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SOME REMARKS ON THE HISTORY OF BIOPHYSICS by Marco Bischof Paper delivered at the 1st Hombroich Symposium on Biophysics, Neuss, Germany, October 3-6, 1995. WHAT IS BIOPHYSICS ? - A LOOK AT SOME BOOKS Someone looking through a number of contemporary textbooks and introductions in biophysics - as I did - and wanting to know exactly what biophysics is and what the field covers, will be quite bewildered. Even the titles of the books with their diversity of names for the field, besides biophysics, such as „Medical Physics“, „Medical and Biological Physics“, „Physical Biology“, „Physical Bases of Medicine and Biology“, and „Molecular Biology“, already show the existence of different interpretations and tendencies. Looking at the tables of content, we find that some books have the application of physical devices and measurements to physiological problems as the only subject of biophysics. Some others are structured according to the different categories of physical phenomena, i.e. the mechanical, thermal, acoustical, electromagnetic and nuclear, gas, fluid etc. aspects of living systems, or according to the different systems in the organism. In not a few instances, life processes such as transport processes, chemical reaction kinetics, the acid-base-balance, and diffusion processes are treated without reference to the organisational level concerned. In general - with a few notable exceptions - the notion of a hierarchy of subsystems within the biological system, and any kind of overall view of the organism as a whole, is completely absent or relegated to the introduction. In only a few instances we find a chapter on theoretical biophysics aimed at a synthesis of all these partial aspects of the biophysical treatment of organisms. Most of the very recent textbooks are dominated by, if not exclusively devoted to, investigations of molecular structures and processes, proteins, nucleic acids, genetic mechanisms, and membrane processes. One of the major modern textbooks, „Biophysics“ by W.Hoppe et al., 2nd edition published in 1982 by Springer, has a clear emphasis on the molecular level (macromolecules, enzymes, molecular interactions, energy transfer etc.), much less space is devoted to the subcellular and cellular levels (organelles, cell architecture, membranes, neurobiophysics), and even less to the level of organs, organ systems and whole organisms (in subjects such as parts of biomechanics, cybernetics) or to whole populations and the interaction of organisms with the environment (environmental biophysics). Physical methods of investigation take very extended space (1/6 of the 950 pages of the volume), while, typically, the treatment of the biological effects of electromagnetic fields is restricted to ionising radiation and that of electrical fields and currents in the organism to membrane potentials, electroreception in fish, and, surprisingly, the control of differentiation and growth by ionic currents. It seems that biophysics covers a very disparate field of investigations; no two textbooks agree on its
scope and range, and no one seems to cover all the relevant questions. Already in 1940, J.R.Loofbourow wrote that
there is „no clear agreement, even among biophysicists, as to what the term biophysics means“ . Today, the situation
has not much changed. CHANGES IN EMPHASIS IN THE COURSE OF THE HISTORY OF THE FIELD Not very surprisingly after our look into the books, many people today would identify biophysics with molecular biology. However, as we will try to show, biophysics is a much wider field and in the course of its history, has not always had this this narrow scope and molecular emphasis. Biophysics is a relatively young field of science. Scientific investigations by means of physical instruments, and the explanation of their results by physical and mathematical concepts, have been carried out since about 1840, and as a separate discipline it has established itself only since about the 1920’s, if not the 1940’s. Although certain isolated problems in physiology had been treated before 1840 in a physical manner, by such men as E.H.Weber, Volkmann, and Johannes Müller, the so-called „Berlin school of physiologists“, including Hermann von Helmholtz, Emil DuBois-Reymond, Ernst von Brücke, and Carl Ludwig, were the first to conduct a „broadly planned, systematic investigation of an extensive field of physiological phenomena in accordance with the most rigourous physical methods“ and assert as a general law that „a vital phenomenon can only be regarded as explained if it has been proven that it appears as a result of the material components of living organisms interacting according to the laws which those same components follow in their interaction outside of living systems“ . This group had set up in 1847 a program which seems to anticipate that of modern biophysics . This program is reflected in the following statements by DuBois-Reymond, taken from Cranefield. In 1841 he wrote “I am gradually returning to Dutrochet’s view ‘the more one advances in the knowledge of physiology, the more one will have reasons for ceasing to believe that the phenomena of life are essentially different from physical phenomena“, and in 1842: „Brücke and I have sworn to make prevail the truth that in the organism no other forces are effective than the purely physical-chemical“. In 1848, in the preface to his famous „Untersuchungen über thierische Electricität“, DuBois-Reymond asserted that „it cannot fail that...physiology...will entirely dissolve into organic physics and chemistry“. In 1856 Adolf Fick, pupil of Ludwig and strong adherent of all the goals of the Berlin school, published
the first textbook of biophysics . But the program of the Berlin school of reducing physiology to physics
and chemistry was quite premature; 19th century physics and chemistry were not sufficient to provide molecular
explanations or any other complete physical models for living systems. As Cranefield has shown, the Berlin school
has failed to carry out its program of 1847 and has mainly lived on through its physiological approach. It was
very successful in establishing experimental methods - which they were, however, by no means the first to introduce.
