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Vaccine Autoimmune Project for Research and Education (VAP)
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Mercury and Autism in the United Kingdom
As noted in Part I, it took Elizabeth Miller, head of immunization at the U.K. Public Health Laboratory Service (PHLS), four weeks to reply to a June 17, 2001 article in the Sunday Times that reported she was to lead a World Health Organization (WHO) investigation into autism and mercury-containing vaccines. When Miller’s letter finally appeared in the newspaper on July 15, it apparently denied reporter Rosie Waterhouse’s claims about an increasing mercury load in vaccine since 1988, although on careful scrutiny, there seemed little substance to the rebuttal. It also came to light that the official U.K. infant mercury exposure was just a fraction of the WHO schedule, despite the statement in the published study that they were “the same.” Such a delay in responding is curious enough in the context of a weekly newspaper, and enhanced in this case by the level of indignation expressed in Miller’s letter when it appeared. The reasons for this unusual occurrence, according to emails obtained under the U.S. Freedom of Information Act, would seem to lie with the U.S. Centers for Disease Control and Prevention (CDC). These few surrendered emails must surely represent a tiny proportion of the exchanges that would have gone on for weeks and months among the PHLS, the CDC, and the WHO. Eleven days had elapsed from the publication of the Sunday Times article, when Elizabeth Miller emailed Robert Chen of the CDC: “Dear Bob, “The information given to me by the licensing authority is that the whole cell DTP/Hib vaccine we currently use contains 50 micrograms thiomersal per dose so that our children if on schedule would have 75 micrograms of ethyl Hg by 4 months of age. They originally told me that the whole cell DTP we used on its own from 1990 (when we adopted our accelerated schedule) up to 1992/3 contained 100 micrograms thiomersal, so exposure to ethyl Hg would have been 150 micrograms by 4 months. We then started using combined DTP/Hib vaccines for which the thiomersal content apparently was 50 ug/dose. The authority is now saying that they have made a mistake and the vaccine we used up to 1992/3 only contained 50 micrograms thiomersal/dose. If this is true, then do we have sufficient exposure to ethyl Hg by 4-6 months of age to pick up an effect? Do I have to give my GPRD grant money from WHO back? Liz” There are several puzzles here. One is, how could it be that the head of the immunization division of the Public Health Laboratory Service needed to apply to the licensing authority to ascertain the content of the vaccines? Then there is Miller’s conviction that the dose had been higher, her annoyance that the U.K. mercury load was half what she had believed (which might have been considered good news), and her strongly expressed concern that she might lose the grant for the WHO research for this reason. The WHO project was certainly in jeopardy. The following day, Thomas Verstraeten, Chen’s colleague at the CDC, wrote to Chen: “Bob, “I think two issues are important in assessing the potential strength of the GPRD study: “1. Maximum exposure and 2. Unbiased controls. “The maximum exposure is indeed relatively low if that was the only T(himerosal) containing vaccine used. My estimate is that you need at least >50 by 3 months or >100 by 6 months to see an effect if there is one which you can barely make (50 at 2 mo and 75 at 4 mo in the UK). “The quality of the comparison group is maybe even more important if you consider all the criticism we have received of comparing high T exposure to no or low T exposure. I am not sure if the GPRD is that reliable that you can be sure that low exposure is really low exposure and not underascertainment in the database. “I hate to say this, but given these concerns, it may not be worth doing this after all. On the other hand, maybe the grant can be given to Harald in Sweden to do his follow-up of the DTaP trial kids….” Verstraeten’s note raises a catalogue of issues, which in light of events must continue to raise concern:
Verstraeten’s qualms, nevertheless, seem to have been pushed aside in the following fortnight in time for Miller’s letter to appear in the Sunday Times confirming, among other things, that her laboratory was to conduct a study on behalf of the WHO, as reported a month earlier. But all the participants in the discussions had known that the official U.K. mercury load was not the same as the WHO load, as the paper was eventually erroneously to state. Could it be that they were driven to this because removing the WHO funding would have drawn attention to the issue of the size of the WHO mercury load, and exposed the whole story to the glare of publicity once again, perhaps on an international basis? It seems impossible to resolve the mystery of the 100µg thimerosal/50µg mercury dose that Miller apparently had believed was contained in the DPT. For instance, the minutes of a Joint Committee on Vaccination and Immunization (JCVI) of Oct. 9, 2000 reported: "A paper comparing the potential levels of thiomersal exposure at 6 months of age through the U.K. and U.S. immunization program was presented. The estimated potential thiomersal exposure through the U.K. program was calculated to range between 0.15 and 0.30 mg (equivalent to 75-150 ug of mercury)." Another JCVI document from the second half of 1999 with the date blanked out seems to refer to the 0.3-mg exposure to thimerosal as current: “The estimated potential thiomersal exposure through the U.K. program is between 0.15 – 0.3mg.” Also, confirming the measurement in volume terms: “A solution of 0.01 or 0.02 percent thiomersal is commonly used in vaccines.” Following publication of the PHLS study, Miller and her co-author Nick Andrews were unable to resolve this matter in public correspondence in on-line Pediatrics. They cited letters written to the author by Philip Bryan of the MHRA: “A subsequent review of the content of thiomersal-containing vaccines revealed that the ‘150 microgram’ calculation was actually based on an incorrect assumption that the ethylmercury content of this