David Gee, Senior Adviser, Science, Policy, Emerging Issues. European Environment Agency

1. “From Miasma and Cholera to Mixtures and Contaminants : some reflections on Causality, Prevention, Precaution and Progress”. David Gee, Senior Adviser, Science, Policy, Emerging Issues. European Environment Agency AFSSET,Paris, Oct 12,2009 Some observations arising from« Late Lessons from early warnings: the precautionary principle 1896-2000, EEA 2001: & 2010 »

2. European Environment Agency, Copenhagen. 1993-? • An “independent” Agency of the European Communities, legally independent from the EU Commission, EU Parliament, and EU Council of Ministers. • We produce nothing but data, information, knowledge on Environment & E & Health for policymakers and the public.

3. On “Independence” • “We (AFSSA) are a dependent body conducting independent expertise”. • Martin Hirsch, former Director of AFSSA. Marras,2004; and in Chapter on Gaucho and French Bees, “Late Lessons from Early Warnings” EEA, 2010.

4. Homo Stupidus as Slow Learners? EEA, 2001;Vol 2 2010

5. Asbestos Timeline

6. Predicted Asbestos Deaths

7. CFCs Chapter: Skin Cancer and Time Lags

8. Summary • On Knowing and not Knowing • From Miasma to Mixtures: Public Health 1840-2009 • Multi-causality & Complexity • Association or Causation? • A Precautionary Approach to Hazards & Risk Analysis • Mobile Phones: Sufficient evidence for Action? • On Biases in Environment & Health Sciences. • On “Progress”….

10. The Complexity of biological/ecological Life brings the unexpected:”Surprises” “Life is the one material process that has discovered that the only way to deal with an unpredictable future is to be able to produce the unexpected” (Antoine Danchin, Biologist, Pasteur Institute, in “The Science of Everything”,Orrel,2007, P 414)

11. Pasteur on Surprises • “Surprise comes to the Prepared Mind” • See CFCs story, in which Joe Farman, who discovered the Ozone hole, had a “prepared mind”, but NASA did not, and missed the hole that was appearing in their satellite data.

12. “Wisdom is to know, that you do not know” (Socrates) An early lesson in humility, lately forgotten by many hubristic scientists ?

13. Acknowledge the Knowledge/Ignorance Hazard Ratio • Which is high (much Knowledge, little Ignorance) for Asbestos, after 111years of research since first “Early Warning” in 1898… • But which is low (little Knowledge, much Ignorance) for Nanotech, GMOs, EMF/RF from mobile phones…. • Partly because Research into Technological Applications is more than on Hazard Implications.(c. 10x for nano currently)

14. A Brief History of Causality in Public Health: From ‘Miasma’ to ‘Mixtures’

15. Early 19th Century: The Public Health Movement:’Miasma’ Multiple, unknown factors relating to multiple health impacts J. S. Mill’s canons of causality (‘difference’, ‘agreement’, ‘concomitant variation’, ‘residues’) “Which are well suited, then and now, to the multiple and unknown agents that epidemiologists face’ (Susser, 1991, AJE)

16. Late 19th Century: Search & Find the Specific Causes of Acute Diseases:’Pathogens’ • Specific, if initially unknown, ‘alien structures’ (Semmelweis, Snow, Budd on fever,cholera, typhoid). • Could be identified by vigorous laboratory work (‘Koch’s postulates’), following Pasteur’s establishment of germ theory.

18. Lessons from Snow on Cholera,1854 • Difference between “knowing enough” for prevention and “understanding” cholera causation (ie mechanisms of action) • Focus on pros & cons of “being wrong” • Value of spatial mapping of potential exposures and disease. • Importance of minority scientific views (Intro., “Late Lessons”, EEA, 2001, P14)

19. Minority Scientific Views? • Science does not require majority rule • “Minority/divergent views must be taken into account: but they must be about more than a “theoretical” risk” (EC Communication on PP; ECJ) “ Risk Assessments can be based on a Respectable minority view” (WTO,2008)

20. Mid 20th Century: Identify Causality of Chronic Diseases with Several Causes:’Criteria’ • Chronic diseases e.g. lung cancer of ‘unknown’ origin from several causes. • ‘Indeterminancy’ requiring probabilistic inference based on criteria for moving from ‘association to causation’. (Hammond, Doll, US Surgeon General, Bradford Hill, Susser).

