CHAPTER IV
The Classification Of Variation And
The Nature Of Substantive Factors
We have now seen that among the normal physiological processes the phenomena of division form a recognisable, and in all likelihood a naturally distinct group. Variations in these respects may thus be regarded as constituting a special class among variations in general.
The substantive variations have only one property in common—the negative one that they are not Meristic. The work of classifying them and distinguishing them according to their several types demands a knowledge of the chemistry of life far higher than that to which science has yet attained. In reference to some of the simplest variations Garrod has introduced the appropriate term "Chemical sports." The condition in man known as Alkaptonuria in which the urine is red is due especially to the absence of the enzyme which decomposes the excretory substance, alkapton. The "chemical sport" here consists in the inability to break up the benzene ring. The chemical feature which distinguishes and is the proximate cause of several colour-varieties can now in a few cases be declared. The work of Miss Wheldale has shown that colour-varieties may be produced by the absence of the chromogen compound the oxidation of which gives rise to sap-colours, by differences in the completeness of this process of oxidation, and by a process of reduction supervening on or perhaps suppressing the oxidation. Some of these processes moreover may be brought about by the combined action of two bodies, the one an enzyme, for example an oxygenase, and the other a substance regarded as a peroxide, contributing the oxygen necessary for the oxidation to take place. Variation in colour may thus be brought about by the addition or omission of any one of the bodies concerned in the action.
Similar variations, or rather similar series of variations will undoubtedly hereafter be identified in reference to all the various kinds of chemical processes upon which the structure and functions of living things depend. The identification of these processes and of the bodies concerned in them will lead to a real classification of Substantive Variations.
To forecast the lines on which such classification will proceed is to look too far ahead. We may nevertheless anticipate with some confidence that future analysis will recognise among the contributing elements, some which are intrinsic and inalienable, and others which are extrinsic and superadded.
We already know that there may be such interdependence among the substantive characters that to disentangle them will be a work of extreme difficulty. The mere fact that in our estimation characters belong to distinct physiological systems is no proof of their actual independence. In illustration may be mentioned the sap-colour in Stocks and the development of hoariness on the leaves and stems, which Miss Saunders's experiments have shown to be intimately connected, so that in certain varieties no hoariness is produced unless the elements for sap-colour are already present in the individual plant.
The first step in the classification of substantive variations is therefore to determine which are due to the addition of new elements or factors, and which are produced by the omission of old ones. A priori there is no valid criterion by which this can be known, and actual experiments in analytical breeding can alone provide the knowledge required. Some very curious results have by this method been obtained, which throw an altogether unexpected light on these problems. For example, in order that the remarkable development of mesoblastic black pigment characteristic of the Silky Fowl should be developed, it is practically certain that two distinct variations from such a type as Gallus bankiva must have occurred. I assume, as is reasonable, that G. bankiva has genetic properties similar to those of the Brown Leghorn breed which has been used in the experiments which Mr. Punnett and I have conducted. Gallus bankiva was not available but the Brown Leghorn agrees with it very closely in colouration, and probably in the general physiology of its pigmentation. Setting aside the various structural differences between the two breeds, the Silky is immediately distinguished from the Leghorn by the fact that the skin of the whole body including that of the face and comb appears to be of a deep purplish colour. The face and comb of the Leghorn are red and the skin of the body is whitish yellow. On examination it is found that the purple colour of the Silky is in reality due to the distribution of a deep black pigment in the mesoblastic membranes throughout the body. The somatopleura, the pleura, pia mater, the dermis, and in most organs the connective tissue and the sheaths of the blood-vessels, are thus impregnated with black. No such pigmentation exists in the Leghorn. As the result of an elaborate series of experimental matings we have proved that the distinction between the Leghorn and the Silky consists primarily in the fact that the Silky possesses a pigment-producing factor, P, which is not present in the Leghorn.
This variation must undoubtedly have been one of addition. But besides this there is another difference of an altogether dissimilar nature; for the Brown Leghorn possesses a factor which has the power of partially or completely restricting the operation of the pigment-producing factor, P. Moreover in respect of this pigment-restricting factor which we may call D, the sexes of the Brown Leghorn differ, for the male is homozygous or DD, but the female is heterozygous, Dd. Thus in order that the black-skinned breed could be evolved from such a type as a Brown Leghorn it must be necessary both that P should be added and that D should drop out. We have not the faintest conception of the process by which either of these events have come to pass, but there is no reasonable doubt that in the evolution of the Silky fowl they did actually happen.
