A chance encounter lets it loose in New South Wales. Then again, it thrives on chance encounters. On January 20, 1919, two strangers find themselves in a railway carriage, sharing the long, rackety train journey from Melbourne to Sydney. It’s midsummer, so perhaps they have a window open, perhaps not. Either way, they can’t help but be near each other, breathing the same air, touching the same objects.

One is an Australian soldier who has served in the Great War that ended the previous November. The other is a civilian, his identity never discovered, his fate unknown. We do know he was ill, because the soldier – documented in medical records only as SL – will later report that his travelling companion was suffering from aches and pains and a fever.

Soon, the virus that has busily been reproducing itself in the first man jumps across to the second. Two days after the journey, SL comes down with the same symptoms. On January 23, and now very ill, he is admitted to Randwick Military Hospital in Sydney’s east, apparently suffering from the disease whose arrival everyone has been dreading. It has all the hallmarks of the terrifying pandemic influenza virus that scythed its way through the world’s population the previous year.

Forty-eight hours later, the doctor who examined SL, the nurse who first attended him, and the orderly who lifted him into bed, are all struck down by the illness. Admissions, mostly of people who have arrived from Melbourne, begin to grow. (Later it will emerge there were already 50 to 100 cases floating about in Melbourne earlier that month, undeclared as the pandemic infection.) With frightening speed, the trickle turns into a wave.

It’s a bitter pill for the authorities, who had dared hope they could keep the country free of the pandemic by being prepared. In the preceding months, Australia has been the only country in the world to have tried, and managed for a time, to stave it off by strictly enforcing maritime and land quarantine. They’d seen what had happened across the way in New Zealand, where it killed close to 9000 people in two months.

But the virus is wily. Now it has escaped into NSW, in a moment, by land, on a train, in a sneeze, a cough, on a table, a cup, a playing card. By the second week of April, around 150 victims are being admitted into Sydney’s hospitals every day. In Victoria, fatally slow to impose quarantine or declare infection, 685 people will die over about eight weeks early in the year, killed by the virus itself or its secondary complications, often a particularly violent case of bacterial pneumonia. By June, Western Australia is reporting a sizeable outbreak. Indigenous populations are hopelessly vulnerable, with a mortality rate approaching 50 per cent in some areas.

Many of the pandemic’s victims will survive but death becomes commonplace. Entire households go down. In southern NSW, in one Cooma family – the story recorded by her sister – a mother of five will pull through but wake from her fever to find the flu has taken her husband, her youngest baby and the child she was carrying.

Health authorities have scrambled to contain it – closing gathering places, from pubs and dance halls to schools and churches, quarantining infected households, setting up inoculation and isolation depots, and making it compulsory to wear a mask in public – but by April, when a second wave hits, the game is up. The best that can be hoped for is to slow the spread and thus not swamp the hospitals.

By the time the disease has run its course, it will have infected 40 per cent of Australia’s population, which stood at about five million.

To put that into perspective, last year’s seasonal flu in Australia, the most widespread in a decade, infected less than 1 per cent of the population. It caused an estimated 1127 deaths but that was in a population of 24 million. In 1919, the pandemic flu infected millions of Australians and killed at least 12,000, possibly 15,000.

And then it was over, reduced to a trickle of deaths by December that year. There were just the reports to be written; the mourning to be managed; and life, post-war, post-pandemic, to be embraced by those still standing.

It wasn’t quite a lucky escape. Still, it wasn’t anywhere near as terrible as it could have been. Despite those figures, Australia emerged comparatively unscathed from what would come to be called, without exaggeration, the deadliest plague in history and the single most deadly event ever recorded.

Elsewhere, the calamitous pandemic widely known as Spanish flu had got underway in the first half of 1918. It peaked in frightful numbers in October that year, just as the world was looking forward to an end to World War I.

