by Livio, Mario
Darwin’s Blunder and the Seeds of Genetics
In the context of our current understanding of genetics, the molecule known as DNA (deoxyribonucleic acid) provides the mechanism responsible for heredity in all living organisms. Very roughly speaking, DNA is made up of genes, which contain the information that codes for proteins, and of some noncoding regions. Physically, DNA is located on elements called chromosomes, of which each individual organism in sexual species has two sets, one inherited from the mother (the female) and one from the father (the male). Consequently, each individual has two sets of all of its genes, where the two copies of a gene may be identical, or slightly different. The different forms of a gene that can be present at a particular location on a chromosome are the variants referred to as alleles.
The modern theory of genetics originated from the mind of an unlikely explorer: a nineteenth-century Moravian priest named Gregor Mendel. He performed a series of seemingly simple experiments in which he cross-pollinated thousands of pea plants that produce only green seeds with plants that produce only yellow seeds. To his surprise, the first offspring generation had only yellow seeds. The next generation, however, had a 3:1 ratio of yellow to green seeds. From these puzzling results, Mendel was able to distill a particulate, or atomistic, theory of heredity. In categorical contrast to blending, Mendel’s theory states that genes (which he called “factors”) are discrete entities that are not only preserved during development but also passed on absolutely unchanged to the next generation. Mendel further added that every offspring inherits one such gene (“factor”) from each parent, and that a given characteristic may not manifest itself in an offspring but can still be passed on to the following generations. These deductions, like Mendel’s experiments themselves, were nothing short of brilliant. Nobody had reached similar conclusions in almost ten thousand years of agriculture. Mendel’s results at once disposed of the notion of blending, since already in the very first offspring generation, all the seeds were not an average of the two parents.
A simple example will help to clarify the key differences between Mendelian and blending heredity, in terms of their effects on natural selection. Even though blending inheritance clearly never used the concept of genes, we can still employ this language while preserving the essence of the process of blending. Imagine that organisms that carry a particular gene A are black, while the bearers of gene a are white. We will start with two individuals, one black and one white, each one having two copies of the respective gene (as in figure 4). If no gene dominates over the other, then in both blending heredity and Mendelian heredity, the offspring from such a couple would be gray, since they would have the gene combination (or genotype) Aa. Now, however, comes the key difference. In the blending theory, the A and the a would physically blend to create a new type of gene that gives its carrier the color gray. We can call this new gene A(1). Such blending would not occur in Mendelian heredity, where each gene would keep its identity. As figure 4 shows, in the grandchildren’s generation, all the offspring would be gray under blending heredity, while they could be black (AA), white (aa), or gray (Aa) under Mendelian heredity. In other words, Mendelian genetics pass down extreme genetic types from one generation to the next, thereby efficiently maintaining genetic variation. In blending heredity, on the other hand, variation is inevitably lost, as all the extreme types vanish rapidly into some intermediate mean. As Jenkin observed correctly, and the following (highly simplified) example will clearly demonstrate, this feature of blending heredity was catastrophic for Darwin’s ideas on natural selection.
Figure 4
Imagine that we start with a population of ten individuals. Nine have the gene combination aa (and are therefore white), and one has the combination Aa (say, by some mutation), which renders it gray. Suppose further that being black is advantageous in terms of survival and reproduction, and that even having a somewhat darker color is better than being entirely white (although the advantage decreases with decreasing darkness). Figure 5 attempts to follow schematically the evolution of such a population under blending heredity. In the first generation, the blending of A with a will produce the new “gene” A(1), which, when mating with aa will yield A(1)a, which will blend again to produce the gene A(2), corresponding to an even lighter and less advantageous color. You can easily see that after a large number (n) of generations, the most that can happen is that the population will be transformed into one with the combinations A(n)A(n), which will be only slightly darker than the original white population. In particular, the color black will become extinct even after the first generation, since its gene will be blended out of existence.
Figure 5
But under Mendelian heredity (figure 6), since the A gene is preserved from one generation to the next, eventually two Aa’s will mate and produce the black AA variety. If black confers an advantage in the environment, then given enough time, natural selection could even turn the entire population black.
The conclusion is simple: For Darwin’s theory of evolution by natural selection to really work, it needed Mendelian heredity. But in the absence of yet-undiscovered genetics, how did Darwin respond to Jenkin’s criticism?
