In our time it is difficult to even imagine that once a banal trauma – a cut, a wound or a burn – could cost a person’s life due to infection and subsequent infection of blood. And such serious diseases as pneumonia, meningitis, tuberculosis or syphilis almost always meant for the patient a death sentence and previous prolonged anguish. Throughout the epidemics of plague, cholera, typhoid and even the flu (“spanish”), whole cities died out: the total number of victims of such outbreaks is estimated at tens and hundreds of thousands.
The history of the development of modern civilization is written in the blood of numerous soldiers who fell on the battlefields. Even now there are pockets of armed confrontation on our planet, and for many centuries before, humanity has been constantly shaking internecine strife and territorial disputes. A minor wound, which does not affect vital organs, still very often caused death, because people did not suspect anything about bacteria and sanitary norms.
Today in every pharmacy you can buy antibiotics of a wide spectrum of action and within a few days to win virtually any infection. But there was such an opportunity relatively recently: some 80 years ago at the disposal of medicine there were only a few effective antiseptics and antibacterial drugs, and now there are hundreds of them. In a short time, pharmaceutical science has made a real breakthrough, but this achievement, strangely enough, has negative consequences.
From our today’s story you will learn the answers to many interesting questions:
- In what year were antibiotics invented?
- From what was the substance with antibacterial properties first isolated?
- >Who introduced the term “antibiotic”, and what was the name of the first such drug?
- The inventor of antibiotics – who is he, and how did he come to his great discovery?
- When was the mass production of antibacterial agents launched?
- What are the pros and cons of inventing new antibiotics?
World to Antibiotics
From the school course of the history of ancient times, we all once learned about the horribly short life expectancy of people. Men and women, miraculously reached the age of thirty, were considered long-livers, but it would be difficult to call them healthy: by this age the skin was covered with numerous defects, teeth rotted and fell out, and the internal organs worked for wear due to poor diet and heavy physical labor.
Infant mortality was on an alarming scale, and the death of women from “maternity fever” was common. It is enough to look at the biography of famous people of the 16th – 19th centuries to see the confirmation of this sad fact: for example, in the family of the great writer and playwright Nikolai Vasilyevich Gogol there were 12 children, including himself: 6 girls and 6 boys. Of these, only 4 sisters survived until adulthood, and the rest of Gogol’s brothers and sisters died either right after birth or as a child from illness. And no wonder, because at the time of the writer’s departure from life, the inventor of antibiotics was not even born yet.
However, at all times people have tried to find a remedy for infectious diseases, even without realizing their infectious nature and the danger of contact with carriers. And what could be the source of medicines, no matter how the gifts of nature? Of herbs, fruits, seeds, roots and fungi, the ancient healers tried to obtain healing medicines from various diseases by experience – more often unsuccessfully, but sometimes they were lucky. The most effective recipes passed from generation to generation, and folk medicine developed. And everything new is, as you know, well forgotten old. Therefore, the true inventor of antibiotics probably lived and healed people for many centuries before the appearance on the modern pharmacy countless countless boxes with tablets.
Ancient History and the Middle Ages
It is known that about two and a half millennia ago, Chinese monasteries used gruel from fermented soybean flour to treat purulent wounds and cuts in warriors who were injured in sword fighting. The meaning of the technique is obvious: the yeast-like microorganisms contained in this improvised “antiseptic” interfered with the reproduction of pyogenic bacteria, and, thus, prevented the infection of blood.
Representatives of another wisest ancient civilization and builders of the pyramids, the Egyptians, also had an inventor of antibiotics in their ranks. True, he did not work with a good purpose – some of the court healers had the idea of tying the ankles of slaves with armbands with moldy bread, damaged by shackles. This allowed to prolong the life of the unfortunate and make them work in the quarries longer.
In medieval Europe, a similar method of treatment of purulent wounds was born: they were treated with cheese whey. The principle of action is the same – yeast against bacteria. Of course, then the doctors did not possess either of these two concepts, but this did not stop them from applying bandages impregnated with serum to the festering wounds received by the soldiers in the fields of the numerous battles between the kingdoms. The person who first came up with this method of treatment, too, can rightly be called the inventor of antibiotics.
