Abstract: The history of the development of microbiology. The history of the development of microbiology and immunology The history of the development of microbiology

Microbiology has come a long way of development, estimated at many millennia. Already in the V.VI millennium BC. a person enjoyed the fruits of the activity of microorganisms, not knowing about their existence. Winemaking, bakery, cheese making, leather dressing. nothing more than processes involving microorganisms. At the same time, in ancient times, scientists and thinkers assumed that many diseases are caused by some kind of invisible extraneous causes that have a living nature.

Consequently, microbiology began long before our era. In its development, it went through several stages, not so much connected chronologically as conditioned by the main achievements and discoveries.

The history of the development of microbiology can be "divided into five stages: heuristic, morphological, physiological, immunological and molecular genetic.

THE HEURISTIC PERIOD (IV III cc. BC. XVI c.) Associated more with the logical and methodological methods of finding the truth, that is, heuristics, than with any experiments and proofs. The thinkers of this period (Hippocrates, the Roman writer Varro, Avicenna, etc.) suggested the nature of infectious diseases, miasms, small invisible animals. These ideas were formulated into a coherent hypothesis many centuries later in the writings of the Italian physician D. Frakastoro (1478-1553), who expressed the idea of ​​living contagia (contagiumvivum), which causes disease. Moreover, each disease is caused by its own contagion. To prevent disease, they were recommended to isolate the patient, quarantine, wear masks, and treat objects with vinegar.

MORPHOLOGICAL PERIOD (XVII FIRST HALF OF XIX centuries) It begins with the discovery of microorganisms by A. Levenguk. At this stage, the ubiquitous distribution of microorganisms was confirmed, the forms of cells, the nature of movement, the habitats of many representatives of the microworld were described. The end of this period is significant in that the knowledge accumulated by this time about microorganisms and the scientific methodological level (in particular, the presence of microscopic technology) allowed scientists to solve three very important (basic) problems for all natural sciences: the study of the nature of fermentation and decay processes, the causes of infectious diseases, the problem of the very origin of microorganisms.

Study of the nature of fermentation and decay processes. The term "fermentation" (fermentatio) to denote all processes occurring with the release of gas was first used by the Dutch alchemist Ya.B. Helmont (1579-1644) Many scientists have tried to define and explain this process. But the closest to understanding the role of yeast in the fermentation process came from the French chemist A.L. Lavoisier (1743 1794) in the study of the quantitative chemical transformations of sugar during alcoholic fermentation, but he did not manage to complete his work, as he became a victim of the terror of the French bourgeois revolution.

Many scientists have studied the fermentation process, but the French botanist C. Canyard de Latour (who investigated the sediment during alcoholic fermentation and discovered living beings), the German naturalists F. Kuetzing ( during the formation of vinegar, drew attention to the mucous membrane on the surface, which also consisted of living organisms) and T. Schwann. But their research was severely criticized by supporters of the theory of the physicochemical nature of fermentation. They were accused of "frivolity of conclusions" and lack of evidence. The second main problem about the microbial nature of infectious diseases was also solved in the morphological period of the development of microbiology.

The first to suggest that diseases are caused by invisible beings were the ancient Greek physician Hippocrates (c. 460 377 BC), Avicenna (c. 980-1037), etc. Despite the fact that the emergence of diseases is now associated with discovered microorganisms, direct evidence was needed. And they were received by a Russian doctor epidemiologist D.S. Samoilovich (1744 1805). Microscopes of that time had a magnification of about 300 times and did not allow detecting the causative agent of the plague, for the detection of which, as is now known, an increase of 800 to 1000 times is required. To prove that the plague is caused by a special pathogen, he infected himself with the discharge of the bubo from a plague-sick person and fell ill with the plague.

Fortunately, D.S. Samoilovich survived. Subsequently, Russian doctors G.N. Minh and O.O. Mochutkovsky, I.I. Mechnikov and others. But the priority in resolving the question of the microbial nature of infectious diseases belongs to the Italian naturalist A. Basi (1773 1856), who was the first to experimentally establish the microbial nature of silkworm disease, he discovered the transmission of the disease when a microscopic fungus was transferred from a sick individual to a healthy one. ... But most researchers were convinced that the causes of all diseases are disruptions in the course of chemical processes in the body. The third problem about the method of emergence and reproduction of microorganisms was solved in a dispute with the then dominant theory of spontaneous generation.

Despite the fact that the Italian scientist L. Spallanzani in the middle of the 18th century. observed under a microscope the division of bacteria, the opinion that they spontaneously arise (arise from rot, dirt, etc.) has not been refuted. This was done by the outstanding French scientist Louis Pasteur (1822 1895), who, with his work, laid the foundation for modern microbiology. In the same period, the development of microbiology began in Russia. The founder of Russian microbiology is L.N. Tsenkovsky (1822 1887). The objects of his research are protozoa, algae, mushrooms. He discovered and described a large number of protozoa, studied their morphology and developmental cycles, showed that there is no sharp border between the world of plants and animals. He organized one of the first Pasteur stations in Russia and proposed a vaccine against anthrax (Tsenkovsky's live vaccine).

PHYSIOLOGICAL PERIOD (SECOND HALF OF THE XIX CENTURY)

The rapid development of microbiology in the 19th century. led to the discovery of many microorganisms: nodule bacteria, nitrifying bacteria, causative agents of many infectious diseases (anthrax, plague, tetanus, diphtheria, cholera, tuberculosis, etc.), tobacco mosaic virus, foot and mouth disease virus, etc. The discovery of new microorganisms was accompanied by the study of not only their structure, but also their vital activity, that is, to replace the morphological-systematic study of the first half of the 19th century. came the physiological study of microorganisms, based on precise experiment.

Therefore, the second half of the XIX century. it is customary to call the physiological period in the development of microbiology. This period is characterized by outstanding discoveries in the field of microbiology, and without exaggeration it could be named after the genius French scientist L. Pasteur Pasteur, because the scientific activity of this scientist covered all the main problems associated with the vital activity of microorganisms. More details about the main scientific discoveries of L. Pasteur and their significance for the protection of human health and human economic activity will be discussed in § 1.3. The first of L. Pasteur's contemporaries who appreciated the significance of his discoveries was the English surgeon J. Lister (1827-1912), who, based on the achievements of L. Pasteur, for the first time introduced the treatment of all surgical instruments with carbolic acid into medical practice. decontamination of operating rooms and achieved a decrease in the number of deaths after operations.

One of the founders of medical microbiology is Robert Koch (1843 - 1910), who developed methods for obtaining pure cultures of bacteria, staining bacteria with microscopy, and photomicrographs. Also known is the Koch triad formulated by R. Koch, which is still used to identify the causative agent of the disease. In 1877 R. Koch isolated the causative agent of anthrax, in 1882 the causative agent of tuberculosis, and in 1905 he was awarded the Nobel Prize for the discovery of the causative agent of cholera. In the physiological period, namely in 1867, M.S. Voronin described nodule bacteria, and almost 20 years later G. Gelrigel and G. Wilfart showed their ability to fix nitrogen. French chemists T. Schlesing, A. Muntz substantiated the microbiological nature of nitrification (1877), and in 1882 P. Degeren established the nature of denitrification, the nature of anaerobic decomposition of plant residues.

Russian scientist P.A. Kostychev created a theory of the microbiological nature of soil formation processes. Finally, in 1892 the Russian botanist D.I.Ivanovsky (1864-1920) discovered the tobacco mosaic virus. In 1898, regardless of D.I. Ivanovsky, the same virus was described by M. Beijerinck. Then the foot and mouth disease virus (F. Leffler, P. Frosch, 1897), yellow fever (W. Reed, 1901) and many other viruses were discovered. However, it became possible to see viral particles only after the invention of the electron microscope, since they are not visible in light microscopes. To date, the kingdom of viruses has up to 1000 disease-causing species. Only recently a number of new DI Ivanovsky viruses have been discovered, including the virus that causes AIDS.

There is no doubt that the period of the discovery of new viruses and bacteria and the study of their morphology and physiology continues to this day. S.N. Vinogradsky (1856 1953) and the Dutch microbiologist M. Beijerinck (1851 1931) introduced the microecological principle of the study of microorganisms. S.N. Vinogradskiy proposed to create specific (elective) conditions enabling the predominant development of one group of microorganisms, discovered in 1893 an anaerobic nitrogen fixer, named after Pasteur Clostridium pasterianum, isolated from the soil microorganisms representing a completely new type of life and called chemolithoautotrophic.

The microecological principle was also developed by M. Beijerinck and applied in the isolation of various groups of microorganisms. 8 years after the discovery of S.N. Vinogradskiy M. Beijerinck isolated Azotobacterchroococcum under aerobic conditions, investigated the physiology of nodule bacteria, denitrification and sulfate reduction processes, etc. Both of these researchers are the founders of the ecological direction of microbiology, associated with the study of the role of microorganisms in the cycle of substances in nature. By the end of the XIX century. differentiation of microbiology into a number of particular areas is outlined: general, medical, soil.

IMMUNOLOGICAL PERIOD (BEGINNING OF THE XX CENTURY) With the beginning of the XX century. begins a new period in microbiology, to which the discoveries of the 19th century led. The works of L. Pasteur on vaccination, I.I. Mechnikov on phagocytosis, P. Ehrlich on the theory of humoral immunity made up the main content of this stage in the development of microbiology, which is rightfully called immunological.

I.I. Metchnikov on how vaccination against many diseases began to be widely used. I.I. Mechnikov showed that the body's defense against pathogenic bacteria is a complex biological reaction, which is based on the ability of phagocytes (macro and microphages) to capture and destroy foreign bodies that have entered the body, including bacteria. Research by I.I. Mechnikov on phagocytosis convincingly proved that, in addition to humoral, there is cellular immunity. I.I. Mechnikov and P. Ehrlich were scientific opponents for many years, each experimentally proving the validity of his theory.

Subsequently, it turned out that there is no contradiction between humoral and phagocytic immunities, since these mechanisms jointly protect the body. And in 1908 I.I. Mechnikov together with P. Ehrlich was awarded the Nobel Prize for the development of the theory of immunity. The immunological period is characterized by the discovery of the main reactions of the immune system to genetically foreign substances (antigens): antibody formation and phagocytosis, delayed-type hypersensitivity (HRT), immediate-type hypersensitivity (HHT), tolerance, and immunological memory.

