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Ed Calabrese


March 2, 2022

Ep 353: Ed Calabrese - Toxicologist, University of Massachusetts, Amherst
00:00 / 01:04
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Host [00:00:59] So, Ed, welcome to the Titans of Nuclear again. It's such a pleasure to have the opportunity to speak with you since the last time, and you look very good today.

Ed Calabrese [00:01:09] Well, thank you very much. A rare compliment.

Host [00:01:14] It's my pleasure. Okay, so you had a very fantastic career so far. I think for the sake of the audience, let's start at the beginning. What was your early introduction into the nuclear industry?

Ed Calabrese [00:01:27] To the nuclear industry? Well, I'd have to say that it was getting thrown into the area of dose response and risk assessment, because I really came up in the nuclear industry as a non-nuclear person. I'm really trained as a chemical toxicologist and was always struck with how dominant the radiation risk assessment was within environmental health. It was extremely dominant and there was so much controversy associated with it. In my younger days, so to speak, I pretty much was one of these guys who bought the party line from the the regulatory agencies. I wrote a lot of books back in the early days, almost a book a year, maybe 10 or 12 books. If you go back and look at everything I wrote, I was an LNT guy all the way. I mean, I believed it like it was religion and taught it like it was religion. And did that for 25 years; it wasn't like... I was kind of a rookie at it. I was on many National Academy of Sciences committees, I recommended adoption of all linear dose responses into federal and state organizations, and essentially was part of the evolving, what you might say, establishment.

Ed Calabrese [00:02:59] And then something happened to me. I must have fallen off my bicycle without wearing a helmet or something like this and suffered some sort of brain damage and began to look at life quite a bit differently. But on a serious venture, I began to become very interested in how cells... Not responded to just showing toxicity effects, I became very interested in how cells protected themselves. And I wanted to see this within a broader evolutionary framework. And the more that I dug into it, the more I realized that cells and whole organisms... We're not really just victims, and that we take insults, that we actually protect ourselves. And that survivors have found ways, that's us, and all the other creatures that are living on Earth today, the survivors have found ways to adapt genetically and epigenetically and otherwise to respond to a whole host of insults, whether they're coming from the chemical world or they're coming from the physical world or psychological stresses, all kinds of stresses, and that we're very resilient. And that resiliency is often best seen at the low dose end.

Ed Calabrese [00:04:27] And when I began to look more fully at this from a laboratory area as well, I found that cells responded differently at low doses as compared to high doses, and the toxicology had made a fundamental error. Risk assessment had made a fundamental error. That you could draw a straight line from an extremely high dose down to, essentially, no dose and claim that the response was directly proportional to the dosage when in fact there was very different biology going on at low doses. And so when you pushed an organism at low dose, it pushed back, and it pushed back not oftentimes just to push back and to make things equal, but overcompensated. And I began to see that, wow, toxic chemicals, mutagens and other kinds of things, radiation, at low doses sometimes were actually producing effects that were making the organism more resilient, stronger. You could call those beneficial effects. And in fact, they were not really predictable by the high dose zone. The high doses were actually blowing away all these adaptive responses which were being upregulated at very low doses. I came to the conclusion that all that which I had believed before, all my 25 years of indoctrination of my students at the University of Massachusetts, that I owe them a great apology, owed myself a great apology. That I, in fact, had been sucked into a perspective that I have now come to the realization was fundamentally incorrect and that it had a lot of implications for regulatory activities in the radiation world, in the chemical world, but also in the way that we live our lives. And the kinds of things that we should do is not to avoid stress, but we actually have to use our intelligence for how to creatively use stress to enhance our resilience, to protect ourselves, and to actually live healthier, better, longer lives. And how that really should become part of a central principle of public health in schools of public health. And I can tell you that it's not. The current situation is overwhelmed by a dogma that is driven by the only thing that's good is lowering your stress to everything in a linear sort of a fashion. And in the end, it's counterproductive, and regulatory policy is based on it. And they're not serving the public; they waste money. And not only not serving the public, it actually hurts the public and hurts their health. It's a very interesting situation. And I haven't seen any real leadership by any regulatory agency anywhere on the face of the earth that is capable of actually seeing what is very obvious within the scientific literature.

Host [00:07:35] Now, I'd like you to walk us through the through line of your research career, because I know that you did a lot of your early work around the hormesis theory and you really centered your work around LNC. So for the audience, that's the linear non threshold for dose response model for radiation induced leukemia. This is something that has a very long research history. If you could just walk us through how this got cemented into how we make decisions for the policymakers and how the educational community has developed theories around it.

