Document 10K8XG8manOJ5xYx66Yq9GOad

To: Jackson, Ryan[jackson.ryan@epa.gov] From: Edward Calabrese Sent: Thur 11/2/2017 9:39:31 AM Subject: new paper Academic Quest.-I .pdf Ryan: This should be a good read for you....please share with your colleagues. Ed 17cv1906 Sierra Club v. EPA ED_001523_00002554-00001 Societal Threats from Ideologically Driven Science Edward J. Calabrese Academic Questions Association of Scholars Acad. Quest. DOI 10.1007/s12129-017-9660-6 ACADEMIC QUESTIONS Darkness in Anthropology: A Conversation with Napoleon Chagnon English Compositionism as Fraud and Failure Student Writing: Strategies to Reverse Ongoing Decline MichadJ. Caber and Heather Harper Does Online Education Rest on a Mistake? In Defense of a Liberal Education: Criticizing the Critical John Attard Critically Thinking about Critical Thinking Robert Weissberg The Fail-Proof Student Janice fiamengo What Does Bawdoin Teach? A Dialogue between Wood and Klingenstein Peter Wood and Tom CJingenst&n Modern Madness Review Essay of MM, Modernity, Madness, by Liah Greenfeld College: Who Profits? Review Essay of Is College Worth It? by William J. Bennett and David Wilezol Poetry by David J. Rothman; Review by Michael Toscano Springer 12 3 17cv1906 Sierra Club v. EPA ED_001523_00002555-00001 Your article is protected by copyright and all rights are held exclusively by Springer Science+Business Media, LLC. This e-offprint is for personal use only and shall not be self archived in electronic repositories. If you wish to self-archive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com". 17cv1906 Sierra Club v. EPA ED_001523_00002555-00002 Author'speraonaloepy Acad. Quest DOI 10.1007/S12129-017-9660-6 UNSETTLED SCIENCE--------------------------------------------------------- e CrossMark Societal Threats from Ideologically Driven Science Edward J. Calabrese # SpringerScience+BusinessMedia, LLC 2017 I remember clearly my first week in graduate school in the entomology department at the University of Massachusetts Amherst in 1971. One of my fellow graduate students had just reported on a potentially important finding relating to a type of circadian rhythm, the twenty-four-hour cycle of biological processes that many organismsexhibit. The key observation occurred between 1:00 a.m. and 4:00 am. He was going to confirm his findings the following day. For reasons that were not shared, my advisor had some doubts about this "major" discovery and decided to be present at the lab between 1:00 a.m. and 4:00 am., along with the department chair (in retrospect, a bad sign). When the student arrived at the lab the next day, my advisor asked whether the significant findings had been confirmed. The student acted very excited, claiming to have confirmed the result, and showed the data. The only problem was that during those ear I y morning hours the student had not been in the lab, where my advisor and chair sat waiting and waiting to see him. The novel discovery proved to be a hoax, and in less than an hour the student had cleared out his office and was never to be seen again. As for me, I got his office and an eye-opening education on honesty in science, I ife in general, and the consequences of unethical behavior. I have never bear too preoccupied with issues of honesty over the years because everyone I have worked with has seemed to be truthful about thei r science. Plus, we have tended to work in very close teems with multiple people checking what everyone else was doing. There have been many disagreements on all aspects of studies and data interpretation, but no chai lenges on the honesty issue. I have real Wi 11 am Broad and N icholas Wade's 1982 book Betrayers of the Truth, al I about Edward J. Calabrese is professor of toxicology in the Department of Environmental Health Sciencesat the Universityof MassachusettsAmherst, Amherst, MA 01002; edwardc@schoolph.umass.edu. Springer Published online: 30 October 2017 17cv1906 Sierra Club v. EPA ED_001523_00002555-00003 Author'speraonaloepy Calabrese fraud and deceit in science, but its stories and scenes seem to belong to a different world from mine. Most of the individuals caught in fraud appear to be in a mad race for some type of academic glory, whereas my life in science has been far more quiet, sedate, and mostly fun. Muller and the History of Dose-Response The issue of honesty and deceit in science would reenter my life exactly forty years after my first week in graduate school. It all started very quietly. I had written a substantial review paper on the history of the I inear dose response, how it came to be accepted and used by regulatory agencies. The dose-response refers to the means by which drugs and other chemicals and physical agents, like radiation, affect biological systemsand how this may be influenced by both the total amount and the rate of agent administered. As has long been my custom, I often send a copy of the draft manuscript to a group of knowledgeable friendly critics prior to journal submission. On this occasion one of the friendly critics, a very experienced expert in the area of genotoxicology, wrote that I had not explained the role of the Nobel laureate Hermann J. Muller and his significance in this area as deeply and insightfully as it probably needed to be covered. He did not clai m to be an expert on M u I ler, who was awarded the 