21. 21st Century:Identifying Multiple Causes of Diverse Impacts from Mixtures: ’Cumulative Judgement’? • Chronic, generational, multi-causal, chaotic, complex disease processes, where the timing of exposure is often critical • Better balance within science and public policymaking between false negatives and false positives • The precautionary principle

22. Paracelsus Revisited:”it’s the Timing of the Dose that makes the poison” • See the story of the marine anti-fouling paint, TBT, Arcachon Bay,France;(EEA 01) • Thalidomide….. • the pregnancy pill, DES (EEA,01) • BPA (EEA,10) • Male Infertility(EEA,10) • all Endocrine Disrupting Substances(WHO,02; EEA,10) • the Faroes Isles Declaration on Developmental & Reproductive Harm, 2007.

23. From “Simple” to “Systems” Science-some illustrations from Late lessons”.

24. Complex systems … a number of attributes • Multiplicity of legitimate perspectives • Non-linearity • Emergence: “the whole is more than the sum of its parts” • Multiplicity of scales • Irreducible uncertainty • Relevance, not precision, is more useful

25. Precision versus Relevance? ‘As the complexity of a system increases our ability to make a precise and yet significant statement about its behaviour diminishes until a threshold is reached beyond which precision and significance (or relevance) become almost mutually exclusive characteristics.’ (Zadeh, 1965)

26. It is usually better to get an approximate answer for the whole problem/issue than a precise answer for an isolated part of the problem

27. Multi-causality where confounders can be co-causal factors. - Genes Host Condition Environmental Exposures s Effects Harm

28. “Effects” to “adverse” effects is usually a continuum.. “when you expose an organism to a toxic substance it responds in a continuum.. there is no abrupt change between a response and no response” ProfClair Patterson, Muskie hearings on lead in Petrol ,US Congress, 1976. But beware of thresholds & tipping points too

29. Environmental Pollutants: Confounders or Co-causal factors? “The early environment, including that prevailing before birth, is not simply an influential variable but a biologic determinant…..what we have labelled as co-variates, confounders and effect modifiers possess a biological reality that we have yet to resolve” Weiss & Bellinger,”Social Ecology of Children’s Vulnerability to Environmental Pollutants”, Env Health Perspectives, V 114, 2006

30. Genes and multi-causality.. • “Few genes play more than a minor role in complex traits like heart disease, autism, schizophrenia or intelligence – maybe such genes do not exist • “Rather than being “caused” by single genes these traits may represent a network perturbation generated by small, almost imperceptible, changes in lots of genes” (Johnjoe McFadden, Professor of Molecular Genetics, Surrey University, 2005)

31. “The Harmony of Opposites” Heraclitus. In which a small change can disrupt a balanced biological or ecological system

32. + + == Host genetics Host state Exposures Harm Illustrations of multi-causality in childhood asthma + + 25% 25% 50% 100% e.g. Allergic sensitivity e.g. Nutritional and immune Status Sex Age • 30% indoor • e.g. • Mites 10% • Pets 5% • Passive • Smoking 5% • NOx 5% • Damp 5% • 20% outdoor • e.g. • Pollen 10% • Industrial • pollution 5% • Traffic • pollution 5% e.g. Asthma in some children Source: EEA, 1999

33. Some implications of multi-causality for the Bradford Hill “Criteria” for moving from “Association to Causation”.(1965) • “Strength”: a strong biological cause can be statistically weak. • “Specificity”: a cause can have several effects • “Temporality”: other causal trends can explain outcome timing differences • “Consistency”: inconsistency from studying complex systems is to be expected

34. Bradford Hill downplayed Statistical Significance.. “Too often I suspect we waste a deal of time, we grasp the shadow and lose the substance, we weaken our capacity to interpret the data and to take reasonable decisions whatever the value of P.” Bradford Hill. 1965, “Environment and Disease: Association or Causation”?

35. Prof.Needleman On Consistency.... ”Consistency in nature does not require that all, or even a majority of studies find the same effect. If all studies of lead showed the same relationship between variables, one would be startled, perhaps justifiably suspicious” Needlemann (1995) ”Making Models of Real World events: the use and abuse of Inference”, Neurotoxicology and Teratology, vol 17, no. 3.

36. “Biological gradient”: can depend on doses of co-causal factors; and may not be linear • “Plausibility” & “Coherence” depend on “today’s” knowledge eg. of mixtures & interactions, and of complex systems….which is currently weak • “Experimental” (ie prevention works) is hard to show under multi-causality • Which means we must put more weight on “Analogy” ie making the most of what we know from relevant experience.