New and Newest Time
Just think – only in the early nineteenth century, when humanity was already storming the ocean expanses and designing aircraft, people first realized the infectiousness of infections and introduced the term “bacterium” (in 1828 Christian Ehrenberg). Prior to this, no physician could trace the direct relationship between contamination of wounds, their suppuration and death of patients. In infirmaries, people were bandaged from any accessible matter and did not change them, without seeing any need for it.
And in 1867 the British surgeon D. Lister put an end to this and even found a remedy for fighting purulent infections and postoperative complications. He suggested using carbolic acid for disinfection of wound surfaces, and for a long time this substance was the only hope for salvation for “heavy” patients of surgery. Lister – if not the inventor of antibiotics, then the pioneer of sanitation and antiseptics, for sure.
The dispute in which the scientific discovery was born
The history of the invention of antibiotic from mold fungi began in the 60s of the nineteenth century in Russia. Two scientists, Alexei Polotebnov and Vyacheslav Manassein, argued about the nature of the ancient trouble – mold, the fight with which is very difficult. Polotebnov believed that the mold acts as the original progenitor of all microbes living on Earth. Manassein categorically disagreed with this point of view – he believed that mold has a unique biological structure and is fundamentally different from other microorganisms.
To support his opinion with facts, Manassein began to study green mold and soon discovered that in the immediate vicinity of her strains there was no colony of bacteria. From this scientist concluded that mold prevents microbes from multiplying and feeding. He shared the results of observations with Polotubnov, he acknowledged his wrong and took up the invention of an antiseptic emulsion based on mold. The resulting agent, Manassein’s former opponent, was able to successfully treat skin infections and non-healing wounds.
The result of the joint research work of the two scientists was a scientific article titled “The Pathological Importance of Mold”, which was published in 1872. But, unfortunately, the then international medical community did not pay proper attention to the work of Russian specialists. And they, in turn, did not translate their research into the plane of development of the drug for internal use, and confined themselves to a local antiseptic. If it were not for these circumstances, who knows, maybe the Russian scientist would be the inventor of antibiotics.
The first antibiotics and antiseptics
By the end of the nineteenth century, the problem of the lack of effectiveness of antiseptics became evident. The solutions available at the time of the doctors were unsuitable for the treatment of infections of internal organs, and during the treatment of wounds they penetrated not deep enough into infected tissues. In addition, the effect of antiseptics was weakened by the body’s biological fluids and was accompanied by numerous side effects.
The time of global changes has come, and scientists of the whole civilized world have begun active research in the field of infectious medicine. Before the official opening of the first antibiotic, 50 years remained …
In what century were antibiotics invented?
The very phenomenon of antibiosis, that is, the ability of some living microorganisms to destroy others or deprive them of the ability to reproduce, was discovered in the eighties of the nineteenth century. The famous French biochemist and microbiologist Louis Pasteur, author of the method of pasteurization of food products, in one of his scientific works, published in 1887, described the antagonism of soil bacteria and rods of Koch – the causative agents of tuberculosis.
The next important step in the right direction was the study by the famous Russian scientist Ivan Mechnikov of the action of acidophilic bacteria contained in fermented milk products on the human digestive tract. Mechnikov argued that fermented baked milk, yogurt, yogurt and other similar beverages have a beneficial effect on health and are even capable of fighting intestinal disorders. Later it was confirmed by the outstanding Russian pediatrician of German-French origin Edward Gartye who tried to treat digestive disorders in children with sour-milk products and described the positive results of therapy.
Even closer to the solution came the field doctor Ernest Duchenne from the French city of Lyon. He saw Arab grooms use mold to treat back injuries sustained by horses from the saddle during long journeys. And, the mold was collected directly from this very saddle. Duchenne took her sample, called Penicillium glaucum, applied against typhoid fever in guinea pigs, and also confirmed the destructive effect of mold on Escherichia coli bacteria (Escherichia coli).
