Dr. Meryl Nass, M.D.
September 10, 2000
Presented at the International Public Conference on
Originally posted on the Anthrax Vaccine
Home Page http://www.anthraxvaccine.org/
Anthrax vaccine was licensed by the Division of Biologic Standards at the National
Institutes of Health in 1970, using limited safety data and efficacy data obtained in
large part from a different anthrax vaccine.
The FDA began licensing vaccines several years later and at the time anthrax was
licensed there was no requirement for demonstrating efficacy in humans. The vaccine
was approved for two limited markets, workers exposed to imported animal products, and lab
investigators using anthrax. Efficacy was demonstrated for cutaneous anthrax but not for
inhalation anthrax in the studies. By the way, you dont need to use a vaccine for
cutaneous anthrax as it is not a fatal disease and is easily treated with antibiotics.
This 1960 paper by Brachman et al used a different, earlier vaccine, but this is the
only efficacy study of an anthrax vaccine ever published, and has been used subsequently
to justify vaccine effectiveness.
A New Hampshire goat hair mill had nine anthrax cases in persons who were not
vaccinated. But only ¼ of the mill workers had received the vaccine, and it was found
that the vaccinated workers worked in areas of the plant where there were lower spore
counts, so they were at lower risk for anthrax than the placebo group.
Two years later the same authors published another evaluation of the vaccine using the
same study population but this time included three additional mills. There were a total of
26 cases of anthrax at the four mills during the study. Five cases occurred in persons who
had received some doses of vaccine and fifteen cases in persons who received placebo
vaccine. Six cases occurred in workers who chose not to participate in the study.
However, the authors now reported that the vaccine was highly effective, and in
performing the statistical analysis, they threw out four of the five anthrax cases in
vaccinated workers for not having received enough doses of vaccine, to calculate a vaccine
effectiveness of 92.5%, rather than an effectiveness of about 65%, had they included the
other four cases. This 92.5% statistic, fallacious back in 1962, and generated by an older
vaccine, has been used ever since to justify the anthrax vaccine program.
This is a table from the 1960's CDC observational study of the current vaccine, which
was required to demonstrate safety so the vaccine could be licensed. There are several
interesting things about this study. First, the investigators performed active
surveillance for local vaccine reactions only, at 24 and 48 hours after giving the
vaccine. They were careful to record local reactions, but paid only cursory attention to
systemic reactions, and did not perform active surveillance for systemic reactions. In
fact, at one mill a large number of systemic reactions were reported, but this was blamed
on an over zealous nurse.
The physician working at that mill pointed out that the reaction rate was no greater
than with other vaccines such as typhoid. No one noticed that typhoid was the most
reactogenic vaccine in use then. Also, notice that the reaction rates are highly variable
from one series to the other, which may suggest a large difference between the lots, or a
major difference in the recording of the effects by the observers. Note also that they
used both the old vaccine, used in the earlier trial, and the current anthrax vaccine,
despite the fact that the old vaccine was 16 years old at the time the study was done.
Over the next 20 years, from 1970 to 1990, only a small number of persons were
vaccinated with this vaccine: between 200 and 2,000, according to Dr. Kwai Chan's GAO
report to Congress. In our discussion with scientists at Fort Dietrich, the
estimates of number of people who may have received this vaccine over a 30 years period
range from somewhere between 200 to about 2,000 at the most. And we dont know who
those individuals are. There has been no follow up
Vaccine recipients were
never studied systematically and as far an anyone knew the vaccine was safe.
In 1985 the FDA was reviewing a number of products that had been licensed prior to the
more stringent regulations, and anthrax vaccine was reviewed by an expert panel. FDA
concluded, Immunization with this vaccine is indicated only for certain occupational
groups with risk of uncontrollable or unavoidable exposure to the organism". They
also pointed out that Inhalation anthrax occurred too infrequently to assess the
protective effect of vaccine against this form of the disease. Despite these
qualifications the decision to vaccinate US troops against anthrax was made as we
developed Operation Desert Shield and Operation Desert Storm.
A number of things were not taken into account then, and have yet to be taken into
account, although 2.5 million military service members: active, reserve and Coast Guard
are in the pipeline to be vaccinated, with 450,000 having already begun the series.
