24 February 2009

The place of biology in the hierarchy of sciences

"Cinderella" becomes a princess, or the place of biology in the hierarchy of sciencesAlexander Alexandrovich Yarilin,


Doctor of Medical Sciences, Head of the Department of Cellular Immunology of the State Scientific Center of the Russian Federation – Institute of Immunology of the Federal Medical and Biological Agency of the Russian Federation
"Ecology and life" No. 12-2008 (published on the website "Elements")

In recent decades, biology, previously considered almost an outsider among the natural sciences, has become a leader attracting increasing public attention, as well as material and human resources. The most impressive is the speed of this transformation. Naturally, the question arises about its causes. The article presents some considerations on this matter.

Features of biologyBiology – the science of life and living objects – traditionally belongs to the complex of natural sciences and is usually considered along with the main ones – physics and chemistry.

But even with the most superficial comparison of this triad, some features of biology that distinguish it from a number of natural science disciplines attract attention.

The main thing is the incredible complexity of the object of study – wildlife – in comparison with the stagnant nature studied by other natural sciences. Moreover, understanding the nature of life presupposes, as an unspoken but obvious condition, a preliminary understanding of the nature of inanimate matter. Of course, this statement should not be understood in the sense that the laws of inanimate matter must first be fully revealed, and then one can turn to the study of life. Rather, an analogy with medicine is appropriate here. Indeed, intervention in a living organism in order to cure diseases presupposes an understanding of the laws underlying vital activity, as well as knowledge of the nature of the disease. But if this principle were carried out literally, medicine as a kind of activity would not have appeared until now. In fact, just as medicine follows the development of biology at a respectful distance, biology develops at some interval after physics and chemistry. This "secondary nature" of biology in relation to physics and chemistry is manifested not only in the field of knowledge and understanding of the laws of living nature, based on more general laws of matter (but not following from them automatically). The methodological base of biology, the tools of this science come from technology, which is the brainchild of physics and chemistry. It is enough to recall that biology was given the creation of a microscope, the development of analytical chemistry methods, etc.

Another essential feature of biology is that its subjects (biologists), being living beings, are at the same time its objects. This gives biology an additional attractiveness compared to other natural sciences and serves as a guarantee of public interest in it at all times.

In addition, biology is the foundation of medicine, which is an applied branch of biology and, being an important incentive for funding, significantly affects the structure of biological research, favoring the development primarily of those areas that are most closely related to medicine.

So, it can be argued that due to the incredible complexity of the object of study, biology in its progress follows physics and chemistry, based on the methods and content of these sciences. At the same time, biology has a special appeal for a living object – a person – not only as a source of knowledge about himself, but also as the basis of medicine and other applied branches of biology, which are playing an increasingly important role in our daily lives day by day.
Biological dualism

The duality of traditional biology is most clearly manifested in the coexistence of its "corpuscular-genetic" and "physiological-metabolic" directions.

It is considered that the development of any natural science begins with observations and accumulation of facts, followed by theoretical understanding and experimental analysis of these facts and the relationships between them. For example, physics quite early separated the study of specific objects (the Universe, the Earth, etc.) from the study of the general laws of the existence of matter, giving rise to independent, albeit more private sciences – astronomy, cosmology, geology, etc. In biology, things were different. Until now, along with general biology, botany, zoology, microbiology, a complex of human sciences (including applied disciplines, including medicine) exist in its depths. Moreover, general biology only about half a century ago established itself as an independent, equal field of biology. In this regard, it is worth remembering that until quite recently there were no school textbooks on biology at all – instead there were textbooks on its private sections – botany, zoology, human anatomy and physiology and the notorious "Fundamentals of Darwinism" as a general biological teaching. All this can be considered, on the one hand, as a manifestation of the special complexity and diversity of the objects of studying biology, and on the other – as a sign of the immaturity of this science.

An excursion into historyLet's try to briefly review the history of biology in order to identify the most general trends in it (which will be needed for further reasoning).

