Alexander Nikolaevich Bazhanov’s Contribution to the Development of Tissue Biology and Evolutionary Morphology

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INTRODUCTION

Alexander Nikolayevich Bazhanov (1934–2019), Doctor of Medical Sciences and Professor, was one of the scientists who worked throughout his entire research career to solve basic issues of histology. He was one of the most prominent representatives of the Orenburg Scientific Histological School. The year 2024 marks the 90th anniversary of his birth and the 5th anniversary of his death.

LIFE MILESTONES OF ALEXANDER BAZHANOV

Alexander Bazhanov was born on January 28, 1934, in Samarskoye village, Yekaterinovsky District, Orenburg Region, to a family of collective farmers. He graduated from the Medical Department of the Orenburg Medical Institute in 1958. From 1955 to 1957, while he was a student, Alexander served as a deputy of the Orenburg City Council of Workers’ Deputies. He was also a member of the city council’s permanent committee on healthcare. After graduating from the institute, Alexander Bazhanov became the chief physician at the Ponomarevsky State Farm Hospital in the Ponomarevsky District of the Orenburg Region. He trained as a histologist at the Orenburg Medical Institute (Fig. 1 and 2) [1–4]. From 1962 to 1965, Alexander Bazhanov was a full-time postgraduate student in the Department of Histology at the Orenburg Medical Institute. He studied under the supervision of Professor Zoya Sergeevna Khlystova. Alexander Bazhanov was offered a position as an assistant professor in the department after completing his postgraduate studies in September of 1965. From February 1 to June 3, 1968, he served as acting head of the Department of Histology while Professor Khlystova was working in Moscow. In 1968, Alexander Bazhanov was elected associate professor in the Department of Histology at the Tselinograd Medical Institute [1–4]. Professor Bazhanov worked in this department from 1968 to 1997. He first served as an associate professor, then as head of the department. The only exception was from December 1986 to October 1987, when he was the head of the Department of Histology at the Stavropol Medical Institute. Professor Bazhanov had a bright start to his scientific research career and continued it until the mid-1990s. He stopped publishing almost entirely due to illness and retirement in the late 1990s. He then moved to the Stepanovsky farm in the Orenburg District of the Orenburg Region, where he lived for about twenty years until his death.

Fig. 1. Alexandr Nikolaevich Bazhanov (1967) (photo from the archive of the Department of Histology, Orenburg State Medical University).

Fig. 2. The staff of the Department of Histology of the Orenburg Medical Institute (1964): top row — graduate student Bazhanov Alexander Nikolaevich, assistant Abdrashitova Emina Hamidovna; bottom row — assistant Savitskaya Lyudmila Andreevna, associate Professor Volodina Evgeniya Petrovna, Professor, head of the Department Zoya Sergeevna Khlystova, graduate student Semchenko Yuri Petrovich. Photo from the archive of the Department of Histology Orenburg Medical University.

However, Professor Bazhanov remained interested in morphological issues even after retirement. His students, coworkers, and colleagues from different cities often sought his advice.

Bazhanov’s scientific legacy includes nearly 100 articles and 3 monographs, two of which were co-authored (Fig. 3) [5–7].

Fig. 3. Monographs, which were prepared by Alexander Nikolaevich Bazhanov (books from the library of the Department of Histology of Orenburg Medical University).

This study aimed to describe Professor Bazhanov’s contributions to the development of fundamental issues in tissue biology.

STUDY OF MORPHOLOGY AND FUNCTION OF THE EPITHELIUM OF THE MUCOSA OF THE HUMAN AND ANIMAL ESOPHAGEAL MEMBRANES

Bazhanov’s research focused on the esophagus of humans and animals. His Candidate of Sciences thesis, titled Histological and Histochemical Characteristics of the Esophageal Mucosa in Ontogenesis and in Experimentation [8], which he defended on March 11, 1966, and several articles, were devoted to various aspects of the esophageal mucosa’s structure [9–12]. He was an author of several articles and a monograph [6] devoted to the comparative morphological and functional characteristics of the esophageal epithelium. This work is based on his Doctor of Science thesis titled “Properties and Distinguishing Features of the Esophageal Epithelium” [13], which he presented on October 8, 1980, at the meeting of Specialty Council D 074.42.01 (Д 074.42.01) at the Novosibirsk State Medical Institute.

Professor Bazhanov obtained new data and resolved disputed issues regarding the esophageal epithelium, including its origin in phylogenesis, transformation patterns in human and animal ontogenesis, morphology, and function of integumentary and glandular epithelia, and in vivo differentiation using Lazarenko’s technique. He also investigated the reactive and adaptive restructuring of the epithelium under various destabilizing factors.

