Chapter V: Introduction: §1 (3)

In all animals the sperm is a microscopic entity. In all animals from the jellyfish to Man with very few exceptions its appearance is extraordinarily similar. It consists of a thicker portion to which is attached a long vibratile process, or flagellum. The eggs of different animals are of very different dimensions. Sometimes they contain immense stores of food material (yolk). Sometimes as they pass to the exterior by the female generative tract they are invested with an additional slimy coat and a leathery or calcareous shell, secreted by special glands. The immature egg of all animals is essentially similar. In the living condition it is a spherical or ellipsoidal body in which a clear spherical vesicle is seen; this vesicle present in all cells is called the _nucleus_. The thicker part or body of the sperm consists mainly of the nucleus of the cell from which it is derived. At fertilization it swells up and unites with the nucleus of the egg. The fertilized egg then divides into two separate segments or cells, and the process of dividing is repeated an indefinite number of times. The cells or segments into which the fertilized egg divides each contain a nucleus, and the process of segmentation which involves the division of cells into two is accompanied by the division of the nucleus of each dividing cell. Like the testis or ovary the substance of all the organs of the animal body is built up of the microscopic bricks which we have called cells. In some tissues like bone and cartilage the bricks are separated by a good deal of mortar. Others, such as the lining membranes of the body, consist simply of cells packed tightly together. At the beginning of embryonic existence all the cells are very much alike. In the course of development the cells of different tissues are considerably differentiated. Throughout all stages the process of cell division always involves the partition of the nucleus in a highly characteristic manner.

The details of this peculiar process, first elucidated by Flemming and others during the seventies, has proved to be of astonishing significance for the further understanding of Mendel’s hypothesis. When a cell is about to divide, the nucleus looks like a tangle of fine threads; and this tangle of fine threads resolves itself into a number of readily distinguishable filaments which become progressively shorter, assuming the appearance of stout rods staining deeply with basic dyes. These rods, visible only with high powers of the microscope, are the _chromosomes_, whose behaviour has provided us with a tangible basis for Mendel’s conception of inheritance, and have thereby permitted an extensive clarification and amplification of the original hypothesis. From one point of view they might be said to have done as much for the Mendelian conception of heredity as the discovery of alpha particles has done for our belief in the atomic structure of matter. As the dividing cell begins to constrict, the chromosomes arrange themselves at its equator, and split longitudinally into halves, each half travelling to opposite poles, where they spin out again into fine threads from which the nuclei of the daughter cells are built up. Thus each of the chromosomes in the nucleus of any cell in the body is structurally equivalent to a corresponding chromosome in the preceding or succeeding cell generation. About the year 1875 it was recognized that this numerical constancy extends beyond the life of a single individual. In every species of animal or plant the number of chromosomes which can be counted in dividing nuclei is a constant for the species.

With the discovery of this fact a new problem arose so soon as the essential features of fertilization were appreciated. How is this constancy maintained from generation to generation of new individuals? Two investigators, Van Beneden and Boveri (1881-3), who worked on the horse threadworm, a form which has only four chromosomes in the dividing cells of the segmenting egg, showed that the egg and sperm each contain only half the number of chromosomes characteristic of the cells of the embryo. This conclusion turned out to be a perfectly general one. Attention was immediately directed to the nuclear changes which happen in the formation of the gametes. Innumerable cell divisions occur in the testis or ovary of an animal. These are at first similar in all respects to those which occur in the segmentation of the developing embryo; but cell division goes on in the testis or ovary throughout life. If we trace backwards the history of an individual sperm or egg in the testis or ovary in which it originates, we find a reduction of the number of chromosomes effected during the last division but one, leading up to the formation of a sperm or ripe egg. This penultimate division of the germ nuclei is preceded by the fusion of the chromosomes lengthwise in pairs. When the division actually takes place, each pair behaves like a single chromosome, splitting in such a way that one member of each pair goes to form each daughter nucleus. The succeeding division being normal, each gamete receives half the number of chromosomes present in ordinary cell division. At fertilization the normal number is restored. Thus each ordinary cell of the body has a chromosome set of which half the components are paternal and half maternal in origin.

In many animals and plants the chromosomes are very distinctly of different sizes and shapes, and can be sorted out into corresponding pairs. Such arrangements are constant for the species, and could only be maintained constant, if each gamete contains one representative of each pair. This means that the maternal and paternal constituents of a pair are distributed in the reduction division to different cells. The chromosomes therefore exist in pairs of which one element is of maternal origin and one of paternal origin. Each gamete receives one element of each pair, just as Mendel supposed that each gamete contained either the paternal or maternal element of his paired “factors.” By a curious coincidence this far-reaching conclusion was first established in the very year which witnessed the application of Mendel’s principles to animals by Bateson in England and Cuenot in France (1902). Its recognition accompanied the elucidation of another peculiarity of nuclear division, also destined to have important theoretical consequences. In many animals there is found to be an unequally mated pair of chromosomes, the XY pair. When this occurs, it occurs in one sex only. In the alternate sex there is a corresponding equal pair (XX). In birds and moths the female is the XY, the male the XX individual. In other animals the male is usually found with sufficiently careful measurement to have an unequal (XY) pair which is equally mated in the female (XX). During the nineties it was found that some animals had in one sex an odd number of chromosomes, a fact which at first sight seemed to conflict with the numerical constancy of the chromosomes. In the early years of the present century American zoologists provided the key to an understanding of the discrepancy. In all such cases the alternate sex has one more chromosome. The case of the large cockroach will serve as an illustration. The male of _Periplaneta americana_ (its technical name) has 33, the female 34 chromosomes. The eggs will all have 17 chromosomes. One-half of the sperm will have 17, the other half 16 chromosomes. If a sperm of the former class fertilizes an egg, the individual produced will be a female (17 + 17 = 34); and if a sperm of the second type fertilizes an egg, the individual produced will be a male (17 + 16 = 33). In an animal with an unequally mated (XY) pair of chromosomes in the male reduction will result in one-half of the sperm carrying the X and one-half the Y chromosome. The eggs will all have the X, since this chromosome is equally paired in the female. Thus an egg fertilized by a Y-bearing sperm will become a male, while an egg fertilized by an X-bearing sperm will develop into a female.

