Pandemic Influenza as a Bioweapon

"Anyone who is honest about this has to admit that if al Qaeda launches a spectacular biological attack which could cause contagious disease to be spread, no entity in the world is prepared for it," Noble said. "Not the U.S., not Europe, not Asia, not Africa."

Since the WSN/33 situation in Korea provides some valuable insight into detection and reporting of bird or human flu, and wire services are carrying stories about biologic attacks by terrorists causing a contagious disease, it is worth reviewing some of the lessons learned from the swine WSN/33 infections.

If pandemic flu is the contagious disease of choice, selection of WSN/33 at this time would offer some advantages. It is already transmissible from human-to-human, has been shown to be lethal in mice, has mutations in NA and PB2 that increase lethality, is widely available, and could be used without genetic manipulation.

As has been seen in Korea, introduction of the agent into pigs would allow it to spread almost undetected. Verification of its spread (or existence) has proven to be exceedingly difficult. Movement from swine to humans has not been reported and all reported isolates are missing the PB2 mutation. This may be due to a survival selection offered by recombining or reassorting with prevalent H9N2 subtypes. Most of the swine isolates have an avian PB2, but even the isolates that have half of a human PB2 have the 3' half of the human gene replaced with avian sequences. Thus, the results from the Korean swine may indicate that starting with a very lethal virus has disadvantages in that a less lethal virus will emerge virtually undetected.

A second choice would be the H5N1 currently causing the high case fatality rate in Vietnam, Thailand, and Cambodia. This version would be even more available, since it is excreted in large amounts by asymptomatic ducks, and is present in multiple organs in fatal infections. Although human-to-human transmission of H5N1 is limited, infecting a few international travelers would generate worldwide panic if these passengers became ill outside of areas with indigenous H5N1. Use of infected currency as a vector for transmission has been widely discussed.

A third approach would involve genetic manipulation. Creating an efficiently transmitted H5N1 would be relatively easy. Swapping a human receptor binding domain from a human flu virus into an H5 backbone would improve transmission efficiency and such an agent would quickly disseminate worldwide. Of course such an agent would be hard to control, and most unvaccinated people would be at risk. Since influenza evolves via recombination, implementation of an efficient laboratiry strain might be eclipsed by a natural version, and there would be uncertainty over the origins of such an agent.

Thus, like WSN/33 in Korean swine, taking credit for such a biologic attack may be difficult, since most countries appear to be unable to even determine if such an attack has happened.

Using influenza as a bio-weapon makes as much sense as issuing plutonium knives to soldiers for use in combat.

There are plenty of reasons for this. For example, the various influenza have an extraordinarily high number of flexible RNA components, which means it mutates at a tremendous clip. A single animal may have half a dozen strains at the same time.

This also means that the strains are in natural selection competition with each other to develop the best strain to insure strain survival. This means that there is a distinct path for a given strain.

To begin with, a strain must be different enough from previous strains so that its hosts immune system does not recognize it and attack it with a specialized and deadly defense. But by not recognizing it, the host immune system overreacts, which can result in what we now call the “cytokine effect”. Between virus over-reproduction that damages the host and the cytokine effect, this makes the new strain deadly to the host.

However, natural selection then kicks in again, as less lethal variants of the strain survive and propagate better than lethal ones. And this happens rapidly as well, so the strain soon becomes just annoying to the host, not deadly. But by then, so many hosts are innovating deadly defenses against the strain, that other strains are able to fill the gap in the host population.

Influenza also swaps RNA segments readily, helping it to adapt and compete. This is why the Mexican swine flu has human, avian, and European and Asian swine elements, and typical influenza tests showed positive for two different strains.

In short, influenza is vastly too complex, too capable, too flexible, and too unpredictable to use as a bio-weapon. Annual vaccinations are based on guesswork, and even if a lethal strain was devised, there is no assurance it will last beyond the first few hosts.

At the same time, the H5N1 strain being innovated naturally has the potential to kill 1 billion people. Nature is that much better at this than we are.

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