Andrew Wakefield Study Jason Machula MBIO 610 Fall 2010
Who is Andrew Wakefield?Born 1956Former British surgeon and researcherSt Mary’s Medical School London Qualified 1981Became fellow of the Royal College of surgeons in 1985Continued studies at University of Toronto became a transplant surgeon specializing in small intestine transplantationBecame senior lecturer and honorary consultant in gastroentology Royal Free Hospital School of Medicine
While researching Chron’s disease, approached by Rosemary Kessick (1995) Parent of autistic son seeking help with his bowel problems and Autism Kessick runs Allergy Induced Autism Focuses on effects of diet on autistic children’s behaviorLead author of study published in 1998: Wakefield AJ, Murch SH, Anthony A, et al. “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”. Lancet 351 (9103): 637–41 (1998).
His ClaimsParents of 8 of the 12 participants made a temporal link to their child’s behavioral abnormalities with the administration of the MMR vaccine"We did not prove an association between measles, mumps, and rubella vaccine and the syndrome described,“ In his 1998 paper published in The LancetHowever in a later press conference, Wakefield suggested that parents space out three separate vaccines instead of the multiple MMR vaccine administered in a single doseClaimed Mesles infections obtained from vaccine causes Autism.Twenty Twenty Interview, Feb 4, 1998: on the MMR vaccine• INTERVIEWER: …do the advantages of continuing with the vaccines outweigh the disadvantages of a problem developing if you, if you continue to have them?• DR ANDREW WAKEFIELD: Well I think it’s a very complex question. Certainly if you continue, as I would recommend to use the single vaccine, you do not incur a greater risk of those diseases in the children, so that you do not lose the benefits of vaccination if you space them over time.• INTERVIEWER: (CUTS) So even measles?• DR ANDREW WAKEFIELD: Well as yet we don’t know, but there is no doubt that if you give three viruses together, three live viruses, then you potentially increase the risk of an adverse event occurring, particularly when one of those viruses influences the immune system in the way that measles does. And it may be, and studies will show this or not, that giving the measles on its own reduces the risk of this particular syndrome developing.
Wakefield AJ. MMR vaccination and autism. Lancet 1999;354:949-50.
Outcome?Reduced vaccinations in UK and all over the world. Before Wakefield published: UK MMR vaccination rates were 92% After publishing: UK MMR vaccination rates dropped below 80% Thomas J. Paranoia Strikes Deep: MMR Vaccine and Autism. Psychiatric Times. 2010;27(3):1-6
AutismWhat is autism? According to the NIH National Institute for Neurological Disorders and Stroke: “Autism spectrum disorder (ASD) is a range of complex neurodevelopment disorders, characterized by social impairments, communication difficulties, and restricted, repetitive, and stereotyped patterns of behavior.” http://www.ninds.nih.gov/disorders/autism/detail_autism.htm
How is autism diagnosed? (Taken from NIH National Institute for Neurological Disorders and Stroke)ASD varies widely in severity and symptoms and may go unrecognized, especially in mildly affected children or when it is masked by more debilitating handicaps. Very early indicators that require evaluation by an expert include:• no babbling or pointing by age 1• no single words by 16 months or two-word phrases by age 2• no response to name• loss of language or social skills• poor eye contact• excessive lining up of toys or objects• no smiling or social responsiveness.Later indicators include:• impaired ability to make friends with peers• impaired ability to initiate or sustain a conversation with others• absence or impairment of imaginative and social play• stereotyped, repetitive, or unusual use of language• restricted patterns of interest that are abnormal in intensity or focus• preoccupation with certain objects or subjects• inflexible adherence to specific routines or rituals. http://www.ninds.nih.gov/disorders/autism/detail_autism.htm
Measles Mumps and Rubella VaccineLicensed in US in 1971Second dose introduced 1989 Banatvala JE, Brown DW (2004). "Rubella". Lancet 363 (9415): 1127–37.Vaccine contains three attenuated virus strainsMeasles and Mumps propagated in chick embryo cell culture Attenuvax Product Sheet. Merck & Co., 2006 Mumpsvax Product Sheet. Merck & Co., 1999Rubella propagated in WI-38 human diploid lung fibroblasts Package Insert, Meruvax II. Merck & Co., 2006 “That stung a little”
The first 20 years alone of measles vaccination prevented an estimated: 52 million infections 17,400 cases of mental retardation 5,200 deathsBloch AB, Orenstein WA, Stetler HC et al. (1985). "Health impact of measles vaccination in the United States". Pediatrics 76 (4): 524–32.
Between 1999 and 2004, efforts to increase measles vaccination coverage by the WHO and UNICEF prevented an estimated 1.4 million deaths worldwide.Centers for Disease Control and Prevention (CDC) (2006). “Progress In Reducing Global Measles Deaths, 1999-2004”. MMWR Morb Mortal Wkly Rep 55 (9): 247–9.
Measles cases reported in the United States, 1944-Cases 1944-1993 are reported in:Centers for Disease Control and Preventi21, 1994 for Morbidity and Mortality WeeklyReport 1993; 42 (No. 53)Cases 1976-2007 are reported in: Centers diseases—United States,  Published July 9,2009 for Morbidity and Mortality Weekly Report 2007; 56 (No. 53)
Data from Health Protection Agency http://www.hpa.org.uk/
…..So what did Wakefield haveagainst the MMR vaccine?