Their anti-vitalistic stance, the assertion that the explanation of life processes must be sought in the ordinary
laws of inorganic nature, had its most significant importance in the implication of an intelligible and accessible
causality, making life processes amenable to experimental investigation. The only biophysical fields developed
by it that continued to be of importance in classical physiology are the mechanical and thermodynamical investigation
of muscular contraction and the electrical study of the nerve impulse. General physiology, however, followed a
quite different course till World War I than the one outlined by the 1847 program. It is only in the program of
the molecular-biological variety of biophysics predominating since about 1960 that this program seems to be carried
out. In the period from the 1920’s, when the first biophysical university institutes were established in Germany and the (presumably) first book carrying the word „biophysics“ in the title was published , till about 1940 the biophysical studies mainly were concerned with the interactions of organisms and radiation, at least in Germany. After investigating the biological effects of high-frequency electromagnetic fields and light - not to forget a study of Gurwitsch’s mitogenetic radiation in 1931 - members of the Frankfurt Institute for the Physical Bases of Medicine, together with other researchers such as Nicholas Timofeeff-Ressovsky, K.G.Zimmer, J.A.Crowther, E.U.Condon and Max Delbrück, became the leading investigators in the elucidation of the biological effects of ionizing radiation. The Frankfurt institute was founded in 1921 by Friedrich Dessauer and in 1934, under the direction of Boris Rajewsky, renamed into (the first) „Institute of Biophysics“ under the umbrella of the Kaiser-Wilhelm-Gesellschaft. Studies of ionizing radiation dominated biophysics in the period and had their second climax in the beginning of the nuclear age in the mid-1940’s , after a first one in the 1920’s. Still in 1955 Otto Glasser noted that biophysics and many books on this subject were unduly dominated by radiation biophysics, which was only one of many subspecialties in this field . From 1950 to 1970 biophysics developed faster than in the 100 years before. While in 1944, when the first volume of Otto Glasser’s „Medical Physics“was published, in the USA the number of workers in the field counted not more than 200, in 1950, when volume II appeared, about 200 institutes or departments were devoted to biophysics . At the same time the scope of the field also greatly expanded. Glasser’s handbook still remains one of the most complete treatments of the full range of biophysical investigations; it also includes physical therapies, mitogenetic radiation (biophotons), the biological effects of light and electromagnetic fields, and a chapter on bioelectric fields by H.S.Burr. However, in the same period of the 1950’s molecular biology experienced its breakthrough with Watson and Crick’s 1953 model of DNA. The first phase of its development (1930-1950) which included the acceptance of the existence of macromolecules, the use of x-ray diffraction analysis (started by Bernal in 1934) for determining molecular structures and the development of extraction methods that avoided degrading of molecules, was characterized by a relatively broad definition of the subject . The term „molecular biology“ was first used by Warren Weaver in 1938 to describe a grant programme by the Rockefeller Foundation promoting „experimental“ or „physiochemical“ biology. He claimed this was a new branch of science in which modern tools were „reaching deeper and deeper into the living organism“. The program was supported by such people as W.T.Astbury, who was the first to describe himself as a molecular biologist, Linus Pauling and Max Perutz. Schroedinger’s little book „What is life ?„ (1944), in which he took up Delbrueck’s idea that the gene could be a molecular structure (Schroedinger called it an „aperiodic crystal“), played an important role in the beginnings of molecular biology. The book inspired many physicists after the war to go into biology. Delbrueck’s idea originally came from Niels Bohr: it concerned the question if not maybe certain aspects of the life of a cell, such as self-replication, could only be explained by a new kind of natural law still to be discovered, in a similar way as classical physics had been replaced by the quantum physical worldview. The inspired search for such new natural laws was one of the main motivations of many of the newly converted molecular biologists .Gunter Stent, Maurice Wilkins, and Francis Crick all have confessed to having been greatly influenced by Schroedinger’s book. Most of them participated in the 1st phage meeting at Woods Hole where a proper school of molecular biology was created in 1945. However, this romantic, even somewhat vitalistic program of the very beginnings of molecular biology was soon turned almost into its opposite, the still ongoing, gigantic