IN 1900, three European botanists independently rediscovered the work of an Austrian monk, Gregor Mendel, whose correct formulation in 1865 of the mechanisms governing the transmission of hereditary traits resulted in the publication of a paper in the Proceedings of the Natural History Society of Brunn the following year. The paper was to remain largely unknown until the turn of the century when Hugo de Vries’, Carl Correns’ and Erich von Tschermak’s simultaneous rediscovery of both Mendel’s 1866 paper and his laws of inheritance would lead to the coining of the term ‘genetics’.

Heredity and variability were of central importance to Charles Darwin’s theory of evolution by natural selection as presented in The Origin of Species in 1859, although to Darwin the laws governing them would forever remain quite unknown. Lacking an adequate account of inheritance and variation, Darwin’s theory was logically incomplete. The black box at the centre of the theory remained dark for decades.

Darwin Statue at the Natural History Museum.

After Darwin’s death in 1882, a number of events began to cause dissent among evolutionists. One such major development was Weissmann’s theory of the germ-plasm, the idea that the germ cells alone (as separate from the other cells of the body, the somatic cells) carry hereditary information from one generation to the next, which largely excluded Jean-Baptiste Lamarck’s theory of ‘soft’ inheritance, or the inheritance of acquired traits. As Mayr points out, Weissmann’s discovery coincided with a growing division of biology into a greater number of specialised fields, such as embryology, ecology, cytology and zoology, each of which gave rise to different habits and perspectives of the evolutionary process. It is possible that these peculiarities led to the deeply drawn divisions over the questions of whether the primary driver of evolution was mutation, intrinsic tendencies or natural selection, and whether evolution was a gradual process, or a jumpy, ‘saltational’ one. Far from fostering unity around a common rejection of Lamarckism, Weissmann’s work served to shine a spotlight on the discord surrounding this latter question, and in the same vein the rediscovery of Mendel’s work acted as a catalyst. The ensuing dispute concerned two schools of scientific study regarding Darwin’s theory in the early 1900s. The Mendelians pointed to Mendel’s garden pea experiments which suggested that, at the level of the gene, inheritance was a process whereby some set of discrete events resulted in a discontinuous variation in trait (for example, in seed shape: either round or angular). These results seemed to contradict the work of a second strand of thought advanced by the so-called “biometric” school whose primary efforts were focused on quantifying Darwin’s notion of continuous variability of traits in biological populations using statistical methods. Though the Darwinian T. H. Huxley was an advocate of discontinuous evolution, this view was primarily associated with the Mendelians, notably Hugo de Vries and William Bateson.

The Mendelians and the biometric Darwinians would remain at bitter loggerheads until as late as the middle of the 20th century, with many biometricians assuming some kind of blending inheritance, and the early Mendelians, conscious of the fact that inheritance is particulate, incorrectly stressing discrete variation. It took the architects of the so-called evolutionary synthesis to show that there was in fact no conflict between particulate inheritance and continuous variation, finally providing a sound biological basis for Darwin’s theory of evolution by natural selection. But was Darwin already in possession of the evidence necessary for an independent rediscovery of the principles of inheritance? Did the populations studied by Darwin display features suggestive of particulate units of inheritance, for example? That is, could the Darwinians plausibly have ‘filled in’ the black box at the centre of natural selection on the basis of Darwin’s work?

HEREDITY, VARIATION AND DARWIN’S THEORY

In sexually reproducing species, individual organisms are typically genetically unique, and therefore populations of such individuals display variation. Although the exact nature of variability wouldn’t be understood until the mid-twentieth century, the connection between variation and inheritance was a fact clear even to the ancients, and forms the basis of all animal and plant breeding. Even so, the responsible mechanisms remained a mystery, which left a large explanatory hole at the centre of Darwin’s theory.

