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Biography of A. G. Knorre (1914-1981)
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He was born in 1914 in St. Petersburg. His father, Georgy Fedorovich Knorre (1891-1962), was an engineer, writer and memoirist. He graduated from the Faculty of Biology of Leningrad State University. After that, he graduated from the postgraduate course at the embryological laboratory of the Department of General and Comparative Morphology of the All-Union Institute of Experimental Medicine under the direction of P. P. Ivanov.
Photo № 10. Knorre Aleksey Georgievich (1914-1981). Biologist, evolutionary morphologist; Professor, Corresponding Member of the Academy of Medical Sciences of the USSR. From the 50's to 1981 headed the Department of Histology and Embryology of the Leningrad Pediatric Medical Institute.
In 1940, he defended his thesis “The differentiation of endoderm in birds” and became a Master of Biological Science. In the period from 1945 to 1955, he was working at the Department of Histology and Embryology of the Military Medical Academy and defended his doctoral thesis " The Differentiation of the Cell Material of Embryonic Rudiments. "
From 1955 to 1981, he held the post of a head of the Department of Histology and Embryology of the Leningrad Pediatric Medical Institute. For a long time he was the editor-in-chief of the journal “Archives of Anatomy, Histology and Embryology”. He possessed outstanding personal qualities, encyclopedic knowledge of literature, history and architecture of his native city. He was the author of more than 140 scientific works devoted not only to histology and embryology, but also to the problems of methodology and philosophical aspects of biology. During his scientific career, he prepared 10 Candidates of Science.
Other young graduate students also were studying reproductive functions of mammals and humans, in addition to G. N. Petrov, at the Department of Histology of the Crimean Medical Institute:
· The study of secretion in the fallopian tubes was carried out by post-graduate student V. A. Korolev (head of the department of biology, professor in the future).
· The study of histophysiology of the male reproductive system was carried out by the post-graduate student B. V. Trotsenko (head of the department of histology, professor in the future).
· The study of changes in the bioelectrical potentials of germ cells during the period of fertilization and cloning of nuclei was carried out by the employee of the department, P. L. Velikiy, who started this work as a student.
The results of the G. N. Petrov researches were presented in 1959 in his PhD thesis.
At introduction it is told: “We believe that the experimental studies on fertilization will help to resolve a number of theoretical and practical issues of biology and medicine”. It was the way to infertility treatment known today as IVF.
From the dissertation of G. N. Petrov “In relation to humans, the data about the fertilization and early stages of development are extremely limited. From literary sources, only a few experiments have been performed on the fertilization of the human egg outside the body. These include the studies of Shetells (1953), who conducted 30 phase-contrast observations of human eggs obtained by gynecological operations by puncture of mature follicles with a diameter from 3 to 16 mm, and tube eggs obtained by washing the fallopian tubes immediately after their removal... The author was not able to observe the later stages of fertilization and cleavage of oocytes. Hamilton (1944), after series of experiments on the fertilization of human oocytes outside the body, had cited the information about the formation and exit of the polar bodies into the per vitelline space only. In the same year, Rock and Minkin (1944), after a number of unsuccessful attempts (800 experiments were performed) observed the development of human egg to the stage of two blastomeres in three cases. The authors indicate that cleavage occurred 10 hours after insemination”.
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In 2002, Professor E. M. Kitaev wrote in his memoirs " From the history of the development of the IVF program in Russia (How it all began... )": “In the early 40's, gynecologists from Harvard Rock, Minkin... were working on fertilization of human oocytes outside the body in the United States during four years. They even published the results of their research, but not being sure that they received true fertilization, they abandoned them, as they felt, futile efforts. The Americans have resumed their work on this problem only in 1978”. (After the birth of the first IVF child in the United Kingdom by R. Edwards and P. Steptoe).
In reality, in the mid-1950s, no one has consistently studied the fertilization and cleavage of an ovum in vitro.
“Ovaries were taken from women with various gynecological diseases during surgical interventions at the medical clinics of Simferopol.
Usually mature follicles in the ovaries were observed at women, when the operation was performed on the 13-14th day from the beginning of the menstrual cycle. Mature follicles as large as 1-1. 5 cm markedly protruded on the surface of the ovary.
To dilute and save the sperm, the following medium was used: 5 cm3 of sterile Ringer's solution, in which was placed a small piece of women oviduct mucous and 100 units of penicillin. There were also added 5-6 drops of proven seminal fluid.