§3

By statistical reasoning Mendel had deduced from his experimental data the existence of entities which behave just as the chromosomes do. He had no direct evidence that his factors had any material basis in the architecture of the germ cells. The new cell anatomy provided independent confirmation of his predictions from an unexpected quarter; but it was not immediately recognized that this was so. Antagonism to the belief that the chromosomes fulfilled the requirements of Mendel’s hypothesis is easily explicable. To Mendel’s first disciples his second and first laws were equally sacrosanct. Mendel’s second law implies that different pairs of hereditary factors behave quite independently of one another. On such an assumption one of two deductions is inevitable. Either the applicability of Mendel’s first law is extremely restricted; or the number of factors is too large to permit of their localization in the chromosomes. The sweet-pea, for instance, has only seven pairs of chromosomes. If Mendel’s second law were as general as the first, only seven pairs of factors could be accounted for by the behaviour of the chromosomes. From this dilemma further development of the atomistic view of heredity was rescued, when it was discovered that Mendel’s second law is only a particular case of the possibilities inherent in the first.

In 1910 Bateson and Punnet first discovered in the sweet-pea what they then called “coupling and repulsion,” or as we now say, _linkage_. Without going into the experimental data, we may define the phenomenon of linkage in the following way. Suppose that these are two varieties A and B which obey Mendel’s first law and two other varieties C and D which likewise conform to its requirements, when crossed with one another. Mendel’s second law stated that in a cross between AC and BD the second generation will consist of the types AC, AD, BC and BD in numerical proportions agreeable to the assumption that it is equally likely that the factor determining A will be present in the same gamete as the factor determining C or the factor determining D. Bateson and Punnet found that this does not always happen. There is another category of cases in which the factor which determines A sticks more or less completely to the factor for C in preference to the factor for D. The detailed analysis of these cases was at first made difficult by Mendel’s literal symbolism, and his way of thinking of factors in _pairs_. But the discovery of linkage at once led Lock to formulate the fruitful suggestion that factors located on the same chromosome pair would satisfy the requirements of linkage, while factors located on different pairs of chromosomes would fit in with Mendel’s second law.

From this point onwards the most spectacular development came from the study of inheritance in animals, and the significance of the chromosomes was immensely reinforced by newly gained knowledge of sex determination. Almost contemporaneously with the discovery of the sex chromosomes or XY mechanism, as we now say, Leonard Doncaster had elucidated in moths the phenomenon of sex-linked inheritance. This was soon found to be of common occurrence in animals. Till this discovery, which was made in 1905, the same results had always been obtained in crosses of pure-bred varieties, whether the male or the female parent displayed one or the other characteristic distinguishing them. Doncaster’s work on the currant moth showed that there is a category of cases which at first sight obey Mendel’s first law in its simplest form when the cross is made in one way, but yield a different type of result when the cross is carried out reciprocally with respect to the sex of the parents. In such cases one sex is only able to transmit certain characters to its offspring of the opposite sex. It was already known that the XY sex (male in Man and most animals) can only transmit its X chromosome to the XX type. The facts did not dovetail at first sight, because sex-linked inheritance was originally elucidated in birds and moths of which the female is the XY type. There was still an attitude of hesitancy towards accepting Lock’s hypothesis, strengthened by the persistence of an incorrect interpretation of the process of reduction which had been made the basis of Weismann’s metaphysical speculations concerning “germinal selection.”