It’s hard to comprehend the devastation this tiny virus caused. And harder still to believe we’ve almost forgotten about it, just a century later. We remember World War I, yet the war, for all its savage arsenals and endless waves of fine young men sent out as cannon fodder, was a far less efficient killing machine. The 1918 flu is thought to have infected up to 500 million people, about one third of the world’s population then. It’s likely to have killed a staggering 50 million people, and possibly as many as 100 million. That’s many more lives than the war stole. The war took four years to clock up its toll; the influenza pandemic managed the bulk of its work in less than a year.

Given the very real possibility of future pandemics – and we had one as recently as 2009, the “swine flu” – the 1918 experience is a chilling reminder of a pandemic’s speed and reach, and the chaos it brings. According to John M. Barry, contemporary medical historian and author of The Great Influenza: “It killed more people in 24 weeks than AIDS has killed in 24 years, more people in a year than the Black Death of the Middle Ages killed in a century. There were many echoes of the Middle Ages in 1918: victims turned blue-black and priests in some of the world’s most modern cities drove horse-drawn carts down the streets, calling upon people to bring out their dead. But this wasn’t the Middle Ages. It was 1918.”

One story from 1918 tells of four women playing bridge together late into the night. By dawn the next day, three were dead from the flu.

This new strain of influenza – an H1N1 virus – struck like a thief in the night. Victims would recall walking down the street and being hit by waves of giddiness, muscles turning to water, a crushing headache. Or they’d go to bed feeling fine and wake up a few hours later horribly ill. One story from 1918 tells of four women playing bridge together late into the night. By dawn the next day, three were dead from flu.

People in poor countries or living in crowded conditions suffered the most, but the pandemic didn’t restrict itself to the servants’ entrance. Famous people who caught it but survived include Kafka, UK Prime Minister David Lloyd George, Walt Disney (then a teenager in the Red Cross ambulance corps), Spain’s King Alfonso XIII, silent screen star Mary Pickford, Ethiopia’s Haile Selassie and even US President Woodrow Wilson, who fell so ill during the signing of the Treaty of Versailles that his own doctor suspected he’d been poisoned.

It killed the rich. It killed the creative. One of the early fatalities in the pandemic was Donald Trump’s German-born grandfather, Friedrich, who died aged 49 in New York, in May 1918. He felt ill while out walking one day and was dead the next. The French surrealist poet Apollinaire survived a shrapnel wound to the temple, only to die two years later, aged 38, from the flu. It also killed legions of soldiers; more than half the US troops who died in Europe were felled by influenza, not enemy fire.

Most influenza epidemics hit hardest among the very young and the very old. Not this one. To everyone’s surprise, the really soaring death rates were among healthy men in their prime, aged 20 to 40, and pregnant women. Of those mothers-to-be who survived, more than a quarter lost the baby.

Why so many of the young and fit? One theory is that the young adults of that particular time lacked the “right” kind of immunity. Exposure to an influenza virus when you’re young can increase resistance to a subsequent infection with the same or similar virus. While that generation were exposed to one kind of flu virus in their childhood (the 1889 pandemic), they were helpless against this new and different one. And their own healthy but frantic immune systems may have killed them. When the immune system goes into overdrive, it can produce what’s known as a cytokine storm and ravage the body.

That age spike is a phenomenon scientists are still trying to explain, because the answer could help predict who is at greatest risk in future pandemics. Could when you were born be a predictor of your immunity profile?

And where did the virus originate? Not Spain. It’s still hotly debated but prime suspects include China, France and even rural Kansas in the United States. It’s likely it sprang from livestock and found a way to spread from human to human. It arrived in waves – the first infecting many but killing few, the second lethal. In an age without antibiotics, it was the secondary infections such as bacterial pneumonia that caused most of the deaths.

By the time it had run its swift course, with a few final echoes in 1920, the pandemic had stalked the globe. Asians were 30 times more likely to die than Europeans. It reached even far-flung places like Western Samoa, as it was then, and Alaska, where it devastated locals.

Heartbreaking photos show ragged bands of little Inuit orphans huddled together, stunned to have had two healthy parents one day and none the next. Indeed, the world of 1918 was left full of orphans. A virus doesn’t have a heart.

