Hermann J Muller revolutionized radiation genetics, received the Nobel Prize for producing gene mutations, and helped to create the linear non-threshold (LNT), the EPA’s default model for cancer risk assessment. Could mistakes he made haunt today’s most dominant global regulatory strategy?
The linear non-threshold (LNT) model operates globally, independent of political and economic philosophy and cultural history. It is a regulatory strategy born out of the leadership, passion, persistence, accomplishments, mistakes, and questionable ethics of one person, Hermann J Muller, who helped to create the linear non-threshold (LNT) single-hit cancer risk assessment model while inspiring Rachel Carson who, in turn, ignited the environmental chemical revolution.
Even though Muller died in 1967, some three years before the creation of the US Environmental Protection Agency (EPA), his reach is long, demonstrating how one person has truly made a difference.
New historical evidence has created a counter-revolution revealing that Muller made fundamental mistakes in the science and manipulated the system to promote his ideas and reputation, which led him to achieve his LNT-based ideological goals.
The litany of serious Muller-led LNT mistakes, ideological-driven biases, and massive self-interest reveals how sometimes the most brilliant amongst their peers can make errors and yet fail to acknowledge what others can see.
Muller First Error
The first and most significant error occurred due to a hasty generalization. He noted that since fruit flies show very few visible mutations (i.e., only 400 out of 20 million), their genome must be highly stable. Muller failed to consider any alternative hypothesis, such as the apparent stability that may result from efficient genetic damage repair. This limited perspective led him to conclude that induced mutations could not be repaired but would either be selected for or eliminated by “natural selection.” This mistake led him to conclude that all induced gene mutations from ionizing radiation are cumulative, irreversible, and irreparable. This initial mistake set a cascade of other errors in motion. While Muller would publish his perspective in 1929, he developed this belief as a graduate student 15 years earlier, expressing this view in an insulting debate in the literature with William Castle, the esteemed Harvard geneticist, who argued that the genome was highly unstable. [1]
Muller’s Proof?
Muller used massive dose rates of X-rays to induce transgenerational phenotypic changes, claiming these were gene mutations but without proof. Muller published his paper in Science, not showing any data. When he finally published the data, it was in a non-peer-reviewed Conference Proceedings, lacking a discussion of his methods. When challenged to prove his gene mutation claim Muller used a reverse mutation approach but was unsuccessful.
The Cascade Continues
During this time, Muller convinced several physicists to create an LNT model based on target theory, excluding genetic damage repair. This became the LNT single-hit model that was passed along to regulatory agencies such as EPA in the 1970s.
As Muller’s gene mutation position was losing standing, Muller pulled a rabbit out of the proverbial hat and kept his dream of the big prize and LNT alive. He helped direct several highly publicized supportive but flawed radiation mutational studies that were never published in the peer-reviewed literature. Science publishing a one-page summary note of the studies from the Manhattan Project. These unpublished studies were used by the National Academy of Sciences (NAS) to support the switch from a threshold to a linear model.
It is now late 1955. The first meeting of the NAS Biological Effects of Atomic Radiation (BEAR) I Genetics Panel is about to occur. A 10-year study report, led by panel member James Neel, on the genetic effects of the atomic bombs on the offspring of survivors was completed, and the findings did not support the LNT model. Muller humiliated Dr. Neel in front of the Panel, getting the panel to
- give Dr. Neel’s report no scientific standing
- Inexplicably convincing the Panel to default back to the unpublished and missing Manhattan Project fruit fly data for their recommendation.
When the Panel report was published in Science (June 1956) with the LNT recommendation, it deliberately misrepresented the scientific record (to enhance the acceptance of their policy positions). After the falsified report was published, the panel was challenged to provide scientific documentation. They refused, with Muller claiming he did not want to share the “dirty laundry” with the public. The documentation, or lack thereof, was never shared.
A Bureaucratic Response Also Cascades
The report of the NAS Panel supporting a switch to the LNT resulted in significant criticism that the policies of the US Atomic Energy Commission (AEC) were adversely affecting the health of the public (e.g., more congenital disabilities and cancers). With Muller’s visible disputes with the AEC in mind, President Eisenhower distanced himself from the AEC, transferring radiation risk assessment from the AEC to the new Federal Radiation Council (FRC). It was an ominous sea change for radiation risk assessment. The FRC immediately, with its advisory committee comprised of LNT supporting radiation geneticists, became committed to the LNT model. This LNT-oriented FRC would become incorporated into the EPA when President Nixon reorganized environmental management, stealthily integrating LNT, in its new home in the EPA, much like a virus in a receptive host, becoming quickly established.
The chemical environmental revolution, initiated by Rachel Carson’s popularized concerns, was also taking place. The EPA adopted the same linear non-threshold approach for chemical carcinogens based upon the identical rationale - since both radiation and chemicals induce mutations, the LNT would work just as well for both.
A Takeaway
The current carcinogen regulatory posture, unchanged over the last 50 years, was the product of Muller’s leadership. Yet, the process of developing and accepting the LNT was based upon a series of mistakes, ideological biases, self-interest, distortions of the scientific record, and a win-at-any-cost attitude. We also find that the agency Congress has granted great authority, the EPA, never looked back to understand the origins of LNT. Why should they? They inherited Muller’s LNT “gene” through the actions of Presidents Eisenhower and Nixon. The EPA can’t really help itself; after all, it’s in their genes.
[1] He ignored the guidance of his advisor Thomas Hunt Morgan to tone down his language.