The young doctor (he was only 23 years old) wrote a thesis on the basis of studies and sent a document to the Paris Institute of Pasteur, but they did not pay attention to the most important scientific work and did not even notify the author about receiving and reading – apparently, they did not take Ernest Duchene seriously from for a young age and a small experience. And it was this Frenchman who came closest to the fateful discovery and could rightly be called the “inventor of antibiotics”. But the fame came to him after his death, in 1949, four years after he was awarded the Nobel Prize for other people.
Chronology of the invention of antibiotics:
1896 – Mycophenolic acid, which destroys the anthrax, is isolated from the mold Penicillium brevicompactum. The author of the study is B. Gozio;
1899 – invented a local antiseptic on the basis of pyocenosis – a substance derived from the bacteria Pseudomonas pyocyanea. Authors – R. Emmerich and O. Lowe;
1928 – A. Fleming discovered an antibiotic penicillin, but could not develop a stable and suitable for mass production medicine;
1935 – D. Gerhard published in the German scientific journal Deutsche Medizinische Wochenschrift an article on the antibacterial effect of Prontozil, and in 1939 received for this study the Nobel Prize in Physiology or Medicine;
1937 – M. Welsh discovered actinomycin – the first antibiotic streptomycin series;
1939 – NA Krasilnikov and AI Korenyako invented the antibiotic of the mycetin, R. Dubois discovered tyrotricin, and at the pharmaceutical plant “Akrihin” began the production of streptocid;
1940 – EB Chain and G. Flory managed to isolate penicillin in crystalline form and created a stable extract;
1942 – Z. Waxman first introduced the term “antibiotic” into medical use.
So, the era of penicillin began only in 1940, when the American followers of A. Fleming’s works succeeded in obtaining from the mold a stable chemical compound with antibacterial action. But first things first.
The inventor of penicillin Alexander Fleming
This name is known from the school bench to any of us, as it is inscribed in “gold letters” in all the textbooks of biology. We should be grateful to this amazing person – talented, purposeful, stubborn and, at the same time, very simple and modest. Alexander Fleming deserves recognition not only as an inventor of antibiotics, but also as a doctor who is completely devoted to science and understands the true purpose of his profession: charity and selfless help to people.
The boy, who changed the course of history, was born on August 6, 1881, in a large Scottish family at the Lochwild farm. Until the age of twelve, Alexander studied at the school of the city of Darvel, then two years at the Kilmarnock Academy, and then moved to London closer to the older brothers who lived and worked in the capital of Great Britain. There the future inventor of antibiotics worked as a clerk and studied at the Royal Polytechnic Institute. To turn his gaze towards medicine, he spodvig example of his brother, Thomas, received a diploma of an ophthalmologist.
Alexander entered the medical school at St. Mary’s Hospital, and in 1901 he managed to get a scholarship there, leave the work in the office and concentrate entirely on his scientific development. Fleming began with surgery and pathological anatomy, but soon came to the conclusion that he would have been much more interested in studying the nature of diseases and preventing their development than observing the consequences on the operating table. Alec (so his name in the family) was experiencing a great craving for laboratories, microscopes and reagents, so he was re-qualified from a surgeon to a microbiologist.
A huge influence on the establishment of Alexander Fleming, as the inventor of antibiotics and the savior of millions of human lives, was made by Professor Almort Wright, who came to St. Mary’s Hospital in 1902. Wright was already a famous scientist at the time – he developed a vaccine for typhoid fever. On the basis of the hospital, the professor laid out his research and in 1906 created a group of young researchers, which included Alexander Fleming, who just completed the course of study and received a doctorate.
Soon came a big trouble – the First World War. Alec served in the Royal Medical Army of Her Majesty in the rank of captain and simultaneously studied the effects of fragmentation wounds by explosives. At the end of hostilities, the young specialist focused on finding a medicine that could help prevent suppuration and ease the fate of wounded soldiers. All his further life, the inventor of antibiotics Alexander Fleming worked in the research laboratory at St. Mary’s Hospital, where he was elected professor and where he made his main discovery.
