Metchnikoff's prescience

I have recently been reading Metchnikoff's "Lectures on the comparative pathology of inflammation", given in 1891 and published in English in 1893.

My first thoughts were that it is probably rare to be able pick up such a book, written in the last decade of the 19th century, where it remains thoroughly readable and fully pertinent to today's science of immunology. There are so many points where he was clearly laying out the right track and where he gave others a course to proceed. But no one of clout seems to have taken it (other than to give it lip sevice before dashing off to deal with something important). He adopted, whole heartedly, the implications of Darwins' evolutionary theory and applied this to the study of an organism's response to infection, trauma and foreign bodies. It is quite clear that he is assaying the responses of multiple different organisms to injurious stimuli and showing how they progressively shaped through the tree of life. In this comparative approach he does not miss out plants and establishes the criticality of "impenetrable" defences for both plants and various other organisms, including crustacea.

His acceptance of evolution was total and it shaped how he would look across a plethora of different life forms to see how they responded to and managed both damage and invasion, whether it was microbial or abiotic.

As a basis for the investigation of inflammation, I would say that this lectures series has immense value. Throughout the book it become apparent that debriding sick (self) cells is a core process and regeneration is an integral part of damage management, with some species using a rapid, replacing regeneration in preference to bothering to repair suspect cells.

Should the discipline of immunology have grown up on inflammation, we might not have diverted off into a conceptual backwater for so long.

That's my take on it.

Metchnikoff, E. "Lectures on the comparative pathology of inflammation delivered at the Pasteur Institute in 1891: delivered at the Pasteur Institute in 1891" Translated into English in 1893 by Starling FA and Starling EH

Now there is a postscript to add to this.

For some reason (probably a new pdf airing), a new search result has just turned up an old publication (2001). It includes an article by Ken Schaffner, on the "Sense of self" debate (ref 6). However, there is also an article by Crist E and Tauber AI on "The phagocyte, the antibody, and agency in immunity: contesting turn-of-the-century aproaches" (pp115-139). This discusses Metchnikoff's "inflammocentric" persepective of immunity. The authors make some fascinating statements and they also highlight revealing quotes that they found in Metchnikoff's publications.

When immunologists make the assumption that antibodies (and T-cells) target "pathogens" they need to think twice about what constitutes a pathogen. Is it (obligatorily) a pathogenic organism? Or is it any agent that has led to tissue damage? Further, is it a single epitope from the agent or a representative suite of unusual epitopes associated with the damage.

Metchnikoff explored – as a central argumentative (dicussive) theme – the comparative evolution of immune mechanisms. It would be a salutatory strategy to emulate this. I have a regular PubMed searches on evolution of immunity and phylogeny of immunity and they have been running for years. Virtually no returns focus on the broad subject of the comparative evolution of immunology. They, instead, tend to focus on micro-evolution in living environments. A book search for the evolution of immunity is equally sparse. This – to my mind – is an indictment of modern research in immunology. It is overwhelmingly focused on minutiae, not on broad principle.

I note that this 2001 book reference link is now not working. Let me know if you – too – cannot find it (jamie at morphostasis.org.uk, replace "at" appropriately).