Thanks, Ed. I was “close,” but one step removed, from knowing the extent of dishonesty and personality clashes that had transpired “before my time.” Professor Ernst Caspari was my Genetics advisor in college (in the end of the 1950s), and I was a member of one of Jim Crow’s NRC committees in the late 1970s with James V. Neel, MD, PhD. The air was sometimes thick with “something mysterious” that had happened, but no one ever volunteered any details — until your many articles of the Muller investigation. Now, all the pieces of the puzzle “have come together.” ☹ 😊
From: Edward Calabrese
Sent: Monday, September 4, 2023 4:39 AM
Here is another recent “LNT-Muller” paper [see attached]. In his Nobel Prize Lecture of December 12, 1946, Hermann J. Muller argued that the dose-response for ionizing radiation-induced germ cell mutations was linear and that there was “no escape from the conclusion that there is no threshold.”
However, a newly discovered commentary by Robert L. Brent (2015) indicated that Curt Stern, after reading a draft of part of Muller’s Nobel Prize Lecture, telephoned Muller, strongly advising him to remove reference to the research-flawed linear non-threshold (LNT)-supportive Ray-Chaudhuri findings and strongly encouraged him to be guided by the threshold supportive data of Ernst Caspari. Brent indicated that Stern recounted this experience during a genetics class at the University of Rochester.
Brent wrote that Muller refused to follow Stern’s advice — thereby proclaiming support for the LNT dose–response while withholding evidence that was contrary during his Nobel Prize Lecture. This finding is of historical importance since Muller’s Nobel Prize Lecture gained considerable international attention and was a turning point in the acceptance of the linearity model for radiation and chemical hereditary and carcinogen risk assessment.
— Ed Calabrese
Over the past decade, GEITP has covered most of Ed Calabrese’s articles — as he has meticulously unraveled the entire fraudulent story of how the Linear No-Threshold (LNT) Model was arrived at in the mid 1950s, how it was based on erroneously interpreted Drosophila (fruit fly) studies by Hermann Joseph Muller (and others) in the 1930s and 1940s, and how the Nobel Prize in Physiology or Medicine in 1946 was awarded (nevertheless) to Muller “for discovery of the production of mutations by means of x-ray irradiation” — when the mutations were, in fact, irradiation-induced DNA damage (breaks) and not mutations at all. ☹
This email summarizes Ed’s last five articles [see attached]; so, let’s call this email blog a Calabrese Festival. This catches me up on his constant barrage of new findings these past 2+ years. 😉
Paper 1 = “Ultra-low doses and biological amplification: Approaching Avogadro’s number” This paper describes evidence establishing that ultra-low doses of diverse chemical agents at concentrations from 10-18 M to 10-24 M (e.g., approaching and/or less than 1 atom or molecule of a substance/cell based on Avogadro’s constant, 6.022 × 1023/mole) are capable of engaging receptor- and intracellular-signaling systems to elicit reproducible effects in a variety of species — from unicellular organisms to humans. Multiple experimental studies have shown that only one, or very few molecules, are needed to activate a cell and/or entire organism via cascade(s) of amplification mechanisms and processes.
For example, ultra-low dose ligand exposure was able to activate both an individual cell, and ~3,000 to 25,000 neighboring cells on average, by about 50%. Such activation of cells and whole organisms typically displayed hormetic-biphasic dose responses*. These findings indicate that numerous diverse phylogenetic systems have evolved highly sensitive detection and signaling mechanisms to enhance survival functions, such as defense against infectious agents, responses to diverse types of pheromone communications (e.g., alarm, sexual attraction), and development of several types of cellular protection/resilience/survival processes. These data suggest that ultra-low dose effects may be far more common than had been previously recognized. Authors posit that such findings have important implications for evolutionary theory and ecological and systems biology, as well as clinical medicine.
*A hormetic-biphasic dose response means that a low dose of an environmental or endogenous chemical agent may trigger, from any organism, the opposite response to that by a very high dose:
Paper 2 = “How did Hermann Muller publish a paper, absent any data, in the journal Science? Ethical questions and implications of Muller’s Nobel Prize” This Letter-to-the-Editor reports the discovery of a 26 Oct 1927 letter of Hermann J. Muller concerning the owner and editor of the journal Science, which suggests an agreement that could have led to Muller’s publication in Science — absent any data — which would have been contributory to both his professional reputation, and perhaps his being considered for, and awarded, a Nobel Prize.