Why should we care about a pandemic, however catastrophic, that happened a century ago? Because it will happen again, even with all our medical advances. It’s why scientists are still raking over clues from the 1918 outbreak. They want to crack the unpredictable workings of that great survivor, the influenza virus.

As far as anyone knows, the single task of a virus is to reproduce, yet it can’t do that by itself. It has to invade and take control of a living cell. The raided cell then begins producing not what it needs but what the viral genes demand: hundreds of thousands of viral proteins, to form new viruses. A mass of them then bursts through the cell surface, usually killing the cell in the process, to swarm through the body, invading other cells.

It doesn’t pay to sell a virus short. As John Barry writes, “[Even if] viruses perform only one task, they are not simple. Nor are they primitive. Highly evolved, elegant in their focus, more efficient at what they do than any fully living being, they have become nearly perfect infectious organisms. And the influenza virus is among the most perfect of these perfect organisms.”

Influenza viruses – there are a number – can be found somewhere in the world at any time. In temperate climates, influenza appears every year as seasonal flu, typically in autumn and winter, in familiar strains. As we know, seasonal flu can cause serious illness and death. However, it’s not usually fatal or extreme in most people.

Pandemic flu is a whole other story. It occurs when a flu virus that is new to humans, or at least very different from seasonal flu viruses, appears – one that most of the population has never encountered.

The 20th century saw three serious influenza pandemics: 1918, the Asian flu in 1957 and the Hong Kong flu in 1968, the last two combined killing a few million people. This century, the 2009 pandemic, known as swine flu, sprang up in Mexico and the US and swept the world. It wasn’t as bad as feared but still killed many thousands.

So does seasonal influenza, which kills roughly between 300,000 and 650,000 people globally each year. In industrialised countries, however, most of the deaths are among those aged over 65. Which isn’t to say we don’t worry about seasonal influenza, especially as it’s now known to greatly raise the risk of life-threatening conditions such as heart attacks. One recent Canadian study found that people, especially older people, were six times more likely to have a heart attack in the week after being diagnosed with influenza, compared to 12 months before or after the infection. Drops in oxygen levels and shifts in blood pressure, as the inflamed body battles the flu, could increase the risk of clots.

Flu’s potential to affect other organs, from heart to brain, played out in a tragic case last year. In August, Carey Alexander, a 13-year-old Sydney schoolboy, was taken to hospital suffering severe flu symptoms. The teenager was so ill he couldn’t walk, yet he was discharged in the early hours of the morning, despite his parents’ concern. Twelve hours later, Carey was dead. Cause of death was found to be borderline myocarditis, an inflammation of the heart muscle most likely brought on by the influenza A virus. It had led to cardiac arrest.

In much of Australia, last year’s seasonal flu was the most widespread in a decade, with two and a half times as many reported cases as in 2016. The season also ran longer than usual, giving plenty of opportunity to catch the bug. Both the old and the young were hospitalised. Says Dr Brendan McMullan, a pediatric infectious diseases specialist at Sydney Children’s Hospital: “We definitely saw more children in hospital with flu. Some had the usual things – breathing difficulties, fever, in need of intravenous support – but some had neurological complications; things like seizures and encephalitis. We do see those during flu seasons, but anecdotally at least, we saw a lot last year.”

The flu is a very clever pathogen because it’s able to juggle its genes … That’s the basic reason flu hasn’t gone away: it’s too mutable.

John Mathews, epidemiologist, University of Melbourne

Most people haven’t been vaccinated against flu, so it’s no surprise when they come down with it. What baffled many of those laid up in bed, aching and feverish, was why they had caught it, and badly, even when they’d had a flu shot.

A flu vaccine is far from perfect, that’s why. A new one has to be devised each year and, while it’s not quite a stab in the dark, it’s part educated guesswork, part gamble. The elusive holy grail for researchers is a once-only, one-size-fits-all flu vaccine that gives 100 per cent protection. If only influenza viruses weren’t quite so mercurial, so variable, the quest would be a whole lot easier. Meanwhile, the vaccine experts advising the World Health Organisation (WHO) have to settle for covering as many bases as they can, says Professor Kanta Subbarao, director of the WHO Collaborating Centre for Reference and Research on Influenza, in Melbourne.

