Monday, August 6, 2012

Regarding Testing Anthrax Vaccine in Children

Below is my recent letter to the Chair of the Presidential Commission for the Study of Bioethical Issues, preceding the Commission's meeting last week.  The Commission's blog mentions some of what was discussed.  The Commission will report its views to the DHHS Secretary by year's end.


Meryl Nass, MD
Board Certified in Internal Medicine
Mount Desert Island Hospital
10 Wayman Lane
Bar Harbor, Maine 04609
(207) 288-5119


July 28, 2012


Dr. Amy Gutmann
President, University of Pennsylvania
1 College Hall, Room 100
Philadelphia, PA 19104-6380


Dear Dr. Gutmann,

I sent a letter regarding anthrax vaccine to the Presidential Commission for the Study of Bioethical Issues in late January 2012 (copy enclosed).  Because Commission staff did not confirm whether my letter was shared with the Commission members, I am writing you directly. 

With respect to anthrax vaccine and its use as a countermeasure in children, I believe my original letter provided considerable detail.  I would just like to emphasize that the vaccine’s efficacy in humans for inhalation anthrax is unknown.  The efficacy of several anthrax vaccines in clinical trials has depended on the species and strain of animal infected, the strain of anthrax used, and the magnitude of the exposure.  In many animal studies, high antibody levels have failed to protect the animals and prevent deaths.

I am enclosing the consent form for testing anthrax vaccine in children developed by CDC and FDA in 2001, after the anthrax letters. It said, "Anthrax vaccine has not been shown to prevent infection when given to people after exposure to anthrax spores," and “You should not consider the vaccine as treatment for anthrax. The vaccine as given in this program has not been shown to give long term protection against anthrax.

After holding 5 hearings on the subject of anthrax vaccine in 1999, the House Committee on Government Reform issued a report titled Unproven Force Protection.[i]  Two of its findings were:

  • Safety of the vaccine is not being monitored adequately. The program is predisposed to ignore or understate potential safety problems due to reliance on a passive adverse event surveillance system and DOD institutional resistance to associating health effects with the vaccine.
  • Efficacy of the vaccine against biological warfare is uncertain. The vaccine was approved for protection against cutaneous (under the skin) infection in an occupational setting, not for use as mass protection against weaponized, aerosolized anthrax. 
Today’s vaccine is the same as that used in 1999 and 2001.  But why use the vaccine anyway?  The immediate medical response to an exposure includes antibiotics and passive immunization with one of several available antibody products, when needed.

There has been concern about late germination of spores, which may remain resident in the lungs for several months.  This concern has led to the recommendation to vaccinate, in addition to providing immediate therapy.  Yet early germination and infection by spores should induce a protective immune response to later spore germination.[ii]  Late germination associated with immune failure can happen, but seems to be a rare event.  Of the 30,000 people offered antibiotics after the anthrax letters, fewer than half completed the prescribed 60 day course, and none developed a late case of anthrax.

I was struck by errors in the presentation of Major General John Parker, M.D. (retired) in May, and by the fact there were no anthrax experts in the room who could answer technical questions germane to the discussion.  It looks like that omission will continue at the August meeting (based on the list of panelists), despite concerns expressed by you at the last meeting regarding the need for clarification of facts regarding anthrax vaccine science. 

General Parker deflected your question of whether those who were familiar with the vaccine, and urged its use, would vaccinate their own children.  He answered that some military members wanted their children to receive the same vaccine protection they had.  Yet if those soldiers were informed the vaccine had not proven protective in humans, would they still want their children vaccinated?  And what of the researchers and government administrators who spoke in favor of a trial in children?  Will they offer their children or grandchildren for testing?

It is difficult to convey the degree of effort expended over many years to promote anthrax immunization, which has created a smokescreen around anthrax vaccine science.  For those unfamiliar with the details, it appears unbelievable.  I can best convey it by using a metaphor:  the BioWatch program.

Pulitzer prize-winning journalist David Willman wrote a recent article on the failures of BioWatch, a federal program employing sensors to identify the offensive use of microorganisms, in Philadelphia and other large cities: 


No matter how much evidence Willman unearthed about the program, official spokespersons kept repeating their mantra about BioWatch’s effectiveness.  Willman’s article shows how the system works to protect favored programs in Washington, regardless of their value. The amount of money involved is phenomenal.  The anthrax vaccine manufacturer has received over 2 billion dollars for anthrax vaccine, after buying the factory for 18 million dollars from the state of Michigan in 1998.

It appears that the focus of the August meeting of the Commission will be on countermeasures in general, rather than anthrax vaccine in particular. Public comments on the ethical implications of pediatric countermeasures research have been solicited.

I’d like to say several things about this.  First, unlike most therapeutic agents, anthrax vaccine has pressing safety and efficacy questions.  Anthrax vaccine should therefore be considered individually by the Commission, with its unique issues in mind, rather than as one of many possible countermeasures.

Next, many countermeasures designed to respond to biological, chemical and radiological agents have been given a manufacturer waiver of liability through the Public Readiness and Emergency Preparedness (PREP) Act. 


The result is that they may not have been developed or tested with the same rigor as other medical products. Yet reliable testing in adults for efficacy and safety should precede testing of such products in children, if at all possible.  Thus the decision to test countermeasures that have liability waivers, including anthrax vaccine, in children, should require a higher level of evidence derived from adults, compared with testing products not given a liability waiver. 

Finally, the press release for this meeting stated, "The Commission is examining whether the U.S. government should do research that could cause harm to protect children from high consequence events with a low or unknown likelihood of happening."  The low/unknown likelihood of such an event would suggest such research cannot meet the requirement of 45 CFR 46.407 for approvable pediatric
research:  which is to present “a reasonable opportunity to further the … alleviation of a serious problem affecting the health and welfare of children.”

Some panelists at the May Commission meeting alluded to the need to balance risk and benefit as a justification to perform pediatric countermeasures research.  45 CFR 46.407 does not call for balancing benefits and risks.  Instead, it provides a nonporous barrier against potential child subject endangerment, designed with child protection as the sole consideration, regardless of any potential benefits for children or society that may be invoked.

Thank you very much for taking the time to serve as Chair of the Commission, and for taking these concerns into consideration.


Sincerely yours,


Meryl Nass, M.D.


Cc:  Presidential Commission for the Study of Bioethical Issues


[ii] Weiss S, Kobiler D, Levy Haim et al. Antibiotics Cure Anthrax in Animal Models. Antimicrobial Agents and Chemotherapy 2011; 55(4): 1533-42.

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