Paper 3 = “The Gofman-Tamplin Cancer Risk Controversy and Its Impact on the Creation of BEIR I and the Acceptance of LNT” The major public dispute between John Gofman and his colleague Arthur Tamplin and the United States Atomic Energy Commission (US AEC) — at the end of the 1960s and during the early 1970s — significantly impacted the course of cancer risk assessment in the US and worldwide. The challenging and provocative testimony of Gofman to the US Senate in early 1970 led to formation of the US National Academy of Sciences (NAS) Biological Effects of Ionizing Radiation I (BEIR I) Committee in order to evaluate the accuracy of claims by Gofman and Tamplin that emissions from nuclear power plants would significantly increase the occurrence of genetic defects and cancers (we now know this is not true).
BEIR I recommended adoption of the linear non-threshold (LNT) dose response model for the assessment of cancer risks from radiation exposures. The US EPA adopted this recommendation and generalized it to incorporate putative chemical carcinogens — thereby affecting cancer risk assessment studies over the next five decades. Despite scientific limitations and ideological framework of their perspectives, Gofman and Tamplin are of considerable historical importance, because they had essential roles in affecting the adoption of LNT by regulatory agencies.
Paper 4 = “Thresholds for radiation-induced mutation? The Muller-Evans debate: A turning point for cancer risk assessment” In 1949 Robley Evans published a paper in Science supporting a threshold dose response for ionizing radiation-induced mutation, contradicting comments of Hermann Muller during his 1946 Nobel Prize Lecture and subsequent presentations. Evans sent a final draft prior to publication to more than 50 leading geneticists/radiologists, including Muller; subsequent correspondence was generally extremely supportive — including letters from the radiation geneticists Curt Stern, James Neel and Donald Charles. Of interest is that Muller engaged in a dispute with Evans, with Evans dismissing Muller’s comments as containing “a few points of scientific interest, and many matters pertaining to personalities and prejudices.”
A cornerstone of the Evans threshold position was the study by Ernst Caspari, which was done under the direction of Curt Stern, at the University of Rochester/Manhattan Project, and for which Muller was a paid consultant, thereby having insider knowledge of the research team, results, and internal debates. Muller published a series of articles after the Evans Science publication that tried to debunk the Caspari findings — claiming that his “control group was aberrantly high,” which caused his threshold conclusion to be incorrect. [However, internal correspondence in 1947 between Muller and Stern reveals that Muller supported the use of Caspari’s “control group,” based on consistency with his own lab data.]
This correspondence shows that Muller reversed his position 3 years later, soon after the Evans publication. In that same 1947 correspondence with Stern, Muller also claimed that the mutational findings of Delta Uphoff, who was replicating the Caspari study, could not be supported because of “aberrantly low control group values,” only to reverse himself to support the LNT model. The present paper links Muller’s threshold rejection/LNT supporting actions to the timing of the debate with Evans concerning Evans’ use of the Caspari data to support the threshold model.
It is of historical significance that the duplicitous actions of Muller were rewarded, with his newly expressed reversed views becoming generally accepted (while his previously documented contrary views were hidden/remained private). At the same time, the marginalizing of the Caspari findings greatly impacted recommendations to support LNT by major advisory committees.
Paper 5 = “Muller mistakes: The linear no-threshold (LNT) dose response and US EPA’s cancer risk assessment policies and practices” This paper identifies the occurrence of *six major conceptual scientific errors of Hermann Muller and describes how these errors led to the creation of the linear no-threshold (LNT) dose-response — which historically continues to be used worldwide for cancer risk assessments for chemical carcinogens and ionizing radiation.
This paper demonstrates the significant role that Muller played in the environmental movement, affecting risk assessment policies and practices that are in force, even now, a half century following his death. This paper lends support to contemporary research that shows significant limitations of the LNT model for cancer risk assessment — thereby wasting billions of dollars of taxpayer money, because “false scientific conclusions” have been made from from “government-policy rules” rather than from accurate cutting-edge science. ☹
*MISTAKE # 1: Major misunderstanding of evolution: Muller’s Mistake proved disastrous for risk assessment and society
MISTAKE # 2: Muller failed to induce gene mutation and did not deserve the Nobel Prize
MISTAKE # 3: Background radiation is an important cause of evolution
MISTAKE # 4: The creation of the LNT single-hit model
MISTAKE # 5: Total dose (piggy bank theory) — not dose rate (repair model) — predicts risk
MISTAKE # 6: Genetic load can be an important factor in the risk of species extinction
Pharmacol Res 2021; 170: 105738
Chem-Biol Interact 2022; 368: 110204
Medicina del Lavoro 2023; 114(1): e2023007
Chem-Biol Interact 2023; 382: 110614
Chem-Biol Interact 2023; 383: 110653
Arch Toxicol 2023 Sep 4; doi: 10.1007/s00204-023-03566-5. PMID: 37665363