Compelling Reasons for a Paradigm Shift in Radiation Safety .. .. (Mohan Doss)

Compelling Reasons for a Paradigm Shift in Radiation Safety and Revised Health Physics Goals Mohan Doss, PhD, MCCPM Medical Physicist, Diagnostic Imaging Fox Chase Cancer Center, Philadelphia, PA E-mail: mohan.doss@fccc.edu

This is a revised version of the presentation given at the meeting of New Jersey Chapter of the Health Physics Society on September 16, 2014 Copyright Š 2014 by Mohan Doss Version 1.11, Release date: Oct 13, 2014

This presentation in its entirety may be copied, shared, and distributed freely without any restriction.

If using individual slides or figures, please acknowledge this presentation as the source.

Disclaimer: Opinions expressed in this presentation are my own professional opinion, and do not necessarily represent those of my employer.

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I will begin the presentation with a brief discussion of the present radiation safety paradigm based on the linear nothreshold hypothesis and the consequences of using this paradigm

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Recap of Current Radiation Safety Paradigm • Based on the linear no-threshold (LNT) extrapolation hypothesis for radiation-induced cancers • Adopted in the 1950s by the various advisory bodies, with concerns about the increasing use of radiation, but not based on any observed harm from low-dose radiation (LDR) • Recommended by most international and national advisory bodies repeatedly over the years (exception: French Academy of Sciences 2005) • Accepted by Most professional organizations • LNT hypothesis is the basis for radiation protection regulations Current radiation safety practices include: Monitoring radiation dose, complying with dose limits Keeping doses As Low As Reasonably Achievable (ALARA) 3

Consequences of using the LNT Hypothesis for Radiation Safety

Zero-threshold concept has a major impact on the uses of radiation – Implies smallest increase in radiation dose increases cancer risk – Results in fear of even the smallest amounts of radiation – Results in precautionary, evasive actions by governments, professional organizations, professionals, and the public to avoid or reduce low doses of radiation – Considerable costs due to ALARA. – Projected benefit of reduced cancers, if LNT hypothesis were true.

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Consequences of using the LNT Hypothesis for Radiation Safety – Real harm to public from the precautionary actions taken to reduce or avoid low radiation doses • Fukushima: LNT hypothesis based evacuation  evacuation-related short-term and long-term casualties, damage to local economy, diminished quality of life • Patients refusing CT scans or Physicians not prescribing CT scans  missed or delayed diagnosis • CT scans with poor diagnostic quality from dose reduction efforts  misdiagnosis • Discouragement of prospective studies of LDR for prevention and treatment of diseases  Possible lack of progress or delay in dealing with many diseases and conditions for which currently no effective treatments available, and animal models have shown promise of LDR • Suppression of nuclear power  Increased energy costs and casualties from use of other more expensive and more hazardous energy sources 5

Current Status of the LNT Hypothesis Evidence published over the past years: Supporting Carcinogenicity of LDR or the LNT hypothesis - A large number of publications Supporting Radiation hormesis or Threshold dose - A large number of publications

LDR carcinogenicity - Subject of debates over the years.

Why is there not a definitive conclusion on this subject, even after more than 50 years of intense study, even on the question whether LDR is beneficial or harmful?

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Now some general remarks on how to resolve controversial issues in science

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How to Resolve Controversial Issues in Science • For some issues, substantial number of publications would be found to support opposing points of view, making the issues controversial.

• However, we know that only one of those views can be correct, and the correct view would be determined when the issue gets resolved in the future.

• Hence, during the period of uncertainty, a substantial number of publications would support the wrong point of view. How is this possible, when both sides claim to use evidence to support their views, as is required in science?

See: Correcting Systemic Deficiencies in our Scientific Infrastructure, M.Doss, http://dose-response.metapress.com/link.asp?id=11h3l8t067886g08

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How to Resolve Controversial Issues in Science • Publications supporting the wrong side likely have faulty data, analysis and/or interpretation, leading the authors to make the wrong conclusion. Also, such publications would ignore or dismiss publications with evidence supporting the opposing point of view • When such faulty publications are identified, discredited, and eliminated from consideration, the single correct conclusion would be reached on the controversial issue • The sooner the scientific community does this, the sooner the issue can be resolved

See: Correcting Systemic Deficiencies in our Scientific Infrastructure, M.Doss, http://dose-response.metapress.com/link.asp?id=11h3l8t067886g08

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Controversial issue: Effect of Low-Dose Radiation on Cancer

Let us try to resolve this issue by following the above prescription – i.e. by examining evidence supporting both sides, and identifying and rejecting publications with faulty data, analysis and/or interpretation.

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First let us review the Evidence Supporting Radiation Hormesis or Threshold Dose for Carcinogenesis

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Threshold Dose of ~50 cGy for increased leukemias in Hiroshima survivors

UNSCEAR. 1958. Report of the United Nations Scientific Committee on the Effects of Atomic Radiation. General Assembly Official Records: Thirteenth session Supplement No. 17 (A/3838). Available: http://www.unscear.org/unscear/en/publications/1958.html Cuttler, 2014. Leukemia incidence of 96,000 Hiroshima atomic bomb survivors is compelling evidence that the LNT model is wrong.

12 http://www.ncbi.nlm.nih.gov/pubmed/24504164

Low-dose radiation (15 cGy) applied 10 times during 5 weeks (Total dose 1.5 Gy) had a cancer therapeutic effect, performing as well as chemotherapy

TBI – whole body irradiation, 15 cGy, 10 times during 5 weeks. COP - Chemotherapy Total body irradiation as treatment for lymphosarcoma. , Chaffey et al., 1976. http://www.ncbi.nlm.nih.gov/pubmed/823140

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Threshold Dose of ~10 Gy for induction of Bone Sarcomas in radium dial painters

Dose-response relationships for radium-induced bone sarcomas., Rowland RE, Stehney AF, Lucas HF. 1983. http://www.ncbi.nlm.nih.gov/pubmed/6862895 Radiation Hormesis and the Linear-No-Threshold Assumption, Charles L. Sanders - 2009, page 44, http://books.google.com/books?isbn=3642037208

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Reduction of breast cancer mortality in Canadian TB patients who had breast dose of ~15 cGy from fluoroscopy

Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis. Miller et al. 1989 http://www.ncbi.nlm.nih.gov/pubmed/2797101 Can Cancer Be Treated with Low Doses of Radiation?

Cuttler & Pollycove 2003 http://www.jpands.org/vol8no4/cuttler.pdf

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Significantly reduced cancer mortality rates in the 12 cGy and 50 cGy cohorts in villages near Mayak nuclear weapons facility

Long-term irradiation effects in the population evacuated from the East-Urals radioactive trace area, V.A. Kostyuchenko, L.Yu. Krestinina, 1994 http://www.sciencedirect.com/science/article/pii/0048969794900809 16

Improved survival of nonHodgkin’s Lymphoma patients when subjected to 10 or 15 cGy total-body or half-body irradiation (TBI or HBI) interspersed between radiation treatments to the tumor (Total dose=1.5 Gy).

Tumors outside the HBI field also regressed in response to the repeated LDR (Pollycove 2007), indicating it is likely the systemic adaptive response (e.g. immune enhancement), not tumor cellkilling from the total dose of 1.5 Gy that led to the cancer preventive effect.

(Sakamoto, 2004) Radiobiological Basis for Cancer Therapy by Total or Half-Body Irradiation http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657505/ (Pollycove, 2007) Radiobiological basis of low-dose irradiation in prevention and therapy of cancer, http://www.ncbi.nlm.nih.gov/pubmed/18648556

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*Reduction of cancers is significant.

Reduction of all cancers in the apartment residents in Taiwan subjected to an average dose of ~5 cGy due to contaminated building materials.

This reduction continued in the 2008 follow-up report, as described in Doss, 2013 Hwang et al., 2006 . Cancer risks in a population with prolonged low dose-rate γ-radiation exposure in radiocontaminated buildings, 1983 – 2002, http://www.ncbi.nlm.nih.gov/pubmed/17178625 18 Doss, 2013, Linear No-Threshold Model vs. Radiation Hormesis. http://www.ncbi.nlm.nih.gov/pubmed/24298226

Reduction of second cancers per kg of tissue in regions of body subjected to radiation dose of ~20 cGy during radiation therapy, in comparison to regions not subjected to any radiation dose

A new method of assessing the dose-carcinogenic effect relationship in patients exposed to ionizing radiation. A concise presentation of preliminary data., Tubiana, et al, 2011, http://www.ncbi.nlm.nih.gov/pubmed/21595074 19

Whole-body low-dose irradiation (15 cGy) applied 10 times during 5 weeks (Total dose 1.5 Gy) for nonHodgkin lymphoma patients had a cancer therapeutic effect, performing better than chemotherapy

TBI – whole body irradiation, 15 cGy x 10 over 5 weeks. CHOP - Chemotherapy Radiobiological basis of low-dose irradiation in prevention and therapy of cancer., Pollycove, 2007, http://www.ncbi.nlm.nih.gov/pubmed/18648556

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I did not find sufficient faults in these studies to overturn the conclusion of reduction of cancers from low-dose radiation or threshold dose for radiation-induced cancers.

