The purpose of this review is to summarize the present status of preparative zonal centrifugation and to indicate where the remaining problems, in the reviewer's opinion, may lie. The field is sufficiently new for interest in practical separartions to be uppermost. However, a number of theoretical problems relating to gradient capacity, zonal rotor configuration and particle—particle interactions remain to be fully explored.

I. I. In his illuminating book on The Nature of Thermodynamics, Bridgeman (1941) points out an intrinsic contradiction between the concepts of physical and biological evolution. In his words: ‘The view that the universe is running down into a condition where its entropy and the amount of disorder are as great as possible has had a profound effect on the views of many biologists on the nature of biological phenomena. It springs to the eye, however, that the tendency of living organisms is to organize their surroundings—that is to “produce” order where formerly there was disorder. Life then appears in some way to oppose the otherwise universal drive to disorder. Does it mean that living organisms do, or may violate the second law of thermodynamics?…’

Among the different fields of natural sciences, physics is concerned with the most basic properties of matter. It is possible to define the necessary physical concepts in a rather unique way and carry out experiments under well-controlled conditions. The interpretation of experiments is therefore comparatively easy. In chemistry the situation is more complicated and the interpretation becomes more ambiguous. Biology finally is characterized by its high degree of complexity, making the detailed analysis difficult. Since the problems of biology are so essential, it is very important to use every tool available to clarify the situation, state the problems as carefully as possible and approximate the solution from as many sides as are feasible. Therefore, not only the methods developed within biology but also those pertinent to chemistry and physics should be applied. For this reason also quantum mechanics may be able to contribute to the elucidation of biological problems.

An intact living muscle has such a regular structure that it diffracts light or X-rays, thereby providing patterns that contain uniquely valuable information. Interpretation of these patterns is not straightforward, but is helped by light microscopy and electron microscopy, which can often provide similar though less reliable information. At all levels of complexity, from that of the fibrils to that of the molecules, structure in a muscle is orderly. No other natural cell assembly is so suited to study by the diffraction method, and the results obtained in recent years are an outstanding example of how this method can elucidate a biological problem. In contrast to protein crystallography, where the system studied is artificial, muscle can be examined in its natural state, during normal activity. The levels of structure explored as yet in muscle are above that of the atoms in the molecules. Such structure is more commonly investigated by electron microscopy, and the application of the diffraction method to living muscle has provided a valuable check on the preparative artifacts that worry the microscopist. The great complexity of a muscle, as compared with a protein crystal, and the fact that the system is only semi-crystalline, giving a much less detailed diffraction pattern, make the problems of interpretation especially difficult. But a great deal of useful information is available about other properties of muscle and its constituents, and the flourishing state of muscle biology at present is a major factor contributing to the successful application of the diffraction method.

Our scientific age is characterized by the extension of our dimensions to the extreme. Radiotelescopes are searching for echoes from the depth of the universe, while electronmicroscopes and X-ray diffractometers make the atomic and molecular structure of matter visible.

Since the earliest intelligent history man has tried to understand the origin of life. Some remarkable scientific advances have been made. The concept of natural selection is firmly established as the basis of organic evolution. Advances in the genetic mechanism of inheritance have shed light on the processes and levels at which evolutionary changes occur. Evolution is understood to be a dynamic process, and the organisms present at any given time are those best suited to the environment by virtue of the history of their predecessors. But a deeper question arises: how free is evolution? Are the particular biomolecular structures and processes in existence now in any way uniquely predetermined, or are they the result of a sequence of accidental occurrences?

The origin of pluripotentiality of the immune system in an individual constitutes a major challenge for students of immunology. A vast number of different substances can be shown to be antigenic in an individual, such that their introduction will induce antibody synthesis. These antibodies, mostly detected as serum immunoglobulins, are distinguished by their Capacity for specific combination with the inducer, the antigen. As the specificity of the antibody towards a given antigen can be shown to reside within the amino acid sequence of the molecule by unfolding-refolding experiments (Haber, 1964), it is generally accepted that the antigen-combining capacity of an antibody molecule is under genetic control. So far, studies trying to disclose any unique features of immunoglobulin versus other systems of protein production have failed to do so. No commonly accepted theory yet exists to explain how this multiplicity of immunological potentiality is created at the level of DNA and it is considered beyond the scope of this article to try to cover in detail the various attempts to solve this problem. The reader is referred to a recent review (Lennox & Cohn, 1967) for further details on this subject. It is the intention of the author to describe how pluripotentiality of the immune system operates at the cellular level and to describe and discuss in more detail how regulation of the expression of immunological capacity takes place at the single cell level.

