FDA’s ‘CBER’: Asleep at the Switch Again – An Ongoing Saga
By Lyn Redwood, RN, MSN, Executive Director
Background: Peter Patriarca, an FDA employee, admitted back in 1999, in a confidential e-mail obtained through FOIA, that, “… the greatest point of vulnerability on this issue is that the systematic review of thimerosal in vaccines by the FDA could have been done years ago and on an ongoing basis as the childhood immunization schedule became more complex. The calculations done by FDA are not complex. I’m not sure if there will be an easy way out of the potential perception that the FDA, CDC and immunization policy bodies may have been “asleep at the switch” re: thimerosal until now”.
Since 1999, an entire generation of children both in the US and internationally has continued to be exposed to thimerosal – and it is time for this to stop. Nobody should be exposed to a known neurotoxin.
The Ongoing Saga: On March 30, 2017, Robert F. Kennedy, Jr., and the World Mercury Project (WMP) team met with the Director of the FDA’s Center for Biologics Evaluation and Research (CBER) Dr. Peter Marks, M.D., Ph.D. and his colleagues to discuss the agency’s ongoing refusal to ban thimerosal, a mercury-based preservative, from vaccines in the United States. CBER is the division of the FDA responsible for approving and monitoring the safety of all biological products, including vaccines, allergenic products, blood and blood products, and cellular, tissue, and gene therapies.
At the meeting, we presented a large amount of research showing the toxicity of thimerosal in humans, animals and cellular models, including at levels similar to those resulting from vaccine exposures. We expressed our alarm regarding the total lack of adequate safety testing of thimerosal prior to licensure, especially given its current use in vaccines approved for infants and pregnant women and its worldwide use in millions of vaccines given to children, particularly in developing countries. Dr. Marks promised to look over the studies and seriously consider our concerns.
After many months of back and forth emails, Dr. Marks sent a letter to us on July 11th that didn’t even look like he was in the same meeting. World Mercury Project was dismayed by CBER’s apparent unwillingness to seriously review the large archive of published science suggesting that using thimerosal is poisoning a generation of American children. From his follow-up response, it is clear that none of the information WMP provided was seriously read or even minimally digested. He made it clear in his letter that CBER does not intend to give any serious consideration to the abundant and mushrooming evidence of thimerosal’s profound toxicity. His letter was simply an exercise in blindly promoting an incredible vaccine industry orthodoxy that is unsupportable by empirical evidence.
Below is my letter back to Dr. Marks. We are awaiting his response.
Re: Response to your letter regarding the use of mercury in prescription drugs and vaccines.
Dear Dr. Marks,
On March 30th, Robert F. Kennedy Jr. and members of the World Mercury Project met with you and your colleagues at the FDA to discuss our concerns regarding the continued use of the mercury-based preservative, thimerosal, in prescription drugs and influenza vaccines administered to pregnant women, infants and children.
During the meeting and in written letters following the meeting, we voiced concerns regarding:
- Lack of adequate safety studies prior to marketing thimerosal as a vaccine preservative.
- Thimerosal’s toxicity and ineffectiveness as a preservative.
- Mercury exposure from thimerosal-containing vaccine administration resulting in mercury levels known to cause adverse outcomes.
- Exposure to vaccine-level thimerosal resulting in harmful depositions of inorganic mercury in the brain.
- The California Environmental Protection Agency’s listing of all mercury-containing products as reproductive and developmental toxicants under their Proposition 65 law.
Thimerosal was removed from all over-the-counter products when the FDA issued final rules in the Federal Register in 1998 acknowledging that thimerosal is not generally recognized as being safe or effective (GRASE). Why is this same product allowed in prescription drugs and vaccines?
At the end of our meeting, you reassured us that you would take our concerns seriously and would “follow the science” wherever it might lead you. For several months after our meeting, I contacted the FDA public liaison Ms. McNeill inquiring when we might expect to hear back from you regarding our concerns. Ms. McNeill told me that we had provided the agency with extensive information and that it was taking additional time to review the material. I was hopeful that FDA might finally, therefore, implement the 2001 recommendation of the Institute of Medicine that pregnant women, infants and children not be exposed to thimerosal-containing vaccines.