vaccine brand was 50 micrograms per dose when it, in fact, was 50 micrograms per 1ml (i.e. 25 micrograms per 0.5ml dose). Ethylmercury exposure through doses of DTP vaccination by 4 months of age, therefore, did not exceed 75 micrograms. I hope this clarifies the confusion.” (Letter: Aug. 3, 2005) “The vaccine product for which the incorrect information on quantity of thiomersal per dose was provided was Trivax AD. This information relating to Trivax AD was supplied some time ago in response to an urgent query at a time when many products containing thiomersal had to be identified. As stated, following subsequent requests for information, it was noted that the initial quantity per dose calculation was actually based on an incorrect assumption that the ethylmercury content of the vaccine brand was 50 micrograms per dose when, in fact, it was 50 micrograms per 1ml (i.e. 25 micrograms per 0.5ml dose). I hope this clarifies the matter.” (Letter: Sept. 5, 2005) Bryan proposed this as an explanation of the Medicines Control Agency briefing note of June 7, 2001, provided by the Department of Health, which stated: "Thiomersal-containing vaccines have been in use for over 60 years and evidence does not support a causal link with autism. Indeed, reported rates of autism have been continuing to rise over the past decade as thiomersal content in routine U.K. childhood program has fallen." It is worth noting, if it was true (and Bryan claims it was an error), that the rising trend in autism in 2001 would have been a product of the early ’90s vaccination, when the routine program dose was said to be higher. Any lowering of dose in the later ’90s would have been too recent to trace. This was a flawed argument, although as it turns out, it was never produced in public. Interestingly, when I challenged Miller and Andrews publicly on the fact that the JCVI documents also gave the figure as a percentage of volume, they did not offer any further defence or explanation. Nor is it clear that the peculiar circumstances of this error as described by Philip Bryan would have been compatible with successive presentations over a 12-month period at the JCVI, including a paper discussing the higher level. (But Bryan also makes the common error of quoting the mercury level in thimerosal as for “ethylmercury” as opposed to mercury per se.) It should also be noted that according to an internal Merck memo “Re: Vaccine Task Force Assignment Thimerosal (Merthiolate) Preservative — Problems, Analysis, Suggestions For Resolution” written under the sub-heading “Problem” by Maurice Hilleman in March 1991: “The regulatory control agencies in some countries, particularly Scandinavia (especially Sweden). but also U.K., Japan, and Switzerland have expressed concern for thimerosal, a mercurial preservative, in vaccines.” The evidence, therefore, is that there had been awareness of the mercury level problem by British health officials — and possibly “concern” — since at least 1991, even though the matter did not become publicly known until the Sunday Times highlighted it in 2001. Against this background, it is surprising that a mix-up of the kind described by Philip Bryan could have continued over an extended period. By Aug. 14, 2001, Elizabeth Miller was requesting from Robert Chen access to background variable confounders in the unpublished CDC Vaccine Safety Datalink (VSD) study co-authored by Chen, and led by Thomas Verstraeten: “I am just about to receive the GPRD data which we propose to use to do the same kind of study you did on the VSD data set. It would be very helpful if you had a protocol describing what you did in your study, in particular what the background variables were that you included as possible confounders. I am on leave from 21 August to 10 September, but Nick, the statistician, who will be working on the data set, is around and you could liaise with him directly.” On Oct. 18, 2001, Miller was seeking further aid from CDC concerning the potential for irregularity in the outcome coding of GPRD. She wrote to Chen: “Dear Bob, “We will shortly be starting our analyses on the GPRD data set and would be grateful if you or someone at your end could look at the list of conditions we have identified as relevant development outcomes (this I am faxing as I do not have it electronically). The codes in the GPRD are Read or Oxmis (Rdoxflaf O or R) and there is not a precise mapping to ICD 9. We have identified all the codes we think are relevant to the outcomes of interest, as you will see we have flagged them as follows: 1 = child psychoses 2 = specific psychopathological symptoms 3 = emotional disturbance 4 = hyperkinetic syndrome 5 = specific developmental delay 6 = mental retardation “I would be interested in any comments. Have we got the right conditions (as judged by text field) and are there any other conditions that we might have missed? “I don’t know what the coding system is for medical conditions on your HMOs but if there is anything similar to the one on the GPRD and if you have a list of the conditions you flagged this would be very helpful to us, not only for the outcomes of interest but also the exclusions and other background conditions that you took account of in the analysis as potential confounders.” The one thing missing was autism. References Miller E., Andrews N. Re: Please can we have correct information about dosage? PEDIATRICS, Sept. 5, 2005: http://pediatrics.aappublications.org/cgi/eletters/114/3/584 Stone J. Re: Re: Please can we have correct information about dosage? PEDIATRICS, Sept. 14, 2005: http://pediatrics.aappublications.org/cgi/eletters/114/3/584 According to the Federal Drug Administration (FDA): Thimerosal is a preservative that has been used in some vaccines since the 1930s, when it was first introduced by the Eli Lilly Company. It is 49.6 percent mercury by weight and is metabolized or degraded into ethylmercury and thiosalicylate.” http://www.fda.gov/cber/vaccine/thimfaq.htm#q3 Hilleman M. Merck internal 1991 memo on thimerosal in medicines. Available at: http://www.safeminds.org/pressroom/press_releases/2005-02-08-LA-Times-Merck-Memo-Thimerosal-Vaccine.pdf Accessed Sept. 1, 2005.
First published on Red Flags |
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