She was able to obtain a substance that was later named crustozin. But in terms of its properties, this drug was much inferior to penicillin, and the production technology itself was labor-intensive and expensive.

It was decided to still buy a license. The seller was Ernst Chain. After this, the development of the technology and its launch into production began. This process was led by Nikolai Kopylov. penicillin was established quite quickly. For this Nikolai Kopylov was awarded

Antibiotics in general and penicillin in particular certainly have truly unique properties. But today, scientists are increasingly concerned that many bacteria and microbes are developing resistance to such therapeutic effects.

This problem now requires careful study and search for possible solutions, because indeed, a time may come when some bacteria will no longer respond to the action of antibiotics.

At the beginning of the last century, many diseases were incurable or difficult to treat. People died from simple infections, sepsis and pneumonia.
Wikimedia Commons/Carlos de Paz ()
A real revolution in medicine occurred in 1928, when penicillin was discovered. In all of human history, there has never been a drug that has saved as many lives as this antibiotic.

Over the course of decades, it has cured millions of people and remains one of the most effective medications to this day. What is penicillin? And to whom does humanity owe its appearance?

What is penicillin?

Penicillin is part of the group of biosynthetic antibiotics and has a bactericidal effect. Unlike many other antiseptics medicines it is safe for humans, since the fungal cells that make up it are fundamentally different from the outer shells of human cells.

The action of the drug is based on inhibition of the vital activity of pathogenic bacteria. It blocks the substance peptidoglycan they produce, thereby preventing the formation of new cells and destroying existing ones.

What is penicillin for?

Penicillin is capable of destroying gram-positive and gram-negative bacteria, anaerobic bacilli, gonococci and actinomycetes.


Since its discovery, it has become the first effective drug against pneumonia, skin and biliary tract infections, anthrax, ENT diseases, syphilis and gonorrhea.

Nowadays, many bacteria have managed to adapt to it, mutated and formed new species, but the antibiotic is still successfully used in surgery to treat acute purulent diseases and remains the last hope for patients with meningitis and furunculosis.

What does penicillin consist of?

The main component of penicillin is the mold fungus penicillium, which forms on products and leads to their spoilage. It can usually be seen as a blue or greenish colored mold. The healing effect of the fungus has been known for a long time. Back in the 19th century, Arab horse breeders removed mold from damp saddles and smeared it on the wounds on the backs of horses.

In 1897, the French physician Ernest Duchenne was the first to test the effects of mold on guinea pigs and managed to cure them of typhus. The scientist presented the results of his discovery at the Pasteur Institute in Paris, but his research did not receive the approval of medical luminaries.

Who discovered penicillin?

The discoverer of penicillin was the British bacteriologist Alexander Fleming, who managed to completely accidentally isolate the drug from a strain of fungi.


For a long time After the discovery, other scientists tried to improve the quality of the drug, but only 10 years later, bacteriologist Howard Flory and chemist Ernst Chain were able to produce a truly pure form of the antibiotic. In 1945, Fleming, Florey and Chain received the Nobel Prize for their achievements.

History of the discovery of penicillin

The history of the discovery of the drug is quite interesting, since the appearance of the antibiotic was a happy accident. During those years, Fleming lived in Scotland and was engaged in research in the field of bacterial medicine. He was quite messy, so he didn’t always clean up the test tubes after tests. One day, a scientist left home for a long time, leaving Petri dishes with staphylococcus colonies dirty.

When Fleming returned, he found that mold was growing on them, and in some places there were areas without bacteria. Based on this, the scientist came to the conclusion that mold is capable of producing substances that kill staphylococci.

Wikimedia Commons / Steve Jurvetson () A bacteriologist isolated penicillin from fungi, but underestimated his discovery, considering the preparation of the medicine too difficult. The work was completed for him by Flory and Chain, who managed to come up with methods for purifying the drug and launching it into mass production.

It is impossible to imagine modern medicine without antibiotics. They help to successfully fight many infectious diseases and save millions of people every year. It should be noted that the discovery of antibiotics happened by accident, and who knows what would have happened to us if not for the research of Scottish professor Alexander Fleming. At the beginning of the last century, he managed to discover a special fungus that was absolutely harmless to humans, but regularly killed pathogens.