Professor Bazhanov studied the origins of the esophageal epithelium and initially proposed that it evolved from the prechordal plate [5, 8]. However, Professor Bazhanov later changed his opinion based on new data he had obtained and began considering the endoderm to be the source of the esophageal epithelium [6, 13]. Professor Bazhanov compared the epithelium of the human esophagus with epithelia of ectodermal and endodermal origin. He noted the following differences: a smoothed basal membrane, a significantly thickened cambium, secretory activity in the intermediate layer, an endocrine function in the glandular component, and a special protective barrier that prevents the epithelium from keratinizing under normal conditions. The main difference between the esophageal epithelium and the intestinal epithelium is the multilayer structure of the latter [8, 13]. The origin of the esophageal epithelium is still debated. Most researchers believe it is endodermal.

Professor Bazhanov discovered that during the embryonic development of humans and other vertebrates, the epithelial lining of organs that originate from the foregut, such as the esophagus, undergoes normal changes. In the early embryogenesis, the esophagus epithelium is single-layered (simple). Then, it is replaced by a multi-row (pseudostratified) epithelium, which is then replaced by a multi-layered (stratified) squamous epithelium. In humans, this occurs during the middle of the fetal period [14–26].

Professor Bazhanov characterized the features of synthetic processes in the epithelial cells of human and animal esophagi at various stages of ontogenesis and in experimental settings based on his analysis of histochemical reactions. He was focused on the integumentary and glandular epithelia of the esophagus. Using histochemical techniques, he studied the exocrine and endocrine cells of the cardiac glands of the human esophagus and identified several types of endocrine cells in these glands [27–30]. Professor Bazhanov concluded that the identified cells may have similar tinctorial properties to those of the A-, B-, and D-cells of the pancreatic islets [29].

At that time, the Department of Histology of the Orenburg Medical Institute used the technique of culturing organs and tissues in the body, which was developed by Fedor Lazarenko [31]. Alexander Bazhanov mastered this technique during his postgraduate studies and used it as the primary technique in his subsequent research. While working in the histology departments at the Orenburg and Tselinograd Medical Institutes, Professor Bazhanov tracked the development of esophageal structures over different time periods (from 1 to 20 days). Epithelial structures were no longer detected in the implants when they were cultivated for more than 20 days, because all implanted tissue components died [5, 6, 8, 13, 32, 33].

Professor Bazhanov discovered that only the youngest cells in the lower layers of the epithelium enter a state of proliferation. Under culture conditions, epithelial growth can manifest in two forms: integumentary layers or submerged strands. In most cases, the integumentary layers are multilayered. The esophageal epithelium rarely grows as a single layer. These single layers were found to differentiate into single-layer structures, such as squamous, cuboidal, and columnar epithelia. Less frequently, they differentiated into pseudostratified epithelia. The epithelium of the newly formed integumentary layers can grow into the underlying connective tissue as submerged strands. Professor Bazhanov demonstrated that newly formed undifferentiated layers and submerged strands differentiate during cultivation. In some cases, differentiation occurs up to the point of keratinization of the epithelial layer [6, 8, 13, 32, 33].

Professor Bazhanov described how the esophageal mucosa epithelium reacts and adapts to chronic exposure to various negative factors. When negative factors are not very intense, the epithelium responds by increasing its synthetic activity and mild thickening of the layer. Strong, irritating stimuli cause a sharp increase in mitotic activity in cambial cells, leading to asynchronous reactive manifestations in the epithelium and connective tissue. This is primarily due to a delay in the epithelium’s reactive potential [8, 13, 34].

The sources of origin, main mechanisms, and differentiation patterns of the esophageal epithelium in human ontogenesis were identified through tissue cultivation using Lazarenko’s technique. For example, under implantation conditions, the esophageal epithelium was found to demonstrate polymorphism of strands, which was reflected by the development of stratified and simple, as well as pseudostratified, epithelia under the same conditions [5, 6, 8, 13, 32, 33]. The growth of the esophageal epithelium in cultures differs significantly from that of ectodermal and endodermal derivatives. Based on the evidence obtained, Professor Bazhanov hypothesized that the esophageal epithelium may originate from the prechordal plate, which demonstrates properties of both the ectoderm and endoderm [5, 8]. This led Professor Bazhanov to reevaluate the origin of the prechordal plate and how its derivatives differentiate.

Professor Bazhanov published several dozen articles on morphology and function of the integumentary and glandular esophageal epithelium and two monographs “Morphology of the Cranial Sections of the Digestive and Respiratory Systems” [5] and “Properties and Distinguishing Features of the Esophageal Epithelium” [6].

DEVELOPMENT OF FUNDAMENTAL ISSUES OF MORPHOGENESIS AND EVOLUTION OF TISSUES

Professor Bazhanov made fundamental contributions to tissue biology by comparing the histological characteristics of the esophageal epithelium in vertebrates. His research focused on the comparative histological analysis of histogenesis and tissue differentiation, using a histogenetic approach in most of his published works.