Microbiology and immunology developed especially rapidly in the 50-60s. twentieth century. This was facilitated by the most important discoveries in the field of molecular biology, genetics, bioorganic chemistry; the emergence of new sciences: genetic engineering, molecular biology, biotechnology, informatics; creation of new methods and the use of scientific equipment. Immunology is the basis for the development of laboratory methods for the diagnosis, prevention and treatment of infectious and many non-infectious diseases, as well as the development of immunobiological drugs (vaccines, immunoglobulins, immunomodulators, allergens, diagnostic drugs). The development and production of immunobiological preparations is engaged in immunobiotechnology, an independent section of immunology.

Modern medical microbiology and immunology have made great strides and play a huge role in the diagnosis, prevention and treatment of infectious and many non-infectious diseases associated with impaired immune system (oncological, autoimmune diseases, organ and tissue transplantation, etc.).

MOLECULAR GENETIC PERIOD (since the 50s of the twentieth century) It is characterized by a number of fundamentally important scientific achievements and discoveries: 1. Deciphering the molecular structure and molecular biological organization of many viruses and bacteria; the discovery of the simplest life forms of the "infectious" prion protein. 2. Deciphering the chemical structure and chemical synthesis of some antigens.

For example, chemical synthesis of lysozyme (D. Sela, 1971), peptides of the AIDS virus (R.V. Petrov, V.T. Ivanov, etc.). 3. Deciphering the structure of antibodiesimmunoglobulins (D. Edelman, R. Porter, 1959). 4. Development of a method for cultures of animal and plant cells and their cultivation on an industrial scale in order to obtain viral antigens. 5. Obtaining recombinant bacteria and recombinant viruses. 6. Creation of hybridomas by fusion of immune B lymphocytes of antibody producers and cancer cells in order to obtain monoclonal antibodies (D. Keller, C. Milstein, 1975). 7. Discovery of immunomodulators of immunocytokinins (interleukins, interferons, myelopeptides, etc.) of endogenous natural regulators of the immune system and their use for the prevention and treatment of various diseases. 8. Obtaining vaccines using biotechnology and genetic engineering techniques (hepatitis B, malaria, HIV antigens and other antigens) and biologically active peptides (interferons, interleukins, growth factors, etc.). 9. Development of synthetic vaccines based on natural or synthetic antigens and their fragments. 10. Discovery of viruses that cause immunodeficiency. 11. Development of fundamentally new methods for the diagnosis of infectious and non-infectious diseases (enzyme immunoassay, radioimmunoassay, immunoblotting, nucleic acid hybridization).

Creation on the basis of these methods of test systems for indication, identification of microorganisms, diagnostics of infectious and non-infectious diseases. In the second half of the twentieth century. the formation of new directions in microbiology continues, new disciplines are spun off from it with their own research objects (virology, mycology), areas that differ in research objectives (general microbiology, technical, agricultural, medical microbiology, genetics of microorganisms, etc.) are distinguished. Many forms of microorganisms have been studied and by about the middle of the 50s. last century A. Kluyver (1888 1956) and K. Niel (1897 1985) formulated the theory of the biochemical unity of life

Wasserman reaction (RW or EDS-Express Diagnosis of Syphilis) is an outdated method for diagnosing syphilis using a serological test. Currently replaced by precipitation microreaction ( anticardiolipin test, MP, RPR- RapidPlasmaReagin). It is named after the German immunologist August Wassermann, who proposed a technique for carrying out this reaction. In clinical practice, often all methods for diagnosing syphilis are called RW or Wasserman's reaction, although this technique has not been used in laboratory diagnostics in Russia since the end of the 20th century. The advantage of the reaction is the simplicity of its implementation, the disadvantage is its low specificity, which leads to false positive results.

Wasserman's reaction is based on the property of the blood serum of patients with syphilis to form a complex with the corresponding antigen, adsorbing complement - a part of normal serum; the antigen is the erythrocytes of sheep blood, the antibody is human serum. If, when adding hemolytic serum, dissolution of erythrocytes (hemolysis) does not occur, the Wasserman reaction is considered positive (there is syphilis), when hemolysis appears, the Wasserman reaction is negative (there is no syphilis). With primary syphilis, the Wasserman reaction becomes positive at 6-8 weeks of the course of the disease (in 90% of cases), with secondary syphilis, it is positive in 98-100% of cases. Together with other serological reactions (RPHA, ELISA, RIF), it allows not only to identify the presence of the pathogen, but also to find out the approximate time of infection. According to this reaction (in addition to examining the patient and other laboratory tests), the effectiveness of the treatment is assessed, it makes it possible to establish the disease of syphilis in the absence of its clinical manifestations; it serves as a criterion for the effectiveness of treatment. A blood test for Wasserman's reaction is necessarily carried out in pregnant women to prevent congenital syphilis in children, donors, etc., they are put before the deregistration of patients with syphilis and when they are issued a marriage license.

A positive Wasserman reaction can also be observed in some diseases of non-syphilitic origin (leprosy, malaria, typhus, relapsing and typhoid fever, smallpox, scarlet fever, influenza, measles, brucellosis, viral pneumonia, infectious mononucleosis, etc.), as well as in some physiological conditions (during menstruation, in the second half of pregnancy in 2% of pregnant women), when taking medications orally - false positive reactions. Therefore, in case of doubt, a re-examination is necessary.

Microbes appeared on our planet earlier than animals and humans. It has been proven that pathogenic microbes existed in ancient times. This is evidenced by the detection of antigens of pathogenic bacteria, for example, the causative agent of the plague, in the remains of ancient burials (mummies). Even before the discovery of microbes, people had guessed about the existence of external factors that cause disease. Therefore, we can say that microbiology arose even before our era and went a long way of development. In accordance with the level of knowledge about microbes, with the advent of new discoveries and methods, as well as the formation of new directions, the history of microbiology can be divided into five periods: 1) heuristic; 2) morphological; 3) physiological; 4) immunological; 5) molecular genetic.

Heuristic period

This period begins from the moment when Hippocrates (III-IV centuries BC) made a guess (heuristic - guess) that diseases transmitted from person to person are caused by invisible, inanimate substances. He called these substances "miasms". It must be said that in ancient times, not knowing about the existence of microbes, people used the fruits of the activity of microbes - winemaking, brewing, baking bread, etc.

Only in the 15th - 16th centuries. the Italian physician and poet Geralimo Fracastoro (1476 - 1553) substantiated the opinion that diseases are caused by "living contagions", which transmit diseases through the air or through objects, that these creatures live in the environment and to fight diseases, isolation of the patient is necessary, destruction contagium, etc. By the way, Fracastoro for these works is considered the founder of epidemiology.

Thus, over two millennia, scientists have gone from guesswork and assumptions to the conviction that human diseases are caused by some invisible living creatures.

Morphological period

This period begins in the late 17th - early 18th centuries, when the Dutch naturalist Anthony van Leeuwenhoek (1632 - 1723) discovered bacteria. The microscope created by him magnified objects 150 - 300 times. Examining everything (water, blood, dental plaque, etc.), Leeuwenhoek found many living "animals", which he called "animalculus". Systematically sketching and describing, he sent letters to the Royal Society of Science in London. These letters were published in scientific journals, and then, in 1695, a book was published entitled "Secrets of Nature, Discovery of Anthony van Leeuwenhoek with a Microscope." Thus, Levenguk marked the beginning of a morphological period that continues to this day. The first Russian to see the microbes was Peter the Great, who visited Levenguk in Holland; he also brought the microscope to Russia, and the first researcher was the doctor M.M. Terekhovsky (1740 - 0796).



After the discovery of Levenguk, the triumphant march of microbiology began. New bacteria, fungi, protozoa were discovered, and at the end of the 19th century. viruses were discovered. To prove the etiological role of microbes in human pathology, animal studies and experiments on self-infection were carried out. It should be noted the bold experiments of the Russian epidemiologist Danila Samoilovich (1724 - 1810), who infected himself with the bubo discharge from a plague patient. Historically, a number of experiments on self-infection with materials or cultures of pathogens taken from a patient with cholera (Petenhofer, I.I. Mechnikov, D.K. Zabolotny, N.F. Gamaleya), typhus (G.N. P. Smirnov), poliomyelitis virus (M.N. Chumakov) and others.

End of the 19th century was marked by the discovery of viruses. In 1892, the Russian botanist D.I. Ivanovsky (1864 - 1920) discovered the kingdom of viruses in the study of tobacco mosaic disease. Then many viruses were discovered that infect humans, animals, plants and bacteria. In the first half of the XX century. an independent discipline was formed - virology, and in 1992 the whole world celebrated the 100th anniversary of the discovery of viruses by D.I. Ivanovsky.

The discovery and emergence of new types of microbes, as well as a change in the pathogenic properties of already known microbes is quite natural, since, on the one hand, the methods of microbiology are being improved, and on the other, representatives of the microworld evolve with the general laws of biology and genetics. In the last 20 - 30 years alone, more than three dozen new and modified variants of known microbes have been discovered. All of them are combined into a group of dangerous unpredictable infections.

In the future, a person also expects the emergence of new or changed pathogens of infectious diseases. An example is the increasing role of T-cell leukemia viruses, hepatitis viruses, prions, etc. in human pathology.

Physiological period

Since the discovery of microbes, naturally, the question arose not only about their role in human pathology, but also about the structure, biological properties, vital processes, ecology, etc.

Therefore, from the middle of the 19th century, an intensive study of the physiology of bacteria began. This period, which began from the 19th century and continues to this day, was conventionally called the physiological period in the development of microbiology.

An important role in this period was played by the works of the outstanding French scientist Louis Pasteur (1822 - 1895). Being a chemist by education, possessing a wide erudition, talent of an experimenter and the wisdom of an organizer of science, L. Pasteur made a number of fundamental fundamental discoveries in many fields of science, which allowed him to become the founder of a number of sciences: microbiology, biotechnology, disinfectology, stereochemistry.

L. Pasteur discovered:

1. The nature of fermentation;

2. Anaerobiosis;

3. Refuted the theory of spontaneous generation;

4. Justified the principle of sterilization;

5. Developed the principle of vaccination and methods of obtaining vaccines.

At the age of 26, L. Pasteur defended his doctoral dissertation "On arsenic compounds of potassium, sodium and ammonia", in which he proved that when growing mushrooms, only certain stereoisomers are assimilated. Thus, L. Pasteur became the founder of stereochemistry.

Before Pasteur, Liebig's chemical theory of fermentation prevailed. Pasteur made a discovery, proving that fermentation (lactic acid, alcoholic, acetic) is a biological phenomenon that is caused by microbes and their enzymes, i.e. Pasteur became the founder of biotechnology.