The personal life of the scientist was developing quite happily – on December 23, 1915, he married with a young colleague Sarah (who was affectionately called “Sarin”), and soon they had a son, Robert, who later also became a doctor. Sarin spoke of her husband: “Alec is a great man, it’s just that no one yet knows about it.” She died in 1949, and four years later the widowed Fleming married another colleague, a Greek woman of Greek origin, Amalia Kottsuri-Vurekas. But the happiness of the couple did not last long – on March 11, 1955, Sir Alexander Fleming, the inventor of antibiotics, died in the arms of his wife from a heart attack.
It is interesting: In his long and fruitful life (74 years) Fleming made an outstanding Masonic career, was awarded the knighthood, 26 medals, 18 international prizes (including Nobel Prize), 25 scientific degrees, 13 government awards and honorary membership in 89 academies of science in the whole world.
On the grave of the famous scientist flaunts a thanksgiving inscription from all mankind: “Here rests Alexander Fleming – the inventor of penicillin.” His personality is most vividly characterized by the fact that Fleming flatly refused to patent his invention. He believed that he had no right to cash in on the drug trade, which directly affects people’s lives.
The modesty of the scientist is also indicated by the fact that he was skeptical of his fame, calling it simply “the myth of Fleming” and denying the feats attributed to him: for example, there were rumors that with the help of penicillin Sir Alexander saved the British Prime Minister Winston Churchill during World War II war. When Churchill fell ill in Carthage in 1943, he was cured by Lord Moran, who used sulfonamides, as Fleming pointed out in response to journalists’ questions.
Unusual history of penicillin discovery
Many great scientific discoveries are made by pure chance – the circumstances are formed successfully, and there is a person next to him who sees an interesting fact and draws conclusions from it. The inventor of antibiotics Alexander Fleming, like all geniuses, was obsessed with his favorite business, impatient, and yet incredibly scattered. There was a creative disorder in his office, and a thorough washing of the retort and object glasses seemed to him a dull exercise.
Let’s follow the chronology of happy accidents:
The first “accidental” discovery Fleming committed in 1922, when he caught a cold, but did not wear a gauze bandage while working with bacterial crops. He just sneezed into the Petri dish, and after a while was surprised to find that the pathogenic bacteria had died under the action of his saliva. So humanity has learned about lysozyme – the natural antibacterial component of our saliva;
The second and most outstanding “accidental” discovery of Fleming brought him the Nobel Prize. In 1928, the scientist made staphylococcus in a nutrient medium from agar-agar and left for the whole August to rest with his family. During this time, in one of the bacterial colonies, the mold fungus Penicillium notatum, which was entered there negligently, multiplied. On his return from vacation, Fleming was surprised to find that the mold had been fenced off from staphylococci with a transparent liquid, in the drops of which not a single bacterium could survive.
Then the future inventor of antibiotics decided to deliberately grow mold in a large flask with water and observe its behavior. From gray-green mold fungi eventually became black, and the water in which they lived, turned yellow. Fleming came to the conclusion that the mold in the process of life emits certain substances, and checked them in action. It turned out that the received liquid even in concentration 1:20 with water completely destroys all bacteria!
Fleming called his invention penicillin and began to explore its properties more thoroughly. He managed to establish by experiment that the liquid kills only the microflora, but does not damage the tissues of the body, and therefore can be used to treat infections in humans. It only remained to somehow absorb the penicillin from the solution and create a stable chemical compound that can be put into industrial production. But this task was beyond the power of the inventor of antibiotics, because he was a microbiologist, not a chemist.
The way to mass production of the first antibiotic
Long 10 years Fleming fought over the development of the drug, but all experiments were unsuccessful – in any alien environment penicillin was destroyed. In 1939, his research interested two English scientists who settled overseas in the United States. They were Professor Howard Walter Flory and his colleague, biochemist Ernst Boris Cheney (Russian origin). They correctly assessed the prospects of penicillin and moved to Oxford to try to find a stable chemical formula of the drug on the basis of the university laboratory and to make the dream of the inventor of antibiotics Alexander Fleming a reality.
