This
series on thimerosal-containing
vaccines (TCV) is a critical review of the subject and what is known
about it at
this
time.
(Spring 2011)
Thimerosal is not my primary area of
interest. I therefore promise to be extra careful documenting the
facts and even more careful commenting on them.
Because the CDC only promotes
vaccines and vaccination, the write-up about Thimerosal in vaccines
on the CDC web site is relatively short:
Thimerosal is a mercury-containing
preservative used in
some vaccines and other products since the 1930's. There is no
convincing evidence of harm caused by the low doses of thimerosal in
vaccines, except for minor reactions like redness and swelling at the
injection site. However, in July 1999, the Public Health Service
agencies, the American Academy of Pediatrics, and vaccine
manufacturers agreed that thimerosal should be reduced or eliminated
in vaccines as a precautionary measure.
[http://www.cdc.gov/vaccinesafety/concerns/thimerosal/index.html]
This
is not exactly true. Thimerosal was not only used in
some vaccines; it was used in
most
if not all vaccines “since the 1930’s”. It is only later that
the mercury preservative was not used in Live Virus Vaccines (LVV)
and even later
that unit-dose vaccines without preservative became available, under
duress.
The
second sentence is no less problematic. Objective evidence of harm in
vivo and in vitro is and has been available for some time, as I will
show in Part III of this series. Whether the CDC will ever be
convinced of
that, is another story.
The
last sentence of the statement is also somewhat misleading. In fact, the
Joint Statement issued by the AAP and the PHS in July 1999 "established the goal of removing the
vaccine preservative thimerosal as soon as possible from vaccines
routinely recommended for infants.”
[http://www.vaccinesafety.edu/AAFP-AAP-ACIP-thimerosal.htm]
So
in 2011, thimerosal has indeed not
been removed from “vaccines”. It has been mostly
eliminated from pediatric vaccines with some still containing traces of the preservative. Adult vaccines and a few pediatric inactivated influenza vaccines currently available in the United States contain as much of the preservative as they did before 1999.
The
above suggests that each of the three sentences of the most visible
CDC information on thimerosal in vaccines is not exactly accurate.
Whether
the Public Health Service agencies, the American
Academy of Pediatrics, and vaccine manufacturers agreed
whole-heartedly or had to agree
is
another story that will be discussed
later.
***
The
FDA licenses vaccines and is at least in theory ultimately
responsible for them.
An
enormous amount of information about thimerosal on the FDA web site
starts with information not too different from that on the CDC web
site except that the FDA specifies that thimerosal was removed from
“all vaccines routinely recommended
for children 6
years of age and younger”.
Thimerosal is a mercury-containing
organic compound
(an organomercurial). Since the 1930s, it has been widely used as a
preservative in a number of biological and drug products, including
many vaccines, to help prevent potentially life threatening
contamination with harmful microbes. Over the past several years,
because of an increasing awareness of the theoretical potential for
neurotoxicity of even low levels of organomercurials and because of
the increased number of thimerosal containing vaccines that had been
added to the infant immunization schedule, concerns about the use of
thimerosal in vaccines and other products have been raised. Indeed,
because of these concerns, the Food and Drug Administration has
worked with, and continues to work with, vaccine manufacturers to
reduce or eliminate thimerosal from vaccines.
Thimerosal has been removed from or reduced to trace
amounts in all vaccines routinely recommended for children 6 years of
age and younger, with the exception of inactivated influenza vaccine.
A preservative-free version of the inactivated influenza vaccine
(contains trace amounts of thimerosal) is available in limited supply
at this time for use in infants, children and pregnant women…
[
http://www.fda.gov/biologicsbloodvaccines/safetyavailability/vaccinesafety/ucm096228.htm]
Unlike the CDC, the FDA discussion of the
subject is so exhaustive that one must wonder whether the goal was
information or a veiled attempt at justification and or exoneration.
The United
States Code of Federal Regulations (CFR) actually required
the addition of a preservative to multi-dose vials of vaccines in
January 1968.