Before Pasteur, there was a theory of spontaneous generation of all living things, i.e. it was believed that animals not only descended from each other, but also arise spontaneously (frogs are born from silt, etc.). Thus, microbes were also generated. Pasteur refuted this proposition with his own experiments. He proved that if sterile broth is left in an open flask, it will germinate, but if sterile broth is placed in a flask that communicates with air through a spiral glass tube, then the broth will not germinate, since bacteria with dust particles from the air will settle on the curved parts of the spiral tube and will not get into the broth.

Pasteur also proved that some bacteria not only do not carry oxygen, but live and multiply only in an oxygen-free environment. Thus, the phenomenon of anaerobiosis was discovered, and a group of microbes was called anaerobes.

Proof of the role of microbes in enzymatic processes led Pasteur to solve a number of practical problems, in particular to the development of a way to fight diseases of wine by heating it at 50-60 ° C in order to destroy bacteria. This method, later called pasteurization, is widely used today in the food industry.

A significant contribution to the development of microbiology during this period was made by the German bacteriologist Robert Koch (1843 - 1910), who proposed the coloring of bacteria, microphotography, a method for obtaining pure cultures, as well as the famous Henle-Koch triad to establish the etiological role of microbes in infectious diseases. According to the triad, three conditions are necessary to prove the role of microbes in the occurrence of a specific disease:

1. That the microbe is found only in the patient and not found in healthy people and patients with other diseases;

2. A pure culture of the microbe must be obtained;

3. The microbe must cause a similar disease if it infects animals.

These principles were put forward by Henle before Koch, Koch formulated and developed them. Nowadays, this triad is of relative importance, since it is sometimes difficult to reproduce a disease in animals (for example, HIV infection) and often the pathogen is found in healthy individuals (carrier).

Thus, the study of the biological and physiological properties of microorganisms from the end of the XIX century. and throughout the XX century. led to the knowledge of the deep processes of the vital activity of bacteria, viruses and protozoa.

Immunological period

This period in the development of microbiology is associated primarily with the names of the French scientist L. Pasteur, the Russian biologist I.I. Mechnikov (1843 - 1916) and the German chemist Paul Ehrlich (1854 - 1915). These scientists can rightfully be called the founders of immunology.

L. Pasteur discovered and developed the principle of vaccination, I.I. Mechnikov - the phagocytic theory, P. Ehrlich expressed a hypothesis about antibodies and developed the humoral theory of immunity.

It should be noted that more than 200 years ago, the English physician Edward Jenner (1749 - 1823) found a way to create immunity to the smallpox pathogen by inoculating a person with the vaccinia virus. It was the greatest discovery, but it was empirical. And only L. Pasteur scientifically substantiated the principle of vaccination, the method of obtaining vaccines and extended it to many countries. In the summer of 1886, the works created by I.I. Mechnikov and his talented student N.F. Gamaley's first Pasteur stations.

Grateful humanity for the discoveries made using funds raised by international subscription, in 1888 built the Pasteur Institute in Paris, which is still operating today. At the Pasteur Institute, such scientists worked as alei, the first Pasteur pupil N.I. M. Bezredka (proposed a method of desensitization), J. Bordet (immunochemist), G. Ramon (developed a method for producing toxoids) and many others.

A huge contribution was made by I.I. Mechnikov, who received the Nobel Prize in 1908 for the development of the theory of phagocytosis. In addition, I.I. Mechnikov was fond of aging processes, the role of normal human microflora, he is rightfully considered the ancestor of gerontology and the doctrine of dysbacteriosis. Opponent I.I. Mechnikov, P. Ehrlich for the humoral theory of immunity was also awarded the Nobel Prize in 1908.

In 1900, R. Koch discovered delayed-type hypersensitivity, in 1902 - 1905. C. Richet, J. Porter, G.P. Sakharov described immediate-type hypersensitivity; in the 1950s, antigen tolerance was discovered (P. Medovar, M. Hasek), immunological memory (F. Burnet). At the same time, the structure of immunoglobulins (R. Porter and E. Edelman) was studied, interferon (A. Isaacs and J. Lindemann) and other immunomodulators were discovered. In addition, numerous studies have been devoted to the study of lymphocytes and their role in immunity, cooperative cell interactions, etc.

Immunology in the middle of the XX century took shape as an independent science with goals, objectives, structure and classification.

Molecular genetic period

The development of molecular biology, genetics, genetic and protein engineering and other sciences in the second half of the 20th century gave impetus to the development of molecular and genetic aspects of microbiology.

During this period, the molecular structure of bacteria and viruses, the structure and composition of their genome, pathogenicity factors and factors of immune defense were deciphered.

Deciphering the genes of bacteria and viruses, their synthesis made it possible to artificially create recombinant DNA and obtain on their basis recombinant strains of microorganisms, which are widely used to obtain biologically active substances (hormones, drugs, food proteins, sugars, etc.). Genetic engineering has made it possible to obtain vaccine and diagnostic preparations (vaccine against hepatitis B, monoclonal antibodies, etc.).

Immunogenetics is being developed, the purpose of which is gene prophylaxis and gene therapy of immunodeficiencies. Genodiagnostics (polymerase chain reaction) is widely used in microbiology.

Great successes have been achieved in the study of the histocompatibility system, which has solved the problems in transplantology during organ and tissue transplantation, the problem of incompatibility between mother and fetus in obstetrics and gynecology.

Chemotherapy and antibiotic therapy of infectious diseases have undergone evolution. A huge number of antiviral and antibacterial drugs have been created.

Thus, advances in microbiology and immunology not only ensured success in the fight against infectious diseases, but also opened up new ways and methods for the diagnosis and treatment of non-infectious diseases.

The stages of development of microbiology are related not so much chronologically as are conditioned by the main achievements and discoveries; therefore, many researchers distinguish different periods, but most often the following: heuristic, morphological, physiological, immunological, and molecular genetic.

HEURISTIC PERIOD (IV III centuries BC XVI century)

It is associated rather with logical and methodological methods of finding the truth, that is, heuristics, than with any experiments and proofs. The thinkers of this period (Hippocrates, the Roman writer Varro, Avicenna, etc.) suggested the nature of infectious diseases, miasms, small invisible animals. These ideas were formulated into a coherent hypothesis many centuries later in the writings of the Italian physician D. Frakastoro (1478-1553), who expressed the idea of ​​living contagion (contagium vivum), which causes disease. Moreover, each disease is caused by its own contagion. To prevent disease, they were recommended to isolate the patient, quarantine, wear masks, and treat objects with vinegar.

MORPHOLOGICAL PERIOD (XVII FIRST HALF OF XIX centuries)

It begins with the discovery of microorganisms by A. Levenguk. At this stage, the ubiquitous distribution of microorganisms was confirmed, the forms of cells, the nature of movement, and the habitats of many representatives of the microworld were described. The end of this period is significant in that the knowledge about microorganisms accumulated by that time and the scientific methodological level (in particular, the presence of microscopic technology) allowed scientists to solve three very important (basic) problems for all natural sciences: the study of the nature of fermentation and decay processes, causes of infectious diseases, the problem of the very origin of microorganisms.

Study of the nature of fermentation and decay processes. The term “fermentation” (fermentatio) was first used by the Dutch alchemist Ya.B. Helmont (1579

1644). Many scientists have tried to define and explain this process. But the closest to understanding the role of yeast in the fermentation process came from the French chemist A.L. Lavoisier (1743 1794) in the study of the quantitative chemical transformations of sugar during alcoholic fermentation, but he did not manage to complete his work, as he became a victim of the terror of the French bourgeois revolution. Many scientists studied the fermentation process, but the French botanist C. Canyard de Latour (he studied the sediment during alcoholic fermentation and discovered living creatures), the German naturalists F Kützing (during the formation of vinegar, he drew attention to the mucous membrane on the surface, which also consisted of living organisms) and T. Schwann. But their research was severely criticized by supporters of the theory of the physicochemical nature of fermentation. They were accused of being “frivolous in conclusions” and lacking evidence.

The second main problem about the microbial nature of infectious diseases was also solved in the morphological period of the development of microbiology. The first to suggest that diseases are caused by invisible creatures were the ancient Greek physician Hippocrates (c. 460 377 BC), Avicenna (c. 980-1037), etc. Despite the fact that the emergence of diseases is now was already associated with open microorganisms, direct evidence was needed. And they were obtained by the Russian doctor epidemiologist D.S. Samoilovich (1744 1805). Microscopes of that time had a magnification of about 300 times and did not allow detecting the causative agent of the plague, for the detection of which, as is now known, an increase of 800 to 1000 times is required. To prove that the plague is caused by a special pathogen, he infected himself with the discharge of the bubo from a person sick with plague and fell ill with the plague. Fortunately, D.S. Samoilovich survived. Subsequently, Russian doctors G.N. Minh and O.O. Mochutkovsky, I.I. Mechnikov and others. But the priority in solving the problem of the microbial nature of infectious diseases belongs to the Italian naturalist A. Basi (1773 - 1856), who was the first to experimentally establish the microbial nature of the silkworm disease, he discovered the transmission of the disease during the transfer of a microscopic fungus from a sick individual to healthy. But the majority of researchers were convinced that the causes of all diseases are disturbances in the course of chemical processes in the body.

The third problem about the mode of emergence and reproduction of microorganisms was resolved in a dispute with the then dominant theory of spontaneous birth. Despite the fact that the Italian scientist L. Spallanzani in the middle of the 18th century. observed under a microscope the division of bacteria, the opinion that they spontaneously arise (arise from rot, dirt, etc.) has not been refuted. This was done by the outstanding French scientist Louis Pasteur (1822 1895), who, with his work, laid the foundation for modern microbiology.

In the same period, the development of microbiology began in Russia. The founder of Russian microbiology is L.N. Tsenkovsky (1822 1887). The objects of his research are protozoa, algae, mushrooms. He discovered and described a large number of protozoa, studied their morphology and developmental cycles, showed that there is no sharp border between the world of plants and animals. He organized one of the first Pasteur stations in Russia and proposed a vaccine against anthrax (Tsenkovsky's live vaccine).

