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 F_{1}, 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.
FOOTNOTES:
[1] Gates, R. R., _Zts. f. Abstammungslehre_, 1911, IV, pp. 341 and 361.