The argument presented in The Origin of Species can be separated into three primary lines of reasoning. The first is his general theory of transmutation, or evolution, and the second is the idea that this evolution is a process of descent with modification from a common ancestor. It is the third part of the argument, Darwin’s assertion that natural selection is the primary driver of evolution, which distinguishes his theory of evolution from those of his predecessors. This is the strand of Darwin’s argument to which variability and heredity are fundamental. Though ignorant of the true nature of inheritance, Darwin was keenly aware of its consequences:

The many slight differences which frequently appear in the offspring from the same parents may be called individual differences. […] These individual differences are of the highest importance for us, as they are often inherited […] and they thus afford materials for natural selection to act on and accumulate, in the same manner as man accumulates in any given direction individual differences in his domesticated production (1859).

The process of natural selection is formulated upon the following four postulates:

Variation — in any given population, individuals display phenotypic variability. Variation in an organisms phenotype may consist of behavioural or physical traits.

Inheritance — some of these characteristics found in the parent organism are reliably found in the offspring. These are known as heritable traits, and contrast with environmentally-influenced characteristics, such as scars or deformations which are typically not passed on.

Struggle for resources — biological populations often produce an excess of offspring, such that more individuals are born than can possibly survive on a limited pool of resources. Only a fraction of the population survives to reproductive age.

Differential survivability — some of these individuals will be better suited to its local environment, by virtue of their individual traits. The probability of these individuals reproducing is increased.

The limited pool of resources, coupled with differential survivability will favour those individuals with certain traits over those with which they are in competition, increasing the frequency of those so-called adaptive traits within a species and decreasing the frequency of deleterious ones. If certain traits appearing in a population do not confer a comparative advantage, or are not heritable, no process of natural selection can occur. Natural selection requires hereditary variability, and any underlying mechanism must respect this fact.

It is testament to Darwin’s theory that the lack of such a mechanism did not dampen its explanatory power. For Darwin and his contemporaries, however, an unsubstantiated belief in blending inheritance was predominant. We find a rather explicit reference to this theory in Darwin’s later work, The Variation of Animals and Plants Under Domestication. In the chapter ‘On Crossing’, he declares that “free crossing has in all cases played an important part in giving uniformity of character to all the members of the same domestic race” before dedicating a footnote to the strange phenomenon of ‘certain characters not blending’.

As was pointed out in a review of The Origin by University of Edinburgh engineering professor Fleeming Jenkin, the assumption of blending inheritance quickly leads to difficulty. Jenkin’s essay had a profound effect on Darwin, who wrote in a correspondence with the botanist J. D. Hooker that “Fleming Jenkyn has given me much trouble, but has been of more real use to me than any other”. Jenkin illustrated this problem with reference to a lucid, but rather racist, thought experiment in an 1867 review of The Origin in the North British Review:

… Suppose a white man to have been wrecked on an island inhabited by negroes…. Our shipwrecked hero would […] have a great many wives and children, […] and yet he would not suffice in any number of generations to turn his subjects’ descendants white. We might expect the throne for some generations to be occupied by a more or less yellow king; but can any one believe that the whole island will gradually acquire a white, or even a yellow population…?

An upshot of blending inheritance is a rapid reduction in variation since such a process would produce offspring which are intermediate between their parent organisms in all characters. Assuming random mating, the variance of a trait is ‘diluted’ by a factor of two each generation which implies that neither natural selection nor even artificial selection is capable of making permanent changes in a population. Recalling that natural selection requires variation capable of being inherited, it is clear that it was incumbent on Darwin to find a mechanism with the ability to generate such variation. His attempt manifested itself as his theory of heritability and variation known as pangenesis, which postulated that particles or ‘gemmules’, which experienced modification during the individual’s lifetime, came together in the germ cells and were then transmitted to the offspring. Of course, this theory rests on the assumption of Lamarckian inheritance, the existence of which Darwin never rejected.

Darwin did have doubts about his theory. In The Variation, for example, he notes that circumcision within the Jewish community, although having been practiced for “so many ages” has produced no effect. The inheritance of acquired characteristics, Darwin also notes, fails when used to explain certain biological phenomena such as eusociality in certain species of insect.

As was laid out by Fisher in The Genetical Theory of Natural Selection, the problems brought about by blending inheritance are not present as consequences of a Mendelian theory: variability is not lost, but instead maintained, even when the forces of evolution are not at work; a form of genetic inertia. Regeneration of genetic variability does not require Lamarckian inheritance. Natural selection is, in fact, enabled by Mendelian heredity: mutations in genes provide the source of new, stable variants on which selection can act.