After receiving the eggs, the follicular fluid of the Graaff's vesicle with the egg was placed in a tub of nutrient medium then added 2-3 drops (previously diluted) of the seminal fluid.
In 2003, Professor E. M. Kitaev told to V. V. Litvinov that the researchers in Leningrad (A. I. Nikitin's group, Leningrad) could not receive a fertilized egg for a long time. Professor E. M. Kitaev wrote in his memoirs " From the history of the development of the IVF program in Russia (How it all began... )" in 2002: “And only after the advice of the same Edwards, the spermatozoa were separated from the seminal plasma and then the sediment was dissolved in a new portion of the medium, they managed to get a suspension of male gametes were able to perform their function in vitro. It turns out that the seminal plasma is destructive for female germ cells. It was one of the first surprises that the researchers encountered in solving the task assigned to them”. At that meeting, Professor E. M. Kitaev learned the details of the G. N. Petrov studies and it seemed to me that he was disappointed that in the 70s of the XX century the researchers did not get acquainted in details with the Crimean works. Perhaps success to the Leningraders would come much sooner if they did it.
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G. N. Petrov diluted the sperm with a special medium (the best was a mix of Ringer's solution with the follicular fluid) and added 2-3 drops of diluted seminal fluid to the obtained human egg and, as a result, received fertilization and cleavage. Thus, the problem of the " destructive effect of" seminal plasma " on female germ cells" was solved as far back as 1955.
Professor E. M. Kitaev writes: “…there are morphological criteria for true fertilization. If, 6-8 hours after the gamete fusion, you see a fragment of the sperm tail in the oocyte cytoplasm, and the formation of one or two polar bodies, and somewhat later you see two male nuclei and female pronuclei, you can be sure that the spermatozoon penetrated the oocyte”.
There is no doubt that G. N. Petrov saw and examined consequentially the stages of fertilization and cleavage of the human ovum in vitro in 1955. It was 13 years earlier than the statements of R. Edwards and P. Steptoe about the emergence of in vitro fertilization technology in 1968.
In 1962, G. N. Petrov reported the presentation: “The process of fertilization of ova of mammals and humans outside the body” in the Academy of Sciences of the Georgian SSR at the meeting of the Society of Zoologists of Georgia. The report was like a bombshell. The following is written in the extract from the protocol № 47 from 29. 01. 1962: “…This work has a great practical and, undoubtedly, theoretical significance. The facts have been done by the author are considered to be reliable... According to experts, this work deserves exceptional attention and it is necessary to continue the extended studies in this direction”. Research continued until 1966, according to articles and reports made by G. N. Petrov.
The last report, presented by G. N. Petrov, became a sensation at the VII All-Union Congress of Histologists, embryologists (Tbilisi, 1966). His conclusion in the original sounds like this: “…Data on fertilization and cleavage of eggs in artificial conditions indicate the possibility of successful transplantation of embryos into the uterus after their cultivation for 2-3 days outside the body. ”
Such conclusions can be made if there are serious practice. Before the message of embryologist R. Edwards and gynecologist P. Steptoe from Cambridge University (Great Britain) about an appearance of IVF technology were three years.
There are not only scientific sources. There are evidences of that time in the mass media, scientific popular journals and statements of major scientists. Here are some of them:
· In 1961, in Leningrad, a meeting was held between Academician P. G. Svetlov and Italian " scientist" D. Petrucci. Petrucci " showed his achievements in the field of fertilization of the human ovum outside the body - a two-week embryo". At a press conference, Petrucci was asked: " Whom do you consider your predecessor? ”. He replied: " Of course, Grigory Petrov, a Soviet scientist from Simferopol”. (Journal “Technique of Youth”, No. 11, 1964, p. 10 - " Life Before Birth" ).
· Professor A. I. Nikitin (Research Institute of Obstetrics and Gynecology and Reproductology n. a. D. O. Ott) describes the arrival of an Italian in his memoirs like that: “The first kind of push that aroused interest in this issue was the arrival of the Italian scientist Petrucci to Leningrad. He became well known as a researcher who managed to grow a human embryo outside the body. The achievement of Petrucci looked incredible. When he told about his experiment in one of the auditorium of the Leningrad Medical Institute, a huge number of people gathered to listen to him. The organizers even had to call the mounted police to maintain order. The audience was impressed by the lecture of the Italian. (From the book " The History of ART in Persons", Moscow, 2007). Surprisingly, Petrucci was got to know with the research of G. N. Petrov and directly referred to them when talking about his own " successes in embryo cultivation up to 14 days" . We even now continue to attribute the priority in studies of the ovum fertilization in vitro to foreign scientists. We continue to ignore or try not to notice that in these works we were one of the first in the world.