Ed Calabrese [00:08:14] Well, the issue of linear dose response, it actually was not the first, it was an outsider itself. The very first dose response model that was adopted by regulatory agencies really across the globe was the threshold dose response. It was adopted and really led by a group of brainy British pharmacologists back in the 1910s and 1920s. Very smart guys. They developed this and it was very influential in terms of regulatory agencies at the time and they applied it universally. They applied it to chemicals, they applied it to drugs, they applied it to agricultural agents and they applied it to radiation as well. In working especially with regards to occupational exposure to radiation, especially in hospitals, but also to patients as well, any biological changes that they would observe, they felt fit within a a threshold model which meant that you could be exposed to a certain level of chemical or radiation below a dangerous threshold. If you exceeded the threshold, then you had to be concerned with potential toxicities that would occur. And eventually, as you go beyond the threshold, toxicities would become much more evident. But with radiation or even things like lead and mercury and so forth, it was believed that there was a a safe level below which if you didn't exceed that threshold level, you didn't really have anything to worry about.

Ed Calabrese [00:10:01] And then what happened was this fellow by the name of Hermann Muller, who won the Nobel Prize in 1946 for being the first to be able to induce gene mutation in a biological organism, which he did in fruit flies, and he did that and reported it anyways for the first time formally in 1927. And Muller, his work wasn't tied into LNT, he was really tied into trying to come up with what he thought was perhaps the underlying mechanism for biological evolution. And he knew that you had to have a way to induce mutation in genes for this to actually happen. They had tried, he and his group from probably 1910 or 1911, until he did it in 1926, 1927, to try to induce gene mutation in fruit flies. And they threw everything except the kitchen sink at the fruit fly. Every every harmful chemical, mercury, formaldehyde, lead, you name it, they threw at it. They even tried various types of ionizing radiation added in different forms and fashions. They were still unable to do it. Muller modified his fruit fly model, made it more susceptible and made the results more specifically identifiable with mutations. And with that, he was able to then, wow, observe for the first time that he could induce what he believed were gene mutations in his fruit flies. And so this became a very notable major discovery. It was really a race to do this. And Muller knew that if he was the first, and he was, then he would probably get the Nobel Prize, which he did get 19 years later. So he was going for it; it had nothing to do with risk assessment, it had everything to do with evolution at the time.

Ed Calabrese [00:12:07] As it turns out, he did not do a good job on his dose response aspects of his study. And so he got a couple of students a year or two after he makes his big discovery, and they do a dose response study with four doses at very high doses of radiation, and they show a linear dose response. And based upon these two student studies, he drew the conclusion that the dose response was fundamentally linear. He called it a proportionality rule, rather; they had not introduced the term linearity at that point. It would be in a few years, within a decade later. But he made the decision that the dose response for radiation induced mutation was linear down to a single ionization. That was the big key with him. He was challenging the belief, the status quo at the time, because at that point, the medical community was saying, "No, the dose response for radiation effects is a threshold effect." And Muller comes in and says, "No, you're wrong. The radiation affecting the genome is linear and it has a lot of implications on birth defects, on cancer, on other kinds of things." And Muller started the revolution. It was Muller.

Ed Calabrese [00:13:36] Now, I would have to tell you that lost in all this conversation is the fact that Muller gave a whopping dose to his fruit flies. And just so that the audience can understand this, the dose that Muller gave to his fruit flies was actually 95 million times greater than background. I mean, 95 million. It's a phenomenally high dose that he gave to his fruit flies. It has nothing to do with any reality that we experience or that any aspect of life in any normal sense that exists is exposed to on this earth. And yet within this setting, he gave an exposure that was unbelievably high, and it really in many ways should have been disqualifying to having any relevance at all to the world that we live in. You have to start dealing with something that's a lot lower and a lot more realistic. And as it turns out, as a result of Muller doing that sort of thing, it raised questions by critics. And some of the critics thought that what Muller probably did was... He's claiming he induced gene mutation, right? Muller introduced the term, what did he call them? Point mutations. In the 1927 science article he called it a plant mutation. Now, he didn't know anything about nucleotides and DNA structure and all that sort of thing that we deal with today, but he believed that he was inducing micro mutations, not these big gross things that people had done in the past and get chromosomes to rearrange and re stick together. Muller was saying, "No, no, I have used these micro we call them point mutations. "But other people felt that, well, maybe this wasn't right. Maybe he was confusing an observation of a phenotypic, a visual change in the subsequent generation, confusing an observation with a mechanism. How did he know he had induced a gene mutation? And he was challenged with this. Maybe he had done the equivalent of shooting his chromosomes in the fruit fly with like a metabolic bazooka and just blowing out chromosomes. And Muller was challenged with this. And this becomes a very basic issue. Did Muller induce gene mutation or didn't he? And he received, as I said, the Nobel Prize for this in 1946. But he was severely challenged on this.

Ed Calabrese [00:16:14] I followed all the disputes and arguments and I even got all the grant proposals that Muller wrote, those who opposed him wrote, and watched these step by step major chess matches between these, what I call "titans of genetics," so to speak, back in that era. And in the course of the disputes I felt that Muller was always losing in the arguments. He's a very smart guy; he's a very bright guy. He's one of the top brains of his era, but he was up against some people who were at least as good and maybe a little bit better in how they designed their experiments. And Muller was repeatedly backed into the so-called, into a corner because all the research pointed to the fact that what he was doing was actually knocking big holes in chromosomes. Today, what we have learned, this is well after he gets his Nobel Prize, today we have learned that at the doses that Muller gave to his fruit flies, instead of inducing a point mutation, knocking out or changing one nucleotide or two, Muller was knocking out tens of thousands, maybe more than that. Just gaping holes in his chromosomes. The chromosomes would recombine and then they would see some genetic change if the animals lived. But even within his studies, a high proportion of his fruit flies just died. And those that lived, the vast majority of those were sterile. And this is a species that's very resistant. And so he was just jacking up those doses.