MENDELIAN INHERITANCE

Before considering the evidence available to the Darwinians regarding Mendelian inheritance, let us briefly recap one of Mendel’s relevant discoveries, his law of segregation.

Mendel crossbred pure-breeding pea plants and noted the characteristics of their progeny over the course of several generations, and his particulate inheritance assumes the equal contribution of genetic material from each parent (with the exception of the sex chromosomes). The material determining the inherited contribution is not fluid, but is composed of discrete bodies, which do not blend, and come in pairs, with one of each pair coming from a respective parent. These elements, we now know, are of course genes.

A. The Law of Segregation

Consider the crossing of two pure-breeding types differing by a pair of discrete traits (an example of such a trait is Mendel’s work on seed colour: green versus yellow), and the mating of their resulting offspring. We shall refer to the progeny of the first crossing as F1, and their offspring as F2. The progeny resulting from this second crossing will consist of some individuals with a genetic likeness to the grandparents, and others with a similarity to the parents, and the ratios of these two forms will be predictable. If we call the respective grandparental forms A and B, and the parental form C, the F2 individuals will display the three possible forms in the proportions 1A : 1B : 2C. The grandparental types are said to reappear or segregate out of the second generation, and the first of Mendel’s laws is therefore known as the law of segregation. Let us illuminate this by way of an example. If we denote the pure-breeding (homozygous) types with reference to their combination of alleles pertaining to the observed trait (BB or bb), and consider the fact that only one of these alleles will pass into each sex cell, we can see that a crossing of these two differing pure-breeding types will result in F1 heterozygotic individuals (with allelic combination Bb). When the F1 generation undergo crossing, the resulting progeny will be found to approximate the ratios determined by the table in Figure 1. Importantly, as we shall discuss later, a finite number of offspring, N, will almost certainly not produce the given ratios exactly, but in the limiting case, as N tends to infinity, the offspring will approach them.

Two differing homozygotes will produce offspring all of the heterozygote kind Bb. These F1 heterozygotes when mated together will produce F2 progeny in the ratio 1BB : 2Bb : 1bb.

Of course, we now know that traits often display dominance, where one allele exercises its full effect regardless of its partner allele. Converse to this is a trait which appears only when its genotype is homozygous for the responsible allele. This trait is said to be recessive. For example, Mendel’s work on the colour of pea seeds discovered yellow to be dominant to green. If we label the allele producing the colour green as b, and the allele responsible for the yellow colour B, we can see from the table above that only one quarter of the offspring will display the trait that is the green seed colour (the bb genotype). Thus, when judging phenotype alone, the ratio will instead appear as 3 : 1 when dominance is at play, rather than the familiar 1 : 2 : 1 ratio with heterozygotes the most common. Thus, we can formulate the law of segregation as follows:

Law of Segregation — during the formation of the gametes, the alleles of each gene segregate such that only one allele of any given gene appears in each gamete.

Darwin himself, it turns out, came across Mendelian ratios in the course of his own breeding experimentation performed from his home at Down House in 1876, though their significance was passed over.

Darwin’s home, at Down House

DARWIN’S EVIDENCE

Darwin himself was clearly in possession of a number of facts which, with the right insight, would likely have led to a particulate theory of heredity akin to that of Mendel. Much of Darwin’s commentary belies the notion that he was ignorant of the underlying principles, however it is evident that he was missing a plausible interpretation.

A. Mutation and Reversion

Reversion to ancestral types, otherwise known as atavism, is the phenomenon in which a trait prevalent in remote ancestors makes a reappearance despite not having been seen in the parent organisms nor even recent ancestors of the individual displaying the atavistic trait. Given Darwin’s self-confessed lack of mathematical ability, he employed the help of the physicist Professor George Stokes to perform a statistical test to determine the probability of such a trait occurring by chance. In The Variation, Darwin devotes an entire chapter to this phenomenon, and obviously recognised its importance to his missing mechanism:

Reversion is not a rare event, depending on some unusual or favourable combination of circumstances, but occurs so regularly with crossed animals and plants, and so regularly with uncrossed breeds, that it is evidently an essential part of the principle of inheritance.