1946 Nobel Prize in Physiology or Medici nefor hisdiscoveryof the productionof mutations by means of X-ray irradiation, but simply had a strong hunch that I wasmissing an important part of the story. Based on my respect for this person's past insights and help, this was more than enough for me to put the paper on hold to learn al I about Muller's life and accomplishments.! obtained numerous articles by Muller, multiple articles about him, a substantial biography, and his December 12, 1946, Nobel Lecture. I even found a 1957 lecture he gave to other Nobel winners posted on the web. It was interesting to hear his voice, see his mannerisms, and follow his train of thought. I started with Muller's earliest papersand followed his career until the very end. Then I read and studied his biography and Nobel Lecture. This method was expansive, since it also forced me to look at the I i ves of other leading scientists of his era who worked with him in one way or another in the area of radiation genetics. This study led me to the previously unexplored world of the history of science, especially the history of radiation, mutation, cancer, and public health. From reading multiple dissertations I came to appreciate the incredible depth and insight that such historiansof science offer, and I was upset that I had never Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00004 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science really taken the time to learn about and from these efforts. So much had I missed! Itwasabit like peeling an onion. The story of Mui ler and his era became progressively more interesting and offered much insight into the scientific process. Little did my friendly critic know that his comment had reawakened in me a latent gene for the unrelenting search for historical truth. In fact, in my freshman year of college I had started out as a history major and then got so inspired by my zoology course that I switched to biology. Now it seemed that I was coming ful I circle. I became particularly fascinated with parts of Muller's life because he was a professor at Amherst College (1940-1945), located in the town where I live, somethingl did not know. I tracked down the house he lived in, which wasjusta short walk to the college and about 1.5 mi les from my home. I learned much about his work on the Manhattan Project with the famous geneticists Curt Stern and Ernst Caspari, and its impact on dose-response. My critic was correct: Muller was very importantin the history of dose-responseand risk assessment. In fact, I learned that Muller created the term "proportionality rule" in 1930 to describe the I inear dose-response and played a key supportive role in the initial creation of the LNT single-hit model in the mid-1930s. The LNT dose-response model assumes that the response is di rectly proportional to dose down to a single molecule. In marked control, the threshold dose-response assumes that there is a safe level of exposure as long as the exposure is below the threshold dose. Manhattan Project and Dose-Response While doing this historical digging, I noticed a potential disparity between what Muller stated in his Nobel Lecture and what I had come to leam about key findings in the mutation study of Caspari and Stern, on which Muller was a paid consultant. In his Nobel Lecture, Muller was quite emphatic that the threshold dose-response model was not scientifically credible and needed to be replaced by the LNT model for risk assessment. I found this very curious, since in August 1946 Caspari finished his major study on the effects of chronic ionizing radiation on mutations in Drosophila and found a threshold response. The genetic damage component of the Manhattan Project was conducted at the University of Rochester under the direction of Stern. It represented the most significant research ever in this area. It had a very strong research team, improved quality control, large-scale studies, and excel lent technical support, among other factors. While Stern, Muller, Caspari, and the rest of the Rochester team Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00005 Author'speraonaloepy Calabrese were expecting that Caspari would confirm their belief in Iinearity, he didn't. In fact, just the opposite happened. H is data demonstrated a threshold dose-response. This was the proverbial fly in the ointment. Had Caspari's data supported a linear dose-response, it would have provided a major boost for the goal of replacing the threshold model with LNT held by Muller, Stern, and most others in the radiation genetics community. This made me wonder whether Mui ler had seen the Caspari findings prior to giving the Nobel Lecture. I figured that he probably had not seen them since he never could otherwise have made the staterrent that he did about the lack of possibility of there being a threshold. Here was the best study to date, one in which Mui ler was an active and influential consultant and knew the quality of the people and research effort. How could he ignore it, or worsestill, dismiss it? I needed to find out what Muller knew and when he came to know it. I contacted some historiansof science and they had no insights on this question, so I ended up purchasingal I the communication I could identify between M ul ler and all the Stern team members. Late one afternoon I