“There are four strains of influenza that cause epidemics,” Subbarao explains. “Two influenza A viruses – H1N1, H3N2 – and two influenza B viruses, two lineages. In any given season, we don’t know which of these four will dominate or whether more than one will circulate, so we include all four components in the vaccine.”

So far, so good. The guesswork, the gamble, lies in deciding – four to six months ahead of the flu season, because that’s how long it takes to make the vaccine – which particular strains representing each of the four to include.

Not surprisingly, a lot can go wrong. For example, the experts could pick the wrong one and the vaccine virus doesn’t match the real virus that ends up circulating. That’s called a “mismatch”, but Subbarao doesn’t believe that’s what happened last year. She says the problem was that the vaccine virus underwent changes during the process of making it.

“Ninety-five per cent of the world’s vaccine is manufactured in chicken’s eggs. Unfortunately, when we take influenza viruses from somebody’s throat and put them into eggs to make a vaccine, there are a few small changes that the virus picks up along the way, in order to grow well in eggs.”

So the vaccine virus could be out of whack with some of the viruses actually going around and won’t induce protective immunity. For that matter, the vaccine against H3N2 hasn’t been very effective for the past five years or so, Subbarao acknowledges. And that’s unfortunate because H3N2 is one of the bad sorts, affecting the whole population. It causes more severe disease, more secondary complications and can be more of a killer for old and young. It was H3N2 that dominated last year, here and in the US especially, although influenza B was also around.

So why bother with a flu shot? Experts insist it’s better than nothing, provides at least partial protection, and can be effective against H1N1 and B viruses. It also lowers the risk of passing flu on to vulnerable groups, such as the elderly or chronically ill. The downside: it doesn’t help everyone; you can get it too early or too late for it to be of much use (late April to mid-May is now recommended); and it may not work as well in people over 65. It’s far from the magic bullet that medical science would like, as virologists such as associate professor Ian Mackay, of the University of Queensland, admit.

“It’s certainly not as effective as other childhood vaccines, like for mumps, measles, and so on,” Mackay says. “The flu vaccine’s effectiveness can be as low as 20 to 30 per cent. Some years, it’s been recorded as even less than that. A good year is about 60 per cent effectiveness.”

Mackay gives a deep sigh when Good Weekend asks why people so often say, “I had the flu shot and then I got the flu.” In other words, they’re convinced they got the flu as a result of the vaccination.

“This really makes me annoyed,” Mackay says. “I don’t know why anybody still believes that in this day and age. There is no infectious [active] influenza virus in these vaccines, so it’s impossible, literally impossible, to get the flu from the vaccine.

“Now, what is not impossible is that at the same time as you got vaccinated, somebody next to you sneezed and you picked up the actual flu then, before the vaccine had its two-week period to get you some immunisation.

“There are also multiples of flu virus circulating, so you’ve got usually a couple of influenza Bs and a couple of influenza As and lots of variants within that. So if the vaccine is only maybe 20 or 30 per cent effective, it will protect you against some things and not others.”

He also dismisses the notion that it’s because people are getting vaccinated that more virulent strains of influenza are springing up. In other words, that having a partially protected population is forcing different, more potent flu variants to emerge – to dodge the immunity – and spread. “There are a couple of arguments against that,” Mackay says. “One is that we don’t have any evidence for it. The second is that very few people in Australia, in some groups, get vaccinated. So very few children, for example, are getting vaccinated, which means people who are massive transmitters of flu virus aren’t getting a lot of vaccine. So that’s not what’s driving it. There’s a lot of variation [mutation] happening in the virus normally.”

For that matter, most of the new and exotic influenza strains start out in parts of the world where vaccination rates are low, such as Mexico or Southeast Asia. New strains are more likely to arise from poor animal husbandry practices, where the virus can jump species. Live animal markets, or wet markets, in Asia are a particular worry to authorities. (For the record, it’s a two-way street: humans often infect animals, especially pigs, with human flu.)