On July 11th, we received your written response to our concerns. I was dismayed by your agency’s apparent unwillingness to seriously review the large archive of published science suggesting that using thimerosal is poisoning a generation of American children. From your follow-up written response, it is clear that none of the information we provided was seriously read or even minimally digested. You make it clear in your letter that you do not intend to give any serious consideration to the abundant and mushrooming evidence of thimerosal’s profound toxicity. Your letter is simply an exercise in blindly promoting an incredible vaccine industry orthodoxy that is unsupportable by empirical evidence.
You cite in your written response FDA’s mushy biologics regulations which define safety as “the relative freedom from harmful effect to persons affected, directly or indirectly, by a product when prudently administered, taking into consideration the character of the product in relation to the condition of the recipient at the time.” 21CFR 600.39(p). You report that in applying this elastic regulatory standard, “FDA must weigh the risk of a vaccine or any drug against its benefits when determining whether a product is safe. If the benefits of the vaccine or other pharmaceutical product outweigh the risks of its side effects, then the FDA finds the product to be safe.” You further acknowledge that “the determination of a products safety is a relative rather than absolute measurement”, entirely subject to FDA’s “discretion and expertise.” Even operating under these malleable standards, FDA should consider that vaccines are products given to healthy individuals, and their risks should be measured by an extremely high bar since they are not treating a disease. Furthermore, FDA has no capacity to evaluate risks of thimerosal since, by FDA’s own admission to Congress, there has never been a long-term safety study performed on thimerosal in any human population including infants and pregnant women.
Vaccines containing thimerosal in the U.S. are predominantly influenza vaccines. Furthermore, thimerosal is still widely used in vaccines given to tens of millions of children in the developing world and, since U.S. policy influences worldwide policy, FDA bears responsibility for these policies. In the U.S., thimerosal-containing vaccines are administered to healthy six-month old infants, young children and pregnant women despite never having been safety tested in those populations. According to their product inserts, influenza vaccines have been associated with an increased incidence of seizures and Guillain-Barre Syndrome. Recent studies have linked influenza vaccines to miscarriage, autism and, possibly, birth defects. A significant percentage of influenza vaccines still contain thimerosal and studies should be done to see if thimerosal played a role in these outcomes. There has been limited testing of influenza vaccines in animal models, however, there have not been any adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, the package inserts for flu vaccines reiterate that flu vaccines “should be given to a pregnant woman only if clearly needed”. In addition, there are numerous VAERS reports of injuries from thimerosal-containing vaccines. Therefore, it is imperative that vaccines administered to sensitive populations (pregnant women, infants and children) be held to the highest standards of safety. I think parents and the American public would be appalled to learn that vaccine safety determinations are “relative” and are within an FDA employee’s “discretion and expertise.” That discretion and expertise should actually require a factual basis, not just opinion. Needless to say, these decisions should be guided by the precautionary principle.
I have organized the remainder of my response into addressing the erroneous claims made in your letter.
Your Claim: The agency evaluates whether a preservative contained in a product is at such levels that when used at the recommended dose is not toxic to the recipient and that the “FDA … has repeatedly found that the vaccines currently being marketed that contain thimerosal are safe…”
WMP Response: Please show us the data used to evaluate thimerosal safety in infants and pregnant women. We do not believe they exist.
In an email discussion regarding the use of thimerosal-containing influenza vaccines administered to pregnant women, infants and children, in 1999, Dr. William Egan, acting Director of the Center for Drugs and Biologics (CDER), recommended that the statement, “The chronic, daily ingestion reported (in several studies-primarily Seychelles study) greatly exceeds the amount of mercury that a pregnant woman would receive from a single annual dose of thimerosal-containing influenza vaccine” “might well be deleted.” Egan went on to justify his recommendation by saying that the statement “…in some ways is misleading. I am not sure that I would want to argue, for example, that one could take the allowed amount of mercury for a year and administer it as a bolus injection with the same outcome as having it spaced out evenly over the year: the issue then becomes one of how much of a bolus can one give at one time without harmful effect and this data does not exist (or at least I’m not aware of them).”
