In April 1789, just 15 months after the arrival of the First Fleet, smallpox ripped through Sydney's Indigenous population.

"Every boat that went down the harbour found them laying dead on the beaches and in the caverns of rocks," First Fleet seaman Newton Fowell wrote.

"How this disease got among them it was impossible to tell."

Smallpox would go on to almost wipe Gadigal people in the Sydney area.

"There would have been a 50 to 90 per cent death rate, which is a huge number," historian Craig Mear said.

"It's gone from Sydney all the way down to South Australia. And they were the major population centres of the Aboriginal people."

How Australia's first pandemic started, and more importantly, who started it, has been fiercely argued for more than a century.

"It is a real mystery," Henry Reynolds, another historian, said.

"None of the people arriving in Sydney in early 1788 had smallpox.

"The long sea voyage meant that either people would have died or got better. So they didn't carry smallpox from Britain."

A painting by William Bradley of members of the First Fleet meeting Indigenous people. ( Supplied: State Library of New South Wales )

A 'wild supposition'

"The surgeons brought smallpox in vials," Mr Mear said.

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Before vaccination, doctors commonly kept jars of smallpox scabs which they would grind up so that they could be sniffed up through the nose or rubbed into scratches in the skin, in a process called variolation.

The aim was to cause a mild case of smallpox, triggering immunity to a more serious infection.

Watkin Tench, the great chronicler of the First Fleet, confirmed doctors brought smallpox with them.

"It is true, that our surgeons had brought out variolous matter in bottles," he wrote.

"But to infer that it was produced from this cause were a supposition so wild as to be unworthy of consideration."

Tench himself wondered if earlier explorers like La Perouse, Cook or Dampier brought the virus, but then asked why smallpox hadn't been seen before then.

Did smallpox arrive from northern Australia?

Throughout the 20th century, many historians suggested smallpox may have been introduced by Asian seafarers in the north of Australia, which then reached Sydney a year after the arrival of the First Fleet.

"It's stretching belief a bit to imagine that it just arrived at the time of the British," Mr Reynolds said.

"People with smallpox have very, very scarred faces and it would have been obvious that there had been a smallpox epidemic, but not even the oldest of the local Aborigines gave any sign."

For Mr Reynolds, that leaves the First Fleet as the only realistic source of the pandemic.

So could smallpox then have been introduced deliberately?

"Everyone, particularly military people, knew that smallpox could have a dramatic effect on war and campaigns and battles," Mr Reynolds said.

"There is no doubt that smallpox was certainly used against Indians in America."

Major Ross — a perfect suspect

Among the military officers of the First Fleet was a man who fought in America — the commander of the marines, Major Robert Ross.

"Without exception the most disagreeable commanding officer I ever knew," was how fellow First Fleet marine Ralph Clark described Major Ross.

"He'd had experience of smallpox use in America, both in the Pontiac rebellion of 1763 and in the American War of Independence," Mr Mear said.

"So he knew its uses and he was a fairly vile sort of a man, by all reports."

Mr Reynolds says there is no evidence directly linking Major Ross to the smallpox pandemic.

Convicts who fought with Aboriginal people have also been suggested as suspects.

"It just seems to me possible that they, would have known what these bottles (of smallpox) contained, they would have known the effect," Mr Reynolds said.

"And it's just possible that they were the ones who thought, 'we'll get back at those blacks, we'll use this material.'

"But, you know, that's totally speculative."

Mr Mear said he wondered if smallpox was introduced through clothing brought from Britain, which he said may have harboured active smallpox viruses.

"So ,if they gave clothes out to the Aboriginal populations, it could be fatal," he said.

A drawing by William Bradley showing British troops firing at Indigenous people. ( Supplied: Mitchell library, State Library of New South Wales )

Australia's first pandemic may remain a mystery

Both Mr Reynolds and Mr Mear agree that unless some extraordinary new evidence emerges, it may never be known exactly how smallpox came to devastate Indigenous Australia.

However, both agree that the impact of smallpox was profound.

"When the settlers moved into the interior, they were meeting communities that were still suffering the demographic effect of the smallpox epidemic," Mr Reynolds said.

"So the populations were much smaller than they had been. And that undoubtedly made the push of the Europeans into the interior of South Eastern Australia, much easier.

Mr Mear goes one step further, wondering if the First Fleet would have survived without the pandemic.

"Aboriginal people were certainly becoming much more aggressive towards the settlers.

"The settlement could have been wiped out without the smallpox. So in my reading of it, yes, it changed the course of history."