received between six hundred and eight hundred pages of correspondence and related material. I reviewedall the material thateveningand found theso-calledsmokinggun. I learned that Stern had sent Muller the manuscript that he and Caspari had prepared on the study on November 6, 1946, after having alerted Muller in September to expect it. Muller acknowledged receipt of theCaspari manuscript and offered preliminary commentson it in a November 12,1946, letter to Stern. In the letter Mulleracknowledgedthat thesefindingsseriouslychallengedthe LNT model, that the study needed to be rep I icated, that Stern needed to get the funds to do this, and that Caspari was a very competent researcher and that Mui ler could not dismiss the study due to inexperienceor other reasons. Thus I knew for the fi rst time that Mui ler had seen theCaspari findingsone month prior to giving his Nobel Lecture and had an excellent sense of its significant implications,and that it could not be dismissed but needed to be repeated. ThisreA/informationtroubledme.lputmyselfinMuller 'spcsitiondflwereabout to receive the Nobel Prize, could I ever state that there was no possibility that the thresholdmodelwasbiologicallyplausibleafter seeingtheCasparistudyfinding^PIn fact, his recommendation fora major repl cation directly contradicted this comment. The repl cation was not trivial and would takea year and require the help of multiple technicals, plus oneasexperienoed as Caspari orStem to di red it. I felt that the best I could do on this matter, if I were in Muller's situation, would be to acknowledge that the shape of the dose-response in the low dose zone remained a viable research question and needed to be resolved. I might have stated that whi Ie I bel eve that the Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00006 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science lineardcee-responseismcst likelythecorrect view,this neededtobe assessedfurther. And yet, while Mui ler acted I ike a scientist in his communications with Stem, in his publ icdemeanorhewasdeceitfulandvery ideological --everythingascientistshould not be. To act this way during the most significant moment in his professional life revealed important character traits in Mui ler, including those of dishonesty, risk taking, manipulation, and arrogance. I held out hope that he may have had new insights that led him to criticize the study and that would provide an explanation for his rejection of Caspari's threshold conclusion. However, a detailed seven-page letter to Stern dated January 14,1947, reaffirmed the November 12,1946, letter. With this now in hand I came to the firm but unsettling conclusion that Muiler was deliberately deceptive in his Nobel Lecture and used this opportunity to achieve a longdreamed-of goal to have LNT as the default model for cancer risk assessment. This was his chance and, apparently, the ends justified the means--again, a rational izat ion that scientists should never accept. In 2012, I published this Muller Nobel Lecture story in the toxicological literature.1 It quickly generated a series of criticisms, mostly ad hom inem attacks on my characterand researchachievements. These were in part related to the fact that Mui ler could not defend himself along with other earl ier defenders of the LNT model.These critics may not have been aware that Muller had himself criticized the work of a deceased scientist, Lewis J. Stadler, who had challenged Muller's gene mutation interpretations from 1931 until his death in 1954 and likewise could not respond to Muller's criticisms in 1956. Dose-Response and Deception The deception issue would not end with Muller's Nobel Lecture, but would serve as the tip of even more troubling revelations. My initial follow-up was to make a detai led evaluation of the Manhattan Project's genetics/radiation research aid see what I could learn from it. With respect to the Caspari research, I learned that Stem at first refused to accept the val idity of these findings, claiming that the only re^on that Caspari observed a threshold was due to a control group that had aberrantly high mutation rates that led to the threshold rather than linearity. To his credit, Caspari dug into the literature and presented convincing evidence that the control group was not aberrant but normal. To his credit, Stern backed 'Edward J. Calabrese, "Muller's Nobel Prize Lecture: When Ideology Prevai led over Science," Toxicological Sciences 126, no. 1 (2012): 1^t; "Muller's Nobel Lectureon Dose-Responsefor Ionizing Radiation: Ideology or Science?' Archivesof Toxicology85, no. 12 (2011): 1495-98; and "Key Studies Used to Support Cancer Risk Assessment Questioned," Environmentaland Molecular Mutagenesis52, no. 8 (2011): 595-606. Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00007 Authofsperaonalcopy Calabrese down--that is, the Caspari control was now considered normal. Did this mean that Stern gave up the effort to minimize the influence of the Caspari findings? Not in the least--but how did he do this? It was subtle and it took both Stem and Caspari to do it, the latter oddly cooperating with efforts to undermine his own study, perhaps due to his sensing of what was important to Stem, his influential supervisor. First, a detai led reading of the paper revealed that essentially the entire discussion centered on why their data should not be accepted until it could be learned why this study showed a threshold, while a companion acute study lead by Warren Spenser completed a year before showed a I inear dose-response. In many ways this was a false argument, since the two studies had more than twenty-five methodological differences aid the issue could never have been practically resolved. They had to know this. Second, the Caspari study was superior to the Spenser study in multiple ways: it was performed second, used better equipment and facilities, and improved temperature controls, among other features. In addition, much was learned during the Spenser study that was transferable to Caspari's efforts. Further, a detailed review of the Spenser study revealed a long list of problems that Stem, Muller, aid others apparently never detected. All of these issues have now been documented, aid seme are serious. The bottom line is that Stern and Muller did not want the Caspari paper to see the light of day, and if it did, they wanted to seriously compromise its impact. This view is actually reflected in Muller's January 14, 1947, letter to Stem. The story gets even more intriguing as we now consider the attempt to replicate Caspari's findings. In fact, it gets much worse, as the historical record shows to what lengths Stern and Mui ler and others under thei r influence, or spel I, would go to twist the truth to advance their ideology. Sometimes this resulted in direct lies, other times in data manipulation, censoring, and other forms of obfuscation and misleading behavior. In the first repl cation study paper, for example, Stern and Delta Uphoff, a master's student at the University of Rochester, conducted that her control was aberrantly low and that this led to data that could not be properly interpreted. This was based on extensive written communicationwith Muller. Mullerhada massiveemountofcontrolmutationdatainstudiesdealingwiththeaforementioned disputewith Lewis Stadler on the nature of gene mutations. In multiple letters that I obtained, Muller unequivocally supported the Caspari control as normal and the Uphoff control as aberrant. Th is write-up was sent to the Atomic Energy Commission by Stern and was classified. When Stern published the Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00008 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science findings a year later, he and Uphoff neglected to inform the scientific community that one year earlier the data that they were now publishing had been uninterpretable (their own written characterization) and that her control group was aberrant based on the data in the publ shed I i terature and in Muller's massive database. A second example involved Muller writing in the scientific literature that the study by Caspari that challenged LNT should not have credibility because of its aberrantly high control group values. Of course, he had the data to support the Caspari findings and had done so in writing in a series of letters with Stern. Despite the duplicity of Muller on this issue, he was never challenged by Stern or Caspari--even though they knew that Muller had directly contradicted his letters to Stern and his publications. The National Academy of Sciencesand LNT It would be bad enough if the story stopped here, but it didn't. It became even worse. The next noteworthy developments occurred when the National Academy of Sciences (NAS) created its Biological Effects of Atomic Radiation (BEAR) I Committee in 1955 and announced its seminal recommendation to switch to linearity in June 1956. This was actually the big ideological payoff for all the past efforts to ensure the success of the LNT. It represented collusion, I should say, inbreeding at the highest levels: the Rockefeller Foundation funded the BEAR committee; Detlev Bronk, president of the NAS, was also president of the Rockefeller Institute for Medical Sciences (later Rockefeller University); and BronkchosethechairmanoftheGeneticsPanel fromtheRockefel lerFoundation. Transcripts reveal that the chair was enticing the panelists with more Rockefeller grant money. The goal was to get the scientific community and the public to go I inear, simple as that. For this to happen, data had to be censored. In addition, the Genetics Panel had to show that it was in close agreement on the scientific basis of radiation-induced mutation risks, which their individual estimates were designed to show. However, the panel was so spl it in their scientific conclusions of radiation-induoed mutation risksthat if they were shared with the public, the policy recommendationsof the panel would have no cred i bi I i ty----or so the panel members, such as Jim Crow, a University of Wisconsin professor of genetics, strongly believed and wrote about in correspondence with Chairman Warren Weaver. <0 Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00009 Author'speraonaloepy Calabrese My Conci usions and T hei r Consequences The findings to support my conclusions have been published in consider able detail2 They reveal that the Genetics Panel misrepresented the research record in the journal Science on several key matters, all of which were needed to get their policy views accepted. The panel voted on these matters, including deciding not to show their data and not to provide any written