Dr. Egan was right then and he is right today; such safety data do not exist. In fact, many toxicologists believe that large bolus dose exposures such as those resulting from thimerosal-containing vaccines are more harmful in comparison to small daily dose exposures that the body is much more capable of excreting without overburdening detoxification pathways in the body. This concern is supported by research that found a mercury dose given acutely may produce toxic effects, whereas the same dose distributed over a period of time may give no evidence of poisoning. (Koos and Longo,1976).
Your Claim: “Thimerosal has a long record of safe and effective use in preventing bacterial and fungal contamination of vaccines with no ill effects other than occasional hypersensitivity and minor local reactions at the site of injection.”.
WMP Response: There is ample evidence provided in multiple studies by federal agencies and independent scientists that spans the last 90 years which documents that thimerosal is neither an effective nor a safe vaccine preservative.
In a study published in the Journal of the American Medical Association in 1948 titled “The bacteriostatic and bactericidal actions of some mercurial compounds on hemolytic streptococci,” the authors vigorously argued that thimerosal was ineffective as a “disinfectant, germicide and antiseptic.” In the review of the literature in this paper, the authors cited eight studies from 1928, 1935, 1937, 1938, and 1944 all of which drew similar conclusions.
In 1975, the FDA convened a panel of experts to evaluate mercury-containing over-the-counter (OTC) products. The panel issued its reports in 1980 and in 1982. The FDA issued a report of the panel’s findings in the Federal Register where they concluded that “some mercury-containing preparations are not effective and others are not safe and effective for OTC topical antimicrobial use”.
With respect to thimerosal in particular, that panel found evidence from 1950 which concluded that “thimerosal was no better than water in protecting mice from potential fatal streptococcal infections.” Additionally, citing a 1935 study, the panel reported that thimerosal was “35.3 times more toxic for embryonic chick heart tissue than for Staphylococcus aureus.” Most of the literature reviewed addressed mercury’s lack of antibacterial properties. One review published in 1971 titled, “Three thousand years of mercury. A plea for abandonment of a dangerous, unproven therapy,” addressed mercury’s lack of effectiveness against fungal contamination as well.
The FDA-appointed expert panel concluded that “thimerosal was not safe for OTC topical use because of its potential for cell damage if applied to broken skin and its allergy potential. It is not effective as a topical antimicrobial because its bacteriostatic action can be reversed.” However, it wasn’t until 1998 that the FDA issued its final report banning the use of thimerosal in topical OTC products because it was not “safe and effective.”
There are also several more recent published reports of thimerosal’s failure as a preservative. Clusters of disease from Group A streptococcus infections were traced back to multi-dose vials of diphtheria toxoid, pertussis, and tetanus toxoid (DPT) vaccine which were contaminated after being opened. Additionally, in 2004, a Chiron plant that manufactured Fluvirin was forced to close because its vaccine was contaminated with Serratia marcescens. This vaccine used thimerosal as a preservative. In this case and in the many others cited, thimerosal failed to prevent bacterial growth.
In response to the reports from the FDA expert panel who reviewed the use of thimerosal in over-the-counter products in the 1980’s, the FDA published in the April 22, 1998 Federal Register Status of Certain Additional Over-the-Counter Drug Category II and III Active Ingredients. (April 22, 1998);63(77):19799-19802. 21 CFR Part 310 [Docket No. 75N-183F, 75N-183D, and 80N-0280 concluding that the use of thimerosal in over the counter products is not “generally recognized as safe or effective” (GRASE).
In the final rulemaking, the FDA states that “safety and effectiveness have not been established for the ingredients (mercury-based preservatives) included in this current final rule and manufacturers have not submitted the necessary data in response to earlier opportunities. The agency’s experience has been that under these circumstances companies have not submitted data in response to yet another opportunity. Consumers will benefit from the early removal from the marketplace of products containing ingredients for which safety and effectiveness has not been established.”
The World Mercury Project would like to know how is it possible that one division of the FDA recognizes that there is absolutely no safety or effectiveness data available for the use of mercury in over the counter products and essentially bans its use, while your FDA division of blood and biologics continues to recklessly allow its widespread use in over 100 prescription products including vaccines?