“Products in multi-dose containers
shall contain a
preservative, except that a preservative need not be added to Yellow
Fever Vaccine; Polio-virus Vaccine, Live Oral; viral vaccine labeled
for use with the jet injector; dried vaccines when the accompanying
diluent contains a preservative; or to an Allergenic Product in 50
percent or more volume (v/v) glycerin. [21 CFR 610.15(a)]
The CFR specified that the preservative used
.[s]hall be sufficiently non-toxic so
that the amount
present in the recommended dose of the product will not be toxic to
the recipient, and in combination used it shall not denature the
specific substance in the product to result in a decrease below the
minimal acceptable potency within the dating period when stored at
the recommended temperature. [21 CFR 610.15(a)]”
***
There were
also several problems with the FDA statement. For the sake of
brevity, only two will be discussed.
Under
“Thimerosal as a preservative”, the FDA states:
“Prior to its introduction in the 1930’s, data
were available in several animal species and humans providing
evidence for its safety and effectiveness as a preservative (Powell
and Jamieson 1931). Since then, thimerosal has been the subject of
several studies (see
Bibliography)
and
has
a
long record of safe and effective use preventing bacterial
and fungal contamination of vaccines, with no ill effects established
other than minor local reactions at the site of injection”
The statement suggests that before
thimerosal was added to vaccines, Powell and Jamieson had shown that
it was safe and effective. This is not exactly true because the FDA
clearly states in the same document that Powell and Jamieson’s 1931
study “was not specifically designed
to examine
toxicity; 7 of 22 subjects were observed for only one day, the
specific clinical assessments were not described, and no laboratory
studies were reported.”
And then there is the mention about
thimerosal being the subject of “several studies” and the
annotation “see Bibliography” immediately followed by “and
has a long record of safe and effective use preventing bacterial and
fungal contamination of vaccines”, all in a chapter
about “Thimerosal in Vaccines”.
Unlike most readers in a rush, I
clicked on “Bibliography” to look at those studies I had never
heard about. They were listed under the title:
“Studies on Safety and Effectiveness
of
Thimerosal”
The words “in vaccines” had
disappeared and there were only 8 studies listed. The very first
two studies were published in 1974, some 43 years after Powell and
Jamieson and the most recent one, on preservatives in nasal
preparations was published in 1989, over twenty years ago. Study # 3
was on urinary cytology and studies # 4, 5, 6 and 8 were on
ophthalmological preparations. The two 1974 studies (# 2 and 7) dealt
with development and standardization of the preservative in general.
There was in fact no study about the
safety and efficacy of thimerosal in vaccines.
***
The second unconvincing FDA
statement was under “Thimerosal Toxicity”. After listing the many
known instances of toxicity of the preservative, the FDA decided to
“prove” that thimerosal was safe by quoting a single reference,
the 2002 study in Lancet by Pichichero et al.
The FDA proposed that the study
proved that
“Blood levels of mercury did not exceed
safety
guidelines for methyl mercury for all infants in these studies.
Further, mercury was cleared from the blood in infants exposed to
thimerosal faster than would be predicted for methyl mercury; infants
excreted significant amounts of mercury in stool after thimerosal
exposure, thus removing mercury from their bodies. These results
suggest that there are differences in the way that thimerosal and
methyl mercury are distributed, metabolized, and excreted. Thimerosal
appears to be removed from the blood and body more rapidly than
methyl mercury.”
In fact, the study had several
limitations affecting its conclusions:
- Only 40 infants who received TCV
were included, 20 aged 2 months and 20 aged 6 months
- Just 21 infants who received
thimerosal-free vaccines were used as controls
- The injected mercury was judged as a
range of mean mercury doses
- Blood draws were done conveniently
when the parents were able to bring the infants back
- Among Hg-exposed infants, blood
samples from twelve 2-month-old were collected from 8 and 21 days after
vaccination and blood samples from thirteen 6-month-old infants were
collected from 8 to 27 days after vaccination, when in all probability
the Hg was no longer in the blood and had settled in tissues including
the brain
- The half life of thimerosal mercury,
that seemed to have impressed someone at the FDA, resulted from
pharmacokinetic calculations whose description was peppered with
statements such as: we developed a
prediction, the expected
concentrations, half-lives of mercury ranging from 1 day to 45 days, we
assumed, elimination of mercury from blood followed a single
compartment model with first-order kinetics, possible half-life, the
difference between the predicted and actual recorded concentrations in
blood, reliable quantitation, and assumption that errors…
***
The extensive statement on the FDA
web site did not include the most important fact of all: A safe range
of level of exposure to ethyl mercury.