justification for their conclusions. Thankfully, these highly prestigious scientists preserved their correspondence reports and notes, which permitted me to discover their deceptions--both as individuals and, more surprising, as an NAS committee--and eventually piece this story together. The 1956 NAS BEAR I Gaieties Panel report and its LNT recommendations would become the most significant document in the seventy-year history of cancer risk assessment. The acceptance of their guidance is the historical basis of why the U.S. and numerous other countries adopted the LNT. As the twig is bent so grows the tree. Two years ago Jerry Cuttier, an active researcher on LNT and radiation, wrote to Marcia McNutt, editor-in-chief of Science, to request that the 1956 article of the BEAR I Genetics Panel be retracted due to my documentation of its deliterate misrepresentation of the scientific record and the major and continuing historical significance of this paper.3 The situation was complicated from the start, since McNutt was also a final st to become the next president of the NAS, and her name was already posted on the NAS website as such. In such a situation, McNutt should have recused herself from deciding on this issue. Since the then-outgoing NAS president Ralph J. Cicerone was strongly disputing my challenging papers at the time, McNutt's conflict of interest with deciding upon the retraction request and her desire to become the next NAS president is obvious. Yet despite her finalist status--and she did become NAS president--McNutt did not recuse herself. Her decision was to deny the request. (The appendix to this article contains three key e-mai I exchanges on this issue.) It was also disturbing that no apparent set of checks and balances existed within Science's organization to ensure proper oversight on such matters. The story of LNT, therefore, is one of leading scientists, from the time of Muller's Nobel Lecture in 1946 to today, being driven by ideology and/or self-interest. Thisshouldnotbewhoweare asscientists.norwhatweshouldaccept. 2Edward J. Calabrese, "On the Originsof the LinearNo-Threshold(LNT) Dogma by Meansof Untruths, Artful Dodgesand Blind Faith," EnvironmentalResearch142 (2015): 432-42. 3Edward J. Calabrese, "LNTgate: HowScientificMisconductby the U.S. NAS Led to GovernmentsAdopting LNT for Cancer Risk Assessment," Envi ronmentalResearch 148 (2016): 535-46. Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00010 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science APPENDIX Marcia McNutt, e-mail message to Jerry Cuttier, August 11,2015 Subject: Science Paper, Genetic Effectsof Atomic Radiation; Evidenceof Scientific Misconduct Dear Dr. Cuttier: We considered careful ly your concerns about the controversy with respect to the I i near no-threshold (LNT) dcee-response model for assessing the risk of radiationinduced cancer. You have requested that Science retract a 1956 paper that takes a positiononthisissue.Standardpractioein Scienceandotherjoumalswouldbenotto consider the retraction of an article more than just a few years old except in extraordinary rcumstances.New discoveries are constantly advancing the frontiers of science, and unless we had some statute of limitations on retractions, we would be constantly retracting old articles after the field has moved on. We can imagine certain exceptions in cases of papers that are still highly influential. In considering this specific request to Science, we asked the following questions: (i) Isthe1956 Science paper trustworthy? Weconcludedthat we cannot produce the information we need to answer this question 60 years post publ cation to the standards that would be required to consider a formal retraction. The authors are no longer I iving. We do not even have a record of the Science editorial standards of that era, much less a review jacket for that paper. This case is so old we would never be able to reconstruct the evidence from al I parties invol ved in our editorial decision. (i i) If the paper is not trustworthy, is the matter a problem of scientific qua! ity or scientific integrity? Because we cannot answer (i), we cannot answer (ii). However, I wi 11 note that many of the concerns raised in the Calabrese paper would fall under the classification of science quality, not science integrity. They would not be grounds for retraction of a paper 60 years after the fact. (iii) DoesthisScience paper still have the "pervasive influence" claimed in the article by Calabrese? We consulted an independent expert whose positions indicate that s/he has no extreme positions on this matter, one way or another. H is/herconsideredv iew isthatthe1956 Science paperwasoneofhundredsof papers over the past half century on this broad topic, and certainly the use of the LNT model by almost all the regulatory agencies, world wide, is now based ona lot more than the NRC report and Dr. Muller'swork. For example, Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00011 Author'speraonaloepy Calabrese if you takea lookattheseriesof NRC "BEIR" [Biological Effects of Ionizing Radiation]4 reports, inthe more recent ones there isnoparticular emphasison Mui ler's work, with the arguments now more based on endpoints that more directly relate to radiation-induced cancer. Based on this analysis, we do not see any reason to consider revising