PHYSIOLOGICAL PERIOD (SECOND HALF of the 19th century) The rapid development of microbiology in the 19th century. led to the discovery of many microorganisms: nodule bacteria, nitrifying bacteria, causative agents of many infectious diseases (anthrax, plague, tetanus, diphtheria, cholera, tuberculosis, etc.), tobacco mosaic virus, foot and mouth disease virus, etc. The discovery of new microorganisms was accompanied by the study of not only their structure, but also their vital activity, that is, to replace the morphological-systematic study of the first half of the 19th century. came the physiological study of microorganisms, based on precise experiment. Therefore, the second half of the XIX century. it is customary to call the physiological period in the development of microbiology.

This period is characterized by outstanding discoveries in the field of microbiology, and without exaggeration it could be named after the genius French scientist L. Pasteur Pasteur, because the scientific activity of this scientist covered all the main problems associated with the vital activity of microorganisms. More details about the main scientific discoveries of L. Pasteur and their significance for the protection of human health and human economic activity will be discussed in § 1.3.

The first of L. Pasteur's contemporaries who appreciated the significance of his discoveries was the English surgeon J. Lister (1827-1912), who, based on the achievements of L. Pasteur, for the first time introduced the treatment of all surgical instruments with carbolic acid into medical practice. decontamination of operating rooms and achieved a decrease in the number of deaths after operations.

One of the founders of medical microbiology is Robert Koch (1843

1910), who was responsible for the development of methods for obtaining pure cultures of bacteria, staining bacteria with microscopy, and micrographs. Also known is the Koch triad formulated by R. Koh, which is still used to identify the causative agent of the disease. In 1877, R. Koch isolated the causative agent of anthrax, in 1882 the causative agent of tuberculosis, and in 1905 he was awarded the Nobel Prize for the discovery of the causative agent of cholera by R. Koch.

In the physiological period, namely in 1867, M.S. Voronin described nodule bacteria, and almost 20 years later G. Gelrigel and G. Wilfart showed their ability to fix nitrogen. French chemists T. Schlesing and A. Muntz substantiated the microbiological nature of nitrification (1877), and in 1882 P. Degeren established the nature of denitrification, the nature of anaerobic decomposition of plant residues. Russian scientist P.A. Kostychev created a theory of the microbiological nature of soil formation processes.

Finally, in 1892 the Russian botanist D.I.Ivanovsky (1864-1920) discovered the tobacco mosaic virus. In 1898, regardless of D.I. Ivanovsky, the same virus was described by M. Beijerinck. Then the foot and mouth disease virus (F. Leffler, P. Frosch, 1897), yellow fever (W. Reed, 1901) and many other viruses were discovered. However, it became possible to see viral particles only after the invention of the electron microscope, since they are not visible in light microscopes. To date, the kingdom of viruses has up to 1000 disease-causing species. Only recently a number of new DI Ivanovsky viruses have been discovered, including the virus that causes AIDS. There is no doubt that the period of the discovery of new viruses and bacteria and the study of their morphology and physiology continues to this day.

S.N. Vinogradskiy (1856–1953) and the Dutch microbiologist M. Beijerink (1851–1931) introduced the microecological principle of the study of microorganisms. S.N. Vinogradskiy proposed to create specific (elective) conditions allowing the predominant development of one group of microorganisms, discovered in 1893 an anaerobic nitrogen fixer, named after Pasteur Clostridium pasterianum, isolated microorganisms from the soil that represent a completely new type of life and are called chemolithoautotrophic ...

The microecological principle was also developed by M. Beijerinck and applied in the isolation of various groups of microorganisms. Eight years after the discovery of S.N. Vinogradskii, M. Beijerinck isolated Azotobacter chroococcum under aerobic conditions, studied the physiology of nodule bacteria, denitrification and sulfate reduction processes, etc. Both of these researchers are the founders of the ecological direction of microbiology, associated with the study of the role of microorganisms in the cycle of substances in nature.

By the end of the XIX century. differentiation of microbiology into a number of particular areas is outlined: general, medical, soil.

IMMUNOLOGICAL PERIOD (BEGINNING OF THE XX CENTURY)

With the onset of the twentieth century. begins a new period in microbiology, to which the discoveries of the 19th century led.

The works of L. Pasteur on vaccination, I.I. Mechnikov on phagocytosis, P. Ehrlich on the theory of humoral immunity made up the main content of this stage in the development of microbiology, which rightfully received the title of immunological.

Paul Ehrlich (1854 - 1915) German physician, bacteriologist and biochemist, one of the founders of immunology and chemotherapy, who put forward the humoral (from the Latin humor liquid) theory of immunity. He believed that immunity arises as a result of the formation of antibodies in the blood that neutralize the poison. This was confirmed by the discovery of anti-toxin antibodies that neutralize toxins in animals that were injected with diphtheria or tetanus toxin (E. Bering, S. Kitazato).

In 1883 he formulated the phagocytic theory of immunity. Human immunity to reinfection has been known for a long time, but the nature of this phenomenon was incomprehensible even after

I.I. Metchnikov on how vaccination against many diseases began to be widely used. I.I. Mechnikov showed that the defense of the body against the disease of creative bacteria is a complex biological reaction, which is based on the ability of phagocytes (macro and microphages) to capture and destroy foreign bodies that have entered the body, including bacteria. Research by I.I. Mechnikov on phagocytosis convincingly proved that, in addition to humoral, there is cellular immunity.

I.I. Mechnikov and P. Ehrlich were scientific opponents for many years, each experimentally proving the validity of his theory. Subsequently, it turned out that there is no contradiction between humoral and phagocytic immunities, since these mechanisms carry out the protection of the organism jointly. And in 1908 I.I. Mechnikov together with P. Ehrlich was awarded the Nobel Prize for the development of the theory of immunity.

The immunological period is characterized by the discovery of the main reactions of the immune system to genetically foreign substances (antigens): antibody formation and phagocytosis, delayed type hypersensitivity (HRT), immediate type hypersensitivity (HHT), tolerance, and immunological memory.

Microbiology and immunology developed especially rapidly in the 50-60s. twentieth century. This was facilitated by the most important discoveries in the field of molecular biology, genetics, and bioorganic chemistry; the emergence of new sciences: genetic engineering, molecular biology, biotechnology, informatics; the creation of new methods and the use of scientific equipment.

Immunology is the basis for the development of laboratory methods for the diagnosis, prevention, and treatment of infectious and many non-infectious diseases, as well as the development of immunobiological drugs (vaccines, immunoglobulins, immunomodulators, allergens, diagnostic drugs). The development and production of immunobiological preparations is engaged in immunobiotechnology, an independent section of immunology. Modern medical microbiology and immunology have achieved great success and play a huge role in the diagnosis, prevention, and treatment of infectious and many non-infectious diseases associated with impaired immune system (oncological, autoimmune diseases, organ and tissue transplantation, etc.).

MOLECULAR-GENETIC PERIOD (from the 50s of the twentieth century)

It is characterized by a number of fundamentally important scientific achievements and discoveries:

1. Deciphering the molecular structure and molecular biological organization of many viruses and bacteria; discovery of the simplest life forms of the “infectious” prion protein.

2. Deciphering the chemical structure and chemical synthesis of some antigens. For example, chemical synthesis of lysozyme (D. Sela, 1971), peptides of the AIDS virus (R.V. Petrov, V.T. Ivanov, etc.).

3. Deciphering the structure of antibodiesimmunoglobulins (D. Edelman, R. Porter, 1959).

4. Development of a method for cultures of animal and plant cells and their cultivation on an industrial scale in order to obtain viral antigens.

5. Obtaining recombinant bacteria and recombinant viruses.

6. Creation of hybridomas by fusion of immune B lymphocytes of antibody producers and cancer cells in order to obtain monoclonal antibodies (D. Keller, C. Milstein, 1975).

7. Discovery of immunomodulators of immunocytokinins (interleukins, interferons, myelopeptides, etc.) of endogenous natural regulators of the immune system and their use for the prevention and treatment of various diseases.

8. Obtaining vaccines using biotechnology and genetic engineering techniques (hepatitis B, malaria, HIV antigens and other antigens) and biologically active peptides (interferons, interleukins, growth factors, etc.).

9. Development of synthetic vaccines based on natural or synthetic antigens and their fragments.

10. Discovery of viruses that cause immunodeficiency.

11. Development of fundamentally new methods for the diagnosis of infectious and non-infectious diseases (enzyme immunoassay, radioimmunoassay, immunoblotting, nucleic acid hybridization). Creation on the basis of these methods of test systems for indication, identification of microorganisms, diagnostics of infectious and non-infectious diseases.

In the second half of the twentieth century. the formation of new directions in microbiology continues, new disciplines are spun off from it with their own research objects (virology, mycology), directions are distinguished that differ in research tasks (general microbiology, technical, agricultural, medical microbiology, genetics of microorganisms, etc.) ... Many forms of microorganisms have been studied, and by about the middle of the 50s. last century A. Kluyver (1888

1956) and K. Niehl (1897 1985) the theory of the biochemical unity of life was formulated.

Introduction

Microbiology(from the Greek micros - small, bios - life, logos - teaching) -science that studies the structure, vital activity and ecology of microorganisms of the smallest life forms of plant or animal origin, invisible to the naked eye.

Microbiology studiesall representatives of the microworld (bacteria, fungi, protozoa, viruses). At its core, microbiology is a biological fundamental science. To study microorganisms, she uses the methods of other sciences, primarily physics, biology, bioorganic chemistry, molecular biology, genetics, cytology, immunology. Like any science, microbiology is divided into general and specific. General microbiology studies the patterns of the structure and life of microorganisms at all levels. molecular, cellular, population; genetics and their relationship with the environment. The subject of study of private microbiology is individual representatives of the microworld, depending on their manifestation and their influence on the environment, living nature, including humans. Private sections of microbiology include: medical, veterinary, agricultural, technical (biotechnology section), marine, space microbiology.

Medical microbiologystudies pathogenic microorganisms for humans: bacteria, viruses, fungi, protozoa. Depending on the nature of the studied pathogenic microorganisms, medical microbiology is divided into bacteriology, virology, mycology, and protozoology.

Each of these disciplines addresses the following issues:

morphology and physiology, i.e. carries out microscopic and other types of research, studies metabolism, nutrition, respiration, growth and reproduction conditions, genetic characteristics of pathogenic microorganisms;

the role of microorganisms in the etiology and pathogenesis of infectious diseases;

main clinical manifestations and prevalence of caused diseases;

specific diagnostics, prevention and treatment of infectious diseases;

ecology of pathogenic microorganisms.

Medical microbiology also includes sanitary, clinical and pharmaceutical microbiology.