We may anticipate that numerous interdependences of this kind will be discovered.
Before any indisputable progress can be made with the problem of evolution it is necessary that we should acquire some real knowledge of the genesis of that class of phenomena which formed the subject of the last chapter. So long as the process of division remains entirely mysterious we can form no conception even of the haziest sort as to the nature of living organisms, or of the proximate causes which determine their forms, still less can we attempt any answer to those remoter questions of origin and destiny which form the subject of the philosopher's contemplation. It is in no spirit of dogmatism that I have ventured to indicate the direction in which I look for a solution, though I have none to offer. It may well be that before any solution is attained, our knowledge of the nature of unorganised matter must first be increased. For a long time yet we may have to halt, but we none the less do well to prepare ourselves to utilise any means of advance that may be offered, by carefully reconnoitering the ground we have to traverse. The real difficulty which blocks our progress is ignorance of the nature of division, or to use the more general term, of repetition.
Let us turn to the more familiar problem of the causes of variation. Now since variation consists as much in meristic change as in alteration in substance or material, there is one great range of problems of causation from which we are as yet entirely cut off. We know nothing of the causation of division, and we have scarcely an observation, experiment or surmise touching the causes by which the meristic processes may be altered.
Of the way in which variations in the substantive composition of organisms are caused we have almost as little real evidence, but we are beginning to know in what such variations must consist. These changes must occur either by the addition or loss of factors.
We must not lose sight of the fact that though the factors operate by the production of enzymes, of bodies on which these enzymes can act, and of intermediary substances necessary to complete the enzyme-action, yet these bodies themselves can scarcely be themselves genetic factors, but consequences of their existence. What then are the factors themselves? Whence do they come? How do they become integral parts of the organism? Whence, for example, came the power which is present in a White Leghorn of destroying—probably reducing—the pigment in its feathers? That power is now a definite possession of the breed, present in all its germ-cells, male and female, taking part in their symmetrical divisions, and passed on equally to all as much as is the protoplasm or any other attribute of the breed. From the body of the bird the critical and efficient substance could in all likelihood be isolated by suitable means, just as the glycogen of the liver can be. But even when this extraction has been accomplished and the reducing body isolated, we shall know no more than we did before respecting the mode by which the power to produce it was conferred on the fowl, any more than we know how the walls of its blood-vessels acquired the power to form a fibrin-ferment.
It is when the scope of such considerations as this are fully grasped that we realise the fatuousness of the conventional treatment which the problem of the causes of variation commonly receives. Environmental change, chemical injury, differences in food supply, in temperature, in moisture, or the like have been proposed as "causes." Admitting as we must do, that changes may be produced—usually inhibitions of development—by subjecting living things to changes in these respects, how can we suppose it in the smallest degree likely that very precise, new, and adaptative powers can be conferred on the germs by such treatment? Reports of positive genetic consequences observed comparable with those I have mentioned, become from time to time current. We should I think regard them with the gravest doubt. Few, so far as I am aware, have ever been confirmed, though clear and repeated confirmation should be demanded before we suffer ourselves at all to build upon such evidence. In a subsequent chapter some of these cases will be considered in detail.
In no class of cases would the transmission of an acquired character superficially appear so probable as in those where power of resisting the attack of a pathogenic organism is acquired in the lifetime of the zygote. The possession of such a power is moreover a distinction comparable with those which differentiate varieties and species. It is due to the development in the blood of specific substances which pervade the whole fluid. This development is exactly one of those "appropriate responses to stimuli" which naturalists who incline to regard adaptation as a direct consequence of an environmental influence might most readily invoke as an illustration of their views. And yet all evidence is definitely unfavourable to the suggestion of an inheritance of the acquired power of resistance. Such change as can be perceived in the virulence of the attacks on successive generations may be most easily regarded as due to the extermination of the more susceptible strains, and perhaps in some measure to variation in the invading organisms themselves, an "acquired character" of quite different import.
The specific "anti-body" may have been produced in response to the stimulus of disease, but the power to produce it without this special stimulus is not included in the germ-cells any more than a pigment. All that they bear is the power to produce the anti-bodies when the stimulus is applied.