Apparently, the first systematic appeal to the scientific study of living objects was human anatomy, which had an obvious applied medical orientation. The successes achieved in antiquity, the Middle Ages and the Renaissance have practically exhausted this field of research. In the Renaissance, in the works of the first physiologists (who studied the circulatory system), the human body "earned". To better understand how the human body functions, deeper chemical knowledge was required, and in the XIX century biochemistry and the doctrine of metabolism were born on their basis. The cell, distinguishable only through a microscope, began to be considered as the basis of a living organism. The emphasis was shifted from macroscopic observation of organs to microscopic analysis of tissue structure. At the end of the XIX century, ideas about the regulation of physiological functions, homeostasis arose and the doctrine of the central nervous system was formed, which became the crown of physiology.

Since, as already noted, this direction in biology was oriented and based primarily on medicine, and the possibilities of physiological research on humans were extremely limited, experimental animals had to be involved to study the processes occurring in the human body. As a result, the acquired knowledge acquired not only a narrowly medical, but also a general biological (extended to representatives of different species) interpretation. Proceeding from similar tasks and similar scientific installations, plant physiology and biochemistry developed in a similar way. This branch of biology can be designated as physiological and metabolic.

Another direction in biology from the very beginning focused on the study of general biological patterns. The initial approach here was the same descriptive approach. The first fundamental generalizations on this path are related to comparative anatomy. On its basis, the idea of the unity of living nature and the relationship between organisms was formed, which formed the basis of biological systematics, laid down in the XVII century.

The next step was to create an evolutionary doctrine, which was greatly facilitated by practical activities on artificial breeding of animals and plants in agricultural practice. Almost simultaneously with the development of Ch . Darwin's doctrine of natural selection as the basis of the evolutionary process, G. Mendel, established the corpuscular nature of heredity. Thanks to the prepared cytological (cellular) basis, this was followed by the rapid development of genetics (the chromosomal theory of heredity, the doctrine of mutations as a source of biological diversity, supplying material for selection, etc.). Genetics of the first half of the XX century was called formal for a reason: to understand the essence of genetic and evolutionary processes, the biochemical nature of units of heredity and objects of selection on it didn't matter at that stage. We will designate this branch of biology as corpuscular-genetic.
Two biologies?

It is easy to see that the approaches underlying the two branches were markedly different. At first, this was due to the difference in initial interests, tasks and concepts, but then it spread to methodological approaches, so that eventually formed two styles of scientific thinking. The differences in the views of the supporters of these "two biologies" were so serious that they answered the cardinal question differently - what is the basis of life.

The position of adherents of the corpuscular-genetic direction was briefly (although not too clear to the uninitiated) formulated by N.V. Timofeev-Resovsky: "The basis of life is invariant reduplication." By invariant reduplication, he understood the doubling of biological objects (ultimately, chromosomes, genes, DNA) with possible deviations from the initial state.

The followers of the physiological and metabolic direction considered metabolism to be the basis of life, the cessation of which is irreversible and means death.

It is impossible not to agree that both understandings of the nature of life are fair, but they are located, as it were, on different levels. Corpuscular-genetic understanding concerns primarily heredity – the process of self-reproduction and the causes of the diversity of living objects, whereas physiological-metabolic understanding is based on the registration of phenotypic manifestations of hereditary traits.

This duality of biology persisted until the middle of the XX century, when events occurred, the result of which was the synthesis of the considered directions. It was this synthesis that served as the basis for the unprecedented progress of biology, which brought it to a leading position in a number of natural sciences.

Synthesis of "two biologies" and the origin of molecular biologyThe Nobel Prize in Physiology and Medicine for 1962 was awarded to J.

Watson, F. Crick and M. Wilkins for deciphering the structure of DNA (work published in 1953). In fact, two different works were awarded the prize. M. Wilkins and R. Franklin subjected DNA crystals to X–ray diffraction analysis (an exemplary example of the synthesis of sciences: methods and principles of physics were used to study chemical structures - macromolecules of key importance for biology). J. Watson and F. Crick made a theoretical generalization regarding the structure of DNA, which made it possible to explain the basic properties of this molecule as a carrier of heredity. Even earlier, biochemist E. Chargaff (who later became an ardent opponent of the "new biology" with its stylistics and ideology) established that the content of the nitrogenous base adenine (A) in DNA is equal to the content of thymine (T), and the content of guanine (G) is equal to the content of cytosine (C); thus, these bases form pairs of A – T and C – G (Chargaff's rule), which served as a key fact for Watson and Crick to build a DNA model. The essence of this model was that DNA is a double helix, and the strands forming it are mutually complementary (in other words, complementary to each other) due to hydrogen bonds between certain nucleotides – exactly those that correspond to each other according to the Chargaff rule. The model made clear the role of DNA as a carrier of heredity, which is encoded by a sequence of nucleotides (the idea of the code was soon formulated by G. Gamov).

