A Critique of the Theory of Evolution/IV
SELECTION AND EVOLUTION
Darwin's Theory of Natural Selection still holds today first place in every discussion of evolution, and for this very reason the theory calls for careful scrutiny; for it is not difficult to show that the expression "natural selection" is to many men a metaphor that carries many meanings, and sometimes different meanings to different men. While I heartily agree with my fellow biologists in ascribing to Darwin himself, and to his work, the first place in biological philosophy, yet recognition of this claim should not deter us from a careful analysis of the situation in the light of work that has been done since Darwin's time.
The Theory of Natural Selection
In his great book on the Origin of Species, Darwin tried to do two things: first, to show that the evidence bearing on evolution makesthat explanation probable. No such great body of evidence had ever been brought together before, and it wrought, as we all know, a revolution in our modes of thinking.
Darwin also set himself the task of showing how evolution might have taken place. He pointed to the influence of the environment, to the effects of use and disuse, and to natural selection. It is to the last theory that his name is especially attached. He appealed to a fact familiar to everyone, that no two individuals are identical and that some of the differences that they show are inherited. He argued that those individuals that are best suited to their environment are the most probable ones to survive and to leave most offspring. In consequence their descendants should in time replace through competition the less well-adapted individuals of the species. This is the process Darwin called natural selection, and Spencer the survival of the fittest.
Stated in these general terms there is nothing in the theory to which anyone is likely to take exception. But let us examine the argument more critically.
If we measure, or weigh, or classify any character shown by the individuals of a population, we find differences. We recognize that some of the differences are due to the varied experiences that the individuals have encountered in the course of their lives, i.e. to their environment, but we also recognize that some of the differences may be due to individuals having different inheritances—different germ plasms. Some familiar examples will help to bring home this relation.
If the leaves of a tree are arranged according to size (fig. 71), we find a continuous series, but there are more leaves of medium size than extremes. If a lot of beans be sorted outaccording to their weights, and those between certain weights put into cylinders, the cylinders, when arranged according to the size of the beans, will appear as shown in figure 72. An imaginary line running over the tops of the piles will give a curve (fig. 73) that corresponds to the curve of probability (fig. 74).
If we stand men in lines according to their height (fig. 75) we get a similar arrangement.
The differences in size shown by the individual beans or by the individual men are due in part to heredity, in part to the environmentin which they have developed. This is a familiar fact of almost every-day observation. It is well shown in the following example. In figure 76 the two boys and the two varieties of corn, which they are holding, differ in height. The pedigrees of the boys (fig. 77) make it probable that their height is largely inherited and the two races of corn are known to belong to a tall and a short race respectively. Here, then, the chief effect or difference is due to heredity. On the other hand, if individuals of the same race develop in a favorable environment the result is different from the development in an unfavorable environment, as shown in figure 78. Here to the right the corn is crowded and in consequence dwarfed, while to the left the same kind of corn has had more room to develop and is taller.
Darwin knew that if selection of particular kinds of individuals of a population takes place the next generation is affected. If the taller men of a community are selected the average of their offspring will be taller than the average of the former population. If selection for tallness again takes place, still taller men will on the average arise. If, amongst these, selection again makes a choice the process would, he thought, continue (fig. 79).
We now recognize that this statement contains an important truth, but we have found that it contains only a part of the truth. Any one who repeats for himself this kind of selection experiment will find that while his average class will often change in the direction of his selection, the process slows down as a rule rather suddenly (fig. 80). He finds, moreover, that the limits of variability are not necessarily transcended as the process continues even although the average may for a while be increased. More tall men may be produced by selection of this kind, but the tallest men are not necessarily any taller than the tallest in the original population.
Selection, then, has not produced anything new, but only more of certain kinds of individuals. Evolution, however, means producing more new things, not more of what already exists.
Darwin seems to have thought that the range of variation shown by the offspring of a given individual about that type of individual would be as wide as the range shown by the original population (fig. 79), but Galton's work has made it clear that this is not the case in a general or mixed population. If the offspring of individuals continued to show, as Darwin seems to have thought, as wide a range on each side of their parents' size, so to speak, as did the original population, then it would follow thatselection could slide successive generations along in the direction of selection.