Ed Calabrese [00:17:59] But what happened was that Muller was a very combative, brainy, unrelenting, pushy guy, a threatening person, so he'd do anything to win, anything to to get his Nobel Prize, actually. Threaten, cajole, do everything. And what happened was that he developed a following, almost like a cult following that was challenging the status quo. He led a group of this new band of radiation geneticists forward. Somehow what happened was that it kind of all merged together with the Manhattan Project that was to develop the atomic bomb for World War II. Because while everybody thinks that the Manhattan Project was just to develop the bomb, and that's really what it was, there were many other aspects to the Manhattan Project. And one was to try to characterize all the genetic effects of ionizing radiation. And in the course of doing that, the big time work was done at the University of Rochester in upstate New York in the United States, and it was done under the leadership of a very excellent geneticist by the name of Curt Stern.

Ed Calabrese [00:19:15] It just so happened that Stern and Muller were buddies; they were close, they knew each other. And Muller had returned from a, well, I'm going to just say a seven or eight year hiatus to Europe, having spent about five years or so in the Soviet Union and a year or two in Germany and a year or so in Edinburgh, in Scotland. He came back to the United States and he got a job, believe it or not, in the town that I am living in and working in, Amherst, Massachusetts. Not at UMass, where I am, but at Amherst College. Literally his apartment... Where he lived, I know exactly the street number, the house he lived in all this time, it's one mile from here. And so Muller was basically back in the States from 1940 to 1945. And in 1943, the the Atomic Energy Commission in the United States was in charge of nuclear development and so forth. They gave a contract to Rochester, and Stern hired Muller as a consultant.

Ed Calabrese [00:20:29] This is where everything kind of goes south in terms of where this LNT is coming from and also, perhaps, where it's born. But we know that Muller birthed it in 1930 when he created the proportionality rule, but it didn't have much credibility; it needed experimental evidence. And I'd have to tell you, I looked at a lot of studies, looked at every study, really, during this time period. And whenever Muller was advocating for the LNT or his proportionality rule, there were many studies that contradicted it. He was a guy who never liked to mention the other side of the story. Muller was always about what supported him. And if there were studies that directly contradicted it, they never surfaced at all. But they surface in my papers, for sure, because I try to put those things in proper balance. But when it came to the issue of what was the nature of the dose response in the low dose zone, the American government through the Atomic Energy Commission wanted to know the answer. And so, key studies were done with mice and with fruit flies. As it turns, out in that study, about 400,000 mice were used. For that era, that is a massive amount of mice, and they got no publications out of that work, if you can believe that. No publications of relevance out of that work that had any impact on deciding anything in relationship to the dose response, human effects, nothing. And there's a story behind there that's really well worth getting into. What a waste, and it was just kind of submerged and never really exposed.

Ed Calabrese [00:22:21] But in the world of where we are today, everything then shifted to the fruit fly. And all our work today, our beliefs come out of this fruit fly work from the Manhattan Project. And this is where deceit and dishonesty begin to emerge within the radiation genetics community, because during this time period, Muller and his cultivated radiation geneticists, they believed, and I mean believed like a religious belief, they believed that the dose response was linear and anything that was outside of linear was not right. It was like a creed. And so what happened in the study at Rochester, what they found was that the LNT wasn't supported. The big dose response. studies were done with hundreds of thousands of fruit flies evaluating the dose response. And when the researcher who was ultimately responsible for doing the chronic aspect of the study, his name was Ernst Caspari, in August of 1946, he brings his data to Curt Stern. And he says, more or less, I'm kind of just characterizing what I think the conversation might have been, "I hate to tell you this, Curt, but we didn't get a linear dose response. Sorry to say, it's a threshold.".

Ed Calabrese [00:23:59] And so what do you do when you're the boss and you have a person who's working for the boss? And this is just a crushing blow. I mean, this is a crushing blow. And so, Stern in his wisdom said, "I'm not accepting at all what you're saying. Your work is not valid." And why wasn't it valid? He said, "Well, because your control group was reading artificially high. There was too much variability in your control group, and I don't believe your results. Your study is not a valid study. And so that's not going to be getting in the way of LNT for me," is pretty much what he told them. But Caspari, the worker, the researcher, he went into the literature and he dug out. lots of stuff, and he came back with articles and he showed that, "I hate to tell you this Curt, but our control group is just like it is within the literature. It was not reading aberrantly high. It was reading what we expected it to be." And Curt, I give him credit; he backed down from his position in light of the data, just like a scientist should do. You challenged him, the student went out and got the data, this challenge discredited that rejection, and he got his advisor to back down.