When in 1914 Doncaster summed up the case for regarding the chromosomes as the material basis of Mendel’s first law, a new era had already dawned. Thomas Hunt Morgan, the central figure of a group of ardent investigators at Columbia, had initiated a body of enquiries which within half a decade eclipsed all other achievements that had succeeded Mendel’s pioneer labours. About the time when Bateson first encountered the phenomenon of linked inheritance Morgan began to rear the fruit-fly Drosophila for breeding experiments. Till then genetic experiment had been held in check by the slow rate at which most convenient animals and plants reproduce and the expense entailed in breeding them in sufficiently large numbers to permit statistical inference. The fruit-fly completes its life cycle, if kept in warm laboratory conditions, in a period of ten days. It is prolific. It feeds on rotten banana skins. It therefore costs little to breed. To these immense advantages it adds two others of supreme importance. It has only four pairs of chromosomes readily distinguishable from one another by size and shape; and it has produced in the laboratory a crop of several hundreds of sports or _mutants_. Each mutant type differs from the wild parent stock in some well-defined characteristic inherited in crosses with the wild type in accordance with Mendel’s first law. The mutant characters are extremely varied. One is distinguished from the red-eyed parent by having white eyes, another by having purple eyes, another by having no eyes at all. One is distinguished by having wings that are practically vestiges, another by wings that turn up at the tips, another by wings that are truncated at their extremities. From the wild type which has a greyish body, one mutant is distinguished by a deep black, another by yellow coloration. The mutant characters are thus in general clear-cut differences lending themselves to easy identification. With an animal that breeds so rapidly and prolifically information accumulated with astonishing rapidity. From data based on the study of a large assemblage of mutant characters there soon emerged the precise requirements of Lock’s hypothesis. All the mutant characters of Drosophila fall into four groups. Members of the same group always tend to stick together in hereditary transmission. Members of different groups like Mendel’s dihybrids behave independently of one another. Of several hundred mutant characters in Drosophila every one belongs to one of these four linkage groups; and the number of chromosome pairs in Drosophila is four.

This discovery was only the beginning of what might well be called one of the faery tales of modern scientific research. In the way of accepting Lock’s hypothesis there were still difficulties. It was in evading the principal difficulty that Morgan’s school extended the atomistic concept of heredity much further than his predecessors had done. Till then the main outcome of experiments on breeding had been to show that Mendel’s principle was of vastly wider applicability than was at first supposed, and to engender the suspicion that the patient unravelling of difficult and elusive cases would establish its universal validity. As yet the world of Mendel’s atoms was without form. Morgan and his colleagues gave it a map. Not content with showing that Mendel’s atoms of heredity have their material basis in the chromosomes, nor with actually identifying which chromosome is significantly associated with a particular mutant character, Morgan went further and localized the region of an individual chromosome in which a particular Mendelian factor resides. He thus gave to Mendel’s factors spatial co-ordinates in the living cell.

At the outset the study of linkage upon which the chromosome map is based was facilitated in the case of Drosophila, because the varieties dealt with were all known to be mutants from a fixed wild type. Thus it was possible to break away from Mendel’s conception of “pairs” of hybridizing characters. The Mendelian factor was replaced by the mutant _gene_, by saying which is implied that a mutant arises because at some point on a particular chromosome a physical change has taken place. The gene is the Mendelian factor for the mutant condition, but no assumptions are made about what determines the wild-type condition. The inter-relationship of different characters is greatly simplified by thinking only of the relation of one _mutant_ gene to another. The discovery that all the genes fall into four groups corresponding to the four groups of chromosomes presented one stumbling-block. Members of the same group in general do not invariably stick together. When two mutants are crossed the numerical proportions of the various types of offspring give a definite value for the probability that the gene A and the gene B will stick together or separate apart. This is a constant for A and B. The constant used in practice is the tendency for A and B to separate. Expressed as a percentage, it is called the _cross-over value_. Some additional information was necessary to explain why A and B do not always stick together, if they are associated with the same chromosome. It was from the solution of this problem that the chromosome map took shape.

Here the sex chromosomes came to the rescue. One very interesting type of sport which has turned up in breeding the fruit-fly is not recognizable by any discrete bodily peculiarity but merely by an abnormality in the number of chromosomes. Of these the first to be discovered was a type of female which has in addition to its usual four pairs of chromosomes an additional Y chromosome. The XXY females yield very extraordinary numerical results both as regards the sex ratio and other characteristics, when used in making crosses involving mutant characters. There is a class of mutant characters in Drosophila, more than a hundred in all, distinguished by the fact that they are not inherited symmetrically with regard to sex. They display linkage _inter se_. They behave as “sex-linked” characters. The introduction of XXY females into crosses involving such mutant characters results in numerical ratios which are inexplicable on any assumption other than the view that the sex-linked gene is referable to the X chromosome alone. Yet, although the sex-linked genes are all borne on the same chromosome, they do not invariably stick together in crossing. The holistic chromosome clearly would not do. An atomistic chromosome had to be put in its place.

The clue to this was provided by studying more closely the extent to which the different genes stick together. Taking all the genes located on the X chromosome this remarkable generalization emerged from Morgan’s researches. If A, B, and C are three sex-linked genes; if the probability that A and B will not stick together is _x_, and the probability that B and C will not stick together is _y_, the probability that A and C will not stick together is either the sum or the difference of _x_ and _y_. The correspondence here stated is, of course, subject to the margin of error permitted by the theory of probability. To interpret this new _law of the linear alignment of the genes_ Morgan made use of a structural peculiarity of the reduction process. When the chromosomes pair in the reduction division, they appear to become twisted. The appearance suggests that in the ensuing split corresponding lengths of the original pair are interchanged. It is very natural to assume that the likelihood that two points will be separated from one another in such a manner is proportional to their distance apart. So if the sex-linked genes are arranged in a series along the length of the chromosome, the probability that A and C will not stick together must be the sum of the probabilities that A and B and B and C will be separated. This is just what experiment had shown to be true. Thus all the genes on the X chromosome can be arranged in a linear series. The intervals between consecutive genes in such a series represents a space dimension.

