Systematic Assessment of Research on Autism Spectrum Disorder (ASD) and Mercury Reveals Conflicts of Interest and the Need for Transparency in Autism Research

Historically, entities with a vested interest in a product that critics have suggested is harmful have consistently used research to back their claims that the product is safe. Prominent examples are: tobacco, lead, bisphenol A, and atrazine. Research literature indicates that about 80–90% of studies with industry affiliation found no harm from the product, while only about 10–20% of studies without industry affiliation found no harm. In parallel to other historical debates, recent studies examining a possible relationship between mercury (Hg) exposure and autism spectrum disorder (ASD) show a similar dichotomy. Studies sponsored and supported by industry or entities with an apparent conflict of interest have most often shown no evidence of harm or no “consistent” evidence of harm, while studies without such affiliations report positive evidence of a Hg/autism association. The potentially causal relationship between Hg exposure and ASD differs from other toxic products since there is a broad coalition of entities for whom a conflict of interest arises. These include influential governmental public health entities, the pharmaceutical industry, and even the coal burning industry. This review includes a systematic literature search of original studies on the potential relationship between Hg and ASD from 1999 to August 2015, finding that of the studies with public health and/or industry affiliation, 86% reported no relationship between Hg and ASD. However, among studies without public health and/or industry affiliation, only 21% find no relationship between Hg and ASD. The discrepancy in these results suggests a bias indicative of a conflict of interest.

[1]  J G DATHAN,et al.  Pink Disease—Ten Years After (The Epilogue) , 1965, British medical journal.

[2]  Heather A. Young,et al.  Thimerosal exposure in infants and neurodevelopmental disorders: An assessment of computerized medical records in the Vaccine Safety Datalink , 2008, Journal of the Neurological Sciences.

[3]  Paul G. King,et al.  Hair Toxic Metal Concentrations and Autism Spectrum Disorder Severity in Young Children , 2012, International journal of environmental research and public health.

[4]  Tanzy Love,et al.  Autism Spectrum Disorder Phenotypes and Prenatal Exposure to Methylmercury , 2013, Epidemiology.

[5]  T. Hayes,et al.  There Is No Denying This: Defusing the Confusion about Atrazine , 2004 .

[6]  S A Glantz,et al.  Constructing "sound science" and "good epidemiology": tobacco, lawyers, and public relations firms. , 2001, American journal of public health.

[7]  Bernard Rimland,et al.  Association between thimerosal-containing vaccine and autism. , 2003, JAMA.

[8]  Renata Majewska,et al.  [Lack of association between thimerosal-containing vaccines and autism]. , 2011, Przeglad epidemiologiczny.

[9]  David A Geier,et al.  An assessment of the impact of thimerosal on childhood neurodevelopmental disorders , 2003, Pediatric rehabilitation.

[10]  Melody S Goodman,et al.  Hepatitis B Vaccination of Male Neonates and Autism Diagnosis, NHIS 1997–2002 , 2010, Journal of toxicology and environmental health. Part A.

[11]  David A Geier,et al.  A prospective study of thimerosal-containing Rho(D)-immune globulin administration as a risk factor for autistic disorders , 2007, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[12]  Patricia K. Baskin,et al.  Transparency in research and reporting: Expanding the effort through new tools for authors and editors , 2015 .

[13]  Joaquin Barnoya,et al.  The tobacco industry's worldwide ETS consultants project: European and Asian components. , 2006, European journal of public health.

[14]  Judith H Miles,et al.  Lack of association between Rh status, Rh immune globulin in pregnancy and autism , 2007, American journal of medical genetics. Part A.

[15]  R. Palmer,et al.  Proximity to point sources of environmental mercury release as a predictor of autism prevalence , 2008 .

[16]  Jeanne Lenzer,et al.  Centers for Disease Control and Prevention: protecting the private good? , 2015, BMJ : British Medical Journal.

[17]  J. Kern,et al.  A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity. , 2009, Acta neurobiologiae experimentalis.

[18]  Jennifer Sass Bending Science: How Special Interests Corrupt Public Health Research , 2008, Environmental Health Perspectives.

