Abstract
The term hormesis was derived by Southam and Ehrlich, 1 who noted earlier literature showing biphasic dose/concentration relationships, previously referred to as the Arndt-Schulz Law or Hueppe’s Rule. 2 Southam initially referred to the biphasic dose response as “toxicotropism”, but replaced it in his paper with the now famous moniker, hormesis. 3 In 1943, hormesis, meaning to excite, was used for the first time in the peer-reviewed literature by Southam and Ehrlich, 1 who reported that low doses of extracts of the red cedar tree enhanced the growth of multiple fungal species at low concentrations while being inhibitory at higher concentrations.
While the term hormesis had made it into major databases, such as the Web of Science, by 1943, its growth as a recognized concept was slow, in part because the field of toxicology for the remaining half of the 20th century was primarily a high dose, few doses hazardous assessment discipline, making the citations of the low dose stimulatory hormesis concept quite limited. The hormesis concept was also linked to homeopathy very early on by Hugo Schulz, who claimed it provided the “Explanatory Principle” of Homeopathy. 4
With these historical issues, the term hormesis or hormetic was cited only about 15 times per year, on average, during the 80’s. The hormetic concept received a boost in 1985 with the first conference on Radiation Hormesis, and was also stimulated by Thomas Luckey’s book, Ionizing Radiation and Hormesis. 5 The peer-reviewed proceedings of this radiation hormesis conference were published in Health Physics (See Calabrese et al. 6 and Furst, 7 as examples). The concept of hormesis also received a boost in 1989 with a public policy debate by Leonard Sagan 8 and Sheldon Wolf 9 entitled Hormesis: Point Counterpoint. Wolf was the first to describe the concept of adaptive response for mutation with low doses of radiation. 10
In the late 1990s, Human and Experimental Toxicology (HET) started to publish a series of hormesis-theme-related articles exploring the scientific foundations of hormesis. By 2000, the terms hormesis or hormetic were cited approximately 400 times per year within the Web of Science database. In 2022, the terms hormesis or hormetic were cited over 20,000 times, continuing the substantial and consistent growth in scientific understanding of hormesis and its generality, affecting all disciplines concerned with the nature of the dose response in the low dose zone.
One of the early HET papers was entitled “Defining Hormesis” (Calabrese and Baldwin 2002), 11 which proved to be of continuing importance as it provides conceptual, scientific, and terminological clarity to the concept of hormesis, something that was needed during its long and controversial history.12–16 In 2023, this conceptual paper (Calabrese and Baldwin, 2002) 11 achieved the milestone of being cited over 1000 times in Google Scholar, making it the most cited paper for HET. It also shows how long it can take the scientific community to “vet” new and challenging concepts and how scientific leaders at the level of journal editor can make a major impact, as in the case with the concept of hormesis and HET providing an objective forum for the scientific community to learn more about its historical foundations, scientific basis, and underlying mechanisms.