Thimerosal Disappears but Autism Remains

COMMENTARY Thimerosal Disappears but Autism Remains

INCE AUTISM WAS DE- tries. With the exception of studies consistent with those of previously scribed in the 1940s, conducted by the 1 single pair of au- published cohort and case-control multiple unfounded thors,5 all studies failed to reject the studies10 and similar ecologic stud- theories of causation and null hypothesis of no association.6 ies conducted in Denmark and corollary “treatments” Relative risks in studies in which it Canada.11,12 Ecologic studies can be haveS been offered. Psychiatry, then a could be estimated were close or be- powerful tools to test causal hypoth- psychoanalytically oriented disci- low unity, and studies were in most eses in circumstances in which ex- pline, posited a psychosocial expla- cases well powered to detect even posure to a risk factor (in this case, nation that blamed “refrigerator” small effects and could adjust for immunizations) is widespread and mothers for the child’s withdrawal background confounding factors. In when the effects of variation in ex- into the autistic bubble, only to be parallel, several studies were con- posure level can be examined (either reached by the interpretations of ducted that failed to identify a spe- by contrasting different countries that therapists engaged in long-term play cific phenotype of mercury- or MMR- systematically differ in their expo- therapy. To name only a few more re- induced autism and failed to find sure levels or by testing trends across cent such theories taken from both evidence of mercury poisoning or of time when sufficient variation in the the persistence of the measles virus level of exposure, as in the case of dis- See also page 19 in children with autism. In 2004, the continuation, occurs). The particu- Institute of Medicine Immunization lar significance of the study by the psychosocial and biological realm Safety Review Committee reviewed Schechter and Grether9 is that it re- of explanations, facilitated commu- all evidence available from epidemio- lies on the California Department of nication and secretin infusion en- logic, biological, molecular, and ani- Developmental Services database, joyed widespread support up to the mal model studies and concluded that which has been systematically used point when the systematic accumu- the evidence favored the rejection of by proponents of the thimerosal hy- lation of carefully controlled clinical both hypotheses with respect to the pothesis to argue that the rising num- trials consistently failed to provide 7 1,2 risk of autism. Since then, more stud- ber of children accessing these ser- support for their efficacy. In the last ies have accumulated that have re- vices—or the “epidemic” of autism— decade, 2 hypotheses on autism- inforced this conclusion, one inde- was linked to the increasing exposure immunization links were raised that pendently reached by scientific and to ethylmercury of US children oc- have had a profound impact in the professional committees around the curring in the 1990s through the field of autism research and practice world.8 changes in the immunization sched- and on public health at large. One in- The study by Schechter and ule. To the contrary, the data ana- criminated the measles component of Grether9 in this issue of the Archives lyzed by Schechter and Grether9 pro- the triple measles-mumps-rubella 3 provides additional evidence of the vide a clear and unambiguous test (MMR) vaccine, the other the lack of association between thimero- that shows that the expected de- amount of thimerosal (about 50% of sal exposure and the risk of autism cline in autism rates following dis- which is ethylmercury) contained in in the US population. Using an eco- continuation of thimerosal in US vac- 4 most other childhood vaccines. The logic design and data from the Cali- cines did not occur. 2 hypotheses are separate, since MMR fornia Department of Developmen- Despite the accumulation of sci- vaccines never contained thimero- tal Services, the authors showed that entific evidence rejecting these 2 hy- sal. Both hypotheses relied on the the prevalence rate of autism in- potheses linking autism to various claim of an autism “epidemic” that ap- creased continuously during the components of childhood vaccines, parently coincided with the introduc- study period even after the discon- these theories and the practices that tion of MMR and/or the increased ex- tinuation of the use of thimerosal in accompany them have not faded posure to ethylmercury due to the US vaccines in 2001. Had there been away. Why? How many more nega- increased number of recommended any risk association between thimero- tive study results are required for the childhood immunizations in the first sal-containing vaccines and autism, belief to go away, and how much 3 years of life. the rate of autism should have de- more spending of public funds on this In testing these hypotheses, criti- creased in young children between issue could even be justified? A full cal epidemiologic investigations were 2004 and 2007. Instead, the rate in- answer to this question is beyond the immediately conducted by different crease did not attenuate, indicating scope of this commentary, but some investigators using a variety of de- that thimerosal exposure bears no re- issues relevant to the development signs (cohort, case-control, and eco- lationship to the risk of autism. The and persistence of this controversy logic) in different samples and coun- findings of Schechter and Grether9 are can be identified in the complex in-