It took two years of painstaking labor to separate the pure substance and clothe it in the form of crystalline salt. When the drug was ready for practical use, Flory and Cheney invited Oxford himself to Fleming, and together the scientists began to test. During the year, it was possible to confirm the effectiveness of penicillin treatment of such diseases as sepsis, gangrene, pneumonia, osteomyelitis, gonorrhea, syphilis.
This is interesting: The correct answer to the question, in what year was the antibiotic penicillin invented – 1941. But the official year for the discovery of penicillin as a chemical is 1928, when it was discovered and described by Alexander Fleming.
The main field of testing for an antibiotic was the Second World War. Because of bitter fighting, it was impossible to establish industrial production of penicillin on the British peninsula, so the first ampoules with saving powder left the conveyor in the United States in 1943. The US government ordered 120 million penicillin units for internal use. From America, the drug was supplied to Europe, and this saved millions of lives. It is difficult to imagine how much the number of victims of this war would have increased, had it not been for the inventor of antibiotics Alexander Fleming and his followers Chain and Flory. Already in the postwar years it was found that penicillin cures even from endocarditis, which until then was a fatal disease in 100% of cases.
Interestingly: In 1945, Alexander Fleming, Ernest Chain and Howard Flory were awarded the Nobel Prize in Medicine and Physiology for the invention of penicillin, the world’s first broad-spectrum antibiotic for internal use.
Significance of the invention of antibiotics
At first glance, the value of this discovery is so obvious that it remains only to put a monument to the inventor of antibiotics and enjoy the fruits of his labors. In the middle of the last century, this opinion prevailed in scientific circles: the medical community was overwhelmed by euphoria from the realization of the opportunities that antibiotics give to mankind. In addition to penicillin, Waksman soon invented streptomycin, active against tuberculous mycobacteria, and it seemed that now there were no obstacles to the complete eradication of epidemics devastating whole cities.
However, even the inventor of antibiotics, Alexander Fleming, foresaw the double effects of using antibacterial drugs and warned of a possible danger. Being a genius microbiologist and understanding the principles of the evolution of living organisms, Fleming was aware of the probability of a gradual adaptation of bacteria to the weapons through which people would try to destroy them. And he did not believe in the complete and unconditional victory of medicine over infections. Unfortunately, the inventor of the first antibiotic was again right …
The positive aspect
The era of antibiotics has changed the world beyond recognition:
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- The average life expectancy in some countries has doubled or tripled;
- Infant mortality decreased by more than 6 times, and the maternal mortality – 8 times;
- The course of treatment for most bacterial infections now takes no more than 21 days;
- None of the previously deadly infectious diseases is now lethal even by 50%;
- Over the past half-century, only a few cases of pandemics (large-scale epidemics) have been reported, with losses estimated at hundreds of people, rather than tens of thousands, as before, before the invention of antibiotics.
But is it possible to say with this that medicine has defeated the infection? Why did they disappear from the face of the Earth in 80 years of antibiotic use?
The Negative Aspect
By the time when the inventor of antibiotics Fleming gave humanity hope in the form of penicillin, science already knew a considerable number of pathogenic and opportunistic microorganisms. As it turned out that some of them are resistant to penicillin, scientists have begun to develop other groups of antibiotics – tetracyclines, cephalosporins, macrolides, aminoglycosides and so on.
There were two ways: either to try to find a remedy against each particular pathogen, or to create a broad spectrum of drugs to be able to treat common infections without recognition and even cope with the diseases of mixed bacterial etiology. Of course, the second way seemed to the scientist wiser, but he led to an unexpected turn.
Under the action of antibiotics, bacteria began to mutate – this mechanism is inherent in nature in any form of life. The new colonies inherited genetic information from the dead “ancestors” and developed mechanisms for protection against bactericidal and bacteriostatic effects of drugs. The treatment of recently responding antibiotic therapies has become ineffective. Scientists invented a new drug, and bacteria – a new weapon. With the widespread and free sale of antibiotics, this process has acquired the character of a vicious circle, which science has not been able to break out to this day. We have created thousands of new kinds of bacteria with our own hands, and we continue to do so.
