History of Linear No-Threshold LNT Model Episode Guide - HPS

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The History of the Linear No-Threshold (LNT) Model Episode Guide Health Physics Society (HPS) June, 2022 The Health Physics Society (HPS) created this series of videos to examine the history of the most controversial question in our field: the LNT model.

The views expressed in these videos do not necessarily represent official positions of the Health Physics Society.

Episode 1: Who Is Dr. Edward Calabrese?

This episode introduces you to Dr. Calabrese and his entry into the field of toxicology and risk assessment.

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Episode 2: LNT Beginnings—Extrapolation From ~100,000,000 x Background?

This episode explains why the LNT model arose and from whence. Surprisingly, it was not in the field of cancer risk assessment but as an attempt to explain the mechanism of evolution.

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Episode 3: Muller Creates a Revolution Hermann Muller claims to be the first to induce gene mutation using high exposures to x rays. Find out if he actually was the first and what role radiation exposures play in the theory of evolution.

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Episode 4: Muller: How Ambition Affects Science Was Muller's Nobel Prize research ever peer reviewed? How did Muller get his Nobel Prize research published in Science without showing any data? What was the evidence that he actually induced gene mutation? This segment takes a deep look into how all this came to be.

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Episode 5: The Big Challenge Muller's claim that he induced gene mutation runs into a number of roadblocks from some powerful and equally talented scientists. This episode explores the trials and challenges that Muller encountered trying to keep both his claims of being the first to induce gene mutation and his linear dose response concept alive.

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Episode 6: The Birth of the LNT Single-Hit Theory World War II is about to start in Europe while Muller is conducting his research. He specifically mentions a student's dissertation during his Noble Prize acceptance speech but neglects to acknowledge the serious limitations of the student's work.

Upon returning to the United States, he influences the Manhattan Project's research agenda in an attempt to resolve the limitations that are casting doubt upon his

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theories. What was learned in that research provided Muller with a way to save his gene mutation theory and LNT model claims.

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Episode 7: Pursuit to Be the First to Discover Gene Mutation This episode is set during the Manhattan Project era in the early 1940s, when the US government introduces new researchers and study designs to gain a deeper understanding of radiation's biological impact. Should a human risk assessment model be based on a mammalian model using mice or an insect model using fruit flies? What happened that threatened the scientific knowledge gained from studying 400,000 mice, leaving scientists to rely on fruit-fly studies for human risk assessment?

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Episode 8: "Fly in the Ointment" This episode is crucial to the historical foundations of the LNT model. During the Manhattan Project, Ernst Caspari's dose-rate study demonstrated a threshold response for gene mutation. It shocked the radiation genetics community and it stood in the path of the LNT model's acceptance. Learn what Muller and others did to discredit these new data. Were they successful?

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Episode 9: Why the First Human Risk Assessment Was Based on Flawed Fruit-Fly Research After the war, Caspari's conclusions regarding a threshold response for gene mutation continued to be challenged. Three new studies by Curt Stern and his graduate student, Delta Uphoff, attempted to save the one-hit theory or LNT model

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and to discredit Caspari's findings. These studies had many complications and were never published in peer-reviewed journals. Data from two chronic studies remain missing but were the basis for the United States adopting LNT. How did this happen?

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Episode 10: The Birth of LNT Activism Aboveground testing of nuclear weapons and the release of radioactive fallout in the United States and across the globe raised public concern. This presented an opportunity for the radiation genetics community to challenge the credibility of the radiation experts at the Atomic Energy Commission by suggesting the fallout would cause birth defects based on an LNT model. These challenges were significant and would lead to the US National Academy of Sciences (NAS) creating a series of six panels to advise the country on the concerns of nuclear energy and weapons, including a most crucial and visible genetics panel.

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Episode 11: Creation of the Biological Effects of Atomic Radiation (BEAR) I Committee This episode highlights the key role of the Rockefeller Foundation in providing funding to create the six panels that served on the NAS committee, especially the genetics panel. Providing the financial support has its privileges, but was it used in an objective and transparent way? How were members selected? The initial charge to the genetics panel may surprise you.

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Episode 12: Was There Scientific Misconduct Among the BEAR Genetics Committee Members?