Ed Calabrese [00:25:23] So you might have thought, "Wow, that really opened it up for the threshold," but actually Curt Stern was not over with his plotting and planning. What he did, along with Caspari, and I don't know how he twisted his arm to do this, but they did, they wrote this entire paper, their entire paper, and they said, "Well, here's our data and we don't want anybody to take it seriously until we can figure out why it didn't show a linear dose response." And they spent six or seven pages in a discussion laying out why, questions and concerns. And I'd have to tell you, the study that was done was the best study to date, the largest study to date, the most competently done study to date. And they rejected their own data.

Ed Calabrese [00:26:20] Now, we sent the paper to... Well, just backing up a little bit, so I knew all these, I knew this situation, right? But I also knew that Muller got his Nobel Prize a couple of months later. And I knew that Muller had been a consultant to this group in Rochester. But when Muller goes to the Nobel Prize group, what he does is he stands up in front of them and he says to them... Now picture this. Muller has been a consultant on this study for three years, right? They followed Muller's recommendations, but he gave them the fruit fly, he followed the recommendations for what he should do. He's a very good consultant, I can say that for sure. But when Muller goes to the Nobel Prize audience, he goes and says to them, "You know, the threshold model is dead. It has no support. There's no basis for it. We have to switch to a linear dose response." And that's it. The future is with linear dose response.

Ed Calabrese [00:27:17] And so I'm saying to myself, "Well, how could Muller say that? Muller had just seen the very best study that ever been done by anybody, he's been a consultant to it, and it shows criticism of the LNT and it supports a threshold dose response model. How could Muller have said this?" And so I said, "Well, the only way that any rational person could have said this..." and Muller was rational, the smartest guy in the room, " that he probably didn't see the data." I said, "I've consulted enough." A lot of times, the people you're consulting with, they don't share all the information with you. Curt Stern probably didn't send him all the data, and Muller just went based upon his own intuition. And so I said, "But is that true? That's an assumption.".

Ed Calabrese [00:27:58] So I then went back and I bought all the letters and correspondence and everything between Muller and Stern and everybody who they touched. And when I got this treasure trove of hundreds and thousands of pages of stuff and went through it, I found actually that on November 6th of 1946, that Curt Stern sent the whole data set and the write up to Muller. And then Muller wrote back to him on November 12th, 1946, a month before his Nobel Prize and said, "I see the Caspari study. It's a very excellent study. I can't believe it. It just challenges LNT. This is a real serious problem for us. We have got to go back in and get more money and you have to replicate this study and see what happens. This is a real serious problem. Caspari's an excellent researcher, I'm not challenging him at all, but this is a serious problem.".

Ed Calabrese [00:28:48] And so, what happened is that I knew I had the smoking gun at that point. I knew that Muller had seen all the data and that Muller didn't offer any criticism, and then Muller said, "We have to replicate it." Like any scientist would say, you replicate everything, replicate it two or three times for all I care, but replicate it and do a good job, see if it holds up. So when Muller goes then to his Nobel Prize speech, well, what happens is that Muller does not share with the audience what he knows. Muller goes in and somehow says to the audience, "There's no possibility of a threshold. It's dead." And Muller has seen the very best studies showing the exact opposite.

Ed Calabrese [00:29:28] Now, if it were me and I was ever so lucky as to have a Nobel Prize and I was to speak in that kind of a circumstance, I'd have said, "You know, dose response is really important issue. We have to get to the bottom of it. I personally support a linear dose response, but we need to study it more because the issue's unresolved." If I were Muller, that's what I'd have said. But that's not what Muller said. Muller had the knowledge and he used his knowledge to deceive the Nobel Prize audience and the world that was listening to all the reporters that were around there. And the only people who knew that he was being deceptive were himself, Curt Stern, Caspari, and maybe one or two others that were in the Stern group and they kept it quiet. They kept it quiet.

Ed Calabrese [00:30:14] And it was during this time period that Curt Stern also then went forward and he got the money to try to replicate the Caspari work. And in the course of it, what happened is that all the good researchers with experience, they all took off. The war was over; they went back to their academic jobs, and Stern was forced to bring on board a first year master's student to take over and try to do the replication of the Caspari work. And in the first two experiments that were done, big experiments, the control groups were profoundly lower than expected, outside the range of the literature and everything else. And when they wrote up their results and sent them to the Atomic Energy Commission, what Stern and the colleague did was... Delta Uphoff, who was the graduate student. They said that, "Our work is uninterpretable. The control groups are too low. They're just not valid." And then in the discussion they specifically stated, "And this resulted as a result of investigator bias." They actually wrote it in their words. This document was a classified document in the bowels of the U.S. Atomic Energy Commission which I was able to get. I saw this, and as they said, their own data was uninterpretable.