Thimerosal!! www.drugs.comEthyl Organomercury compound, (was) used as preservative in vaccines In one 1928 incident, 12 of 21 children vaccinated for Diptheria with a vaccine without any preservative died from a Staph infection. (FDA)Doesn’t reduce vaccine effectiveness like current (at the time) preservativesStudies show it is safer than inorganic or methyl organomercuryUS began removing it from vaccines as a precaution in 1999 Removed from all childhood vaccines except influenza by 2001Currently only found in Flu vaccine (trace amounts)Appears to be cleared by body after some time (weeks) Clarkson TW, Magos L (2006). "The toxicology of mercury and its Chemical compounds". Crit Rev Toxicol 36 (8): 609–62.
Studies:Stokstad E, Science 12 September 2003:Vol. 301. no. 5639, pp. 1454 - 1455 Danish Study Study done in Japan
Additional Yokohama Study data ,Hideo Honda, et al., No Effect of MMR Withdrawal on the Incidence of Autism: aTotal Population Study. Journal of Child Psychology and Psychiatry 46:6 (2005), pp 572–579
Another Danish Study Another Danish Study“Thimerosal and the Occurrence of Autism: Negative Ecological Evidence from Danish Population- Based Data” Pediatrics, Kreesten M. Madsen, MD (September 2003)
Study done in Swedenwww.sciencebasedmedicine.org
UK StudyJames A Kaye, et al., Mumps, Mmeasles, and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time TrendAnalysis. BMJ Volume 322. 24 February, 2001
Loring Dales, et al., Time Trends in Autism and in MMR Immunization Coverage in California. JAMA. 2001;285(9):1183-1185
CDC, WHO, NIH, NEJM, and dozens of others, report that there is no correlation between Autism and the MMR vaccine
Any Support for Wakefield?http://jennymccarthyimages.blogspot.com/ http://www.zuguide.com/blog/2008/12/05/yes-man-aka- liar-liar-part-ii/
14studies.org• About Us• This website was compiled by the founders of Generation Rescue, Jenny McCarthy’s autism organization. Generation Rescue is a parent-founded and parent-led non-profit organization with more than 1,000 parent volunteers all over the world.• The Generation Rescue website provides a wealth of information about autism. Please consider taking the time to learn more about: biomedical intervention, finding a doctor, finding a rescue angel, learning about the success stories of others, and learning about vaccinating safely.• For more information, check out www.generationrescue.org
Actually, Wakefield’s paper was retracted by the Lancet The Lancet, Volume 375, Issue 9713, Page 445, 6 February 2010 (retraction)Controversy arose as soon as his study was publishedIncreased when the UK made no plans or efforts to offer a single vaccine alternativeWakefield left the Royal Free Hospital blaming the unpopularity of his results in 2001Continued clinical research in US with controversial researcher Jeff Bradstreet
Allegations of misconduct presented in the Sunday Times (London) or Channel 4 by investigator Brian DeerDate reported:Feb 2004: Some of parents in study were recruited by a UK lawyer preparing a lawsuit against the MMR manufacturers 24 hrs prior to release of Sunday Times report: Lancet retracts an interpretation in the paper and state that Wakefield’s research is “fatally flawed.” 10 of 12 coauthors involved in retractionNovember 2004: Prior to paper’s release Wakefield filed patent application for a single measles virus.Wakefield files Libel charges against “everyone.” but has his actions frozen until General Medical Council proceedings against him conclude. He was forced to pursue charges or drop them.November 2005: Channel 4 lawyers submit pleadings to the court:
(i) Had dishonestly and irresponsibly spread fear that the MMR vaccine mightcause autism in some children, even though he knew that his ownlaboratorys tests dramatically contradicted his claims and he knew or oughtto have known that there was absolutely no scientific basis at all for his beliefthat MMR should be broken up into single vaccines.(ii) In spreading such fear, also acted dishonestly and irresponsibly, byrepeatedly failing to disclose conflicts of interest and/or material information,including his association with contemplated litigation against themanufacturers of MMR and his application for a patent for a vaccine formeasles which, if effective, and if the MMR vaccine had been underminedand/or withdrawn on safety grounds, would have been commercially veryvaluable.(iii) Caused medical colleagues serious unease by carrying out researchtests on vulnerable children outside the terms or in breach of the permissiongiven by an ethics committee, in particular by subjecting those children tohighly invasive and sometimes distressing clinical procedures and therebyabusing them.(iv) Has been unremittingly evasive and dishonest in an effort to cover up hiswrong-doing.
Proceedings continued for two years until:Reported December 2006: A figure from the Legal Services Commission showed that Wakefield received £435,643 from lawyers responsible for MMR lawsuit (previously undisclosed), payments began two years prior to paper’s releaseWithin ten days Wakefield dropped his libel charges and was forced to pay Channel 4’s legal feesUK GMC charged Wakefield with serious professional misconduct, including dishonesty, hearings began 2007January 28, 2010 Wakefield found guilty of all charges Data fixing, caused life-threatening complications in one participant, improper recruitment of participants, invasive procedures performed without proper approval and contrary to participants interests, etc……the list goes on
Effects• Unvaccinated children, increased illness and deaths• Bad reputation for vaccines• Research hours and money wasted?
Future thoughtsTotal number of vaccines?Autism Linked to Juandice? US News & World Report, MSNBC, etc. Based off of studies in DenmarkFetal stem cell links?Maternal Antibodies contribution? Singer HS, etal., Antibodies against fetal brain in sera of mothers with autistic children. J Neuroimmunol. 2008 Feb;194(1-2):165-72. Epub 2008 Feb 21