This generalization (which quickly became generally accepted) was followed by intensive research that developed these ideas and "embedded" them in the context of traditional biochemical concepts. Important milestones were: the study of the directed transfer of biological information from DNA to RNA (and from it to protein); decoding the code when transferring information from nucleic acids to proteins; the discovery of enzymes that catalyze the synthesis of DNA, RNA and proteins, as well as subcellular structures in which these processes occur. The entire chain of events from DNA replication to protein synthesis could be reproduced outside the cell.

Today it is clear that it was the discovery of the double helix structure of DNA that caused a rapidly growing avalanche of important results of general scientific significance, which inevitably led to nothing other than the synthesis of previously disconnected and seemingly incompatible branches of biology. Genes had acquired a "biochemical flesh", their work could now be represented in the form of biochemical processes. The biochemical basis of genetic processes has become clear in principle, and physiological patterns have been substantiated at the molecular level. Molecular rethinking, which initially affected the doctrine of heredity, quickly spread to the analysis of the basics of cell physiology, and then the organism. Nowadays, any research claiming heuristic and conceptual significance should include molecular, preferably molecular-genetic, reinforcement.

Thus was born a new science – molecular biology, and under its auspices there was a synthesis of corpuscular-genetic and physiological-metabolic directions of biology.

Fruits of the biological revolutionIn addition to the revolution in the understanding of wildlife, these results led to the creation of a new methodology that greatly enriched the possibilities of experimental biology.

Cloning of biological objects at the level of genes and cells has become one of the effective methodological approaches (it is too early to talk about cloning organisms for scientific analysis). In comparison with the previously existing methods of separation of molecules and cells, cloning has provided huge advantages due to a reduction in labor intensity, time and material costs, as well as a noticeable increase in efficiency. Sequencing methods have been significantly improved – the determination of the sequence of monomers in the composition of macromolecules, which have proved particularly successful for the study of nucleic acids. Based on new knowledge in the field of molecular and cellular biology, methods of matrix protein biosynthesis have been developed that are incomparable in speed and efficiency with traditional chemical synthesis. Finally, it was possible to develop methods of manipulating genes – they learned to "cut out" and "embed" them into cells, selectively control their activity, etc. All these approaches, surprisingly quickly developed within the framework of molecular biology, served as the basis for genetic engineering, which arose in the 70s of the XX century, just a quarter of a century after the deciphering of the structure of DNA - the discovery of the double helix. The techniques of genetic and, more broadly, molecular engineering have become intensively used in scientific research, which has significantly increased their evidentiary power. They have even been introduced into routine laboratory practice (for example, polymerase chain reaction has been widely used in medical diagnostics since the 80s to determine tissue compatibility, etc.). These methodological approaches have essentially revolutionized biotechnology.
[Polymerase chain reaction (PCR) is a method of molecular biology that significantly increases the low concentrations of individual DNA fragments in biological material (sample). In addition to the simple reproduction of DNA copies (amplification), PCR makes possible many other manipulations with genetic material (introduction of mutations, splicing of DNA fragments, etc.) and is widely used in biology and medicine (for example, for the diagnosis of hereditary or infectious diseases, establishing kinship, isolation and cloning of genes, etc.).]

Exact scienceUnlike physics and chemistry, which were originally exact sciences, biology claimed to be accurate only in a few of its sections (for example, genetics).

This was due to the fact that usually (especially in the framework of the physiological and metabolic direction) researchers were content with mixtures of molecules and cells, which they analyzed using methods that allow for different interpretations of the results. The use of molecular methods of analysis has made biology an exact science, since it allowed it to use pure biological substances (molecules, cells) in the study and apply methods that give unambiguous results. In this regard, the evidentiary power of biological research conducted using the new methodology has significantly increased. The consequence of these changes, in turn, was a sharp acceleration of the progress of biology: the amount of knowledge gained over the past decades is comparable to the amount accumulated in the field of biology over several centuries of its existence.

Ideological goals – global projectsIt is impossible not to mention such features of the development of modern biology as the focus on obtaining universal and fundamental results within the framework of global projects.

