Evolution’s Fast Lane - The Monster at Our Door: The Global Threat of Avian Flu - page 5

the barrier between birds and humans.” 19 Cells in the respiratory systems of swine have the right receptors
for both avian and human HA and thus can contract diverse subtypes of influenza A—they are ideal viral
blenders. Their critical role, moreover, is supported by epidemiological history: influenza epidemics and
pandemics usually emerge first in southern China (especially in Guangdong and the Pearl River Delta)
where huge numbers of pigs, domestic ducks, and wild waterfowl live in traditional ecological intimacy.
It should be stressed, however, that reassortment, like mutational drift, is a scattershot process. As a
leading researcher at the National Institutes of Health explains, “the vast majority of reassortants between
avian and human (or mammalian) influenza viruses contain a gene . . . or gene constellation that prevents
the virus replicating efficiently in primates.” Nevertheless, “some 25 percent of the resulting recombin-
ant viruses would still be potentially virulent for humans if one of the two parents is a human influenza
virus.” 20 On rare occasions, it is also possible for novel influenza subtypes to emerge through recom-
bination: the splicing together of parts of genes (coding for the same protein) from different species. In
a controversial 2001 article in Science, three Australian researchers proposed that the devastating 1918
pandemic was triggered by a recombination event involving the HA gene. The spike head, they argued,
derived from a swine lineage, while the stalk was encoded by a human gene. This recombinant hemag-
glutinin, they suggest, may have had “an unusual tissue specificity, such that it spread from the upper res-
piratory tract to the lungs.” 21 (Later, to make matters more complex, we will examine two other possible
mechanisms of pandemic emergence: dormancy and direct species jump.)
Whether or not recombination is part of influenza A's repertoire, few other human pathogens—apart
from the HIV retrovirus (world champion at wily mutation) and the chief malaria parasite, Plasmodium
falciparum, seem so invincible. Yet influenza does have its weak points, as can be seen as we complete
our sketch of its progress through a host: next, the progeny viruses must be assembled and then execute
their escape from the dying host cell. Although research shows that the M1 protein is probably the “major
virus assembly organizer,” the complex choreography that produces new viral particles out of the sep-
arately replicated gene strands and proteins is incompletely understood. 22 The final assembly takes the
form of a budding of the new viruses from the cellular membrane. This is sticky business; the problem is
that the strong affinity of the HA molecules for the external neuraminic acid residues—the very property
that made viral entry possible—now blocks the exit. Neuraminidase (henceforth: NA) overcomes this di-
lemma by attacking and removing the neuraminic acid residues—if HA is the burglar, NA is the escape
artist. Their complementary roles are so important that virologists classify influenza A subtypes by their
specific HA and NA: the formula adapted in 1980 is H x N y . (Please remember this. It will avoid confusion
later on when you meet a series of bad characters named H3N2, H9N1, H5N1, and so on.)
However the NA mushrooms are more vulnerable than are the HA spikes to antivirals that imitate
neuraminic (sialic) acid residues and plug strategic portals in their three-dimensional structures. The de-
velopment of powerful neuraminidase inhibitors—zanamivir (Relenza) in 1993 and oseltamivir (Tamiflu)
in 1997—has been a major breakthrough in the treatment of annual influenza. More importantly, zanam-
ivir and oseltamivir are the only medications that are thus far effective in preventing or moderating the
acute onset of avian flu (or, for that matter, lab-made clones of the deadly 1918 strain). 23 Because of the
difficulties of administering zanamivir—it requires an inhaler—oral oseltamivir tablets are seen as the
only practical alternative for mass prophylaxis. Indeed, until (and if) avian flu vaccines become widely
available, oseltamivir, as Science points out, “would be the world's only initial defense against a pandemic
that could kill millions of people.” 24 For several years the world's top influenza experts have been urging
a crash program to increase oseltamivir production; it is currently manufactured by Roche in a single fact-
ory in Switzerland. An international stockpile could then be set aside for emergency use by the WHO.
These warnings, as we shall see later, have largely been ignored, and oseltamivir inventories remain woe-