Atomic Show #218 – Ed Calabrese – Researching Dose Response
Dr. Ed Calabrese is a professor of toxicology at the University of Massachusetts in Amherst, MA. For the past twenty years, he has focused his research on understanding the response of a variety of organisms and tissues to a variety of chemicals and radiation as doses vary from extremely low to quite high. He is one of the world’s leading experts in the general scientific field of dose response.
The first third of this interview focuses on Dr. Calabrese’s career turn from toxicology in general to dose response in particular as he relates the story of his initial interest in the subject as the result of a laboratory mistake as an undergraduate. That mistake turned into a series of experiments and his first published paper, but it also encouraged him to find a different career path that focused more on chemical toxicity for animals rather than plants.
The remaining part of the interview traces Dr. Calabrese’s more recent efforts to understand the roots of conventional wisdom in the field of dose response. In these efforts, Calabrese has returned to an early academic interest in studying history. For his first semester as a freshman in college, Ed Calabrese was a history major. After exposure to science courses he realized he was more interested in pursuing a scientific career than one in history, but he never lost the history gene — as he put it.
Aside: I recently spoke to a history professor at the University of Virginia, During our conversation, I inquired about the possibility of entering their graduate program. He was quite discouraging about career opportunities in the field. He was much more supportive of my interest when I made it clear that I was not looking for a new career, just new knowledge. End Aside.
The story that Dr. Calabrese has uncovered and meticulously researched though original source material like correspondence and academic papers is one that has had a major impact on all of our lives, even though it might have started with a rather innocuous beginning.
Hermann Muller, a Nobel Prize winning geneticist, had decided by the late 1920s that radiation harmed living organisms by damaging DNA in direct proportion to the amount of radiation achieved. For each “hit” of radiation there was a finite, greater that zero chance of a damaging event and no possibility of positive events that might result in an overall positive effect — at least that is what Muller thought and what he taught to a number of disciples.
Though he marginalized himself through his political activities and spent most of the 1930s running genetics research programs in the Soviet Union, Muller returned to the United States at the beginning of World War II. Despite his scientific publications and accomplishments, the best job he could find in the US was a job teaching at Amherst College, a small undergraduate school in the same town where Calabrese teaches today. He did some paid consulting work for researchers working on the Manhattan Project at the University of Rochester; he was one of the few scientists at the time who had any experience at all in testing radiation responses on living creatures.
The University of Rochester hosted two research efforts on radiation effects associated with the Manhattan Project, one involving more than 250,000 mice and one involving Drosophila — the fruit flies that Muller had been researching since his graduate days at Columbia before WWI.
The mouse research data was essentially lost and resulted in only two documents published more than a decade after the end of WWII, so, by default, the information extracted from the Drosophila experiments was the basis for post war radiation effects assumptions.
Dr. Calabrese has published detailed, peer-reviewed papers about how Muller’s determination of a linear response mechanism based on the “hit theory” became accepted, despite the discovery of inconvenient evidence by his own associates that falsified the theory and indicated that radiation effects on complex living organisms could not be explained by a straight line or even a straight line with a fudge factor like the dose and dose rate effectiveness factor applied to certain regions in the linear model.
During this interview, Calabrese shares the story he has uncovered and demonstrates that he not only has a gift for science and history, but he also has the gift of gab. My guess is that he is a popular lecturer at his university; I couldn’t believe that we had been talking so long once his story was finished.
I hope you enjoy this episode of the Atomic Show and share it widely.
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Muller was quite likely correct in stating that chronic dose rates of over 5000 mSv/year are bad for health and the dose-effect relationship may very well be linear beyond 5000 mSv/year even for completely chronic exposure. No doubt Dr. Calabrese will find some agreement here as well.
Muller was incorrect in his formulation, which is that 5000 mSv/year is in any way a low dose rate. It isn’t in any way relevant to nuclear power risk, even from old LWRs (for instance the biggest land contamination seen in Fukushima is about 700 mSv/year).
So, one might say Muller was correct but the statement was as irrelevant to nuclear radiation risks as it was correct.
We see hormetic effects up to about 2 mSv/day, so the worst affected areas in Fukushima are benign. Muller’s 14 mSv/day is well outside the hormetic range and well into the damaging range.
The problem with Muller is that he did not limit his push for a linear dose response assumption to the dose region where he actually performed testing. He also purposely ignored data and later covered his tracks with obfuscating papers produced by compatriots.
Please listen carefully to the interview. Dr. Calabrese is a polite man, but he clearly states that the overall situation that he uncovered could most generously be described as academic misconduct.
Thanks very much for this.
Perhaps in your future discussion with Dr. Calabrese you could ask him to comment on his opinion about extending animal hormesis observations to humans – and whether there is good evidence to support it (and if so, which evidence is most robust scientifically).
I have compiled a list of human studies that provide robust evidence for threshold dose-response or radiation hormesis in human studies, and it is available at: http://evidence-for-threshold-or-hormesis.blogspot.com/
Try using static pages, like normal Blogspot blogs do.
That is a rather impolite way of suggesting changes to someone else’s blog.
Exactly how would I comment there or use his “contact” links, when nothing displays?
Thanks, but last time I asked Dr. Calabrese, he declined to cite any specific epidemiological study.
Just wondering if he may have changed his outlook – and if not, why not.
That would be Ed Calabrese of the global warming denying Cato Institute, formerly with the tobacco causes cancer denying Tobacco Institute.