(REPRINTED) ARCH GEN PSYCHIATRY/ VOL 65 (NO. 1), JAN 2008 WWW.ARCHGENPSYCHIATRY.COM 15 Downloaded from www.archgenpsychiatry.com at CDC-Information Center, on January 8, 2008 ©2008 American Medical Association. All rights reserved. terplay between academic medicine, use of a hyperbaric oxygen cham- REFERENCES social policy influences, families of au- ber, and testosterone suppres- 16 tistic children, and the public. sion. All are of unproven efficacy, 1. Williams KW, Wray JJ, Wheeler DM. Intravenous In the 1990s, most of the fund- and many are dangerous. secretin for autism spectrum disorder. Cochrane Da- ing in autism research went ini- Childhood vaccines have been tabase Syst Rev. 2005;(3):CD003495. tially to genetic research, consis- one of the most important ad- 2. Mostert MP. Facilitated communication since 1995: a review of published studies. J Autism Dev Disord. tent with the strong evidence of vances of modern medicine in the 2001;31(3):287-313. autism as a genetic disorder. As a re- 20th century. Unfortunately, once 3. Wakefield AJ, Murch SH, Anthony A, Linnell J, Cas- sult, the United States, as did most vaccine programs have been suc- son DM, Malik M, Berelowitz M, Dhillon AP, Thom- other countries, failed to track the cessful at controlling preventable in- son MA, Harvey P, Valentine A, Davies SE, Walker- fectious diseases, people shift their Smith JA. Ileal-lymphoid-nodular hyperplasia, non- incidence of autism and related dis- specific colitis, and pervasive developmental orders. Much-needed epidemio- attention to the potential adverse ef- disorder in children [partially retracted in: Lan- logic approaches to the study of au- fects of vaccines (which are rare but cet. 2004;363(9411):750]. Lancet. 1998;351 tism and other disorders were not can nevertheless be serious). Deaths (9103):637-641. developed or funded. Thus, as the of young children occurred in Eu- 4. Ball LK, Ball R, Pratt D. An assessment of thimerosal use in childhood vaccines. Pediatrics. number of children diagnosed as rope because of the MMR-autism 2001;107(5):1147-1154. having autism grew, concerns about scare, and as shown in a recent US 5. Geier DA, Geier MR. An assessment of the im- an epidemic were appropriately measles outbreak,17 children’s health pact of thimerosal on childhood neurodevelop- raised in the public. Available data was put at risk by parents who re- mental disorders. Pediatr Rehabil. 2003;6(2): fused to vaccinate their children be- 97-102. suggest that broadening of the au- 6. Doja A, Roberts W. Immunizations and autism: a tism concept, changes in diagnos- cause of the supposed vaccine- review of the literature. Can J Neurol Sci. 2006; tic criteria, diagnostic substitution, autism link. Parents of autistic 33(4):341-346. improvements in educational poli- children should be reassured that au- 7. Institute of Medicine. Immunization Safety Re- cies, and increased awareness have tism in their child did not occur view: Vaccines and Autism. Washington, DC: Na- tional Academies Press; 2004. played a major role in explaining the through immunizations. Their au- 8. Andreae MC, Freed GL, Katz SL. Safety concerns increasing numbers of children iden- tistic children, and their siblings, regarding combination vaccines: perspective of tified with autism.13,14 New moni- should be normally vaccinated, and select European countries. Hum Vaccin. 2005; toring programs such as those as there is no evidence of mercury 1(1):1-5. poisoning in autism, they should 9. Schechter R, Grether JK. Continuing increases in developed in recent years by the autism reported to California’s developmental ser- Centers for Disease Control and Pre- avoid ineffective and dangerous vices system: mercury in retrograde. Arch Gen vention will help to address these “treatments” such as chelation Psychiatry. 2008;65(1):19-24. questions in the near future. therapy for their children. 10. Parker SK, Schwartz B, Todd J, Pickering LK. Outside academic circles, pow- Thimerosal-containing vaccines and autistic spectrum disorder: a critical review of published origi- erful advocacy groups developed and Eric Fombonne, MD nal data. Pediatrics. 2004;114(3):793-804. started to lobby decision makers to 11. Madsen KM, Lauritsen MB, Pedersen CB, Thorsen influence decisions about which au- Correspondence: Dr Fombonne, De- P, Plesner AM, Andersen PH, Mortensen PB. tism research to fund and even how partmentofPsychiatry,MontrealChil- Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based to conduct it. Unaware of scientific dren’sHospital,4018SteCatherineW, data. Pediatrics. 2003;112(3, pt 1):604-606. studies, or worse, doubtful of their Montreal, QC H3Z 1P2, Canada (eric 12. Fombonne E, Zakarian R, Bennett A, Meng L, results, bestselling writers, journal- [email protected]). McLean-Heywood D. Pervasive developmental dis- ists, and politicians were drawn to Financial Disclosure: In the United orders in Montreal, Quebec, Canada: prevalence embrace conspiracy theories that Kingdom, Dr Fombonne has pro- and links with immunizations. Pediatrics. 2006; 118(1):e139-e150. portrayed vaccine manufacturers and vided advice on the epidemiology 13. Shattuck PT. Diagnostic substitution and chang- the Centers for Disease Control and and clinical aspects of autism to sci- ing autism prevalence. Pediatrics. 2006;117 Prevention as public enemies.15 Law entists advising parents, MMR vac- (4):1438-1439. firms saw an opportunity to obtain cine manufacturers, and several gov- 14. Wazana A, Besnahan M, Kline J. The autism epidemic: fact or artifact? J Am Acad Child Adolesc large financial compensations from ernment committees between 1998 Psychiatry. 2007;46(6):721-730. the US Vaccine Injury Compensa- and 2001. In the United States, he 15. Epstein RA. It did happen here: fear and loathing tion Court or before local federal has been a consultant to ad hoc com- on the vaccine trail. Health Aff (Millwood). 2005; courts, the viscous US legal process mittees from the Institute of Medi- 24(3):740-743. allowing for fermentation of mis- cine and the American Academy of 16. Geier DA, Geier MR. A clinical trial of combined anti-androgen and anti-heavy metal therapy in conceptions. Exploiting further Pediatrics. Dr Fombonne is an ex- autistic disorders. Neuro Endocrinol Lett. 2006; families’ beliefs and their under- pert witness for the US Department 27(6):833-838. standable desire to try everything of Health and Social Services and for 17. Parker AA, Staggs W, Dayan GH, Ortega-Sanchez possible to help their children, char- vaccine manufacturers in the US thi- IR, Rota PA, Lowe L, Boardman P, Teclaw R, Graves C, LeBaron CW. Implications of a 2005 measles out- latans developed alternative (and lu- merosal litigation. None of his re- break in Indiana for sustained elimination of measles crative) “treatments” for autism, search has ever been funded by the in the United States. N Engl J Med. 2006;355(5): which included chelation therapy, pharmaceutical industry. 447-455.

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