Nuclear Weapons: The Final Pandemic Preventing Proliferation and Achieving Abolition New understandings of radiation effects, and new evidence from Chernobyl Ian Fairlie Independent consultant on radiation and health

New Information on Radiation Risks Dr Ian Fairlie Consultant on Radiation in the Environment London United Kingdom

Radiation – a brief intro Untargeted Radiation Effects -a paradigm shift Some Chernobyl Findings

Radiation – in a nutshell main sources main sources radiation risks radiation risks dose-response relationship dose-response relationship politics politics uncertainties uncertainties

Main Sources background radiation background radiation medical exposures medical exposures test bomb fallout from 1950s and 1960s test bomb fallout from 1950s and 1960s Average dose UK = 2.6 mSv/a Average dose US = ~3.5 mSv/a (0.35 rem) (1 mSv = 0.1 rem)

Examples of Exposures ( mSv) mean Effective Dose (whole-body) 10 mSv = 1 rem A-bomb survivors (mean dose) 200 Space station - per year 170 Radiation worker limit - per year 20 Background radiation - per year Public limit (EU) - per year 1 Return flight – Boston to London 0.1 Chest X-ray 0.05

Radiation Risks 1. difficult to determine at low levels 2. wide differences of view 3. major interests involved (eg military) 4. public fear of radiation = often much heat: less light

Feared Risks: 8 points after (Meara, 2002) invisible √ invisible √ inequitably distributed √ inequitably distributed √ difficult to avoid √ difficult to avoid √ cause hidden or irreversible damage √ cause hidden or irreversible damage √ dangerous to future generations √ dangerous to future generations √ cause dread illnesses, ie cancer √ cause dread illnesses, ie cancer √ difficult to explain simply √ difficult to explain simply √ differing views among scientists √ differing views among scientists √√=radiation

Risks at low doses

Dose-Response: Latest LSS Data source: Brenner et al, 2003

Risks: Annual Radiation Limits (1 rem = 10 mSv) Occupational 1934~44 rem 1950~15 rem rem rem + ALARA rem + ALARA Public rem rem rem rem rem + exceptions rem + no exceptions

Radiation Risks: Politics and Science military pressure to reduce RBE values military pressure to reduce RBE values U mining opposition to worker limits U mining opposition to worker limits hormesis: radiation is good for you hormesis: radiation is good for you Sellafield leuks: invented infective hypothesis? Sellafield leuks: invented infective hypothesis? denial of Alice Stewart’s studies denial of Alice Stewart’s studies denial of new effects of radiation denial of new effects of radiation current ICRP proposals to dilute safety limits (using background radiation as excuse) current ICRP proposals to dilute safety limits (using background radiation as excuse)

Background Radiation EXTERNAL Primordial radionuclides in soil*20% Cosmic rays 17% INTERNAL Rn-222*, Rn-220* 50% K-40 8% U-238, Th progenies 4% * wide variation between countries (worldwide average given) sources: Thorne (2003); UNSCEAR (2000, annex B) AVERAGE DOSE (WORLDWIDE) = 2.5 mSv/a

Background Radiation HPA-RP* estimated ~ 6,000 UK cancer deaths per year (~5% of cancer deaths) HPA-RP* estimated ~ 6,000 UK cancer deaths per year (~5% of cancer deaths) reason why women >40 years have miscarriages/spontaneous abortions reason why women >40 years have miscarriages/spontaneous abortions partly connected with ageing: why we are not immortal partly connected with ageing: why we are not immortal connected)** with leukemias the reason for long latency periods? connected)** with leukemias the reason for long latency periods? * Robb JD (1994) ** Comare, (1986)

Uncertainties in Doses and Risks 1. ENVIRO. MODELS - transport of nuclides 2. BIOKINETIC MODELS - nuclide distn’s in organs 3. DOSIMETRIC MODELS - absorbed doses in organs 4. w R - for different rad’n types 5. w T - to add organ doses (Sv) 6. Apply a RISK- apply cancer risks from RERF 7. DDREF- for low doses/dose rates = ICRP cancer risk estimate

Uncertainties in dose estimates

Uncertainties in Dose Coefficients Goossens LHJ, Harper FT, Harrison JD, Hora SC, Kraan BCP, Cooke RM (1998) Probabilistic Accident Consequence Uncertainty Analysis: Uncertainty Assessment for Internal Dosimetry: Main Report. Prepared for U.S. Nuclear Regulatory Commission, Washington, DC , USA. And for Commission of the European Communities, DG XII and XI, B-I049 Brussels Belgium. NUREG/CR-6571 EUR NuclideIntakeOrgan U Range = (ratio of 95 th /5 th percentiles) Cs-137ingestion red bone marrow 4 I-131inhalationthyroid9 Sr-90ingestion 240 Pu-239ingestion 1,300 Sr-90inhalationlungs5,300 Ce-144inhalation 8,500 Pu-239ingestion bone surface 20,000