[19]  J. Meakins,et al.  Institute of Medicine report. , 2000, Canadian journal of surgery. Journal canadien de chirurgie.

[20]  Joanna Burger,et al.  Pesticide Regulation amid the Influence of Industry , 2014 .

[21]  Michael Aschner,et al.  Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge. , 2006, Neurotoxicology.

[22]  M. Desoto,et al.  Sorting out the spinning of autism: heavy metals and the question of incidence. , 2010, Acta neurobiologiae experimentalis.

[23]  Walter Wymer,et al.  Book Review: A Question of Intent: A Great American Battle with a Deadly Industry, David Kessler, Public Affairs, New York, 2001 , 2002 .

[24]  Norio Ozaki,et al.  Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder. , 2015, Vaccine.

[25]  M. Desoto,et al.  Fish Consumption Advisories and the Surprising Relationship to Prevalence Rate of Developmental Disability as Reported by Public Schools , 2012 .

[26]  Pietro Apostoli,et al.  Lack of Correlation Between Metallic Elements Analyzed in Hair by ICP-MS and Autism , 2011, Journal of Autism and Developmental Disorders.

[27]  K. Brownell,et al.  The perils of ignoring history: Big Tobacco played dirty and millions died. How similar is Big Food? , 2009, The Milbank quarterly.

[28]  Zachary Stein,et al.  The value of ecologic studies: mercury concentration in ambient air and the risk of autism , 2011, Reviews on environmental health.

[29]  Thanaa M. Rabah,et al.  Heavy metals and trace elements in hair and urine of a sample of arab children with autistic spectrum disorder. , 2011, Maedica.

[30]  Cathleen K. Yoshida,et al.  Prenatal and neonatal peripheral blood mercury levels and autism spectrum disorders. , 2014, Environmental research.

[31]  David A Geier,et al.  A comparative evaluation of the effects of MMR immunization and mercury doses from thimerosal-containing childhood vaccines on the population prevalence of autism. , 2004, Medical science monitor : international medical journal of experimental and clinical research.

[32]  James B. Adams,et al.  Mercury, Lead, and Zinc in Baby Teeth of Children with Autism Versus Controls , 2007, Journal of toxicology and environmental health. Part A.

[33]  Stanton A Glantz,et al.  Old ways, new means: tobacco industry funding of academic and private sector scientists since the Master Settlement Agreement , 2007, Tobacco Control.

[34]  Marco Molinari,et al.  Associations among exposure to methylmercury, reduced Reelin expression, and gender in the cerebellum of developing mice. , 2014, Neurotoxicology.

[35]  C. Hughes,et al.  An Extensive New Literature Concerning Low-Dose Effects of Bisphenol A Shows the Need for a New Risk Assessment , 2005, Environmental health perspectives.

[36]  A. El-Ansary,et al.  A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders , 2014, Behavioral and Brain Functions.

[37]  Patrick Ip,et al.  Mercury Exposure in Children With Autistic Spectrum Disorder: Case-Control Study , 2004, Journal of child neurology.

[38]  M. Obrenovich,et al.  Altered Heavy Metals and Transketolase Found in Autistic Spectrum Disorder , 2011, Biological Trace Element Research.

[39]  David Quig,et al.  Toxicological Status of Children with Autism vs. Neurotypical Children and the Association with Autism Severity , 2013, Biological Trace Element Research.

[40]  Mads Melbye,et al.  Association Between Thimerosal-Containing Vaccine and Autism , 2003 .

[41]  Gene P. Sackett,et al.  Erratum: “Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior” , 2016, Environmental health perspectives.

[42]  J. Harney,et al.  Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders. , 2014, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[43]  M. Hanson,et al.  The dental amalgam issue. A review , 1991, Experientia.

[44]  Mark F Blaxill,et al.  Reduced Levels of Mercury in First Baby Haircuts of Autistic Children , 2003, International journal of toxicology.

[45]  H. Tokuomi,et al.  [Minamata disease]. , 1968, Naika. Internal medicine.