What Doesn’t Kill You Makes You Stronger
Darwin was a genius in many ways, but he definitely was not a sharp mathematician. In his autobiography, he acknowledged, “I attempted mathematics, and even went during the summer of 1828 with a private tutor (a very dull man) to Barmouth, 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 of algebra . . . I do not believe that I should ever have succeeded beyond a very low grade.” That being the case, arguments in The Origin are generally qualitative rather than quantitative, especially when it comes to the production of evolutionary change. In the few places where Darwin attempted to do simple calculations in The Origin, he managed occasionally to botch them. No wonder, then, that in one of his letters to Wallace, after reading Jenkin’s rather mathematical criticism, he confessed, “I was blind and thought that single variations might be preserved much oftener than I now see is possible or probable.” Still, it would have been amazing to think that Darwin had been totally unaware of the potential swamping effect of blending heredity until he read Jenkin’s article. And indeed he wasn’t. As early as 1842, twenty-five years before the publication of Jenkin’s review, Darwin had already observed, “If in any country or district all animals of one species be allowed freely to cross, any small tendency in them to vary will be constantly counteracted.” In reality, Darwin even relied to some extent on swamping to produce populational integrity in the face of the tendency of individuals to depart from their type due to variations. How did he then fail to understand how difficult it would be for a “sport” (a single variation) to fight off the averaging force of blending? Darwin’s blunder and his slowness to recognize the point raised by Jenkin probably reflected on one hand his conceptual difficulties with heredity in general, and on the other, his residual overattachment to the idea that variations had to be scarce. The latter may have partially been a consequence of his general theory of reproduction and development, in which he assumed that only developmental stress triggered variations. Darwin’s bafflement with heredity ran much deeper, as can be seen from the following inconsistency. At one point in The Origin, Darwin noted:
When a character which has been lost in a breed, reappears after a great number of generations, the most probable hypothesis is, not that the offspring suddenly take after an ancestor some hundred generations distant, but that in each successive generation there has been a tendency to reproduce the character in question, which at last, under unknown favourable conditions, gains an ascendancy.
Figure 6
This notion of some latent “tendency” departed manifestly from normal blending heredity, and in many ways it was close in spirit to Mendelian heredity. Yet it apparently did not occur to Darwin, at least initially, to invoke this idea of latency in his struggle to respond to Jenkin
. Instead, Darwin decided to change the emphasis from the role he had previously assigned to single variations to that of individual differences (the wide spectrum of tiny differences occurring frequently, which was supposed to be distributed continuously throughout the population), in supplying the “raw materials” for natural selection to effect. In other words, Darwin now relied on an entire continuum of variations for the production of evolution by natural selection over many generations.
In a letter to Wallace on January 22, 1869, the distressed Darwin wrote, “I have been interrupted in my regular work in preparing a new edition of the ‘Origin,’ which has cost me much labour, and which I hope I have considerably improved in two or three important points. I always thought individual differences more important than single variations, but now I have come to the conclusion that they [individual differences] are of paramount importance, and in this I believe I agree with you. Fleeming Jenkin’s arguments have convinced me.” To reflect his new emphasis, Darwin amended the fifth edition and subsequent editions of The Origin by changing singulars referring to individuals into plurals, as in “any variation” turning into “variations,” and “an individual” into “individual differences.” He also added a few new paragraphs in the fifth edition, two of which, in particular, are of great interest. In one, he admitted openly:
I saw, also, that the preservation in a state of nature of any occasional deviation of structure, such as a monstrosity, would be a rare event; and that, if preserved, it would generally be lost by subsequent intercrossing with ordinary individuals. Nevertheless, until reading an able and valuable article in the “North British Review” (1867), I did not appreciate how rarely single variations, whether slight or strongly marked, could be perpetrated.
In the other paragraph, Darwin presented his own brief summary of Jenkin’s swamping argument. This paragraph is fascinating because of two apparently small yet extremely significant differences from Jenkin’s original text. First, Darwin assumes here that a pair of animals has two hundred offspring, of which two survive to reproduce. In spite of his nonmathematical background, therefore, Darwin appears to have anticipated already in 1869 the correction to Jenkin pointed out in A. S. Davis’s letter to Nature in 1871: For the population not to disappear, two offspring, on the average, must survive. Second, and even more intriguing, Darwin assumes in his summary that only half of the offspring of the “sport” inherit the favorable variation. Note, however, that this assumption is contrary to the predictions of blending heredity! Unfortunately, Darwin was still unable at that time to elaborate on the possible consequences of a nonblending theory of heredity, and he accepted Jenkin’s conclusions without any further discussion.
There are, nevertheless, quite a few signs that Darwin had not been happy with blending heredity for quite a while. In a letter he wrote in 1857 to the biologist Thomas Henry Huxley, his friend and champion in the public arena, he explained:
Approaching the subject [of evolution] from the side which attracts me most, viz inheritance, I have lately been inclined to speculate very crudely and indistinctly, that propagation by true fertilization, will turn out to be a sort of mixture and not true fusion, of two distinct individuals, or rather innumerable individuals, as each parent has its parents and ancestors. I can understand on no other view the way in which crossed forms go back to so large an extent to ancestral forms. But all this, of course, is infinitely crude.
Crude or not, this observation was extremely insightful. Darwin recognized here that the combination of paternal and maternal heredity material was more like the shuffling together of two packs of cards rather than like the mixing of paints.
