This is an important question given the high stakes. The Department informs us in its latest official written update on the vaccine, dated Aug. 15, that, for example, up to an estimated 3 million deaths could result from aerosolized release of 100 kg (220 pounds) of anthrax spores upwind of the Washington, D.C., area.

Anthrax, which is colorless, odorless and tasteless, does not spread person-to-person. The bacterium's spores can be spread in the air. One deep breath, which could mean inhaling many thousands of spores, can be fatal, if antibiotics are not taken before symptoms develop.

And, of course, the biological warfare, or BW, threat to U.S. forces is considerable. "At least seven countries, including several hostile to Western democracies — Iran, Iraq, Libya and North Korea — now possess or are pursuing offensive BW capabilities," according to the report.

Questions on Giving It Out

Since March 1998, about 1 million doses of anthrax vaccine have been given to about 520,000 service members. But there is now a vaccine shortage, and vaccination in the military has greatly slowed down.

Meanwhile, critics of the vaccine have raised many questions about its safety. More than 400 members of the military have either quit or faced court-martial rather than take the anthrax vaccine for fear of side effects reported, such as extreme fatigue, headaches, muscular problems and insomnia.

In any case, the Food and Drug Administration (FDA) has blocked release of vaccine produced at the BioPort Corporation in Lansing, Mich., because there have been a series of problems at the manufacturing plant, including contamination of lots of the vaccine and questions surrounding the company's quality assurance records.

The company plans to ask the FDA to license a new manufacturing facility. On its Web site, BioPort says it "remains on track to meet target dates for submissions to the FDA for the company's renovated anthrax vaccine manufacturing facilities. Once approval for the facility is obtained [from the FDA], BioPort will continue to deliver on its obligation to meet the needs of the Department of Defense for the protection of the men and women in our armed service."

The Defense Department (DoD) says in its report that the company has addressed the FDA's concerns.

Until the FDA approves additional anthrax vaccine, the small amounts still available for use will be designated for special mission units and research, according to the DoD.

Full vaccination against anthrax is said to occur after six doses are given over 18 months. Yearly boosters are also required.

Since Sept. 11, the DoD and BioPort have been receiving requests from civilians for the vaccine.

What’s the Science?

But should the vaccine be made commercially available one day, what would its value be against an anthrax attack? I, for one, would want to feel convinced that the vaccine works, that any claims for the vaccine's efficacy are based on solid science.

The DoD states: "The evidence of vaccine effectiveness against aerosol exposure to anthrax spores is persuasive, based on both human and animal studies."

But let's look more closely.

First the key research on animals. Some of the data come from experiments on immunity with thousands of guinea pigs. Research on guinea pigs also focuses, among other things, on determining the vaccine's potency. In other words, guinea pigs are considered important for tests on efficacy.

So, taking all the available data into account, after being immunized with the anthrax vaccine, how many guinea pigs survive after being "challenged" with anthrax?

Overall, depending on the natural-occurring (as opposed to genetically manipulated) strains of anthrax that were used, survival rates in several studies varied from 23 percent to 71 percent when the guinea pigs inhaled the anthrax. (The range is wide most likely at least in part because different strains were tested.)

This is hardly persuasive evidence of efficacy. Rather, the data point to moderate protection.

But let's carry on with non-human primates, particularly Rhesus monkeys, which the DoD report says are the animals "that best mimic humans for inhalational anthrax."

The DoD refers to five studies of Rhesus monkeys given one or two doses of the vaccine. The overall results show that "62 of 65 vaccinated monkeys survived lethal aerosol challenge with hundreds of times the median fatal dose." That's 95 percent protection. And, "in these studies, 18 unvaccinated monkeys were challenged and all died."

Now that's impressive. Actually, quite spectacular. But let's look more closely at what the military has often claimed, particularly at congressional hearings, are its best data supporting the vaccine's ability to fight off aerosolized anthrax.

For example, two monkey studies, important to the overall data and conducted at the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md., were brief reports presented at international meetings.

