[ RadSafe ] Reply to comments of Carol Marcus and Mohan Doss

Wed Oct 14 09:12:27 CDT 2015

Dear Mohan:  

Since the first reply mail this morning did not transfer the attachment I send the mail here again.  

Thank you for your statements in reply to Peter Crane.  You are quite right and I agree even if you quoted only a fraction of the evidence that shows the BEIR VII report to be seriously flawed.  

I add below a statement I had sent in 2005 to Dr. Douple, who was secretary with the BEIR committee.  The work by Dr. Pollycove and myself was misquoted by BEIR VII in a manner that is unacceptable in science.  Peter Crane referred in his statement recently to the BEIR VII treatment of Pollycove's and my work and he liked it - obviously without having read the paper by Pollycove and myself.  The NRC should be aware of BEIR VII having misinterpreted our work. And I hope Peter sees it too.  

Best regards, 
Ludwig

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Ludwig E. Feinendegen, MD 				Wannental 45
Professor emeritus, Nuclear Medicine 			D-88131-Lindau
Heinrich-Heine-University Duesseldorf			Germany		
Germany
							Tel.: (+49)(0)8382 – 75673
							Fax: (+49)(0)8382 – 947626
e-mail: feinendegen at gmx.net

Evan B. Douple, Ph.D.					August 6, 2005
Scholar, Nuclear and Radiation Studies Board
Sixth Floor
500 Fifth Street, NW
Washington, DC  20001
USA

Re: Draft BEIR VII Report

Dear Dr. Douple:

Following our discussion in Spokane at the annual meeting of the Health Physics Society and as promised, I send below a few remarks which I believe are pertinent to evaluate the impact the report likely will have.  I had the privilege to see the draft of the report and read in it.  Several statements in the report refer to work I had done together with Dr. Myron Pollycove.  

To me, the report presents a very large and most useful set of data on low-dose effects of ionizing radiation.  The various epidemiological and experimental data obviously serve the attempt to illuminate the question as to the probability of low doses to cause cancer.  

Even if I have not been able yet to read the report in all details carefully, it is apparent to me that the discussion and interpretation of many data pointedly tend to justify the linear-no-threshold (LNT) hypothesis down to zero dose without proper consideration of equally justifiable alternative hypotheses.  This imbalance was obvious also in the sessions devoted to the report in Spokane and in the recent summary statement to the public.  Contrary to the report by the French Academy of Sciences, Paris, dated March 30, 2005, the BEIR VII report appears exclusive and does not use much experimental and epidemiological evidence for other models than given by the LNT hypothesis.  This discrepancy between two carefully working academic institutions at the highest level challenges the impartiality of the BEIR VII report committee – in fact, it creates an embarrassment for the National Academies in Washington.

A particular weakness is the narrow view on the functions of adaptive responses.  Again and again, adaptive responses are seen mainly in terms of low-dose induced resistance against renewed irradiation, whereas there is much evidence for low-dose induced adaptive responses to express non-specific system reactions to toxins that differ from radiation but may act on the same biological targets.  Only rare remarks pertain to this lack of toxin-specific response pattern.  On the contrary, the report stresses the toxin-specific response, as, for instance, regarding the particular gene responses to various oxidative agents in S. Cerevisiae.  When observations on microorganisms or cells or animals do not relate to low-dose induced DNA damage and repair, they appear uninteresting in the report, presumably because of their uselessness to favor the LNT-hypothesis.

In this context, the BEIR VII report even distorts or neglects published material.  Two such situations, as I indicated to you shortly in Spokane, concern my paper with Pollycove (M. Pollycove, L.E. Feinendegen. -  Radiation-induced versus endogenous DNA damage: possible effect of inducible protectice responses in mitigating endogenous damage. - Human and Experim. Toxicol.  22:  290-306, 2003).  Permit to be more specific:

On page 71, the draft of the report states: 

“The implication of these results (on gene expressions following challenges by  different oxydizing agents)  is that each agent that is toxic to S. cerevisiae produces its own unique spectrum of cellular damage, with some overlap.  The relevance of these comparisons for this report lie in the attempts that have been made to explain low-dose ionizing radiation as no more than a special case of oxidative damage (Pollycove and Feinendegen 2003).  If this were true, then low doses of ionizing radiation would be insignificant against the levels of naturally occurring reactive oxygen species and could therefore be ignored as having no detrimental health effects”.  

