as experts wrestle with the yearly challenges of making the next vaccine,
they are always, in the backs of their minds, worrying about "the
next big one" a killer flu whose coat proteins are so radically
different form existing strains that they could take the immune systems
of the entire world's human population by surprise. How do such major
variants appear? Where do they come from?
names of several of the 20th century's worst flues offer
some clues. In 1957, there was the Asian flu. Then, in 1968, there was
the Hong Kong flu which infected 50 million Americans and left 70,000
dead in little more than six weeks. Then there was the Shanghai flu.
Then the Taiwan flu. Now think. Where have recent reports of bird flu
come from? Mainland China. Tawian. Thailand. Vietnam. Do you see a pattern?
why should so many particularly dangerous strains originate in Asia?
And what does this have to do with current fears about the new Asian
strains of avian flu? The answer, according to one fascinating hypothesis,
is hinted at by the name of yet another nasty strain: "swine flu."
a few decades ago, the difference between deadly flu strains and ordinary
flu strains was a mystery. But when the Hong Kong flu hit in 1968, new
molecular tools enabled researchers to study its genes and proteins.
When the Hong Kong strains were compared them with other influenza strains,
the results were surprising. Several coat proteins on the Hong Kong
strain looked remarkably like proteins isolated from a ducks strain.
In fact, the Hong Kong strain carried six protein-coding genes from
normal human flu strains, and two genes form a duck strain. Similar
analyses were performed on virus samples preserved from the 1957 epidemic.
Sure enough, the deadly Asian Flu had carried five genes from human
strains and three from avian strains.
believe that the deadly Hong Kong virus that circulated in 1997 (strain
H5N1) was carried genes that originated in three separate strains of
avian influenza. Current evidence indicates that these strains came
form quail, geese, and teal from mainland China.
all previous experiments had shown that pure avian flu strains either
failed to survive and reproduce in humans, or hung on for a couple of
days and then disappeared. But if avian strains didn't live in humans,
and if human strains didnšt infect ducks, how did some strains end up
with genes from both groups? And how did those "bird flu"
strains "learn" to infect humans?
to one strong hypothesis originated and championed by Robert Webster
of St Jude's Hospital in Memphis TN, the answer lives in farmyards.
Webster noted that both human and avian flu strains can infect pigs
at the same time. And when that occurs, the door is opened to gene-swapping
between strains. How? If
virus particles from both human and avian strains infect a single cell
of a pig at the same time, their genomes can get mixed up and recombined
as viral genes are copied and assembled into new virus particles. At
least some of the resulting new viruses appear to contain a deadly combination
of traits. They carry enough human-strain genes to enable them to infect
people readily. But they also contain coat proteins from duck strains
that make them look completely new to human immune systems. And that
makes them doubly dangerous.
This schematic illustrates Webster's hypothesis that human and
avian influenza strains can both infect pigs where genes form
different strains can be mixed.
brings us back to the question of why these nasty strains often emerge
in Asia. As you probably know, many Asian countries are very densely
populated, and depend on intensive agriculture. In rural areas, animals
are raised very differently than they are in the United States. In many
places, farmers raise chickens, pigs, and other species in very close
association with each other and with humans. Can you see the
connection? In these sorts of situations, birds (which can carry avian
flu strains) come into regular close contact with humans (which can
carry human flu strains) and pigs (which can often host both avian and
human strains). This situation significantly increases the chances of
forming a deadly recombinant strain.
you can also understand why global officials are so worried about the
new bird flu strains in Asia this year. These trains have spread like
wildfire among domestic poultry in China,
South Korea, Vietnam, Cambodia and Indonesia, Malaysia, Japan, Taiwan,
and even as far away as Pakistan. They kill a large percentage of the
birds they infect. Meanwhile, some strains in Thailand, Vietnam,
and Cambodia occasionally jumped directly from birds to humans
and had killed at least 15 people by the end of January 2004.
far, this bird flu does not appear to be transferred effectively from
one human to another. (The people who have been infected apparently
got sick after handling sick birds.) But if one of these strains happens
to infect a human who is also infected by a fast-spreading human strain,
the result could be a new "killer" flu. And with today'Ws
high speed global travel, that strain could spread around the world
with lethal speed. So stay tuned for further developments!