Lancaster University | Pandemics

Hello. In this short video, we'll bring the story of flu up to date, looking at the pandemics we've had since 1918.
You may have seen the video in which we looked at how the H1N1 pandemic flu of 1918, the so-called Spanish
flu, left descendants that returned each year as seasonal flu.
In one year, 1947, the seasonal flu was particularly severe. Occasionally this will happen. Usually because
antigenic drift, the capacity of the flu virus to evolve away from the host immune system, had been particularly
strong in that year. One other bad year of seasonal flu in the UK was 1999 to 2000. In years of this kind, it isn't
unusual for half a million people to die worldwide.
More recently, the winter of 2014 -2015 was predicted to be a severe year in the northern hemisphere but,
fortunately, things turned out to be milder than expected. The important point to grasp for the moment is that even
seasonal flus can be very severe on occasions. But the difference between a seasonal flu and a pandemic flu isn't
just one of severity.
To illustrate this, we need to go back to 1957. In that year, a completely new variant of flu appeared, causing the
second pandemic of the 20th century. Its origins seem to be in East Asia, and it was, therefore, nicknamed Asian
flu. Its subtype was not H1N1, like the Spanish flu, but H2N2. This change led to the introduction of a new phrase
to describe how flu evolves. This is antigenic shift.
Whereas antigenic drift refers to the relatively slow accumulation of changes in the virus, as a result of evolution to
avoid the host immune system, antigenic shift implies the replacement of one predominant strain of flu with a
completely new one. And that is, indeed, what happened.
After the first surge of the H2N2 pandemic, the subsequent years saw H2N2 returning as a seasonal flu. H1N1,
the seasonal descendant of the 1918 Spanish flu pandemic, appeared to have gone extinct. In the light of these
events, the World Health Organization developed a definition of pandemic flu which required antigenic shift.
Now, things weren't actually quite that simple, but that fact wasn't realised until a few years later. In fact, we now
know that the H2N2 pandemic strain was actually partly descended from the previous seasonal H1N1 as a result
of our hybridisation process with a bird flu strain. The mechanism by which these hybridisation events occur is
called reassortment. And this is another of the crucial concepts for understanding of flu biology.
We'll look at the structure of the flu virus in a related video, and see in some detail exactly how reassortment
works, and consider the circumstances in which it might happen. The second reason why it's premature to believe
that the Spanish flu, or more correctly, its distant seasonal descendants was extinct, is also something we'll come

to shortly.
For another 10 years after 1957, the descendants of the Asian flu strain, H2N2, returned as a seasonal flu,
antigenically drifting each year, always trying to stay just one step ahead of the host's immune system. Then in
1968, there was a third pandemic. The antigenic shift on this occasion was the appearance of H3N2. Since the
first cases were detected in Hong Kong that year, the 1968 pandemic was referred to as Hong Kong flu.
As the antigenic shift theory predicted, H2N2 disappeared. And from 1969 onwards, H3N2 occupied the seasonal
flu slot. It's generally believed now that the H3N2 strain was also a reassortment, this time between the H2N2
seasonal virus, and again, a bird flu virus. Neither the 1957 Asian flu pandemic nor the 1968 Hong Kong flu
pandemic were anywhere as severe as 1918's Spanish flu.
The death toll around the world in 1957 was just over 2 million, and it was slightly less than that in the H3N2
pandemic of 1968. These figures are, of course, rather worse than even the most virulent seasonal flu years. But,
nevertheless, the world was spared the kind of massive calamity that had occurred in 1918.
The occurrence of two flu pandemics inside barely more than a decade was really a warning development,
because it showed that flu pandemics need not necessarily be rare events. And it lent weight to the suggestion
that they are rather part of influenza's normal ecology, and that we should expect more of them in the future. And,
indeed, it was less than a decade later, in 1977, that yet another subtype surfaced. This one, however, was
altogether more mysterious. And its origins are still disputed even today.
Russian flu, as it was called, was first detected in 1977, in the Soviet Union. It soon spread around the world, but
was considerably less severe than any of the previous pandemics. And, in fact, it was barely worse than a bad
seasonal flu year. The subtype of Russian flu was H1N1, which is, of course, the same as Spanish flu, and the
seasonal flus that had circulated from 1918 up to 1957.
But when the molecular analysis came in a few years later, it revealed the astonishing fact that this new strain,
Russian flu, was a descendant of Spanish flu, and what's more, it looked exactly like the pre-1957 seasonal H1N1
strain. This presented some difficulties for the by-now accepted antigenic shift theory. Long extinct strains of flu
were simply not expected just to come back from the dead after 20 years as some kind of viral zombie.
So, soon a consensus of opinion developed that Russian flu must be a laboratory escapee - a strain of flu kept in
the freezer since the 1950s, and somehow getting back out into the world 20 years later to cause the Russian flu
outbreak of 1977. We'll probably never know for sure, but that looks like the only way to explain the virtual identity
between Russian flu of 1977 and the last seasonal descendant of Spanish flu in 1957.
Whatever the origins of Russian flu, it didn't succeed in driving Hong Kong flu off the scene. After 1977, there

were, therefore, two seasonal flu strains circulating every winter. A seasonal descendant of Russian flu, and a
seasonal descendant of Hong Kong flu, which stubbornly defied the antigenic shift theory, and kept circulating.
Some years, H1N1 would be the predominant form, and other years, H3N2, and often both.
And this proved that there was no particular reason why human populations couldn't support more than one strain
of seasonal flu. After this turbulent period in the third quarter of the 20th century, things settled down. We had to
wait until the 21st century for our next flu pandemic.
In 2009, a new pandemic strain emerged, apparently from Mexico. Although, as is often the case with pandemics,
its exact origins were disputed. Nobody, after all, particularly likes to have a horrible disease named after them.
Mexican flu was also an H1N1, but of a variety quite different to Spanish flu and its Russian flu descendants.
2009's version of H1N1 looked more like the kind of flu already observed in pigs, hence its other nickname, swine
flu.
Whereas the 1957 and 1968 pandemics had been produced by reassortments between human seasonal strains
and bird flu, the 2009 pandemic strain was a reassortment of two pig flu strains, neither of which had previously
shown any potential to spread within humans. Generally, flu viruses that come straight from other species into
humans are very severe.
For instance, every year, several poultry farmers, mostly in the poorer parts of the world, catch bird flu and the
fatality rate is extremely high. The prediction might have been that a swine flu would be similarly virulent in
humans. However, we were lucky in 2009, much as we had been in 1957 and 1968, and the pandemic was far
less severe than any reasonable predictions might have suggested. Now, the descendants of swine flu circulate
as a seasonal variant, but once again, as in 1977, H3N2 seasonal flu has refused to go quietly, and continues to
co-circulate.
The reason why H3N2 is so persistent in human populations, having survived two potential antigenic shift events,
is still unclear. In 2009, it was Russian flu's descendants that were the loser. By 2011, hardly any cases of H1N1
descended from Russian flu had been recorded. Spanish flu's resuscitation as Russian flu had, therefore, come to
an end after 34 years of seasonal circulation.
As I record this, in late 2015, the world of influenza has settled down again. The aftershocks of the 2009 pandemic
have faded, and we're now in what we would call a normal situation, with H1N1 and H3N2 circulating as seasonal
flus. This was the situation before 2009, but the difference now is that the seasonal H1N1 is a descendant of
swine flu, whereas our previous seasonal H1N1 was a descendant of Russian flu. Nevertheless, if we've learned
one thing from our experience of influenza in the last century, it must be that we cannot predict the time, origin, or

severity of the next pandemic. And this is why the study of the influenza virus is of pressing importance.