Science denial is nothing to be proud of.
Final warning. If you cannot contribute information to the discussion, you will no longer be welcome here.
Disappointingly, it appears Bob Applebaum is justified in being suspicious of Ed Calabrese’s objectivity.
Here find Dr. Calabrese in a recent seven minute monologue denying CO2 in climate change, and railing against the EPA in broad and highly misleading generalizations. http://www.cato.org/multimedia/media-highlights-radio/edward-j-calabreses-latest-commentary-we-need-new-earth-day-read
Science denial is nothing to be proud of.
You are misinformed. Despite the headline, that monologue was NOT from Dr. Calabrese. If you listened to my interview with him, you would recognize that he has a distinctive voice with an accent associated with people from the Boston area. The CATO institute’s Mike Rosen was the sole speaker on that 7 minute clip. He is supposedly reading from Dr. Calabrese’s work, but he interjects so many of his own opinions and reactions that it is impossible to determine which specific passages came from Calabrese’s paper. It does not even provide a specific reference so that a listener can go and check. Calabrese is a prolific author; I have copies of about 6 different papers that he has published within the last year and I am pretty sure that my collection is not complete.
I’m not sure why CATO decided to publish this report in a manner that makes it appear that it is Calabrese’s work and not a derivative of his work that has been altered enough to change the message completely.
Thank you for pointing it out, however. I suspect that Dr. Calabrese will be interested in knowing of its existence.
I located Dr. Calabrese’s original article — which was produced on request, but without being paid — for CATO on the occasion of Earth Day 2014.
It would be interesting to compare a straight reading of that column with the editorialized reading produced for the Mike Rosen show.
Yes, thank you for correcting me. Mike Rosen fooled me. Thank you also for linking the original commentary. A minor point on the original commentary is that captopril is not the active substance from a viper venom, but rather a synthetic mimic of one part of a viper venom molecule.
Googling on “Tobacco Institute Calabrese” I find a webpage of “Legacy Tobacco Documentation” which lists ‘Calabrese’ as ‘mentioned’. It’s not clear from this that Dr Edward Calabrese was ever arguing for the harmlessness of tobacco smoking. If he was, can you provide a relevant link?
Oh dear, that would be horrifying. I already contributed information, read my previous comment. Here’s some more information, it’s called Haeckel’s embryos.
Creationist Jonathon Wells used problems with Ernest Haeckel’s illustrations of the embryos of different species in order to convince other creationists, that evolution is a fraud.
The creationists loved it! Not that it has any relevance to the science of biology.
DeNiAr Calabrese is doing his version of Haeckel’s embryos.
Good to hear from you. I hope you will answer my question.
1. If we understand that LNT is accurate can you help me understand the comparative risks for a person who receives a does of 50 mSv over one year as compared to other common risks like walking across the street, or pumping gasoline into a car?
2. Do you agree with the concept of cumulative dose as it relates to a single person and then as it relates to a whole population of an area?
Thanks for your help in understanding.
By the way… Are Ernest Haeckel’s drawings of embryos still be used in current Biology text books? I have not looked at any of the current ones.
Pitiful yourself. Being totally unable to find an article from Calabrese that suits your agenda you invent ideas for him that he doesn’t hold. Can you please limit yourself to pointing out actual articles written by Dr Calabrese – or are you only an ad hominem nutcase?
Rod, thank you for a wonderful interview. A follow-up interview would be wonderful.
There is something missing but admirable in this interview. Dr. Calabrese’s work is not accepted by the National Academy of Sciences. He has trouble finding a publisher for both his science and history of science papers. So much so that he and a few others founded their own journal. What is missing is “bitterness”. How can you be rejected so long and not sound a little bit bitter? So, next time you two talk, please ask how he maintains a positive attitude.
Calabrese’s work is not accepted the same way a creationist’s work or a homeopath’s work is not accepted.
Have you a link in support of your assertions?
Oh, I see, those areas of science that touch on deep philosophical or political issues are limited to investigations that only support the current consensus. I am very glad to understand this and I really think we need to reject all science that has come down to us that rejected the then current consensus.
Frankly, I am not concerned with the labels you toss out, only with the truth of the assertions. Calabrese’s work might be rejected for the same reason as a Creation’s work is – perhaps Calabrese is quoting scripture and building his case from the authority of Scripture. I will listen and read carefully to see if this is the case. This was the reason the Supreme Court rejected Creationist teaching in schools.
Or perhaps like the homepath’s work – there are no double blind studies but rather general observations that are not supported by careful lines of research. I will listen and read carefully to see if this is the case.
On the other hand… if you are rejecting him ONLY because of his former associations, or only because of the conclusions he draws, you are free to refute his studies by doing some of your own.
Frankly, I am not convinced that the Atomic Bomb survivor studies have much real application to the issues we normally face with Radiation exposure. It is simple for a non-scientist to recognize that a very rapid one time event may have very different effects than a slow gradual one. I believe it is worth studying the slow gradual effects as well.
Dr. Calabrese provides an excellent explanation of his generally positive outlook in the speech he gave at McMaster University on the occasion of them honoring him as a pioneer in the field of hormesis.
I hope that it comes through in my communications that I am also quite happy and have a positive outlook for the future. The American people for whom I work have been exceedingly generous to me, even though I topped out as a Commander and even though I ended up folding my company and allowing our patent to go into the public domain. I have the luxury of being able to spend my time pulling threads and weaving together the story of how the elites have attempted to keep fission suppressed like a bunch of arrogant Lilliputians tried to keep Gulliver tied down.
