Darwin’s Invention: Inheritance and the “Mad Dream” of Pangenesis

William F McComas. The American Biology Teacher. Volume 74, Issue 2. February 2012.

Textbooks typically share almost nothing of the history of biology beyond the occasional image, along with the birth and death dates of a few iconic scientists accompanied by brief descriptions of their discoveries. This is unfortunate. Historical accounts can humanize the sciences and reveal much about the underlying personal dimensions of scientific work and thought. Also, recounting the story behind a discovery can provide wonderfully engaging examples of the twists, turns, people, and politics associated with the way science really advances and, as such, teach important lessons about science as a process.

Unfortunately even reading scientific papers can fail to provide much insight into how science works. When the Nobel-winning British biologist Peter Medawar (1963) asked “Is the scientific paper a fraud?” he was not implying that scientists deliberately misrepresent their work. He was suggesting that by the time a scientific paper or book is written, the discovery looks both neat and orderly and somewhat inevitable. Unfortunately science publishers simply do not have the space to provide detailed descriptions of experiments that fail along with discussions of every false start and blind alley elements that are associated even with successful endeavors. If the full picture of scientific discovery is not provided by scientists and such accounts are absent from science textbooks and classroom discussions, students may fail to identify with science as a career and with the human side of scientists revealed by their false starts, moments of doubt, and even mistakes. Science is the province not of geniuses who never err but of hardworking men and women who are attracted to problems and determined to solve them.

Here, to counter the lack of accessible examples detailing the process of science, I would like to recount a fascinating episode in the history of biology in which Charles Darwin literally invented an explanation for inheritance. This explanation accounted for a variety of fascinating phenomena even as it turned out to be completely wrong. The story is both interesting and engaging and shows an iconic scientist acting quite human as he responded to a need and then defended a favored view even in the face of little evidence, the lack of widespread support, and a clear record of personal doubt. This first of a two-part discussion will focus on Darwin’s invention, to be followed soon by an examination of what can be learned—and taught—by considering this example to teach many important lessons about the nature of science itself.

Darwin’s Puzzles: Grafting, Regeneration, and Delayed Inheritance

It would be impossible to review the life and work of Charles Darwin and not conclude that he was intrigued and energized by the myriad puzzles and questions nature presented. His work is filled with questions, ranging from color and plumage variations in pigeons, to the actions of carnivorous plants, to the ecological contributions of the lowly earthworm, to much more lofty challenges like an explanation for the origin of new species.

Darwin would be known as a masterful biologist even if he had not successfully tackled this last question, but of course, he will forever be remembered for providing an explanation for how evolution occurs in his book On the Ongin oj Species, published in November 1859 (the sixth and final edition was published in 1872). In each edition of the Origin, Darwin (1859) did something that few scientists today would be brave enough to consider. He included an entire chapter devoted to the “Difficulties on Theory” to point out concerns that he believed others might have with his notion of descent with modification, even adding another chapter, “Miscellaneous Objections to the Theory of Natural Selection,” in later editions. Two of the most vexing and important issues that Darwin mentioned dealt with the laws that guided inheritance and the source of new variation, but more about these problems in the next section after we turn our attention to a few smaller puzzles.

In addition to the concerns noted in the Origin, Darwin was intrigued by a range of perplexing aspects of the natural world that demanded explanation. For instance, he was curious about the issue of graft hybrids in which the offspring of a branch from one species of plant when growing on another occasionally had characters of both the graft and the stock. He wanted to understand why some organisms (such as plants, worms, some amphibians and reptiles, etc.) could replace lost body parts through regeneration. How did the stump of a lizard’s limb know how to regrow the lost toes? Another puzzling issue, called “reversion,” “atavism,” or “throwback,” begged for explanation. Reversions occur when a trait appears that was seen only in a remote ancestor but not in more immediate ones. Darwin (1859) questioned why a “character… lost in a breed, suddenly reappears after a great number of generations…” (pp. 160-161).