Discovery of penicillin

And it was like this. In 1906, Fleming, as a student, practiced in the clinical microbiology laboratory at St. Mary's Hospital in London. In 1922, he discovered a substance that destroys bacteria in human body- lysozyme. Somewhat later, in 1928, Fleming noticed that mold cultures destroy colonies of pathogenic microbes - streptococci and staphylococci. After this, the researcher began to conduct targeted experiments, but for a long time penicillin remained invisible in scientific circles. The fact is that its discovery and application did not fit into the concept of strengthening the immune system accepted at that time.

Nevertheless, Fleming continued his research, managing to develop not only in the field of science, but also in art. By the way, the specialist’s artistic talent was realized in a very original way. Fleming knew how to draw, and created his works with the help of microbes and bacteria. Every separate species microorganisms have their own color. And so that the colonies of microbes spread within a given framework, without spoiling the overall color scheme, the artist separated them with borders made of penicillin.

Until 1942, Fleming improved the new drug, and finally it began to be used for its intended purpose. At the height of World War II in the United States, the production of penicillin was put on an assembly line, which saved tens of thousands of American and allied soldiers from gangrene and amputation of limbs.

Until 1939, it was not possible to develop an effective culture. In 1941, the first injections of penicillin were made, but due to the small amount of it, the patient could not be saved. But after a few months, the drug was accumulated in sufficient quantities for an effective dose. The first person to be saved with the new antibiotic was a 15-year-old boy with an untreatable blood poisoning.

The value of penicillin in medicine

Subsequently, large enough funds were invested in the production of penicillin to put production on a large scale. The method of producing the antibiotic was improved, and since 1952, relatively cheap penicillin began to be used on an almost global scale. Today, its modifications are widely used to treat serious diseases and infections that previously would most likely have led to inevitable death. It is absolutely no exaggeration to say that in the entire history of mankind there has never been a medicine that would have saved as many lives as penicillin did.

Inventor: Alexander Fleming
A 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 They are not always aware of how much they owe to these medicinal drugs.

Humanity 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 of 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 was fatal, that sepsis was a real scourge of all surgical patients, who died in large numbers from blood poisoning, that typhoid was considered a most dangerous and intractable disease, and pneumonic plague inevitably led the patient to death.

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

Even more striking is the impact of these drugs on military medicine. It’s 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, microbes, among which there are many dangerous pathogens. Under normal conditions, our skin prevents them from penetrating inside. body.

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

The person died not so much from the wound itself, but from wound complications. Medicine was powerless against them. In the best case, the doctor managed to amputate the affected organ and thereby stopped the spread of the disease.

To combat wound complications, it was necessary to learn to paralyze the microbes that cause these complications, to learn to neutralize the cocci that got into the wound. But how to achieve this? It turned out that you can fight microorganisms directly with their help, since some microorganisms, in the course of their life activity, release substances that can destroy 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 the action of certain other microbes. But it is clear that solving this problem required enormous work - it is not easy to understand the life and relationships of microorganisms, it is even more difficult to understand which of them are at enmity with each other and how one microbe defeats another.

However, the hardest thing was to imagine that the formidable enemy of cocci has long been well known to man, that he has been living side by side with him for thousands of years, every now and then reminding you of yourself. It turned out to be ordinary mold - an insignificant fungus that is always present in the air in the form of spores and willingly grows on anything old and damp, be it a cellar wall or a piece of wood.

However, the bactericidal properties of mold were known back in 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 study green molds (penicillium glaucum in Latin). He sowed mold on a nutrient medium and was amazed to note that where the mold grew, bacteria never developed. From this Manassein concluded that mold prevents the growth of microorganisms.

Polotebnov later observed the same thing: the liquid in which mold appeared always remained transparent, therefore, it 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 such an easily accessible substance as mold.

The attempt was successful: the ulcers, covered with an emulsion containing mold, healed quickly. 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.

The remarkable properties of mold were rediscovered half a century later by the Scot Alexander Fleming. From his youth, Fleming dreamed of finding a substance that could destroy pathogenic bacteria, and persistently studied microbiology.

Fleming's laboratory was located in a small room in the pathology department of one of the large London hospitals. This room was always stuffy, cramped and chaotic. 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. Old dishes with cultures of microbial colonies were still on the shelves of the laboratory - Fleming always considered cleaning his room a waste of time.