Darwin himself was extraordinarily careful, however, in the statements he made in this connection and it is rather by implication than by actual reference that one can ascribe thismeaning to his views. His contemporaries and many of his followers, however, appear to have accepted this sliding scale interpretation as the cardinal doctrine of evolution. If this is doubted or my statement is challenged then one must explain why de Vries' mutation theory met with so little enthusiasm amongst the older group of zoölogists and botanists; and one must explain why Johannsen's splendid work met with such bitter opposition from the English school—the biometricians—who amongst the post-Darwinian school are assumed to be the lineal descendants of Darwin.
And in this connection we should not forget that just this sort of process was supposed to take place in the inheritance of use and disuse. What is gained in one generation forms the basis for further gains in the next generation. Now, Darwin not only believed that acquired characters are inherited but turned more and more to this explanation in his later writings. Let us, however, not make too much of the matter; for it is much less important to find out whether Darwin's ideas were vague, than it is to make sure that our own ideas are clear.
If I have made several statements here that appear dogmatic let me now attempt to justify them, or at least give the evidence which seems to me to make them probable.
The work of the Danish botanist, Johannsen, has given us the most carefully analyzed case of selection that has ever been obtained. There are, moreover, special reasons why the material that he used is better suited to give definite information than any other so far studied. Johannsen worked with the common bean, weighing the seeds or else measuring them. These beans if taken from many plants at random give the typical curve of probability (fig. 74). The plant multiplies by self-fertilization. Taking advantage of this fact Johannsen kept the seeds of each plant separate from the others, and raised from them a new generation. When curves were made from these new groups it was found that some of them had different modes from that of the original general population (fig. 81 A-E, bottom group). They are shown in the upper groups (A, B, C, D, E). But do not understand me to say that the offspring of each bean gave a different mode.
On the contrary, some of the lines would be the same.
The result means that the general population is made up of definite kinds of individuals that may have been sorted out.
That his conclusion is correct is shown by rearing a new generation from any plant or indeed from several plants of any one of these lines. Each line repeats the same modal class. There is no further breaking up into groups. Within the line it does not matter at all whether one chooses a big bean or a little one—they will give the same result. In a word, the germ plasm in each of these lines is pure, or homozygous, as we say. The differences that we find between the weights (or sizes) of the individual beans are due to external conditions to which they have been subjected.
In a word, Johannsen's work shows that the frequency distribution of a pure line is due to factors that are extrinsic to the germ plasm. It does not matter then which individuals in a pure line are used to breed from, for they all carry the same germ plasm.
We can now understand more clearly howselection acting on a general population brings about results in the direction of selection.
An individual is picked out from the population in order to get a particular kind of germ plasm. Although the different classes of individuals may overlap, so that one can not always judge an individual from its appearance, nevertheless on the whole chance favors the picking out of the kind of germ plasm sought.
In species with separate sexes there is the further difficulty that two individuals must be chosen for each mating, and superficial examination of them does not insure that they belong to the same group—their germ plasm cannot be inspected. Hence selection of biparental forms is a precarious process, now going forward, now backwards, now standing still. In time, however, the process forward is almost certain to take place if the selection is from a heterogeneous population. Johannsen's work was simplified because he started with pure lines. In fact, had he not done so his work would not have been essentially different from that of any selection experiment of a pure race of animals or plants. Whether Johannsenrealized the importance of the condition or not is uncertain—curiously he laid no emphasis on it in the first edition of his "Elemente der exakten Erblichkeitslehre".
It has since been pointed out by Jennings and by Pearl that a race that reproduces by self-fertilization as does this bean, automatically becomes pure in all of the factors that make up its germ plasm. Since self-fertilization is the normal process in this bean the purity of the germ plasm already existed when Johannsen began to experiment.
How Has Selection in Domesticated Animals and Plants Brought About Its Results?
If then selection does not bring about transgressive variation in a general population, how can selection produce anything new? If it can not produce anything new, is there any other way in which selection becomes an agent in evolution?
We can get some light on this question if we turn to what man has done with his domesticated animals and plants. Through selection,i.e., artificial selection, man has undoubtedly brought about changes as remarkable as any shown by wild animals and plants. We know, moreover, a good deal about how these changes have been wrought.
(1) By crossing different wild species or by crossing wild with races already domesticated new combinations have been made. Parts of one individual have been combined with parts of others, creating new combinations. It is possible even that characters that are entirely new may be produced by the interaction of factors brought into recombination.
