Scientists in the Dutch city of Rotterdam know precisely what it takes for a bird flu to mutate into a potential human pandemic strain -- because they've created just such mutant viruses in the laboratory.
So as they watch with some trepidation the emergence in China of a strain of bird flu previously unknown in humans, they also argue it vindicates their controversial decision to conduct these risky experiments despite fierce opposition.
Above all else, what the world needs to know about this new strain of H7N9 bird flu is how likely it is to be able to spread efficiently among human populations.
And according to Ab Osterhaus, a world leading flu researcher who is head of viroscience of the Erasmus Medical Center in the Netherlands, studies his team and another in the United States have been doing are the best way to find out.
"At the moment we don't know whether we should go for a full-blown alert or whether we can sit back and say this is just a minor thing," Osterhaus told Reuters in a telephone interview.
"(To answer that) we need to know what this virus needs to become transmissible."
With 10 cases of the new H7N9 bird flu confirmed in people in China since Sunday, including at least four deaths, Beijing is mobilizing resources against the threat.
Japan and Hong Kong said they had also stepped up vigilance against the virus, and Vietnam banned imports of Chinese poultry.
Making a monster?
The scientific work that can answer key risk questions is known as "gain of function" or GOF research. Its aim is to identify combinations of genetic changes, or mutations, that allow an animal virus to jump to humans.
By finding the mutations needed, researchers and ultimately health authorities are better prepared to assess how likely it is that a new virus could become dangerous and if so how soon they should begin developing drugs, vaccines and other scientific defenses.
Yet such work is highly controversial.
When two teams of scientists announced in late 2011 they had found out how to make a another strain of bird flu - H5N1 - into a form that could spread between people, alarm bells rang so loudly at the U.S. National Science Advisory Board for Biosecurity (NSABB) that it took the unprecedented step of seeking to censor publication of the studies.
In a series of GOF experiments, the scientists induced mutations into the H5N1 virus that made it transmissible among mammals through droplets in the air.
The NSABB said it feared details of the work, carried out by Ron Fouchier at the Rotterdam lab and by a second team led by Yoshihiro Kawaoka at the University of Wisconsin, could fall into the wrong hands and be used for bioterrorism.
"The fear was that they were making a monster," said Wendy Barclay, a flu virologist at Imperial College London.
An acrimonious debate ensued and flu researchers around the world agreed to a year-long moratorium on further experiments of this type until fears could be allayed.
Yet throughout the moratorium, some scientists argued the research was vital to preparing for the next flu pandemic, and that to abandon it would leave the world in the dark when new flu strains emerged.
Viruses jump from animals to humans
Barclay, who was a signatory on an open letter in January from 40 scientists calling for an end to the moratorium on bird flu transmissibility research, says current events in China underline why.
"What this H7N9 emergence does is show for sure that flu will emerge at regular intervals from animal sources," she said.
"And it underscores the fact that for each virus, we don't know whether it will be readily transmissible between humans when it emerges, or whether it will turn out to be a zoonotic dead end because when it reaches the human host there are barriers it can't overcome."
Some scientists, however, remain unconvinced of the value of deliberately manipulating viruses in laboratories - however secure they may be - to create and then analyze mutant flu strains that can spread between mammals.
Writing in the scientific journal Nature last week, Simon Wain-Hobson, chair of the Washington-based Foundation for Vaccine Research in the United States, accused flu researchers of going down a dangerous blind alley.
"The world has never been more densely populated," he wrote. "Is it appropriate for civilian scientists to make microbes more dangerous?"
Osterhaus, who has looked at genetic sequencing data from the new H7N9 bird flu strain samples in China and found some worrisome mutations have already occurred in the H7N9 strain, says such concerns are far outweighed by the fear of not knowing the potential risk of an emerging new virus.
"This virus might be on the brink of gaining function of transmissibility (in humans). I think it's crucial to know the rules of the game."