If we could conceive of an organism like one of those to which disease may be due becoming actually incorporated with the system of its host, so as to form a constituent of its germ-cells and to take part in the symmetry of their divisions, we should have something analogous to the case of a species which acquires a new factor and emits a dominant variety. When we see the phenomenon in this light we realise the obscurity of the problem. The appearance of recessive varieties is comparatively easy to understand. All that is implied is the omission of a constituent. How precisely the omission is effected we cannot suggest, but it is not very difficult to suppose that by some mechanical fault of cell-division a power may be lost. Such variation by unpacking, or analysis of a previously existing complex, though unaccountable, is not inconceivable. But whence come the new dominants? Whether we imagine that they are created by some rearrangement or other change internal to the organism, or whether we try to conceive them as due to the assumption of something from without we are confronted by equally hopeless difficulty.
The mystery of the origin of a dominant increases when it is realised that there is scarcely any recent and authentic account of such an event occurring under critical observation, which can be taken as a basis for discussion. The literature of horticulture for example abounds in cases alleged, but I do not think anyone can produce an illustration quite free from doubt. Such evidence is usually open to the suspicion that the plant was either introduced by some accident, or that it arose from a cross with a pre-existing dominant, or that it owed its origin to the meeting of complementary factors. In medical literature almost alone however, there are numerous records of the spontaneous origin of various abnormal conditions in man which habitually behave as dominants, and of the authenticity of some of these there can be no doubt.
When we know that such conditions as hereditary cataract or various deformities of the fingers behave as dominants, we recognize that those conditions must be due to the addition of some element to the constitution of the normal man. In the collections of pedigrees relating to such pathological dominants there are usually to be found alleged instances of the origin of the condition de novo. Not only do these records occur with such frequency that they cannot be readily set aside as errors, but from general considerations it must be obvious that as these malformations are not common to normal humanity they must at some moment of time have been introduced. The lay reader may not be so much impressed with the difficulty as we are. He is accustomed to regard the origin of any new character as equally mysterious, but when once dominants are distinguished from recessives the problem wears a new aspect. Thus the appearance of high artistic gifts, whether as an attribute of a race or as a sporadic event among the children of parents destitute of such faculties, is not very surprising, for we feel fairly sure that the faculty is a recessive, due to the loss of a controlling or inhibiting factor; but the de novo origin of brachydactylous fingers in a child of normal parents is of quite a different nature, and must indicate the action of some new specific cause.
Whether such evidence is applicable to the general problem of evolution may with some plausibility be questioned; but there is an obvious significance in the fact that it is among these pathological occurrences that we meet with phenomena most nearly resembling the spontaneous origin of dominant factors, and I cannot see such pedigrees as these without recalling Virchow's aphorism that every variation owes its origin to some pathological accident. In the evolution of domestic poultry, if Gallus bankiva be indeed the parent form of all our breeds, at least some half dozen new factors must have been added during the process. In bankiva there is, for example, no factor for rose comb, pea comb, barring on the feathers, or for the various dominant types of dark plumage. Whence came all these? It is, I think, by no means impossible that some other wild species now extinct did take part in the constitution of domestic poultry. It seems indeed to me improbable that the heavy breeds descend from bankiva. Both in regard to domestic races of fowls, pigeons, and some other forms, the belief in origin within the period of human civilization from one simple primitive wild type seems on a balance of probabilities insecurely founded, but allowing something for multiplicity of origin we still fall far short of the requisite total of factors. Elements exist in our domesticated breeds which we may feel with confidence have come in since their captivity began. Such elements in fowls are dominant whiteness, extra toe, feathered leg, frizzling, etc., so that even hypothetical extension of the range of origin is only a slight alleviation of the difficulty.
Somehow or other, therefore, we must recognize that dominant factors do arise. Whether they are created by internal change, or whether, as seems to me not wholly beyond possibility, they obtain entrance from without, there is no evidence to show. If they were proved to enter from without, like pathogenic organisms, we should have to account for the extraordinary fact that they are distributed with fair constancy to half the gametes of the heterozygote.
In proportion as the nature of dominants grows more clear so does it become increasingly difficult to make any plausible suggestion as to their possible derivation. On the other hand the origin of a recessive variety by the loss of a factor is a process so readily imagined that our wonder is rather that the phenomenon is not observed far more often. Some slip in the accurate working of the mechanical process of division, and a factor gets left out, the loss being attested by the appearance of a recessive variety in some subsequent generation.