If you become aware of such faults in any of these studies, please do let me know.

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Now some evidence showing a trend of reduced cancers with increased background radiation exposures

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Trend of lower cancer mortality rates associated with higher background radiation levels in the different states of USA

FRIGERIO, N. A., et al. 1973. Argonne Radiological Impact Program (ARIP). Part I. Carcinogenic hazard from low-level, low-rate radiation. Argonne National Lab., Ill. http://www.iaea.org/inis/collection/NCLCollectionStore/_Public/05/119/5119810.pdf 23

Maps of Radon Levels and Lung Cancer In the following maps of Radon Levels and Lung Cancer:

• High levels of radon are generally seen to be associated with lower levels of lung cancer • Higher incidence of lung cancer is generally seen to be associated with lower levels of radon.

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Radon Levels and Lung Cancer in Ireland Lung Cancer relative risk, both sexes

The regions of the country having higher radon levels (dark brown color) marked in green ovals are seen to have generally lower levels of lung cancer (green color) in the map on the right. The areas that have high levels of lung cancer (dark blue color) marked in red ovals are generally seen to correspond to lower levels of radon (white or yellow color) in the map on the left.

Radiation Doses Received by the Irish Population 2014 https://www.rpii.ie/pubs/reports/radiation/RPII_Radiation_Dos es_Irish_Population_2014.pdf All Ireland lung cancer atlas 1995-2007 http://www.ncri.ie/sites/ncri/files/atlas/2007/Lung%20cancer.p df 25

Radon Levels and Lung Cancer in UK

The regions of the country having higher radon levels (dark blue color) marked in green ovals are seen to have generally lower levels of lung cancer (dark blue or light blue) in the map on the right. The areas that have higher levels of lung cancer (dark red color) marked in red ovals are generally seen to correspond to lower levels of radon (light blue color) in the map on the left.

Radon levels in UK: http://archive.defra.gov.uk/evidence/statistics/environment/radioact/kf/rakf02.htm UK Cancer Atlas: http://publications.cancerresearchuk.org/downloads/product/CS_CS_ATLAS_UK%26IRE.pdf

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Radon Levels and Lung Cancer in USA

The regions of the country having higher radon levels (red color) marked in white ovals are seen to have generally lower levels of lung cancer (blue color) in the map on the right. The areas that have higher levels of lung cancer (red color) marked in black ovals are generally seen to correspond to lower levels of radon (dark blue color) in the map on the left.

Radon levels: http://energy.lbl.gov/ie/high-radon/frac4.htm Lung, Trachea, bronchus, pleura cancer mortality: http://ratecalc.cancer.gov/ratecalc/ 27

Whereas multiple confounding factors would affect the cancer rates in such studies of correlations of cancers with background radiation, the confounding factors would likely on the average largely cancel out when the large unselected whole countries’ populations and long time periods are considered. The persistence of the trend of reduced cancers with increased radiation doses in these data indicates the trend observed may be a signal rather than due to a systematic error due to the confounding factors.

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Now let us review the Evidence Supporting LDR Carcinogenicity or the LNT Hypothesis

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Is there any evidence to support LDR carcinogenicity or LNT hypothesis?

The most important and most often-quoted evidence is Atomic Bomb Survivor data.

BEIR VII Report, Page 141

BEIR VII Report http://www.nap.edu/openbook.php?record_id=11340 30

Atomic Bomb Survivor Data have been described as the Gold Standard for Assessing LDR Cancer Risks by Influential Scientists (HALL & BRENNER, 2008)

(HALL & BRENNER, 2008) Cancer risks from diagnostic radiology. http://www.ncbi.nlm.nih.gov/pubmed/18440940

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Linearity of Dose-Response in Atomic Bomb Survivor Cancer Data

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The data seem to be consistent with the LNT hypothesis. Note the reduction in the ERR at ~0.5 Gy, though not significant

BEIR VII Report http://www.nap.edu/openbook.php?record_id=11340 33

As a function of dose, ERRs seem to: go up from 0 to 0.3 Gy, go down for 0.3 to 0.7 Gy go up for doses above 0.7 Gy

ERR does not appear to be a linear function of dose The text of the (Ozasa 2012) paper says there is significant curvature in dose-response in the 0-2 Gy range, and there is lower than expected cancer rates in the 0.3-0.7 Gy range (see text on next slide).

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases., Ozasa et al, 2012, Errata 2013 http://www.rrjournal.org/doi/abs/10.1667/RROL05.1 34

Curvature in Dose-Response in Atomic Bomb Survivor Cancer Mortality Data (Ozasa, 2012) Page 234, Ozasa et al. 2012

Page 238, Ozasa et al. 2012

Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases., Ozasa et al, 2012, http://www.ncbi.nlm.nih.gov/pubmed/22171960 35

Ozasa et al. used a linear dose-response function to fit the atomic bomb survivor data to extract the ERRs Page 231, Ozasa et al. 2012

Since the data has significant curvature, the linear model does not fit the data (though Ozasa et al. state in their paper that over the whole dose range, the linear model provided the best fit). Since the LNT hypothesis does not fit the data, the ERRs for low doses in Figure 4 of (Ozasa et al., 2012), based as they are on the fit using the LNT hypothesis, are parameters determined from the fit, but cannot be considered to be the excess risk of cancer from low doses of radiation.

For more detailed analysis of the LSS 14 data, please see the Blog at: http://lss-14-report-analysis.blogspot.com/ Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases., Ozasa et al, 2012, http://www.ncbi.nlm.nih.gov/pubmed/22171960 36

Is there any explanation for the significantly reduced cancers for doses near 0.5 Gy?

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Possible explanation for the lower than expected cancer rates at 0.5 Gy • Up-regulation of adaptive protection due to LDR (Feinendegen, L.E., et al. 2013), in the lowest dose cohorts (0 to ~20 cGy) would reduce cancers in these subjects • Note that there was no un-irradiated control group from which baseline cancer rates were determined for use in calculating ERRs. The ERRs were determined by fitting the whole dataset to a linear functional form for dose response (after accounting for other factors).

• Since cancer rates in the low dose subjects would effectively determine the baseline cancer rates during the fitting process, there would be a negative bias in the baseline cancer rates used to generate the ERRs. (Doss, 2013) Feinendegen, L.E., et al. 2013, Hormesis by Low Dose Radiation Effects: Low-Dose Cancer Risk Modeling Must Recognize UpRegulation of Protection, in Therapeutic Nuclear Medicine. http://www.springer.com/medicine/radiology/book/978-3-54036718-5 Doss, 2012: Evidence Supporting Radiation Hormesis in Atomic Bomb Survivor Cancer Mortality Data. http://doseresponse.metapress.com/link.asp?id=r3158310701545m5 Doss, 2013, Linear No-Threshold Model vs. Radiation Hormesis. http://www.ncbi.nlm.nih.gov/pubmed/24298226 38

Correcting ERR for Bias In Baseline Cancer Rate If δ is the percentage bias in the measured baseline cancer mortality rate, it can be shown that the ERR(corr), ERR corrected for the bias, is given by the following equation, as shown in Appendix A of (Doss, 2012):

The (Ozasa 2013) data was corrected for an estimated bias of -20% in the baseline cancer mortality rate (Doss, 2013). The resulting ERR plot is shown in next slide.

(Doss, 2012) Evidence Supporting Radiation Hormesis in Atomic Bomb Survivor Cancer Mortality Data.

M. Doss, 2012. http://dose-response.metapress.com/link.asp?id=r3158310701545m5 Doss, 2013, Linear No-Threshold Model vs. Radiation Hormesis. http://www.ncbi.nlm.nih.gov/pubmed/24298226 (Ozasa et al 2013) Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases., http://www.rrjournal.org/doi/abs/10.1667/RROL05.1 39

The shape of dose-response curve, with the correction for the bias in the baseline cancer rate, is consistent with the concept of radiation hormesis.