Sanitary microbiologystudies the microflora of the environment, the relationship of microflora with the body, the effect of microflora and its waste products on human health, develops measures to prevent the adverse effects of microorganisms on humans. The focus of clinical microbiology. The role of opportunistic microorganisms in the occurrence of human diseases, diagnosis and prevention of these diseases.

Pharmaceutical microbiologyinvestigates infectious diseases of medicinal plants, damage to medicinal plants and raw materials under the influence of microorganisms, contamination of medicinal products during preparation, as well as finished dosage forms, methods of asepsis and antiseptics, disinfection in the production of medicinal products, technology for obtaining microbiological and immunological diagnostic, prophylactic and therapeutic preparations ...

Veterinary microbiologystudies the same issues as medical microbiology, but in relation to microorganisms that cause diseases in animals.

Microflora of soil, flora, its influence on fertility, soil composition, infectious diseases of plants, etc. are the focus of agricultural microbiology.

Marine and space microbiologystudies, respectively, the microflora of seas and reservoirs and outer space and other planets.

Technical Microbiology,being a part of biotechnology, it develops a technology for obtaining various products from microorganisms for the national economy and medicine (antibiotics, vaccines, enzymes, proteins, vitamins). The basis of modern biotechnology is genetic engineering.

The history of the development of microbiology

Microbiology has come a long way of development, estimated at many millennia. Already in the V.VI millennium BC. a person enjoyed the fruits of the activity of microorganisms, not knowing about their existence. Winemaking, bakery, cheese making, leather dressing. nothing more than processes involving microorganisms. At the same time, in ancient times, scientists and thinkers assumed that many diseases are caused by some kind of invisible extraneous causes that have a living nature.

Consequently, microbiology began long before our era. In its development, it went through several stages, not so much connected chronologically as conditioned by the main achievements and discoveries.

THE HEURISTIC PERIOD (IV III cc. BC. XVI c.) Associated more with the logical and methodological methods of finding the truth, that is, heuristics, than with any experiments and proofs. The thinkers of this period (Hippocrates, the Roman writer Varro, Avicenna, etc.) suggested the nature of infectious diseases, miasms, small invisible animals. These ideas were formulated into a coherent hypothesis many centuries later in the writings of the Italian physician D. Frakastoro (1478-1553), who expressed the idea of ​​living contagia (contagiumvivum), which causes disease. Moreover, each disease is caused by its own contagion. To prevent disease, they were recommended to isolate the patient, quarantine, wear masks, and treat objects with vinegar.

MORPHOLOGICAL PERIOD (XVII FIRST HALF OF XIX centuries) It begins with the discovery of microorganisms by A. Levenguk. At this stage, the ubiquitous distribution of microorganisms was confirmed, the forms of cells, the nature of movement, the habitats of many representatives of the microworld were described. The end of this period is significant in that the knowledge accumulated by this time about microorganisms and the scientific methodological level (in particular, the presence of microscopic technology) allowed scientists to solve three very important (basic) problems for all natural sciences: the study of the nature of fermentation and decay processes, the causes of infectious diseases, the problem of the very origin of microorganisms.

Study of the nature of fermentation and decay processes. The term "fermentation" (fermentatio) to denote all processes occurring with the release of gas was first used by the Dutch alchemist Ya.B. Helmont (1579-1644) Many scientists have tried to define and explain this process. But the closest to understanding the role of yeast in the fermentation process came from the French chemist A.L. Lavoisier (1743 1794) in the study of the quantitative chemical transformations of sugar during alcoholic fermentation, but he did not manage to complete his work, as he became a victim of the terror of the French bourgeois revolution.

Many scientists have studied the fermentation process, but the French botanist C. Canyard de Latour (who investigated the sediment during alcoholic fermentation and discovered living beings), the German naturalists F. Kuetzing ( during the formation of vinegar, drew attention to the mucous membrane on the surface, which also consisted of living organisms) and T. Schwann. But their research was severely criticized by supporters of the theory of the physicochemical nature of fermentation. They were accused of "frivolity of conclusions" and lack of evidence. The second main problem about the microbial nature of infectious diseases was also solved in the morphological period of the development of microbiology.

The first to suggest that diseases are caused by invisible beings were the ancient Greek physician Hippocrates (c. 460 377 BC), Avicenna (c. 980-1037), etc. Despite the fact that the emergence of diseases is now associated with discovered microorganisms, direct evidence was needed. And they were received by a Russian doctor epidemiologist D.S. Samoilovich (1744 1805). Microscopes of that time had a magnification of about 300 times and did not allow detecting the causative agent of the plague, for the detection of which, as is now known, an increase of 800 to 1000 times is required. To prove that the plague is caused by a special pathogen, he infected himself with the discharge of the bubo from a plague-sick person and fell ill with the plague.

Fortunately, D.S. Samoilovich survived. Subsequently, Russian doctors G.N. Minh and O.O. Mochutkovsky, I.I. Mechnikov and others. But the priority in resolving the question of the microbial nature of infectious diseases belongs to the Italian naturalist A. Basi (1773 1856), who was the first to experimentally establish the microbial nature of silkworm disease, he discovered the transmission of the disease when a microscopic fungus was transferred from a sick individual to a healthy one. ... But most researchers were convinced that the causes of all diseases are disruptions in the course of chemical processes in the body. The third problem about the method of emergence and reproduction of microorganisms was solved in a dispute with the then dominant theory of spontaneous generation.

Despite the fact that the Italian scientist L. Spallanzani in the middle of the 18th century. observed under a microscope the division of bacteria, the opinion that they spontaneously arise (arise from rot, dirt, etc.) has not been refuted. This was done by the outstanding French scientist Louis Pasteur (1822 1895), who, with his work, laid the foundation for modern microbiology. In the same period, the development of microbiology began in Russia. The founder of Russian microbiology is L.N. Tsenkovsky (1822 1887). The objects of his research are protozoa, algae, mushrooms. He discovered and described a large number of protozoa, studied their morphology and developmental cycles, showed that there is no sharp border between the world of plants and animals. He organized one of the first Pasteur stations in Russia and proposed a vaccine against anthrax (Tsenkovsky's live vaccine).

PHYSIOLOGICAL PERIOD (SECOND HALF OF THE XIX CENTURY)

The rapid development of microbiology in the 19th century. led to the discovery of many microorganisms: nodule bacteria, nitrifying bacteria, causative agents of many infectious diseases (anthrax, plague, tetanus, diphtheria, cholera, tuberculosis, etc.), tobacco mosaic virus, foot and mouth disease virus, etc. The discovery of new microorganisms was accompanied by the study of not only their structure, but also their vital activity, that is, to replace the morphological-systematic study of the first half of the 19th century. came the physiological study of microorganisms, based on precise experiment.

Therefore, the second half of the XIX century. it is customary to call the physiological period in the development of microbiology. This period is characterized by outstanding discoveries in the field of microbiology, and without exaggeration it could be named after the genius French scientist L. Pasteur Pasteur, because the scientific activity of this scientist covered all the main problems associated with the vital activity of microorganisms. More details about the main scientific discoveries of L. Pasteur and their significance for the protection of human health and human economic activity will be discussed in § 1.3. The first of L. Pasteur's contemporaries who appreciated the significance of his discoveries was the English surgeon J. Lister (1827-1912), who, based on the achievements of L. Pasteur, for the first time introduced the treatment of all surgical instruments with carbolic acid into medical practice. decontamination of operating rooms and achieved a decrease in the number of deaths after operations.

One of the founders of medical microbiology is Robert Koch (1843 - 1910), who developed methods for obtaining pure cultures of bacteria, staining bacteria with microscopy, and photomicrographs. Also known is the Koch triad formulated by R. Koch, which is still used to identify the causative agent of the disease. In 1877 R. Koch isolated the causative agent of anthrax, in 1882 the causative agent of tuberculosis, and in 1905 he was awarded the Nobel Prize for the discovery of the causative agent of cholera. In the physiological period, namely in 1867, M.S. Voronin described nodule bacteria, and almost 20 years later G. Gelrigel and G. Wilfart showed their ability to fix nitrogen. French chemists T. Schlesing, A. Muntz substantiated the microbiological nature of nitrification (1877), and in 1882 P. Degeren established the nature of denitrification, the nature of anaerobic decomposition of plant residues.

Russian scientist P.A. Kostychev created a theory of the microbiological nature of soil formation processes. Finally, in 1892 the Russian botanist D.I.Ivanovsky (1864-1920) discovered the tobacco mosaic virus. In 1898, regardless of D.I. Ivanovsky, the same virus was described by M. Beijerinck. Then the foot and mouth disease virus (F. Leffler, P. Frosch, 1897), yellow fever (W. Reed, 1901) and many other viruses were discovered. However, it became possible to see viral particles only after the invention of the electron microscope, since they are not visible in light microscopes. To date, the kingdom of viruses has up to 1000 disease-causing species. Only recently a number of new DI Ivanovsky viruses have been discovered, including the virus that causes AIDS.

There is no doubt that the period of the discovery of new viruses and bacteria and the study of their morphology and physiology continues to this day. S.N. Vinogradsky (1856 1953) and the Dutch microbiologist M. Beijerinck (1851 1931) introduced the microecological principle of the study of microorganisms. S.N. Vinogradskiy proposed to create specific (elective) conditions enabling the predominant development of one group of microorganisms, discovered in 1893 an anaerobic nitrogen fixer, named after Pasteur Clostridium pasterianum, isolated from the soil microorganisms representing a completely new type of life and called chemolithoautotrophic.

The microecological principle was also developed by M. Beijerinck and applied in the isolation of various groups of microorganisms. 8 years after the discovery of S.N. Vinogradskiy M. Beijerinck isolated Azotobacterchroococcum under aerobic conditions, investigated the physiology of nodule bacteria, denitrification and sulfate reduction processes, etc. Both of these researchers are the founders of the ecological direction of microbiology, associated with the study of the role of microorganisms in the cycle of substances in nature. By the end of the XIX century. differentiation of microbiology into a number of particular areas is outlined: general, medical, soil.

IMMUNOLOGICAL PERIOD (BEGINNING OF THE XX CENTURY) With the beginning of the XX century. begins a new period in microbiology, to which the discoveries of the 19th century led. The works of L. Pasteur on vaccination, I.I. Mechnikov on phagocytosis, P. Ehrlich on the theory of humoral immunity made up the main content of this stage in the development of microbiology, which is rightfully called immunological.