Your claim: “Under the FDA Modernization Act (FDAMA) of 1997, the FDA conducted a comprehensive review of the use of thimerosal in childhood vaccines. Conducted in 1999, this review found no evidence of harm from the use of thimerosal as a vaccine preservative, other than local hypersensitivity reactions (Ball et al. 2001).”
WMP Response: It’s disturbing that according to internal emails obtained by FOIA, Dr. Ball never conducted an extensive review of reports of harm. On November 23, 1998, Dr. Leslie Ball of the FDA asked internal reviewers to perform a Medwatch query on thimerosal. Medwatch is the FDA’s database for reporting adverse drug events. On January 7, 1999, Dr. Ball was informed by Fredrick Varricchio of FDA that there were 7000 reports containing the word thimerosal on FDA’s Medwatch. He stated, “I have some results for you. Problem is that there are 7000 reports that mention thimerosal. What to do now. Obviously looking at all 7,000 is a brute force approach.” Dr. Ball responded by saying, “perhaps you can get records on a subset of 50 or so we can look at them and get a general feel for what’s been reported before we go any further.” In a subsequent email on January 19th, Mr. Varricchio noted that the “plan is to get whatever is on the summary for every 100th report.” This means that only 70 adverse events out of 7000 reported to the FDA were actually reviewed by Dr. Ball and her team. This email calls into question the findings reported by Dr. Ball and also suggests that an extensive investigation has never been conducted by the FDA with regard to adverse events associated with the use of thimerosal. Would you allow any other medical product to be widely used based on review of one percent of the information available?
I am also, Sir, frankly shocked at your unwillingness to acknowledge the robust body of literature that has been published the last 18 years since concerns regarding thimerosal first surfaced within the FDA in 1999.
There are literally hundreds of peer-reviewed, published studies that document the toxicity of thimerosal. Many of these investigated levels of mercury known to occur from vaccine exposure in cell and animal models. In 2013, Jose G. Dorea published a meta-analysis of thimerosal research related to vaccine exposure. Dorea searched major databases for human and experimental studies that addressed issues related to early life exposure to TCVs. The author concluded that: “ a) mercury load in fetuses, neonates, and infants resulting from TCVs remains in blood of neonates and infants at sufficient concentration and for enough time to penetrate the brain and to exert a neurologic impact and a probable influence on neurodevelopment of susceptible infants; b) etHg metabolism related to neurodevelopmental delays has been demonstrated experimentally and observed in population studies; c) unlike chronic Hg exposure during pregnancy, neurodevelopmental effects caused by acute (repeated/cumulative) early life exposure to TCV-etHg remain unrecognized; and d) the uncertainty surrounding low-dose toxicity of etHg is challenging but recent evidence indicates that avoiding cumulative insults by alkyl-mercury forms (which include Thimerosal) is warranted.” Dorea emphasized the importance of “a) maintaining trust in vaccines while reinforcing current public health policies to abate mercury exposure in infancy; b) supporting WHO policies that recommend vaccination to prevent and control existing and impending infectious diseases; and c) not confusing the ‘need’ to use a specific ‘product’ (TCV) by accepting as ‘innocuous’ (or without consequences) the presence of a proven ‘toxic alkyl-mercury’ (etHg) at levels that have not been proven to be toxicologically safe.”
For your convenience, I have included a sampling of 35 abstracts that represent the more current state of the science regarding thimerosal that has emerged since 1999 as an appendix. Even if Dr. Ball’s review had been adequate at that time, surely 18 years of further research should prompt an updated evaluation by the FDA.
Your Claim: A 2014 modeling study by your own Centers for Biologics Evaluation and Research employee, Dr. Robert Mitkus, showed that “peak body burdens of mercury following episodic exposures to thimerosal in this worst case did not exceed the corresponding safe body burden of mercury from MeHg at any time”.
WMP Response: The Mitkus study reported that the body burden of mercury in infants, over the first 4.5 years of life following yearly exposures to thimerosal from annual flu vaccines, was two orders of magnitude lower than that estimated for exposures to the lowest regulatory threshold for MeHg over the same time period. The author relies completely on these findings to conclude that their pharmacokinetic analysis supports the safety of thimerosal when used as a preservative at current levels in certain multi-dose infant vaccines in the United States. Mitkus fails to acknowledge the past levels of exposure that infants received from vaccines starting in the late 1980s and extending well into 2000, that were 187.5 mcg etHg the first year of life versus 12.5 mcg etHg from flu vaccines annually. He also makes the assumption that there are no other mercury exposures outside of thimerosal, which is not supported by either established science or common sense.