Linear No-Threshold Model vs. Radiation Hormesis, Doss, 2013. http://www.ncbi.nlm.nih.gov/pubmed/24298226

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LNT hypothesis cannot explain the non-linearity in doseresponse (reduction of cancer rates near 0.5 Gy) whereas the alternative radiation hormesis hypothesis has a possible explanation.

According to the radiation hormesis hypothesis, low-dose radiation would reduce rather than increase cancer risk.

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Dose-Threshold in Atomic Bomb Survivor Cancer Mortality Data

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Threshold Dose Analysis in Ozasa 2012 Study Abstract says:

On Page 231:

The functional form they used for threshold analysis: (d)=β2(d–d0) for d>d0 or (d)=0 for d d0, where d0 is the threshold, did not allow the ERR values to extend into negative values whereas one of the data points and 95% CI of several of the data points (in Figure 4) do extend into negative values.

Part of Fig. 4 For detailed analysis, see the Blog at: http://lss-14-report-analysis.blogspot.com/ Ozasa et al, 2012, http://www.ncbi.nlm.nih.gov/pubmed/22171960 Doss, 2013. http://www.ncbi.nlm.nih.gov/pubmed/24298226

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Threshold Dose Analysis in Ozasa 2012 Study If they had used a more generalized functional form, they would not have concluded that zero dose is the best estimate of the dose threshold, as the lower bounds of the 95% CIs would have been below zero for low doses.

(Doss et al., 2012) (Doss, 2013).

See Figure 2 of (Doss, 2013), for the results from such a calculation, for example.

Part of Figure 2 of (Doss, 2013)

Thus, the Ozasa 2012 data do not support the absence of a threshold dose, contrary to the claims of the paper.

Note: Ozasa et al. were given a chance to respond to our Comments (Doss et al., 2012) prior to its publication by Radiation Research, but they did not respond with a refutation of our analysis and conclusion.

For detailed analysis, see the Blog at: http://lss-14-report-analysis.blogspot.com/ (Doss et al., 2012) Comments on "Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003, Ozasa et al. 2012�, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662863/ (Doss, 2013). http://www.ncbi.nlm.nih.gov/pubmed/24298226

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The Latest Atomic Bomb Survivor Data support neither the “Linearity” nor the “No-Threshold Dose” aspect of the LNT hypothesis

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Scientists supporting LNT hypothesis implicitly acknowledge the qualitative change in Atomic Bomb Survivor data, i.e., that they no longer support the LNT hypothesis or LDR carcinogenicity

They refer to older (Preston et al., 2007) data to raise LDR cancer concerns, not the newer (Ozasa et al., 2012) data

(Preston et al., 2007): http://www.ncbi.nlm.nih.gov/pubmed/17722996 (Ozasa et al, 2012): http://www.ncbi.nlm.nih.gov/pubmed/22171960 46

Recent Articles that Do Not Refer to Ozasa 2012 data to raise LDR Cancer Concerns but use older data, e.g. Preston 2007 1.

BRENNER, D. J. 2014. What we know and what we don't know about cancer risks associated with radiation doses from radiological imaging. Br J Radiol, 87, 20130629. Available: http://www.ncbi.nlm.nih.gov/pubmed/24198200

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BRIX, G. & NEKOLLA, E. A. 2014. Response to letter by Doss: addition of diagnostic CT scan does not increase the cancer risk in patients undergoing SPECT studies. Eur J Nucl Med Mol Imaging, 41 Suppl 1, 148-9. Available: http://www.ncbi.nlm.nih.gov/pubmed/24595466

3.

BRIX, G., NEKOLLA, E. A., BOROWSKI, M. & NOSSKE, D. 2013. Radiation risk and protection of patients in clinical SPECT/CT. Eur J Nucl Med Mol Imaging. Available: http://www.ncbi.nlm.nih.gov/pubmed/24052089

4.

CUCINOTTA, F. A. 2014. Space radiation risks for astronauts on multiple International Space Station missions. PLoS One, 9, e96099. Available: http://www.ncbi.nlm.nih.gov/pubmed/24759903

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MIGLIORETTI, D. L., JOHNSON, E., WILLIAMS, A., GREENLEE, R. T., et al. 2013. The use of computed tomography in pediatrics and the associated radiation exposure and estimated cancer risk. JAMA Pediatr, 167, 700-7. Available: http://www.ncbi.nlm.nih.gov/pubmed/23754213

6.

STEWARD, M. J., TAYLOR, S. A. & HALLIGAN, S. 2014. Abdominal computed tomography, colonography and radiation exposure: what the surgeon needs to know. Colorectal Disease, 16, 347-352. Available: http://dx.doi.org/10.1111/codi.12451

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Non-citation of the latest Atomic Bomb Survivor Data In the latest published debate on health effects of low-dose radiation, (Doss,2014) atomic bomb survivor data were not quoted for claiming LDR carcinogenicity in Opening Statement – unlike in previous such debates.

In the Rebuttal, older Atomic Bomb Survivor data and their analysis were used to support LDR concerns, and the newer Ozasa et al.

2012 data were not used.

(Doss,2014) Point/Counterpoint: Low-dose radiation is beneficial, not harmful. Doss, M., Little, M. P. & Orton, C. G. 2014.

In Medical Physics Journal: http://www.ncbi.nlm.nih.gov/pubmed/24989368 48

The Atomic Bomb Survivor Data, declared as the most important data for determining lowdose radiation health effects by BEIR VII report, and referred to as gold standard for estimating low-dose radiation cancer risks by influential scientists, no longer give support to the LNT hypothesis.

This is not only the conclusion from the analysis presented here, but also has been acknowledged by leading scientists implicitly, by their actions of not quoting the latest atomic bomb survivor data to raise low-dose radiation cancer concerns.

When the most important data do not support a hypothesis, the hypothesis has to be rejected.

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Other Claims of LDR Carcinogenicity

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Other Claims of LDR Carcinogenicity 15-country study of radiation workers (Cardis, 2005)

These data were used in BEIR VII report and in many publications to lend support to claims of LDR cancer risk (Cardis, 2005) Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC558612/ 51

With Problems Identified in the Canadian Data (CNSC 2011), the 15-country study of radiation workers data no longer provide evidence for LDR carcinogenicity (Zablotska, 2013)

(CNSC 2011) CNSC. INFO-0811. Verifying Canadian Nuclear Energy Worker Radiation Risk: A Reanalysis of Cancer Mortality in Canadian Nuclear Energy Workers (1957-1994) Summary Report, Canadian Nuclear Safety Commission.

2011 https://nuclearsafety.gc.ca/pubs_catalogue/uploads/INFO0811_e.pdf Published June 2011.

(Zablotska, 2013) Zablotska, L.B., R.S. Lane, and P.A. Thompson, A reanalysis of cancer mortality in Canadian nuclear workers (1956-1994) based on revised exposure and cohort data. Br J Cancer, 2013. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887280/ 52

The main evidence provided in the BEIR VII report for LNT hypothesis/LDR carcinogenicity (the Atomic bomb survivor data and the 15country study of radiation workers) no longer provide support for LNT hypothesis/LDR carcinogenicity The low-dose radiation cancer risk estimates of BEIR VII report based on their use of the LNT hypothesis therefore do not have any validity.

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Other Claims of LDR Carcinogenicity • In the recent debate on the health effects of LDR (Doss,2014), consistency of childhood cancer risk factors from Oxford and Japanese (atomic bomb survivor) studies was stated as evidence for carcinogenicity of in-utero LDR exposure.

• However, for the Japanese cohort: – Leukemias observed only following high dose radiation (Wakeford,2013) – Risk coefficients were calculated using the LNT hypothesis, creating illusion of leukemias from LDR whereas none was observed

• Also, cohort studies, which are superior to case-control studies, have not shown increased leukemia risk (Brent, 2014).

(Wakeford,2013) Risk coefficients for childhood cancer after intrauterine irradiation: a review, http://www.ncbi.nlm.nih.gov/pubmed/12943238 (Brent, 2014), “Carcinogenic risks of prenatal ionizing radiation,” http://dx.doi.org/10.1016/j.siny.2013.11.009 (Doss, 2014), Point/Counterpoint: Low-dose radiation is beneficial, not harmful. http://www.ncbi.nlm.nih.gov/pubmed/24989368 54

Other Claims of LDR Carcinogenicity Increase of Childhood Leukemias with increased Natural Background Radiation (Kendall, 2013) This study does not consider confounding factors such as breastfeeding. Since the 95% CI for total leukemia relative risk is 1.01-1.13, (see part of Table 3 below), small changes in the results from consideration of such factors could make the increased leukemias statistically insignificant. Hence, we should wait for better data/analysis before drawing a conclusion on this subject.