People like EL and Lovins bother me, but I am quite confident that they are on the losing side. If they feel like they are winning, it is only because they suffer from “groupthink.” All of their friends might agree with their nonsense, but the other 6,930,900,000 people in the world think that humans would be far better off by taking advantage of the natural gift of a truly abundant, inexhaustible, emission free and potentially cheap energy source.
That hormesis (and by extension critiques of LNT) is like creationism cannot be substantiated. I hope the link below comes through. Nina Federoff has commented that hormetic responses are widespread in nature, and cites Calabrese. She was the president of the AAAS. If you look at the relevant bibliography around critics of LNT, including the French Academy of Scientists, you will see that the folks are published widely.
Now: some hormesis researchers are ignorant of climate science; my guess is vice versa. It would be great if proponents of the right ideas all lined up. But they don’t. Some proponents of Renewable Energy reject nuclear power based on radiophobia, and hysterical calls to evacuate whole hemispheres. Is that science? Some supporters of nuclear power, in fact nuclear engineers, repudiate climate change. The world is annoyingly complex and, this is my view obviously, right thinking in one area does not often carry over to other areas.
oh: since we’re on the topic of associating hormesis with creationism (when it actually makes sense in light of evolution), someone please explain to me how evolution and LNT go together? Even Caldicott goes positively florid about the diversity of life having evolved in a sea of radiation (I can quote chapter and verse). but then she makes the bogus distinction between natural and unnatural isotopes.
Except not all her distinctions are bogus, and its a mistake to mischaracterize them as such. See Comparing Japan’s Radiation Release to “Background Radiation” for one virulent anti-nuclear example (not Caldicott). The point is that the distinction between natural and unnatural isotopes is bogus only for external exposure, once something is inhaled or ingested things get complicated — welcome to biology. Its why the UNSCEAR, ICRP, and protection agencies have the concept of “committed dose”: once you’ve absorbed x mcg I-I31 or Cs-137 or Sr-90, how much exposure are you committed to — and where — over the biological lifetime of these isotopes? Once they’re inside you, you can’t just walk away.
Radon is a bit different in that as a noble gas it isn’t absorbed. But it decays to radioactive Polonium-218 which as a metal can accumulate on dust, and when inhaled can transfer to lung tissue, and again decay to radioactive Pb-214 and At-218 and so on.
In contrast to Kr-85 which decays in one shot to stable Rb-85. Here is one case where an unnatural isotope is far less hazardous than a seemingly similar natural one (Radon): “In terms of radiotoxicity, 440 Bq of Kr-85 is equivalent to 1 Bq of radon-222, without considering the rest of the radon decay chain.” See http://en.wikipedia.org/wiki/Krypton-85. Kr-85 has many beneficial industrial uses and is not considered highly hazardous. But it is radioactive so one does have to keep track of where it is in what amount and what’s going on.
And being a radioactive byproduct of nuclear fission, Kr-85 emissions may also be seen as an attack vector for those who would really not see nuclear power at all. Relative radiotoxicity be damned — LNT Lives!!!! 😮
hey ed: you misunderstood my point because of my shorthand. My fault. The point is dose and dose incorporates (so to speak) whether the radiation source is external or internal, hi/low LET (linear energy transfer) etc.
btw, the point in the interview about caspari’s results not being used until a mechanism was found to explain the results, what calabrese calls the huge burden of proof put on any questioning of LNT, makes me think of what biology would have looked like had darwin/wallace’s discovery of natural selection been put aside until the mechanisms had been discovered.
I’ll reply to my own lousy sentences. that should be “dose and dose rates incorporate….”
I’m going to have to listen to this podcast again because I can hardly believe what I’m hearing. There’s been a lot a research on scientific fraud recently pointing out lots of dubious papers, ‘junk’ papers etc. None of them were mainstream name scientists. This is the first time I’ve seen fraud from mainstream big name Western scientists. The issue is: Is a white lie that leads to a good outcome justified? I think most of us would answer yes. We all tell our children such lies. Here are scientists treating the public like children.
One of the big problems I have with “white lies” is that their value depends on the judgement of the liar. What if the outcome desired is not necessarily such a good one?
Some people have excused the conduct of Muller and his co-conspirators as justified because they were working to halt the nuclear weapons race and stop atmospheric testing of nuclear weapons.
They eventually succeeded in scaring people enough about radiation and the risk of “fallout” to gain the required political momentum to achieve the limited test ban treaty. Was that such a valuable outcome that it was worth imposing irrational fear of radiation?
I think that proposition can be effectively debated.
A lie can give both a short-term benefit and long-term harm. The real scandal is the number of scientists who continue to hold these beliefs today; indicating that it’s not science that matters to them but being “respectable”.
Despite all of the “suggestions” by Calabrese to the contrary, there does not seem to be an adequate basis to accept the Caspari and Stern (1947) results on a threshold dose, which have been described (see below) as preliminary, suggestive, and contradicted by later efforts to re-produce the study. I find Calabrese to be informative, and more or less accurate in his summaries of these papers (and much of the historical context), but unclear why he thinks the matter is settled, and why two subsequent studies (recommending the Caspari and Stern results NOT be accepted without further work and evidence) are not better highlighted and given merit in his charge that knowledgeable experts in the field “lied” about scientific conclusions and participated in a “coverup”?