our policy for this paper. Science considers this case closed and will not reconsider the decision. Dr. Marcia K. McNutt Editor-in-Chief,Science family of journals American Association for the Advancement of Science 1200 New York Avenue N.W. Washington, D.C. 20005 Edward A. Calabrese, e-mail message to Marcia McNutt, August 19, 2015 Subject: NAS 1956 Paper Retraction Dear Dr. McNutt: I read your e-mail letter to D r. Cuttier, reject i ng h is request (and others) to retract the NAS BEAR I, Committee Genetics Panel published in Science in June, 1956, due to its multiple incidentsof seriousfalsificationand fabrication. I have careful ly studied your five reasons for this decision. Wh i Ie I commend you for your d i rectness and transparency i n shari ng the basis of the decision, I have concluded that your analysis of the issue was faulty on each of the five reasons (see attached or below) aid contradicted by the factual record in a number of cases. While I know you wrote that the decision was "final," I hope that you wi 11 be open to the new analysis aid that you will reconsider this issue. Sincerely, Edward J. Calabrese, Ph. D. Department of Environmental Health Sciences School of Public Health and Health Sciences Un i versi ty of Massachusetts Amherst, MA 01003 4See, for example, National Research Counci I of the National Academies, Health Effects of Exposure to Low Leveisof lonizingRadiation:BEIRVII Phase2 (Washington,DC: The National AcademiesPress, 2006). Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00012 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science Issue#1: Is the situation extraordinarygiven the 60 year time lag? The situation is extraordinary because the LNT model for cancer risk assessment continues to dominate all regulatory agencies, affects clinical treatments, environmental regulations, clean-up cosls, medical treatment strategies, all needlessly wasting massive resources. In fact, it is widely believed that the recommendations by the NAS BEAR I Committee, Genetics F&nel to switch from threshold to the LNT model was the most significant event in the history of risk assessment. It is also extraordinary because substantial contemporary toxicological discoveries have revealed serious failings with the LNT model with findings more consistent with the threshold and hormesis models. Issue#2: New discoveriesareconstantly advancing the frontiersof science: Contrary to your statement, my letterdidnotchallengeanolderpaper(i.e., NAS Genetics Panel Science paper, 1956) based on new discoveries such as DNA repai r, adaptive responses, apoptosis, and hormesis that could create non-l inear dose-responses. It is, however, challenging this paper because it falsified and fabricated the research record and it continues to affect, in significant ways, the beliefs and actions of regulatory agencies, influential governmental and non governmental organizations, educational institutions, materials and practices, and leaders in the risk assessment field--all without their knowledge that the Genetics Panel paper in Science is now recognized as being based on fraud and deception. Issue #3: Is the Science paper trustworthy? You claim that this is not knowable because: new standards for evaluation; because the authorsare not alive; and the 1950s recordkeeping is poor and without knowledge of how this paper was reviewed. The issues of falsification and fabrication are historical ly founded and have long been addressed by professional standards in the sciences and their journals. My published articles have shown that the research record was deliberately altered in the Science paper by the Genetics Panel and I possess and cited the text of letters and memos documenting the scientific misconduct and the reasons why the falsif ication/fabrication was done. The fact that none of the Panel members are al i ve is adequately compensated by the factual record which is substantive and unequivocal, with high internal and external consistency. It is not significant to the present case whether the Genetics Panel paper in Science received a peer review, as most reports by high level advisory committees are usually stand-alone and not subject Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00013 Author'spersonaloepy Calabrese to standard peer-review processes, as are papers of individual scientists. Nonetheless, all papers need integrity and honest reporting. My published papers have shown that the BEAR I Genetics Panel failed in this regard in multiple and critical ways, affecting key conclusions and acceptance of their findings by the scientific community, governmental agencies, and the general public. Issue#4: Is the problem one of scientific quality or integrity? You do not provide any specific evidence, but offer a general statement that many examples cited in the Calabrese (2015) paper concerned scientific qua! ity rather than integrity. The fact that there were important issues raised about scientific quality (e.g., the obvious description of Jim Crow's research method) does not detract from the integrity issue. The key point is that it was becauseofthe poor data quality that the Panel decided to cover up their scientific weaknesses (i.e., poor quality) so that their goal of aswitchto LNT could occur. The central issue is that the F^nel was not honest and altered