Untargeted Effects of Radiation: - a paradigm shift Hall EJ and Hei TK. (2003) Genomic instability and bystander effects. Oncogene vol 22, pp “Both genomic instability and the bystander effect are phenomena, discovered relatively recently, that result in a paradigm shift in our understanding of radiation biology.” Baverstock K (2000) Radiation-induced genomic instability: a paradigm- breaking phenomenon and its relevance to environmentally induced cancer. Mutation Research 454 (2000) 89–109. Belyakov OV et al (2005) Classical radiation biology, the bystander effect and paradigms: a reply. Hum Exp Toxicol 24(10):537–542. Bridges BA (2001) Radiation and germline mutation at repeat sequences: Are we in the middle of a paradigm shift? Radiat Res 156 (5 Pt 2): Matsumoto H, Hamada N, Takahashi A, Kobayashi Y, Ohnishi T. (2007) J Radiat Res (Tokyo). 48(2): Vanguards of paradigm shift in radiation biology: radiation-induced adaptive and bystander responses. Morgan WF (2002) Genomic instability and bystander effects: a paradigm shift in radiation biology? Mil Med. 167(2 Suppl):44-5. Waldren CA (2004) Classical radiation biology dogma, bystander effects and paradigm shifts. Hum Exp Toxicol. 23(2):

Untargeted Effects 1. Genomic instability (damage in progeny of irradiated cells) 2. Bystander effects (damage to unirradiated cells) 3.Tandem repeat [minisatellite] mutations (damage to DNA without DNA being hit)

Classic Explanation for Radiation’s Effects

Observed Effects of Genomic Instability micronucleus chromosome aberration aberration cell death cell death gene genemutation mitotic failure gene genemutation mutation

Genomic Instability appears after generations appears after generations induced at low doses induced at low doses induced at very high frequency induced at very high frequency in vitro and in vivo in vitro and in vivo mechanisms not known mechanisms not known bystander mechanisms involved bystander mechanisms involved

Bystander Effects 2.Signals via gap junctions 1.Signals via medium/plasma

Bystander Effects induced at very low doses induced at very low doses induced at very high frequency induced at very high frequency affects genetic and somatic cells affects genetic and somatic cells in vitro and in vivo in vitro and in vivo thought to be via chemical signals, thought to be via chemical signals, eg cytokines or ROS eg cytokines or ROS

Observed Bystander Effects cell proliferation mutations mutations chromosome aberrations chromosome aberrations changes in damage-inducible proteins changes in damage-inducible proteins changes in reactive oxygen species changes in reactive oxygen species genomic instability genomic instability cell death (ie could be protective) cell death (ie could be protective) in vitro and in vivo in vitro and in vivo

Bystander effect: dose response Mothersill and Seymour, 1999

Tandem Repeats in DNA eg “…AGGGTT…”

DNA Tandem Repeat Mutations mini and micro satellites – non-coding DNA mini and micro satellites – non-coding DNA but increasingly thought to be functional but increasingly thought to be functional associated with many diseases associated with many diseases hypermutable: very sensitive to radiation hypermutable: very sensitive to radiation not known how mutations are caused not known how mutations are caused (ie not by direct DNA damage) (ie not by direct DNA damage) appears to be passed to future generations appears to be passed to future generations

Untargeted effects - important at low doses Risk Dose

Cell Death Cell Survival Untargeted Effects increased risk decreased risk Genetic Factors Inflammatory Responses

Untargeted Effects: are we underestimating radiation risks at low doses? derive risks from classic effects at high doses derive risks from classic effects at high doses new effects occur at much lower doses new effects occur at much lower doses new effects are in addition to classic effects new effects are in addition to classic effects transgenerational effects? transgenerational effects? possible radiosensitive sub-populations? possible radiosensitive sub-populations? little or no dose dependence DDREF ≈ 1 not 2? little or no dose dependence DDREF ≈ 1 not 2?