enterprise of analyzing systematically a broad range of molecular details. Maybe it was inevitable. When in 1937 the eminent biologist Barbara McClintock met Max Delbrueck, maybe the single most influential figure of the founders of molecular biology, she considered his approach to be fundamentally flawed . „He has never developed a feeling for the organism“, she said. The second phase of molecular biology (1950 onwards) clearly is characterized by a narrowing down of the subject to the investigation of biological „specificity“ (molecular „information“), involving the study of proteins and nucleic acids in view to understand genetical structures and mechanisms. This trend was not without influence on the development of biophysics proper, as is reflected in the Study Program in Biophysical Science, Boulder, Colorado, 20 July-16 August 1958, organized by the Biophysics and Biophysical Chemistry Study Section of the U.S.National Institutes of Health . Its objective was to „encourage the further blending of concepts and methods of physical science with those of life science in the investigation of biological problems“, in other words, to further physicalize biology. Its approach was that of molecular biology. Basically, molecular biology and mainstream biophysics as they have developed since the 1950’s because of their extreme emphasis on molecular and physicochemical aspects of physiology have to be considered as being in the tradition of physiological chemistry rather than physiological physics. They are based rather on the kind of work exemplified by Höber’s „Physical Chemistry of Cells and Tissues“ (1945) , and later, Setlow and Pollard’s „Molecular Biophysics“ (1962) , and represent a late triumph of the reductionist program of the Berlin school of 1847. However, this approach has long remained foreign to the practice of physiological science. As Cranefield wrote in 1957 , „there is ample indication that during the last few decades physiologists in all countries have not considered the elucidation of molecular mechanisms, the dissolving of physiology into biophysics and biochemistry as their immediate goal. (...) As for the theoretical bias of modern physiology, it is still common to define physiology as the physics and chemistry of life and to assume that the mechanistic stand is correct. Nevertheless, a position sometimes called organicism holds a very wide popularity today: the position that is identified with the frequent use of such concepts as homeostasis, integration, adaptation, organization, and whole organism. These biological concepts are essentially neutral but to some they carry a flavor of vitalism“. This alternative current of physiological and biological thinking which can refer to Claude Bernard who rejected German reductionism, represented by such names as A.G.Gurwitsch, E.S.Russell, E.Rignano, P.Weiss, J.Needham, D’Arcy Thompson, J.S.Haldane, J.Barcroft, W.H.Cannon, C.H.Waddington, A.Meyer-Abich and L. von Bertalanffy, has only quite recently fallen into disregard. Correspondingly, there is also in biophysics another tendency which has developed since the 1920’s and
has not always been eclipsed by the dominating school to the degree it seems to be today. In Germany, it has been
represented by the work of Walter Beier and his school at the Institute of Biophysics of the University of Jena
(German Democratic Republic) . Applying the findings of the school of the Austro-Canadian biologist Ludwig von
Bertalanffy to biophysics, Beier has developed a systemic, comprehensive approach which always aims at the wholeness
of the system considered. In this approach a system is not viewed as a conglomerate of parts and it does not investigate
isolated phenomena, but rather the wide field of interactions. Biological processes on each systemic level, i.e.,
molecular, cellular, tissue, organ, and organismic, are considered in the context of the higher level in which
they are embedded. Besides systems theory, Beier’s approach is based on the irreversible (non-equilibrium) thermodynamics
of open systems (while earlier biophysics uses equilibrium thermodynamics), information theory, cybernetics, and
uses tools such as factorial analysis. He also follows Rashevsky who introduced relational and similarity