The model developed by Mitkus relied solely on blood levels and did not take into consideration the accumulation of mercury in the brain tissue. Data from the Burbacher study that assessed exposures from both methyl and ethyl mercury in infant non-human primates, based on vaccine level exposures, found that although there was little accumulation of Hg in the blood with repeated vaccinations, accumulation of Hg in the brain of infants did occur. In fact, there was a much higher proportion of inorganic Hg in the brain of thimerosal monkeys than in the brains of MeHg monkeys (up to 71% vs. 10%). Absolute inorganic Hg concentrations in the brains of the thimerosal-exposed monkeys were approximately twice that of the MeHg monkeys. Burbacher concluded that “the safety of thimerosal drawn from blood Hg clearance data in human infants receiving vaccines may not be valid, given the significantly slower half-life of Hg in the brain as observed in the infant macaques.” But that is exactly what Mitkus does in his model and reports in his study.
Mitkus also makes the statement that thimerosal is more quickly and extensively metabolized to inorganic mercury in the brain than is MeHg and that process of dealkylation “may be” a detoxification step. According to Burbacher, who is the author of the studies relied on by Mitkus in the development of his model, the statement that dealkylation may be a detoxification process is purely speculative and has not been established. Mitkus is referring to previous reports that have indicated that dealkylation of Hg is a detoxification process that helps to protect the central nervous system (Magos 2003; Magos et al. 1985). These reports are largely based on histology and histochemistry studies of adult rodents exposed to Hg for a short period of time. The results of these studies indicated that damage to the cerebellum was observed only in MeHg-treated animals that had much lower levels of inorganic Hg in the brain than animals comparably treated with ethylmercury. Moreover, the results did not indicate the presence of inorganic Hg deposits in the area where the cerebellar damage was localized (granular layer). In contrast, previous studies of adult M. fascicularis monkeys exposed chronically to MeHg have indicated that demethylation of Hg occurs in the brain over a long period of time after MeHg exposure and that this is not a detoxification process (Charleston et al. 1994, 1995, 1996; Vahter et al. 1994, 1995). Results from these studies indicated higher inorganic Hg concentrations in the brain 6 months after MeHg exposure had ended, whereas organic Hg had cleared from the brain. The estimated half-life of organic Hg in the brain of these adult monkeys was consistent across various brain regions at approximately 37 days (similar to the brain half-life in the Burbacher study). Stereologic and autometallographic studies on the brains of these adult monkeys indicated that the persistence of inorganic Hg in the brain was associated with a significant increase in the number of microglia in the brain. (Charleston et al. 1994, 1995, 1996). The microgliosis and neuroinflamation documented in the brains of the adult monkeys in association with deposits of inorganic mercury are two hallmark findings in brain tissue of both children and adults with autism. Neuropathological studies of brain tissues from cerebellum, midfrontal, and cingulate gyrus obtained at autopsy from 11 patients with autism demonstrated the presence of an active neuroinflammatory processes in the cerebral cortex, white matter and, most notably, the cerebellum. In a subsequent study, microglia appeared markedly activated in five of 13 cases with autism, including two of three under age six, and marginally activated in an additional four of 13 cases. The authors concluded that microglial activation “represents a neuropathological alteration in a sizeable fraction of cases with autism. Given its early presence, microglial activation may play a central role in the pathogenesis of autism in a substantial proportion of patients.”
In responding to the Mitkus study, I also need to refer back to previous meetings with FDA CBER employees. When FDA assigned its pediatrician, Dr. Leslie Ball, to oversee the review, analysis and public reporting of thimerosal, Dr. Ball had little knowledge of toxicology or thimerosal. In 1999, Dr. Ball and her colleagues conducted an analysis that was prompted by the Food and Drug Modernization Act of 1997 which required FDA to compile a list of drugs and food that contain “intentionally” introduced mercury compounds and provide a qualitative and quantitative analysis of the exposure levels. They reported that the limits of exposure to mercury for an infant in the first year of life should be between 200-230 mcg total. Infants are exposed to approximately 80 to 100 mcg of organic mercury from environmental sources alone. Therefore, additional exposures from thimerosal-containing vaccines should be below 120 to 130 mcg the first year of life according to the FDA’s own findings. At the time this analysis was done, American children were routinely receiving 187.5 mcg of organic mercury during the first year of life from vaccines. This means American children were being exposed to cumulative levels of organic mercury in excess of federal safety guidelines.