This statement given above in bold regarding the Pollycove-Feinendegen paper is not correct.  In fact, this paper clearly emphasizes that DNA double strand breaks (DSB) per primary oxidative DNA damage (DNA-adducts) are likely to be 105 times more probable from ionizing radiation than from endogenous oxidative attacks.  This precludes the belief that damage from low-dose ionizing radiation may be no more than a special case of oxidative damage.  Moreover, the paper emphasizes that the radiogenic reactive oxygen species (ROS) may encompass a broad spectrum of species, and that many of these ROS may be similar to those produced endogenously by oxidative metabolism and various compartmentalized biochemical reactions.  The obvious distortion of the Pollycove-Feinendegen paper misleads the reader and discredits the authors.  The BEIR VII report should have said that the above paper comes to the conclusion that endogenous DNA damage is much more frequent than DNA damage from background radiation, in support to the well known fact that cancer arises much more frequent from other causes than radiation.  The argument continues that low-dose induced adaptive protection, as is well documented, encompasses biological systems as a whole and does not just pertain to DNA repair.  Thus, adaptive responses may not only increase DNA repair and, thus, resistance against DNA damage from renewed irradiation, they rather operate systemically also involving prevention of DNA damage by scavenging, and damage removal by apoptosis, cell differentiation, and immune response, i.e. operate at various levels of biological organization.  The consequence, then, is the prediction that adaptive protection in all likelihood also operates against non-radiogenic cancer.  This situation finds appropriate room for discussion in the report by the French Academy of Sciences, but not in the BEIR VII report.    

On pages 579-580, the issue of non-radiogenic DNA damage, especially DSB, comes up again.  Here, BEIR VII states:

 “Pollycove and Feinendegen have made a theoretical argument that the hazards of radiation exposure are negligible in comparison to DNA damage that results from
oxidative processes during normal metabolism.  They argue that endogenous processes, autoxidation, depurination and/or deamination can lead to cellular DNA damage which resembles that produced by ionizing radiation.  Oxidative damage is much more complex than they appreciate and involves predominantly proteins and mitochondrial targets associated with transcription, protein trafficking and vacuolar functions (Thorpe and others 2004).  The identity of the particular radical species generated endogenously in undamaged cells is unknown, and therefore yields of endogenous single strand breaks (SSBs) and double strand breaks (DSBs) cannot be reliably estimated a priori.  Direct measurements of SSBs in unirradiated cells indicate levels several orders of magnitude below that estimated by Pollycove and Feinendegen.  The authors’ hypothesis that endogenous processes within cells give rise to significant levels of DSBs from SSBs in close proximity is speculative and not supported by current experimental information.”  

The above quotation, again, implies that radiation-induced oxidative damage is much more complex than Pollycove and Feinendegen appreciate.  However and as stated above,  Pollycove and Feinendegen make it a point to stress that their calculations indicate that DSBs per DNA- oxyadduct are 10 5 times more frequent than are DSBs from endogenous DNA-oxyadducts.  One can hardly state more explicitly that radiation is much more potent to cause severe DNA damage than are endogenous ROS.  Yet, the BEIR VII report ignores this emphasis by Pollycove and Feinendegen.  

