Hormesis: Path and Progression to Significance

This paper tells the story of how hormesis became recognized as a fundamental concept in biology, affecting toxicology, microbiology, medicine, public health, agriculture, and all areas related to enhancing biological performance. This paper assesses how hormesis enhances resilience to normal aging and protects against a broad spectrum of neurodegenerative, cardiovascular, and other diseases, as well as trauma and other threats to health and well-being. This paper also explains the application of hormesis to several neurodegenerative diseases such as Parkinson’s and Huntington’s disease, macrophage polarization and its systematic adaptive protections, and the role of hormesis in enhancing stem cell functioning and medical application

The Maturing of Hormesis as a Credible Dose-Response Model

Hormesis is a dose-response phenomenon that has received little recognition, credibility and acceptance as evidenced by its absence from major toxicological/risk assessment texts, governmental regulatory dose-response modeling for risk assessment, and non-visibility in major professional toxicological society national meetings. This paper traces the historical evolution of the hormetic dose-response hypothesis, why this model is not only credible but also more common than the widely accepted threshold model in direct comparative evaluation, and how the toxicological community made a critical error in rejecting hormesis, a rejection sustained over 70 years

The Emergence of the Dose–Response Concept in Biology and Medicine

A historical assessment of the origin of the dose–response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e., hormetic) dose–response models emerged in the late 19th and early 20th centuries and competed for acceptance and dominance. Particular attention is directed to the hormetic model for which a general description and evaluation is provided, including its historical basis, and how it was marginalized by the medical and pharmacology communities in the early decades of the 20th century

A glance into how the cold war and governmental loyalty investigations came to affect a leading U.S. radiation geneticist: Lewis J. Stadler’s nightmare

This paper describes an episode in the life of the prominent plant radiation geneticist, Lewis J. Stadler (1897–1954) during which he became a target of the Federal Bureau of Investigation (FBI) concerning loyalty to the United States due to possible associations with the communist party. The research is based on considerable private correspondence of Dr. Stadler, the FBI interrogatory questions and Dr. Stadler’s answers and letters of support for Dr. Stadler by leading scientists such as, Hermann J. Muller

PREDICTING LOW DOSE EFFECTS FOR CHEMICALS IN HIGH THROUGH-PUT STUDIES

High through-put studies commonly use automated systems with 96-well plates in which multiple chemicals are tested at multiple doses using log-2 dose increments after a suitable incubation period. There are typically multiple (ranging from five to eleven) doses on each chemical, and occasionally plate replications of the dose-response studies. The target endpoint for such studies is typically the LC50, but for some chemicals, there may be multiple doses below a benchmark dose where there is no apparent adverse response relative to control response. We show how an estimation approach can lead to clearly interpretable results about response in the low dose region using data from a high throughput study of 2189 chemicals on yeast. Accurate estimates can be obtained of response for study chemicals by using best linear unbiased predictors (BLUPs) in a mixed model, and summarized via plots with expected response (assuming no low-dose effect) with confidence intervals for response below the benchmark dose for each chemical, providing an informative summary of response at low doses. We conclude that this approach can provide valuable insights that would be missed if the observational data were only considered through the lens of statistical methods appropriate for experimental studies