The FDA consulted with an expert in the field of toxicology, Dr. Barry Rumack, MD, to better understand the potential impact of these exposure levels. Dr. Rumack had a private consulting practice where he offered “toxicologic and pharmacologic evaluation of drugs, biological and potentially toxic or hazardous agents for government and industry”. After creating several scenarios based on infants’ ages and weights, Dr. Rumack modeled both blood and body burden levels.
The models predicted sharp peaks of mercury concentrations in both blood and tissue, in a stair step sequence following each of the new thimerosal-containing vaccines given during the first six months of life. Based on these models, Rumack predicted exposure to thimerosal-containing vaccines was dosing American children with mercury levels far exceeding all three federal safety guidelines established by EPA, FDA and ATSDR. There was no point in time from birth to approximately 16-18 months of age that infants were below the EPA guidelines for allowable mercury exposure. In fact, according to the models, blood and body burden levels of mercury peaked at six months of age at a shockingly high level of 120 ng/liter. To put this in perspective, the CDC classifies mercury poisoning as blood levels of mercury greater than 10 ng/liter. What is even more concerning is that the models developed by Dr. Rumack did not take into account background exposures from environmental and dietary sources of mercury.
In reporting the mercury exposure levels that result from thimerosal containing vaccines, the FDA chose not to report the findings from Rumack and Ball. Instead, they averaged the exposures over the first six months of life, even though the exposures only occurred at birth, two, four, and six months of age or during four days out of 180 days. In doing so, the agency could report that the exposures were below FDA and ATSDR guidelines in an effort to minimize concern.
In discussing this with independent toxicologists, I have been told that averaging exposures is not appropriate due to the fact that large bolus dose exposures are known to be more injurious than small daily dose exposures. If the FDA had reported the exposure levels from a daily dose perspective, it would reveal that infants were being exposed to mercury far in excess of ALL federal safety guidelines: FDA, ATSDR and EPA.
For example, my son at two months of age weighed 5 kg and received 62.5mcg Et Hg from his vaccines. According to the EPA methyl mercury guidelines of .1 mcg per kg per day, his maximum exposure level for that one day was 0.5 mcg of mercury. He received 125 times his daily allowable exposure level or 125 days of his daily allowable exposure. An analogy would be that it would be allowable to give my infant son a ½ tsp of Tylenol four times a day (320 mg), but if I gave him a 30-day dose of Tylenol (9,600 mg) on one day, it would be lethal. When I personally asked Dr. Ball why she reported the mercury exposure levels in this deceptive fashion, she responded, “That is what I was told to do.”
In a subsequent email to her superiors at FDA on July 6th, 1999 (six months after she had started her review of thimerosal), marked as being highly important and confidential and obtained through a Freedom of Information Act request, Dr. Ball asked Norman Baylor, PH D, Director of the Office of Vaccines Research Review, “Has the application of these calculations as exposure guidelines received the sign off by toxicologists? In prior discussions, the toxicologists seemed reluctant to state any Hg (mercury) level was “safe”.” Although there was no response back from Dr. Baylor in the FOIA documents we received, it is obvious that the answer was no.
By 2000, there was already a mountain of evidence that thimerosal was unsafe and ineffective. For example, in 1987 the Commission of the European Communities initiated a research project on 10 known or suspected spindle poisons including thimerosal. In 1993, as described in Mutation Research, 287 (1993) 17-22 thimerosal was identified as a strong inhibitor of microtubular assembly, a process which is essential for proper neuronal development. In 2000, Stajich et al. measured blood Hg levels in newborns administered the Hepatitis B vaccine, containing 12.5 mcg ethyl mercury, and found elevated post-immunization concentrations relative to pre-immunization levels in all neonates studied. Levels of blood mercury after exposure in low birth weight infants were 7.36 mcg/L (± 4.99). One infant was found to have mercury levels of 23.6 mcg/L after exposure, which supports the inter-individual variability of mercury intoxication. The study subjects had measurable blood Hg concentrations prior to immunization, indicating that risk assessment must include background mercury levels from other sources.