An example is the Human Genome project, aimed at the complete decoding of the human genome. At first glance, such knowledge looks redundant, similar to formal cataloging. However, upon closer examination, it is not difficult to make sure that this is not the case. For example, by studying the functioning of cells, researchers currently tend to determine the expression of all the genes involved in their work. Without their specification, it would be impossible to decipher the results obtained and, therefore, it would be impossible to judge the functions of the cell. To date, the genome of not only humans, but also mice, fruit flies, and the Cenorabditis elegans worm, which are favorite models of genetic and molecular biological research, has been completely decoded. Now, within the framework of proteomics, a similar cataloging of human and animal proteins is being carried out, which is already relevant to the realization of physiological functions of the body and can become the most complete expression of the synthesis of corpuscular-genetic and physiological-metabolic directions of biology.
[Proteomics is the science of proteins and their interaction (in particular, in the human body). Among the processes studied by her are protein synthesis, their modification, decomposition and replacement inside the body. Previously, the study of proteins was the content of one of the sections of biochemistry.]

Changing ideas about biology and its roleThe widespread penetration of molecular biology into all biological disciplines has given rise to the idea that traditional biological sciences (cytology, biochemistry, physiology) and even their individual sections (in medicine, for example, oncology, hematology, immunology) lose their individuality and turn into sections of a single molecular biology.

This view reflects the maximalism of adherents of the molecular approach in biology. However, similar episodes were noted not only in the history of biology and usually ended with the restoration of the sovereignty of scientific disciplines, which have their own specific tasks, objects and methods of research. For example, with any degree of penetration of molecular approaches into cell biology, the cell will always remain an independent biological object, not reducible to the sum of its molecules and generating special tasks and methodological approaches. To an even greater extent, the boundaries of the use of molecular approaches are felt during the transition from the molecular genetic and ontogenetic levels of life organization to the population and biosphere levels. Nevertheless, it is obvious that the ideological and methodological unity of biology has significantly strengthened due to the introduction of principles and methods of molecular approaches.

As already noted, the transition of biology to the molecular level has given rise to a new biotechnology. Its essence consists in the industrial use of methods of modern biology (in particular, genetic engineering) for the production of many practically significant biological products: new drugs and diagnostic drugs, food products, reagents for scientific research, etc. The most typical product of such production is recombinant (artificially created and possessing new properties) proteins, the synthesis of which is controlled new genes implanted in cells. Biotechnological production has long exceeded the traditional industry in terms of profitability – only computer technologies can compete with it. In this regard, the influence of biology on our everyday life has significantly increased, which, in turn, contributed to the growth of public attention to it.

New opportunities – new challengesThe increase in technical capabilities and the dramatic expansion of the influence of biology on people's lives has already created new problems.

Everyone knows the debate about the acceptability of genetically modified foods. The high profitability of biotechnological industries creates a tendency to unwittingly and implicitly impose their products (including medicines and food) with consequences that are still difficult to predict. The extremely rapid and seemingly uncontrollable progress of science itself has for some time inspired fear that biology will penetrate into the forbidden areas of human existence and affect such aspects of it as, for example, human individuality, the laws and limits of human existence, etc. The combination of the amazing progress of biotechnology with the successes of psychobiology gives rise to new concerns. Moratoriums established from time to time on research in certain areas of biology are always temporary and cannot stop the development of biology in all its forms and manifestations accessible to human capabilities. However, the very appearance of problems and fears of this kind is a sure evidence of the success of biology (previously they were afraid of radiation and chemical pollution, now they are products of biotechnology).

Practical applicationsThe general reasoning on this topic is vividly illustrated by concrete examples.

In the 1970s, a phenomenon called "apoptosis" was discovered, the meaning of which can be figuratively conveyed as the suicide of cells in the interests of a multicellular organism.
[Apoptosis is a programmed cell death accompanied by a set of characteristic features different in unicellular and multicellular organisms: for example, cell compression, condensation and fragmentation of chromatin filling chromosomes, compaction of cell membranes (therefore, during apoptosis, the contents of the cell do not enter the environment).]