The first study (Uphoff and Stern 1947) begins with the following: “It is not justified to accept without further studies the different outcome of the acute and chronic experiments as evidence for the action of different mechanisms in the effect of irradiation on mutations.”
The second report (Uphoff and Stern 1949) concludes with the following: “Viewing all experiments together, it appears that radiation at low dosages, administered at low intensity induces mutation in Drosophila sperm. There is no threshold below which radiation fails to induce mutations.”
The arguments made by Calabrese can be found in the following (and summarized in the atomic insights podcast above). Calabrese raises a number of “doubts” and uncertainties about the two subsequent studies, but I don’t find any of them to be “reasonable enough” to permit dismissal (or to claim satisfactory testing and resolving of uncertainties in the original result). If you haven’t independently confirmed the result in a subsequent study, it remains unconfirmed (and Muller has always stated that the Caspari and Stern result, which was high quality and compelling, needed to be replicated). Doubts and implications about subsequent results, in this instance, do not count as adequate testing or replication of the original result.
I also find Calabrese’s implications about some of the subsequent scientific work to be circumstantial (and not particularly compelling). Perhaps even misleading and inaccurate.
1) Calabrese suggests Uphoff was not up to the task, and “didn’t have it together as a student in this area.” She has an extensive record of subsequent scientific work, and this early research was overseen by the very capable and esteemed investigator in the original study. If Uphoff was the weak link, she’s not the only accountable person involved with the study.
2) Calabrese implies that bias may have been involved with the subsequent study results (specifically highlighted in the 1947 study by the authors). What Calabrese doesn’t mention is that this possibility is highlighted in the text specifically to alert readers that the study authors were aware of this possibility, and to rule it out. The next sentence reads “It is unlikely that this is the case,” and the reasons are given why.
3) Calabrese highlights that the authors promised a more detailed account of the study at a later time (and no such subsequent account was published). This is neither unusual, alarming, or relevant to the question of the validity of the follow-up studies, or whether the original result was adequately replicated or not. Unless Calabrese has statements to the contrary in the historiographic record (letters, correspondence, or other documentary evidence he has examined, which appears to be quite extensive), there is no reason to be suspicious of this. Any effort to make it so is reading into evidence that doesn’t exist (in this instance the non-evidence of a paper that appears to have never been written or published in the first place).
Honestly, I don’t find Muller to be in error in his 1946 Nobel Prize Lecture! Scientists who wish to be taken seriously (e.g., speaking on the occasion of receiving a Nobel Prize “for the discovery of the production of mutations by means of X-ray irradiation” clearly counts as this) don’t typically go out on a limb and challenge available science on the basis of a preliminary draft manuscript that has not yet been replicated or made available for peer review and evaluation by the larger scientific community. Science doesn’t work this way, and Muller appears to be correct to press the issue in correspondence on this draft study, and demand a higher caliber of evidence (prospective or independently verified) that can be brought to bear on the topic.
I am often amused by the way you continue to attempt to define science. Can you remind us all again what your qualifications and experience are?
In your lengthy, rather distorted comment, you made the following statement:
Science works by following the scientific method. A scientist who is in receipt of data from an experiment conducted by his own respected colleagues that contradicts a theory that — by his own admission — had only been tested in a limited range of doses would be violating that method when he says there is no escape from the conclusion that the theory works over all ranges of dose. Once again, here is the direct quote from Muller’s Nobel Prize acceptance speech.
An honest scientist would not have made such a definitive statement as “no escape from the conclusion” when he had contradictory data in hand, especially when that data did not come from left field, but from his own colleagues.
I strongly suspect there was a political reason why Muller, a guy who could only land a teaching job at Amherst College during WWII, received almost instantaneous rehabilitation from the “scientific community” by the decision to award him the Nobel Prize in 1946, just a little over a year after Hiroshima and Nagasaki. His 1927 work “proving” damage at all doses from radiation fitted numerous agendas and suddenly became important enough to merit the most notable prize in biology, which is, not surprisingly, chosen by a politically selected group of people.
It’s clear to me that you haven’t read the original Caspari and Stern (1947) study. The scientific context for the previous work was well established according to the study authors:
The Caspari and Stern (1947) paper looked at whether very low doses spread over “a considerable time” [21 days] held to this general rule (and observed result). They found that it did not. They excluded a number of factors to explain this result, and did not exclude others. They recommended that further work is needed before accepting the result of their study. That brings to three the number of papers directly related to this study (all overseen by at least one of the primary investigators) who specifically recommend NOT accepting (but further study) in order to exclude other lines of evidence. Muller’s review of the unpublished draft findings of his colleagues (which had not yet been made available to the scientific community for assessment and review), and recommendation to fund and advance further work on their research in private correspondence, is entirely consistent with the stated conclusions of these papers, the high caliber of evidence required by rigorous and confirmatory testing of unexpected scientific results, and his summary of established work in his Nobel Prize speech. Caspari and Stern (1947) conclude:
Subsequent testing for “1) low sensitivity to irradiation of aged sperm, 2) dependence of induced mutation frequency at low dosages on a time factor, and 3) errors of sampling that might have obscured a true difference between control and experimental rates” [summarized in Uphoff and Stern 1949] concluded that “… all three new tests gave an increased frequency of mutations in the treated sperm as opposed to the controls … There is no threshold below which radiation fails to induce mutations.”