(Kendall, 2013) A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other 55 cancers in Great Britain during 1980-2006 http://www.ncbi.nlm.nih.gov/pubmed/22766784

Other Claims of LDR Carcinogenicity • The studies of cancers following childhood CT scans (Pearce, 2012) and (Mathews, 2013).

These studies have methodological issues and the pattern of observed cancers is not consistent with current knowledge, raising major doubts about their conclusion (Walsh, 2014).

(Pearce, 2012) Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3418594/ (Mathews, 2013) Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660619/ (Walsh, 2014) Risks from CT scans--what do recent studies tell us? http://www.ncbi.nlm.nih.gov/pubmed/24594968 56

Other Claims of LDR Carcinogenicity Taiwan Study of Population in Radiocontaminated Buildings (Hwang, 2008)

Hwang, 2008) report the slightly increased risk for leukemias and breast cancers in the radiated group while not mentioning the reduction in other cancer types, which resulted in reduction in overall cancer rates. Their statement present a misleading picture.

The observed reduction of total cancers in the radiated cohort in the (Hwang 2006) study continues in the (Hwang 2008) study, as discussed in (Doss, 2013) and in the blog below.

(Hwang 2008). Estimates of relative risks for cancers in a population after prolonged low-dose-rate radiation exposure: a follow-up assessment from 1983 to 2005. http://www.ncbi.nlm.nih.gov/pubmed/18666807 (Hwang 2006). Cancer risks in a population with prolonged low dose-rate gamma-radiation exposure in radiocontaminated buildings, 19832002. http://www.ncbi.nlm.nih.gov/pubmed/17178625 (Doss,2013) Linear No-Threshold Model vs. Radiation Hormesis, http://www.ncbi.nlm.nih.gov/pubmed/24298226 More details in Blog: Misleading Conclusions in Taiwan Apartment Dwellers Study http://taiwan-apt-cancer-data-analysis.blogspot.com/ 57

Other Claims of LDR Carcinogenicity Breast Cancers in Canadian TB Patients who Underwent Fluoroscopy Table 1, (Miller 1989)

Table III (Howe, 1996)

Instead of separating low dose groups into finer bins (10 cGy) like (Miller 1989) did (Table 1), (Howe, 1996) lumped 0.01-0.49 Gy into a single bin (Table III), effectively making the reduction in cancers at 0.15 Gy in Miller study disappear.

See Discussion in Blog: Misleading Conclusions in Breast Cancer Study http://miller-breast-cancer-study.blogspot.com/ (Howe, 1996), Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study. http://www.ncbi.nlm.nih.gov/pubmed/8643829 (Miller, 1989) Mortality from breast cancer after irradiation during fluoroscopic examinations in patients being treated for tuberculosis.

58 http://www.ncbi.nlm.nih.gov/pubmed/2797101

As seen in previous slides, many articles have tended to hide the reduction of cancers from low doses of radiation or make claims of low-dose radiation cancer risk with defective data or faulty analysis/interpretation. We should not accept conclusions of these publications at face value, but dig deeper to see if there has been faulty representation and/or faulty analysis of the data.

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Claims of support for LNT Hypothesis Study of DNA Double-strand Breaks following CT scans

• Linearity of dose-response was reported for the number of DNA Double-strand breaks (DSBs) one hour after CT scan (Halm, 2014).

• Because of the observed DNA DSBs, cancer concerns are raised.

(Halm, 2014) Halm BM, Franke AA, Lai JF, Turner HC, Brenner DJ, Zohrabian VM, Dimauro R, γ-H2AX foci are increased in lymphocytes in vivo in young children 1 h after very low-dose X-irradiation: a pilot study. http://www.ncbi.nlm.nih.gov/pubmed/24756254

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Other activities that result in DNA damage • A short bout of exercise at moderate and high intensity (5 min) can cause an increase in DNA damage. Possible cancer concerns were raised. (Fogarty, M.C., et al. 2011) • Learning results in increased DNA DSBs in the brain (mouse study).

Possible link to Alzheimer’s disease was mentioned. (Suberbielle E et al. 2013) The concerns regarding increased DNA damage from such activities are not justified, as the adaptive protection due to the increased DNA damage is beneficial to health. (Doss, 2014)

Fogarty, M.C., et al. 2011, Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation. http://www.ncbi.nlm.nih.gov/pubmed/20839226 Suberbielle E et al. 2013. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-beta. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637871/ (Doss, 2014) See discussion of DNA damage in Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases, http://dose-response.metapress.com/link.asp?id=m665004074w5xl13 (Blog) Also see the blog “Deadly DNA Damage” http://dossreport.blogspot.com/

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Misguided concerns from Short-term Increased DNA Damage • These concerns completely ignore the body’s adaptive response of increased protection, which would reduce the endogenous DNA damage, and so reduce the overall DNA damage in the long term. E.g. For mice (Osipov, 2013), For drosophila (Koana 2010) • Ignoring the adaptive response, one will arrive at the wrong conclusion.

• Exercise improves physical health, including reducing cancers, in spite of the increased DNA damage from the exercise • Learning activities slow down cognitive decline in the elderly, in spite of the increased DNA damage from learning activities.

• Short-term increased DNA damage following exercise & thinking improve physical and brain health due to the adaptive response, and improved protection from the enhanced defenses.

Osipov 2013, In vivo gamma-irradiation low dose threshold for suppression of DNA double strand breaks below the spontaneous level in mouse blood and spleen cells. http://www.ncbi.nlm.nih.gov/pubmed/23664857 Koana 2010, A U-shaped dose-response relationship between x radiation and sex-linked recessive lethal mutation in male germ cells of Drosophila http://www.ncbi.nlm.nih.gov/pubmed/20681798 62

Importance of Considering Adaptive Response The Anti-angiogenesis therapy for cancer, based on the knowledge that angiogenesis is needed for the growth of tumors,

ultimately results in more aggressive tumors,

because the tumor’s adaptive response to the anti-angiogenesis therapy, of increasing other angiogenesis factors, was ignored (Pà ez-Ribes, 2009).

(PĂ ez-Ribes, 2009) Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. http://www.ncbi.nlm.nih.gov/pubmed/19249680

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Importance of Considering Adaptive Response

Adaptive response of tumors to the antiangiogenesis treatment was ignored.

Resulted in no improvement in survival compared to placebo. Resulted in: “higher rates of neurocognitive decline, increased symptom severity, and decline in health-related quality of life”.

(Gilbert, 2014) A Randomized Trial of Bevacizumab for Newly Diagnosed Glioblastoma, http://www.ncbi.nlm.nih.gov/pubmed/24552317

Ignoring Adaptive Response was harmful to patients. Please don’t do this.

Adaptive response from LDR resulted in improved survival, better than chemotherapy (Pollycove, 2007) Radiobiological basis of low-dose irradiation in prevention and therapy of cancer., http://www.ncbi.nlm.nih.gov/pubmed/18648556 More discussion of adaptive response in: The importance of adaptive response in cancer prevention and therapy, M. Doss, http://dx.doi.org/10.1118/1.4773027

Utilizing Adaptive Response 64 benefited patients. Please do this.

Please note that there is endogenous DNA damage occurring even in the absence of any radiation. The effect of adaptive response due to low dose radiation would be reduction of the endogenous damage in the subsequent period, due to the enhanced defenses. This results in reducing the final total damage.

The previous slide showed how important it is to include adaptive response in our considerations.

When the effect of adaptive response is included, there is no linear increase in final total damage with dose for low doses, and no reason to even propose the LNT hypothesis.

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Large Number of Articles Challenging LDR Concerns Have Been Published

by Many Authors in the past, with no Effective Rebuttal

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Large Number of Articles Challenging LDR Concerns with no Effective Rebuttal 1.

2.

3.

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CALABRESE, E. J. & BALDWIN, L. A. 2000. Radiation hormesis: its historical foundations as a biological hypothesis. Hum Exp Toxicol, 19, 4175. http://het.sagepub.com/content/19/1/41 CAMERON, J. R. 2002. Radiation increased the longevity of British radiologists. Br J Radiol, 75, 6379. http://www.birpublications.org/doi/full/10.1259/bjr.75.895.750637 CHOI, N. C., TIMOTHY, A. R., KAUFMAN, S. D., CAREY, R. W. & AISENBERG, A. C. 1979. Low dose fractionated whole body irradiation in the treatment of advanced non-Hodgkin's lymphoma. Cancer, 43, 163642. http://www.ncbi.nlm.nih.gov/pubmed/582159 67 COHEN, B. 2007. The Cancer Risk from Low-Level Radiation. In: TACK, D. & GEVENOIS, P. (eds.) Radiation Dose from Adult and Pediatric Multidetector Computed Tomography.Berlin: SpringerVerlag. http://rd.springer.com/chapter/10.1007/174_2011_401 CUTTLER, J. M. & POLLYCOVE, M. 2003. Can Cancer Be Treated with Low Doses of Radiation? Journal of American Physicians and Surgeons. http://www.jpands.org/vol8no4/cuttler.pdf

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Large Number of Articles Challenging LDR Concerns with no Effective Rebuttal 6.