These types of conference reports, which are sometimes run as supplements to a medical bulletin or journal, are typically thought of by scientists as brief presentations of research findings. They were published in a little-known bulletin (the Salisbury Medical Bulletin-Special Supplement no.87 in 1996).

Monkey Tests

This doesn't necessarily mean that the science is poorly conducted, but it might well be. How do you know unless the research undergoes careful scrutiny? This raises a red flag, considering that the data from these reports are being used as part of a scientific package of information in a high-stakes situation for declarations about the vaccine's efficacy.

And another question must be asked about the monkey studies: Can the data be extrapolated to humans?

One reason for pointing to the Rhesus monkey as a good mimic for humans is that there is evidence that pathological findings in the lungs infected by anthrax in both monkeys and humans are similar. But is that enough to go on?

Maybe not. Let's zero in on the conclusion of one of the brief reports itself. Here the authors are discussing the difference between partial protection from the vaccine in guinea pigs and the high level of efficacy in rhesus monkeys.

The authors conclude: "These findings suggest the importance of various, specific immune mechanisms against inhalation anthrax may vary in different animal species, or that the ability of the licensed human anthrax vaccine to stimulate cell-mediated immunity may be greater in some species than others."

There is also no method available today to compare the immune responses of Rhesus monkeys to an anthrax vaccine with those of humans. What is needed is what is termed a "marker," some signal in the immune defense process that is similar to both species.

In April 1999, Dr. Kwai-Cheung Chan, then Director of Special Studies and Evaluations (National Security and International Affairs Division) of the United States Government Accounting Office (GAO) had this to say to a congressional committee investigating the anthrax vaccine: "Taking all the evidence into account, it's likely that the vaccine does give some protection, but to what extent, against what amount of anthrax, against which strains and how long protection lasts, are not known."

Other Considerations

And speaking about strains, there is the issue of whether an attack from anthrax might involve a genetically engineered strain that the vaccine cannot fight. Here we find ourselves in the realm of the Great Unknown.

We have to also keep in mind that animal tests run in a lab do not mimic battlefield conditions or those that might occur should a bio-war target be a civilian population, for the reasons that the GAO's Chan cited.

Now we come to the efficacy data on humans — really just one controlled study that is often cited by the military as suggestive evidence that the vaccine works against aerosolized anthrax. And this is the research that led to approval of the vaccine by the FDA in 1970.

The study involved vaccinating 149 mill workers who in those days were in danger of being exposed via the skin to anthrax in animal products. No one developed anthrax. And of the 448 people at the mill who were left unvaccinated, five cases of inhalation anthrax occurred..

But even the DoD report indicates that, "despite the obvious trend, the number of cases of inhalation anthrax are too small for the difference between groups to be statistically conclusive by itself." The DoD refers to a "follow-up" by the Centers of Disease Control and Prevention which further suggests the vaccine worked — but here again, it's more indicative of a trend than hard scientific evidence.

When all is said and done, what we now essentially have is a hodge-podge of data about efficacy, ranging from the almost irrelevant to the modest — data that does not reassure me on scientific grounds that the vaccine is effective.

Reason for Hope, or Not?

I can understand the DoD's strong feelings: "The consequences of unvaccinated Service Members becoming biological warfare casualties would be tragic enough, but the consequences would be graver than their deaths alone. Their individual deaths may jeopardize the capability and survival of entire military units, as well as the success of the military mission."

But we need a vaccine based solidly on good and detailed science — and not one based on hope and apparent desperation.

And, given the difficulties that are all too apparent in developing a vaccine that would protect against a weaponized attack of anthrax (likely one involving a genetically altered form of the bacterium and one that could easily be changed), it might also make a ton of sense to start thinking about other methods to prevent anthrax-related tragedies.

Congress should hold hearings on what some of those other methods might be and also on the need for research to better understand how an anthrax infection develops in the body. It also might be valuable to spend some tax dollars on figuring out ways to stop the infection once it occurs. Better late than never.