37. Some Non monotonic Dose-Response-Curves Schulte-Oehlmann et al. 2001 BPA and no. of embryos in snails BPA and Cell proliferation vom Saal et al. 1997 DES and prostate size in mice HCB and prostate cell androgen activity

38. Bradford Hill recognised his “criteria” were asymmetrical The presence of the “criteria” provides good evidence for causation; their absence may not provide good evidence against a real association. Given what we now know about multi-causality and complexity in biological systems, this asymmetry is now larger than in 1965

39. Analogy from Asbestos? An Early Warning on Nanotubes, Nature, May, 2008. • “The latest study (showing potential for mesothelioma from long, thin fibres, in rats) suggests there could be a reason for concern” Dr, Steffi Friedrichs, Director, Nanotech Industries Association • “We cannot afford to not exploit this incredible material but neither can we afford to get it wrong, as we did with Asbestos”. Dr. Andrew Maynard, Woodrow Wilson International Centre

40. A Precautionary Framework for Risk Analysis. 1+2 Risk assessment Broad framing of questions and goals Scientific assessment of risk, uncertainties and ignorance 1 2 EffectivenessEvaluations of Actions Action options assessment Stakeholder participation and review 6 3 4 5 5+6 Risk Communication Communication andimplementation of assessments, options, actions Action decisions(Precautionary “trigger”) 3+4 Risk Management EEA based on US Presidential Commission on Risk (1997), Royal Commission on Environmental Pollution (1998) and NAS, Science and Risk, 2008.

41. ‘The Irish Potato Famine and Precaution-1846 "Are you to hesitate in averting famine which may come, because it possibly may not come? Are you to sit in cabinet, and consider and calculate how much diarrhoea, and bloody flux, and dysentery, a people can bear before it become necessary for you to provide them with food? The precautions may be superfluous, but what is the danger where precautions are required? Is it not better to err on the side of precaution than to neglect it utterly?" Source: Sir Robert Peel, UK Parliament, 27 March 1846

42. Measuring is not Knowing:The Marine Environment and the Precautionary Principle “huge amounts of data are available, but …we have reached a sort of plateau in …the understanding of what the information is telling us …. This is what led to the precautionary principle, after all – we do not know whether, in our studied ecosystem, a loss of diversity would matter, and it might”. Marine Pollution Bulletin, Vol 34, No. 9, pp. 680-681, 1997

43. A working definition of the Precautionary Principle based on “Late Lessons” “The PP provides justification for public policy actions in situations of scientific complexity, uncertainty and ignorance, where there may be a need to act in order to avoid, or reduce, potentially serious or irreversible threats to health or the environment, using an appropriate level of scientific evidence, and taking into account the likely pros and cons of action and inaction”. EEA, 2002

44. Sufficient evidence for action? “The Case for Action” “…. we must surely ask what is involved in our decision... it almost inevitably leads us to introduce differential standards before we convict.” Bradford Hill, Association or Causation, 1965

45. Bradford Hill on different Strengths of Evidence for different situations, 1965 • “relatively slight evidence”for pregnancy pill ban • “fair evidence” for reduced/eliminated exposure to probable carcinogenic oil at work • “Very strong evidence”for public restrictions on smoking or diets. Bradford Hill, The Environment & Disease: Association or Causation?”, Proc Roy. Soc Med ,1965, 58, 295-300.

46. Some Generic Levels of Evidence….. • Beyond all reasonable doubt • Reasonable certainty • Balance of probabilities/evidence • Strong possibility • Scientific suspicion of risk • Negligible/insignificant • That are appropriate for different purposes eg criminal or civil law, precaution or prevention

47. SCENHIR on Mobile Phones, 2007: “The perils of the precis?” “Since 2001 extensive research has been conducted.. no health effect has been consistently demonstrated at exposure limits below the limits of ICNIRP”. (P4 Abstract)..

48. But look what’s in the Text! • ..for “ less than 10 years” exposure…. • “For longer term use, data are sparse, since only some recent studies have reasonably large numbers of long term users. Any conclusion therefore is uncertain and tentative”. • “in particular for acoustic neuroma some data indicate that an association …….with RF fields from mobile telephony is possible... there is limited evidence of a weak association. (P 28)

49. “No evidence of Harm is not Evidence of No Harm”

50. “Danish Scientists: Mobile phone is Safe” (June 2008) • “No health danger has been proven..this doesn’t necessarily lead to the conclusion that mobile radiation doesn’t pose a problem” • Since the research doesn’t definitely show that radiation is dangerous a potential damaging effect is likely to be limited” (Danish Council for Strategic Research, on TDC Comms website ,June 2008.