Ed Calabrese [00:31:37] Now, the important thing to note is that when they finally... All the research was done and then Curt Stern decided that he was going to publish the findings of his work, what he did was he took the Caspari work that had now been shown to be valid and he brought up again that it had too high of a control group, which was false. And then what happened is that he reactivated the Delta Uphoff work which did have the aberrant controls and said that they were normal. And when he tied all this research together, he came out with support for a linear dose response relationship. And it's on the basis of that. And they published it in the journal "Science" as a single one page note. And at the end of that one page note, they had no details except the summary information. They said that they would share all their methods and materials in support of data in a subsequent paper, which they never actually did. Totally, another misrepresentation.

Ed Calabrese [00:32:39] But the interesting thing here is that the radiation genetics community became totally dependent upon this one paper in "Science," and it was a paper in which there was dishonesty raised. You have an investigator in Curt Stern and in Delta Uphoff who had written that this work was uninterpretable and that it was based upon investigator bias. And then five or six or seven months later when they published it in "Science," they never shared that information with anyone. Now, I was lucky to have found it. And also, I'd have to tell you too, that Muller and Stern exchanged lots of information on whose control group was valid, Delta Uphoff or the Caspari one. Things were swirling around because Mueller was involved, lots of controversy over control group background variability. It had hundreds of thousands and many more than that fruit flies in different studies. He unequivocally in his letters and cables and whatever, however they were communicating, and I have copies of all of these, he unequivocally states and writes that the control group that was valid was the Caspari control group and he supported that and the Delta Uphoff was not. And Muller, in subsequent articles, he goes and he praises the Delta Uphoff experiments and so forth. And I have him in direct contradictions and lies. This is a Nobel Prize winner lying in his Nobel Prize speech, lying in publications afterward, and everybody believing them. And a little circle of friends like Caspari and Stern and these others, they know the dishonesties and they to some extent participated in those dishonesties. And it's the beginning of corruption at the very high level within the scientific community led by leaders, Nobel Prize winners.

Ed Calabrese [00:34:58] And it gets worse because what happens? Well, we enter the realm of atomic bomb testing after World War II. Above ground, we have fallout issues and it all leads to what's going on here with with radiation and medical radiation, but also with fallout throughout the world. And so the National Academy of Sciences in the U.S. creates a big panel in 1955, and they give them essentially nine months to get their report together. And they want to know what's happening, what are the risks associated with radiation in many different domains, but medicine as well as in genetics. And so what happens here? Now, you won't believe this because this is really just hard to believe, but they were put together by the Rockefeller Foundation who gave the money to the U.S. National Academy of Sciences to do this. Now, the president of the Rockefeller Medical Institute, doing medical research, it will become the famous Rockefeller University, that person was the same as the president of the National Academy of Sciences. His name was Detlev Bronk, and he was also a member of the Rockefeller Foundation. So when the Rockefeller Foundation gave the money to the National Academy, they're really giving it to, he was giving it to himself. And the Rockefeller Foundation had funded all the radiation geneticists and they really knew their positions on everything. They had funded Muller about $4 million in the last five years. They had funded the others very substantial amounts of money. They knew their beliefs on the nature of the dose response. And so what they did was they hand-picked, you might say, a genetics jury with all of them believing in one thing: LNT. And so once you stack the jury, you're waiting for a result and you know what the result's going to be.

Ed Calabrese [00:37:01] But at the time, the basic belief in the world was that the fundamental dose response was still a threshold. But within the very first meeting or two of this genetics committee in 1955 and early 1956, one of the members read the equivalence of the geneticists' version of the Apostles' Creed; they read their basic belief. And their basic belief, the radiation mantra, was that all damages is cumulative, it's irreparable, it's irreversible, and as a result of that, the dose response has to be linear. It was read into the record. There was no dissent, there was no dispute. This was what they believed. And once you have a set belief, you know what the answer is going to be. And it was not a way to actually bring up a debate on what is the nature of dose response in the low dose zone. You have to bring up people that can actually debate on both sides of the issue. There was no debate. And I was looking for the debate. I have all the transcripts, I have everything. It was just, "This is what we believe.".

Ed Calabrese [00:38:09] Now, two things happened that were really very significant at this point, and right in the beginning. And that is... Now I said it was 1955, it was November when they first met. It's really 10 years after the dropping of the atomic bomb in Japan, 1945, in August. Now, during that time period, that 10 year period, the Japanese government and the U.S. government had established lots of research activities going on to try to figure out the impacts of the bombs on the Japanese population. And they studied the offspring of survivors for 10 years and they still continue to study them even to the present time. But a big interim study was done after 10 years and it was following 75,000 children that had been born. And I would have thought that these kids would have had all kinds of birth defects, maybe three eyes, maybe, you know, four ears. Who knows what could have happened based upon everything that you've read in science fiction and what have you. But looking at these people, studying them in the most objective way, they had thousands of workers helping them, they found no significant treatment effects in 75,000, looking at the offspring of the survivors. And they'd been exposed to a rather broad range including high doses of radiation.