What was not considered when the decision to vaccinate troops against anthrax was
- First, long-term safety of the vaccine has never been established.
- Second, the old efficacy rate was fallacious and came from an older vaccine-- no one
knew how effective this newer vaccine would be.
- Third, the stockpile was old and many lots had expired but been re-dated, as if they
were new, with only a retest of potency.
- Fourth, the lots were extremely heterogeneous, with variable side effects and potency.
- Fifth, the manufacturer was far out of compliance with good manufacturing practices, and
had never had its anthrax line properly inspected. Sixth, use for prophylaxis against
biological warfare was not an FDA approved indication.
Even if the efficacy rate for this vaccine in mill workers were known, it would
probably bear very little relationship to efficacy in a bio warfare setting, where spore
counts would be much higher and anthrax strains would be specially selected for virulence.
The fact that genetically engineered anthrax had been shown to evade vaccine protection
was ignored. Monkey data were cited but guinea pig data, which showed very poor efficacy
against virulent strains, was ignored.
Although the stockpile was old there was no FDA approved standard operating procedure
for re-using expired lots, and no retesting for degradents, preservatives or sterility
took place before approving the use of expired vaccine. It is now known that the potency
test is unreliable and unreproducible. Finally, there had never been a protocol added to
the vaccine license, which was required before reusing expired vaccine, yet FDA had
permitted the manufacturer to continually redate old vaccine stocks since 1970.
This appears to have been no aberration. The military had a policy of storing vaccines
for very long periods. In fact, they knew that if licensed vaccines were stored in bulk
rather than in small vials they would legally last indefinitely, and if they were
investigational vaccines they would never expire, no matter how stored, according
to FDA regulations.
It turned out that some lots were 40 times as potent as other lots. The manufacturing
process had never been required to demonstrate lot-to-lot product consistency, although
that is part of FDAs normal requirement for vaccines. The result is that studies
performed on one lot might not be applicable to other lots, and that problems and side
effects from one lot could not be predicted from studies on a different lot.
Although FDA was legally required to inspect the anthrax portion of the manufacturing
plant every two years, it did not fulfill this obligation, and appears to have allowed the
Army to perform its own inspections. When FDA finally went in and did a thorough
inspection one month before the current vaccine program began, they found so many problems
that they immediately quarantined 11 lots of vaccine, and the manufacturer
"voluntarily" shut down for major repairs and renovations. Although those
renovations have since been completed, the FDA has not allowed the manufacturer to reopen,
and new lots of vaccine that have been made in the last 15 months remain under quarantine.
Because prophylaxis against biological warfare was not an FDA approved indication for
the vaccine, such use both during the Gulf War and presently should only have been
conducted using an investigational new drug protocol. This would have required the
informed consent of vaccine recipients. The Defense Department actually did obtain an IND
for adding inhalation to the vaccine indications in 1996.
Although they claim it does not affect the current use, the IND's existence opens up an
interesting legal question of whether troops receiving vaccine to protect against
inhalation anthrax should be covered by IND protection. This will likely be resolved in
After the vaccine was used on 150,000 US troops in the Gulf War one would expect that
we would now have a good idea about safety of the vaccine. However, that is not the case.
The very large question of whether Gulf War Illness is related to anthrax vaccination has
not yet been resolved. Why is that?
Although the Defense Department and Veterans Administration have spent over
150 million dollars sponsoring over 120 studies of Gulf War Illness, not a single one of
these studies in the United States has examined the relationship between anthrax vaccine
and Gulf War Illness, although sixteen other Gulf War exposures have been studied.
Instead the Defense Department has used a different strategy. A number of expert
scientific panels were convened between 1994 and 1996. They were asked to comment on
whether anthrax and botulinum toxoid vaccines could perhaps contribute to Gulf War
Illness. None of the panels presented here, with the exception of the Presidential
Advisory Committee, cited any references.
In the absence of data they drew the following conclusions: The NIH Technology
Assessment Workshop said, no long term adverse effects have been documented.
The VA said both vaccines, anthrax and botulinum toxoid have been used for many
years without adverse effects. All three review panels, The Institute of Medicine,
Presidential Advisory Committee and the Defense Science Board Review panels all stated
that no long-term adverse effects have been documented or would be expected. Further study
of the potential adverse effects of vaccines in this population is not recommended by any
of the three panels nor is it endorsed in this plan."
