Bless you! Meet the flu hunters trying to stop the next pandemic in its tracks

An issue critical to the health of millions of people all over the planet was decided by a small group of international scientists. For the first time, it was not about coronaviruses, although these experts know a lot about that. The task in hand was to save us from a bug we have been fighting for a long time. It's an adversary that could be as dangerous as Covid. The heads of a handful of international institutions are the flu hunters, who track this old foe as it changes and changes in its fight for survival.

For the first time since Covid struck, the annual meeting was held in the plateglass anonymity of the World Health Organization building, with a few participants on the internet. The scientists came armed with a lot of data and decades of experience to decide which strains of the flu should be in the next vaccine. There can be wrangling and even political positioning when each has their own opinion. China, the US, Australia, Japan and Russia are involved. It is not always easy. They made their recommendation public with what should have been a white smoke. If they have got it right, thousands of lives will be saved.

The meeting was chaired by Dr John McCauley, who has attended these meetings for more than a decade. A man in his 60s, grey-haired and jocular, has spent a lifetime watching the devious twists and turns of the shapeshifting virus. The Worldwide Influenza Centre is based in London at the Francis Crick Institute. In the months leading up to the meeting, he was busy taking delivery of large numbers of boxes of carefully packaged, potentially lethal human flu virus samples from 90 centers in Europe. In a normal year, the Crick gets 120 or 130 shipments containing about 5,000 samples. Scientists will compare the viruses in the other boxes to their own samples when they are shipped out. The story of friendship, colonialism and cooperation is told in the labels.

Flu hunters know better than to underestimate their enemy. If you can’t see it just now, it’s probably only hiding

There are periods in which we are very busy and periods in which we are extremely busy. He patiently explains the complex nature of the virus, with just an occasional flash of irritation suppressed at this interruption to his life-saving work. He strides briskly in his white coat between his small glass office and the dark, closed-off labs behind it. There is a restriction on entry to the labs when there is live flu.

The flu virus samples start to flood in January. Cardboard boxes containing the evidence of its latest mutations are brought in and transferred to freezers at -80C, where they will last for a couple of weeks while lab staff get to work. The word "testing" is inadequate for what they have to do. He says it is about isolating the virus, propagating the virus, doing the genetic analysis, doing the antigenic analysis, and doing the drug resistance analysis. The February meeting must be informed by how the virus is changing.

Something unusual has been happening. For the past two winters, there has been no flu. Some strains have vanished completely. The flu hunters know better than to underestimate their opponent. It's probably only hiding if you can see it now. Flu can be a killer. It's not just a cold. The man flu is not the flu. If you think you have the flu, you probably haven't. A bout will keep you in bed for a long time. In 1918, it killed at least 20 million people and caused at least 6 million to be killed, if it hadn't been for vaccines. It's a complicated foe that is very good at evolving and changing to escape vaccines.

B, a historically human variety, and A, the animal variety, can jump species and cause epidemics. Flu B has been with us for 10,000 years. Hippocrates knew about that one. Flu A comes from animals and birds. People who are in daily contact with animals such as pigs and chickens can pick up the virus. The man caught bird flu from his ducks. He fed about 100 of them and 20 of them lived in the house. He was the first person in Britain to test positive for H5N1. He was banned from adopting more because he had to kill all the birds. The good news is that the strain was not able to spread to anyone else.

There has been a lot of bird flu in the UK and across Europe. It started in the wild swans in England. Domestic birds pick up the virus. Whole flocks have to be slaughtered when it gets into poultry. The risk that farm workers will contract the virus is always there.

The bird strain of flu can't be transmitted from a farm worker to another person. The nightmare scenario is where the virus can be passed on. You are in a potential Pandemic territory. The Spanish flu came from birds. At the end of the first world war, a lethal strain of Flu A infections called H1N1 killed scores of soldiers and young people. The strain was no longer causing devastation because so many people had been exposed to it.

There was a swine flu outbreak in Mexico and the southern US in 2009. It caused a huge scare, but less deaths than feared, with up to half a million deaths worldwide. It was bad, but not as bad as 1918.

The Pandemic Flu is so deadly because it is caused by a bird or animal virus that is unknown to the human immune system. Viruses kill when we are not prepared. People are breathing in each other's air in the winter when seasonal flus surge. Up to 646,000 people die of flu in a normal year.

The shot has to contain a cocktail because a vaccine against one flu strain won't always defend against another. There are two strains of Flu A in the current vaccine. The latter arrived in 1968 and killed millions. Each of these strains has evolved different versions, which have complicated code numbers and may be named after the place they were first spotted, such as Victoria, Yamagata, Texas or Bangladesh. Flu is not picky; it will happily change.