FAROOQUE, A., MATHUR, R., VERMA, A., KAUL, V., BHATT, A. N., ADHIKARI, J. S., AFRIN, F., SINGH, S. & DWARAKANATH, B. S. 2011. Low-dose radiation therapy of cancer: role of immune enhancement. Expert Rev Anticancer Ther, 11, 791-802. http://www.ncbi.nlm.nih.gov/pubmed/21554054 7. FEINENDEGEN, L. E. 2005. Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiol, 78, 37. http://www.ncbi.nlm.nih.gov/pubmed/15673519 8. FEINENDEGEN, L. E., POLLYCOVE, M. & NEUMANN, R. D. 2013. Hormesis

by Low Dose Radiation Effects: Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection. In: BAUM, R. P. (ed.) Therapeutic Nuclear Medicine. Springer. http://rd.springer.com/chapter/10.1007/174_2012_686 9. JAWOROWSKI, Z. 1997. Beneficial effects of radiation and regulatory policy. Australas Phys Eng Sci Med, 20, 12538. http://www.ncbi.nlm.nih.gov/pubmed/9409013 10. LIU, S. Z. 2007. Cancer control related to stimulation of immunity by lowdose radiation.Dose Response, 5, 3947. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2477702/ 68

Large Number of Articles Challenging LDR Concerns with no Effective Rebuttal 11. LUCKEY, T. D. 1980. Hormesis with ionizing radiation, Boca Raton, Fla., CRC Press.http://books.google.com/books?id=adZqAAAAMAAJ 12. LUCKEY, T. D. 1991. Radiation hormesis, Boca Raton, Fla., CRC Press.http://books.google.com/books?isbn=0849361591 13. LUCKEY, T. D. 2006. Radiation hormesis: the good, the bad, and the ugly. Dose Response,4, 16990. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2477686/ 14. LUCKEY, T. D. 2008. Atomic bomb health benefits. Dose Response, 6, 36982.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592990/ 15. POLLYCOVE, M. 2007. Radiobiological Basis of Low-Dose Irradiation in Prevention and Therapy of Cancer. Dose-Response, 5, 2638.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2477707/ 16. SAKAMOTO, K. 2004. Radiobiological basis for cancer therapy by total or half-body irradiation. Nonlinearity Biol Toxicol Med, 2, 293316. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2657505/ 17. SANDERS, C. L. 2010. Radiation hormesis and the linear-no-threshold assumption,Heidelberg, Springer. http://rd.springer.com/book/10.1007%2F978-3-642-03720-7 69

Large Number of Articles Challenging LDR Concerns with no Effective Rebuttal 18. SCOTT, B. R. 2008. It's time for a new low-dose-radiation risk assessment paradigm--one that acknowledges hormesis. Dose Response, 6, 33351. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592992/ 19. TAKATORI, M., HATTORI, S. & YAGI, M. 2010. Clinical significance of lowdose radiation therapy: radiation hormesis. International Journal of Low Radiation, 7, 511519. http://inderscience.metapress.com/content/n228864021m58031/ 20. TUBIANA, M., DIALLO, I., CHAVAUDRA, J., LEFKOPOULOS, D., BOURHIS, J., GIRINSKY, T., BRIDER, A., HAWKINS, M., HADDY, N., EL-FAYECH, C., ADJADJ, E., CLERO, E. & DE VATHAIRE, F. 2011. A new method of assessing the dose-carcinogenic effect relationship in patients exposed to ionizing radiation. A concise presentation of preliminary data. Health Phys, 100, 296-9. http://www.ncbi.nlm.nih.gov/pubmed/21595074 21. TUBIANA, M., FEINENDEGEN, L. E., YANG, C. & KAMINSKI, J. M. 2009. The linear no-threshold relationship is inconsistent with radiation biologic and experimental data.Radiology, 251, 1322. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2663584/ 22. VAISERMAN, A. M. 2010. Radiation hormesis: historical perspective and implications for low-dose cancer risk assessment. Dose Response, 8, 17291. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2889502/ 70

Large Number of Articles Challenging LDR Concerns with no Effective Rebuttal (Listed Below are Articles in which I was an author or co-author) Note: The articles have been published in many different journals.

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Comments on "Studies of the mortality of atomic bomb survivors, Report 14, 1950-2003: an overview of cancer and noncancer diseases, Ozasa et al. 2012). M. Doss, B. L. Egleston and S. Litwin, Radiat Res 178, 244-245 (2012).

Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662863/ Evidence Supporting Radiation Hormesis in Atomic Bomb Survivor Cancer Mortality Data.

M. Doss, Dose Response. 10, 584-592 (2012). Available at: http://doseresponse.metapress.com/link.asp?id=r3158310701545m5 Shifting the Paradigm in Radiation Safety. M. Doss, Dose Response. 10, 562-583 (2012).

Available at: http://dose-response.metapress.com/link.asp?id=a35338004706373w The importance of adaptive response in cancer prevention and therapy, M. Doss, Medical Physics, 40, 032302 (2013). Available at: http://dx.doi.org/10.1118/1.4773027 Linear No-Threshold Model vs. Radiation Hormesis, M. Doss, Dose Response. 11, 480–497 (2013). Available at: http://dose-response.metapress.com/link.asp?id=c577154j89t86l81 No Increased Risk of Cancer from CT Scans, M. Doss, American Journal of Roentgenology, 2014;202:W410. 10.2214/AJR.13.11525. Available at: http://www.ajronline.org/doi/full/10.2214/AJR.13.11525 Linear No-Threshold Model May Not Be Appropriate for Estimating Cancer Risk from CT, Mohan Doss, Radiology, Jan 2014, Vol. 270, No. 1:307–308. Available at: 71 http://pubs.rsna.org/doi/pdf/10.1148/radiol.13131661

Large Number of Articles Challenging LDR Concerns – with no effective rebuttal 8.

Conclusion of Increased Risk of Cataracts Associated with CT Scans of the Head May Not be Justified, M. Doss, American Journal of Roentgenology, 2014;202:W413-W. 10.2214/AJR.13.11867. Available at: http://www.ajronline.org/doi/full/10.2214/AJR.13.11867 9. Low Dose Radiation Adaptive Protection to Control Neurodegenerative Diseases, M. Doss, Dose-Response, 12:277–287, 2014, Available at: http://dose-response.metapress.com/link.asp?id=m665004074w5xl13 10. Correcting Systemic Deficiencies in our Scientific Infrastructure, M.Doss, DoseResponse, 12:185–201, 2014, Available at: http://doseresponse.metapress.com/link.asp?id=11h3l8t067886g08 11. Commentary: Ethical Issues of Current Health-Protection Policies on Low-Dose Ionizing Radiation, Yehoshua Socol, Ludwik Dobrzyński, Mohan Doss, Ludwig E. Feinendegen, Marek K. Janiak, Mark L. Miller, Charles L. Sanders, Bobby R. Scott, Brant Ulsh, Alexander Vaiserman, Dose Response. (2013). Available at: http://dose-response.metapress.com/link.asp?id=pl8x435l31602846 12. Adoption of Linear No-Threshold Model Violated Basic Scientific Principles and Was Harmful, Mohan Doss, Archives of Toxicology, 2014, Available at: http://rd.springer.com/content/pdf/10.1007%2Fs00204-014-1208-8.pdf 72

Large Number of Articles Challenging LDR Concerns – with no effective rebuttal 13. Comment on "NAIRAS aircraft radiation model development, dose climatology, and initial validation" by Christopher J. Mertens, Matthias M. Meier, Steven Brown, Ryan B. Norman, and Xiaojing Xu", Yehoshua Socol, Jerry M. Cuttler, Ludwik Dobrzyński, Mohan Doss, Ludwig E. Feinendegen, Krzysztof W. Fornalski, Marek K. Janiak, Mark L. Miller, Kanokporn Noy Rithidech, Charles L. Sanders, Bobby R. Scott, Brant Ulsh, Alexander Vaiserman, and James Welsh, Space Weather, 12, 120–121, 2014. Available at: http://onlinelibrary.wiley.com/enhanced/doi/10.1002/2013SW001021/ 14. Addition of diagnostic CT scan does not increase the cancer risk in patients undergoing SPECT studies, Mohan Doss, European Journal of Nuclear Medicine and Molecular Imaging, 2014. Available at:http://nuclearmedicineandmolecularimaginggateway.net/ArticlePage.aspx?DOI= 10.1007/s00259-014-2711-0 15. Radiation doses from radiological imaging do not increase the risk of cancer. Letter to the editor regarding the article by Brenner: “What we know and what we don't know about cancer risks associated with radiation doses from radiological imaging", Mohan Doss, British Journal of Radiology, 2014;87:20140085. Available at: http://www.birpublications.org/doi/full/10.1259/bjr.20140085 73

Large Number of Articles Challenging LDR Concerns – with no effective rebuttal 16. Radiation Dose Justification and Optimization Should Not be Applied to Medical Imaging in Emergency Medicine - (Letter to the Editor regarding "Sierzenski, et al. Applications of justification and optimization in medical imaging: examples of clinical guidance for computed tomography use in emergency medicine. Ann Emerg Med. Jan 2014;63(1):25-32.), Mohan Doss, Annals of Emergency Medicine, Sep 2014;64, (3):332–333. Available at: http://www.sciencedirect.com/science/article/pii/S0196064414005174.