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Here is a statement by Academician of the Academy of Medical Sciences of the USSR, Doctor of Medical Sciences, Professor L. S. Persianinov, who at that time held the post of Director of the All-Union Scientific Research Institute of Obstetrics and Gynecology at the Ministry of Health of the USSR: “As for Petrucci, I'm not very inclined to believe in his work. He did not publish any scientific article. Italian colleagues, whom I was interested in, also do not know his works. Well, as for the breeding of artificial people, I personally think it is unlikely that mankind will ever get to it”… Paradoxically, B. V. Leonov got the first pregnancy in vitro the USSR in that Institute in 1986 exactly.
The article " At the Origins of Life", published on 10. 01. 1962 in the newspaper “Crimean Truth”, tells about the work of a young scientist G. N. Petrov from the Crimean Medical Institute. There is talk about an infertility treatment by the method now is known as IVF in the provincial newspaper (1962): “Now the real prospects of transplanting the early embryo into the mother's body in case of infertility are opened before Soviet scientists”. It has been suggested that Petrov's studies may possibly be used in the treatment of human diseases – “Is it possible to use embryonic tissue for the treatment of certain serious human diseases? Maybe the secret of prolonging life and renewing of an aging organism is laid in it”. This is so in tune with what we are doing today! IVF is in bloom, the use of stem cells in the treatment of diseases becomes a reality. All this was expressed back in 1962 - the USSR, the Crimea, Simferopol. The following is a description of how the scientist worked: “…G. N. Petrov succeeded in more than 40 experiments with a living human cell. One day during 29 hours, without going away, he (G. N. Petrov) observed the process of fertilization in vitro. The observation log is completely marked with figures showing the development of " K-01" - Crimean " Pets”.
The article " Let happiness come to them" was published on September 30, 1962 in the newspaper “Crimean Truth” and told about the research at the Department of Histology in the Crimean Medical Institute and the use of an infertile female’s egg for the fertilization and further transfer of the embryo into the uterine cavity. The journalist wrote that dozens of letters came to the Department of Histology of Crimean Medical Institute from couples suffering from infertility. From the article: “" Here is one of them: “I strongly urge you to help to make our family happier. My husband and I want to have a child more than anything else does. However, no treatment helps me … Hope only for your experiences. I would very much like to be you’re the first patient”… Further in the article follows the description of the professor's technique: B. P. Khvatov assumes to operatively remove from the ovary a mature egg at first. Then he fertilizes it outside the body and after several days of development (corresponding to the time during which the fertilized egg resides in the tubes) place it in the uterus already ready for attachment of the embryo. Further development of the fetus will go the usual, quite natural way". Thus, the IVF method was described in the Crimean city Simferopol in 1962.
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Article “Embryology to medicine” is in the popular science magazine " Science and Life" (No. 3, 1962) by Professor Khvatov B. P.: “We set as our immediate goal of the development of a technique for transplanting a 3-4 day egg fertilized outside the body into the uterus of a woman suffering from infertility. The egg, needed for fertilization outside the body, can be taken from the same woman, whom it will be then transplanted into the uterus”. There was no information about this subject even in the special medical literature at that time in the world. 5 years share this article with the beginning of the studies of Professor R. Edwards. Further B. P. Khvatov writes: “Let me remind you, by the way, that the first experiments on fertilization and cultivation of the embryo of an animal (rabbit) outside the body were carried out by the Russian obstetrician V. S. Gruzdev in 1897. The human embryo developed outside the mother's body for three days in the experiments of G. N. Petrov in 1955. The study of the initial stages of the development of the human organism will allow scientists not only to solve important questions of practical medicine, but also to clue the many unexplored secrets of life that have long been of interest to mankind”.
In the '60s, Petrov G. N. was remembered the several times a day in the oral section " Science of the Crimea" during the excursion routes of trolley buses, which were taking vacationers to the South Coast of Crimea. This was a task for the guides to remind that our scientists were not born yesterday. (" Petrucci or Petrov? The Incredible History of a Forgotten Sensation", newspaper " Southern Capital" on 10. 01. 1997).