Ed Calabrese [00:39:29] Now, the person in charge of this was a doctor, James V. Neel, a University of Michigan professor, and he was on this National Academy of Sciences Committee. So at the very first meeting of this National Academy of Sciences Committee, Dr. Neel brings to the committee his 300 page report just done on all the offspring of all the people who survived the atomic bomb and went on to have kids within that time period. And as it turn outs, they found no treatment effects. Muller and the group knew this. Muller stood up at the meeting and Muller said, in effect, that we're not going to give any scientific standing to this report. Now, this is a 10 year report on humans and the most significant exposure possible, and they chose not to give it standing and they chose not to review it. So what did this National Academy of Sciences Committee do? They decided to go back and to base their work on the invalid Drosophila studies led by Curt Stern and Delta Uphoff 10 years before that I've just criticized. This is a brand new finding. I've been into this game for a long time, and I didn't know that in fact, this National Academy of Scientists Committee gave no standing to this report. And they just blew it away, and they based their entire recommendations upon an invalid fruit fly study.

Ed Calabrese [00:41:09] Now, I'll give Jim Neel his credit. Jim Neel was able to get his report over to a parallel committee over in the U.K., and they looked at his report in considerable detail. And I have all the letters between him and that committee. I know what they criticized, what they didn't criticize and how it all came out. In their final report, they were extremely complimentary of him and his work. And their work had a very, very powerful impact on the British recommendation. While in the U.S. we were saying, "Oh, every exposure is harmful down to a single ionization," the British report was very threshhold-like. Totally different and was very much influenced by the Neel mutation report from Hiroshima and Nagasaki that in fact, our committee in the U.S. refused to give standing to. It's an absolute striking... What can I say? It's a devastating, devastating illustration of bias and in not doing your job and being unethical and not being explicit and then hiding that, hiding it... I tell you, it was hidden for 70 years, and I found it by accident. I don't even know how I found it after so many years myself. It never had been discussed.

Ed Calabrese [00:42:27] And an interesting thing in this is that I've read Jim Neel's autobiography, "Physician to the Gene Pool." Very nice book. He never mentions this at all, ever, at all in his write up. It was even hidden at his level. You would think that this was a scandalous sort of a thing. But to make things even worse, to make things really even worse, this National Academy of Sciences Committee, in addition to playing that sort of a dishonest game, because they had figured out what the answer was anyway, they just knew everything was linear, but they were asked to estimate the number of birth defects in the U.S. population if adults had been exposed to a certain level of radiation to their gonads and follow them from 1 to 10 generations, that sort of thing. They were given one month to write up their reports. It had to be done independently. There were 12 geneticists on the committee. Three felt it was a crazy assignment and too uncertain and and refused to do it, but nine did.

Ed Calabrese [00:43:34] Now I got copies of all of the nine reports. I have them right behind me in this office; I could pull them out in 30 seconds if you wanted to see them. All nine. And in these reports... So even though they were forced to assume that everything was linear, but even though they were forced to assume linear, the estimates of damage were incredibly variable. The geneticists didn't agree with each other. They were all over the lot. And so when all these reports came in, what happened is this guy, James Crow, who was collating the data, got in touch with the chairman of the committee and he goes, "We have a serious problem." And they say "Well, what's that?" He says, "The serious problem is that we don't agree with each other. We're all over the lot. And if we share our uncertainty with the general public and scientific community, they will never accept any of our recommendations, including a linear recommendation. And this is a serious problem that we have."

Ed Calabrese [00:44:43] And so what Crow does, on his own, is he removes, removes the three most variable estimates. And so now instead of having nine, you have six. And you have shrunk the uncertainty down now from thousands and thousands of fold down to 750. And that's still too big. And so the committee in their plotting and scheming, they made a de facto judgment with no basis to say that the uncertainty was only 100 fold. This became an acceptable amount, what they could live with and think that the scientific community or the public might say is acceptable. So when they wrote their report up and published it in the journal "Science," what they said was this. They said, "We challenged our geneticists to estimate the number of birth defects and so forth in the U.S. population with such an exposure, and six of the geneticists took up the challenge." Six. Now, I know it's nine. They said it was six. And the estimates came up to a 100 fold variation. And I'm looking at this science paper, and I'm looking at this National Academy of Sciences Committee, and I'm saying these guys are fraudulent. They lied, they misled, and they published it in the journal "Science." Their report got front page in "The New York Times," got front page in "The Washington Post," and got front page every place. And they were called, at the time, the equivalent of the genetics dream team. All the brainiest, the best and the brightest. The best and the brightest were very deceptive, led by a Nobel Prize winner who had a long history now, once it gets exposed that way.

Ed Calabrese [00:46:38] And so what happens here is that nobody decides that they can question these people, a dream team, the best and the brightest. And this particular focus is carried forward into our regulatory arena once the U.S. EPA is created in 1970. In 1956, this committee made the recommendation, the critical recommendation, and it was to go linear. It was to go linear based upon the the Delta Uphoff-Curt Stern findings which were invalid and to ignore the actual human data of many others, but also the big human data which was coming out of Hiroshima and Nagasaki, not giving any standing whatsoever, and to hide that fact. And then at the same time, they had other screwups along the way too. They were really dealing with the reproductive cells in males and the reproductive cells in males, as we came to learn, mature males had lost their DNA repair, lost the capacity to repair any sort of genetic damage. But when you look at all somatic cells and even much younger cells that are reproductive cells, they have that full capacity. So they were even misunderstanding, doing the study in the incorrect way and then misapplying it to the kinds of end points like cancer that they were going to apply them to.