Darwin also considered the widely known account of Lord Morton’s mare. In the story, Morton’s mare mated with a quagga (a now-extinct zebra-like animal) and gave birth to a hybrid resembling both parents. No surprise in that. However, when the mare mated next—this time with a white stallion—the offspring had stripes on its legs (Endersby 2009). This gave rise to the false explanation that somehow the male quagga could influence the traits of future offspring of his former mate. The idea that a male can influence the traits in future offspring of a female with which he had once mated is called “telegony.” Telegony was first applied to the Greek gods who were thought to be able to work their wiles with human women and later affect future children produced by these women even when their next husbands were mere mortals. Greek gods aside, the story of Lord Morton’s mare (also called the principle of delayed action inheritance) provided yet another curious issue to pique Darwin’s curiosity.

Darwin’s Problems: Variation and Inheritance

The problems just discussed are fascinating curiosities, but Darwin faced far more serious issues, as we will see. Evolution by natural selection depended on inheritance and on a source of new variation on which nature could perform the act of selection. Like naturalists, farmers, and generations of parents before him, Darwin certainly recognized that inheritance occurred. After all, children frequently look like their parents, and female calves from good milk producers often grow to become productive cows. The problem was that, beyond a few basic principles established by Victorian naturalists, a firm set of rules to explain inheritance eluded even Charles Darwin, who spent countless hours exploring this issue in a wide range of domestic plants and animals. His inquiries in this area are discussed in detail in Variations of Animals and Plants under Domestication (Darwin, 1868a, b).

Darwin realized that there needed to be a source of new varieties of traits on which selection could operate but only if these varieties could be inherited. As Darwin said, “it is obvious that a variation which is not inherited throws no light on the derivation of species, nor is of any service to man…” (1868a, p. 1). This last comment may have a sort of double meaning in that variations are the necessary raw material to those engaged in the selective breeding that leads to new and improved kinds of crops and farm animals along with fancier pigeons and dogs. Additionally, it may be that Darwin was referring to himself in suggesting that his inability to explain the source of variation would negatively influence his view of descent with modification because heritability was vital. Even in Origin (1859), Darwin voiced frustration when saying “we must… acknowledge plainly our ignorance of the cause of each particular variation” (p. 131); he offers hope that the problem might be solved, but in an unexpected fashion to a modern audience.

For those who know only the shallow textbook story of the history of evolution, that Lamarck was wrong and Darwin was right, there should be great surprise in noting that Darwin fully accepted the Lamarckian principle of “use and disuse” as contributing to new variants. In the first edition of the Origin, Darwin (1859) suggests that the flightless insects found on islands lost the ability to fly and some burrowing mammals lost their sight through disuse. He further noted the “inherited development of the udders in cows and goats … where they are habitually milked” (Darwin, 1859, p. 11).

This logic extended even to the final version of Origin (1872), with a section called “Effects of the increased use and disuse of part, as controlled by natural selection.” His interest in the effect of use and disuse is reflected in other texts. Consider this statement from Variation (1868b, p. 371):

Organs frequently used for a purpose are selected for by the environment; whereas, organs or parts that are not used will eventually be diminished in function in successive generations (i.e., the domesticated duck flies less and… its limb-bones have become diminished in comparison to the wild duck).

Winther (2000) did a masterful job exploring Darwin’s mindset on the topic of variation and inheritance and neatly concluded that Darwin accepted that “changes in the conditions of life ultimately caused all genuinely new variation…” (p. 434). As Darwin stated, “changes of any kind in the conditions of life, even extremely slight changes, often suffice to cause variability” (1868b, p. 270). Darwin clearly accepted the proposition that these variations could be inherited, which makes him a proponent of both the principle of use and disuse and the inheritance of these acquired characteristics. One of the very few elements in the history of biology often included in biology texts is the comparison of Darwinian to Lamarckian evolution. It is the height of irony that this particular contrast is made, given that Darwin himself was a Lamarckian!

Another major problem faced by Darwin was the general lack of an understanding of how inheritance occurs. Some then current ideas actually caused problems for natural selection. For instance, one of the common explanations for inheritance involved the principle of blending. Just as it sounds, blending (or the “paint pot” hypothesis) is the idea that when two individuals mate, their heritable material creates an average of the traits from the parents. Even though there was evidence that some traits seemed to be stronger than others, the basic idea was one of compromise rather than dominance. Darwin did not fully accept the basic notion of blending and offered the contrary example that the siblings from one pair of parents were not entirely the same (1868b) as might be expected if blending occurred. However, even with unequal blending there was still a problem. In situations where a useful trait was possessed by a small number of individuals, it was thought that such a trait would be overpowered or swamped by the more common characteristic, thus causing the less common versions of the trait simply to fade away over time.