In the mid-1990s, a former student of G. N. Petrov returned from Germany. He enthusiastically said that the local scientists had exclaimed: “Are you from Simferopol? Oh, give our greetings to Herr Petrov! Tell him that we remember his scientific discoveries on the artificial fertilization of human eggs”. (“Komsomol Truth in Ukraine", 10. 01. 1997., " The first artificial man was created in the Crimea" ).
“Four roses... instead of the Nobel Prize” is the newspaper article in " The Medical Bulletin" (№ 16, № 17, November 2010, (Crimean State Medical University named after S. I. Georgievskiy). The article presents the memoirs of Professor of Histology B. V. Trotsenko and Professor of Biology V. A. Korolev who participated in those unique studies of reproductive function in mammals and humans in the mid-1950s. Memories are extremely valuable, since without them it is impossible to reconstruct some facts about those events. Both say that the scientists have attempted to transfer embryos to the uterine cavity at different times. From the article: “The announcement of the Nobel laureate name in Medicine and Physiology caused a significant resonance in our university in 2010. Someone was happy for science in general. Someone was sad, remembering that this " history" with artificial fertilization had begun at our institute in the 1950s… Only two participants and eye-witnesses of those years’ events are in good health now - Professor Boris Viktorovich Trotsenko and Professor Vitaliy Aleksandrovich Korolev.
CHAPTER 2. Organization of Obstetric Assistance. Maternity Welfare Clinic in Prevention of Maternity and Perinatal Disease Incidence and Mortality
Obstetric assistance is provided in special out-patient and in-patient hospitals, including: maternity welfare clinic, maternity home, obstetric department of a hospital, doctor’s assistant and obstetric station.
Maternity Welfare in Prevention of Maternity and Perinatal Disease Incidence and Mortality
Out-patient obstetric-gynecologic assistance is provided in maternity welfare clinics, gynecologic rooms of central regional hospitals, village out-patient clinics, out-patient general medical clinics, doctor’s assistant obstetric rooms, family planning centers, rooms for patient’s examination in polyclinics.
The basis of treatment-and-preventive work of maternity welfare clinic is a principle of proving service to women according to place of their residence (a territorial-district principle).
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The majority of maternity welfare clinics are functional subdivisions of maternity home, polyclinic, sanitary-medical unit or any other medical establishment and are subordinated to them. Some maternity welfare clinics are independent establishments and are subordinated to local health care bodies.
A maternity welfare clinic may be located in a standard or adapted building, or occupy a part of building belonging to obstetric in-patient hospital, polyclinic or medical unit.
Each maternity welfare clinic should have a gowning room for patients and staff, registry, waiting hall, offices of hospital manager, chief obstetrician, statistician, consulting rooms of obstetricians, doctors-specialists (therapist, dentist), procedure unit for intravenous and intramuscular injections, procedure unit for vaginal examination, endoscopy room, rooms for ultrasound examination, electrocardiogram examination, cardiotocography examination, sterilization, room for psychotherapeutic preparation of pregnant for birth, a room for “Maternity School”, family planning room, matron’s room, lavatories, etc. In some cities, big maternity welfare centres are equipped, which besides their everyday work fulfill the functions of a consultative center of polyclinic obstetric assistance. They are provided with modern diagnostic equipment, consulting rooms of specialists, rooms for special treatment (noncarrying of pregnancy, immunoincompatlible pregnancy, etc. )
The capacity of maternity welfare clinic is determined by a number of doctors’ districts, which are formed in accordance with population number, amount of patients’ visits. One obstetric district includes a territory with approximately 4, 000-4, 500 women, among whom 3, 000-3, 500 persons are older than 15 years and 2, 100 women are of childbearing age.
The main tasks of maternity welfare clinic are:
• clinical examination of pregnant;
• antenatal protection of fetus;
• prophylaxis of pregnancy, childbirth, puerperal period complications;
• providing qualified obstetric assistance to population of attached district;
• work on family planning;
• preservation of reproductive health of population;
• introduction into practice of modern methods of diagnosis and treatment of pathologic pregnancy, diseases of puerperas, new methods of out-patient obstetric assistance;
• provision of human rights in the sphere of maternity and childhood protection;
• providing succession in examination and treatment of pregnant, puerperant, maintaining permanent connection with maternity home, emergency, other medical-prophylactic establishments (antituberculous, dermatovenerologic, cancer dispensary, endocrinological, cardiologic, nephrological in-patient departments, etc. ).
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