More serious still is the statement that “The authors’ hypothesis that endogenous processes within cells give rise to significant levels of DSBs from SSBs in close proximity is speculative and not supported by current experimental information.”  Irrespective of the fact that the Pollycove-Feinendegen paper gives proper references to relate SSBs to DSBs,  the issue obviously is the incidence of DSBs in non-irradiated cells.  The following reports fully support the statement by Pollycove and Feinendegen that in the order of about 0.1 endogenous DSB likely occur in mammalian cells per day from endogenous sources: 1). Vilenchik MM, Knudson AG.  Endogenous DNA double-strand breaks: Production, fidelity of repair and induction of cancer.  Proc. Natl. Acad. Sci US 100: 12871-12976, 2003; and  2) Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC.  Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks.  Nature Cell Biol  6(2):168-70, 2004; and 3) Rothkamm K, Löbrich M.  Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses.  Proc Natl Acad Sci US  100: 5057-5062, 2003.  The latter paper reports on the incidence of DSB in non-irradiated cells.  This amounts to an average of about 0.04 – 0.06 per cell at steady state, in their MRC culture cells in the confluent state.  Assuming a repair half time of  1.5 hours, the production rate per cell per day would be about 0.05 x 1.5 hrs x 1/ln2 =  0.05 x ~ 2 = 0.1.  This is close to the value calculated by Pollycove and Feinendegen.  The BEIR VII report, however, does not even mention any one of these reports in the context of endogenous DSB production.  

In summary, the BEIR VII report appears to me seriously deficient.  I do not think that short corrections here and here may suffice to bring the report up-to-date.  In fact, I take the liberty to suggest to have the report carefully re-edited to serve the scientific community and public alike in a manner that complies with serious scientific work. 

I am sorry to bring this up in the way I did.  But more is at stake than a short lasting effect as it is commonly the case with ordinary newspaper reports.  The extensive collection of literature is enormously helpful.  It should serve a better purpose than an apparent biased approach to risk assessment. 

With best regards,
Sincerely yours,

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-----Ursprüngliche Nachricht-----
Von: radsafe-bounces at health.phys.iit.edu [mailto:radsafe-bounces at health.phys.iit.edu] Im Auftrag von Doss, Mohan
Gesendet: Dienstag, 13. Oktober 2015 18:21
An: RADSAFE
Betreff: Re: [ RadSafe ] Reply to comments of Carol Marcus and Mohan Doss