Untargeted Effects: Implications for safety? CERRIE Committee (2004) was divided CERRIE Committee (2004) was divided authoritative scientists (Hall, Dubrova, Little, Wright, Prise etc) – state that perceived risks have increased authoritative scientists (Hall, Dubrova, Little, Wright, Prise etc) – state that perceived risks have increased ICRP view … knowledge is insufficiently developed for RP purposes... ICRP view … knowledge is insufficiently developed for RP purposes... ie sanguine view, not precautionary ie sanguine view, not precautionary

Chernobyl Accident (1986) “..foremost nuclear catastrophe in human history” IAEA (1996) “..its magnitude and scope, the size of the affected populations, and its long-term consequences make it, by far, the worst industrial disaster on record” IAEA/WHO (2005) “..radioactivity released ~200 times that from Hiroshima or Nagasaki” WHO/IPHECA (1995)

Chernobyl Fallout

Doses from Chernobyl Fallout sources: *Cardis et al, 2005; ** TORCH (2006) Size Average Dose (mSv) Collective Dose (Person Sv) Liquidators*240, ,000 High contam areas* 270, ,500 Evacuees in 1986* 116,000333,800 Low contam areas* 5 m 1050,000 Rest of Europe** 600 m ~0.4240,000 Rest of World** 4,000 m ~2.5 x ,000 TOTAL ~400,000 ~400,000 estimated deaths ~20,000

Chernobyl: observed health effects thyroid cancer leukaemia solid cancer non-cancer effects minisatellite mutations mental health + psychosocial

Epidemiology studies: care required differing diagnostic criteria used differing diagnostic criteria used insufficient/poorly matched control groups insufficient/poorly matched control groups small numbers – low statistical power small numbers – low statistical power confounding factors and biases confounding factors and biases nil or poor dose estimates nil or poor dose estimates Only use reliable studies

Thyroid Cancer Incidence Jacob et al (2005)

Leukemias in Clean-up Workers Ivanov (1997)

Cancer Relative Risks 95% CIs All sites 1.20* 1.14 – 1.27 Bladder1.55* 1.21 – 1.99 Colon1.31* 1.03 – 1.67 Lung1.28* 1.13 – 1.46 Breast 2.2 (1.8) N/A Solid Cancers Okeanov et al (2004), Pukkala et al (2006) *RRs statistically significant at 95%

Cardiovascular Disease Russian cleanup workers ERR/Sv = 0.54 (Ivanov et al, 2000) (is consistent with A-Bomb studies ERR/Sv = 0.17) (Pierce et al, 2003)

Non-cancer effects in A-bomb survivors (Preston and Pierce, 2003) ERR/Sv 95% CIs heart disease to 0.26 stroke to 0.22 respiratory disease to 0.32 digestive disease to 0.32 all statistically significant at 95% level

Transgeneration Effects DNA minisatellite mutation incidence doubled in Belarus and Ukraine DNA minisatellite mutation incidence doubled in Belarus and Ukraine mutations in fathers not mothers mutations in fathers not mothers passed to their children passed to their children Dubrova et al (1996, 1997, 2002)

Chernobyl: conclusions terrible consequences terrible consequences health effects still occurring health effects still occurring different health effects appearing different health effects appearing needs for more research + funding needs for more research + funding need to question denials by many governments need to question denials by many governments