Darwin battled the Victorian scientific establishment over the rules that guided inheritance and its underlying mechanisms and entered the fray with his own unique explanation for how traits could pass from parents to offspring. In the process, he also accounted for a range of related phenomena, including the source of new variation. Darwin’s proposal went by the curious name pangenesis.

Darwin’s Invention: Pangenesis

For a mechanism, Darwin seems to have unwittingly looked back to the Greek physician Hippocrates (ca. 410 B.C.), who suggested that tiny particles or “seeds” produced by various body parts were transmitted to offspring (Lonie, 1981). This mechanism was called pangenesis (Moore, 1993), a term that means “originating from everywhere.” Interestingly, Hippocrates further implied that changes to the adult could, through this mechanism, be shared with future offspring—which makes him a Lamarckian too.

When physician-naturalist William Ogle reminded Darwin of the similarity between his ideas and those of Hippocrates, he stated, “I wish I had known of these views of Hippocrates, before I had published, for they seem almost identical with mine—merely a change of terms … (Letter 5987 to William Ogle, 6 March 1868). Given that the ancient scholars were read during Victorian times, it is likely that Darwin may have become vaguely acquainted with the principle of pangenesis years earlier, even without retaining a clear memory of the link.

The basic idea of Darwinian pangenesis may also have had other roots. As a student in Edinburgh, Darwin studied with Robert Grant, who was an admirer of Lamarck. Also, as a professional naturalist, Darwin had experiences with a variety of marine invertebrates that exhibit reproductive strategies that include alternation of generations and various survival mechanisms involving particles called “gemmules.” Darwin seems to have combined the ancient view with several modern assumptions and invented the principle of pangenesis as an explanation to account for a variety of puzzling phenomena, including inheritance itself. Most importantly he believed that pangenesis could provide the source for the all-important variation required by natural selection. In addition to his letters, Darwin’s most extensive descriptions of pangenesis are found in both editions of Variation oj Animals and Plants under Domestication (1868b, 1875) and in Descent of Man (1871b, 1874).

The minute message-carrying gemmules were thought to be released by all organs in the body (i.e., there were stomach gemmules, skin gemmules, etc.). These site-specific gemmules were thought to disperse throughout the body and collect in the reproductive cells. As Darwin explained in Variation (1868a, p. 377), gemmules are collected from all parts of the system to constitute the sexual elements, and their development in the next generation forms a new being (1868a, p. 377). In Descent oj Man (1874), Darwin added that “gemmules may remain undeveloped during the early years of life or during successive generations; and their development into units or cells, like those from which they were derived, depends on their affinity for, and union with other units” (p. 228).

The most interesting aspect of pangenesis is that if some environmental stimulus caused a change in a body part, either by injury or by use and/or disuse, the “new” gemmules produced by that part would be different from those that would originally have developed there. In the case of the example provided in the illustration, a liver that successfully repels an attack of some toxin would then emit gemmules with at least some of that toxin-fighting ability. Using a digital analogy, it was as if the liver gemmules were reprogramme d by the action of the toxin. These reprogramme d gemmules would make their way to the reproductive organs and, if mating occurrs, guide the development of the liver in the newly forming offspring in a new way (Olby 1963; Gieson, 1969; Endersby 2009).

Pangenesis and the Problems It Solved

One of the hallmarks of a productive scientific idea is the range of phenomena for which it accounts. By this measure, pangenesis must have seemed like an extraordinarily productive notion and one that its founder was likely to accept as accurate. With this one idea it was possible to explain a huge number of related puzzles presented by the natural world. For instance, by assuming that gemmules could lie dormant for generations, “reversion” (the sudden reappearance of old traits) is easily explained. Gemmules provided by a male might remain in circulation in his mare and cause a permanent change in the inheritance pattern as in the assumed case with the horse and quagga. Even regeneration could be explained neatly by pangenesis. Perhaps a severed limb, before its removal, sent out into the body gemmules that “remembered” the proper limb structure and later regrouped to direct its reconstruction.

