In a recent issue of International Journal of Epidemiology, Kuzawa stated that Darwin lacked an understanding of the material basis of heredity, and his Pangenesis had fatal flaws.1 It is likely that this viewpoint is not supported by recent evidence.
Darwin regarded his The Origin of Species as an ‘abstract’—an incomplete explanation of his theory of evolution. He knew that all his conclusions would remain incomplete until the essential foundation stones of inheritance and variation were located. In 1868, he published The Variation of Animals and Plants under Domestication. It is in this two-volume work that Darwin came nearest to the subject of genetics. Of the work’s 28 chapters, the first 10 consist of a veritable catalogue of variations. In the 11th chapter, Darwin examined four unusual forms of trait production: bud variations (mutation), graft hybrids and the direct actions of the male element on the female (later called xenia and telegony). Next three long chapters, 12–14, are entitled ‘inheritance’. Chapters 15–19 handled hybridism. Chapters 20 and 21 consisted of detours into the mechanism of artificial and natural selection, whereas chapters 22–26 focused on the ‘laws of variation’.2 Darwin clearly described almost all genetic phenomena of fundamental importance.
It was Darwin’s attempt not only to strengthen his theory of natural selection, but more importantly to describe and understand the root cause of variation—for variation is the fountainhead of evolution. Darwin concluded The Variation by formulating his Pangenesis. He proposed that cells are not only able to grow by self-division, but also are capable of ‘throwing off’ minute informative molecules, which he called gemmules (the embryonic form of our modern genes). These gemmules are capable of self-replication, dormancy, variation, circulation throughout the body and entering the sex cells. The appearance of the same characters in parent and offspring is made possible by the production of gemmules by all parts of parent’s body. If the cells of one part of the body undergo change as a result of environmental change, they consequently throw off modified gemmules, which are transmitted to the offspring, thus accounting for the inheritance of acquired characters. Gemmules released in the stock would be transferred into the scion and incorporated into the sex cells and meristematic cells in the scion, resulting in heritable changes of the scion and their progenies, thus explaining graft hybridization. In addition, Pangenesis can also explain prepotency (later called dominance inheritance or Mendelian inheritance), reversion, regeneration, xenia, telegony and many other facts pertaining to variation, heredity and development.3 It was in this theory of heredity that Darwin tried to account for all the observable facts he had described in the preceding 26 chapters, and laws of inheritance—a considerable variety of phenomena to unite under a common theory. It should be noted that the word ‘gene’ evolved from de Vries’s term pangens, itself a substitute of ‘gemmules’ in Darwin’s Pangenesis.
Darwin’s Pangenesis never gained wide acceptance, and Darwin watched it die a scientific death. Surely, Galton’s blood transfusion experiments designed to test it should have been accepted as fatal. From his experiment that rabbits of one variety, with a large proportion of the blood of another variety in their veins, did not produce mongrelized offspring, Galton concluded that Darwin’s Pangenesis was incorrect.4 During the 1950s and 1970s, however, there was a considerable body of experimental evidence for genetic changes induced by blood transfusion. Among 50 reports we collected, 45 obtained positive results and only 5 obtained negative results.3 In addition, there is increasing evidence for the inheritance of acquired characters, graft hybridization, xenia and telegony, which Pangenesis supposedly explains.5–8
The basic postulate of Darwin’s Pangenesis was the existence of the gemmules and their production by cells. No one had detected a gemmule; yet, Darwin was convinced that they must exist, because, if they did exist, a considerable variety of phenomena would be united under a common theory. Surprisingly, in 1948, the detection of free-circulating nucleic acids in human plasma samples was reported for the first time by Mandel and Metais. During the past several decades, the presence of free-circulating nucleic acids in plasma and serum of healthy and diseased human beings has been a well-established phenomenon.9 Circulating nucleic acids can be actively released from living cells. Their release into the blood is also thought to be related to dying cells (whether necrotic or apoptotic).10 In plants, cell-to-cell channels, called plasmodesmata, connect each cell to its neighbours, facilitating the exchange of large molecules. It has been well documented that mRNA, small RNAs and large DNA pieces may move between the cells and around the plant. One can gain some insights by comparing Darwin’s gemmules with circulating nucleic acids. Now we can affirm that Darwin’s idea that gemmules are the molecular carriers of hereditary characters, multiply by self-replication and circulate throughout the organism has been removed from the position of a provisional hypothesis to that of a well-founded theory. In light of the supporting evidence, is it proper to say that Darwin lacked an understanding of the material basis of heredity, and his Pangenesis has fatal flaws?