While Darwin’s ideas in this letter can definitely be considered impressive forerunners of Mendelian genetics, Darwin was eventually driven by his frustration with blending heredity to develop a completely wrong theory known as pangenesis. In Darwin’s pangenesis, the entire body was supposed to issue instructions to the reproductive cells. “I assume,” he wrote in his book The Variation of Animals and Plants Under Domestication,
that cells, before their conversion into completely passive or “formed material” throw off minute granules or atoms, which circulate freely through the system, and when supplied with proper nutriment multiply by self-division, subsequently becoming developed into cells like those from which they were derived. . . . Hence, speaking strictly, it is not the reproductive elements . . . which generate new organisms, but the cells themselves throughout the body.
To Darwin, the great advantage that pangenesis offered over blending was that if some adaptive change were to occur during the lifetime of an organism, then the granules (or “gemmules,” as he called them) could take note of the change, lodge in the reproductive organs, and ensure that the change would be transmitted to the next generation. Unfortunately, pangenesis was taking heredity precisely in the opposite direction from which modern genetics was about to direct it—it is the fertilized egg that instructs the development of the entire body, not the other way around. Confused, Darwin clung to this misguided theory with similar conviction to that which he exhibited when he had previously held on to his correct theory of natural selection. In spite of vehement attacks by the scientific community, Darwin wrote to his great supporter Joseph Dalton Hooker in 1868: “I fully believe that each cell does actually throw off an atom or gemmule of its contents; but whether or not, this hypothesis serves as a useful connecting link for various grand classes of physiological facts, which at present stand absolutely isolated.” He also added with confidence that even “if pangenesis is now stillborn, it will, thank God, at some future time reappear, begotten by some other father, and christened by some other name.” This was a perfect example of a brilliant idea—particulate inheritance—that failed miserably because it had been incorporated into the wrong mechanism for its implementation: pangenesis.
Nowhere did Darwin articulate more clearly his atomistic, essentially Mendelian, ideas of heredity than in an exchange with Wallace in 1866. First, in a letter written on January 22, he noted, “I know of a good many varieties, which must be so called, that will not blend or intermix, but produce offspring quite like either parent.” Failing to see Darwin’s point, Wallace replied on February 4, “If you ‘know varieties that will not blend or intermix, but produce offspring quite like either parent,’ is not that the very physiological test of a species which is wanting for the complete proof of the ‘origin of species.’ ”
Realizing the misunderstanding, Darwin was quick to correct Wallace in his next letter:
I do not think you understand what I mean by the nonblending of certain varieties. It does not refer to fertility. An instance will explain. I crossed the Painted Lady and Purple sweet peas, which are very differently coloured varieties, and got, even out of the same pod, both varieties perfect, but none intermediate. Something of this kind, I should think, must occur at first with your butterflies and the three forms of Lythrum; though these cases are in appearance so wonderful, I do not know that they are really more so than every female in the world producing distinct male and female offspring.
This letter is remarkable in two ways. First, Darwin describes here the results of experiments similar to those conducted by Mendel—actually, the very experiments that had led Mendel to the formulation of Mendelian heredity. Darwin came pretty close to discovering the Mendelian 3:1 ratio by himself. After he crossed the common snapdragon (having bilateral symmetry) with the peloric (star-shaped) form, the first generation of offspring were all of the common type, and the second had eighty-eight common to thirty-seven peloric (a ratio of 2.4:1). Second, Darwin points out the obvious fact that the simple observation that all offspring are either male or female, rather than some intermediate hermaphrodite, in itself argues against “paint-pot” blending! So the evidence of the proper form of heredity was right there in front of Darwin’s eyes. As he had already remarked in The Origin: “The slight degree of variability in hybrids from the first cross or in the first generation
, in contrast with their extreme variability in the succeeding generations, is a curious fact and deserves attention.” Note also that the entire Darwin-Wallace correspondence above took place before the publication of Jenkin’s review. All the same, even though Darwin came tantalizingly close to Mendel’s discovery, he did not grasp its all-encompassing generality, and he failed to recognize its vital importance for natural selection.
To fully understand Darwin’s attitude toward particulate heredity, there are a few other nagging questions that need to be resolved. Gregor Mendel read the seminal paper describing his experiments and his theory of genetics—“Versuche über Pflanzen-Hybriden” (“Experiments in Plant Hybridization”)—to the Brünn (Moravia) Natural History Society in 1865. Is it possible that Darwin read that paper at some point? Were his letters to Wallace in 1866 inspired (to some extent at least) by Mendel’s work rather than representing his own insights? If he had read Mendel’s paper, why didn’t he see that Mendel’s results provided the definitive answer to Jenkin’s criticism?
Intriguingly, no fewer than three books published between 1982 and 2000 alleged that copies of Mendel’s paper had been found in Darwin’s library, and a fourth book (published in 2000) even claimed that Darwin had supplied Mendel’s name for inclusion in the Encyclopaedia Britannica, under an entry of “hybridism.” Obviously, if this last claim were shown to be true, it would mean that Darwin was fully aware of Mendel’s work.