17. CT Radiation Dose Optimization is Not Advisable in View of Current Knowledge, Mohan Doss, J Am Coll Radiol. 2014;11:745-6. Available at: http://www.sciencedirect.com/science/article/pii/S1546144014001550.

18. Atomic Bomb Survivor Cataract Surgery Prevalence Data are Consistent with Non-zero Threshold Dose - Comment on Article by Nakashima et al. 2013, Mohan Doss, Brian L. Egleston, Samuel Litwin, Health Phys. 2014 Sep;107(3):262-3. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25068966 19. Point/Counterpoint: Low-dose radiation is beneficial, not harmful, Mohan Doss, Mark P. Little, and Colin G. Orton, Medical Physics, 41, 070601 (2014). http://scitation.aip.org/content/aapm/journal/medphys/41/7/10.1118/1.4881095

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Conclusion from the analysis of the publications supporting both sides of the controversial issue of effect of low-dose radiation on cancer: The publications with faulty data, analysis, or interpretation have been eliminated, resulting in a definitive conclusion.

The controversy has been resolved.

Low-dose radiation is not carcinogenic. Low-dose radiation results in reduced cancers, with a threshold dose for induction of increased cancers from radiation.

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Current Status of the Controversial Issue of Effect of LDR on Cancer- Summary • Considerable published evidence for radiation hormesis and for threshold dose response • The main evidence usually quoted for LDR carcinogenicity or LNT hypothesis – atomic bomb survivor data – no longer provide evidence for LDR cancer concerns • Faults have been identified in publications claiming LDR carcinogenicity, negating their conclusions • No credible evidence exists for LDR carcinogenicity

If you know of any evidence for LDR carcinogenicity that appears to be credible, please research to confirm its credibility, and let me know.

Conclusion: The controversy regarding LDR has been resolved. LDR is not carcinogenic, and may be beneficial to human health.

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When was the hypothesis of radiation hormesis proposed?

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T.D. Luckey’s Book Published in 1980

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What was the Impact of not studying Radiation Hormesis for cancer prevention in the 1980s?

If small clinical trials of cancer prevention using radiation hormesis had been conducted in the 1980s, they would have demonstrated reduction of cancers following low-dose radiation. This would have led to optimization of the cancer prevention, and adoption of radiation hormesis as a method of cancer prevention.

Worldwide Impact of not studying radiation hormesis in 1980s: Current worldwide cancer mortality rate: ~7.6 M per year Assume 10% reduction in cancer mortality from the use of radiation hormesis (this is a conservative assumption – see data in the earlier slides).

Estimate 760K reduction of cancer deaths per year by using radiation hormesis Preventable cancer death toll over last 20 years from not using radiation hormesis ~15M Cancer deaths occurring now which could have been prevented using radiation hormesis: >2000 per day

More than 2000 preventable cancer deaths are likely occurring presently every day in the world because of not studying radiation hormesis in the 1980s.

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Consequences of using the LNT Hypothesis for Radiation Safety

Previously listed harms from the use of LNT hypothesis: • Evacuation-related Casualties in Fukushima • Missed/Delayed diagnoses and Misdiagnoses due to CT scan radiation-dose concerns • Possible lack of progress in controlling aging-related diseases • Increased casualties and environmental degradation from suppression of safer, cleaner nuclear power • Excessive costs from ALARA with no benefit

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The immensity of the harm and the many different ways in which harm has been caused by the use of LNT hypothesis and LDR cancer concerns have led many professionals from different countries and a wide variety of backgrounds to join together, in an attempt to overcome the menace of the current radiation safety paradigm based on the LNT hypothesis

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Scientists for Accurate Radiation Information (SARI) Because of concerns about the harm to the public from the use of the LNT hypothesis and the fear of LDR, a new international group of scientists called “Scientists for Accurate Radiation Information� or SARI was formed in 2013, with the mission: To help prevent unnecessary, radiation-phobia-related deaths, morbidity, and injuries associated with distrust of radio-medical diagnostics/therapies and from nuclear/radiological emergencies through countering phobia-promoting misinformation spread by alarmists via the news and other media including journal publications.

SARI Website: http://radiationeffects.org/ 82

SARI Membership List on 9/9/2014 MEMBERS: 1.

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Adams, Rod, MS, Atomic Insights LLC Allison, Wade, PhD, Emeritus Professor of Physics, University of Oxford Anderson, Rip, PhD, Sandia National Laboratories (Retired) Angwin, Meredith, BS, MS, Carnot Communications Borders, Rex, MS, DOE/NNSA Brodsky, Allen, Sc.D., CHP, CIH, DABR, Georgetown University Brooks, Tony, PhD, Washington State University (Retired) Brozowski, George, BS, Radiation Technology, U.S. EPA, Region 6 Cai, Lu, MD, PhD, University of Louisville Cohen, Mervyn, MBChB, Indiana University Conca, Jim, PhD, Center for Laboratory Sciences, RJLee Group, Inc. Leslie E. Corrice, MA, Self-employed / Semi-retired Cox, Morgan, MS, Cuttler, Jerry M, DSc in Nuclear Sciences, Cuttler & Associates Davey, Chris, B.S., King Abdullah University of Science and Technology (KAUST) Denman, Matt, PhD, Sandia National Laboratories Dobrzynski, Ludwik, D.Sc., National Center for Nuclear Research, Poland Doss, Mohan, PhD, Associate Professor, Fox Chase Cancer Center Dube, Scott, M.S., Morton Plant Hospital Easty, Mack, MD, U.S.Army (retired) Esposito, Vincent J., PhD, Adjunct Prof. Uni of Pittsburgh (Retired) Farooque, Abdullah, MS, Institute of Nuclear Medicine and Allied Sciences, Drdo, Delhi, India Feinendegen, Ludwig E., MD, Heinrich-Heine University University Dusseldorf, Germany Fellman, Alan, Ph.D., Dade Moeller & Associates, Inc. Fornalski, Krzysztof, Ph.D., Eng, Polish Nuclear Society (PTN) Franz J, Freibert, Ph.D., Los Alamos National Laboratory Gomez, Leo, PhD, Sandia National Laboratories (Retired) Hansen, Richard (Rick), BS, National Security Technologies, LLC (NSTec) Haque, Munima, PhD, Southeast University, Dhaka, Bangaladesh Hart, John, DC, MHSc, Sherman College of Chiropractic Hayes, Rob, PhD, Nuclear Waste Partnership LLC/WIPP Hiserodt, Ed, BS, Controls & Power, Inc Hylko, Jim, MS (MPH), Enercon Federal Services, Inc. Janiak, Marek K., Professor of medical sci., Military Institute of Hygiene & Epidemiology, Warsaw, Poland Kaspar, Matthew, MS, DOE/NNSA Kesavan, P.C., Ph.D., M.S. Swaminathan Research Foundation, India Kollar, Lenka, MS, Nuclear Undone LLC Laster, Brenda, Ph.D., Ben Gurion University

