"A proliferation of pathogens through the 20th century"

Published In the August 2008 edition of the Scandinavian Journal of Immunology.

Links to the original article:

It points out that the meaning of "pathogen" has shifted over the last 120-130 years.

Additional notes:

The dominant and extant trend is to regard "a pathogen" as "a disease causing micro-organism." This has, effectively, wrapped us up in a perceptual "Gordian Knot". Until the definition of pathogen is returned to "any agent that damages cells/tissues" it is almost impossible to escape from the resulting conceptual straightjacket that is imposed on us by this misappropriation of the word "pathogen". Consider this statement: "Pathogens provoke aggressive anamnestic immune responses." Now interpret these pathogen induced aggressive anamnestic immune responses from the restricted "just micro-organism" persepective and then from the far broader "any damaging agent" perspective. The first and most important change is that the inflammo-immune system's major role can now be expanded to encompass the management and repair all cell/tissue damage.

It should be an inescapable conclusion that the meaning of "pathogen" is still in transition. Its original meaning was "a specific causative agent of disease". Many people now define it as a "causative agent of disease - especially a bacterium or a virus" or something along those lines. However, there is a greater transition towards it becoming a synonym and replacement for a "pathogenic organism": this is now well under way - particularly in its extensive use in the bio-medical literature. Some dictionaries already define a pathogen as "a disease causing organism". I believe that there is an imperative to consider whether this drift should be allowed to continue and if its procession should be reversed. In the published article I suggested, "Perhaps the prevailing theories of self/non-self-discrimination and of immune system function were fully compatible with this interpretation of pathogen – anomalies and anachronisms are only now coming into focus." This may be better expressed as "Perhaps the prevailing theories of self-/non-self-discrimination and of immune system function failed to highlight the anomalies and anachronisms that would have arrested this drift: they are only now coming into focus."

This challenge could be summed up in this pertinent question: "Is asbestos a pathogen? (or more precisely, does an asbestos fibre qualify as a pathogen when it causes disease?)" I believe you ought to answer yes; and this response straightaway exposes the general misuse of this term.

The term pathogenic bacterium may seem to be more or less the same as a bacterial pathogen. But these is a clear difference in emphasis. In the first it the bacterium that is the principal property; this has the expected properties of a bacterium with the additional property of being able to cause damage. In the second, it is the pathogen that is the principal property; this has the "expected" properties of a pathogen with the additional property of also being a bacterium. To me, it seems that there is far more emphasis on – and scope for – a variety of pathogenic mechanisms in the first than in the second. So, in addition to advocating a return of pathogen to mean any agent that causes disease or damage, I suggest that we should use pathogenic organism rather than an organismal pathogen (where organism is the generic proxy for bacterium, virus, fungus etc) unless there is a compelling reason to emphasise the second.

The article ends by suggesting that an alternative shorthand might be called for to replace pathogen where we really mean a (potentially) pathogenic (micro-)organism.

Pathogerm could prove to be an appropriate substitute; this name is both "twee" and rather colloquial. Both these properties would act as appropriate reminders that this is nothing other than a convenient abbreviation that hides a wealth of deeper properties. It has the advantage of sounding similar to pathogen but remaining clearly distinct.

Pathobiont would be suitable alternative. This term has already been introduced by Mazmanian et al . However, they had a quite specific definition in mind: a commensal (intestinal) bacterium with pathogenic potential. Promotion of this term to a more general use should only be done with their agreement. Nevertheless, Wiktionary already defines a pathobiont as "Any pathological (disease-causing) organism" – so perhaps this is the best candidate.

The perspective persists that aggressive adaptive immune responses are caused by the interaction of TLRs (toll like receptors – expressed on dendritic cells) with PAMPs (pathogen associated molecular patterns). However, as highlighted, PAMPs should really be regarded as MAMPs (microbe associated molecular patterns). Since several million different bacterial species are non-pathogenic to man and only about 50 are regularly pathogenic, why do we not become awash with (metabolically expensive) aggressive adaptive immune responses to these non-pathogenic species (particularly the 500 or so different commensal species that live within and upon our bodies)? There is something not consistent and quite illogical here. Oral and gut bacteria are both encouraged to inhabit us and they are useful to us and play a protective role. If their MAMPs were to regularly provoke the adaptive immune system into an aggressive response, the outcome could be a devastating inflammation of our mouths and gut (it looks as though Crohn's disease, ulcerative colitis and the mouth ulcers of Behcet's syndrome may be unwelcome examples of such misdirected aggressive immune responses). This should indicate to us that these aggressive responses are channelled away from aggression when the encounter is with non-pathogenic, commensal or symbiotic organisms – which seem to be welcomed and encouraged into colonising our mouths and gut.