Ed Calabrese [00:48:18] And so it becomes extremely interesting further because it goes back to what their basic belief is. What was their mantra? They said, "All damage is harmful. All damage; you can't repair any damage." And then in 1958, two years later, one of their own, Bill Russell from Oak Ridge National Labs, he publishes a landmark study in which he shows that, in fact, there is such a thing as repair of genetic damage. And he shows it in mice and he shows that in female mice, in fact, you could even give them 27,000 times higher than background. 27,000 times higher than background. And you have a threshold. You don't even see damage up to that point. And it really contrasts with the belief that all damage, all exposure is harmful, even down to a single ionization. Well, I mean, again, you have two of their own, two of their own people challenge the basic beliefs. And I can tell you this, I've followed both of these guys careers, the two younger guys who challenged the group. And at some point after they made their challenge, they were afraid to challenge anymore. They were, you might say, silenced by the group. And it's very interesting to see this. And you can see this whenever you are challenging a basic belief and there are certain groups in power, you know that if you challenge them that your chances to be successful are pretty... You have to play the political game. You really know where the power is, and if you're going to challenge the power then you might not get your grant funded. You might not get this promotion. You just have to play it close to the vest.

Ed Calabrese [00:50:15] And I watched and I could see when this initial paper on the DNA repair sort of thing was coming out, they wrote to Muller and they tried to soften it. They tried... "What do you think about this, Herman? What do you think about that?" They wanted to make it so... Just treat him so he wouldn't come down and be harmful to them, really. So it becomes very political and it becomes very judgmental. And then what happened next? I have to tell you, when EPA was created, the EPA got the National Academy of Sciences to take a new look at dose response in radiation, and they published a report in 1972. And that report in 1972 was a crucial one because it's part of what they call the BEIR, the biological effects of ionizing radiation, B-E-I-R, the sequence that we have today, BEIR I, BEIR II, BEIR III, BEIR IV, all the way to the present time. And that group acknowledged for the first time, that in fact, yeah, there is such a thing as DNA repair, and how do we deal with that? "Well, we do see that there's such a thing as a threshold in the females in these mice that was happening here. We don't quite see that in the male, although we know that there is such a thing as repair in the male, and substantial repair." And so what happened was that in 1972, the U.S. National Academy of Sciences, they reaffirmed the LNT recommendation of 1956. And this was big because the mouse studies had 1 to 2 million mice in them. They had gigantic numbers. They were just gigantic studies. And so they provided the foundation that would be the homing pigeon for epidemiologic studies that weren't really too secure. And so they provided them the scientific stability with a number. And this is carried forward all the way to the present time.

Ed Calabrese [00:52:28] But something you need to know is that these studies that were carried out back at Oak Ridge and all the way through, really, the 1950s and into the '60s and so forth, were the basis for that BEIR report. In 1995, a gentleman by the name of Paul Selby, who was a longtime worker at Oak Ridge and worked with the Russells, William Russell and his wife, who were in charge of these studies, he, for reasons that were unrelated to that work went back into the data sets and noticed something that was unusual with the control group data. And then he would go evenings back into the files and he spent many a night there compiling work that would allow him to evaluate something. And he came to the conclusion that in fact, there was a serious flaw in all the Oak Ridge research findings tied into their control groups. And so what happened is that he brought this information to highest level people in the Department of Energy. They looked at his criticisms, a very thick dossier, and they concluded that he had standing; his criticism had standing. And they brought together four people from around the world to look at his criticism and brought the Russells together and Selby together for a big powwow to see what was what.

Ed Calabrese [00:54:03] And so the bottom line in all that sort of thing was that the group of four experts concluded that Selby was correct, that the Russells had made a significant error in their control group mutational estimates. It wasn't like a minor error. And what happened was that they forced the Russells and they forced Selby to publish their work and correct the error in the scientific literature. Now what that meant was that was that the Russell work was in fact off by 120%. It was a gigantic error. And then Selby had them much higher than that. And they wrote this up in a highly technical work, very few people could really understand it all, but it was there.

Ed Calabrese [00:54:51] I go back in later and find it, and then I go and then I apply it back to where that BEIR I committee was. If they had had the right data, the right information in 1972, what would they have concluded? Well, they would have concluded not that there was a linear dose response because the female was showing a hormetic response and the male was showing a threshold response. The entire conclusion that EPA drew from that, which was to support a linear dose response, was now shown to be incorrect. And the entire historical foundation of where the EPA's position is has been now shown to be incorrect. And these things are coming out with new publications in the last couple of years. This is all new and has not been shown to really have occurred that way.