The law of the linear alignment of the genes was soon found to apply to the other groups of linked characters. Abnormalities in the number of chromosomes have made it possible to identify each of the remaining three linkage groups of the fruit-fly with its corresponding pair of chromosomes. The first chromosome map of Drosophila was constructed in 1916. It revealed the suggestive coincidence that the number of ascertained points on each pair of chromosomes is roughly proportional to its size. There is now very little doubt that the work of the Columbia school has revealed an aspect of inheritance which is of general significance. After years of patient work with the relatively slow breeding sweet-pea, Punnet has at length elucidated seven linkage groups corresponding to its seven pairs of chromosomes. He has constructed a chromosome map of a seed plant on the basis of the principle first established for the fruit-fly. A law which holds good for two organisms so far apart in the evolutionary scale can hardly be supposed to be lacking in universal validity. The chromosome hypothesis may now take its place as one of the major generalizations of biological science. The law of linear alignment has transformed Mendel’s original conception of inheritance in a way which might be compared with the elaboration of Dalton’s hypothesis after the discovery of the law of combination of gases by volume. Mendel’s atoms of heredity are now units spatially localized in larger units of microscopically visible dimensions. These supermolecules are the chromosomes.

Being a portion of living matter the chromosome is constantly undergoing chemical change. Some critics of the chromosome hypothesis have based objections upon this circumstance. The difficulty is more apparent than real. Like the individuality of the modern atom the individuality of the chromosome must be conceived in statistical terms. For the discussion of the more familiar chemical reactions the statical atom of traditional chemistry is adequate. For the interpretation of hybridization experiments the diagrammatic chromosome of the text-book suffices. In the field of radioactivity the statical atom makes way for a dynamical model. So also in the domain of cell physiology we conceive the chromosome as an ever-changing entity. The logical situation is analogous in the two cases. Those who hold with Dr. Haldane that the biologist must interpret his data in a manner different from that in which the chemist or physicist interpret theirs have now to fall back on the contention that the Mendelian view is only a partial picture of heredity transmission. Anything which might have been said in favour of this contention ten years ago has been weakened by recent work on the inheritance of size. The pioneers of Mendelism selected clear-cut hereditary differences which ordinarily manifest themselves in any environment in which the animal or plant can live. They succeeded in showing that a vast number of hereditary differences involving a great variety of anatomical and physiological features conform to the requirements of Mendel’s hypothesis. There was one category of phenomena which remained obscure till quite recently. Differences in size, height, body weight and the like vary greatly with environmental conditions. Two stocks may be distinguished from one another by the fact that the average member of one is measurably different from the average member of another; but any given individual of one stock may be indistinguishable from another individual of the other, because, even when the environment is standardized as much as is practicable, the range of variability of the two stocks overlaps. The analysis of such cases cannot be undertaken by the ordinary technique of Mendelian experiments; but certain statistical requirements of Mendel’s laws may nevertheless be verified. By elementary statistical reasoning we can deduce that the coefficient of variability of the progeny of a cross between two inbred stocks must be a minimum in the first generation and a maximum in the second. This has been shown to be true in a number of crosses in which it is impossible to distinguish individual genetic types by direct observation.

There is no longer any adequate reason to support the contention that Mendel’s atomistic concept leads us to an incomplete understanding of biparental inheritance in animals and plants. Those who assert that it is so are now forced to fall back upon the last resort of obscurantism by appealing to the magnitude of our ignorance. The modern theory of the gene is a statistical construction consistently developed by a logical interpretation similar to that adopted in elaborating the great generalizations of physical science. The mechanist is often accused of attributing vital processes to “chance” combinations of phenomena. If the word chance is used to imply that we do not know the precise conditions which determine such combinations, the statement is hardly exceptionable. It might also imply that the phenomena which biologists study can be successfully interpreted in terms of the mathematical laws of chance. The history of Mendelism shows that these laws provide a fruitful basis for predicting the behaviour of living systems, even where physico-chemical hypotheses at present fail to throw light on the phenomena which the biologist studies. The biologist is able to progress to greater certainty of prediction only when he interprets his data with the same logical method employed by the chemist and physicist to deduce physical “laws.” Whatever the future holds in store for further interpretation of heredity and variation on physico-chemical lines, the progress already achieved has at every stage involved elimination of holistic concepts by the ruthless application of mechanistic logic. To the application of physico-chemical hypotheses no branch of physiology has proved more recalcitrant than the physiology of inheritance. No branch of physiology might more suitably be chosen to cast doubt on Dr. Haldane’s recent statement that “anything which can properly be called scientific physiology is impossible apart from the assumption of _holism_.”