Dear Peter,
    I see a major difference between your approach and mine on this subject. As a scientist, the final arbiter for me is evidence, and I rely strictly on evidence to pass my conclusions. You said you are not a scientist, but rely on others (Ian Fairlie, Jan Beyea) or advisory bodies (NAS). You also belittle concepts because they are supported by those who you consider as not reliable (Ann Coulter, Lyndon LaRouche). I examine the contents of the statements by such people rather than dismissing their views outright. These differences explain why our discussion/debate is not getting anywhere, e.g. you do not respond to the evidence that I quote. You may note I have indeed participated in debates/discussions in journals and in symposia on the subject, with scientists and physicians. Though they do not declare winners in these debates/discussions, I refuted the evidences quoted by my opponents whereas they did not refute the evidences I quoted.  So I have effectively won the debate.  Let me now discuss the reliability of the approach taken by people/groups you have relied on. 
   BEIR VII stated the atomic bomb survivor data are the most important data for estimating health effects of radiation. Also, Dr. Fairlie made the following statement in Nov 24, 2011 "In fact, there’s quite a lot of evidence of effects below these levels. For a start, the Japanese bomb survivors’ data[5] – the major study on which all radiation authorities base current risk estimates – suggests some effects at doses below 100mSv." (see at http://www.ianfairlie.org/news/are-radiation-risks-overrated/ ). However, in his Comments on the NRC Petition, Dr. Fairlie does not refer to these data at all.  Why did he not use these most important data? You may note that these data, with improved statistics, do not support the LNT model any longer, but are consistent with radiation hormesis. You may think this is just my opinion, but other scientists who are long-time supporters of the LNT model are agreeing implicitly with this conclusion, since they have stopped referring to these data in support of the LNT model. For example, Dr. Mark Little, in the 2009 debate in Radiology available at  http://www.ncbi.nlm.nih.gov/pubmed/19332841 , said: "Most of the information on radiation-induced cancer risk comes from (a) the Japanese atomic bomb survivors (b) .....". However, in the more recent debate in 2013 http://www.ncbi.nlm.nih.gov/pubmed/24989368 he did not use the atomic bomb survivor data to justify low-dose radiation cancer risk. In my opinion, scientists should rely on data to pass conclusions, should not ignore important data, and they should not use their prior conclusions to bias which data to use. You may note there are plenty of faulty data in published literature (hence the controversy in the subject) and so one would be able to quote a lot of literature supporting the LNT model. Careful scrutiny is needed to weed out the faulty articles. If you are not a scientist, it would be hard to do this. 
  Dr. Fairlie also quotes data that have been discredited already, e.g. the (Pearce, 2012) publication on childhood CT scans. This publication is quite faulty as shown by many articles since then, including the recent article by Dr. John Boice http://www.ncbi.nlm.nih.gov/pubmed/25816281 . 
  I will be responding to this and other evidences Dr. Fairlie has quoted sometime soon, when I submit my comments to NRC. I have found the evidences to be weak or not credible. 
  Re: NAS, BEIR VII Report: I have not been impressed with the quality of their work. The BEIR VII Report quoted 2005 Cardis et al. article on 15-country study of radiation workers to support the radiation cancer risk factors. Even a graduate student would see that Canadian data in that study were far off from other data, and were the reason for the conclusion of Cardis et al. 2005 study. Instead of asking the authors to investigate the discrepancy, NAS quoted the data to support radiation cancer risk coefficients. These data have since been discredited due to major problems identified in the Canadian data. BEIR VII report also ignored many of the data that showed reduction of cancers following low-dose radiation exposures. They ignored the immune system which plays a major role in cancer prevention, and as you may know low-dose radiation boosts the immune system. With so many flaws, BEIR VII report is not a reliable document. Again, the quality of the contents is what matters, not who or how many support the views. 
   Re: Thyroid cancers vs. all cancers: I consider all cancers as major problems to be addressed and solved but we do have to prioritize. You ignored 30% reduction of all cancers. Hence my comment.
   What do I know about thyroid cancer? I will be writing about thyroid cancer (and other cancers also) in a journal article in the near future. I will let you know when it is published, and you will find out what I know.
   Re: corrupting influence of money in this field:  For the origin of the LNT model there is documentary evidence showing BEAR I/II Genetics Panel members were motivated by research funds when they exaggerated the risks of low-dose radiation. I was shocked to read what the members wrote in their letter exchanges, as reported in a journal article. I could not believe it and asked for copy of the letters from the archives. When they sent the copies, I saw that the letters do indeed have those statements. Regarding money corrupting my views on radiation hormesis: My work/responsibilities in diagnostic imaging would be reduced if LNT model is no longer used in regulations. If my views were motivated by money, I would have supported the LNT model. 
    With best regards,
                                         Mohan

-----Original Message-----
From: radsafe-bounces at agni.phys.iit.edu [mailto:radsafe-bounces at agni.phys.iit.edu] On Behalf Of Peter Crane
Sent: Monday, October 12, 2015 4:03 PM
To: RADSAFE
Subject: [ RadSafe ] Reply to comments of Carol Marcus and Mohan Doss

Dear RADSAFERs:

In recent days, both Carol Marcus and Mohan Doss have responded to earlier comments of mine on the hormesis petitions now before the NRC. I had pointed out that Carol, ten years ago, had asserted that children were three times as radiosensitive as adults, whereas her petition specifically asked that all differences in radiation protection based on age or pregnancy status should be abolished, and I asked what had changed in these ten years. I also noted that Carol's argument was that the post-Chernobyl cancers could not have been caused by radiation, and were therefore irrelevant to the hormesis debate, whereas Mohan's argument was that the radiation doses from Chernobyl were so high that they were irrelevant to the question of the effects of low-dose radiation. Given that Mohan's petition claimed to support Carol's, I hoped that he would address this inconsistency. Their responses, to which I will reply further down, are as follows:

1. 
What happened in the last ten years, Peter, is that I read more and more of the scientific literature.  A good scientist changes his/her mind based upon reputable data.  Therefore, over my scientific life I have changed my mind about numerous ideas.

Carol S. Marcus, Ph.D., M.D.