[46]  K. Michael Cummings,et al.  The Cigarette Controversy , 2007, Cancer Epidemiology Biomarkers & Prevention.

[47]  David A Geier,et al.  Neurodevelopmental disorders, maternal Rh-negativity, and Rho(D) immune globulins: a multi-center assessment. , 2008, Neuro endocrinology letters.

[48]  Jane Levine,et al.  Authors' financial relationships with the food and beverage industry and their published positions on the fat substitute olestra. , 2003, American journal of public health.

[49]  Francine Laden,et al.  Perinatal Air Pollutant Exposures and Autism Spectrum Disorder in the Children of Nurses’ Health Study II Participants , 2013, Environmental health perspectives.

[50]  M. Lauritsen,et al.  Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. , 2003, Pediatrics.

[51]  S. Soden,et al.  24-Hour Provoked Urine Excretion Test for Heavy Metals in Children with Autism and Typically Developing Controls, a Pilot Study , 2007, Clinical toxicology.

[52]  Hiroshi Yasuda,et al.  Assessment of Infantile Mineral Imbalances in Autism Spectrum Disorders (ASDs) , 2013, International journal of environmental research and public health.

[53]  Diane Simpson,et al.  Autism and thimerosal-containing vaccines: lack of consistent evidence for an association. , 2003, American journal of preventive medicine.

[54]  A. Mack,et al.  Continuing Increases in Autism Reported to California’s Developmental Services System: Mercury in Retrograde , 2009 .

[55]  David A Geier,et al.  An Evaluation of the Effects of Thimerosal on Neurodevelopmental Disorders Reported Following DTP and Hib Vaccines in Comparison to DTPH Vaccine in the United States , 2006, Journal of toxicology and environmental health. Part A.

[56]  David A Geier,et al.  A Case Series of Children with Apparent Mercury Toxic Encephalopathies Manifesting with Clinical Symptoms of Regressive Autistic Disorders , 2007, Journal of toxicology and environmental health. Part A.

[57]  Thomas Clarkson,et al.  Comparison of Blood and Brain Mercury Levels in Infant Monkeys Exposed to Methylmercury or Vaccines Containing Thimerosal , 2005, Environmental health perspectives.

[58]  K. Eto,et al.  Ultrastructural changes of human sural nerves in the neuropathy induced by intrauterine methylmercury poisoning (so-called fetal Minamata disease) , 1978, Virchows Archiv. B, Cell pathology.

[59]  Ben Alderson-Day,et al.  A Comparison of Urinary Mercury between Children with Autism Spectrum Disorders and Control Children , 2012, PloS one.

[60]  D. Austin,et al.  Ancestry of Pink Disease (Infantile Acrodynia) Identified as a Risk Factor for Autism Spectrum Disorders , 2011, Journal of toxicology and environmental health. Part A.

[61]  Lora D. Delwiche,et al.  Blood Mercury Concentrations in CHARGE Study Children with and without Autism , 2009, Environmental health perspectives.

[62]  Elihu D Richter,et al.  Conflicts of interest and scientific integrity. , 2005, International journal of occupational and environmental health.

[63]  Paul G. King,et al.  A Case-Control Study Evaluating the Relationship Between Thimerosal-Containing Haemophilus influenzae Type b Vaccine Administration and the Risk for a Pervasive Developmental Disorder Diagnosis in the United States , 2014, Biological Trace Element Research.

[64]  M. Wong,et al.  Environmental mercury contamination in China: sources and impacts. , 2007, Environment international.

[65]  K. McComas,et al.  Session 5: Nutrition communication The role of trust in health communication and the effect of conflicts of interest among scientists , 2008, Proceedings of the Nutrition Society.

[66]  Steven G. Gilbert,et al.  Doubt Is Their Product: How Industry’s Assault on Science Threatens Your Health , 2009, Environmental Health Perspectives.

[67]  Lisa K. Sykes,et al.  Thimerosal as discrimination: vaccine disparity in the UN Minamata Convention on mercury. , 2014, Indian journal of medical ethics.

