a "forgotten pandemic.'

But it was a huge global calamity.

In terms of the number of deaths

we're saying 50 to 100 million - far greater than the casualties of the

first world war.

Roughly around May, April May 1918 when

you know the carnage of the First World War is is graphic and horrendous but at

the same time this this unknown enemy is starting to sweep through the US, Europe,

the trenches and it is recorded by the Spanish press and it becomes dubbed as

the 'Spanish flu' because they are neutral.

Well at the time in the 1920s

they estimated that maybe 20 million had died. By the late 20th century that

figure it went up to 25 million. In the 21st century with scientists and

historians now getting together to work much more closely, that figure has now

been upped to fifty to a hundred million people killed.

This virus killed more

people in the first 25 weeks than HIV/AIDS has killed in 25 years -

horrendous! Those mortality statistics are staggering.

We don't know exactly why some flu strains are much more severe than others and why some of

them would would be more likely to kill people or cause very severe disease.

What is particular about avian and pandemic viruses is that they replicate deep

inside our lungs. When our cells detect this they trigger

very strongly an immune response this leads to an influx of white blood cells

and fluids into our lungs and it restricts the amount of air space that

we have to breathe.

The symptoms are very graphic and very very striking so you

know it's said that some people drowned in their own phlegm, so if it was hitting

or effecting the lungs - people were spurting blood

from their ears and their noses. Descriptions of people turning blue or

purple so you know it was really really severe and people just dropping down in the streets

Those that succumbed to the flu were in the age group 20 to 40 years

which is very unusual for an influenza epidemic or pandemic and scientists and

historians are now still looking to see why.

There's really two ways that people

died in 1918 they either died from the initial flu infection or they died from

a enormously strong immune response to that virus were their lungs just filled

up with fluids from trying to attack the virus that got into their lungs.

So traditionally everyone sort of said oh well it's the trenches you know the

conditions of the war and that's why it was so fatal but when you think well you

know how did it spread so rapidly around the world to places that are not part of

the theatre of war.

I think the traditional explanation is it starts in

Kansas in an army camp and then the troops bringing it over to the trenches,

Europe but there's still so many, many unknowns.

So mathematical modelers have

long been interested in the 1918 pandemic and one of the questions is to

try and disentangle how its spread around the world and exactly what the

routes have been. Given a perfect data you could work backwards and try to

infer where it's come from.

Whereabouts does it arrive in a country, does it

arrive multiple times or thinking about multiple countries where is the first place?

If you understand the origin of a pandemic then you understanding about

where it's come from and maybe you can stop that in future.

Almost certainly it was a bird flu originally but then we also know that

that flu or something very similar to it was in pigs at the same time. Maybe it's

somebody who works very closely with birds or who works very closely with

pigs or has some other exposure like that.

One of the big really open questions in flu research and flu Public Health is -

How does the virus adapt from one species to another, how does for example

a virus in pigs or in Birds get into humans and then start transmitting?

Then the key question is - how does the virus then adapt within that person to stop

being a pig virus or a bird virus and become a human virus? in other words to

be able to transmit from human to human and it's probably some very quick

evolutionary process that is going on within that human and in many cases

won't be successful, but in a few cases we'll and that's when the virus can

start spreading between humans and become a flu pandemic and then stay in

humans as regular seasonal flu.

Just as people were celebrating Armistice Day

and there was hope that it was dying down but then it resurged and a far more

deadly and virulent strain emerged.

So this the second wave really spread like

wildfire affecting a third or quarter of the population of the world and it was

short-lived so it petered out not long afterwards maybe in 1920/1921 but it was

it was in the sense short-lived.

What happened was is that virus continued to

transmit among humans, in fact it continued until 1957 to transmit between

humans and probably what happened there is that the virus adapted to humans.

It wasn't this avian or swine virus that came in and was accidentally more

pathogenic in humans.

In a lab here in Cambridge we study both seasonal flu and

pandemic flu from the standpoint of - how does the virus evolve? And how can we

predict that evolution and make vaccines to try to artificially evolve the virus

both in the laboratory and in the computer to understand what its gonna do

next and to make vaccines against those strains that will evolve in the future.

So this is the basic science of studying evolution

trying to predict that evolution. Something that's nobody has ever been

able to do for a complex organism. And then working to use that understanding

to make better vaccines.

On the pandemic flu side we do a similar thing where we

look to see how that virus is changing - that virus how it changes in birds and

how it changes in birds and in other species and to try to see what

possible variants out there might be but there might be and again to make

vaccines that could protect against all of those variants that we see.

Flu is very difficult to eradicate because it's constantly mutating and changing its

genetic information. We work on the influenza virus and in particular on the

enzyme that copies the genetic information of the virus when this

enters our cells. Specifically we're interested in how this enzyme can do

this activity and how it inserts mutations in a viral genome that leads

to the formation of the new strains to which we need to develop new vaccines.

And we are also interested in when this enzyme messes up how it triggers the

innate immune resistant and helps cause disease.

We really don't know why we

haven't seen a pandemic as deadly the 1918 pandemic. Scientists and

public health officials are extremely concerned the national risk register

which is the way that our government plans what are all the risks to civil

society in the UK. There's only two events that are up there in terms of the

most catastrophic and that's a terrorist event or a influenza pandemic.

There is a real threat that there can be such pandemics for example the H5 in the H7

flu viruses that have infected now close to 2,000 people and killed about half of

them. There has been with the H7 viruses some transmission from human to human

not very efficient and it hasn't really taken off. If either of those viruses did

adapt to really transmit well between humans, there's a real concern that it

could be as bad as the 1918 virus and this is why there is so much research

done for the public good to try to understand what's happening and so much

work done by people in public health and preparing in hospitals in case something

like that happens.

Well experts like to say it's not if- but when?

Coming at it as a mathematician

it's happened a lot of times in the past, it'll probably happen again.

The 1918 pandemic is difficult because of lack of data but the most

recent influenza pandemic we had was in 2009 and from that pandemic there is

some very good data. If we understand how the 2009 pandemic spread maybe that

tells us something we can use to help control future pandemics. We can't stop

them, the alternative is at least to allocate our resources better to try and

reduce the number of cases in each place.

Looking back a hundred years to the last

pandemic also invites the question of - a hundred years from now what will we be

like in terms of how well we are protected against flu? Or what things we

could do to protect ourselves in some situations? Surely we'll be in a

situation where we know more about what viruses are in the world

and where they are, surveillance will be so much better.

Surely we'll be in a better situation where we have better drugs and better

vaccines because we know more about the virus so we know more about its

weaknesses, we know more about our immune systems and we know how to enable them

to fight those pathogens better.

At some point we will have a universal vaccine

that will protect us against flu for the rest of our lives. When this is is a

whole other question. There are a great number of approaches and really good

ideas to doing this.There are already attempts at this that are at a quite

advanced stage.

It might be ten years from now,

it might be twenty or thirty or

forty years from now we really don't know.