The Presidential Advisory Committee produced a series of final reports as further
information about Gulf War exposures continued to come to light. In 1996 they said,
The Committee concludes it is unlikely that health effects reported by Gulf War
Veterans today are the result of exposure to the botulinum toxoid or anthrax vaccines,
used alone or in combination. They cited five references for this claim, all of
which were to Defense Department briefers. The Institute of Medicine said, The
Committee knows of no evidence of any chronic effect. The Defense Department
attempted to sidestep any actual study of anthrax vaccine and Gulf War veterans
illnesses. They said it was impossible to do a study because the Gulf War vaccination
records have all been lost.
However, the document cited here indicates that the Gulf War vaccine records had
actually been classified rather than lost. It says All original records and
documents used in identifying units and personnel immunized during Operation Desert Storm
are still considered classified information. But Dr. Philip Pittman at Fort Detrick
studied the effect of booster doses of anthrax and botulinum toxoid vaccines several years
after the Gulf War. To do this, he was able to identify 400 service members at Fort Bragg
who had received anthrax and botulinum vaccinations during the Gulf War. Somehow, the
names of vaccine recipients, the dates of vaccination and the numbers of doses for all 400
participants at Fort Bragg were found.
The results of his study were interesting. They showed that systemic reactions
occurred in 44% of the recipients of vaccine. However, subjects received botulinum
vaccine in one arm and anthrax in the other, so it is uncertain how many of these
reactions are due to the anthrax vaccine alone. This study also showed that after 30 days,
3% of the subjects continued to have adverse systemic reactions. Whether their problems
resolved is unknown. This appears to be an unprecedented rate of long term reactions, but
it was ignored.
What then can be said about Gulf War Illness and anthrax vaccination? There has only
been one study done and it was performed in England on service members who had received
the British anthrax vaccine, which is similar but not identical to the one used on US
troops. This study was published in the Lancet in January of 1999 and the authors wrote,
vaccination against biological warfare and multiple routine vaccinations were
associated with this CDC multi-symptom syndrome, (which is a definition of Gulf War
Syndrome) in the Gulf War cohort. An accompanying commentary, written by Dr. Stephen
Straus of the NIH, said vaccination against plague and anthrax before deployment
to the Gulf correlated highly with illness.
The investigators speculate that these vaccines more so than the routine ones given to
service personnel had unanticipated effects. Therefore we do not yet know
conclusively whether anthrax vaccine caused or contributed to the development of Gulf War
Illness, but we suspect it. Further evidence comes from the large number of gulf era
service members who received anthrax vaccine, but were never sent to the Gulf, and
subsequently developed typical Gulf War Illnesses. They all received more than one
vaccination so we cant say which has caused their illness, but they had no other
Gulf exposures, so the vaccine connection is very significant.
Despite all these unanswered questions, the decision was made to begin vaccinating all
US service members against anthrax in early 1998. And not only anthrax: vaccines against a
number of other biological warfare threat agents are in development. Recently the
military's Joint Vaccine Acquisition Program, the umbrella program under which all these
vaccines will be developed, has talked about a total of 40-50 new vaccines for all service
members. This program was initially funded in 1997 by Congress with 322 million dollars,
and it has subsequently received additional appropriations.
There might be a relationship between the militarys interest in vaccinating
troops, and the pharmaceutical industry's interest in vaccinating civilians. After
passage of a Federal law in 1986, which made vaccine manufacturers no longer liable for
adverse effects unless there was a production error, the financial climate for vaccine
manufacturers started to improve. Furthermore, advances in genetic engineering made it
much easier to create new antigens and microorganisms for vaccines. It is conceivable that
the military vaccine program will be developing new techniques and possibly new vaccine
adjuvants that will be tested on the military population and used later in civilian
I'd like to speak briefly about reporting and reviewing adverse events. The anthrax
vaccine program began vaccinating service members in March of 1998. In eleven months
550,000 vaccine doses had been administered but only 39 VAERS (Vaccine Adverse Effects
Reporting System) reports had been filed with the FDA. When Congressman Shays asked the
Defense Department about the vaccine program, because of the large number of reports of
serious illnesses that had reached Congress, he was presented with this slide and was told
that the total adverse reaction rate was only .007%, and that anthrax vaccine was safer
than childhood vaccines. What DOD did was to take the total number of reports to FDA of
adverse effects and call it the sum total of all adverse events.