III. THE NATURE OF LIFE

“I am sorry then, I have pretended to be a philosopher: for I find
your questions very perplexing; and am in danger, if my answer be
too rigid and severe, of passing for a pedant and scholastic: if
it be too easy and free, of being taken for a preacher of vice and
immorality. However, to satisfy you, I shall deliver my opinion
upon the matter, and shall only desire you to esteem it of as
little consequence as I do myself. By that means you will neither
think it worthy of your ridicule nor your anger.”--David Hume, _The
Sceptic_

§1

Since a man must needs live before he can be a philosopher, no problem of philosophy is more fundamental than the nature of life. There is also no issue which provides more scope for vague, barren and undisciplined discussion. A Regius Professor of Moral Philosophy, whether he accepts the fact with resignation or refuses to do so, is a piece of living matter. Perhaps this is why physicists are more vocal than biologists in promoting a pacific solution of the territorial dispute between science and traditional philosophy. At the present moment it is the fashion among those who are writing on scientific philosophy either to neglect the contribution of the biologist to the world symposium, or to assume that the biologist in dealing with living matter operates with different methods and different concepts from those employed in physics. No phase in the history of biology is more fitted than the present to illustrate the fundamental unity of scientific method. In no branch of science is the limit of applicability of scientific method a more significant issue.

Since a scientific concept is only a way of describing a class of properties, the nature of life cannot refer to anything but the nature of the properties of living things. Having arrived at some general classification of the characteristic properties of living things, a discussion of the nature of life in the light of modern biological science presents two issues of pre-eminent interest. One is how far the _methods_ employed in physical science have been successful and are likely to continue to prove successful in dealing with the properties of living matter. The other is how the increasing measure of success which attends the utilization of purely physical _concepts_ to interpret the properties of living matter is calculated to influence our evaluation of the place of science in human thought. Whatever differences of interpretation may exist among biologists on matters of detail, it should at least be possible to infer from a survey of the progress of biology whether the study of living matter is progressing satisfactorily along the lines of quantitative analysis of experimental data towards greater certainty of prediction, and whether there is good reason to believe that the preservation of the teleological standpoint in dealing with living matter is likely to ensure conspicuous success in the same direction.

It may be admitted that there exists among biologists more unanimity with reference to the first than towards the second issue. Every infant science makes use of notions peculiar to its own province. Chemistry has but lately passed beyond the stage when the concept of _affinity_ first became amenable to interpretation in thermodynamical quantities. There are still many biologists who would assert that the concept of _adaptation_ demarcates the province of biology from that of physics and chemistry by an impassable gulf. There are others, fewer in number, who, surveying the teleological growing pains of the more exact sciences and bearing in mind that only 300 years have passed since the properties of familiar chemical compounds were literally personified as spirits of wood, spirits of salt and the like, do not feel compelled to regard the concept of adaptation as final. They are able to entertain the possibility that those properties which enable an organism to maintain its continued existence as an organism are not permanently more incapable of physical interpretation than the polarization of a voltaic battery, a phenomenon which the consistent teleologist would presumably regard as an attempt on the part of the latter to save its own life. Clearly the onus of defining what precisely is implied in the concept of adaptation lies on those who assert its uniqueness. Until the vitalist is more definite on this issue, the mechanist is under no obligation to refrain from classifying the properties of living matter in the light of his own experience. The mechanist denies that anything is to be gained by clinging to the teleological standpoint with its implication of some extra- or intra-mundane purpose which has been abandoned in all branches of science that lay claim to exactitude. He refuses to deal with living matter except in as far as it is considered as a series of “events” whose characteristics must be interpreted with rigid economy of hypothesis.

In approaching any lump of living matter, let us say the author of these essays, as an object of the external world, the maintenance of economy of hypothesis compels the enquirer to seek as far as possible a common basis for the characteristic properties of living and non-living systems. This necessitates a clear definition of the distinction between the two. Taking a comparatively complex organism, as, for instance, the common frog, a distinction might be attempted along the following lines. In the first place, its possibilities of behaviour are more varied than those of any machine which can be manufactured by man; yet, while possessing a greater range of reversible response than any non-living system, it would be difficult to specify in a living system any single activity which could not be reproduced by a mechanical system. Apart from this diversity, which we may refer to under the generic term _reactivity_, living matter is characterized in general by the wide range of external influences which are significant in determining its characteristic reversible responses. This peculiarity, in view of the subjective preconceptions implicit in the older terms irritability, sensation, etc., may be denoted by the term _receptivity_. Here again it is impossible to isolate any single agency (or “_stimulus_”) capable of evoking reversible change in any living system and incapable of evoking reversible change in any non-living system. Finally--and at first sight--a more diagnostic difference between living and non-living matter is seen in the property of _reproduction_ (taken in the broader sense of the term, to include growth). A given piece of living matter comes into being in our experience only through the agency of other pieces of living matter closely resembling itself.