Consistently with this presentation of the facts we find that, as in our domesticated animals and plants, a diversity of recessives may appear within a moderately short period, and that when variations come they often do not come alone. Witness the cultural history of the Sweet Pea, Primula Sinensis, Primula obconica, Nemesia strumosa and many such examples in which variation when it did come was abundant. The fact cannot be too often emphasized that in the vast proportion of these examples of substantive variation under domestication, as well as of substantive variation in the natural state, the change has come about by omission, not by addition. To take, for example, the case of the Potato, in which so many spontaneous bud-variations have been recorded, East after a careful study of the evidence has lately declared his belief that all are of this nature, and the opinion might be extended to many other groups of cases whether of bud or seminal variation. Morgan draws the same conclusion in reference to the many varieties he has studied in Drosophila.
In the Sweet Pea, a form which is beyond suspicion of having been crossed with anything else, and has certainly produced all the multitude of types which we now possess by variations from one wild species, there is only one character of the modern types which could, with any plausibility, be referred to a factor not originally forming part of the constituents of the wild species. This is the waved edge, so characteristic of the "Spencer" varieties; for the cross between a smooth-edged and a waved type gives an intermediate not unfrequently. Nevertheless there is practically no doubt that this is merely an imperfection in the dominance of the smooth edge, and we may feel sure that any plant homozygous for smooth edge would show no wave at all. Hence it is quite possible that even the appearance of the original waved type, Countess Spencer, was due to the loss of one of the factors for smooth edge at some time in the history of the Sweet Pea.
In the case of the Chinese Primrose (Primula Sinensis) one dominant factor has been introduced in modern times, probably within the last six years at most. This is the factor which causes suppression of the yellow eye, giving rise to the curious type known as "Queen Alexandra." Mr. R. P. Gregory's experiments proved that this was a very definite dominant, and the element responsible for this development is undoubtedly an addition to the original ingredient-properties, with which the species was endowed. Unfortunately, as happens in almost every case of the kind, the origin of this important novelty appears to be lost. Its behaviour, however, when crossed with various other types is that of a simple dominant giving an ordinary 3:1 ratio. There is therefore no real doubt that it came into existence by the definite addition of a new factor, for if it was simply a case of the appearance of a new character made by combination of two previously existing complementary factors we should expect that when Queen Alexandra was self-fertilised a 9:7 ratio would be a fairly common result, which is not in practice found.
In Oenothera Gates[1] has observed the appearance, in a large sowing of about 1,000 Oenothera rubrinervis, of a single individual having considerably more red pigment in the calyx than is usual in rubrinervis. The whole of the hypanthium in the flowers of this plant was red instead of green as in rubrinervis, and the whole of the sepals were red in the bud-stage, except for small green areas at the base. This type behaved as a dominant over rubrinervis, but so far a pure-breeding individual was not found. Admittedly the variation of this plant from the type of rubrinervis can be represented as one of degree, though there is a very sensible gap in the series between the new form which Gates names "rubricalyx" and the reddest rubrinervis seen in his cultures. It must certainly be recognised as a new dominant. Gates, rightly as I consider, regards the distinction between rubrinervis and rubricalyx as a quantitative one, and the same remark applies to certain other types differing in the amount of anthocyanin which they produce. I do not understand the argument which Gates introduces to the effect that the difference between such quantitative types cannot be represented in terms of presence and absence. We are quite accustomed to the fact that in the rabbit self-colour segregates from the Dutch-marked type. These two types differ in a manner which we may reasonably regard as quantitative. It is no doubt possible that the self-coloured type contains an ingredient which enables the colour to spread over the whole body, but it is, I think, perhaps more easy to regard the Dutch type as a form from which a part of the colour is absent. It may be spoken of in terms I have used, as a subtraction-stage in colour. Following a similar method we may regard rubricalyx as an addition-stage in colour-variation. The fact that crosses between rubrinervis, or rubricalyx and Lamarckiana give a mixture of types in F1, does not I think show, as Gates declares, that there is any system here at work to which a factorial or Mendelian analysis does not apply; but that question may be more fitly discussed in connexion with the other problems raised by the behaviour of Oenothera species in their crosses.
I do, however, feel that, interesting as this case must be admitted to be, we cannot quite satisfactorily discuss it as an illustration of the de novo origin of a dominant factor. The difference between the novelty and the type is quantitative, and it is not unreasonable to think of such a difference being brought about by some "pathological accident" in a cell-division.