One of many such cases that he discusses in The Variation is the occasional appearance in England of the black-shouldered peacock, which differs in outward appearance from the common peacock. According to Darwin, they appear suddenly but “propagate their kind quite truly”, and are said “at all times and in many places to reappear”.

During his experimentation, Darwin also stumbled upon numerous examples of certain traits’ refusal to display blending inheritance. As we’ve previously discussed, these “sports”, or spontaneous variations, were assumed by Darwin to be relatively rare occurrences, appearing suddenly and often being of a monstrous nature. It is evident to us now that such monstrous traits were occasioned by genetic mutations. De Vries, one of the rediscoverers of Mendel, claimed that his later work as presented in The Mutation Theory is “in full accord with the principles laid down by Darwin”, and states that Darwin was well aware of mutation and singular variation, an assertion which certainly seems plausible.

B. Evidence of Mendelian Ratios and Dominance

In the chapter of The Origin called “Hybridism”, Darwin talks of “one species impressing its likeness on the hybrid” during crossbreeding. Almost a decade later, in The Variation, Darwin enunciates this phenomenon of “prepotency” more clearly, writing:

When two forms are crossed, one is not rarely found to be prepotent in the transmission of character over the other; and this we can explain only by again assuming that the one form has some advantage in the number, vigour, or affinity of its gemmules, except in those cases, where certain characters are present in the one form and latent in the other. For instance, there is a latent tendency in all pigeons to become blue, and, when a blue pigeon is crossed with one of any other colour, the blue tint is generally prepotent.

If we replace the word ‘gemmules’, which we can now recognise as the hereditary factor of pangenesis, with the word ‘alleles’, the paragraph is a lucid description of the concept of genetic dominance.

In the second volume of The Variation, Darwin details an experiment in which he crossed a snapdragon (Antirrhinum majus) with narrow, tubular flowers (peloric) with plants displaying the normal, asymmetrical flower type. None of this progeny were of peloric type, however when these F1 plants were allowed to self-fertilise, 37 out of 127 F2 seedlings were of the high-symmetric type, with the remaining 90 displaying the ordinary flower shape, two of which displayed an intermediate type. In other words, the F2 offspring displayed flower shape in a 2.43 : 1 ratio. Whilst much of the literature holds this as proof that Darwin was in possession of evidence of the 3 : 1 ratio, this is not a tenable position. We see Darwin repeatedly outsourcing his statistical analyses to relatives and colleagues, but if he had been proficient himself he might have recognised the uncertainties present in his results. A sample size of 127 will carry an error of ± 8.9%, which means that the 90 ordinary flower morphs would subsume both a 2 : 1 ratio and 3 : 1 ratio within the uncertainty. It is implausible to declare it as evidence from which Darwin should have deduced a ratio at all, let alone the correct one. This nicely demonstrates how important the growing use of statistics was in nineteenth century biology.

Asymmetrical Antirrhinum majus flower

Looking to Darwin’s 1877 publication The Different Forms of Flowers on Plants of the Same Species, however, we can see the results of his prolific experimentation on distylous Primula hybrids. Throughout the book, Darwin presents his results in tables, some of which contain clearer examples of Mendelian ratios. A heterostylous species is one in which multiple morphological types of flowers exist in the population, and if the number of morphs is two, they are termed distylous. The flower morphs vary in the lengths of the pistil and stamens, and these traits are discontinuous. In one morph the stamens are short and the pistils are long; in the second morph the stamens are long and the pistils are short. In distylous species, the long-styled morphs are now known to be homozygous ss for the alleles at several loci in a supergene controlling style and pistil length, and the species should therefore be expected to display morphs in the familiar 3 : 1 Mendelian ratio. With respect to the Primula auricula, Darwin reports that he has been “informed by a man who raises this species extensively in Scotland [that] about one fourth of the seedlings appear long-styled”. Darwin’s own experiments confirmed exactly this, his results noting 75 short-styled offspring and 25 long-styled. It is, of course, mere coincidence that Darwin’s results displayed such exactitude, and indeed seems amazing that he failed to find a deeper connection to some mechanism of heredity.