(2) New characters appear from time to time in domesticated and in wild species. These, like the mutants in Drosophila, are fully equipped at the start. Since they breed true and follow Mendel's laws it is possible to combine them with characters of the wild type or with those of other mutant races.
Amongst the new mutant factors there may be some whose chief effect is on the character that the breeder is already selecting. Such a modification will be likely to attract attention. Superficially it may appear that thefactor for the original character has varied, while the truth may be that another factor has appeared that has modified a character already present. In fact, many or all Mendelian factors that affect the same organ may be said to be modifiers of each other's effects. Thus the factor for vermilion causes the eye to be one color, and the factor for eosin another color, while eosin vermilion is different from both. Eosin may be said to be a modifier of vermilion or vermilion of eosin. In general, however, it is convenient to use the term "modifier" for cases in which the factor causes a detectable change in a character already present or conspicuous.
One of the most interesting, and at the same time most treacherous, kinds of modifying factors is that which produces an effect only when some other factor is present. Thus Bridges has shown that there is a factor called "cream" that does not affect the red color of the eye of the wild fly, yet makes "eosin" much paler (fig. 82). Another factor "whiting" which produces no effect on red makes eosin entirely white. Since cream or whiting may be carried by red eyed flies without their presence being seen until eosin is used, the experimenter must be continually on the lookout for such factors which may lead to erroneous conclusions unless detected. As yet breeders have not realized the important rôle that modifiers have played in their results, but there are indications at least that the heaping up of modifying factors has been one of the ways in whichhighly specialized domesticated animals have been produced. Selection has accomplished this result not by changing factors, but by picking up modifying factors. The demonstration of the presence of these factors has already been made in some cases. Their study promises to be one of the most instructive fields for further work bearing on the selection hypothesis.
In addition to these well recognized methods by which artificial selection has produced new things we come now to a question that is the very crux of the selection theory today. Our whole conception of selection turns on the answer that we give to this matter and if I appear insistent and go into some detail it is because I think that the matter is worth very careful consideration.
Are Factors Changed Through Selection?
As we have seen, the variation that we find from individual to individual is due in part to the environment; this can generally be demonstrated. Other differences in anordinary population are recognized as due to different genetic (hereditary) combinations. No one will dispute this statement. But is all the variability accounted for in these two ways? May not a factor itself fluctuate? Is it not a priori probable that factors do fluctuate? Why, in a word, should we regard factors as inviolate when we see that everything else in organisms is more or less in amount? I do not know of any a priori reason why a factor may not fluctuate, unless it is, as I like to think, a chemical molecule. We are, however, dealing here not with generalities but with evidence, and there are three known methods by means of which it has been shown that variability, other than environmental or recombinational, is not due to variability in a factor, nor to various "potencies" possessed by the same factors.
(1) By making the stock uniform for all of its factors—chief factors and modifiers alike. Any change in such a stock produced by selection would then be due to a change in one or more of the factors themselves. Johannsen's experiment is an example of this sort.
(2) The second method is one that iscapable of demonstrating that the effects of selection are actually due to modifiers. It has been worked out in our laboratory, chiefly by Muller, and used in a particular case to demonstrate that selection produced its effect by isolating modifying factors. For example, a mutant type called truncate appeared, characterized by shorter wings, usually square at the end, (fig. 83a). The wings varied from those of normal length to wings much shorter (fig. 83b). For three years the mutant stock was bred from individuals having the shorter wings until at last a stock was obtained in which some of the individuals had wings much shorter than the body. By means of linkage experiments it was shown that at least three factors were present that modified the wings. These were isolated by means of their linkage relations, and their mutual influence on the production of truncate wings was shown.
An experiment of this kind can only be carried out in a case where the groups of linked gens are known. At present Drosophila is the only animal (or plant) sufficiently well known to make this test possible, but this does not prove that the method is of no value. On the contrary it shows that any claim that factors can themselves be changed can have no finality until the claim can be tested out by means of the linkage test. For instance, bar eye (fig. 31) arose as a mutation. All our stock has descended from a single original mutant. But Zeleny has shown that selection within our stock will make the bar eye narrower or broader according to the direction of selection. It remains to be shown in this case how selection has produced its effects, and this can be done by utilizing the same process that was used in the case of truncate.
