Evolution’s Fast Lane - The Monster at Our Door: The Global Threat of Avian Flu - page 4

The complex details of RNA transcription and replication are best left to a good virology textbook,
but two general aspects of influenza's reproduction are key to understanding its success as a pathogen.
First, RNA synthesis is radically error prone. All cellular life (as well as some viruses) depends upon the
scrupulous accuracy of DNA polymerase in duplicating genetic information; like an obsessive scholar,
it proofreads and corrects every copy of DNA, and the resulting error rate (in bacteria and humans) is
thus less than one mistake in every billion nucleotides copied. RNA polymerases, on the other hand, are
careless hacks who do not proof or correct their copy. As a result, the error rates in influenza and some
other RNA viruses are 1 million times greater than in DNA-based genomes. Each new strand of RNA is
a mutant, differing on average from its parental template by at least one nucleotide. (Its progeny are often
characterized as a “mutant swarm” or “quasi species” because of their extreme variability.) Influenza, in
fact, lives at the very edge of what evolutionary biologists call “error catastrophe.” If the error rate were
any higher, information integrity would be lost, and the genome would decay into utter gibberish. 13
To aficionados of complexity theory, then, influenza is an outstanding example of a self-organized
system on the edge of chaos. * Such perilous fine-tuning is supposed to optimize complexity and enhance
evolutionary fitness, but for what purpose? In wild ducks, genetic hypervariability has seemingly lost its
raison d'être ; older strains of influenza find it easy to earn a living, and different subtypes can coexist
peacefully with another. Evolution, according to Robert Webster and William Bean, has resulted in stasis
as “the long-term survival of the avian viruses appears to favor those that have not changed, and selection
is primarily negative.” 14 In humans and other secondary hosts, however, influenza comes under ferocious
attack from sophisticated immune systems. This generates intense selective pressure, which in turn kicks
evolution into fast forward. “The molecular clocks of RNA viruses,” writes evolutionary biologist John
Holland, “can spin at blinding speeds as compared to those of their hosts.” Indeed, their rates of evolution
“proceed up to millions-fold faster than that of their hosts.” 15
Influenza A's extraordinary heterogeneity thus becomes a resource for resisting the immune-system
onslaught. As rapidly as antibodies defeat one influenza strain, others, more resistant, emerge to take its
place—a single amino acid substitution can suffice to thwart an antibody attack. This irresistible drift of
influenza's antigenic characteristics ensures its survival in the face of the antibody blitz. Indeed, accord-
ing to leading researchers, “it may be that human influenza A is unique in that it is able to produce a
series of antigenically selected mutants that are as fit as the parental population and is the only virus that
undergoes true antigenic drift.” 16 Yet if these point mutations ensure influenza viability as a disease from
season to season, they do not totally outwit immunological memory. “[T]he high level of partial immunity
remaining in the community,” Dorothy Crawford explains, “ensures that antigenic drift will not cause a
pandemic.” 17
The influenza genome, however, has a second, even more extraordinary, trick up its sleeve: because
its RNA is packaged in separate segments, a co-infection of a host cell by two different subtypes of in-
fluenza can result in a reassortment of their constituent genes. Under the right circumstances, influenzas
can trade replicating RNPs like kids swap baseball cards, with the resulting hybrids having gene segments
from different parents. Thus the pandemic Asian flu of 1957 contained three avian segments (including a
novel HA) along with five RNPs from the previously circulating human subtype. Likewise, the pandemic
Hong Kong subtype of 1968 retained six segments of the 1957 genome while adding new avian genes
for HA and one of the polymerases. In both cases, the reassortants combined avian surface proteins with
human-adapted internal proteins; this enabled them to overcome what Taubenberger and Reid character-
ize as “the twin challenges of being 'new' to its host, while being supremely well adapted to it.” 18
But, given the species barrier raised by HA specificity, how do co-infections of avian and human vir-
uses ever occur? Until the 1997 outbreak, it was generally believed that antigenic shift required the inter-
mediary of pigs: “[F]or influenza viruses, the species barrier to pigs is relatively low when compared with