considerations and optimization principles into biophysics. THE SITUATION TODAY As we have seen, today in biophysics such a holistic approach is not widespread. The textbooks rather reflect the fragmentation of contemporary science with its excessive analysis, lack of synthesis and of a viable theory of life. Biology has lost the wholeness of life, if not life itself, from its view. In spite of the programmatic postulate which has accompanied it since 1847, biophysics still has not developed into a theoretical biology. Beier is one of the few biophysicist aware of the central importance of theoretical biophysics as a complex, interdisciplinary branch of science, and has also shown a practicable way to develop theoretical models. His approach, developed in the 1960’s and 1970’s, can now be used as a starting point for the development of a modern, holistic, and organicist (non-reductionist) biophysics which should place much emphasis on investigating the holistic functions of organisms, such as self-regulation in growth and healing, morphogenesis etc. Besides the conceptual tools that Beier has brought into play, such a new approach in biophysics must call upon many new developments in science, such as nonlinear electrodynamics, deterministic chaos, cavity quantum electrodynamics, and the physics of the vacuum. Full use of the consequences of quantum physics, such as the Heisenberg indeterminacy, the holistic principle inherent in the quantum picture, and non-locality, has not yet been made . Dürr also points to the fact that in molecular biology and chemistry the phase relationships of the electrons are not taken into account (only the intensities) and that the phase structure of the wave formed by the superposition of the partial waves of the millions of electrons in the DNA double helix molecule, may contain, in holographically coded form, additional important information. A most fundamental element of such a new approach in biophysics will probably be a shift from the molecular
to the field aspect of living matter, as proposed by Welch and by Popp et al. , among others, which seems
to be the only viable way to synthetize the myriads of molecular details science has amassed, into a holistic model
of the organism. One of the most important goals of applied biophysics in the near future must be the development
of non-invasive methods to assess the functional state of whole and intact organisms, and that of the organism’s
subsystems in the context of the whole organism . This goal may be realized by measuring the electromagnetic field
produced by the living organism; any interpretation that leads to useful results has to be based on a model of
the organism making regulation processes accessible at the field level. BIOPHYSICS: THE PHYSICS OF BIOLOGY Any discussion of the future of biophysics inevitably leads to the fundamental question of the relationship between physics and biology. It seems clear that, besides drawing upon new developments in physics, a new biophysics also must become more biological again. Any program of reducing biology to physics and chemistry has to consider that the actual physical laws have been obtained from the investigation of non-living phenomena, easier to investigate by the physical approach because they are less complex. Maybe the reason for the failure of biophysics to develop a theory of life is just this reductionistic approach postulating that life processes should be explained by the already known physicochemical laws of non-living nature. Not a few scientists of past decades, most notably J.S.Haldane and Adolf Meyer-Abich , as well as contemporary ones (e.g., Dale A.Miller , Gunter Albrecht-Buehler ) have postulated that the principles governing life are more fundamental than those of non-living matter, and therefore biology should replace physics as the paradigmatic „leitwissenschaft“ (leading science). Without subscribing to any vitalistic notions, Beier takes a similar stance and shows a way which may lead beyond the ages-old controversy. He postulates that physics has to change and enlarge in order to describe biological phenomena; he rejects a reduction of biology to contemporary physics, but does not exclude one to a future, enlarged physics. According to Beier, to achieve a mathematization of biology, the biophysicist should not simply copy physics. „Biophysics has to contribute to the establishment of purely biological postulates and principles without reducing these to physics. We can consider this method as an enlargement of physics. Physics in a sense ‘incorporates’ biology, via biophysics. Such a procedure can be taken by the materialist as well as by the vitalist from their respective standpoints to be a justification of their views. This again shows clearly the uselessness of a mechanist-vitalist controversy“. Rashevsky wrote that according to the Goedel theorem there must be physical phenomena which cannot be deducted from the laws of physics, even when they do not contradict those laws, and it cannot be decided if biology does not belong to this class of phenomena. Rashevsky and his school based their work on the presumption that biological phenomena are governed by such non-deductable principles. To identify and formulate these more fundamental laws of life of which the known physical laws may turn
out to be special cases, in the same way as the laws of classical Newtonian physics turned out to be special, restricted
cases of the laws of quantum physics, should be the most noble goal of a new biophysics. Biophysics is predestined
to take on this task. These laws have to be formulated in a mathematical way, but not necessarily metrically, as
Rashevsky has shown.
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