I.I. Metchnikov on how vaccination against many diseases began to be widely used. I.I. Mechnikov showed that the body's defense against pathogenic bacteria is a complex biological reaction, which is based on the ability of phagocytes (macro and microphages) to capture and destroy foreign bodies that have entered the body, including bacteria. Research by I.I. Mechnikov on phagocytosis convincingly proved that, in addition to humoral, there is cellular immunity. I.I. Mechnikov and P. Ehrlich were scientific opponents for many years, each experimentally proving the validity of his theory.

Subsequently, it turned out that there is no contradiction between humoral and phagocytic immunities, since these mechanisms jointly protect the body. And in 1908 I.I. Mechnikov together with P. Ehrlich was awarded the Nobel Prize for the development of the theory of immunity. The immunological period is characterized by the discovery of the main reactions of the immune system to genetically foreign substances (antigens): antibody formation and phagocytosis, delayed-type hypersensitivity (HRT), immediate-type hypersensitivity (HHT), tolerance, and immunological memory.

Microbiology and immunology developed especially rapidly in the 50-60s. twentieth century. This was facilitated by the most important discoveries in the field of molecular biology, genetics, bioorganic chemistry; the emergence of new sciences: genetic engineering, molecular biology, biotechnology, informatics; creation of new methods and the use of scientific equipment. Immunology is the basis for the development of laboratory methods for the diagnosis, prevention and treatment of infectious and many non-infectious diseases, as well as the development of immunobiological drugs (vaccines, immunoglobulins, immunomodulators, allergens, diagnostic drugs). The development and production of immunobiological preparations is engaged in immunobiotechnology, an independent section of immunology.

Modern medical microbiology and immunology have made great strides and play a huge role in the diagnosis, prevention and treatment of infectious and many non-infectious diseases associated with impaired immune system (oncological, autoimmune diseases, organ and tissue transplantation, etc.).

For example, chemical synthesis of lysozyme (D. Sela, 1971), peptides of the AIDS virus (R.V. Petrov, V.T. Ivanov, etc.). 3. Deciphering the structure of antibodiesimmunoglobulins (D. Edelman, R. Porter, 1959). 4. Development of a method for cultures of animal and plant cells and their cultivation on an industrial scale in order to obtain viral antigens. 5. Obtaining recombinant bacteria and recombinant viruses. 6. Creation of hybridomas by fusion of immune B lymphocytes of antibody producers and cancer cells in order to obtain monoclonal antibodies (D. Keller, C. Milstein, 1975). 7. Discovery of immunomodulators of immunocytokinins (interleukins, interferons, myelopeptides, etc.) of endogenous natural regulators of the immune system and their use for the prevention and treatment of various diseases. 8. Obtaining vaccines using biotechnology and genetic engineering techniques (hepatitis B, malaria, HIV antigens and other antigens) and biologically active peptides (interferons, interleukins, growth factors, etc.). 9. Development of synthetic vaccines based on natural or synthetic antigens and their fragments. 10. Discovery of viruses that cause immunodeficiency. 11. Development of fundamentally new methods for the diagnosis of infectious and non-infectious diseases (enzyme immunoassay, radioimmunoassay, immunoblotting, nucleic acid hybridization).

Creation on the basis of these methods of test systems for indication, identification of microorganisms, diagnostics of infectious and non-infectious diseases. In the second half of the twentieth century. the formation of new directions in microbiology continues, new disciplines are spun off from it with their own research objects (virology, mycology), areas that differ in research objectives (general microbiology, technical, agricultural, medical microbiology, genetics of microorganisms, etc.) are distinguished. Many forms of microorganisms have been studied and by about the middle of the 50s. last century A. Kluyver (1888 1956) and K. Niel (1897 1985) formulated the theory of the biochemical unity of life

Wasserman reaction (RW or EDS-Express Diagnosis of Syphilis) is an outdated method for diagnosing syphilis using a serological test. Currently replaced by precipitation microreaction ( anticardiolipin test, MP, RPR- RapidPlasmaReagin). Named for German immunologist August Wassermann<#"justify">This is an agglutination reaction used to diagnose typhoid fever and some typhoid-paratyphoid diseases.

Proposed in 1896 by the French physician F. Widal (F. Widal, 1862-1929). V. p. It is based on the ability of antibodies (agglutinins), formed in the body during the disease and persisting for a long time after recovery, to cause adhesion of typhoid microorganisms, specific antibodies (agglutinins) are found in the patient's blood from the 2nd week of illness.

To formulate Vidal's reaction, blood is taken from the cubital vein in an amount of 2-3 ml with a syringe and allowed to coagulate. The formed clot is separated, and the serum is aspirated into a clean test tube and 3 series of dilutions of the patient's serum from 1: 100 to 1: 800 are prepared from it as follows: 1 ml (20 drops) of saline is poured into all test tubes; then with the same pipette, 1 ml of serum diluted 1:50 is poured into the first tube, mixed with saline, thus a dilution of 1: 100 is obtained, 1 ml of serum is transferred from this tube into the next tube, mixed with saline, a dilution of 1 is obtained: 200 also receive dilutions of 1: 400 and 1: 800 in each of the three rows.

The agglutination reaction of Widzl is carried out in a volume of 1 ml of liquid, therefore, 1 ml is removed from the last test tube after mixing the liquid. A separate control tube is filled with 1 ml of serum-free saline. This control is set to check the possibility of spontaneous agglutination of antigen (diagnosticum) in each row (antigen control). In all test tubes of each row corresponding to the inscriptions, 2 drops of diagnosticum are instilled. The stand is placed in a thermostat for 2 hours at 37 ° C and then left at room temperature for a day. The reaction is taken into account in the next lesson.

In the sera of patients, there can be both specific and group antibodies, which differ in titer height. A specific agglutination reaction usually goes up to a higher titer. The reaction is considered positive if agglutination has occurred at least in the first tube with a dilution of 1: 200. It usually occurs at high dilutions. If there is a group agglutination with two or three antigens, then the causative agent of the disease is considered the microbe with which agglutination occurred in the highest dilution of serum.

If agglutination occurs when a culture of the pathogen is added to the human blood serum, the reaction is considered positive. To diagnose typhoid fever, Vidal's reaction is performed many times, taking into account its indications in dynamics and in connection with the history<#"justify">Conclusion

During its development, microbiology not only learned a lot from related sciences (for example, immunology, biochemistry, biophysics and genetics), but also gave a powerful impetus for their further development. Microbiology studies morphology, physiology, genetics, taxonomy, ecology, and the relationship of microorganisms with other creatures. Since microorganisms are very diverse, special areas of it are engaged in their more detailed study: virology, bacteriology, mycology, protozoology, etc. The abundance of factual material accumulated over a relatively short period of scientific development of microbiology (from the second half of the 19th century) contributed to the division of microbiology into a number of specialized areas: medical, veterinary, technical, space, etc.

Medical microbiology studies microorganisms, pathogenic and opportunistic for humans, their ecology and prevalence, methods of their isolation and identification, as well as issues of epidemiology, specific therapy and prevention of diseases caused by them.

The study of the entire complex of interactions within the “microorganism-microorganism” ecosystem, whether it is a microbe-commensal or a microbe-pathogen, remains an urgent problem of medical microbiology.

Bibliography

1. Pokrovsky V.I. "Medical microbiology, immunology, virology". A textbook for farm students. Universities, 2002.

Borisov L.B. "Medical Microbiology, Virology and Immunology". A textbook for students of honey. Universities, 1994.

Vorobiev A.A. "Microbiology". A textbook for students of honey. Universities, 1994.

A.I. Korotyaev "Medical Microbiology, Virology and Immunology", 1998.

Bukrinskaya A.G. "Virology", 1986.

L. B. Borisov. Medical microbiology, virology, immunology. M .: OOO "MIA", 2010.736 p.

Pozdeev O.K. Medical Microbiology. M .: GEOTAR-MED, 2001.754 p.


MINISTRY OF EDUCATION AND SCIENCE OF THE REPUBLIC OF KAZAKHSTAN
EAST KAZAKHSTAN STATE UNIVERSITY IM. S. AMANZHOLOVA

Department of Biology

ESSAY

By discipline: "Biology and development of microorganisms and viruses"

On the topic: "The history of the development of microbiology"

Completed: students of group UBG-09 (A)
Grushkovskaya D., Fefelova N.
Checked by: Kalenova K.Sh.

Ust-Kamenogorsk, 2011

Plan:
Introduction ………………………………………………………………………… ... 3

1. DISCOVERY OF MICROORGANISMS ………………………………………………………………………………………………………………………………………… ... 4
2. DESCRIPTIVE (MORPHOLOGICAL) PERIOD IN THE DEVELOPMENT OF MICROBIOLOGY (LATE 17 C - MIDDLE 19 C) ……………………………………………………………………………………………………………….
2.1. Development of ideas about the nature of fermentation and decay processes ... ... 5
2.2. Development of ideas about the microbial nature of infectious diseases ……………………………………………………………………… .7
3.PHYSIOLOGICAL PERIOD (PASTEROVSKY) (SECOND HALF OF THE 19th CENTURY) …………………………………………………………… .8
3.1. Scientific activity of Louis Pasteur ………………………………………… 8
3.2. The development of microbiology in the second half of the 19th century ………………… ... 10
4. DEVELOPMENT OF MICROBIOLOGY IN THE 20TH CENTURY ………………………………… 15

Conclusion.................... ............................. . .............................. ................... .......... eighteen

Literature .................... ............................. . .............................. ................... .......... 19

INTRODUCTION

Microbiology is a science that studies the structure, taxonomy, physiology, biochemistry, genetics and ecology of organisms that are small and invisible to the naked eye. These organisms are called microorganisms or microbes.
For a long time, a person lived surrounded by invisible creatures, used the products of their vital activity (for example, when baking bread from sour dough, making wine and vinegar), suffered when these creatures caused diseases or spoiled food supplies, but did not suspect their presence ... I didn’t suspect because I didn’t see, and I didn’t see because the sizes of these micro-creatures were much lower than the limit of visibility that the human eye is capable of. It is known that a person with normal vision at an optimal distance (25-30 cm) can distinguish an object with a size of 0.07-0.08 mm in the form of a point. A person cannot notice fewer objects. This is determined by the structural features of his organ of vision.
Attempts to overcome the created natural barrier and expand the capabilities of the human eye were made long ago. So, during archaeological excavations in Ancient Babylon, biconvex lenses were found - the simplest optical instruments. The lenses were made of cut rock crystal. We can assume that with their invention, man made the first step on the path to the microcosm.
Further improvement of optical technology dates back to the 16th and 17th centuries. and is associated with the development of astronomy. During this time the first telescopes were constructed by Dutch glass grinders. It turned out that if the lenses are positioned differently than in a telescope, then you can get an increase in very small objects. A microscope of this type was created in 1610 by G. Galileo. The invention of the microscope opened up new possibilities for studying wildlife.
One of the first microscope, consisting of two biconvex lenses, giving an increase of about 30 times, was designed and used to study the structure of plants by the English physicist and inventor R. Hooke. Examining the cork cuts, he discovered the correct cellular structure of the wood tissue. These cells were later called "cells" by him and are depicted in the book "Micrography". It was R. Hooke who introduced the term "cell" to designate those structural units of which a complex living organism is built. Further penetration into the secrets of the microworld is inextricably linked with the improvement of optical devices.