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Mahn, Jeffrey, MS, Sandia National Laboratories (Retired) Malenfant, Richard, MS, MBA, Los Alamos National Laboratory (Retired) Marcus, Carol Silber, B.S., M.S., Ph.D., M.D., ABNM, Self + UCLA McCollough, Cynthia H., PhD, Professor, Medical Physics and Biomedical Engineering Director, CT Clinical Innovation Center, Mayo Clinic Miller, Mark, MS, Sandia National Laboratories Mortazavi, SMJ, PhD, Professor, Shiraz University of Medical Sciences Orient, Jane, BA, BS, MD, Individual Practitioner of Medicine, Editor of Doctors for Disaster Preparedness Newsletter and Civil Defense Perspectives Osborn, Doug, PhD, Sandia National Laboratories Payne, Steven S., PhD, DOE/NNSA Pennington, Charles, MS/MBA, Private Consultant Philbin, Jeff, PhD, Nuclear Safety Associates Rangacharyulu, Chary, PhD, University of Saskatchewan, Canada Reeves, Glen I., MD, Applied Research Associates, Inc. Rithidech, Kanokporn Noy, PhD, Professor of Research Pathology, Stony Brook University Ruedig, Elizabeth, PhD, Postdoctoral Fellow, Colorado State University Sackett, John, PhD, Argonne National Laboratory (retired) Sacks, Bill, PhD, MD, FDA’s Center for Devices and Radiological Health (Retired) Sacks, Miriam, RT, Kaiser Permanente, Washington, DC (Retired) Sanders, Charles L, PhD, (Retired) Scott, B.R., PhD, Lovelace Respiratory Research Institute (LRRI) Shanahan, John A., PhD, M.Sc., B.Sc., President, Go Nuclear, Inc. Siegel, Jeffry, PhD, Nuclear Physics Enterprises Socol, Yehoshua, PhD, Falcon Analytics, Israel Stabin, Michael, PhD, Vanderbilt University Ulsh, Brant, PhD, CHP, MH Chew and Associates Vaiserman, Alexander, PhD, Institute of Gerontology, Kiev Weiner, Ruth F., PhD, Sandia National Laboratories Welsh, James, MS, MD, University of Wisconsin

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Cravens, Gwyneth, MA, Self-employed writer Fujita, Hiroyuki, 4-Year University, Writer, translator, corporate trainer Jennetta, Andrea, B.A., Fuel Cycle Week / Int’l. Nuclear Associates, Inc. Lewis, Patricia, Free Enterprise Radon Health Mine Meyerson, Gregory, PhD, North Carolina A and T University Morales, Bert, BS, MBA, UniTech Services Group Rowland, Tawnya, BS, Bus. Admin, Lovelace Respiratory Research Institute Terrell, Rebecca, Nurse, MBA, The New American magazine (environmental issues contributor) 83 75. Trujillo, Jennifer, BS, Eye Associates of New Mexico

SARI Activities Google Group formed to facilitate discussions Discussions on: • • • •

Articles in journals, news media, etc. raising fear of LDR Publications on health effects of LDR How to overcome the fear of LDR among the public How to encourage a change in the radiation safety paradigm

Letters to Government Leaders, Advisory Bodies, Journal Editors.

Letters to the Editor in response to Journal articles Comments to government agencies E.g. SARI’s Response to EPA’s ANPR on Nuclear Power Operations: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OAR-2013-0689-0477

See SARI website for more Letters, etc: http://radiationeffects.org/ 84

Society for Radiation Information (Japan)

At about the same time SARI was formed, an organization called Society for Radiation Information (SRI) was formed in Japan with a similar objective, to reduce the harm caused by the LDR concerns and fears.

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Notwithstanding the arguments and evidence that have accumulated over the years against the LNT hypothesis, international and national advisory bodies such as NAS, ICRP, NCRP, UNSCEAR, IAEA, WHO, etc. continue to support the use of the LNT hypothesis.

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What is the reaction of regulatory agencies, professional organizations, etc. when the evidence against the LNT hypothesis are brought to their attention?

Typical reaction: They refer to reports by the various national and international advisory organizations NAS, ICRP, NCRP, UNSCEAR, IAEA, WHO, etc. that support the LNT hypothesis.

Their conclusion: Scientific consensus favors the use of the LNT hypothesis, and until the consensus changes, they will continue to use the LNT hypothesis, notwithstanding the evidence against it.

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Since evidence and logic don’t seem to sway the professional organizations and regulatory agencies as they clutch the advisory body reports for support, we need to show why the advisory body recommendations to use the LNT hypothesis should not be followed, in spite of their consensus of recommendations.

Hence the need to analyze the origin of the LNT hypothesis and its persistence.

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Why was the LNT hypothesis adopted by the advisory committees in the 1950s?

NAS BEAR I Committee was the first advisory body to recommend the use of the LNT hypothesis

Radiation protection: the NCRP guidelines and some considerations for the future, Sinclair, 1981, http://www.ncbi.nlm.nih.gov/pubmed/7342492 89

Why did BEAR I recommend LNT hypothesis in 1956?

The leading proponent of LNT hypothesis and genetic harm from low-dose radiation was Hermann J. Muller.

He was a member of the Genetics Panel of the BEAR I Committee of NAS

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Muller’s Claim of No Threshold Dose Was Not Justifiable Herman J. Muller’s Nobel Prize Lecture (Muller, 1946)

400 r is not low dose, and conclusion of no threshold dose is not justifiable based on this observation.

(Muller 1946) Muller Nobel Prize lecture, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1946/muller-lecture.html

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Additional Reason Why Muller’s Conclusion of No Threshold Dose was not Justified Muller was aware of data – not yet published – that showed presence of a threshold dose for radiationinduced genetic mutations. In spite of this, he made the statement “no escape from the conclusion that there is no threshold dose” in his Nobel Lecture.

(Calabrese, 2013)

(Calabrese, 2013) 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. http://www.ncbi.nlm.nih.gov/pubmed/23912675

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The conclusion of Muller that there is no threshold dose for genetic mutations violated basic scientific principles. (Doss, 2014)

Adoption of Linear No-Threshold Model Violated Basic Scientific Principles and Was Harmful, Mohan Doss, Archives of Toxicology, 2014, http://rd.springer.com/content/pdf/10.1007%2Fs00204-014-1208-8.pdf

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Why did BEAR I recommend LNT hypothesis in 1956? • Evidence from letters of correspondence of the Committee Members indicates self-interest may have motivated adoption of LNT hypothesis by BEAR I Genetics committee (Calabrese, 2014).

(Calabrese, 2014) The Genetics Panel of the NAS BEAR I Committee (1956): epistolary evidence suggests self-interest may have prompted an exaggeration of radiation risks that led to the adoption of the LNT cancer risk assessment model. http://www.ncbi.nlm.nih.gov/pubmed/24993953 The Technological Infrastructure of Science, Seltzer, 2007, Ph.D. Dissertation, http://scholar.lib.vt.edu/theses/available/etd-09142007-000938/ 94

Why did BEAR I recommend LNT hypothesis in 1956?

http://www.ncbi.nlm.nih.gov/pubmed/24993953

THIS IS VERY TROUBLING INDEED.

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More Reasons for Adoption of LNT hypothesis in 1950s • The concern of increased cancers from LDR based on increased leukemias in atomic bomb survivors (Calabrese, 2009) – No excess leukemias at low doses, but linearity at low doses was claimed raising carcinogenic concerns about LDR (Lewis, 1957). (Note: UNSCEAR Report 1958 showed threshold dose) – Strong support by an accompanying editorial in Science (Dus,1957) • Pacifist campaign in progress at the time for the prevention of atmospheric testing of atomic weapons (Jaworowski, 2010).

Missing in these reasons was any scientific reason, i.e., evidence CALABRESE, E. J. 2009. The road to linearity: why linearity at low doses became the basis for carcinogen risk assessment. http://www.ncbi.nlm.nih.gov/pubmed/19247635 DUS, G. 1957. Loaded Dice. Science, 125, 963. Available: http://www.ncbi.nlm.nih.gov/pubmed/17778552 LEWIS, E. B. 1957. Leukemia and ionizing radiation. Science, 125, 965-72. Available: http://www.ncbi.nlm.nih.gov/pubmed/13421705 JAWOROWSKI, Z. 2010. Radiation hormesis--a remedy for fear. http://www.ncbi.nlm.nih.gov/pubmed/20332170

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Whereas the advisory bodies adopted the LNT hypothesis in the 1950s for extraneous reasons, the radiation safety paradigm was reviewed multiple times by various advisory committees since then, and they have repeatedly endorsed the use of the LNT hypothesis.

As we have seen, there is plenty of evidence and arguments against the LNT hypothesis, dating as far back as 1958.

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How can advisory committees repeatedly come to the wrong conclusion?

By ignoring or dismissing evidence contradicting their conclusion E.g. BEIR VII report dismissed the importance of immune system in preventing cancer. It also dismissed the enhanced immune system response from LDR by stating (on page 333): “Although evidence for stimulatory effects from low doses has been presented, little if any evidence is offered concerning the ultimate deleterious effects that may occur.�

This statement ignores all the evidence presented earlier for the reduction of cancers from LDR, most of it pre-dating the BEIR VII report.

