Darwin's gemmules and oncogenes.

In a recent issue of Annals of Oncology, Purushotham and Sullivan [1] reviewed Darwin’s legacy to cancer and medicine. However, they did not discuss Darwin’s Pangenesis, which provides a novel mechanism for cancerometastasis. Darwin habitually thought big. But the cell theory allowed him to think small. He wrote The Origin of Species without any reference to cellular structure in animals and plants, and the word ‘cell’ is not to be found in the index of the book. In his The Variations of Animals and Plants under Domestication, Darwin greatly expanded the cell theory and was the first to think out a molecular theory of heredity, Pangenesis, one of the first attempts to explain the mechanism of heredity at a quasichemical or at least a subcellular level. He proposed that cells not only are able to grow by means of cell division but are also capable of ‘throwing off’ gemmules—minute informative molecules—that are self-replicating and circulating. These gemmules circulate throughout the organism, penetrate other nascent cells and modify their subsequent development [2]. It should be noted that the word ‘gene’, which was coined by Wilhelm Johannsen (1909), was derived from Hugo de Vries’s term ‘pangen (pangene)’, itself a substitute of ‘gemmules’, genetic elements in Pangenesis. Obviously, Darwin’s hypothetical gemmules are the embryonic form of our modern genes. Now, we can affirm that Darwin’s idea that gemmules are the molecular carriers of hereditary characters, they multiply by selfreplication and they circulate throughout the organisms has been removed from the position of a provisional hypothesis to that of a well-founded theory. In 1869, one year after the publication of Darwin’s Pangenesis, Friedrich Miescher discovered nucleic acid, which soon came to be regarded as a likely candidate for the role of ‘substance of heredity’. In 1948, the detection of free-circulating nucleic acids in plasma samples of human was reported for the first time by Mandel and Metais. Over 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 [3]. Obviously, Darwin’s so-called gemmules are analogues to circulating nucleic acids. It is now clear that oncogenes can circulate in the plasma fraction of blood. Recently, Garcia-Olmo et al. [4] presented a ‘genometastasis hypothesis’, which indicates that metastasis might occur via transfection of susceptible cells located in distant target organs with dominant oncogenes that derived from the primary tumor and are circulating in the plasma. This hypothesis is consistent with Darwin’s Pangenesis.