Another mutant stock called beaded (fig. 84), has been bred for five years and selected for wings showing more beading. In extreme cases the wings have been reduced to mere stumps (see stumpy, fig. 5), but the stock shows great variability. It is probable hereas Dexter has shown, that a number of mutant factors that act as modifiers have been picked up in the course of the selection, and when it is recalled that during those five years over 125 new characters have appeared elsewhere it does not seem improbable that factors also have appeared that modify the wings of this stock.
(3) The third method is one that has been developed principally by East for plants; also by MacDowell for rabbits and flies. Themethod does not claim to prove that modifiers are present, but it shows why certain results are in harmony with that expectation and can not be accounted for on the basis that a factor has changed. Let me give an example. When a Belgian hare with large body was crossed to a common rabbit with a small body the hybrid was intermediate in size. When the hybrid was crossed back to the smaller type it produced rabbits of various sizes in apparently a continuous series. MacDowell made measurements of the range of variability in the first and in the second generations.
Classification in relation to parents based on skull lengths and ulna lengths, to show the relative variability of two measurements and of the first generation (F1) and the back cross (B. C.)
same table continued
He found that the variability was smaller in the first generation than in the secondgeneration (back cross). This is what is expected if several factor-differences were involved, because the hybrids of the first generation are expected to be more uniform in factorial composition than are those in the second generation which are produced by recombination of the factors introduced through their grandparents. Excellent illustrations of the same kinds of results have been found in Indian corn. As shown in figure 85 the length of the cob in F1 is intermediate between the parent types while in F2 the range is wider and both of the original types are recovered. East states that similar relations have been found for 18 characters in corn. Emerson has recently furnished further illustrations of the same relations in the length of stalks in beans.
A similar case is shown by a cross between fantail and common pigeons (fig. 86). The latter have twelve feathers in the tail, while the selected race from which the fantails came had between 28 and 38 feathers in the tail. The F1 offspring (forty-one individuals) showed (fig. 87) between 12 and 20 tail feathers, while in F2 the numbers varied between 12 and 25. Here one of the grand-parental types reappears in large numbers, while the extreme of the other grand-parental type did not reappear (in the counts obtained), although the F2 number would probably overlap the lower limits of the race of fantail grandparents had not a selected (surviving) lot been taken for the figures given in the table.
The preceding account attempts to point out how I should prefer to interpret the problem of selection in the light of the most recent work on breeding. But I would give a very incomplete account of the whole situation if I neglected to include some important work which has led some of my fellow-workers to a very different conclusion.
Castle in particular is the champion of a view based on his results with hooded rats. Starting with individuals which have a narrow black stripe down the back he selected for a narrower stripe in one direction and for abroader stripe in the other. As the diagram shows (fig. 88) Castle has succeeded in producing in one direction a race in which the dorsal stripe has disappeared and in the other direction a race in which the black has extended over the back and sides, leaving only a white mark on the belly. Neither of these extremes occurs, he believes, in the ordinary hooded race of domesticated rats. In other words no matter how many of them came under observation the extreme types of his experiment would not be found.
Castle claims that the factor for hoodedness must be a single Mendelian unit, because if hooded rats are crossed to wild gray rats with uniform coat and their offspring are inbred there are produced in F2 three uniform rats to one hooded rat. Castle advances the hypothesis that factors—by which he means Mendelian factors—may themselves vary in much the same way as do the characters that they stand for. He argues, in so many words, that since we judge a factor by the kind of character it produces, when the character varies the factor that stands for it may have changed.
As early as 1903 Cuénot had carried out experiments with spotted mice similar to those of Castle with rats. Cuénot found that spotted crossed to uniform coat color gave in F2 a ratio of three uniform to one spotted, yet selection of those spotted mice with more white in their coat produced mice in successive generations that had more and more white. Conversely Cuénot showed that selection of those spotted mice that had more color in their coat produced mice with more and more color and less white. Cuénot does not however bring up in this connection the question as to how selection in these spotted mice brings about its results.
Without attempting to discuss these results at the length that they deserve let me briefly state why I think Castle's evidence fails to establish his conclusion.
In the first place one of the premises may be wrong. The three to one ratio in F2 by no means proves that all conditions of hoodedness are due to one factor. The result shows at most that one factor that gives the hooded types is a simple Mendelian factor. The changes in this type may be caused by modifying factorsthat can show an effect only when hoodedness is itself present. That this is not an imaginary objection but a real one is shown by an experiment that Castle himself made which furnishes the ground for the second objection.