Thanks for that … replication is one of the “main principles” of science and the experimental method, especially when the result is unexpected and contradicts available research. Was there something else you were hoping to show with your reference?
Caspari and Stern (1947) tested for total doses and dose rates significantly below this in Drosophila “aged” sperm (and specifically recommended results NOT be accepted until further testing was done excluding other factors that “may have depressed the mutation rate in our experiments”). What do you think Muller has misstated (equating to a “lie” and a “coverup” and charges of scientific misconduct as you and Calabrese appear to be claiming)? The coverup, as far as I can tell, is much of the evidence and careful scientific work made in each of these studies and reports (including the original Caspari and Stern findings, and the appropriate response of Muller to carefully consider this research, investigator comments on draft results, and sufficiently advance it in the future).
Did you listen to the interview? Dr. Calabrese provided a detailed account of the original source documents that he has uncovered and provided explanations of why he is so firmly convinced that the actions constituted misconduct.
You can also find a meticulous explanation in the following citation: Calabrese Edward J. How the US National Academy of Sciences misled the world community on cancer risk assessment: new findings challenge historical foundations of the linear dose response, Arch Toxicol (2013) 87:2063–2081
Yes I did (I even quoted from it). I also provided a source where Calabrese details his argument (in addition to the one you provide above). You are avoiding the issue.
None of the papers above suggest an adequate basis to accept the Caspari and Stern (1947) result, one has to only look at the evidence in the original paper and the statement of the original authors as clearly indicated. Caspari and Stern (1947) did not rule out age of sperm, and other factors, “… which may have depressed the mutation rate in our experiments.” Subsequent research did not verify the original result (or exclude previous uncertainties), but instead concluded to the contrary: “There is no threshold below which radiation fails to induce mutations.”
If Calabrese is “firmly convinced” (as you put it) to the contrary, he is doing so in error and has not read these papers closely enough (or perhaps has read too much into them). His claim that Muller erred in concealing this equivocal data (then only in draft form) is misleading and specious. In fact, it appears he did entirely the opposite, and did much to advance it’s cause (recommending funding and subsequent research to confirm early draft results and address uncertainties acknowledged by the original investigators). Calabrese hasn’t made his case, and you haven’t responded to the substantive details of this debate?
Muller provided the statement in Caspari’s conclusion that questioned the data he had collected. Muller sought funding for follow-up studies so he would have an input in the way results were interpreted. You have bought into the coverup and narrative hook, line, and sinker because it supports your existing agenda.
Remember, Calabrese dug into the history BECAUSE he could not explain why his carefully conducted experiments over a forty year career as a professional toxicologist did not match the LNT presumption.
This conclusion is a key feature of the analysis (not a supplementary observation added post facto and irrelevant to the final result). It’s there because the evidence supports it (not because a third party engaged in scientific deception put it there). Your comment makes no sense.
First of all, I must apologize. I misremembered what I had read. Muller did not add a statement to Caspari’s conclusion. He apparently asked for a key statement to be removed.
This conclusion is a key feature of the analysis (not a supplementary observation added post facto and irrelevant to the final result). It’s there because the evidence supports it (not because a third party engaged in scientific deception put it there). Your comment makes no sense.
Agreed that the conclusion in a scientific paper is a key feature of the analysis. I also agree that the conclusion should not be revised post facto by a third party who is engaged in scientific deception to promote a pre-existing agenda.
That is why the following paragraph is so important to the story.
(Bold emphasis added, italics in original)
(Source: Calabrese Edward J., Key Studies Used to Support Cancer Risk Assessment Questioned, Environmental and Molecular Mutagenesis, June 2011 page 3.)
PS – If anyone would like to read the full paper cited above, please contact me via email.
The original AEC version of the paper contains all of the statements I quoted above, including the following: “Before accepting the dependence on the time factor of radiation effects on mutation rate at low doses, it will be necessary to exclude all of the factors discussed above which may have depressed the mutation rate in our experiments.”
Whether the sentence you highlight was left in or taken out of the study does not change the methodological observation that key dependent variables were not excluded from the study and that further research is recommended by the authors (in the original AEC account) before accepting the result.
The subsequent published version also contains the following:
I don’t see where the subsequent published account precludes the possibility for a threshold dose, should fully adequate studies refine the methodology and exclude major dependent variables. Subsequent research did not confirm this result, but instead found that “There is no threshold below which radiation fails to induce mutations.”
Muller appears to have been correct to advance this research to a high standard before reporting on it prior to publication. His speech before the Nobel Committee is entirely consistent with established science to the dose and dose rates he specifies. And his appearance in the acknowledgements page suggests to me that he did not stand in the way of making this research available to a wider audience, but actually helped to facilitate it. Hardly what one expects from someone with ulterior motives (where publication of results in a timely manner and in a high quality scientific journal counts as “firmly convincing” evidence of scientific misconduct).
There is a lot that is misleading, and even inaccurate, in Calabrese’s account. He hasn’t provided a window onto the past (but mainly into his own assumptions and faulty readings of the historical and documentary record). Like yourself, I highly encourage people to read Calabrese (and more importantly the original source material on which his assumptions and implications draw upon). Short of that, you can easily look at key sections of the primary studies I have highlighted above. There is little doubt that the Caspari and Stern results (in preliminary draft or published form) was of very high quality and was not considered “settled science” at the time (as clearly indicated by the primary investigators of the study). Presenting it as such, so as to falsely accuse (without supporting evidence) another scientist of lying and scientific misconduct, is dishonest and a distortion of the historical record. If others find Calabrese’s argument compelling, it’s certainly not for lack of better evidence to the contrary.