Recognition of the distinction between dominant and recessive characters has, it must be conceded, created a very serious obstacle in the way of any rational and concrete theory of evolution. While variations of all kinds could be regarded as manifestations of some mysterious instability of organisms this difficulty did not occur to the mind of evolutionists. To most of those who have taken part in genetic analysis it has become a permanent and continual obsession. With regard to the origin of recessive variations, there is, as we have seen, no special difficulty. They are negative and are due to absences, but as soon as it is understood that dominants are caused by an addition we are completely at a loss to account for their origin, for we cannot surmise any source from which they may have been derived. Just as when typhoid fever breaks out in his district the medical officer of health knows for certain that the bacillus of typhoid fever has by some means been brought into that district so do we know that when first dominant white fowls arose in the evolution of the domestic breeds, by some means the factor for dominant whiteness got into a bird, or into at least one of its germ-cells. Whence it came we cannot surmise.
Whether we look to the outer world or to some rearrangement within the organism itself, the prospect of finding a source of such new elements is equally hopeless.
Leaving this fundamental question aside as one which it is as yet quite unprofitable to discuss, we are on safe ground in foreseeing that the future classification of substantive variations, which genetic research must before long make possible, will be based on a reference to the modes of action of the several factors. Some will be seen to produce their effects by oxidation, some by reduction, some by generating substances of various types, sugars, enzymes, activators, and so forth. It may thus be anticipated that the relation of varieties to each other and to types from which they are derived will be expressible in terms of definite synthetical formulae. Clearly it will not for an indefinite time be possible to do this in practice for more than a few species and for characters especially amenable to experimental tests, but as soon as the applicability of such treatment is generally understood the influence on systematics must be immediate and profound, for the nature of the problem will at length be clear and, though the ideal may be unattainable, its significance cannot be gainsaid.
Note.—With hesitation I allow this chapter to appear in the form in which it was printed a year ago, but in passing it for the press after that interval I feel it necessary to call attention to a possible line of argument not hitherto introduced.
In all our discussions we have felt justified in declaring that the dominance of any character indicates that some factor is present which is responsible for the production of that character. Where there is no definite dominance and the heterozygote is of an intermediate nature we should be unable to declare on which side the factor concerned was present and from which side it was absent. The degree of dominance becomes thus the deciding criterion by which we distinguish the existence of factors. But it should be clearly realized that in any given case the argument can with perfect logic be inverted. We already recognize cases in which by the presence of an inhibiting factor a character may be suppressed and purely as a matter of symbolical expression we might apply the same conception of inhibition to any example of factorial influence whatever. For instance we say that in as much as two normal persons do not have brachydactylous children, there must be some factor in these abnormal persons which causes the modification. Our conclusion is based on the observed fact that the modification is a dominant. But it may be that normal persons are homozygous in respect of some factor N, which prevents the appearance of brachydactyly, and that in any one heterozygous, Nn, for this inhibiting factor, brachydactyly can appear. Similarly the round pea we say contains R, a factor which confers this property of roundness, without which its seeds would be wrinkled. But here we know that the wrinkled seed is in reality one having compound starch-grains, and that the heterozygote, though outwardly round enough, is intermediate in that starch-character. If we chose to say that the compoundness of the grains is due to a factor C and that two doses of it are needed to make the seed wrinkled, I know no evidence by which such a thesis could be actually refuted. That such reasoning is seemingly perverse must be conceded; but when we consider the extraordinary difficulties which beset any attempt to conceive the mode of origin of a new dominant factor, we are bound to remember that there is this other line of argument which avoids that difficulty altogether. In the case of the "Alexandra"-eye in Primula, or the red calyx in Gates's Oenothera, inverting the reasoning adopted in the text, we may see that only the Primula homozygous for the yellow eye can develop it and that two doses of the factor for the rubrinervis calyx are required to prevent that part of the plant from being red.
We may proceed further and extend this mode of reasoning to all cases of genetic variation, and thus conceive of all alike as due to loss of factors present in the original complex. Until we can recognize factors by means more direct than are provided by a perception of their effects, this doubt cannot be positively removed. For all practical purposes of symbolic expression we may still continue to use in our analyses the modes of representation hitherto adopted, but we must not, merely on the ground of its apparent perversity, refuse to admit that the line of argument here indicated may some day prove sound.