Dear Editor,
I would like to thank the authors of this letter for providing an interesting perspective and for publishing many thought-provoking articles on the topic of Darwin’s pangenesis over the years.
While the relationship between Darwin’s gemmules and extracellular vesicles (EVs) is a highly interesting and hotly debated topic, it represents only a very minor component of my paper on EVs in bone development and regeneration, which was merely included to provide some brief historical context. While I am happy to concede that horizontal DNA transfer is not my area of academic expertise (nor the central theme of my publication), I would like to provide the following response to the points raised.
The pangenesis hypothesis proposed by Charles Darwin describes the release of heritable information by all cells in the body and their assembly in the gonads.1 The authors are entirely correct in their statement that EVs can facilitate the horizontal transfer of genetic material (including genomic, mitochondrial, and viral DNA) between cells.2 However, to the best of my knowledge, there currently exists no evidence linking EVs to the exchange of heritable information that is passed from parent to offspring. Rather, data published in the field has largely demonstrated horizontal DNA transfer in maintaining cellular homeostasis, modulating immune responses, and regulating tumor progression.3,4,5,6 In my opinion, this makes EVs quite distinct from the gemmules proposed by Darwin.
I think it is important to emphasize that the presence of DNA has not been described in all EVs (or EV subsets), and no publications have (yet) reported the presence/functions of EV-DNA in bone development/regeneration. Additionally, naked DNA or DNA associated with non-vesicular entities has been a major confounding factor in the field, which has only recently started to be more convincingly addressed through the application of advanced techniques such as nano flow cytometry.7 This publication has shed some light on long-standing questions concerning the distribution of DNA between EV subsets and its apparent differential localization within particles of varying sizes. However, the role of smaller non-vesicular extracellular particles (NVEPs) such as liposomes and exomeres in DNA transfer is also something that needs to be considered.8 NVEPs are common in EV preparations but have often not been extensively reported and could account for differences observed in the field.9 I ask, would the authors also include NVEPs in their definition of gemmules? These are all interesting points, and I do not mean to be intentionally provocative here. Instead, I feel we are perhaps not in the position to make a clear and definitive link between EVs and Darwin’s gemmules at this point.
I hope that the authors are satisfied that I felt it premature to comment on the presence of DNA in EVs, particularly given the focus of the paper in question. I sincerely hope they understand my position on the matter. Nonetheless, I thank them for prompting an interesting discussion.
Yours sincerely, Dr. Owen Davies.
References
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