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The UK has begun G lobal flu surveillance. The year before the WHO was launched, Christopher Andrewes was involved in talks about the UN organisation's work. The Spanish flu was a horror story and a priority. The Worldwide Influenza Centre was set up by Andrewes in 1948 under the auspices of the National Institute for Medical Research in London. The NIMR became part of the Francis Crick Institute.

The obituaries of Andrewes paint him as a brilliant British boffin.

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Andrewes helped discover the flu in 1933. The first ever flu vaccine was given to Dennis Busby three years later. He wasn't paraded like Margaret Keenan, the first person in the world to receive an approved Covid vaccine. A vital global breakthrough went undetected in those days.

The stories have become folklore among the virologists who have followed Andrewes down the years. He prepared the vaccine himself, so was it ethical to jab him at an age when most boys are at school?

Sir John Skehel was the previous head of the Worldwide Influenza Centre and he was an expert in how the flu enters human cells. Skehel ran the centre from 1975 to 1993 and was the director of the NIMR from 2006 to 2007.

Would you like to meet him? The 81-year-old recipient of a string of awards is working in a small office in the same building as the one he is from. The two discuss the difficulties in tracking the flu caused by the coronaviruses.

We are trying to get some virus from Hong Kong, but there are no flights.

Skehel says that Hong Kong is an important laboratory. In 1997 they picked up the H5N1 bird flu.

In the past, Hong Kong has been able to see what is happening in mainland China. Some of the samples they collect are from southern China and the scientists are trained in the UK. The UK may not be able to get those sorts of insights as China takes over Hong Kong.

The Crick, Atlanta and Memphis in the US are one of seven WHO global reference centers. Two watch for animal viruses that might jump to humans, and five are devoted to human flu. They are on the lookout for a flu outbreak in chickens in Egypt and pigs in Central America because of the possibility that farm workers and families with animals will get sick.

National Influenza Centres are feeding into those WHO hubs. Prof Maria Zambon is the head of the UK Health Security Agency. Prof Neil Ferguson was one of the key members of the government's Sage advisory committee. She is an adviser to the WHO. She never stops working.

At Mill Hill, Zambon was part of the core group. She says there is a strong historical thread from Andrewes to the present day. She is not surprised that many of the people she knew 25 years ago are still fighting the flu. You take that passion with you.

Flu is a major public health threat even when the world is engulfed in a Pandemic. We haven't solved the problem yet.

She is involved in the response to Covid at UKHSA and Imperial College. The answer is yes, and no, she says.

The first sars virus was identified in 2003 by a team of international virologists, who analysed samples from . She led the UK's efforts to understand another coronaviruses, Mers, that turned up in two people who had traveled to the UK and spread to two others. She advised the WHO on it.

Thanks to the historical UK effort, the world is in a better place to deal with the coronaviruses. The UK has a vaccine effectiveness system that is second to none.

One or two examples of things that are representative are what the team at the national Influenza centre sends to the Crick. We will give it to them if we see anything strange. They are getting a digest of the viruses from us.

Each of the UK administrations has its own collection and analysis of flu samples. Dr Catherine Moore is the head of flu surveillance at Public Health Wales. Her field is looking at changes in the human and viral genomes to diagnose diseases. She developed a test to detect the genetic material of the coronaviruses within a month after it was recognised.

Moore shares the enthusiasm of the two men. She is the custodian of a system that has been running for 40 years. It's an absolute joy to be a small part of the Global Influenza Response System.

She says that gathering high-quality data that can indicate the drift of virus strains is more important than the number of flu samples they collect. The severe end of the spectrum is what they operate within the hospital system in Wales.

Moore has 44 GP practices. The Royal College of General Practitioners runs a network of 245 in England. The reports of flu diagnoses from selected practices around the country have been compiled by the GP. The transition to a system where flu samples are dispatched to centralised public health laboratories for testing took place in 1994. We all now know how to get the flu, and the GP used to be at the end of it all. Flu is easy to catch, so it was a high-risk occupation. People in low-risk groups with flu-like symptoms are now able to request home test kits and submit their own samples, thanks to Covid.

Prof Simon de Lusignan, an academic GP at the University of Oxford who runs the network organizing sample collection in England, says that one of the things the Pandemic has done is make it easier to take a sample. The flu kit is sent by a charity. The patient posts the throat swab to the lab teams for analysis. Some people need to see their GP in person, such as older people who may have a chest infection and small babies, but they should stay warm, drink fluids and get over it at home.