Pangenesis could prevent swamping because gemmules might reproduce themselves after being released from an organ, making it possible for a few changed gemmules to “become sufficiently numerous to overpower and supplant the old [existing] gemmules” (Darwin, 1868b, p. 395). This realization must have given Darwin a great degree of satisfaction because it would permit him to respond to the important criticism of Fleemingjenkin, who suggested that the swamping would make natural selection impossible by removing rare but useful traits from the population. Darwin charitably gave Jenkin some credit for the development of pangenesis by saying “Fleeming Jenkin has given me much trouble, but has been of more real use to me than any other essay or review” (cited in Browne, 2002, p. 282).

Finally, and most importantly, pangenesis would explain the source of new variation through use and disuse. Even if it is not an accurate argument, as any biology student would suggest, pangenesis does explain how inheritance works (all before the discovery of Mendel’s laws, the gene, and DNA). Such explanatory strength should have firmly convinced Darwin of the validity of pangenesis but, as we will see, he spent considerable time convincing others even as he continued to persuade himself.

Pangenesis: Reception and Reaction

The reception of pangenesis by the scientific community was decidedly mixed, although it inspired the work of scientists such as De Vries, von Nageli, Weisman, Brooks, Spencer, and even Darwin’s own cousin Francis Galton, as we will see later (Kampourakis, 2012). Darwin seems to have had his own doubts, but he alternately defended and coyly criticized the idea for the remainder of his life. Had he fully accepted pangenesis, the concept would surely have featured in later editions of the Origin, yet it never appeared. Hodge (2010) suggests that “the Darwin of pangenesis is … another Darwin” (p. 130) who failed to unite the ideas contained in pangenesis with those of natural selection. Even when writing extensively about pangenesis in Variation, Darwin refers to the idea as a provisional hypothesis. This phrase is interesting; perhaps Darwin wanted his readers to see the idea as something even less than hypothetical. A measure of the ebb and flow of Darwin’s own support for the idea may be sensed in these passages from letters to his scientific colleagues, letters regarding his “child,” pangenesis.

In a letter to J. D. Hooker (3 February 1868), Darwin wrote, “I did read Pangenesis the other evening, but even this, my beloved child, as I had fancied, quite disgusted me” (Darwin, F, 1887, p. 75).

In another letter to Hooker (23 February 1868), he wrote, “I feel sure 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.” In this same letter he says that “Now all these points and many others are connected together, whether truly or falsely is another question, by Pangenesis. You see I die hard, and stick up for my poor child” (Darwin, F, 1887, p. 78).

To Asa Gray, the major U.S. supporter of evolution, Darwin remarked: “[Y] ou give an excellent idea of pangenesis—an infant cherished by few as yet, except his tender parent, but which will live a long life” (Letter 6167, 8 May 1868).

Writing to Alfred Rüssel Wallace (27 February 1868), Darwin stated that “I had given up the great god Pan as a stillborn deity” (Darwin, F, 1887, p. 80).

In March 1870, Darwin wrote to E. Ray Lankester, a prominent evolutionist who would later become the director of the British Museum of Natural History (15 March 1870), and refers to pangenesis as “my much despised child, Pangenesis who I think will some day, under some better nurse, turn out a fine stripling [a young lad]” (Darwin, F, 1887, p. 120).

In spite of the apparent support for pangenesis given the range of phenomena it seemed to explain, the idea never seemed to catch on with biologists. Even Huxley, when asked by Darwin to comment on the idea of pangenesis before publication, said in a letter of 1 June 1865 that he would put on his “sharpest spectacles and best thinking cap” and “not write till I have thought well on the subject” (Huxley, 1900). Two weeks later, on 16 July 1865, after reviewing the idea, Huxley cautioned Darwin by saying “But all I say is, publish your views, not so much in the shape of formed conclusions, as of hypothetical developments…” (Huxley, 1900). This was but faint encouragement, and there is not further written record about Huxley’s opinions regarding pangenesis.