INTELLECTUAL BARRIERS

It is clear that the Darwinians were in the possession of a substantial body of evidence pointing to Mendelian, particulate inheritance, but were the conceptual elements necessary to comprehend Mendelian inheritance available to Darwin?

Darwin’s Education

Unlike Mendel, who had received a scientific education in mathematics, physics and chemistry (alongside his theological studies), Darwin was untrained in the hard sciences and as such was lacking in mathematical ability. He dismissed complex mathematical arguments and wrote to a friend, “I have no faith in anything short of actual measurement and the Rule of Three [a simple mathematical calculation],”. In his autobiography, he writes:

I attempted mathematics, […] but I got on very slowly. The work was repugnant to me, chiefly from my not being able to see any meaning in the early steps in algebra. This impatience was very foolish, and in after years I have deeply regretted that I did not proceed far enough at least to understand something of the great leading principles of mathematics; for men thus endowed seem to have an extra sense.

In the nineteenth century, science was becoming increasingly receptive to mathematical ideas, and this development was likely far from contingent. In the words of historian John Merz, writing on European scientific thought, a view was developing that science “is based upon numbering and calculating — in short, upon mathematical processes; and the progress of science depends as much upon introducing mathematical notions into subject which are apparently not mathematical, as upon the extension of mathematical methods and conceptions themselves.” This growing mathematization of biology is particularly noticeable in the study of inheritance, where Francis Galton, Darwin’s cousin, led the way in establishing statistics as an effective method in the analysis. Just as Darwin had been aided with his statistical testing by Sir George Stokes, he again sought external help from Galton following another of his experiments. He wondered whether or not the height differences in plants he had crossed were consequences of random variation. Doing that, however, had required Darwin’s dreaded mathematics.

Galton, contemporaneously with Mendel, had written Hereditary Genius, a totally mathematical treatment of heredity. Just like Mendel, it was Galton’s intention to show the role played by chance in the course of hereditary transmission, “and to establish the importance of an intelligent use of the laws of chance and of the statistical methods that are based upon them, in expressing the conditions under which heredity acts”. Despite echoing Mendel here, Galton would soon become a pioneer of the biometric school of biology to whom the Mendelians were staunchly opposed.

Fisher and the Mendel controversy

Much is often made of Darwin’s lack of mathematical background, but this has likely been overplayed. While it is certainly true that Mendel’s mathematical talents enabled him to skilfully unpack the laws of heredity, there is evidence to suggest that he may have arrived at such a theory before his famous experiments had even begun.

Ronald Fisher is widely known for his contributions to statistics and his work in synthesising the two antagonistic schools of biology, the details of which are laid out in his 1930 watershed text The Genetical Theory of Natural Selection. Fisher dedicates a section of the book to the concept of particulate inheritance where he points out that the modern genetical system (excluding special features like dominance and linkage) could have been inferred by any abstract thinker in the middle of the nineteenth century:

It is a remarkable fact that had any thinker in the middle of the nineteenth century undertaken, as a piece of abstract and theoretical analysis, the task of constructing a particulate theory of inheritance, he would have been led on the basis of a few very simple assumptions, to produce a system identical with the modern scheme of Mendelian inheritance.

He argues that the admitted non-inheritance of mutilations and scars would have prepared this theorist to conceive of the hereditary nature of organisms as being something definite. An assumption that this hereditary nature was determined entirely by the aggregate of the hereditary particles, combined with an assumption that certain organisms were capable of breeding true, would lead to the notion of organisms receiving a definite portion of the hereditary particles from each parent, and that consequently the idea that a given organism will transmit only a corresponding portion to each of its offspring. The imaginary theorist, Fisher claims, would scarcely have failed to imagine a conceptual framework in which each particle (gene) had its own place (locus), which could be occupied by a gene of a different kind, had the parentage been different. Organisms which received like particles on a given loci (homozygotes) from their parents, would necessarily pass on genes of this type to all of their offspring; whereas those receiving different types from their parents would have an equal chance of transmitting either kind. If two heterozygotes were to be mated, each homozygous form would be expected to appear in a quarter of the offspring, with the remaining offspring being heterozygous.

