Originator of the hormesis concept: Rudolf Virchow or Hugo Schulz

Abstract

In 2006, Henschler disputed the claim of Calabrese and Baldwin that Hugo Schulz should be considered the originator of the hormesis concept. Henschler cited an 1854 paper by Rudolf Virchow on the effects of two agents on the beating of cilia, which showed a hormetic–biphasic dose response. The interpretation of Henschler became broadly accepted over the past decade based on citations in the literature. However, a recent translation of the Virchow paper from German into English reveals that the claims of Henschler are not supported by the article.

Introduction

In 2006, Henschler published a clarifying statement on the origin of hormesis. ¹ He noted that Calabrese and Baldwin ^{2 –6} reported that Hugo Schulz, professor of pharmacology at the University of Greifswald, was the first to report hormesis. ^7,8 Henschler indicated that our paper had identified several earlier papers that indicated low-dose stimulatory effects of toxic agents, but these papers did not include the necessary experimental findings for an adequate evaluation. Therefore, Schulz was elevated to the title of the first to demonstrate hormesis. However, in his own search of the early historical literature, Henschler ¹ noted that he “uncovered a remarkable report of Rudolf Virchow” that was dated August 28, 1853 (i.e. the year of Schulz’s birth) and published in 1854, ⁹ some 30 years prior to Schulz’s first presentation of his findings and 33 years prior to his first publication on the topic. ^7,8 Multiple papers have cited the 2006 paper of Henschler and have now proclaimed that Virchow was the first to show hormesis. ^{10 –14}

Revised Conclusion

For a variety of reasons, I just arranged to have the 1854 published paper of Virchow translated into English. ⁹ To my surprise, I find that the translation did not confirm the conclusion of Henschler. In Table 1, I place side by side the key translated segments of the Virchow paper and how Henschler characterized it in the Human & Experimental Toxicology publication. The translation does not indicate that (1) gradated concentrations of sodium hydroxide were used or (2) he tested low and high concentrations. Thus, the article fails to document that a hormetic–biphasic dose response was observed. Thus, Henschler’s conclusion that “Virchow’s short paper is the very first example of the demonstration of the phenomena of hormesis” is not supported with the evidence presented. Thus, at least for the present Hugo Schulz is still the “father” of hormesis.

Table 1.

Comparison of key Henschler ¹ and Virchow ⁹ paragraphs.^a,b

Henschler, 2006

Virchow, 1854

In those days, pathologists were well aware that, after the death of an individual, the ciliae continue beating for many hours, sometimes even for a few days. Observing the fading activity of the ciliae under the microscope, Virchow exposed the layer to gradated concentrations of sodium hydroxide. At low concentrations, he saw a vivid increase in the power and frequency of beating for considerable periods of time, whereas higher concentrations and longer exposure times paralyzed the beating activity, and finally led to cell death. Virchow wrote down this observation in a (very) short communication of just one and half pages. 8 He gave no figures of the concentrations used and the number of experiments performed, but stressed that he could reproduce the phenomenon regularly again and again. The same response could be elicited with potassium hydroxide. Page 348, right column

Coincidentally, while examining a human trachea, I recently succeeded in discovering a chemical agent that acts as a stimulant for cilia. When I added potash solution to an object whose vigorous motions had partly become very weak or had party stopped altogether, I was able to observe the motions reemerge in every part and continue in duration until corrosion set in that resulted in the destruction of the parts themselves. Later, I replicated this experiment under different conditions and could confirm the same findings over and over again. Even using the trachea of another human corpse in which the ciliary motion had partly stopped in places or in general was very weak and in which the ciliary epithelium had been easily destroyed though the mere application of water, I was able to bring about the phenomenon in great intensity through the addition of potash solution even if only for a short period of time. In contrast, by using better preserved, fresher mucous membranes, it was possible to bring about the revival of motion for a seemingly long time. Page 1, 2nd paragraph

^aThe relevant Virchow (1854) paragraph fails to mention “gradated concentrations” and low and high concentrations that Henschler (2006) claimed that it did.

^bThe Virchow (1854) paragraph was translated to English by the University of Massachusetts Translation Service (October 2017).