In the years following publication of pangenesis, Darwin’s own celebrity likely blunted any strong criticisms, but few scientists accepted the “provisional hypothesis” by applying it to their own work. In the second edition of Variation, Darwin (1875) included a long footnote in which he reviewed and generally dismissed “references to the more important articles” (p. 350) against pangenesis. Ironically, the basic rules of inheritance were available during Darwin’s time through the work of Gregor Mendel. However, there is no evidence that Darwin had access to the obscure journal of the Brno (Brunn) Natural History Society, in which Mendel published in 1866. However, there is the tantalizing suggestion by Kampourakis (2012) that Darwin owned at least two books citing Mendel’s work. However, he likely did not read or sense the importance of these ideas, nor is there any assurance that Darwin would have understood the mathematical argument on which the nascent science of genetics was founded.

Interestingly, the most serious challenge to pangenesis came from within his family. Darwin’s half cousin Francis Galton (often called the father of eugenics) conducted a series of experiments to test the notion that gemmules moved throughout the body to transmit information to the gametes. The experiment was simple. With help from an experienced zoo keeper, Galton took common mongrel rabbits and transfused their blood with that of the pure-bred silver-gray variety. The idea was that the gemmules circulating in the blood of one variety would cross over to the other and change the inheritance pattern in future generations. It did not, and the silver-gray rabbits continued to breed true. Even though Darwin was aware of the experience and even enthusiastic about the results, Galton published without sharing the negative finding. The episode played out in the pages of the Proceedings oj the Royal Society (Galton, 1871) and Nature (Darwin, 1871a) and has been discussed engagingly by Gillham (2001) in his biography of Galton. Darwin was clearly annoyed at not being given a chance to react in advance to the disappointing result and responded to Galton in Nature somewhat adamantly,

I have not said one word about the blood, or about any fluid proper to any circulating system. It is, indeed obvious that the presence of gemmules in the blood can form no necessary part of my hypothesis; for I refer in illustration of it to the lowest animals, such as the Protozoa, which do not possess blood or any vessels; and I refer to plants in which the fluid, when present in the vessels, cannot be considered as true blood. (Darwin, 1871a, p. 502)

Galton apologized in the next month’s issue of the journal and blamed himself for falsely assuming that Darwin’s phrase “circulating freely” implied that blood was involved. There is no evidence that anyone again attempted an experiment to determine the veracity of pangenesis and its messenger gemmules. As is often the case in science, if an idea seems to work, that is evidence enough to the proponents that the idea might actually be the truth. Perhaps that is the case with Darwin, but perhaps he understood that the tide of opinion had turned against him. Writing to fellow naturalist Henry Bates in 1868, Darwin said that “The poor infant Pangenesis will expire, unblessed & uncussed by the world, but I have faith in a future & better world for the poor dear child” (cited in Browne, 2002, p. 285). This certainly sounds like a man wanting to have it both ways.

Pangenesis: The Legacy

In 1889, biologist Hugo De Vries was inspired by Darwin’s work and developed the principle of “intracellular pangenesis” to explain inheritance by suggesting that traits are carried by tiny particles he called “pangens” in honor of pangenesis. Gone was the requirement that these pangens would change in response to use/disuse and injury factors that Darwin had suggested, but the intellectual link between Darwin and early modern principles of inheritance is clear. When the name for the hereditary particle was coined by Wilhelm Johannsen in 1909, it was called the “gene” (Mawer, 2006) perhaps after Darwin’s “unblessed poor infant” pangenesis.

As Darwin noted in a letter to his American evolution supporter Asa Grey “Pangenesis will be called a mad dream [but]… I shall be pretty well satisfied if you think it is a dream worth publishing (Letter 5649 to Asa Grey 16 October 1867). While pangenesis can be characterized as a mad dream, I have had several goals in mind in providing this account of its history First, it is a fascinating story that sheds much light on the thinking of one of the most productive biologists in history. Second, it provides the background necessary to tie a rich and interesting aspect of the history of biology to a large number of useful lessons in the nature of science. These are the lessons we will consider in part two of this article, “Darwin’s Error: Pangenesis and the Nature of Science,” in the next issue of The American Biology Teacher.