Professor Bazhanov discovered that the epithelial lining of the esophagus undergoes regular transformations during vertebrate evolution. For example, the simple epithelium typical of the esophagus of many lower vertebrates transforms into a pseudostratified epithelium that produces mucus. This transformation can be observed in some fish, all amphibians, and most reptiles. From this pseudostratified epithelium, stratified mucous epithelium is formed, which is found in some reptiles. During the evolution of vertebrates, this stratified epithelium evolved into a stratified squamous epithelium in all birds and mammals [6, 13].

In addition, Professor Bazhanov demonstrated that the divergent nature of esophageal epithelial differentiation is evident in embryonic histogenesis and at various stages of organism evolution. He proposed that this divergence causes the epithelium to combine its original endodermal properties with its newly acquired, convergent features as a stratified epithelial cover [6, 13].

It should be noted that, as a researcher, Professor Bazhanov was not afraid to abandon his own ideas when new facts refuted them. This can be traced through his evolving views on the nature of the prechordal plate and its derivatives. In the early 1960s, Professor Bazhanov believed that the esophageal epithelium originates from a special primordial tissue that is distinct from both the ectoderm and the endoderm and may originate from the prechordal plate [5, 8]. Professor Bazhanov considered the results of culturing the esophageal epithelium in vivo using the Lazarenko’s technique as the most compelling evidence supporting the theory that the esophageal epithelium originates from the prechordal plate. However, based on new data he obtained in the 1970s and 1980s, Professor Bazhanov suggested that the prechordal plate has an endodermal origin. In addition, he challenged the suggestion that the prechordal plate is responsible for the epithelial histogenesis in the pharynx, esophagus, air-bearing structures of the lungs, and branchiogenic glands [6, 13]. Professor Bazhanov based his conclusion on the characteristic location of the prechordal plate and the structure and volume of its derivatives.

Among Professor Bazhanov’s works on comparative and evolutionary morphology [5–7, 35–41], the monograph “Phylogenetic Foundations of Animal Tissue Organization” [7] should be particularly mentioned, which was co-authored with Igor Borisov and Pavel Dunaev. The monograph discusses the origin of multicellular organisms, the emergence and transformation of tissues throughout evolution and ontogenesis, and the classification of tissues. Phylogenetic reconstructions of the evolutionary changes in tissues of various organs of humans and vertebrates are especially interesting.

Many of the ideas presented in this monograph are still discussed. For example, the authors stated that Mechnikov’s theory of parenchymella (phagocytella) was not well-substantiated. According to Bazhanov and his co-authors, the endothelium should not be classified as an epithelial tissue because it most likely shares a common stem cell with the hematopoietic lineage. Regarding the levels of organization of organisms, the authors stated that morphological and functional criteria are used to classify tissues and that genetic criteria are used to classify histogenetic units. Based on cell differentiation and evolutionary changes, lineages can be identified. These subunits play an equal role in the organization of organisms and can be classified by three groups of criteria [7, 40].

APPLIED RESEARCH IN HISTOLOGY, CYTOLOGY, AND EMBRYOLOGY

Professor Bazhanov primarily focused on fundamental issues of histology, but he also constantly investigated applied issues in medicine and biology. For example, his first published work discusses reactive changes in the skin caused by antiseptic agents, such as iodine solution and formalin [42]. Several of his works explored the morphological and functional characteristics of the esophagus, testes, and pancreas in various pathological conditions such as Barrett esophagus, hypoxia, clinical death, and post-resuscitation period [43–46]. Professor Bazhanov demonstrated that hypoxia negatively affects the spermatogenic epithelium during the final stages of the post-resuscitation period, resulting in the formation of abnormal germ cells and disruption of their differentiation. During the degeneration and death of germ cells, the spermatogenic epithelium of convoluted seminiferous tubules contains spermatocytes and spermatids with large nuclei, as well as multinucleated forms of developing germ cells. The article by Professor Bazhanov should also be mentioned [47], which described patterns of insulin content changes in rats at different post-resuscitation stages.