the research record to promote this goal. I suspect that if the data qual ity were good, they would not have "needed" to I ieand deceive. However, their LNT goal was more important than truth. Issue#5: The continuing "pervasive influence" of the 1956 paper: Youcitean unnamed knowledgeableindependentconsultantwho told you that the LNT is now based on many more papers than the NRC report and Mui ler's work. Fi rst, the Calabrese (2015) paper never states that the LNT was based on Muller's research. Itstatesthat Muller used his influence to promoteacceptance of the LNT by being dishonest in his spoken and written words, all of which were documented. The paper traced the initial acceptance of the LNT to the work of Curt Stern and his students and these were highly criticized in the Calabrese paper. It was the Stern papers that the BEAR I Genetics Panel based their beliefs upon and cited in subsequent Congressional testimony (1957). You stated that the more recent BEIR reports do not base their recommendations on Mui ler's work and focus now on cancer. In multiple papers I show that within one year of BEAR I, that major advisory groups had generalized the Genetics Panel recommendation from genetic risk to cancer risk assessment. We have also documented that the U.S. EPA in the late 1970s specifical ly rel ied on the BEAR Genetics F&nei 1956 recommendation when it adopted LNT, showing clearly that your assertions are incorrect. More specifically, Roy Albert, Chair of theEPACarcinogenGroup,inhis1994paperin CriticalRevia/vsinToxicology, has reportedthatEPAadoptedtheLNTmodel oftheAtomicEnergyComm ission(who Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00014 Author'speraonaloepy Societal Threats from IdeologicallyDriven Science adopted the BEAR I, Genetics F^nel report) that had beenappl ied to esti mating risk for fallout from atomic weapon tests. Restated that it was clear, simple, and easily understood and was plausible based on the I inearity of the mutation response (see BEAR I) withi n the framework of target theory. He then noted that "any difference between chemical carcinogens and ionizing radiation could be waved aside as both cause genetic damage." Thus, the BEAR I report in Science served as the critical foundation for the current EPA LNT cancer risk assessment. A vast number of published papers with experimental data contradict the LNT model. Infact,themega-mouse(24,000mice)studyoftheFDAtoestimate the shape of the dcee-response in the low dose zone showed a striking hormetic dose-response for bladder cancer as emphasized by a 14-member expert panel of theSocietyofToxicologyDetailed Japanese studies with DDT showed clear hormetic dose-responses for carcinogenicity. Numerous whole animal cancer bioassays with ionizing radiation show reduced cancer risks and life extension at low doses in multiple models. These and numerous other findings, along with the above conceptual developments (DNA repair, adaptive response, etc.) all happened after BEAR I. If anything, the LNT model decision should have been reversed except for the ideological grip that has long enveloped this field. I nsummary, this response add resseseach issue that your letter used tosupport your rejection of the request to retract the NAS 1956 Science paper due to research misconduct. The evidence presented here provides an objective basis for you to reconsider the proposal to retract the 1956 NAS Genetics Panel Science paper. The evidence is convincing that misconduct did occur, and the issue is too important to continue to ignore. Science hasaprofessional and moral responsibi I i ty to correct this continuing scientific deceit. Marcia McNutt, e-mail message to Edward A. Calabrese, August 19, 2015 Subject: NAS 1956 Paper Retraction Dr. Calabrese: I happened to be at a large gathering of distinguished scientists today, most of whom have published in Science, and I asked them the fol lowing question: "Do you believe it would be permissiblefor Science to retractyour paper (or any other researcher's paper) based on evidence put forth by a third party claiming Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00015 Author'speraonaloepy Calabrese scientific misconduct, without allowing you the opportunity to rebut the claims?' There was not a person who bel ieved that it would be appropriateor ethical for Science to retract a paper under those ci rcumstances. Examples that were given by thisdistinguishedgroup for why due process needed to be given to both sides before action is taken inducted: & Possibility of conflict of interest on the part of the third party; & Situations in which so-called "evidenoe of misconduct'" was taken out of context aid either misinterpreted or purposely misrepresented; & Limited knowledgeof third parties as to the entire story; e.g., believing that a result was based on X when it was based on Y. You obviously answer "yes" to the question above, otherwise you would not continue to press this issue, but you are the only person I haveencounteredso far of that opinion. Science will not be changing its policy. Please respect that the matter is closed. Sincerely, Marcia McNutt Editor-in-Chief,Science family of journals American Association for the Advancement of Science 1200 New York Avenue N.W. Washington, D.C. 20005 Springer 17cv1906 Sierra Club v. EPA ED_001523_00002555-00016