It is worth mentioning that in spite
of the present obsession with the subject, responsible agencies have
yet to agree on the supposedly safe levels for methyl
mercury: The EPA estimate of 0.1 µg/kg body
weight/day is only a fraction of the WHO estimate of 0.47 µg/kg
body
weight/day.
***
The FDA information included
conclusions and recommendations by the
Immunization Safety Review Committee of the
Institute of Medicine.
In October 2001, the committee
concluded:
- That although the hypothesis that
exposure to thimerosal-containing vaccines could be associated with
neurodevelopmental disorders is not established and rests on indirect
and incomplete information, primarily from analogies with methylmercury
and levels of maximum mercury exposure from vaccines given in children,
the hypothesis is biologically plausible.
- That the evidence is inadequate to
accept or reject a causal relationship between thimerosal exposures
from childhood vaccines and the neurodevelopmental disorders of autism,
ADHD, and speech or language delay.
Among other things, the committee
recommended, “that full consideration be given by appropriate
professional societies and government agencies to removing thimerosal
from vaccines administered to infants, children, or pregnant women in
the United States” and “that appropriate professional societies
and governmental agencies review their policies about the non-vaccine
biological and pharmaceutical products that contain thimerosal and
are used by infants, children, and pregnant women in the United
States.”
[http://www.vaccinesafety.edu/IOM-thimerosal-10-01-01.htm]
Unfortunately in 2004, with
thousands of cases of autism having been filed, the same IOM
committee decided, based on epidemiological studies that the “body
of evidence favors rejection of a causal relationship between
thimerosal-containing vaccines and autism, and that hypotheses
generated to date concerning a biological mechanism for such
causality are theoretical only.”
Multiple articles criticizing the
above-mentioned epidemiological studies from Sweden, Denmark and the
US have been published, including several by this writer.
***
For those interested, a bibliography
review of adverse reports related to thimerosal was provided in a
press release on March 17, 2002 by the well-known law firm of Waters
and Kraus. [http://www.vaccinationnews.com/DailyNews/March2002/Waters%2526KrausPressRelease3-17-02.htm]
Chronology of
Thimerosal in Vaccines
In 1927, Morris Kharasch an Organic
Chemist filed a patent application for an alkyl mercuric sulfur
compound with “potential” antiseptic and antibacterial properties
and assigns it to Eli Lilly and Co.
Two years later, Eli Lilly & Co.
registered the product under the trade name Merthiolate.
[Other names for
ethylmercurithiosalicylate sodium are Thimerasol, Thiomerosal;
Thiomersal; Thimersalate; Thiomersalate; Merfamin; Merthiolate
sodium; Mertorgan; Merzonin and Sodium ethylmercuric thiosalicylate
…]
Thimerosal is 49.6 percent mercury
by weight and is metabolized into ethylmercury and thiosalicylate.
As mentioned earlier, thimerosal has
been the preferred preservative in vaccines since the late 1930s
supposedly because of its
ability to prevent contamination of multiple-dose vials by killing
pathogenic organisms and fungi.
Years ago, I proposed that
thimerosal was really added to vaccines to prevent contamination on
the production line and not in the doctor’s office. In the fall of
2004, thousands of doses of influenza vaccine at Chiron Labs in the
UK were condemned and discarded because of contamination with
Serratia Marascans.
The FDA had found “serious
problems of bacterial contamination” at the influenza
vaccine plant in England in 2003, “16
months
before
British regulators effectively closed the site and
impounded its flu shots because of fears they were tainted.”
[http://www.washingtonpost.com/wp-dyn/articles/A58482-2004Nov17.html]
For 50 years, we pediatricians
obediently used thimerosal-laced vaccines and said nothing. Why we
were fooled for so long will be explained later.