SIGNIFICANCE OF ALEXANDER BAZHANOV’S RESEARCH BY PROMINENT RUSSIAN MORPHOLOGISTS

As previously mentioned, Professor Bazhanov frequently addressed controversial histology issues in his publications. His work inspired active discussions in journals such as the Archives of Anatomy, Histology, and Embryology (Arkhiv anatomii, gistologii i embriologii). From 1978 to 1988, five reviews of Bazhanov’s work were published by prominent Soviet morphologists, including Alexey Knorre, Georgiy Schmidt, Nikolay Kochetov, and Moisey Shubich [48–52]. Alexey Knorre, editor-in-chief of the Archives of Anatomy, Histology, and Embryology journal and corresponding member of the USSR Academy of Medical Sciences, published an extensive review of the joint monograph co-authored by Alexander Bazhanov [5]. The review thoroughly discussed all of its chapters. Knorre wrote, “This small yet significant joint monograph is completely devoted to clarifying the histogenetic specificity of foregut derivatives. The authors selected Lazarenko’s implantation technique as the primary method for resolving this controversial issue in histology <...>. The authors of the monograph gathered substantial information on the behavior of foregut derivatives under implantation conditions (Lasarenko’s term for “cultivation in the body”) <...>. The Orenburg histological school is renowned for its preparation and microphotography techniques. During a visit to the department, the reviewer saw excellent demonstrations of these techniques, including preparations and color slides of the studies presented in the monograph.” Knorre concluded that “it is important to emphasize the clear value and interest of the factual material obtained through many years of dedicated work by a large group of authors.”

In 1978, Knorre published a positive review [50] on Bazhanov’s monograph, “Properties and Distinguishing Features of the Esophageal Epithelium” [6]. On page 160 of that review, Knorre wrote, “This implies that the publication of this book is urgent and will contribute positively to the ongoing debate about controversial but not pointless issues on the origin and nature of foregut epithelia. This issue is not purely academic. The author correctly emphasizes that the problem involves their medical aspects related with dangerous blastomatous developmental anomalies.” For this reason, discussions surrounding the issue cannot be pointless.”

Professor Schmidt [51] wrote another review of this monograph. He wrote that “Properties and Distinguishing Features of the Esophageal Epithelium” by Bazhanov is a serious monograph “based on a large body of comparative embryological and histological data on various vertebrate groups that Bazhanov investigated personally. The author’s research is clearly thorough and honest.”

The monograph “Phylogenetic Foundations of Animal Tissue Organization” by Bazhanov, Borisov, and Dunaev received controversial reviews [7]. After the monograph was published, Kochetov reviewed it negatively in Archives of Anatomy, Histology, and Embryology [48]. Kochetov concluded that, “by suggesting new ‘basic concepts of histology,’ the authors had appropriately challenged the validity of these ideas. Therefore, it appears that they did not accomplish the task they set out to do.”

Some time later, Shubich published a more balanced review, highly appreciative of the authors’ work [52]. He concluded that “in general, the reviewed monograph deserves a high appraisal. It synthesized a large body of evidence from various fields of biology and developed novel theories regarding the origins of multicellular organisms and the evolution of tissues. In addition, it introduced new theoretical concepts to general histology. Given the difficulty and extraordinary nature of the task, it is unreasonable to expect a clear approach to determining the limits of factual data extrapolation or all statements being completely persuasive. Though the monograph is challenging to read, morphologists who master its content will deepen their understanding of evolution and greatly expand their theoretical knowledge.”

CONCLUSION

Professor Bazhanov primarily focused his research on developing fundamental histology. His research on embryonic morphogenesis, focusing on the esophagus, helped determine the origins and progression of digestive organ alterations during embryonic development, and also advanced the study of controversial issues in tissue biology. Comparative histological papers made significant contributions to the development of evolutionary issues in histology. Professor Bazhanov’s research was widely recognized during his lifetime as being important to advancing modern tissue biology. These studies have remained relevant even several decades after they were completed.

ADDITIONAL INFORMATION

Author contributions: The author confirms that his authorship complies with the ICMJE criteria (he developed the article’s design, collected and processed the material, prepared the text and illustrations, and reviewed and approved the final version prior to publication). The author agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding sources: The author declares no external funding was received for this research and analytical work.

Disclosure of interests: The author has no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

About the authors

Nikolay N. Shevlyuk

Author for correspondence.
Email: k_histology@orgma.ru
ORCID iD: 0000-0001-9299-0571
SPIN-code: 6952-0466

Dr. Sci. (Biology)

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2. Fig. 1. Bazhanov Alexander Nikolayevich (1967). Photo from the archive of the Department of Histology Orenburg Medical University.

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3. Fig. 2. The staff of the Department of Histology of the Orenburg Medical Institute (1964): top row — graduate student Bazhanov Alexander Nikolaevich, assistant Abdrashitova Emina Hamidovna; bottom row — assistant Savitskaya Lyudmila Andreevna, associate Professor Volodina Evgeniya Petrovna, Professor, head of the Department Zoya Sergeevna Khlystova, graduate student Semchenko Yuri Petrovich. Photo from the archive of the Department of Histology Orenburg Medical University.

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4. Fig. 3. Monographs, which were prepared by Alexander Nikolaevich Bazhanov (books from the library of the Department of Histology of Orenburg Medical University).

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