References Brenner DJ, Doll R, Goodhead DT, Hall EJ, Land CE, Little JB, Lubing JH, Preston DL, Preston JR, Puskin JS, Ron E, Sachs RK, Samet JM, Setlow RB and Zaider M (2003) Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. (2003) PNAS Nov 25, 2003, vol. 100 no –13766 Cardis E (2005) Cancer effects of the Chernobyl accident (presentation at IAEA/WHO Conference ‘Environmental and Health Consequences of the Chernobyl Accident’) CERRIE (2004) Report of the Committee Examining Radiation Risks of Internal Emitters London, October (accessed February 12, 2006) Day R, Gorin MB and Eller AW (1995) Prevalence of lens changes in Ukrainian children residing around Chernobyl Health Physics Dubrova YE, Grant G, Chumak AA, Stezhka VA, Karakasian AN (2002) Elevated minisatellite mutation rate in the post-Chernobyl families from Ukraine. Am J Human Genet 71: Dubrova YE, Nesterov VN, Krouchinsky NG, Ostapenko VA, Neumann R, Neil DL and Jeffreys AJ (1996) Human minisatellite mutation rate after the Chernobyl accident. Nature Dubrova YE, Nesterov VN, Krouchinsky NG, Ostapenko VA, Vergnaud G, Giraudeau, Buard J and Jeffreys AJ (1997) Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident. Mutat. Res. 381, European Commission (1998) Atlas of Caesium Deposition on Europe after the Chernobyl Accident. European Commission. EUR EN RU. Brussels Goossens LHJ, Harper FT, Harrison JD, Hora SC, Kraan BCP, Cooke RM (1998) Probabilistic Accident Consequence Uncertainty Analysis: Uncertainty Assessment for Internal Dosimetry: Main Report. Prepared for U.S. Nuclear Regulatory Commission, Washington, DC , USA. And for Commission of the European Communities, DG XII and XI, B-I049 Brussels Belgium. NUREG/CR-6571 EUR IAEA/WHO (2005a) Health Effects of the Chernobyl Accident and Special Health Care Programmes. Report of the UN Chernobyl Forum Expert Group “Health” (EGH) Working draft. July IAEA/WHO (2005b) Environmental Consequences of the Chernobyl Accident and their Remediation. Report of the UN Chernobyl Forum Expert Group “Environment” (EGE) Working draft. August 2005 IAEA/WHO/EC (1996) One Decade After Chernobyl: Summing up the Consequences of the Accident. Ivanov VK et al (2000) Radiation-epidemiology analysis of incidence of non-cancer diseases among the Chernobyl liquidators. Health Physics 78, Ivanov VK, Tsyb AF, Gorsky AI, et al (1997) Thyroid cancer among "liquidators" of the Chernobyl accident. Br J Radiol 70: Jacob P, Meckbach R, Ulanovski A, Schotola C and Pröhl G (2005) Thyroid exposure of Belarusian and Ukrainian children due to the Chernobyl accident and resulting thyroid cancer risk. GSF-Bericht 01/05, Neuherberg: GSF-Forschungszentrum mbH, 72S.; mit Anhang Meara J (2002) Getting the Message Across: Is Communicating the Risk Worth it? J of Radiation Protection Vol 22 pp Okeanov AE, Sosnovskaya EY, Priatkina OP (2004) A national cancer registry to assess trends after the Chernobyl accident. Swiss Med Wkly 134:645-9 Preston DL, Shimuzu Y, Pierce DA, Suyama A and Mabuchhi K (2003) Studies of mortality of Atomic Bomb survivors. Report 13: Solid Cancer and Non-cancer Disease Mortality: Radiation Research 160, Pukkala E, Poliakov S, Ryzhov A, Kesminiene A, Drozdovich V, Kovgan L, Kyyrönen P, Malakhova I V, Gulak L and Cardis E Breast cancer in Belarus and Ukraine after the Chernobyl Accident. (2006) International Journal of Cancer, in press Robb JD (1994) Estimates of Radiation Detriment in a UK Population. NRPB Report R-260 National Radiological Protection Board, Chilton, Oxon Thorne MC (2003) Background radiation: natural and man-made. J Radiol Prot vol 23(1) pp UNSCEAR (2000) United Nations Scientific Committee on the Effects of Atomic Radiation Report to the General Assembly, with Scientific Annexes. (New York:UN) Annex B US DoE (1987) Report of Interlaboratory Task Group. Health and Environmental Consequences of the Chernobyl Nuclear Power Plant Accident. US Department of Energy DOE/ER-0332 NTIS Springfield VA WHO/IPHECA (1995) Health Consequences of the Chernobyl Accident, Results of the International Programme on the Health Effects of the Chernobyl Accident (IPHECA). Summary Report. World Health Organisation.

Reading List Books Caufield C (1990) Multiple Exposures: Chronicles of the Radiation Age. Penguin Books. London UK Caufield C (1990) Multiple Exposures: Chronicles of the Radiation Age. Penguin Books. London UK Greene G (1999) The Woman Who Knew Too Much. University of Michigan Press. Ann Arbor, MI, US Greene G (1999) The Woman Who Knew Too Much. University of Michigan Press. Ann Arbor, MI, US Proctor RN (1995) Cancer Wars: How Politics Shapes What We Know and Don’t Know about Radiation. Basic Books. New York, NY, US Proctor RN (1995) Cancer Wars: How Politics Shapes What We Know and Don’t Know about Radiation. Basic Books. New York, NY, USArticles Greenberg M (1991) The Evolution of Attitudes to the Human Hazards of Ionising Radiation and to its Investigators. Am J of Industrial Medicine Vol 20 pp Greenberg M (1991) The Evolution of Attitudes to the Human Hazards of Ionising Radiation and to its Investigators. Am J of Industrial Medicine Vol 20 pp Rose G (1991) Environmental Health: Problems and Prospects. J of Royal College of Physicians of London Vol 25 No 1, pp Rose G (1991) Environmental Health: Problems and Prospects. J of Royal College of Physicians of London Vol 25 No 1, pp Stewart AM (1991) Evaluation of Delayed Effects of Ionising Radiation: an Historical Perspective. Am J of Industrial Medicine Vol 20 pp Stewart AM (1991) Evaluation of Delayed Effects of Ionising Radiation: an Historical Perspective. Am J of Industrial Medicine Vol 20 pp

My grateful thanks to Dr David Sumner Dr Keith Baverstock Professor Eric Wright (any errors remain the author’s responsibility)