In terms of its fundamental nature and significance, this phenomenon is comparable to cell division and differentiation. Its discovery was carried out by traditional methods, which for the first twenty years were also used for its study, which turned out to be very ineffective. But later (when biologists realized the significance of the discovery), molecular genetic approaches were used for analysis, choosing the mentioned worm C. elegans as an object - because of the high stability of the number of cells in this organism and the convenience of working with it. After that, a list of genes related to apoptosis was quickly established, their homologues (genes with the same structure) were identified in mammals, their role in this process was established, so that the mechanisms of apoptosis were generally deciphered.

For several years of work using the principles and methods of molecular biology, a problem that had not been amenable to research by traditional methods for decades was essentially solved.

Although the problems of medical diagnosis (and especially the prevention and treatment of cancer) are of concern to everyone, they have not yet been fundamentally solved, so oncology seems to be perhaps the most suitable springboard for the development of new approaches of practical importance. One of them concerns the search and production of tumor antigens, i.e. substances peculiar to tumor cells, but foreign to a healthy organism (at least an adult) and causing the formation of appropriate antibodies. Tumor antigens could become the basis of antitumor vaccines.

The first tumor antigen was discovered by G. I. Abelev in the early 1960s. Then many researchers were engaged in them, but their identification and isolation remained difficult problems. Molecular biology has made it possible to develop a relatively simple and effective approach to the creation of cancer vaccines. And even if it has not yet been possible to create sufficiently effective vaccines, this is more a problem of incomplete knowledge about the mechanisms of antitumor immunity than a consequence of imperfect technologies.

One of the most striking examples of using the methods of modern cellular and molecular biology as the basis of biotechnological production can be the industry of monoclonal antibodies, without which neither modern science nor medicine is unthinkable today.
[Monoclonal antibodies are produced by immune cells belonging to a single cell clone (i.e. derived from a single progenitor cell). They can be produced for almost any substance with which the antibody will specifically bind, which allows them to be widely used in biochemistry, molecular biology and medicine to detect a certain substance or purify it.]

Such antibodies are a very sensitive tool for the analysis of biological macromolecules. They are used in immunochemical analysis to identify and isolate substances, measure their concentration, and in medicine – for diagnostics. Traditionally, they were obtained by immunizing animals, i.e. by injecting them with a substance against which they wanted to get antibodies. However, a mixture of antibodies produced by different clones of cells responsible for the immune response was formed. Therefore, it was not possible to obtain standard preparations for the production of antibodies with the required specificity (selectivity) before.

This was done with the help of hybridom, a new technology based on the fusion of cells of immunized animals (usually mice) with tumor cells. Hybrid cells turn out to be virtually immortal and have a high ability to reproduce.

Using cell cloning methods, as well as a number of other techniques that facilitate the selection of hybrids, scientists isolate a clone of exactly those cells that produce the required antibodies. The resulting cells (these are hybridomas) combine the ability to produce specific antibodies with immortality. Such cells can be multiplied in any quantity and maintained indefinitely. The antibodies formed by them are homogeneous, and in other qualities they meet the requirements for the purest chemical reagents.

Hybridomas have caused a revolution not only in immunology, but also in medicine and biology in general. With the help of monoclonal antibodies, molecules and cells are already successfully identified, diseases are diagnosed, they are used to treat malignant tumors and other pathologies. However, mouse antibodies are foreign to the human body, which, in turn, produces antibodies to these antibodies, neutralizing them. But this problem was solved thanks to genetic engineering: all parts of the antibody molecule, except for a small area that determines its specificity, are replaced with human analogues. As a result, the antibodies, while maintaining specificity, cease to be foreign to humans.

The number of variants of monoclonal antibodies produced has long been in the hundreds of thousands, and their production remains one of the record profitability.

***

It seems that now we can return to the search for an answer to the question posed at the beginning of the article: why biology, which has been in the rearguard of natural sciences for centuries, has taken equal positions next to physics and chemistry, and even outstrips them in terms of development rates and funding scales. The proposed answer is that in the middle of the XX century there was a unification of two different approaches to the study of life – corpuscular-genetic and physiological-metabolic directions of biology. This synthesis, which resulted in the birth of a new science – molecular biology, provided a sharp increase in the capabilities of biology in all aspects, led to a rapid accumulation of accurate knowledge and created the basis for the development of new technologies, the influence of which extends far beyond science and penetrates deeper into our everyday life, causing close public interest.


Portal "Eternal youth" www.vechnayamolodost.ru24.02.2009

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