Second. If the factor has really changed its potency, then if a very dark individual from one end of the series is crossed to a wild rat and the second generation raised we should expect that the hooded F2 rats would all be dark like their dark grandparent. When Castle made this test he found that there were many grades of hooded rats in the F2 progeny. They were darker, it is true, as a group than were the original hooded group at the beginning of the selection experiment, but they gave many intermediate grades. Castle attempts to explain this by the assumption that the factor made pure by selection became contaminated by its normal allelomorph in the F1 parent, but not only does this assumption appear to beg the whole question, but it is in flat contradiction with what we have observed in hundreds of Mendelian cases where no evidence for such a contamination exists.
Later Castle crossed some of the extracted rats of average grade (3.01) from the plus series to the same wild race and got F2 hooded rats from this cross. These F2 hooded rats did not further approach the ordinary range but were nearer the extreme selected plus hooded rats (3.33) than were the F2's extracted from the first cross (2.59). Castle concludes from this that multiple factors can not account for the result. As a matter of fact, Castle's evidence as published does not establish his conclusion because the wild rats used in the second experiment may have carried plus modifiers. This could only be determined by suitable tests which Castle does not furnish. This is the crucial point, without which the evidence carries no conviction.
Furthermore, from Castle's point of view, these latest results would seem to increase the difficulty of interpretation of his first F2 extracted cross, and it is now the first result that calls for explanation if one accepts his later conclusion.
These and other objections that might be taken up show, I think, that Castle'sexperiment with hooded rats fails entirely to establish his contention of change in potency of the germ or of contamination of factors, while on the contrary they are in entire accord with the view that he is dealing with a case of modifying factors.
Equally important are the results that Jennings has obtained with certain protozoa. Paramecium multiplies by dividing across in themiddle, each half replacing its lacking part. Both the small nucleus (micronucleus) and the large nucleus (macronucleus) divide at each division of the body. Jennings found that while individuals descended from a single paramecium vary in size (fig. 89), yet the population from a large individual is the same as the population derived from a small individual. In other words, selection produces no result and the probable explanation is, of course, that the different sizes of individuals are due to the environment, while the constancy of the type is genetic. Jennings found a number of races of paramecium of different sizes living under natural conditions. The largest individual of a small race might overlap the smallest individual of other larger races (fig. 89); nevertheless each kind reproduced its particular race. The results are like those of Johannsen in a general way, but differ in that reproduction takes place in paramecium by direct division instead of through self-fertilization as in beans, and also in that the paramecia were probably not homozygous. Since, however, so far as known no "reduction" takes place in paramecium at each division, the genetic composition of parent and offspring should be the same. Whether pseudo-parthenogenesis that Woodruff and Erdmann have found occurring in paramecium at intervals involves a redistribution of the hereditary factors is not clear. Jennings's evidence seems incompatible with such a view.
More recently one of Jennings's students, Middleton, has made a careful series of selection experiments with Stylonychia (fig. 90) in which he selected for lines showing more rapidor slower rates of division. His observations seem to show that his selection separated two such lines that came from the same original stock. The rapidity of the effects of selection seems to preclude the explanation that pseudo-parthenogenesis has complicated the results. Nevertheless, the results are of such a kind as to suggest that they were due to selection of vegetative (somatic) differences and that no genetic change of factors was involved, for his conclusion that the rapidity with which the effects gained by long selection might be suddenly reversed when selection was reversed is hardly consistent with an interpretation of the results based on changes in the "potencies" of the factors present.
Equally striking are the interesting experiments that Jennings has recently carried out with Difflugia (fig. 91). This protozoon secretes a shell about itself which has a characteristic shape, and often carries spines. The opening at one end of the shell through which the protoplasm protrudes to make the pseudopodia is surrounded by a rim having a characteristic pattern. The protoplasm containsseveral nuclei and in addition there is scattered material or particles called chromidia that are supposed to be chromatic in nature and related to the material of the nuclei, possibly by direct interchange.