One thing that is missing from your interpretation of this history is that — in 1946 — it was Muller’s “hit theory” and linear dose response that were the unproven, radically-different interpretations of the health effects of low dose radiation.
People who had been observing the way that radiation affected humans that worked with X-rays and radioactive materials like radium had decided — after more that a quarter of a century of observation — that radiation was something that had positive overall effects at low doses but that above a certain limit, the effects could be quite harmful.
Responsible bodies of professionals, including medical doctors, established limits with a conservative safety factor of 10, with the limits being 10% of the observed dose that caused any visible negative effects. The visible negative effect used as the basis for the safety limit was a minor skin erythema – akin to a very minor burn.
Muller and his grant givers — mainly the Rockefeller Foundation and certain decision makers on the Manhattan Project — had a different goal in mind. They determined that they would use experiments that found almost invisible genetic effects on fruit flies using high dose radiation to propose a radical new theory that every “hit” from an ionizing event caused some damage even if it was invisible. Using their eugenics theories about the importance of the human “gene pool” they postulated that the delayed or probabilistic effects of radiation were something that should frighten everyone.
Muller got awarded a reputation rehabilitating, credibility-enhancing Nobel Prize in 1946, just over a year after the atomic bombs were dropped. He continued pressing his radical theory based on the fruit fly work that he and his friends continued to do with Rockefeller Foundation and AEC grants at schools with substantial influence from similar funding sources.
In 1956, the Biological Effects of Atomic Radiation (BEAR) genetics committee was stacked with geneticists who all subscribed to the radical, fruit fly-based, hit theory. That committee was chaired by Warren Weaver of the Rockefeller Foundation. Weaver was a trustee and was THE person who approved foundation grants in genetics.
Calabrese has discovered correspondence among some members of the committee indicating that they KNEW they were exaggerating the effects and dangers of low dose radiation but they knew that position would result in greater support for their scientific field of genetics research.
I’m away from my desktop right now, but I will find the specific quotes and provide them in a couple of days.
There is little historical doubt that the LNT was designed purposely by people who understood exactly what they were doing. They replaced the safety-providing, but easily met, threshold model with one that enabled regulators to continue ratcheting down the allowable dose in the name of never being safe enough. Their incorrect, imposed model said that there was “no safe dose,” only doses with acceptable risk — with “acceptable” being a loosely defined word subject to continuous revision.
One more thing. Though Muller’s fruit fly experiments ONLY revealed the fact that high doses of X-rays delivered at a high dose rate could cause measurable mutations, the proponents of the “hit theory” somehow convinced enough important people that the results gave some insight into human cancer origins. Considering what we now know about what we don’t know with regard to how cancers originate and develop, acceptance of that extension of the fruit fly data seems almost inconceivable.
by Edward J. Calabrese, Ph.D. Provided via email to blog owner
The problem with Muller’s Nobel Lecture was the near absolutism of his dose response statements. There were other published papers that did not support linearity which he failed to cite as well as important weaknesses and limitations in references he used to support linearity. There was also the newly completed study of Caspari that assessed responses at the lowest dose rate yet tested. In my opinion, Muller misled the scientific community at the Nobel Lecture by denying the possibility of a threshold and strongly advocating the need to switch to a linear perspective, especially when he was aware of the Caspari findings. As noted in my writings and comments on the matter, Muller could have indicated that while he supported a linear perspective, the issue was still unresolved and required further experimentation. This is exactly what he was advocating in private but not in public. You cannot have it both ways. There was no justification for his duplicity on the matter.
Muller would subsequently go on to write in several papers that Caspari’s research yielded a threshold because the control group had falsely high values, restating the original claim of Stern. Yet, the published literature, Muller’s own published articles and his private correspondence on this precise point were used to support Caspari. These points are documented in detail in my publications, including Muller’s quotes. The statements by Muller that challenged the Caspari controls contradict his data, publications, and letters. Given his unique knowledge of this technical issue (i.e., control group mutation rate), it is very unlikely that Muller’s incorrect statements about Caspari’s control were errors but rather deliberate deceptions. Muller was using these deceptions to discredit Caspari’s work in order to support linearity as well as to protect his own reputation. In these instances I believe that evidence indicates he was dishonest.
When the initial challenge of the Caspari work concerning the control group failed, Stern tried to find ways to prevent its acceptance. The discussion of the Caspari and Stern paper is a scholarly attempt to create a research straw man. That is, they demanded to know why the findings of Caspari differed from those of Spencer and Stern for the acute findings before the Caspari findings should be accepted. As pointed out in my papers, there were so many differences between the two studies (i.e., Spencer and Caspari) it would not be possible to determine why they differed. No attempt was ever made to resolve the issue. Given the differences between the two studies this is not surprising. The perplexing “Discussion” was an attempt by Stern to preserve the reputation of Caspari while denying influence to his work while keeping the LNT model alive. Furthermore, I reported numerous limitations in the Spencer research that called into question its validity for the low dose effects. These limitations were either missed by Stern and Muller or deliberately ignored.