Ed Calabrese [00:55:44] And so what happens next, if there's a final stage in this crazy story, it's really the the report of the Hiroshima and Nagasaki leukemia studies. This work was published in 1957, May of 1957 in the journal "Science." And it was in work that was looking about quantitative risk assessment and trying to apply radiation to leukemia. And so in this major paper, what we find came out of Caltech geneticists, that they were arguing that the relationship was a linear dose response relationship and it was supported by other types of work with ankylosing spondylitis and other types of radiation induced leukemia of the thymus gland, things of that nature. And so I went into this in some considerable detail, and what I found was was pretty striking. And that was that the research, when you really take a look at it, it's pretty amazing. If you look at the data that emerged from all the leukemia studies that came out of the Atomic Bomb Casualty Commission that was done in conjunction with the U.N. and the National Academy, if you go back and you look at these data, and you follow the dose response relationships, the dose response relationships actually do not support a linear dose response. But my findings demonstrate an inverted U-shaped dose response, a J-shape. And this is just bizarre. This is all published within the last year or two in major publications. And even if you go into the National Academy of Sciences, the National Academy of Sciences Medical Group, and you take a look at their evaluation of the dose responses, they acknowledge a J-shaped response in data, and they say, "We don't even want to deal with that. It's just contrary to what our beliefs are." And actually, it's written within the discussions that have, within their conversations that are recorded. And all that exists and I found all of that to be the case. But when I went in and did deeper dives, I found that to be the case.

Ed Calabrese [00:58:56] But the point that I'm trying to make here is that when this 1957 paper was published, it was given great standing. It was given an editorial by the the editor of "Science." It was debated the very next week on this big program on U.S. television called "Meet the Press." It was discussed in congressional hearings two weeks later, and it was given all kinds of standing. And yet the paper was factually in error and did not include all the data and was biased and didn't recognize acknowledged limitations in the studies that were used to support it. And so as it turns out, the historical foundations of LNT are really extremely problematic and they have a long reach because they're affecting us today. But when you go back and you look at things, you look at the people that we were expecting to provide our guidance, the people that were expected to be the experts, the people who were expected to be objective, the people who we wanted to bring fairness to the table, they brought anything other than fairness to the table. And these experts have been accepted as gods by the regulatory agencies today in all countries. And they have had, in my opinion, significant ethical failings in our entire regulatory domain, and the area of cancer risk assessment has, in fact, been based upon lies, inaccuracies, misrepresentations of the data by people who are viewed as champions, people that they give Nobel Prizes to, people that they name presentations after, people that have all kinds of awards named after them. These are our heroes, and these are the people who were actually corrupted by science and have led us to where we are, into a scientific community that's totally anti-science, afraid to look at their past, afraid to see, in fact, that they were duped. They were duped and became part of a cult and gave up their independence of thought.

Ed Calabrese [01:01:35] So when I go back and when I take a look at... Yes, I believed in LNT for a long time, and I first began to question it within my hormesis research because it was showing me adaptive responses at low levels. But I didn't realize how bad things really were. I didn't realize that, on top of that, it wasn't the fact that LNT was just a mistake. Yeah, LNT's a mistake, I can understand that. If you don't study right, it can be a mistake. But this isn't really a mistake. This is actually a deliberate attempt, a deliberate and a successful attempt to mislead the scientific community and the general public and to take over regulatory programs. And that's what we have in the world today. It's deliberate. It's really deliberate. So this is what we live with.

Host [01:02:34] Now not to end on a negative note, because we are running out of time, what is the recourse here? Because as you've talked about, science really does play a huge role in informing policy and regulation, especially now when it's been applied to the nuclear sector. So in your opinion, what is the recourse here and what is the pathway forward?

Ed Calabrese [01:02:52] What is the path forward? The path forward is that science is supposed to be self-correcting. That's the nature of science; that's how we all grew up. In regulatory science, it appears not to be self-correcting. Regulatory science has to become self-correcting. You need to have the light shine on this. And if the light would shine on it, then in fact, it might have a chance. I went to the editor-in-chief of "Science," who is now the President of the U.S. National Academy of Sciences, and challenged her with all the information that I've shared today and more, for her to retract that 1956 deceptive paper that committed scientific misconduct, and she refused to do it. So if we continue to have leadership that reinforces the past, then there's no way out, because that's where the power is. The power has to be challenged by people who are seeking the truth. And unless that happens, that's the path forward. The power has to be challenged by those who are seeking the truth. And whatever the truth is, then let it ride with that. But right now, we have a scientific community that is very afraid, very afraid to challenge the people in power, very afraid to... Yeah, they follow the truth in a lot of other ways, but won't follow the truth here. And it's a very sad state of affairs as far as I'm concerned.

Host [01:04:30] Yeah, it is a very sad state of affairs. But thank you so much, Ed. I remember the first time I heard this story, it read like a conspiracy novel. And it's always fascinating to hear about your work. And thank you for being on Titans of Nuclear.

Ed Calabrese [01:04:42] You take care.

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