At the beginning of this article I have used the quotation "The repetition of a catchword can hold analysis in fetters for fifty years and more." (Benjamin N. Cardozo, 1870-1938). However, Francis Bacon (1561-1626: perhaps, the "father of natural philosophy" – which is now commonly called "science") – has much to say on this in his comments on "Idols of the Mind" in Novum Organum (copy here, see sections XLIII and LIX):-

XLIII "There are also idols formed by the intercourse and association of men with each other, which I call Idols of the Market-place, on account of the commerce and consort of men there. For it is by discourse that men associate; and words are imposed according to the apprehension of the vulgar. And therefore the ill and unfit choice of words wonderfully obstructs the understanding. Nor do the definitions or explanations wherewith in some things learned men are wont to guard and defend themselves, by any means set the matter right. But words plainly force and overrule the understanding, and throw all into confusion, and lead men away into numberless empty controversies and idle fancies."

LIX "But the Idols of the Market Place are the most troublesome of all – idols which have crept into the understanding through the alliances of words and names. For men believe that their reason governs words; but it is also true that words react on the understanding; and this it is that has rendered philosophy and the sciences sophistical and inactive. Now words, being commonly framed and applied according to the capacity of the vulgar, follow those lines of division which are most obvious to the vulgar understanding. And whenever an understanding of greater acuteness or a more diligent observation would alter those lines to suit the true divisions of nature, words stand in the way and resist the change. Whence it comes to pass that the high and formal discussions of learned men end oftentimes in disputes about words and names; with which (according to the use and wisdom of the mathematicians) it would be more prudent to begin, and so by means of definitions reduce them to order. Yet even definitions cannot cure this evil in dealing with natural and material things, since the definitions themselves consist of words, and those words beget others. So that it is necessary to recur to individual instances, and those in due series and order, as I shall say presently when I come to the method and scheme for the formation of notions and axioms."

Pathogenic probably came to us via the French from their pathogenique. They also use the term pathogene (both as a noun and as an adjective according to some dictionaries). They have been much more faithful to its original meaning as the following definitions (of pathogene) demonstrate:

I received these helpful comments from Jeff Aronson ("When I use a word .. " series in the BMJ/QJM) in response to my contact:

"The datings may need revision. The following are the dates of the earliest examples given in the OED:

This and your bibliometric data seem to argue that pathogen is a back-formation from (say) pathogenetic. However:

The earliest citation of "pathogen" in OED establishes that the micro-organism meaning was already there in 1880: 1880 Libr. Universal Knowl. VI. 647 Pathogen [the micrococcus of] contagion. I am not sure if the definition that you cite under the heading of Merriam Webster from 1880 is actually from that date, but if it is, that also suggests that the restriction in meaning to organisms was not particularly insidious. There seems to be no earlier use of the word to mean anything other than that."

My search for the first use of "pathogen" was gleaned largely from Nature and Science – these being the only sources that I could access. I have made an assumption that these journals typified general use but maybe that is not so. Whatever, there are two points worth making: first, Metchnikoff avoided this term – perhaps deliberately; second, the recent discovery and interest in microbial disease (the era of Koch and Pasteur) seems to have carried with it an early supposition that most disease would turn out to have an infective origin/element (and, perhaps, they will prove right).

Nearly all of us would wince at the use of "a cardiac heart" or "a pulmonary lung". So, if we can all agree that "a pathogenic organism" is a legitimate and correct expression, then the subsequent use of "pathogen" as a synonym and substitute for a "pathogenic organism" implicitly endorses the legitimacy of the phrase "a pathogenic pathogen".

American influence

I guess that there might be a pattern here. In the USA, there is a corporate tendency to take on a language element from abroad and then stamp a clear Americanisation on it. This is exemplified by their spelling of meter and liter. As a nation they have stalwartly resisted metrication – meterication? – and yet, where it is "reluctantly" adopted, they still feel the need to Americanise it. On the cruel side, we might interpret it this way: this relatively newly emerged nation – who quickly rose to a position of global dominance – feel the need to stamp their unique ownership and authority on language. Or, more likely, it is just a parochial mass action effect where the outside "brake" to halt divergences was not previously felt (globalisation will change this). Perhaps a justification is that it simplifies spelling; but it does so at the expense of loosing sight of derivation. On the cruel side, this amounts to an arrogance that ignores the etymology and origin of terms and ideas. These potential criticisms are ones that American academia should assess for themselves and then adjust if they find this expedient (I guess there are already many North Americans who have sympathy with this). It seems likely that this pattern has also affected "pathogen", originally "pathogene" – from the French – who have remained much truer to its original meaning. I will end by suggesting that we should strive to be the servants of language rather than its masters.