The problem of resistance
Gene mutations and acquired resistance to antibiotics, which was warned by the inventor of penicillin Alexander Fleming – is the harsh reality of our days. Moreover, nature bypasses man in this “arms race” with ever-increasing speed.
Here are a few examples:
Tetracycline – appeared in 1950, resistant to it bacteria – in 1959;
Methicillin – in 1960, resistant bacteria – in 1962;
Vancomycin – in 1972, resistant bacteria – in 1988;
Daptomycin – in 2003, bacteria – a year later, in 2004.
How is this possible? The fact is that the bacteria multiply very quickly – literally every 20 minutes there is a new colony that inherits genetic information from previous generations. The more often the patient is treated with the same drug, the better it “acquaints” with it its pathogenic flora, and the more likely that the bacteria mutate for reasons of self-protection. And if a person will take antibiotics from different groups uncontrolled, bacteria can grow in his body that are resistant to several or even to all antibacterial drugs! This phenomenon is called multidrug resistance and is a huge threat.
The first such bacteria were discovered as far back as the 60s of the 20th century, that is, only 20 years after the invention of antibiotics and the beginning of their mass use. Further – worse. For example, in 1974, about 2% of cases of staphylococcal infections were resistant to methicillin in the USA, 22% in 1995, and 63% in 2007. And now MRSA (multidrug-resistant staphylococcus) takes 19,000 lives every year in America alone.
The mutation of bacteria, about the possibility of which the inventor of antibiotics Fleming warned himself, has now acquired the character of a catastrophe for three reasons:
People take antibiotics without need and control. Medicine and pharmacy are thoroughly commercialized, doctors prescribe antibacterial drugs, even knowing that they will not help, plus pharmacists dispense such pills without a prescription to all lovers of self-medication;
- New antibiotics are practically not produced. The invention, testing, certification and commercial launch of such drugs costs several million dollars. It is much easier and more advantageous to take the active substance, which already has an internationally patented name, to release it under a different brand, to advertise and begin to paddle money;
- Antibiotics enter our body with food. Suffice it to say that about 80% of the market for antibacterial drugs in the United States is oriented not toward medicine, but to the food industry – with their help, food producers avoid losses from livestock diseases and pest activity affecting fruit and cereals. In Russia, at the local level, the situation is much better, but one can not ignore the flow of cheap imports.
The saddest thing is that humanity itself is to blame for this situation. To remedy it or at least postpone the dangerous consequences, international efforts, general awareness and determination are required. But in fact people are guided only by commercial considerations.
Conclusions and prospects
Is the inventor of antibiotics “put us a pig”, inventing penicillin in the distant 1928? Of course not. But, as is often the case with a formidable weapon that fell into the hands of a man, antibiotics were misused, which led to a new disaster.
Sir Alexander Fleming clearly articulated three main principles for the use of antibiotics:
- Identification of the pathogen and the administration of the drug;
- Selection of a dosage sufficient for complete and final recovery;
- Continuity of treatment and accuracy of admission.
Unfortunately, people often neglect these simple and reasonable rules: they do not pass tests, do not go to the doctor, buy antibiotics in the pharmacy themselves, take them to alleviate unpleasant symptoms and give up therapy halfway. This is the surest way to mutation and acquired resistance – mutilated, but not antibiotic-finished bacteria remember their “offender”, they invent another enzyme, with which they can dissolve its cellular membranes and devour, and transfer the weapon to the next generations. So, multidrug resistance is formed – a new problem of modern infectology, which was foreseen by the inventor of antibiotics Fleming.
Although we can not influence the policy of pharmaceutical and food corporations, we are quite capable of correctly treating our health and the health of our children: try to choose safe foods, take antibiotics only if necessary and strictly according to the doctor’s prescription.