§2

Were the more obscure process of sexual reproduction universally characteristic of living matter, this distinction would appear especially fundamental. Experimental biology is far from the achievement of a complete physico-chemical analysis of asexual reproduction in any type of organism. On the other hand, in the life cycles of those multitudes of micro-organisms which multiply by simple fission after attaining a certain limit of growth, there is nothing which compels an unprejudiced investigator to regard the process as more intrinsically incapable of physical interpretation than the splitting into two of a liquid drop. Although our knowledge of the nature of sexual reproduction is fragmentary, in this very field some particularly spectacular advances have been registered in substituting physical agencies as effective instruments for initiating processes which at one time were only amenable to the influences of living matter itself. Thirty years have now passed since Loeb’s discovery that changes in the osmotic pressure of the external medium or alteration of the permeability of the egg itself, leading to changes in its own internal osmotic pressure, can initiate without any assistance from the sperm the development of the ovum into a new and complete organism. That discovery was the starting-point of a body of investigations whose influence has radiated into many other fields of biological enquiry. Especially noteworthy in this connexion is the work of Warburg during the last decade. Warburg was able to show that sea-urchin eggs, and later animal cells in general, if rapidly dehydrated and ground to a powder, will, like the intact cell, absorb oxygen for some time when moistened. He showed also that this property, like respiration in the intact cell, can be abolished by the action of cyanides and other classes of tissue poisons. By doing so, Warburg has taken a characteristic and highly complex property of living matter out of the realm of vitalism into that of physical chemistry. His analysis went further. Experiment showed that three classes of poisons which inhibit tissue respiration can be distinguished by their quantitative relations. Of these, the efficacy of one class, the cyanides, was shown by Warburg to be correlated with the iron content of the cell. On the hypothesis that iron catalysis is the main factor in the oxidation of organic material in the cell, Warburg manufactured suspensions of charcoal with a high iron content capable of catalysing the auto-oxidation of sugars, fats, etc. The catalytic activity of these suspensions was found to be related quantitatively to the three categories of respiratory poisons in a manner closely parallel to the action of the latter on tissue respiration.

Though reproduction is, in some respects, to the biologist at least, the most fundamental of all the three features which I have defined above, the ever-changing reactivity and manifold receptivity to external influences so characteristic of living matter pre-eminently engage our attention in connexion with the more intimate and subtle issues of a field of enquiry which biology may yet claim. I refer to the analysis of human behaviour. In this connexion I shall mention progress in three directions as illustrating the transition from teleological to quantitative treatment during the last half century; namely, the physical analysis of the events which constitute an isolated unit of response or reflex, the integration of reflexes in the normal behaviour of animals, and the determination of new behaviour patterns along the lines laid down by Pavlov’s school. With regard to the first, we will consider the effect of flashing a bright light upon an animal that has been previously kept in the dark. The characteristic response, let us say, blinking of the eyelids, and the intervening events involved are, first, a physical change in a receptive area, namely, the retina; secondly, the propagation of the disturbance there set up along a certain path, the nervous system; thirdly, the liberation of a considerable quantity of energy at the seat of response or effector organ, that is to say, the muscles of the eyelid.

Our knowledge of the nature of receptivity is least complete. That it is a measurable physical event is beyond dispute. When light impinges upon a given area of the retina there follows a characteristic series of changes in electrical potential of the excited area with reference to a non-excited area. Through the work of Jolly, Adrian and others the sequence, the time relations and the magnitude of these changes are being related to the intensity and duration of the stimulus within predictable limits for a given species. These events initiate the propagation of the disturbance known as the nervous impulse. The nervous impulse is a physical event whose space-time relations can be defined as concretely as the passage of an electric current through a wire. Three-quarters of a century ago Helmholtz showed that the time which elapses between the application of a stimulus to a nerve and contraction of its attached muscle is a linear function of the distance between the latter and the point of application of the stimulus. The conception of the nervous impulse as a physical event had been, till this discovery, entirely repugnant to scientific thought. We now know not only, as Helmholtz showed, that the nervous impulse has definite space-time co-ordinates, but that it has the dimensions of energy. Its passage corresponds to the rate of propagation of an electrical change of an analogous character to the electrical response of the excited retina. The total energy of its propagation has been recently measured by Gerrard and A. V. Hill from determinations of heat production during its passage. Its mass relations are attested by a measurable increase in the carbon dioxide production of stimulated nerve. The rate of propagation of the nervous impulse varies like all chemical reactions in a characteristic way with increase in temperature. The goal of the nervous impulse after it has traversed one or more synapses in the central nervous system is the effecter organ itself--in the case of blinking of the eyelids, a muscle fibre. During the past two decades a series of brilliant researches based on calorimetric methods have revolutionized our knowledge of the final component of the reflex. A. V. Hill and Meyerhof have correlated the chemical and energetic changes accompanying muscular contraction with a precision of the order expected in purely physico-chemical determinations. They have shown that the total energy of muscular contraction can be quantitatively related to the energy liberated _in vitro_ by the breakdown into lactic acid of an amount of glycogen equivalent to that which is converted into lactic acid in the actual contractile process.

Passing from the analysis of the constituent events of the reflex to the integration of reflexes in normal behaviour, we are faced with a striking change in the attitude of enquiry adopted in the study of those aspects of behaviour determined by generalized stimuli such as light and gravity and denoted by the term _tropisms_. Three-quarters of a century ago, after Helmholtz had dispelled the belief that identified the nervous impulse with an imponderable psychical principle, biologists like Lubbock were content for the most part with the statement that the moth flies towards the candle because it likes the light. The work of Loeb and others has shown that the state of contraction of particular groups of muscles is reflexly determined by the stimulation of particular areas of the retina. It is a mechanical necessity that when different areas are unequally stimulated, differences in tension of different groups of muscles will bring the body into such a position that symmetrically opposite areas will be equally illuminated. The animal must move, as in fact it does, along the path of the incident beam, whether by so doing it brings itself into a brighter, or, as can easily be arranged experimentally, a darker situation. Whereas the older and purely teleological attitude permits us to predict nothing of consequence, the objective interpretation of tropisms by experimental methods permits us to make many verifiable predictions, as, for instance, the fact that the moth will move in circles, if one eye is blackened, owing to the fact that the muscles on that side will be more relaxed.