1 DISCOVERY OF MICROORGANISMS

Microorganisms were discovered at the end of the 17th century, but their activity and even their practical application were known much earlier. For example, products of alcoholic, lactic acid, and acetic acid fermentation were prepared and used in the most ancient times. The usefulness of these products was explained by the presence of a "living spirit" in them. However, the idea of ​​the existence of invisible creatures began to appear when identifying the causes of infectious diseases. So, Hippocrates (6th century BC), and later Varro (2nd century) suggested that infectious diseases are caused by invisible creatures. But only in the 16th century, the Italian scientist Giralamo Fracastoro came to the conclusion that the transmission of diseases from person to person is carried out with the help of the smallest living creatures, to which he gave the name contagium vivum. However, there was no evidence of such assumptions.
If we assume that microbiology arose at the moment when a person saw the first microorganisms, then we can accurately indicate the "birthday" of microbiology and the name of the discoverer. This man is the Dutchman Anthony van Leeuwenhoek (1632-1723), a manufacturer from Delft. Having become interested in the structure of flax fiber, he polished several coarse lenses for himself. Later, Leeuwenhoek was carried away by this delicate and painstaking work and achieved great perfection in the manufacture of lenses, which he called "microscopes". Outwardly, these were single biconvex glasses, set in silver or brass, however, in terms of their optical properties, the Levenguk lenses, which gave a magnification of 200 - 270 times, were unmatched. To evaluate them, it is enough to recall that the theoretical limit of magnification of a biconvex lens is 250 - 300 times.
Having no natural education, but possessing a natural curiosity, Levenguk looked with interest at everything that came to hand: water from a pond, dental plaque, pepper infusion, saliva, blood, and much more. In 1673, Leeuwenhoek began to send the results of his observations to the Royal Society of London, of which he was later elected a member. In total, Leeuwenhoek wrote over 170 letters to the Royal Society of London, and later bequeathed to him 26 of his famous "microscopes". Here is an excerpt from one letter: “On April 24, 1676, I looked at the water under a microscope and with great surprise I saw in it a huge number of the smallest living creatures. Some of them were 3 - 4 times longer in length than in width, although they were not thicker than the hairs covering the body of the lice. Others had a regular oval shape. There was also a third type of organisms - the most numerous - the smallest creatures with tails. " By comparing the description in this passage with the optical capabilities of the lenses available to Levenguk, it can be concluded that Levenguk was the first to see bacteria in 1676.
Levenguk found microorganisms everywhere and came to the conclusion that the surrounding world was densely populated with microscopic inhabitants. All the microorganisms he saw, including bacteria, Leeuwenhoek considered small animals, which he called "animals", and was convinced that they are arranged in the same way as large organisms, that is, they have digestive organs, legs, tails, etc. .d.
Levenguk's discoveries were so unexpected and even fantastic that for almost 50 subsequent years they caused general amazement. While in Holland in 1698, Peter I visited Levenguk and talked with him. From this trip, Peter I brought a microscope to Russia, and later, in 1716, the first domestic microscopes were made in the workshops at his court.

2. DESCRIPTIVE (MORPHOLOGICAL) PERIOD IN THE DEVELOPMENT OF MICROBIOLOGY (LATE 17 C - MIDDLE 19 C)

2.1. Development of ideas about the nature of fermentation and decay processes

Many processes carried out by microorganisms have been known to man since time immemorial. First of all, this is rotting and fermentation. In the works of ancient Greek and Roman authors, you can find recipes for making wine, sour milk, bread, testifying to the widespread use of fermentation in everyday life. In the Middle Ages, alchemists did not ignore these processes and studied them along with other purely chemical transformations. It was during this period that attempts were made to elucidate the nature of fermentation processes.
The term "fermentation" ("fermentatio") was first used by the Dutch alchemist Ya.B. van Helmont (1577-1644). J. van Helmont found a similarity between the gas formed during the fermentation of grape juice (carbon dioxide), the gas released during the combustion of coal, and the gas that appears “when vinegar is poured on lime stones”, i.e. when alkali interacts with acid. Based on this, J. van Helmont came to the conclusion that all the chemical transformations described above are of the same nature. Later fermentation began to be distinguished from the group of chemical processes accompanied by gas evolution. To designate the material driving force of fermentation, its active principle, the term "enzyme" was used. The view of fermentation and decay as purely chemical processes was formulated in 1697 by the German physician and chemist G.E. Stahl (1660-1734). According to G. Stahl, fermentation and decay are chemical transformations under the influence of "enzyme" molecules, which transfer their inherent internal active movement to the molecules of the fermented substrate, i.e. act as a kind of reaction catalysts. G. Stahl's views on the nature of the processes of decay and fermentation were fully shared and defended by one of the greatest chemists of his time, J. Liebig. However, this point of view was not accepted by all researchers.
One of the first guesses about the connection of the "globules" (yeast) described by Levenguk with the phenomena of fermentation and decay belongs to the French naturalist J.L.L. Buffon (1707-1788). The French chemist A. Lavoisier (1743-1794), who studied quantitatively the chemical transformations of sugar during alcoholic fermentation, came very close to understanding the role of yeast in the fermentation process. In 1793 he wrote: “A little brewer's yeast is enough to give the first impetus to fermentation: it then continues by itself. I will report elsewhere on the effect of the enzyme in general. " However, he failed to do this: A. Lavoisier fell victim to the terror of the French bourgeois revolution.
The period of intensive microscopic observations began in the 30s of the 19th century. In 1827, the French chemist J. Demazières (1783-1862) described the structure of the yeast Mycoderma cerevisiae, which forms a film on the surface of beer, and, convinced that these are the smallest animals, attributed them to ciliates. However, in the work of J. Demazière, there is no indication of a possible connection between the fermentation process and a film developing on the surface of a fermenting liquid. 10 years later, the French botanist Ch. Canyard de Latour (1777-1859) undertook a thorough microscopic study of the sediment formed during alcoholic fermentation, and came to the conclusion that it consists of living things, the vital activity of which is the cause of fermentation. Almost simultaneously, the German naturalist F. Kützing (1807-1893), while studying the formation of vinegar from alcohol, drew attention to a slimy mass that looks like a film on the surface of a liquid containing alcohol. Studying the mucous mass, F. Kützing found that it consists of microscopic living organisms and is directly related to the accumulation of vinegar in the environment. Another German naturalist T. Schwann (1810-1882) came to similar conclusions.
Thus, C. Canyard de Latour, F. Kützing and T. Schwann independently and almost simultaneously came to the conclusion about the connection between fermentation processes and the vital activity of microscopic living beings. The main conclusion from these studies was clearly formulated by F. Kützing: “Now we have to consider each fermentation process differently than chemistry has considered them until now. The whole process of alcoholic fermentation depends on the presence of yeast, and acetic fermentation depends on the presence of the vinegar uterus. "
However, the ideas about the biological nature of the fermentation "enzyme" expressed by three researchers have not received recognition. Moreover, they were severely criticized by adherents of the theory of the physicochemical nature of fermentation, who accused their scientific opponents of "frivolity in conclusions" and the absence of any evidence to support this "strange hypothesis." The dominant theory remained the theory of the physicochemical nature of fermentation processes.

2.2. Development of ideas about the microbial nature of infectious diseases

Even the ancient Greek physician Hippocrates (c. 460-377 BC) suggested that infectious diseases are caused by invisible living beings. Avicenna (c. 980-1037) in the "Canon of Medicine" wrote about the "invisible" causative agents of plague, smallpox and other diseases. Similar thoughts can be found in the writings of the Italian physician, astronomer and poet G. Frakastro (1478-1553).
The Russian doctor-epidemiologist D.S. was deeply convinced that infectious diseases are caused by living microscopic beings. Samoilovich (1744-1805), who tried to detect the causative agent of the plague under a microscope. This he did not succeed due to the imperfection of microscopes and microscopic technology. However, the measures for disinfection and isolation of patients developed by D.S. Samoilovich in accordance with his idea turned out to be very effective in combating epidemics and became widely known throughout the world.
It is worth mentioning that D. Samoilovich's contemporary M. Terekhovsky (1740-1796) - the first Russian protistologist - experimenter established the living nature of protozoa and in 1775 for the first time in the world applied an experimental research method to microorganisms, determining the effect of temperature, electric discharges, mercuric chloride, opium, acids and alkalis for their viability. Studying the movement, growth and reproduction of microorganisms under strictly controlled conditions, Terekhovsky was the first to point out that growth and increase in size precede division. He also proved the impossibility of spontaneous generation of protozoa in various boiled liquids (infusions). He outlined his observations in the work "On the liqueur chaos of Linnaeus."
In 1827, the Italian naturalist A. Bassi (1773-1856), while studying the disease of silkworms, discovered the transmission of the disease when a microscopic fungus was transferred from a sick individual to a healthy one. Thus, A. Bassi was the first to experimentally prove the microbial nature of this disease. The idea of ​​the microbial nature of infectious diseases has not been recognized for a long time. The prevailing theory was that various disorders in the course of chemical processes in the body were considered the causes of diseases.
In 1846, the German anatomist F. Henle (1809-1885) in his book "Guide to Rational Pathology" clearly defined the basic provisions for the recognition of infectious diseases. Later, the ideas of F. Henle, formulated in a general form (F. Henle himself did not manage to see a single causative agent of human infectious diseases), were experimentally substantiated by R. Koch and entered science under the name "Henle-Koch triad".