The continuing goal of Stern was to prevent the Caspari findings from being accepted. This is seen in his personal correspondence which referred to this issue as the “Caspari problem”. It is also seen in correspondence with Dr. Demerec, the head of genetics at Cold Spring Harbor, who asked Caspari what could be done to “save the (one) hit model”. Stern did attempt his version of saving the hit model with his multiple deceptive acts in which he “managed” the research and publication of Delta Uphoff’s attempts to replicate the findings of Caspari.
The story of Muller, Stern and the National Academy of Sciences, BEAR I Genetics Panel and the acceptance of LNT is important because it is based on deceptions at the highest level of science and scientific organization leadership. The story is documented in numerous peer-reviewed journals of highest quality.
I appreciated the opportunity to discuss my discoveries and the reasons for my judgments in the conversation with Rod Adams. I respect the fact that others may have different opinions or interpretations after making their own detailed search of the available information.
At the risk of continuing to be accused of conspiracy thinking, I’d like to add that both Curt Stern and M. Demerec were well supported by the Rockefeller Foundation.
How hard would it have been for the grantors to tell recipients that “whatever else you do, maintain pressure to implement linear no threshold dose assumption for radiation?”
How many researchers do you know who are immune to funding pressure?
This summarizes the argument very nicely. For the charge of deception or duplicity (repeated in the comments above), the claims by Muller in his Nobel Speech have to be seen (or made) to be absolute, or “near” absolute (as the case may be). Unequivocal as Calabrese describes elsewhere (pg. 3). The entire argument, of several papers (and an abundance of circumstantial claims) boil down to one paragraph and the tone or attribute (and claimed evidentiary basis) of this statement.
Where Calabrese sees absolutism, I see a clearly stated and challengeable (i.e., testable) scientific claim. One that is open to question, and can be scrutinized and advanced with future work. “We believe” is highly qualified, and the specific statement makes an evidentiary claim for dose levels to 400 r and dose rates of 0.01 r minute (which is a significant level above the doses and dose rates tested in a “first of a kind experiment” by Spencer and Stern and Caspari and Stern at 25 r and 50 r and presented in preliminary and incomplete draft form). His statement does not preclude the possibility that future work will examine dose levels and dose rates below the level indicated in his speech so as to indicate whether, as he suggests, there is “no escape” from the general rule. Believing in general rules is not a shortcoming of scientists at the time, especially those engaged in careful experimental methods to support their findings on a clearly specified basis (and, as it turns out, to extend their findings into areas previously untested as clearly indicated in private correspondence). A colloquialism may be sloppy, but it is hardly an indictable offense.
Calabrese recommends an alternative: “Muller could have indicated that while he supported a linear perspective, the issue was still unresolved and required further experimentation.” An unusually vague and indecisive statement, it is worth adding, particularly on the occasion of receiving a Nobel Prize for your achievements in knowledge and advancing science on the production of mutations. I don’t see why another alternative is not an option. That someone else who has empirically tested these results, and found a different result at low doses or low dose rates, indicate such in their results: “we have examined evidence for linearity in mutation rates below 400 r and 0.01 r minute in Drosophila melanogaster, and found they don’t hold to the general pattern as described by Muller (1946). After careful consideration of the available literature and our own research, here are the reasons why and our recommendations for how research in this area can be further advanced and developed in the future.”
I doubt many specialists in the field found Muller’s statements as unchallengeable or not worthy of follow up research and extension. As Weber spoke about decades ago, “Every scientific fulfillment raises new questions; it asks to be surpassed and outdated.” I find a lot of support for regular questioning of results and tracking down and exploring multiple lines of evidence and argumentation in the speech and correspondence examined by Calabrese. In other words, normal science. The fact that Muller is the main catalyst for some of this (advancing initial results for low doses and low dose rates that conflict with his own findings) speaks clearly to his ethics and professional conduct to advance science of a high quality in his field.
Muller’s banquet speech is also very interesting on some of these points.
I agree, and I appreciate Calabrese’s willingness to further discuss his work in this setting, in numerous detailed articles in the scientific and historical literature, and elsewhere. A area of inquiry that is static is not generating new insights, and Calabrese has done much to advance public interest, raise new questions, and stimulate new research in this area. Muller writes about “fearlessness” in his banquet speech. A commitment to method and critical inquiry that Weber (by comparison) spoke about many decades ago, and that Calabrese (similarly) highlights as a central tenant to the vocation and ethics of science.
I appreciate your willingness to revise your view of Calabrese’s contributions to advancing public interest, raising new questions and stimulating new research.
Your concluding paragraph at 9:06 PM on 2014/08/21 was quite refreshing compared to your conclusion at 3:36 PM on 2014/08/19 – to wit:
Calabrese is not the only one who has been studying this history and Muller is not the only scientist who pushed for the linear, no-threshold dose response assumption based on the “hit theory” at a time when there were grave concerns within the scientific community about the way that atomic energy had been introduced to most of the world.
In the numerous decades since Muller’s time, when Rockefeller Foundation-sponsored biologists/geneticists insisted that molecular behavior was the basis for most observed attributes of living organisms, scientists have learned a great deal more about the way that cells, tissues, organs and whole bodies function as systems. (The book linked above received at least one critical review by a scientist involved in the research. My point is that the funding influenced the direction of the research, and that the Rockefeller Foundation — and other major players in the economic establishment — had a major economic reason to seek to increase fear of radiation.)