When Difflugia divides, part of the protoplasm protrudes from the opening and a new shell is secreted about this mass which becomes a daughter individual. The behavior of the nucleus and of the chromidia at this time is obscure, but there is some evidence that their materials may be irregularly distributedbetween parent and offspring. If this is correct, and if in the protozoa the chromatin has the same influence that it seems to have in higher animals, the mode of reproduction in Difflugia would be expected to give little more than random sampling of the germ plasm.
Jennings was able by means of selection to get from the descendants of one original individual a number of different types that themselves bred true, except in so far as selection could affect another change in them. In this connection it is interesting to note that Leidyhas published figures of Difflugia (fig. 92) that show that a great many "types" exist. If through sexual union (a process that occurs in Difflugia) the germ plasm (chromatin) of these wild types has in times past been recombined, then selection would be expected to separate certain types again, if, at division, irregular sampling of the germ plasm takes place. Until these points are settled the bearing of these important experiments of Jennings on the general problem of selection is uncertain.
How Does Natural Selection Influence the Course of Evolution?
The question still remains: Does selection play any rôle in evolution, and, if so, in what sense? Does the elimination of the unfit influence the course of evolution, except in the negative sense of leaving more room for the fit? There is something further to be said in this connection, although opinions may differ as to whether the following interpretation of the term "natural selection" is the only possible one.
If through a mutation a character appears that is neither advantageous nor disadvantageous, but indifferent, the chance that it may become established in the race is extremely small, although by good luck such a thing may occur rarely. It makes no difference whether the character in question is a dominant or arecessive one, the chance of its becoming established is exactly the same. If through a mutation a character appears that has an injurious effect, however slight this may be, it has practically no chance of becoming established.
If through a mutation a character appears that has a beneficial influence on the individual, the chance that the individual will survive is increased, not only for itself, but for all of itsdescendants that come to inherit this character. It is this increase in the number of individuals possessing a particular character, that might have an influence on the course of evolution. This gives a better chance for improvement by several successive steps; but not because the species is more likely to mutate again in the same direction. An imaginary example will illustrate how this happens: When elephants had trunks less than a foot long, the chance of getting trunks more than one foot long was in proportion to the length of trunks already present and to the number of individuals; but increment in trunk length is no more likely to occur from an animal having a trunk more than one foot long than from an animal with a shorter trunk.
The case is analogous to tossing pennies. At any stage in the game the chance of accumulating a hundred heads is in proportion to the number of heads already obtained, and to the number of throws still to be made. But the number of heads obtained has no influence on the number of heads that will appear in the next throw.
Owing then to this property of the germ plasm to duplicate itself in a large number of samples not only is an opportunity furnished to an advantageous variation to become extensively multiplied, but the presence of a large number of individuals of a given sort prejudices the probable future result.
The question may be raised as to whether it is desirable to call selection a creative process. There are so many supernatural and mystical implications that hang around the term creative that one can not be too careful in stating in what sense the term is to be used. If by creative is meant that something is made out of nothing, then of course there is no need for the scientist to try to answer such a question. But if by a creative process is meant that something is made out of something else, then there are two alternatives to be reckoned with.
First, if it were true that selection of an individual of a certain kind determines that new variations in the same direction occur as a consequence of the selection, then selection would certainly be creative. How this could occur might be quite unintelligible, but of course itmight be claimed that the point is not whether we can explain how creation takes place, but whether we can get verifiable evidence that such a kind of thing happens. This possibility is disposed of by the fact that there is no evidence that selection determines the direction in which variation occurs.
Second, if you mean by a creative process that by picking out a certain kind of individual and multiplying its numbers a better chance is furnished that a certain end result will be obtained, such a process may be said to be creative. This is, I think, the proper use of the term creative in a mechanistic sense.
In reviewing the evidence relating to selection I have tried to handle the problem as objectively as I could.
The evidence shows clearly that the characters of wild animals and plants, as well as those of domesticated races, are inherited both in the wild and in the domesticated forms according to Mendel's Law.
The causes of the mutations that give riseto new characters we do not know, although we have no reason for supposing that they are due to other than natural processes.
Evolution has taken place by the incorporation into the race of those mutations that are beneficial to the life and reproduction of the organism. Natural selection as here defined means both the increase in the number of individuals that results after a beneficial mutation has occurred (owing to the ability of living matter to propagate) and also that this preponderance of certain kinds of individuals in a population makes some further results more probable than others. More than this, natural selection can not mean, if factors are fixed and are not changed by selection.