Flu pandemics are a sure thing. But what is not a sure thing at all is which viral strain will be the one to cause the next pandemic.

The most recent potential candidate is the H7N9 strain that first reared its head earlier this year. To date, there have been around 130 confirmed infections and 30 deaths from the new strain.

Like H5N1, the even more lethal strain of influenza that is still sporadically rearing its head, the number of cases has been small. But the worry is what will happen if the strain becomes easily transmissible.

Researchers at the Chinese Shantou University and the University of Hong Kong, with U.S. and Chinese colleagues, reported last week that such a switch to easy human-to-human transmissibility is likely possible for H7N9.

In experiments published in the May 23, 2012, online issue of Science, they showed that the virus does not currently spread via the air between ferrets – which are the best model for humans as far as the flu virus is concerned – but does spread via direct contact. They concluded that "under appropriate conditions human-to-human transmission of the H7N9 virus may be possible."

Whether such transmission ever comes to pass, especially at the pandemic scale, is anyone's guess.

At the annual meeting of the American Society for Microbiology last week, Ron Atlas, of the University of Louisville, reminded the audience at a panel discussion on flu viruses that "before [H7N9], it was concern over H5N1."

That strain, whose death rate is even higher than the roughly 25 percent of H7N9, has been giving health officials nightmares for a decade now. Although the scientific consensus is that H5N1 could mutate in a way that would make it easily transmissible between humans, to date it hasn't.

H5N1 is "just a couple of mutations away" from easy transmissibility," Albert Osterhaus, from the Dutch Erasmus Medical Center Department of Viroscience, told the panel audience. "It's very easy for the virus to accumulate these mutations, and yet, it did not happen." The question is whether the reason is luck, or something about the virus that researchers do not yet understand: "To a certain extent, it's still a black box."

And researchers worry not just about strains that cause high lethality in humans. In fact, Robert Webster, of St Jude Children's Research Hospital, said that another strain, H9N2, is "probably the most dangerous [strain] out there," H9N2 is spread across all of Eurasia in the primary host of flu virus, namely, chickens. It causes no apparent disease, but shares a lot of genetic material with H7N9, suggesting that it, too, could turn lethal.

"We've been watching it evolve in Bangladesh, and it's scary how it's become humanized," Webster said.

Given the impossibility of predicting which strain will cause the next pandemic, what's needed is either a universal vaccine or general pandemic preparedness.

Researchers are making progress on the former. In the May 24, 2013, issue of Nature, Sanofi scientists reported success in generating broadly neutralizing antibodies with a vaccine made up of self-assembling influenza nanoparticles, and FDA researchers reported on a viral vector last month that might be useful for a universal vaccine.

But until such a vaccine becomes a clinical reality, the best defense is general preparedness. Such preparedness starts with access to information, and scientists on the panel praised China – where most pandemic flu strains originate due to the country's high concentration of both pigs and humans, as well as its poultry markets – for its openness in reporting cases, and their outcomes.

Though lax regulation and oversight remain a problem, China has opted for greater transparency and collaboration with the FDA since scandals like contaminated heparin severely damaged its reputation. (See BioWorld Today, May 23, 2013.)

In terms of pandemic threats, too, Chinese officials appear to have learned from the past. "The H5N1 episodes, we didn't know what was going on in China," Webster said. "This is night and day."

Scientific openness has been a bone of contention just as governmental openness has. Research on highly lethal influenza strains like H5N1 and H7N9, has raised concerns that such knowledge could be used for nefarious purposes. Such concerns culminated in a temporary voluntary moratorium on such research in 2012 and early 2013. (See BioWorld Today, Jan 24, 2013.)

But the panel was unanimous in their opinion that what is needed is more research, not less.

Osterhaus did not dismiss the possibility of bioterrorist applications of research on highly lethal flu strains altogether. But "the idea that bioterrorists would be able to make these viruses – I don't think that's very likely," he said. "These are sophisticated experiments with a high likelihood of injuring yourself." He laid the risk of high death tolls from influenza viruses squarely at another door: "Nature," he said, "is the main bioterrorist."