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Systemic Deficiencies in our Scientific Infrastructure The fact that BEIR VII report and other reports by advisory bodies could ignore published evidence against the LNT hypothesis and continue their support for the LNT hypothesis over the past decades indicates there are

major systemic deficiencies in the operation of the advisory bodies, which lead our scientific infrastructure DOSS, M. 2014. Correcting systemic deficiencies in our scientific infrastructure. Dose Response, 12, 185-201. Available: http://www.ncbi.nlm.nih.gov/pubmed/24910580 99

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Senior Leaderships of Regulatory Agencies and Professional Organizations cannot trust these advisory body reports until such deficiencies in the operation of the advisory bodies are identified and corrected. cannot clutch these reports as support for taking actions that are harming patients and the public based on published evidence. should examine the published evidence and use their own scientific judgment . should approach the advisory bodies and ask them to justify continued use of the LNT hypothesis in view of the unscientific manner by which it was adopted, published evidence against it and the harms it has caused.

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It is clear from the evidence and arguments presented that we need to change the radiation safety paradigm

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Reasons to Change the Radiation Safety Paradigm- Summary • The current LNT hypothesis-based radiation safety paradigm was adopted apparently because of self-interest by BEAR I Genetics Committee Members, without evidence for harm caused by LDR, and without any scientific evidence for it.

• Repeated recommendations by advisory bodies supporting the LNT hypothesis ignored the existing evidence against it • The main evidence used by advisory bodies for the current paradigm – atomic bomb survivor data – no longer supports the LNT hypothesis or LDR cancer concerns.

• Tremendous harm has been caused to the public due to the current radiation safety paradigm’s claim of no threshold dose • Current paradigm has prevented study and use of LDR for prevention of aging-related diseases for which there are presently no method of prevention, and for which animal models have shown promise, including cancer, Alzheimer’s, Parkinson’s, etc.

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Reasons to Change the Radiation Safety Paradigm • Changing the paradigm would reduce fear of low dose radiation This would enable wider use of nuclear power, to reduce energy costs and casualties from use of other more costly and less safe power sources • Enable Study of Potential Beneficial Effects of Low Dose Radiation (Doss, 2012)  Cancer prevention and therapy, with reduced or no side effects  Prevention or control of aging-related non-cancer diseases  Reduction of adverse side effects of cancer therapies  Reduction of inactivity related diseases or conditions in the infirm

Note: Every day of delay in studying/using radiation hormesis is likely contributing to >2000 preventable cancer deaths in the world. (Doss, 2014)

(Doss, 2012) Shifting the Paradigm in Radiation Safety. http://dose-response.metapress.com/link.asp?id=a35338004706373w (Doss, 2014) Correcting Systemic Deficiencies in our Scientific Infrastructure, http://dose-response.metapress.com/link.asp?id=11h3l8t067886g08

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Why Change Health Physics Goals?

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Why Change Health Physics Goals?

Current Mission of the Health Physics Society is: Excellence in the science and practice of radiation safety. http://hps.org/aboutthesociety/historyandmission/mission.html

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The bulk of the present efforts in radiation safety are based on LNT hypothesis and LDR concerns.

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Evidence presented indicates these efforts based on LDR concerns do not impact on radiation safety.

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However, radiation safety regulations require us to keep doses ALARA, and so justify and fund the present efforts.

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How Long will Current Radiation Safety Regulations Last?

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Legal Basis for EPA’s Radiation Safety Regulations

See: SARI’s Response to EPA’s ANPR on Nuclear Power Operations: http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OAR-2013-0689-0477 and Page 6511 of EPA’s ANPR: http://www.gpo.gov/fdsys/pkg/FR-2014-02-04/pdf/2014-02307.pdf

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Do EPA’s Radiation Safety Regulations for LDR Comply with the Congressional Mandate?

Based on the evidence and arguments presented, LDR is not carcinogenic but is cancer preventive.

Hence, current EPA regulations for LDR do not “protect health or minimize danger to life” which is EPA’s Congressional mandate inherited from AEC.

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Similar Situation in Canada Nuclear Safety and Control Act of the Parliament: http://laws-lois.justice.gc.ca/eng/acts/N-28.3/page-2.html#h-3

The purpose of this Act is to provide for – the limitation, to a reasonable level and in a manner that is consistent with Canada’s international obligations, of the risks to national security, the health and safety of persons and the environment that are associated with the development, production and use of nuclear energy and the production, possession and use of nuclear substances, prescribed equipment and prescribed information; In view of the evidence against the LNT hypothesis, low-dose regulations do not provide for the health and safety of persons and so do not comply with the mandate of the Parliament 109

How Long will Current Radiation Safety Regulations Last?

• The public and the Congress would not support present EPA radiation safety regulations relating to LDR if they become aware the regulations are not meeting the Congressional mandate of protecting public health. • Without LNT-hypothesis-based regulations for LDR, there would be no ALARA, and there would be no justification or funds for present radiation safety efforts relating to LDR.

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More reasons to change health physics goals • • •

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Current health physics society goal: Focus is on radiation safety, i.e.

Maintenance of health at the same level as in the absence of any additional radiation exposure Goal would be laudable if there were no cancers or other major diseases in the absence of additional radiation exposure Cancer remains unconquered, and Alzheimer’s disease is becoming a major burden for the society. LNT hypothesis has discouraged investigation of LDR for prevention of cancer in spite of published evidence. It has prevented study of LDR for controlling neurodegenerative diseases in spite of promising evidence in animal studies The aspirations of the world population to improve their quality of life requires more energy, which would degrade the environment, harming public health. Current fear of LDR is preventing wider use of nuclear power. Education of the public can reduce fear of LDR, help increased use of nuclear power, and reduce degradation of environment.

The health needs of the population are different now, in comparison to 1950s when the Health Physics Society was formed.

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Why change health physics goals?

Present health physics society’s mission and goals do not address these major public health issues

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Revised Health Physics Goals Suggested Revised Mission for Health Physics: Excellence in the scientifically justified safe use of radiation for improvement of health and in other applications The new suggested goals to include: • Improvement of health with scientifically justified safe use of radiation • Radiation safety in other uses of radiation • Education of public to reduce fear of low-dose radiation • Campaign to counter misinformation in professional publications and in popular media on low-dose radiation • Challenge/debate/education of individuals and organizations spreading misinformation on low-dose radiation health effects

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Summary LNT hypothesis based radiation safety paradigm is not justifiable any longer – it is time for a change  Evidence has accumulated for radiation hormesis/threshold dose  Main evidence quoted for LDR carcinogenicity – atomic bomb survivor data - no longer support LNT hypothesis  No credible evidence exists for LDR cancer risk; Too many false alarms have been raised regarding LDR  The fear of LDR from the use of LNT hypothesis has done tremendous harm  LNT hypothesis was adopted by BEAR I Genetics Committee in the 1950s, not based on evidence of harm from LDR but apparently because of self-interest of the Committee members.  Advisory bodies have ignored published evidence in continuing 114 to support the LNT hypothesis over the years.

Summary (continued) Health Physics Goals Need to be Revised  Current public health needs are different from the 1950s. Cancer remains unconquered, Alzheimer’s disease is becoming a major concern with the aging population.  Accumulating evidence indicates LDR may reduce aging-related diseases including cancer, Alzheimer’s, Parkinson’s, etc.  The worldwide population aspires for higher living standards, requiring more energy production. This can degrade environment, affecting health.  Reducing fear of LDR can enable increased use of safer nuclear power, for reduced degradation of environment, reducing the adverse impact on health.

Present health physics society mission and goals do not address these major public health issues 115

Revised Health Physics Goals Suggested Revised Mission for Health Physics: Excellence in the scientifically justified safe use of radiation for improvement of health and in other applications The new suggested goals to include: • Improvement of health with scientifically justified safe use of radiation • Radiation safety in other uses of radiation • Education of public to reduce fear of low-dose radiation • Campaign to counter misinformation in professional publications and in popular media on low-dose radiation • Challenge/debate/education of individuals and organizations spreading misinformation on low-dose radiation health effects

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Please click on the link below to a Survey, and give your opinion on the presentation, and your suggestions for future course of action. Thanks.

Survey Link: https://www.surveymonkey.com/s/Compelling When you complete the survey, a summary of the survey results will be shown.

To see a Summary of Survey Results: http://goo.gl/9hltqc 117

I wish to thank New Jersey Chapter of the Health Physics Society and its Secretary Robert Tokarz for giving me an opportunity to make this presentation.

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