By the end of the nineteenth century, experimental biologists were generally disposed to the belief that the analysis of the reflex and the integration of reflex systems were problems not of apologetics but of energetics. Investigation had been confined to those aspects of behaviour which are for practical purposes invariable responses to a particular situation. From the human standpoint the most fascinating feature of the behaviour of an organism is, after all, the extent to which its behaviour is conditioned not by the immediate but by the antecedent situation. In the opening years of this century the researches of Sherrington were elucidating the integration of reflexes in normal behaviour. Restricted as they were to the decerebrate animal, the traditional distinction between reflex and voluntary activity remained as a defeatist formula in biological nomenclature. The distinction was not a gratuitous olive branch to introspective philosophy. It had its objective basis in the domain of behaviour which is not uniquely determined by the immediate stimulus, when all synchronous conditions have been standardized. That distinction has been superseded to-day by the work of Pavlov’s school, which has shown, first, that in the higher animals with the cerebrum intact, new reflex systems can be built up experimentally under perfectly definable and reproducible conditions; that the relations between such conditioned reflexes can be defined in the language of space and time; and that the concept of sensation can be externalized by reference to the ability of a given stimulus to become a specific agent in the building up of a new reflex system. In short, it is legitimate to anticipate the possibility of giving a complete specification of how such an animal as a dog will behave in a given situation without recourse to the traditional nomenclature of memory, consciousness, sensation, etc.

Pavlov’s work is now accessible to the English reader through two translations of the Russian physiologist’s own writings and several excellent résumés, such as the one given in Lovatt Evans’ _Recent Advances in Physiology_. How far-reaching are its consequences has not been widely recognized even by biologists themselves. Experimental biology, during its brief career, has attempted to accommodate itself to the introspective temper of traditional philosophy by a compromise explicitly formulated in the writings of Descartes, who bequeathed to physiology the dualism of mind and matter. In conformity with the Chaldæan mythos, many philosophers, Descartes among them, have endowed Man alone with soulfulness. The coming of the Evolutionary hypothesis has broken down so inflexible a distinction between Man and other forms of living matter. Evolutionists in the nineteenth century, like Haeckel, were prepared to equip the Amœba with a soul. In our time the Cartesian compromise has again shifted its boundaries. By the beginning of this century the moth once more had gone to join the candle. Still Man stood with a little family of mammals around him, each with one leg on either side of the frontier that separates the universe of space and time from the Platonic world of universals. Pavlov has taken those aspects of behaviour which would have been referred twenty years ago to exclusively introspective concepts, and has treated them successfully as predictable configurations in a space-time framework. The little family of mammals has been let through the tollgate of the Cartesian compromise. A new school of psychologists has come into being with the express object of making psychology a physical science, relieving Man, the celestial pilgrim, of his burden of soul.

Philosophers have always had a legitimate cause for complaint that biologists were unable to deal with those aspects of human life which interest people most. The distinction between reflex and voluntary activity provided the fullest absolution for that amiable libertarianism which we all entertain under the influence of alcohol and love. Because that distinction was implicit in the outlook of the most radical mechanists of the last generation, Loeb among them, Dr. Haldane finds it so easy to point out the inadequacy of the mechanistic outlook. In the light of Pavlov’s work we can now envisage the possibility that the methods of physical science will one day claim the whole field of what can be properly called knowledge. If I am right in cherishing such an opinion, it would thus appear that the investigation of the conditioned reflex initiates a new epoch in biology, pregnant with more far-reaching philosophical implications than the evolutionary speculations of the nineteenth century. The fact that no reference to the conditioned reflex is contained in Dr. Haldane’s Gifford Lectures may in part account for the fact that he can so easily dispose of the mechanistic position. The modern mechanist does not say that thought and love and heroism do not exist. He says, show me behaviour to which you apply the adjectives thoughtful or loving or heroic, and we will, one fine day, endeavour to arrive at predictable conclusions with reference to it by following the only method of enquiry which we have learned by experience to trust. When Dr. Haldane goes out of his way to dispose of the puerile formula that thought is a secretion of the brain, as bile is a secretion of the liver, and does so, I gather, under the impression that mechanists either believe it to mean something or alternatively shut their eyes to the major problems of existence, I can only respectfully suggest that he is flogging a dead horse, while the living ones are getting out of the vitalistic stables.

I have endeavoured so far to indicate the increasing measure of success that has crowned the application of physical methods and the use of physical concepts in modern biological investigation. I have attempted to illustrate the continuous retreat from teleological concepts that has accompanied this advance. In asking what progress may be anticipated from encouraging the teleological attitude to the nature of life, I wish now to urge that the important advances of biological science during the last hundred years have not only involved continual abandonment of teleological concepts, but have consistently been made in the teeth of opposition from the vitalists, organicists and holists of their time. A century ago, in the same year that witnessed Wöhler’s announcement of the successful synthesis of Urea, the great chemist Henry wrote (1827) concerning organic compounds: “It is not probable that we shall ever attain the power of imitating Nature in these operations. For in the functions of a living plant a directing principle appears to be concerned peculiar to animated bodies and superior to and differing from the cause which has been termed chemical affinity.” Only six years before Helmholtz’s determination of the velocity of the nervous impulse in 1851, Johannes Müller had declared that to measure the propagation of that imponderable psychical principle was a theoretical absurdity.