Dr. Calabrese provides a concise summary and documents that support his conclusion that the BEAR genetics panel members are guilty of scientific misconduct. Nonetheless, the recommendations of this panel resulted in the most significant document affecting radiation and chemical cancer risk assessment in the entire history of the field. Yet today, it is facing important challenges, which are detailed in this episode.

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Episode 13: Is Lower Always Better?

This episode attempts to place the concept of cancer risk assessment in perspective and questions if continually trying to lower exposures to toxic substances is the best policy. The adoption of the precautionary principle drives public health and environmental principles and practices, which will be explored and challenged based on new scientific developments.

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Episode 14: Should the Genetics Panel Science Paper Be Retracted?

In 2015, Dr. Calabrese and others requested that the editor in chief retract the seminal publication of the NAS BEAR I Genetics Panel article in Science. Their discovery and conclusions were based on an alleged falsification and fabrication of the research record. A transparent record of their exchanges with the editor in chief is provided in the documents portion of this project, showing the basis for the editor in chief's decision not to retract the article. Would you agree with that decision after knowing more about the history and how this article helped to shape our existing regulations?

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Episode 15: Follow the Money Trail: "We Are Just All Conspirators Here Together" In this episode, we take you back in time, soon after the NAS BEAR I Genetics Panel report is released in the summer of 1956. Two of the panel members meet in Copenhagen, Denmark, during a large conference sponsored by the World Health Organization where one of them, James Neel, publicly confronts Hermann Muller about the need to include human data in genetics research. Neel's 10-year study of the Atomic Bomb Survivors found no genetic effects in that population, but these results were excluded from the deliberations by Muller's explicit powerful influence.

Tensions increased between these men, bitter conflicts surfaced, forcing other geneticists to choose sides in the conflict, and motives were uncovered.

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Episode 16: The Most Important Paper in Cancer Risk Assessment That Affects Policy in the US A new chair of the US NAS BEAR I Genetics Panel, George Beadle, comes up with a way to refocus the panel, and we are introduced to a new geneticist, Edward Lewis, who produces the most influential paper on risk assessment that has affected US policy. What was Beadle's message to the panel that refocused its efforts, and how did Lewis' paper become so influential?

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Episode 17: Studies With a Surprising Low-Dose Health Effect Dr. Calabrese provides a detailed and critical look at the influential Lewis paper in Science. He identifies newly found concerns and contradictions in Lewis' congressional testimony that question his objectivity and honesty.

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Episode 18: Ideology Trumps Science, Precautionary Principle Saves the LNT Modern risk assessment was forged by a compromise between those who believed that lower is always better and others who demanded proof. The compromise was the adoption of the Precautionary Principle, whose natural offspring is the LNT model. This is a policy that exists today, and it is largely due to the work of Lewis.

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Episode 19: Genetic Repair Acknowledged From 1930 onward, the belief that all gene mutation damage was not reparable, and that it was irreversible and cumulative, led to the LNT model. In 1958, William Russell proved this assumption wrong, shocking the radiation genetics world. How did the NAS BEAR II Genetics Panel incorporate this new finding without changing its beliefs in the LNT model?

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Episode 20: BEIR I Acknowledges Repair but Keeps LNT. Why? Dr. Calabrese describes how the BEAR Committee evolves into to the Biological Effects of Ionizing Radiation (BEIR) Committee. The US Environmental Protection Agency (EPA) assumed the oversight of the new BEIR Committee in 1970, and by 1972, the first BEIR Committee provided its recommendations, which acknowledged genetic repair but stayed with the LNT model for cancer risk assessment based on William Russell's research.

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Episode 21: BEIR I Mistake Revealed, LNT Challenged, Threshold Supported An amazing and unexpected story is told by Dr. Calabrese on how Dr. Paul Selby, colleague of William Russell, discovered a significant error in his control-group data that had been used to support the 1972 BEIR II Committee LNT recommendation.

The Department of Energy conducted an ethics investigation that compelled William Russell to correct the errors which, after correction, supported a threshold model.

The US EPA maintains its reliance on the LNT model for cancer risk assessment despite these corrections.

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Episode 22: Making Sense of History and a Path Forward by Dr. Calabrese Dr. Calabrese discusses how we can make sense of these historical events that many in our field may never have known or previously heard about, as we were taught a different history at our academic institutions. He provides answers to questions like: What impact has the linear no-threshold model had on society? What should we do next to strengthen the scientific basis of radiation protection moving forward?

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