[68]  Barbara Goodson,et al.  Prenatal and Infant Exposure to Thimerosal From Vaccines and Immunoglobulins and Risk of Autism , 2010, Pediatrics.

[69]  P. Mierzejewski,et al.  Age-dependent lower or higher levels of hair mercury in autistic children than in healthy controls. , 2010, Acta neurobiologiae experimentalis.

[70]  N R Cozzarelli,et al.  Unfettered access to published results , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Martyn A. Sharpe,et al.  B-Lymphocytes from a Population of Children with Autism Spectrum Disorder and Their Unaffected Siblings Exhibit Hypersensitivity to Thimerosal , 2013, Journal of toxicology.

[72]  E. Cooper,et al.  Infections, Toxic Chemicals and Dietary Peptides Binding to Lymphocyte Receptors and Tissue Enzymes are Major Instigators of Autoimmunity in Autism , 2003, International journal of immunopathology and pharmacology.

[73]  Paul G. King,et al.  The risk of neurodevelopmental disorders following a Thimerosal-preserved DTaP formulation in comparison to its Thimerosal- reduced formulation in the vaccine adverse event reporting system (VAERS) , 2014 .

[74]  Mark R. Geier,et al.  A Case-Control Study of Mercury Burden in Children with Autistic Spectrum Disorders , 2003 .

[75]  Nicholas R Cozzarelli,et al.  UPSIDE: Uniform principle for sharing integral data and materials expeditiously. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[76]  Jennifer Sass,et al.  Credibility of Scientists: Conflict of Interest and Bias , 2006, Environmental health perspectives.

[77]  Eric Boerwinkle,et al.  Seafood Consumption and Blood Mercury Concentrations in Jamaican Children With and Without Autism Spectrum Disorders , 2012, Neurotoxicity Research.

[78]  Gehan A. Mostafa,et al.  Antineuronal antibodies in autistic children: relation to blood mercury , 2007 .

[79]  Kim Van Naarden Braun,et al.  Trends in the Prevalence of Autism Spectrum Disorder, Cerebral Palsy, Hearing Loss, Intellectual Disability, and Vision Impairment, Metropolitan Atlanta, 1991–2010 , 2015, PloS one.

[80]  Inkyu Han,et al.  Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury. , 2015, The Science of the total environment.

[81]  Janet K. Kern,et al.  A two-phase study evaluating the relationship between Thimerosal-containing vaccine administration and the risk for an autism spectrum disorder diagnosis in the United States , 2013, Translational Neurodegeneration.

[82]  Erin E. Kent,et al.  Heavy Metal in Children’s Tooth Enamel: Related to Autism and Disruptive Behaviors? , 2012, Journal of autism and developmental disorders.

[83]  L. Al-Ayadhi,et al.  The Possible Association between Elevated Levels of Blood Mercury and the Increased Frequency of Serum Anti-myelin Basic Protein Auto-antibodies in Autistic Children , 2015 .

[84]  Jean-Marie Manus,et al.  Ortho Clinical Diagnostics , 2008 .

[85]  Alan D. Attie,et al.  The Republican War on Science , 2005 .

[86]  Allal Ouhtit,et al.  Decreased glutathione and elevated hair mercury levels are associated with nutritional deficiency-based autism in Oman , 2014, Experimental biology and medicine.

[87]  S M Bartell,et al.  An Evaluation of Surrogate Chemical Exposure Measures and Autism Prevalence in Texas , 2009, Journal of toxicology and environmental health. Part A.

[88]  David Hanson,et al.  A Personal Perspective on the Initial Federal Health-Based Regulation to Remove Lead from Gasoline , 2009, Environmental health perspectives.

[89]  C Lenti,et al.  Normal concentrations of heavy metals in autistic spectrum disorders. , 2012, Minerva pediatrica.

[90]  Vijendra K. Singh,et al.  Detection of Antinuclear and Antilaminin Antibodies in Autistic Children Who Received Thimerosal-Containing Vaccines , 2004, Journal of Biomedical Science.

[91]  Zachary Stein,et al.  Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas. , 2006, Health & place.