It is not unlikely that before another celebration of the centenary of Wöhler’s achievement, Fischer’s synthesis of an octadecapeptide will have been surpassed by the manufacture of complex proteins in the laboratory. Looking forward a little in the light of what success has crowned the construction of physical models of vital processes, it is, as Sir Edward Sharpey Schafer scandalously suggested at a meeting of the British Association some years ago, perfectly legitimate to entertain the possibility, even the likelihood, that scientists will one day construct from artificially synthesized organic materials, systems with so wide a range of reversible reactivity and receptivity to external influences that they would be called organisms, if met with in Nature. While taking a more hopeful view in this matter than some biologists, I would remark that the validity of the mechanistic outlook is quite independent of this possibility. The security of any dynamical system of treating the motions of the heavenly bodies is independent of the possibility that human effort could manufacture a new satellite for Jupiter.

§3

If we can assert that the present phase of biological enquiry is a peculiarly fruitful one, and that there is no reason to see any immediate cessation of progress in the use of physical concepts as the basis of our analysis of the properties of living matter, can we not go further and state that we have absolutely no encouragement for entertaining the hope that any deeper knowledge will accrue from apostrophizing under the sobriquets of entelechy, life force, élan vital that elusive entity to which, perhaps, the poet William Blake referred as Old Nobodaddy? It is doubtful whether we shall see a recrudescence of such frankly animistic devices as these. As biology becomes more technical and more exact, an aptitude for rehabilitating oriental mysticism in somewhat unusual verbiage will be regarded as an insufficient equipment for entering the field of biological controversy. The investigator who abandons physics for the pursuit of biology will contribute new ideas. Fruitful contributions need no longer be expected from those who combine the pursuit of literature with an amiable interest in natural history. The days of Butler and Bergson are passed.

Dr. Haldane, the most vigorous contemporary critic of the mechanistic standpoint, is very anxious to avoid any suspicion of being tainted with the cruder forms of vitalism. He disowns any allegiance to the life force, élan vital et hoc genus omne, except in so far as he, somewhat mysteriously, contrives to introduce an adventitious deity into the latter portion of his Gifford Lectures. This does not make its appearance until his major thesis is complete. Anxious as is Dr. Haldane to disclaim adherence to the tenets of vitalism, he is very definite in denying the possibility that atomistic concepts will ever successfully deal with the problem of what he calls “conscious behaviour.” In the light of Pavlov’s work we see that the problem of what is usually called conscious behaviour, or as we should rather say _conditioned behaviour_, can now be approached as a problem in the study of those conditions which determine whether a new reflex will, or will not, be brought into being. We may state this in other words by enquiring how the passage of impulses along particular tracts in the central nervous system _influences the facility with which the nervous impulse will pass across a particular type of synapse_. Since the problem of the conductivity of the synapse is, as we have seen, an essentially physical problem, it is not overstating the case to say that the work of Pavlov’s school has brought the study of what Dr. Haldane calls “conscious behaviour” within the realm of physical enquiry. Once this is fully grasped it no longer seems incredible that the interpretation of conditioned behaviour will eventually come within the scope of physico-chemical analysis. Contrary to the holistic standpoint, we are thus led to an atomistic concept of individuality. This I shall venture to formulate as _the statistical probability that in an immensely elaborate system of reversible reactions a certain number of states characteristic of any given moment will be reproducible at another moment_.

In his Lowell lectures Professor A. V. Hill lays down two general conclusions derived from the extension of modern biological enquiry. First, as I have endeavoured to show, there is no limit to the extent to which the mechanisms of life can be elucidated with the aid of physical methods and concepts. Second, that, however far we get, we shall still find function, adaptation, organization and purpose in the processes we explore. I would venture to suggest that, however alluring such a compromise between vitalism and mechanism may appear, these two conclusions, though formally in nowise inconsistent, are, nevertheless, in practice incompatible. As Henderson points out in his _Fitness of the Environment_, if we wish to indulge in teleological phantasies, we can find as much scope in physics and chemistry as in biology. We do not dismiss the hypothesis that thunderstorms occur when a blue unicorn sneezes on Uranus, because it is actually possible to disprove so engaging a fancy, but simply because other ways of treating thunderstorms lead to more useful conclusions.

Hence it seems to me that as we come to understand more and more about the mechanics of living systems by using methods of which Professor Hill is so brilliant an exponent, we shall inevitably find ourselves talking less and less about purpose and function. In consequence many of the problems which now engage the attention of philosophers will be relegated to the same status as the philosopher’s stone. No doubt such a change will come very gradually, so gradually that we shall hardly notice it. Nevertheless, one may venture to predict that philosophers, already forced by the developments of modern physics to divert their attention from the pretentious crossword puzzles of the Hegelian tradition, will sooner or later be driven to take account of the post-evolutionary developments in biology, and more especially those which have their starting-point in Pavlov’s researches.