The vaccine strain selection meetings at the WHO started in the early 1970s and take place twice a year. They recommend the vaccine for the northern and southern hemispheres in February, with a meeting six months later for the southern hemisphere.

Three strains used to be recommended by the meeting. Manufacturing technology has improved to accommodate four. It is difficult. Chicken eggs can be used to grow some virus strains, but not all of them can be grown successfully. The committee usually gets it right about 70% to 80% of the time.

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It is an educated bet. The strains that are most prevalent in the world can change within six months. It can be painful when it does.

A mismatch is a nightmare. The experts got it wrong. The vaccine did not protect against H3N2 and the H1N1 strain of Flu A. The Texas strain of H3N2 was chosen by the meeting in February of last year. There was a different strain of H3N2 from Switzerland that was spreading faster. It was too late to change horses. If vaccine production was stopped, there wouldn't have been enough of it. The number of excess winter deaths in England and Wales was the highest in a decade.

Something strange is happening with Flu B. Victoria and Yamagata are the two B strains in the vaccine. At the start of the year, half of the intensive care unit beds in the UK were filled with people with Yamagata viruses. We haven't seen a B Yamagata lineage virus for over a year in these laboratories.

What is going on? The experts don't know. The flu hunters can't get ahead of it. Predicting what it will do next is difficult. There are strange things happening. China has only reported Flu B and no Flu A, the animal variety, so the speculation is that it is not circulating. Yamagata and one of the substrains of H3N2 have not been seen in the US since March 2020.

The answer has to do with the Covid epidemic. The winter of 2020-21 was the first year of the Pandemic. There wasn't anything to say about the flu. Social distance and mask-wearing prevented the flu and coronaviruses. They were able to clear the work at the Crick. They hadn't been able to do that since 2008.

Is it really because of all the mask-wearing that there are fewer reports of flu? Is it that people are not going to the doctor or hospital because they are staying at home with a raging fever?

It has been hard to read because of the Pandemic. She says she has never seen anything like this in her entire career.

She says that things were looking bad before the Pandemic hit. There were at least two H3N2 substrains that were not great matches for the vaccine in Wales. She says that Moore was expecting a tricky winter. Social distancing, masks and working from home are some of the measures that stopped the spread of the flu. We have had two years of nothing. In the rest of Europe, there is no signal for flu.

We’ve got a massive epidemic in UK birds. We have a human infection from it and birds are dying. Nobody seems to care

Flu can disappear and come roaring back. The strains for next winter have been chosen by the committee. It includes a B Yamagata-type strain in spite of its apparent disappearance, along with H1N1 (Victoria), H3N2 (Darwin) and B (Austria). There is less natural immunity against flu. People don't have the antibodies from getting ill, at least not the ones from recent strains.

All of us have immunity to the flu. People who were born before 1957 have some resilience to H1N1. It was present for 40 or so years after the 1918 pandemic, but older people have some protection against it. In the swine flu epidemic of 2009, it was working people who died. Moore asked if he had heard of the original antigenic sin. Your immune system remembers the first flu strain you came into contact with. You will be better protected against strains of H1N1 than against those of H3N2. The 1968-69 Hong Kong flu epidemic was caused by H3N2 and those who were born in the few years before that are likely to have more immunity. H3N2 hits old people harder.

Flu travels the world. There are no border controls in Hong Kong or Bangladesh. Sharing samples of virus is important for global cooperation. The flu virus will not be sent to countries with labs that are less secure. The country asked for samples from the UK. He was not impressed with their safety protocols. I asked if they would do this with the disease. They said they wouldn't do that. 40% of people who are exposed to this virus are killed. What is the difference?

Flu hunters have decades of experience but there are always anxious moments. Moore is worried about Alan and his ducks. The UK is in the middle of a massive epidemic of bird flu.

She can't comprehend the lack of interest. It is part of the same family of viruses. It's remarkable that flu has been treated like a cold. It's not. She says people need to be reminded to take flu seriously after the coronaviruses epidemic is over.

A Christmas epidemic like no other? They thought that in 1918.

We are getting on top of the flu. There are really positive developments in flu vaccinations. The vaccine gives older people a boost in their immune systems, which helps them fight the flu.

The future of flu vaccines is likely to be based on the success of the Pfizer/BioNTech and Moderna vaccines. The companies want to see how they can adapt it. If a new coronaviruses variant turns up, the vaccines can be altered quickly. Depending on the prevailing strains, the Covid and flu vaccines could be changed every year.

Will we ever get to a point where we don't have to worry about flu?

Our best hope will be vaccines. The flu hunters are in control of us.