I also find it disturbing that safety assessments you reference take the position that thimerosal is a necessary ingredient for influenza vaccines. This, of course, is not true. Influenza manufacturers presently make approximately two-thirds of the U.S. influenza vaccine supply without the use of thimerosal by placing the vaccine in a single dose vial or syringe, which completely eliminates the need for a preservative.
Your Claim: The scientific evidence collected over the past 15 years does not show any evidence of harm, including serious neurodevelopmental disorders from the use of thimerosal in vaccines. The Institute of Medicine report from 2004 concluded that the evidence favors rejection of a link between thimerosal and autism based on several epidemiological studies.
WMP Response: A causal relationship between autism and vaccinations cannot be proven or rejected based on evidence from population-based epidemiologic studies – period. Epidemiological studies, by definition, are not designed to prove causality; they can provide only statistical associations. Therefore, the committee’s conclusion that the “body of epidemiologic evidence favors rejection of a causal relationship…” has no scientific meaning.
Further, in the IOM report the committee admitted that population-based studies would not be able to detect subpopulations that could be genetically more vulnerable to mercury at lower doses than typical. On page 139, the report states that “This hypothesis cannot be excluded by epidemiological data from large population groups that do not show an association between a vaccine and an adverse outcome. Depending upon the frequency of the genetic defect, a rare event caused by genetic susceptibility could be missed even in large study samples.”
What you also failed to acknowledge is that several of the same epidemiological studies reviewed by the IOM in 2004 documented an association between thimerosal-containing vaccine exposures during infancy and the subsequent development of motor and phonic tics. Tics are a family of neurological disorders that are also associated with a diagnosis of autism. A significant association between Hg exposure from thimerosal-containing childhood vaccines and a diagnosis of tic disorder (TD) has now been found in six epidemiological studies (Verstraeten et al. 2003, Andrews et al. 2004, Thompson et al. 2007, Young et al, 2008, Barile et al. 2012, Geier et al. 2015). The Thompson study states that, “The replication of the findings regarding tics suggests the potential need for further studies.” Tozzi et al. 2009, also found trends towards increased motor and phonic tics with increased thimerosal exposure but these did not reach statistical significance, possibly because of the lack of a non-exposed control group. These studies employed various epidemiological methods such as case–control or cohort designs, and were conducted on cohorts of children from several different countries. In addition, several of these studies observed significant dose-dependent relationships between Hg exposure from thimerosal in vaccines and the risk of diagnosed TD. A study by Young et al. found a dose-dependent relationship between increasing Hg exposure from thimerosal in vaccines given between birth and seven months and also between birth and 13 months of age and the risk of a diagnosed TD. Researchers observed that, for a 100 μg Hg difference in exposure between birth and seven months of age, the risk for diagnosed TD was significantly increased (3.39-fold). For the same 100 μg Hg difference in exposure between birth and 13 months of age, the risk for diagnosed tics was also found to be significantly increased (4.11-fold).
Autism etiology and severity have also been associated with mercury levels. In June of this year, the international journal Science of the Total Environment published a compelling study from the Republic of Korea. The study identifies a strong relationship between prenatal and early childhood exposure to mercury and autistic behaviors in five-year-olds. The MOCEH study examines environmental exposures during pregnancy and childhood and their effects on children’s growth and development. A unique feature is that it includes five different blood samples: maternal blood from early and late pregnancy; cord blood; and samples from children at two and three years of age. In addition, the study asks mothers to complete three follow-up surveys and—when their child reaches age five—the 65-item Social Responsiveness Scale (SRS), which assesses autistic behaviors.