It thus appears that all the main characteristics of the Mendelian system flow from assumptions of particulate inheritance of the simplest character, and could have been deduced a priori had any one conceived it possible that the laws of inheritance could really be simple and definite.

While such a chain of thought may seem too complex to have been instantiated in the mind of a nineteenth century thinker, Fisher later came to the conclusion that Mendel had, in fact, very likely arrived at his theory precisely in this way. In 1936, Fisher subjected to a statistical analysis Mendel’s experiments in which he supposedly discovered the 3 : 1 Mendelian ratio. Fisher analysed Mendel’s data and found that the fit to Mendel’s theoretical expectations was too good. Using χ2 analysis, Fisher found that the probability of obtaining a fit as good as Mendel’s (an average ratio of 2.98 : 1) was only 7 in 100, 000. More impressive was Fisher’s analysis of Mendel’s separate experiments showing a 2 : 1 ratio, for it appears Mendel got an equally close fit for a wrong conclusion. Constructing a history of Mendel’s experiments, Fisher concluded that Mendel “designed them as a demonstration for others rather than for his own enlightenment.”

If Fisher’s analysis is correct, then we are presented with a case of the laws of inheritance being deduced on a logical, rather than experimental basis. For a deduction of this kind, mathematical ability would likely have been irrelevant.

One great area of difference between Mendel and Darwin was Darwin’s failure to distinguish between the concept of inheritance of a trait and the embryological development of that trait. Darwin wrote in The Variation that “inheritance must be looked at as merely a form of growth”. For this reason, the subject dealt with by Mendel would have seemed to many of his contemporaries a partial work. The greatest intellectual barrier faced by Darwin may, therefore, simply have been his approach to biology.

Moravia, Mendel and the Darwinian Approach

At the turn of the nineteenth century, the European state of Moravia (part of the Austro-Hungarian Empire) was home to many agricultural and scientific societies, and the economic importance of the sheep industry to the state fostered an interest in breeding. At a meeting of the Sheep Breeders’ Society in 1837, Cyrill Napp, the new Abbot of the monastery at Brunn, declared his interest in the mechanism of heredity and how it could be utilised to improve the quality of his animals. He argued that the breeders should seek to discover the fundamental mechanisms in order to turn the art of breeding into a science: ‘What we should have been dealing with is not the theory and process of breeding. But the question should be: what is inherited and how?’. How do we explain the constancy with which organisms grow true to the form of their species? The research would be concluded in 1865 by Napp’s protegee, Mendel. The fact is that throughout Darwin’s life, his preoccupations were different to those of the animal breeders. Darwin’s attention was focused on the processes of transformation and evolution, not on the mechanisms required for conservation. A blind spot may have developed for Darwin as a consequence of differential interest in these two processes.

St Thomas’ Church at Brno (previously Brunn Monastery)

It appears that a second blind spot appeared as a function of Darwin’s commitment to gradualism. As a naturalist, Darwin’s approach to reasoning was concerned with interdependence as opposed to the abstract, reductionist one of Mendel. Where Mendel stripped away all but the necessary components for his analysis, Darwin analysed objections to his theory without questioning the assumptions of the worldview characterised by an aversion to discontinuity and adherence to blending. We can see this in Darwin’s theory of pangenesis: a speculative theory aiming to unify all of the contradictory observations in heredity and development. So too can it be seen in Darwin’s response to Jenkin’s swamping objection. Presumably due to his preconceptions, Darwin downplays the role of single variations, rather than considering from first principles an alternative mechanism that would act to conserve variation.

Though the seeming incompatibility of particulate inheritance and gradual evolution would confound biologists for decades, Darwin’s prejudices clearly did much to blind him to the possibility of discrete factors being the agents responsible for heredity and variation. While Fisher’s analysis of Mendel’s results show that a lack of mathematical sophistication was not a necessary barrier to a Darwinian rediscovery of Mendel’s laws, we can be fairly sure that Darwin’s commitments to unbridled gradualism and prescientific notions such as blending inheritance were obstacles to the filling in of natural selection’s ‘black box’.