People like Feinendegen, Pollycove, and Neumann have identified and described defenses like “scavenging of toxins;—molecular repair, especially of DNA;—removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses,—- followed by replacement of lost elements.” (From abstract of a Chapter in Medical Radiology: Radiation Oncology Springer-Verlag, Berlin 2012 titled “Hormesis by Low Dose Radiation Effects: Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection”)
However, we are still regulating radiation based on the linear assumption. Worse, we are still treated to vociferous actions by anti-radiation, antinuclear energy activists who point to that dated linear model as proven science that allows them to instill irrational fear that produces measurable harm to real human beings because linearity says there “is no safe dose.”
I do not always express myself scientifically or unemotionally because I am not a scientist, and I am sometimes driven by the emotion of anger at the harm that has been done by suppressing the gift of atomic energy. That suppression has been based partly on understandable fear of the unknown, but mainly out of additional irrational fear that has been stoked with money provided by elites who already have access to all of the energy they need.
Some of the key supporters of the fear promotion campaign are motivated to limit access to atomic energy supplies so that they can keep prices of competitive energy sources as high as the market will bear for all of the rest of us.
Thanks for acknowledging this, but I don’t consider this much of a modification of my views. I strongly agree with Calabrese that it is important to adhere to independent ethics and rigorous methods in science, but I still disagree with his historical argument and it’s misleading basis (along the lines I have suggested in the rest of my comment).
All great advances in science (human understanding in general) benefit from sustained debate and critical engagement, being challenged in our views, and coming up with stronger arguments to defend, extend, and better document our understandings. Rather than see my comments as a sustained criticism to debunk someone’s work, this is very far from the case, I think it would be more appropriate to view such active and sustained discussions as working towards making such arguments stronger and more effective (regardless of the outcome of these debates).
All in all, I don’t think claims of scientific misconduct and “lying” (deception or cover up) are particularly effective in making the strongest and most evidence based argument for calling into question received results, or moving research in the direction of new insights and advances in science. It definitely helps in getting headlines (and Calabrese has had his fair share on this basis), but when looking closely at the evidence points to the opposite conclusion (as I believe it does here), it’s the substance of the argument that prevails at the end of the day (especially among folks who are regularly engaged with these issues, and who are familiar with these long standing historical debates, institutional developments, scientific foundations, and historical figures).
Like Calabrese, I appreciate the opportunity to have this discussion, and to look more closely at this primary historical source material and to interrogate it for insights into science, ethics, and new advances at the time in the frontiers of evolution and genetics and the newly emerging science of molecular biology (which Muller did a great deal to help to establish and advance). Calabrese spoke eloquently about respect for different opinions and interpretations in his comment, a view I share. This doesn’t mean we don’t defend our views (as Calabrese has done) and incorporate new insights from our debate and discussions (less certain of “absolutes” as the case may be, and more informed about critical perspectives and broader intellectual and scientific debates in the future).
HOW ABOUT TELLING US A BIT ABOUT YOURSELF?
Although constantly accused of being a “troll”, I have seen nothing from you in respect to you countering that claim by stating your “interests” in offering your arguments. A simple bio about yourself might help those such as myself draw conclusions about your motivation and credibility.
The blog owner knows my identity and background (and that’s all I’m willing to disclose on the site). Unless the policies of the site change, you’re going to have to be satisfied with that. Very broadly, I have advanced degrees in the social sciences, have taught at the University level, worked as a consultant in climate and environmental public policy, and am not currently working in any energy related field (although I don’t preclude that possibility in the future).
If you’re curious why I don’t disclose my identity on the site … give it a while, you might even see the reason below in a minute or two.
Its no secret you aren’t liked here. But are you implying some sort of threat posed by individuals here? It seems to be SOP for some here to make a big deal out of those of us that post anonymously. For myself, I think I have exposed more about myself than most here, despite my online moniker. Frankly, just because someone posts using an actual name doesn’t mean the name is offered honestly, or even that the person is who they say they are. Nor does the use of one’s name guarantee credibility. I’m not interested in WHO you are. WHAT you are is my interest. Can you state clearly why you cannot offer more information? Are you actually afraid of some here? For myself, I kinda regret providing the information I have, due to my stated opinions regarding Israel’s murderous and illegal treatment of the Palestinians.
Its not that I fear posters here, rather that I fear the long arm of the Israeli hasbara machine, which is way too quick to label any criticism of Israel as anti-semitic. Careers have been ruined due to criticisms of Israel.
But I don’t understand your trepidation, when you are merely arguing energy issues. What are you afraid of? It really does damage your credibility when you disclose so little about yourself.
Careers have been ruined due to criticisms of Israel.
True. Good thing I no longer have a career to worry about. I do worry sometimes that there might be other ramifications of my inability to jump on the “defend Israel at all costs, even that of personal integrity or morality” bandwagon. Oh well. Some risks must simply be accepted.
“defend Israel at all costs, even that of personal integrity or morality”
I see you fully understand the high cost of standing on Israel’s side. I wish that loss was not passed on to our nation through the despicable actions of our “leaders”. I cringe every time one of these characterless posturing puppets talks about our “shared values” with Israel, such as that crone HRC just did. Much like NE, the prevalent narrative about our relationship with Israel is a complete fabrication, carefully nurtured to coerce the population into accepting an alliance with a country committing grave crimes and human rights abuses against an entire people. Everything we purport ourselves to be is repudiated by our support of Israel’s actions and policies concerning the Palestinian people.
Here, a jewish man who survived the holocaust is quoted, and describes it far better than I can…
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