However, it turned out that the military had instituted a policy to limit the reports
of adverse events before the first vaccination was ever given! Although normally
physicians and vaccine recipients are encouraged to report to FDA any adverse reaction
they choose, military medical personnel were told that only adverse reactions which
resulted in hospitalization, or more than 24 hours of lost duty time could be reported
to FDA. This kept the reporting rates remarkably low. When the difficulties in
reporting adverse effects to FDA were reported in Congressional testimony in July 1999,
the policy immediately changed. There are now about 1500 reports of adverse reactions to
anthrax vaccine received by FDA, and approximately one in every three hundred vaccine
recipients has officially reported an adverse reaction, despite continuing stories of
obstructions being placed in the way of reporting.
What kinds of reactions are being seen? Data from a study conducted by Dr. Pittman in
1998 on Seventh Day Adventists who had served as human guinea pigs at Fort Detrick in the
1960s and the 1970s. Many of these people received anthrax vaccine and had
never been followed up. However, 25 years after the program, named Operation White
Coat ended, all the alumni were invited back to Fort Detrick for a weekend of
fellowship, and asked to participate in the following study. What questions were asked
regarding their symptoms?
The following list of twelve symptoms was given to each participant and they were asked
to comment on frequency and severity. Please note that all of these symptoms are what is
seen in Gulf War Illness, and now these are the chronic symptoms most commonly seen in
those reporting problems after anthrax vaccination. While I'm on this subject, vaccine
recipients also report a variety of neurologic disorders, especially tremors, and
endrocrine disorders. We suspect these to have an autoimmune basis. A recent autopsy of a
vaccine recipient showed death to be due to coronary artery vasculitis, or what appears to
be a series of heart attacks occurring shortly after vaccination, and due to autoimmunity.
With 1500 VAERS filed why hasnt FDA stopped the program?
Well, this is one page from a list of the VAERS reports received by FDA that I got
through the Freedom on Information Act. This report lists seven people who have filed
adverse event reports. You can see that it is extremely difficult to tell what the
severity of the symptoms is and what the duration is. Two of these people report severe
fatigue but fatigue is a very subjective symptom. The FDA has not paid it a lot of
attention, although chronic fatigue syndrome and fibromyalgia are commonly seen in both
Gulf War Illness and the post anthrax vaccine syndrome. FDA has its own list of terms that
are used to describe adverse reactions.
The system is called COSTART and the terms that are used, tend to confuse, rather than
illuminate the adverse reactions. For instance, the term asthenia, used twice on this
page, is one that has been out of use for a century. The term " Immune system
disorder," is not specific enough to be useful, and thus likely to be ignored. I have
reviewed hundreds of these VAERS reports and it is my belief that this system makes it
impossible to tell whether different people are reporting the same types of illnesses, and
it is therefore impossible to tell whether their reactions are due to the vaccine.
The VAERS reports are received by a private company working as a contractor for FDA,
and put into this format, then reviewed by FDA personnel. I think that the only way for
FDA experts to get an accurate idea of vaccine reactions is for them to review more
detailed reports, contact treating physicians directly, or investigate sufficient numbers
of actual cases. Currently they are required only to investigate deaths.
The Defense Department did initiate its own study to resolve the question of long-term
safety of the vaccine in September of 1998 amidst all of the controversy. This was done at
Tripler Army Medical Center and 603 medical personnel were enrolled in an observational
study. These data were presented in April 1999 to Congress. 43% of vaccine recipients
had mild systemic reactions, and 5% had moderate or severe systemic reactions after one of
the first four vaccine doses
This is a later GAO report to Congress, from July of 1999. It shows that over 60% of
males reported muscle soreness after each vaccination and 60-80% of females reported the
same thing. It shows that 2-5% of males and 4-14% of females sought medical attention
after one of their first three vaccinations, and that 1-2% of males, but 4-5% of females
missed at least one shift of work after receiving a vaccine dose. This vaccine causes
adverse reactions in females at three times the rate of males. However, follow-up
information on this study has not been released, so even though the Defense Department
knows what happened to these 603 people, Congress and the rest of us have no
information.about any persisting medical problems, which was the question this study was
designed to resolve.