One day, having decided to write an article about staphylococci, Fleming looked into these cups and discovered that many of the cultures there were covered with mold. This, however, was not surprising - apparently mold spores had been brought into the laboratory through the window. Another thing was surprising: when Fleming began to explore culture, in many There was no trace of staphylococci in the cups - there was only mold and transparent, dew-like drops.

Has ordinary mold really destroyed all pathogenic microbes? Fleming immediately decided to test his guess and placed some mold in a test tube with nutrient broth. When the fungus developed, it settled in the same various bacteria and put it in the thermostat. Having then examined the nutrient medium, Fleming discovered that light and transparent spots had formed between the mold and the colonies of bacteria - the mold seemed to constrain the microbes, preventing them from growing near them.

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 gathered in tight spaces. “Felt” changed its color several times: first it was white, then green, then black. The nutrient broth also changed color - it turned from transparent to yellow.

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

Fleming realized that he was on the verge of an important discovery. He abandoned all his affairs and stopped other research. The mold fungus penicillium notatum is now entirely absorbed his attention. For further experiments, Fleming needed gallons of mold broth - he studied on what day of growth, in what growth medium and on what nutrient medium the action of the mysterious yellow substance would be most effective in destroying 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 a rabbit's vein, abdominal cavity white mouse, washed the skin with broth and even dropped it into the eyes - no unpleasant phenomena were observed. In a test tube, a diluted yellow substance - a product secreted by mold - inhibited the growth of staphylococci, but did not disrupt the functions of blood leukocytes. Fleming called this substance penicillin.

From then on, he constantly thought about an important question: how to isolate the active substance from a filtered mold broth? Alas, it turned out to be extremely complicated matter. Meanwhile, it was clear that introducing an unrefined broth into a person’s blood, which contained a foreign protein, was certainly dangerous.

Fleming's young colleagues, doctors like him, not chemists, made many attempts resolve this problem. Working in makeshift conditions, they spent a lot of time and energy but achieved nothing. Every time after purification, penicillin decomposed and lost its healing properties.

In the end, Fleming realized that this task was beyond his capabilities and that the solution should be left to others. In February 1929, he made a report at the London Medical Research Club about the unusually strong antibacterial agent he had found. This message did not attract 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 theme for collaboration. The difficulty of isolating purified penicillin attracted them. A strain (a culture of microbes isolated from certain sources) sent there by Fleming turned out to be at Oxford University. It was with this that they began to experiment.

To convert penicillin into medicinal product, it had to be combined with some substance soluble in water, but in such a way that, being purified, it would not lose its amazing properties. For a long time, this problem seemed insoluble - penicillin was quickly destroyed in an acidic environment (which is why, by the way, it could not be taken orally) and did not last long in an alkaline environment; it easily went into ether, but if it was not placed on ice, it was destroyed in it too .

Only after many experiments was it possible to filter the liquid secreted by the fungus and containing aminopenicillic acid in a complex way and dissolve it in a special organic solvent in which potassium salts, which are highly soluble in water, were not soluble. After exposure to potassium acetate, white crystals of the potassium salt of penicillin precipitated. After doing 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 proportion of one in a million, had a powerful bactericidal property - deadly cocci placed in this environment died within a few minutes. At the same time, the drug injected into the vein not only did not kill it, but had no effect on the animal at all.

Several other scientists joined Cheyne's experiments. The effect of penicillin was extensively studied on 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 remained alive. The rest died after a few. It was soon discovered that penicillin destroys not only cocci, but also gangrene pathogens.

In 1942, penicillin was tested on a patient who was dying of meningitis. Very soon he recovered. The news of this produced great impression. However, it was not possible to establish production of the new drug in warring England. Flory went to the USA, and here in 1943 in the city of Peoria, Dr. Coghill's laboratory first began industrial production penicillin. In 1945, Fleming, Florey 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 obtained in 1942 by Professor Zinaida Ermolyeva. There was a war going on. Hospitals were overcrowded with wounded people 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, Ermolyeva went to the front to test the effect of her drug. Before the operation, Ermolyeva gave all the wounded an intramuscular injection of penicillin. After this, most fighters’ wounds healed without any complications or suppuration, without fever.

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

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

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.