This emphasises the confusion

I came across this statement (in a paper) a few days ago: "Inflammation is a highly regulated process involved both in the response to pathogens as well as in tissue homeostasis." If we strip this instance of "pathogen" of its assumed meaning (a pathogenic organism) and revert to a generic interpretation of "pathogen" (any agent that causes cell/tissue damage) then we see, immediately, how this restrictive and specific interpretation of "pathogen" obstructs our understanding. The "as well" is exposed as tautological thinking. A {pathogenic organism = organism + damage}. "Organism" and "pathogen" are distinct and separate entities. They just happen to coincide in "pathogenic organisms". They must be viewed and assessed separately, not as a (con)fused (monolithic) whole.

Also, these two sentences have recently appeared in articles. First:

"Inflammation is an integrated immune process that is rapidly initiated either when tissues are damaged or by pathogenic infections." If this were changed to " .... initiated when tissues are damaged either by abiotic or biotic agents" then it would still be correct and, probably, exact.

Second:

"Plants are invaded by an array of pathogens of which only a few succeed in causing disease." So what is a pathogen? This sort of statement only emerges from the misappropriation of pathogen. To be "correct" it needs to say " .. an array of potentially pathogenic organisms of which ..." etc.

The following is incontrovertible

Whatever the causes or sequence of events that led up to modern interpretations of "pathogen" (and these would probably be challenged by at least a few) one thing is incontrovertible. The extant interpretation of pathogen is shifting or has already changed. For many, there is no longer even room for "a specific causative agent of disease, especially a micro-organism". It is now overwhelmingly interpreted as "a micro-organism that causes disease". The shift is undeniable.

The four English Dictionaries held in the Wessex Medical Library (Southampton General Hospital) have these definitions for a "pathogen".

Thus it is absolutely clear that the generic meaning of pathogen was well established and quite legitimate before this mass trend to a hijacking of the word for a much more specific (but confused) meaning. Now that journals with "pathogen" in their title have appeared (eg, PLOS Pathogens, Pathogens and disease and many others – search "pathogen + journal"), it is hard to see how a reversal can take place without considerable upheaval and a monumental climb down.

Especially a micro-organism is a rider forced on the definition writers to reflect this common – mass action – interpretation of "pathogen". This had led to the overwhelming trend towards "pathogen" becoming an acceptable synonym for a "pathogenic micro-organism".

I have just found this 1996 article (Journal of Medical Humanities, March 1996, Volume 17, Issue 1, pp 45-50) by Richard Sobel, entitled "The physician as pathogen" that applies this generic meaning of pathogen within the title (it is partially behind a pay wall so I can only assert that it is the article title that uses this interpretation of pathogen).

This article from Casadevall and Pirofski is one of the few to bring attention to the confusion generated by the loose use of the word "pathogen". Another article skirting the subject is here . (I am not cited in either.)

An interesting statistic

Now that Google has placed a large body of books and articles on Google Books, they have become searchable. Words and phrases can be searched to see when they started to appear in the literature. Searching this database suggests that pathogenesis was the word used most to begin with. Pathogenic followed, then pathogenicity and finally pathogen. Pathogenesis overwhelmingly retains its general connotation; so, for the most part, does pathogenic. Pathogenicity has become dominantly associated with "disease causing organisms" although its general definition remains compatible with abiotic agents. Pathogen is moving towards being seen as the exclusive "property" of biotic organisms. Here are the graphs:

I have just come across this article, published around about the same time as my article, in which these authors highlight – what should be – the general nature of a "pathogen". If anyone comes across others that have addressed this issue, I would appreciate being informed so that I can give them credit.

Also, note the logical non sequitor in this common definition, "The word 'pathogen' means any disease-producing agent (especially a virus or bacterium or other microorganism)." First it says any disease-producing agent. Then it says it is especially a micro-organism. What it should acknowledge is a statement like this, "The word 'pathogen' means "any" disease-producing agent; the mass action of common usage is tending to restrict the generic nature of "any agent" to the specific meaning of "a disease causing micro-organism."

Thanks to Alan Orme for pointing me in the direction of reference [4] "The Unfolding of Language" by G. Deutscher .