In March 2000, at the request of the Defense Department, an Institute of Medicine
Committee investigating Gulf War Illness exposures reported on the evidence for safety of
the anthrax vaccine. They said, The Committee concludes that in the peer reviewed
literature there is inadequate, insufficient evidence to determine whether an association
does or does not exist between anthrax vaccination and long term adverse health outcomes.
This finding means that the evidence reviewed by the committee is of insufficient quality,
consistency or statistical power to permit a conclusion regarding the presence or absence
of an association between the vaccine and a health outcome in humans."
Does vaccination of troops against biological warfare agents even make sense
strategically? This slide from DARPA, the military's Defense Advanced Research
Projects Agency, lists over 65 known biological warfare agents, which are naturally
occurring. In addition, there are an infinite number of microorganisms that may be created
using genetic engineering. There are less than 10 vaccines effective against these agents.
It takes an estimated ten years, once one is aware of a microbial pathogen, to develop an
effective and safe vaccine against it.
The fact that we did not have an effective and safe anthrax vaccine at the time of the
Gulf War, and now 10 years later we still do not have one, makes this perfectly clear.
Furthermore, if we vaccinate against anthrax, an enemy can just pick a different
microorganism to use. If an enemy genetically engineers a new virulent organism, we will
not even be able to begin developing a vaccine against it until after it has presented
itself--in other words, after if has been used. For these simple reasons, the use of
vaccines against the threat of biological warfare will never provide an effective defense.
Dr. Ken Alibek, formerly the number two man in the Soviet Unions biological
warfare program, has made this perfectly clear. We need to stop deceiving people
that vaccines are the most effective protection and start developing new therapeutic and
preventive approaches and means based on a broad spectrum protection.
How has the FDA responded to the question of vaccines for the biological warfare
threat? They have bought into the Defense Departments plan completely. In fact, FDA
itself is helping to develop newer vaccines against anthrax and other threat agents.
This new DNA plasmid encoding anthrax vaccine was developed at the Center for Biologics
Evaluation and Research, FDAs center for vaccine oversight. How can FDA provide
proper oversight for vaccines developed by its own staff? Shouldn't FDA's scientists be
helping the Defense Department to understand that vaccines are not "the answer",
rather than helping them stitch together the emperor's new clothes?
Katherine Zoon, the Director of the FDA's CBER, the woman in charge of vaccine
oversight for every vaccine used in the United States, has served on an Advisory Board for
Biological Warfare for DARPA and has advocated rapid approval of new biological warfare
vaccines. In this recently published article, she implies that the FDA review process may
be limited to only six months for such products. She also says, After these vaccines
are licensed and administered, the safety and adverse reactions of these vaccines should
Ignoring Federal law, Dr. Zoon is suggesting that biowarfare vaccines be licensed and
used on humans and only afterwards should their safety profile be ascertained. We have
already learned that for the current anthrax vaccine, post marketing surveillance is
essentially limited to VAERS reporting, and VAERS reporting is close to useless. Should
the military be given carte blanche to field biowarfare vaccines and then determine
whether they cause adverse reactions? Clearly, if the case of anthrax vaccine is any
example, the military will do their best to prevent meaningful oversight and cover up
Dr. Katherine Zoon, Director of the Center for Biologics Evaluation and Research at
FDA, who is in charge of assuring that federal laws are followed and that public health is
protected with respect to vaccines, has forgotten where her primary responsibilities lie. For
advocating that vaccines be administered before their safety and adverse reactions are
known she should immediately lose her job.
The FDA has focused more on assisting the Defense Department, than in assuring the
public health. It is critical that FDAs priorities be immediately turned around, or
the repercussions will have grave effects on the health of both our military and civilians
of the United States.
For more information on the Anthrax Vaccine,
see the following publication from the Centers For Disease Control
"Use of Anthrax Vaccine in the United
States. Recommendations of the Advisory Committee on Immunization Practices."