The investigators report a significant linear relationship between mercury exposure and autistic behaviors (as indicated by a scaled score called an SRS T-score). Strikingly, they find that with a doubling of blood mercury levels at four time points (late pregnancy, cord blood, and at two and three years of age), SRS T-scores are significantly higher. They also looked specifically at SRS T-scores greater than or equal to 60. Sixty and above is the accepted threshold for detecting “mild to moderate” deficits of social behavior related to autism; scores of 76 or more are in the “severe” range. In these analyses, the same linear relationship holds for late pregnancy and birth (i.e., cord blood). With a doubling of blood mercury levels at these two time points, there is a 31% and 28% increase, respectively, in the risk of an SRS T-score of 60 or more. Finally, the researchers identify a stronger association between late-pregnancy mercury exposure and autistic behaviors in five-year-old boys versus five-year-old girls, perhaps due to mercury’s endocrine-disrupting properties.
Your Claim: Schechter and Grether, 2008, showed that California’s rates of autism continued to rise while thimerosal was being phased out from three of the early childhood vaccines.
WMP Response: This study has significant limitations in addressing what was really going on in the time period from 1999 to 2003. Schechter and Grether estimated exposure for each birth cohort but made no attempt to look at the actual thimerosal exposures of individual children relative to their diagnosis. In fact, looking at the data for the CDDS for the years immediately following their study, there was a notable flattening of the autism prevalence growth curve in the 2004-2006 birth cohorts, suggesting a possible effect of thimerosal phase-out. At the same time, however, any downward effect on autism rates would have been blunted by three national autism awareness campaigns, by Autism Speaks, the CDC and the AAP , starting early in 2005 and continuing into 2006 which raised public awareness dramatically.
While thimerosal was being phased out of the Hepatitis B, Hib and DTaP vaccines over those four years, thimerosal exposure through influenza vaccines was increasing. In 2004, the CDC started recommending flu shots for pregnant women in any trimester. In 2004, over 90% of the supply of influenza vaccines contained thimerosal. Studies of methyl mercury show that mercury is typically 1.7 times higher in cord blood than in maternal blood and there are no studies investigating the pharmacokinetics of ethylmercury in pregnancy. Concurrently, in January 2003, the CDC recommended flu shots with thimerosal for all children starting at six months of age. The idea that children were no longer being exposed to thimerosal was and is a fallacy.
Beyond California, in the spring of 2016, the CDC’s ADDM network finally reported the autism prevalence of children born in 2004. For the first time that data did not show an increase in autism prevalence compared to the 2002 birth year cohort. They both had a one in 68 prevalence. This suggests that the removal of thimerosal from the three pediatric vaccines may have flattened autism rates prior to the widespread uptake of the flu vaccine and increased awareness. That same paper, based on children born in 2004, reported a prevalence of Autism Spectrum Disorders with IQ<70 of 4.0 per 1000. This was a 15% drop from the previous report based on children born in 2002, when the prevalence of ASDs with IQ<70 was 4.7 per 1000. Note that this had nothing to do with percentages of the ASD population or additional higher-functioning children being diagnosed – this meant that there were actually fewer severely affected children on a population basis.
Finally, your focus on autism ignores the evidence of thimerosal’s associations with a range of other disorders including ADHD, speech disorders, seizure disorders, autoimmunity and eczema and the broader associations of mercury with auditory and speech impairment, nephrotoxicity and somatosensory disorders. According to the CDC, one in six American children of the thimerosal generation now suffers from a neurodevelopmental disorder. An HHS funded study found that 54% of children have a chronic disease. What evidence have you, if any, that thimerosal is not a major culprit in the epidemics that have devastated this generation? “None” is the answer!
Dr. Marks, I perceive you to be a smart man and sincere in your desire to protect children from harm. Do you, as an individual, not as the Director of CBER, really believe that the continued use of thimerosal in products given to pregnant women, infants and children, when it is completely unnecessary, is appropriate? I’m appealing to you as the mother of a young man who will never be able to take advantage of his full potential because he was harmed by thimerosal and other sources of mercury. It is my life’s mission, much like the mother who started MADD, to protect all children from this completely unnecessary exposure to mercury. I ask that you please again take our concerns to heart and help support our efforts instead of regurgitating the inaccurate and indefensible positions of your agency.
Lyn Redwood RN, MSN, Executive Director
World Mercury Project
Read our overview — background and all of the letters between FDA and World Mercury Project.