[92]  L. Al-Ayadhi,et al.  Heavy metals and trace elements in hair samples of autistic children in central Saudi Arabia. , 2005, Neurosciences.

[93]  J WARKANY,et al.  Mercury in the urine of children with acrodynia. , 1948, Lancet.

[94]  A Dally,et al.  The rise and fall of pink disease. , 1997, Social history of medicine : the journal of the Society for the Social History of Medicine.

[95]  Stepan Melnyk,et al.  Increased Susceptibility to Ethylmercury-Induced Mitochondrial Dysfunction in a Subset of Autism Lymphoblastoid Cell Lines , 2015, Journal of toxicology.

[96]  Vijendra K Singh,et al.  Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine‐derived thimerosal , 2006, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[97]  A. Brandt Inventing conflicts of interest: a history of tobacco industry tactics. , 2012, American journal of public health.

[98]  Stanton A Glantz,et al.  Tobacco Industry Efforts Undermining Evidence Linking Secondhand Smoke With Cardiovascular Disease , 2007, Circulation.

[99]  Janet K. Kern,et al.  Blood mercury levels in autism spectrum disorder: Is there a threshold level? , 2010, Acta neurobiologiae experimentalis.

[100]  S. Eddy,et al.  Sharing Publication-Related Data and Materials: Responsibilities of Authorship in the Life Sciences1 , 2003, Plant Physiology.

[101]  Thanaa M. Rabah,et al.  Efficacy of DMSA Therapy in a Sample of Arab Children with Autistic Spectrum Disorder. , 2012, Maedica.

[102]  J. Gregg,et al.  Correlations Between Gene Expression and Mercury Levels in Blood of Boys With and Without Autism , 2009, Neurotoxicity Research.

[103]  John Slade,et al.  A Question of Intent: A Great American Battle with a Deadly Industry , 2001, Nature Medicine.

[104]  L. Croen,et al.  Autism Spectrum Disorders in Relation to Distribution of Hazardous Air Pollutants in the San Francisco Bay Area , 2006, Environmental health perspectives.

[105]  Thanaa M. Rabah,et al.  Toxic Metals and Essential Elements in Hair and Severity of Symptoms among Children with Autism. , 2012, Maedica.

[106]  A. Geetha,et al.  Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism , 2011, Biological Trace Element Research.

[107]  Robert L Davis,et al.  Safety of thimerosal-containing vaccines: a two-phased study of computerized health maintenance organization databases. , 2003, Pediatrics.

[108]  Nick Andrews,et al.  Thimerosal Exposure in Infants and Developmental Disorders: A Retrospective Cohort Study in the United Kingdom Does Not Support a Causal Association , 2004, Pediatrics.

[109]  S. Al-Saad,et al.  Toxic trace elements in the hair of children with autism , 2005, Autism : the international journal of research and practice.

[110]  M. Desoto,et al.  Blood Levels of Mercury Are Related to Diagnosis of Autism: A Reanalysis of an Important Data Set , 2007, Journal of child neurology.

[111]  Pamela M Ling,et al.  Meanings & motives. Experts debating tobacco addiction. , 2008, American journal of public health.

[112]  Rebecca L Morgan,et al.  Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. , 2012, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[113]  Stepan Melnyk,et al.  Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[114]  David A Geier,et al.  Neurodevelopmental Disorders after Thimerosal-Containing Vaccines: A Brief Communication , 2003, Experimental biology and medicine.

[115]  Heba A Yassa,et al.  Autism: a form of lead and mercury toxicity. , 2014, Environmental toxicology and pharmacology.

[116]  Geir Bjørklund,et al.  Levels of Metals in the Blood and Specific Porphyrins in the Urine in Children with Autism Spectrum Disorders , 2014, Biological Trace Element Research.

[117]  Brian S. Hooker,et al.  A Dose-Response Relationship between Organic Mercury Exposure from Thimerosal-Containing Vaccines and Neurodevelopmental Disorders , 2014, International journal of environmental research and public health.

[118]  David A Geier,et al.  A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. , 2005, Medical science monitor : international medical journal of experimental and clinical research.