Mηδέν ἄγαν—nothing in excess. These words of the old Greek saying might well find a place in modern Biology. The maintenance of order and balance—homeostasis, as the physiologist would have it—is an attribute of all living things. At a molecular level the study of control and regulation, involving the conjugate concepts of structure and function is a central theme of Biophysics. How is it that an enzyme, by the braking effect of its end products, is prevented from going too far, or, alternatively, by the accumulation of other metabolic substances in its environment, is brought into play? How is it that a working respiratory protein like haemoglobin, by the reciprocal action of its metabolic opposite, carbon dioxide, is aided in the taking up of oxygen in the lungs and the giving it off in the tissues? These are problems of linkage. From one point of view they may be thought of in terms of information— the communication between ligand and macromolecule and between one part of the macromolecule and another. From a different point of view they may be thought of in terms of the storage and transfer of energy, of the way in which the work of introducing ligand, the same or different, at another. The analysis may be pitched either at the phenomenological, or at the mechanistic, level; but whatever the approach it profits cosiderably from the introduction of the concept of the binding potential.

Very early in the era of isotopic tracers it became apparent that tracer fluxes did not always come out as one had predicted from classical measurements of transport by osmosis or diffusion. Thus Hevesy, Hofer & Krogh (1935) determined the water permeability of frog skin from osmotic uptake of water as well as from measurements of its permeability to heavy water. They found the first method to give values some 4–5 times higher than the latter. Although this result at first seemed disappointing, it was soon realized that the two types of experiments provided more information about the nature of osmosis through real membranes than had been available before. Thus it was shown that the results might be explained in terms of interaction between water molecules moving in bulk, possibly through pores in the membrane (Ussing, 1952; Koefoed-Johnsen & Ussing, 1953; Andersen & Ussing, 1957).

Microtubule proteins have recently been prepared and characterized from a number of diverse sources. Renaud, Rowe & Gibbons (1966, 1968) have obtained a protein from acetone powders of Tetrahymena pyriformis cilia and from isolated outer fibre doublets of this same species. The protein has an actin-like amino acid composition, a minimum subunit weight of 55000, and 7·5 free sulphydryl groups per mole of monomer. Stephens (1968a) has fractionated sea-urchin flagella, following the procedure of Gibbons (1965), to obtain the isolated outer fibres and has found the protein to have properties virtually identical to those of its ciliary counterpart. Both the flagellar and the ciliary outer-fibre proteins contain 1 mole of bound guanine nucleotide per mole of protein subunit (Stephens, Renaud & Gibbons, 1967).

What I shall try to do in this essay is not to produce a serious, accurate account of the immense amount of work in this field but, rather, to comment in a very general way on some of the new ideas in the advances of molecular biology, on the background of classical biological thought both histological and biochemical.

Biophysicists, who, by definition, apply physical and mathematical principles to their analysis of biological problems for the understanding of the functions of living organisms, are to a great extent concerned with basic characteristics more or less common to all organisms. As pointed out by Griffin (1958) in his book on acoustic orientation, it may well be that ‘this fruitful preoccupation with the universals of protoplasm tends to foster an unduly restricted view of its many intricate potentialities’. The knowledge of the many ways in which animals and plants are adapted for a ‘successful life’ has had a great impact upon the concepts of evolution and natural selection. As a contribution to the proper understanding of these concepts the study of the biophysical principles, by which various geometrically oriented tissues serve different functions, becomes of special interest.

The following history of the formation of the International Union for Pure and Applied Biophysics (IUPAB) has been assembled from several published accounts in Nature and Science, to which has been added material from the minutes of the meetings of some of the bodies concerned. The introductory paragraphs have been taken from articles by Sutherland (1963) and by Bolt & Sutherland (1960).