3. PHYSIOLOGICAL PERIOD (PASTEROVSKY) (SECOND HALF OF THE 19th CENTURY)

3.1. Scientific activity of Louis Pasteur

The beginning of the physiological period dates back to the 60s of the 19th century and is associated with the activities of an outstanding French scientist, chemist by profession, Louis Pasteur (1822-1895). Microbiology owes Pasteur not only its rapid development, but also its establishment as a science. The most important discoveries that brought him worldwide fame are associated with Pasteur's name: fermentation (1857), spontaneous generation (1860), diseases of wine and beer (1865), diseases of silkworms (1868), infection and vaccines (1881), rabies (1885) ...
Pasteur began his scientific career with work on crystallography. He found that upon recrystallization of salts of optically inactive racemic tartaric acid, two types of crystals are formed. A solution prepared from crystals of one type rotates the plane of polarized light to the right, from crystals of another type to the left. Further, Pasteur found that a mold that grew in a solution of racemic tartaric acid consumes only one of the isomeric forms (dextrorotatory). This observation allowed Pasteur to draw a conclusion about the specific effect of microorganisms on substrates and served as a theoretical basis for the subsequent study of the physiology of microorganisms. Pasteur's observations of lower molds drew his attention to microorganisms in general.
In 1854 Pasteur was promoted to tenured professor at the University of Lille. It was here that he began his microbiological research, which laid the foundation for microbiology as an independent scientific discipline.
The reason for the beginning of the study of fermentation processes was the appeal to Pasteur of the Lille manufacturer with a request to help find out the reasons for systematic failures in the fermentation of beet juice to obtain alcohol. The research results published at the end of 1857 proved beyond doubt that the process of alcoholic fermentation is the result of the vital activity of a certain group of microorganisms - yeast and occurs in conditions without access to air.
Almost simultaneously with the study of alcoholic fermentation, Pasteur began to study lactic acid fermentation and also showed that this type of fermentation is caused by microorganisms, which he called "lactic acid yeast." The results of the research Pasteur outlined in his published works "Memoir on lactic acid fermentation".
Indeed, the results of Pasteur's research are not just new scientific data, they are a bold refutation of the then dominant theory of the physicochemical nature of fermentation, supported and defended by the largest scientific authorities of that time: I. Berzelius, E. Mitscherlich, J. Liebig. Lactic acid fermentation is the simplest "chemical" process of decomposition of a sugar molecule into two trioses, and the proof that this decay is associated with the vital activity of microscopic organisms was a weighty argument supporting the theory of the biological nature of fermentation.
The second argument in support of the biological nature of fermentation was the experimental proof by Pasteur of the possibility of alcoholic fermentation on a protein-free medium. According to the chemical theory of fermentation, the latter is the result of the catalytic activity of an "enzyme", which is a substance of a protein nature.
The study of butyric fermentation led Pasteur to the conclusion that the life of some microorganisms not only can proceed in the absence of free oxygen, but the latter is harmful to them. The results of these observations were published in 1861 in a message entitled "Animalculi-ciliates, living without free oxygen and causing fermentation." The discovery of the negative effect of free oxygen on the butyric fermentation process was, perhaps, the last moment that completely refuted the theory of the chemical nature of fermentation, since it was oxygen that was assigned the role of a compound that gave the first impetus to the internal movement of the protein particles of the "enzyme". Through a series of studies in the field of fermentation, Pasteur convincingly proved the inconsistency of the chemical theory of fermentation, forcing his opponents to admit their delusions. For his work on the study of anaerobiosis in 1861 Pasteur received an award from the French Academy of Sciences and a medal from the Royal Society of London. The result of twenty years of research in the field of fermentation was summed up by Pasteur in "Research on beer, its diseases, their causes, ways to make it stable, with the application of a new theory of fermentation" (1876).
In 1865, the French government asked Pasteur to help silkworm breeders who suffered great losses due to diseases of silkworms. Pasteur devoted about five years to the study of this issue and came to the conclusion that diseases of silkworms are caused by certain microorganisms. Pasteur studied in detail the course of the disease - pebrins of silkworms and developed practical recommendations for combating the disease: he proposed to look under a microscope in the bodies of butterflies and pupae for pathogens, separate diseased individuals and destroy them, etc.
Having established the microbial nature of infectious diseases of silkworms, Pasteur came to the conclusion that diseases of animals and humans are also caused by the influence of microorganisms. His first work in this direction was the proof that childbirth fever, widespread in the period described, is caused by a certain microscopic pathogen. Pasteur identified the causative agent of fever, showed that the reason for it was disregard for the rules of antiseptics on the part of medical personnel, and developed methods of protection against the penetration of the pathogen into the body.
Further work of Pasteur in the study of infectious diseases led to the discovery of the causative agents of chicken cholera, osteomyelitis, purulent abscesses, one of the causative agents of gas gangrene. In this way, Pasteur showed and proved that each disease is generated by a specific microorganism.
In 1879, while studying chicken cholera, Pasteur developed a method for obtaining cultures of microbes that lose their ability to be the causative agent of the disease, that is, they lose virulence, and used this discovery to protect the body from subsequent infection. The latter formed the basis for the creation of the theory of immunity.
Pasteur's study of infectious diseases was combined with the development of measures to actively combat them. Based on the technique of obtaining weakened cultures of virulent microorganisms, called "vaccines", Pasteur found ways to combat anthrax and rabies. Pasteur's vaccines have spread worldwide. Institutions where rabies vaccinations are carried out are named Pasteur stations after Pasteur.
Pasteur's works were appreciated by his contemporaries and received international recognition. In 1888, a research institute was built in Paris for Pasteur, using funds raised by international subscription, which now bears his name. Pasteur was the first director of this institute. The discoveries of L. Pasteur showed how diverse, unusual, active the microcosm invisible to the naked eye is and what a huge field of activity is its study.

3.2. The development of microbiology in the second half of the 19th century

Assessing the successes achieved by microbiology in the second half of the 19th century, the French researcher P. Tennery in his work "Historical sketch of the development of natural science in Europe" wrote: "In the face of bacteriological discoveries, the history of other natural sciences in the last decades of the 19th century seems somewhat paler."
The successes of microbiology during this period are directly related to new ideas and methodological approaches introduced into microbiological research by L. Pasteur. Among the first to appreciate the significance of Pasteur's discoveries was the English surgeon J. Lister, he realized that the cause of a large percentage of deaths after operations is, firstly, the infection of wounds with bacteria due to ignorance and, secondly, non-observance of elementary rules of antiseptics ...
One of the founders of medical microbiology, along with Pasteur, was the German microbiologist R. Koch (1843-1910), who studied the causative agents of infectious diseases. Koch began his research while still a rural doctor with the study of anthrax, and in 1877 published a work on the causative agent of this disease - Bacillus anthracis. Following this, Koch's attention was drawn to another serious and widespread disease of the time - tuberculosis. In 1882, Koch announced the discovery of the causative agent of tuberculosis, which was named in his honor "Koch's wand". (In 1905, Koch was awarded the Nobel Prize for his study of tuberculosis.) Koch was also responsible for the discovery in 1883 of the causative agent of cholera.
Koch paid much attention to the development of microbiological research methods. He designed a lighting apparatus, proposed a method for microphotography of bacteria, developed methods for staining bacteria with aniline dyes, and proposed a method for growing microorganisms on solid nutrient media using gelatin. Obtaining bacteria in the form of pure cultures opened up new approaches for a more in-depth study of their properties and served as an impetus for the further rapid development of microbiology. Pure cultures of the causative agents of cholera, tuberculosis, diphtheria, plague, glanders, and croupous pneumonia were isolated.
Koch experimentally substantiated the provisions on the recognition of infectious diseases put forward earlier by F. Henle, which entered science under the name of the "Henle-Koch triad" (later, however, it turned out that it was not applicable to all infectious agents).
The founder of Russian microbiology is L. Tsenkovsky (1822-1887). The object of his research was microscopic protozoa, algae, fungi. He discovered and described a large number of protozoa, studied their morphology and developmental cycles. This allowed him to conclude that there is no sharp border between the world of plants and animals. He also organized one of the first Pasteur stations in Russia and proposed a vaccine against anthrax ("Zenkovsky's live vaccine").
The name of I. Mechnikov (1845-1916) is associated with the development of a new direction in microbiology - immunology. For the first time in science, Mechnikov developed and experimentally confirmed the biological theory of immunity, which went down in history as Mechnikov's phagocytic theory. This theory is based on the concept of cellular defenses of the body. Mechnikov in experiments on animals (daphnia, starfish larvae) proved that leukocytes and other cells of mesodermal origin have the ability to capture and digest foreign particles (including microbes) that enter the body. This phenomenon, called phagocytosis, formed the basis of the phagocytic theory of immunity and received universal recognition. Further developing the questions raised, Mechnikov formulated the general theory of inflammation as a defense reaction of the body and created a new direction in immunology - the doctrine of antigenic specificity. At present, it is becoming increasingly important in connection with the development of the problem of organ and tissue transplantation, and the study of cancer immunology.
Among the most important works of Mechnikov in the field of medical microbiology are studies of the pathogenesis of cholera and the biology of cholera-like vibrios, syphilis, tuberculosis, and relapsing fever. Mechnikov is the founder of the theory of microbial antagonism, which served as the basis for the development of the science of antibiotic therapy. The idea of ​​microbial antagonism was used by Mechnikov when developing the problem of longevity. Studying the phenomenon of aging in the body, Mechnikov came to the conclusion. That the most important reason for it is the chronic poisoning of the body with putrefaction products produced in the large intestine by putrefactive bacteria.
Of practical interest are Mechnikov's early works on the use of the Isaria destructor fungus to combat the pest of fields - the bread beetle. They give reason to consider Mechnikov the founder of the biological method of combating pests of agricultural plants, a method that is increasingly being used and popular today.
Thus, I.I. Mechnikov, an outstanding Russian biologist who combined the qualities of an experimenter, teacher and propagandist of scientific knowledge, was a man of great spirit and work, the highest award of which was the Nobel Prize for research on phagocytosis in 1909.
One of the largest scientists in the field of microbiology is a friend and colleague of I. Mechnikov N.F. Gamaleya (1859-1949). Gamaleya devoted his entire life to the study of infectious diseases and the development of measures to combat their pathogens. Gamaleya made a major contribution to the study of tuberculosis, cholera, and rabies; in 1886, together with I. Mechnikov, he organized the first Pasteur station in Odessa and introduced rabies vaccinations into the practice. He discovered avian vibrio - the causative agent of a cholera-like disease in birds - and named it Mechnikov's vibrio in honor of Ilya Ilyich. Then the vaccine against human cholera was received.
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