In 1980 and for reasons not as yet
completely clear, the FDA suddenly started examining
over-the-counter (OTC) products containing thimerosal. Citing
concerns about toxicity and inefficacy, the agency then began banning
some OTC thimerosal-containing ointments and topical products.
In 1991, world-renowned vaccine
developer Maurice Hilleman PhD sent a memo to Dr. Gordon Douglas,
Head of Merck’s Vaccine Division telling him that Sweden is
requiring thimerosal-free single-dose packaging of all products as
soon as can be reasonably achieved. Hilleman wrote: “For
babies: The 25 µg of mercury in a single 0.5 ml dose and
extrapolated to a 6 lb baby would be 25 X the adjusted Swedish daily
allowance of 1.0 µg for a baby of that size …. If 8 doses of
thimerosal-containing vaccine were given in the first six months of
life (3 DPT, 2 HIB and 3 Hepatitis B), the 200 µg of mercury
given,
say an average size of 12 lbs pounds would be about 87 X the Swedish
daily allowance of 2.3 µg of mercury for a baby of that size.”
Dr. Hilleman also told Douglas that
in order of toxicity, methyl and ethyl salts were most toxic. Mercury
vapor was intermediate and inorganic salts least toxic.
[Interestingly, we still have
“experts” in 2011 who still claim that ethyl mercuric compounds
are “safer” than methyl compounds.]
Merck and other manufacturers
obliged and immediately produced mercury-free vaccines for
Scandinavian infants and children.
Our U.S. children were not as lucky.
Not only did they keep getting thimerosal-laced pediatric vaccines,
they actually received more of them, including a dose in the nursery.
Six years later, New Jersey
Representative Frank Pallone cleverly attached a short amendment of
133 words to the FDA reauthorization bill to “compile a list of
drugs and foods that contain intentionally
introduced
mercury compounds and … [to] provide a quantitative and qualitative
analysis of the mercury compounds in the list” within two years.
The Food and Drug Administration
Modernization Act (FDAMA) was signed into law on November 21,
1997.
On October 22, 1998, the FDA ban on
the use of several other OTC mercury-containing compounds went into
effect because A. the safety and effectiveness of the mercury
components had not been established and B. the manufacturers had not
submitted data to the contrary.
During the following months, the
FDA’s best experts from the Center for Biologics Evaluation and
Research (CBER) researched and discussed the issue in depth. After
they were done, they had to acknowledge that because safety studies
about ethylmercury were
non-existent and because toxic levels of the compound were still
unknown, they were unable to determine how toxic the thimerosal
concentrations of up to 0.01 percent in more than 30 US-licensed
vaccines were.
Even though they did not agree on
its toxicity level, the FDA, the EPA and the
Agency for Toxic Substances and Disease Registry (ATSDR) knew much
more about methyl mercury
toxicity.
After much deliberation, CBER
decided to consider thimerosal’s toxicity in reference to the EPA’s
methyl mercury guidelines. It is then that it became evident that the
mercury content of pediatric vaccines administered during the first
six months of life exceeded
the EPA reference
dose (RfD) for methyl mercury of 0.1 micrograms per kilogram body
weight per day (µg/kg/day).
With the FDAMA deadline of Nov. 27,
1999 approaching, things heated up. Something needed to be urgently done
concerning thimerosal in vaccines and more specifically pediatric vaccines.
In early June 1999, Neal Halsey, MD,
FAAP, chairman of the American Academy of Pediatrics Committee on
Infectious Diseases and Director of the Institute for Vaccine Safety
at Johns Hopkins University was invited to a meet with the FDA team.
At the meeting, he was provided with the latest findings and alerted
about the urgency to do something regarding the amounts of thimerosal
in pediatric vaccines.
Dr. Halsey became alarmed and
discussed the subject with his committee and the AAP hierarchy.
At a National Immunization
Conference held on June 25, 1999, Dr. Halsey met with
key people at the CDC and realized that they were looking at the
situation from a totally different angle. They were mostly interested
in safeguarding their excellent vaccination programs while Halsey and
most pediatricians were more worried by the day about the serious
ethical and legal implications of the mercury in vaccines issue.