Aside from the hit-and-miss nature of the vaccines themselves, one of the unknowns is just how long immunity lasts, whether it’s the kind induced by vaccine, or by natural infection. “We do know immunity tends to wane over time,” explains John Mathews, an epidemiologist and professorial fellow in the School of Population Health at the University of Melbourne, “even the natural immunity, and it probably wanes even more quickly for vaccine immunity.” Age makes a difference, he says. “If you give a healthy young person vaccine, then the protective immunity might last six months, or even into the next season, and natural immunity tends to lasts longer. Neither of those will last as long if you’re elderly.”

Why? Because just as older people start losing their ordinary memory, their body’s immune “memory” also fades. It forgets how to fight off infections it might have encountered previously. It’s the reason two new and stronger-dose vaccines for older people have now been approved by the federal government for use here. And, in response to the number of seriously ill children hospitalised with flu last year, NSW and Victoria are now offering free influenza shots to all children aged six months to under five years.

As for this year’s upcoming seasonal flu, what can we expect? “There is no way of knowing if we’re in for a bad year,” says Kanta Subbarao. “If we’ve had a very bad season before, we hope that means everyone will have some natural immunity to that particular virus, so one of the others might have a chance at causing the epidemic – and H1N1 and influenza B epidemics are not as severe as H3N2. H3N2 sweeps through a community. Are we likely to see it happening again, two years in a row? Usually we say no, but the United States just had that happen, two years in a row. So really, nobody knows.”

More importantly, when are we due for another pandemic? For the past 300 years, the average has been three per century but viruses don’t follow a timetable. A “spillover event”, where a virus finds a way to survive in a new host, could happen at any time, with terrible consequences. Ebola was a spillover event, from bats to humans.

“The flu is a very clever pathogen because it’s able to juggle its genes,” says Mathews. “So if you happen to be infected by two different strains of flu virus and they get into the same cell, they can recombine their genes and produce something that’s quite novel.”

That ability – known as reassortment – to create an entirely new, or even just relatively new, hybrid virus, might explain why the 1918 virus was so devastating. It also explains why influenza is such a survivor. It’s constantly getting a makeover. Although its major impact in the hemispheres is seasonal, in the tropics it busily ticks over all year round, with plenty of time to shapeshift and bypass immunity we might have built up.

“That’s the basic reason flu hasn’t gone away: it’s too mutable,” Mathews says. It’s why other vaccines provide more permanent protection. “For example, the virus that causes smallpox can’t change in ways to escape immunity induced by a previous smallpox infection or vaccination.”

Still, it’s not as if world health authorities are asleep at the wheel. In recent years, for example, the WHO has been keeping a close eye on H7N9, an avian flu virus in China. For now, it’s only being transmitted from bird to human, not human to human, and, says Ian Mackay, a poultry vaccination program seems to have reduced the likelihood of a spillover.

That’s also good news for animals. In past years, mass slaughters have quietly been carried out on infected livestock as a pre-emptive measure. In 2003, for example, the WHO identified a new virus in European poultry farms. It infected 83 people and killed one, a vet. Public health authorities in the Netherlands, Belgium and Germany slaughtered nearly 30 million animals, mostly poultry but some swine.

We do know another pandemic will happen. We just don’t have a date. Says Kanta Subbarao: “There was one famous influenza virologist who said, well, we had a pandemic in 1957, the next one in ’68, then there was a novel virus that emerged in ’77. So he wrote these papers saying it would happen every 10 or 11 years. Everybody waited the 11 years and nothing happened.

“It’s notoriously difficult to predict what happens with flu. What most people will say comfortably is that we will have a pandemic in the future. When the right combination of events come together – a virus that has acquired the properties to be able to infect and spread in people and a population that is not immune – you’ll have a pandemic.”

To read more from Good Weekend magazine, visit our page at The Sydney Morning Herald or The Age.