2.
Dear Peter,
    It is interesting that you did not respond to the considerable amount of new evidence since 2005 for radiation hormesis (that I referred to). However, you picked the least important among the cancers (~0.3% of all cancer deaths in USA) - thyroid cancer  - whose incidence is highly prone to overdiagnosis and overtreatment - and pointed out some apparent discrepancies between my statements and Carol Marcus's statements. Chernobyl situation is somewhat complex, and I will respond to this issue after studying it further. Your objections to the petitions have no merit based on the vast evidence for radiation hormesis which you did not refute. 
   With best regards,
                                            Mohan 

To Carol, I would say that it is admirable that she continues to read in her field, and that she is willing to change her mind in the directions that the data takes her. (If she has read my comments on her petition, she will even find herself praised in at least three places, though implicitly criticized in others.) I would note that much of her reading must have been compressed into the last three years, for it was as recently as 2012 that she co-authored SNMMI guidelines that included this statement: “A causative role for 131I in carcinogenesis, other than for thyroid cancer in children at Chernobyl, is difficult to establish." Like Bill Lipton, I would be fascinated to know precisely what piece or pieces of evidence produced the epiphany that Chernobyl really didn't cause any cancers after all. 

The same guidelines said, citing BEIR VII, “No threshold for radiation-induced carcinogenesis has been firmly established.” Again, I would love to know what made you decide, in the intervening three years, that BEIR VII was part of a 69-year conspiracy to bamboozle the world about radiation, rather than an authoritative source in the field. 

In response to Mohan, I should acknowledge that I am not a scientist or a physician. In my comments to the NRC, I incorporated by reference the comments of Dr. Ian Fairlie, which may be found at the Regulations.gov website. As far as whether my thinking the views of BEIR VII, Dr. Fairlie, Dr. Jan Beyea, the National Academies of Science, etc. etc. more credible than yours is "without merit," just because I am not a scientist, I would cite the maxim of the great Samuel Johnson, that "a man may declare an egg bad although he cannot lay eggs himself." I find what BEIR VII said about the Feinendegen and Pollycove position persuasive, and I cannot imagine that the NAS would come to any different conclusion now, notwithstanding that the supporters of hormesis now include not only Lyndon LaRouche, who has touted it for 30 years, but also Ann Coulter. 

I am fascinated, Mohan, by your statement that I "picked the least important of the cancers." I realize that this is a comparative statement, but it seems to imply that thyroid cancer in UNimportant. Was that your intent? If so, and you think that all there is to estimating the importance of a disease is the fatality rate, no doubt you would rate river blindness as utterly insignificant.

May I respectfully ask what if anything you know about thyroid cancer, apart from the fatality rate? Are you aware that it is a lifelong condition, because of the need to remain on medication, and that many patients have difficulty arriving at a dose that comes close to restoring their pre-illness quality of life? You might want to check the current issue of "Thyroid," published by the American Thyroid Association, for an article on the impacts of thyroid cancer on the quality of life. In addition, the people who die of the disease are in general just as dead as those who succumb to statistically more lethal diseases. There were about 1600 of them in the U.S. last year.

Mohan, you attribute the views of the mainstream radiation establishment to the corrupting effect of money. If we go down that path, why should we not be even more inclined to link advocacy of hormesis to the corporations that have contributed to the hormesis movement over time, such as R. J. Reynolds, Philip Morris, Lorillard, British American Tobacco, ExxonMobil, Rohm & Haas, and NiPERA, an arm of the Nickel Institute? To be quite clear, I'm not suggesting that you or Carol or anyone else is a paid lackey of these companies, I'm just making the point that the argument about money can cut in more than one direction.

Finally, I do look forward to hearing your thoughts, whenever you are ready to share them with RADSAFE, on the contradiction between your and Carol's view of the post-Chernobyl thyroid cancers.

Best regards,
Peter 

Peter Crane, NRC Counsel for Special Projects (retired) 

"Some cats got it and some cats ain't." -- from "Speedo's Back in Town," by the Coasters

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