After much haggling the two sides
agreed that:
1. Thimerosal had to be removed from
pediatric vaccines.
2. A “careful” joint public
statement by the Public Health Service (PHS) and the American Academy
of Pediatrics (AAP) would be issued to pre-empt the FDA announcement
scheduled for sometime in July (1999) and the inevitable press frenzy
it was certain to create.
On June 28, 1999, the Interagency
Vaccine Group (IAG) held a conference to review the updated FDA risk
assessment information and created a special workgroup to examine all
thimerosal related matters. Meanwhile, officials from the CDC
immunization branch met in a hurry with their own toxicologists and
with the vaccine companies’ risk assessors.
Because of the urgency of the
situation, Dr. Halsey and leading AAP officials organized an
“informal” meeting to be held on June 30, 1999 at the AAP offices
in Washington, D.C. and invited “everyone”. This avoided
the long delays required for a formal meeting.
Disagreements still existed between
the organizations and even within the organizations. The AAP
committee on Infectious Diseases and the AAP committee on
Environmental Health were still
as divided on
the issue as were the agencies and the Academy.
The proposed actions ranged from
immediately stopping administration of all vaccines containing
thimerosal to infants six month-old or younger to encouraging the
elimination of thimerosal by vaccine manufacturers.
It was decided at the end of the
long and tumultuous session that no statement would be issued until
after the July 4 weekend when a PHS and AAP unified public statement
would be released.
A good summary of that unified
public statement by the PHS and the AAP can be found in the July 14,
2000 MMWR. [http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4927a5.htm]
As formulated in the joint
statement, the goal was to remove thimerosal from vaccines routinely
recommended for infants as soon as possible
while reassuring everyone that no evidence existed of any harm caused
by low levels of thimerosal in vaccines.
The groups had at last agreed
to remove thimerosal from pediatric vaccines but very
clearly, many had done so under duress.
Slowly, US babies received less and
less thimerosal in their vaccines.
The 1999 decision had little
economic effect on the manufacture of thimerosal and of
thimerosal-containing vaccines. Thimerosal is still being produced
in enormous quantities and millions of thimerosal-laced doses of
vaccines are still being packaged and shipped daily … to “Third
World” countries.
***
I do not know how many of my
pediatric colleagues are as upset as I am about being duped into
believing for so long that the quantities of mercury we injected into
infants and children were insignificant.
I know for sure that Dr. Neal
Halsey was absolutely right when he said:
''In most vaccine containers,
thimerosal is listed
as a mercury derivative, a hundredth of a percent. And what I
believed, and what everybody else believed, was that it was truly a
trace, a biologically insignificant amount. My honest belief is that
if the labels had had the mercury content in micrograms, this would
have been uncovered years ago. But the fact is, no one did the
calculation.''
In the third slide of a power- point
presentation titled “Commentary on Potential Risk from
Thimerosal for Infants”, Dr. Halsey mentioned that excellent point
again.
In the following slide, Dr. Halsey
listed situations where thimerosal (in large doses) was proved to be
neurotoxic.
The rest of the presentation is full
of useful information.
[http://www.iom.edu/~/media/Files/Activity%20Files/PublicHealth/ImmunizationSafety/Halsey.pdf]
***
I find the following disturbing:
- That the CDC, the FDA and other organizations are still
downplaying the
problem by stating that thimerosal “has been used since the 1930’s with
no convincing evidence of harm, except for local reactions”
- That some “experts” still insist on comparing the danger from
injecting
TCV into infants to eating half a tuna fish sandwich
- That certain TCV vaccines that were not routinely administered
during
pregnancy in the past, are now not only recommended but encouraged
- That when Scandinavian countries chose to remove mercury from
vaccines,
US vaccine makers immediately complied yet never considered doing the
same for infants in the United States until forced to do so years later
- That to this day, vaccine companies are still producing millions of doses of TCV and shipping them to "Third World" countries
This last atrocious state of affairs is the subject of Part
II of this series.
In Memoriam: Philip B Rudnick
PhD ~ December
23, 2010
F. Edward
Yazbak MD, FAAP
Falmouth,
Massachusetts
