Branded as “crazy” by experts, an international team of scientists has generated an influenza virus with similar characteristics to the 1918 pandemic influenza virus that killed an estimated 50 million people. This controversial new study, which has split the scientific community, aimed at investigating the possibility of a pandemic influenza virus emerging from the pool of influenza viruses currently circulating in wild birds. The study has been published in Cell Host & Microbe.
The virus that caused the 1918 flu pandemic (H1N1), which remains the most devastating outbreak of disease recorded yet, is thought to have avian origins although some controversy surrounds this suggestion. It is known that wild birds possess a diverse pool of influenza viruses, some of which could produce viral proteins with similar characteristics to those found in the 1918 pandemic influenza virus. It is therefore possible that these naturally circulating viruses could result in the emergence of influenza viruses with similar pandemic capabilities, but the likelihood remained unknown.
In order to assess the risk of this happening, an international team of researchers headed by Yoshihiro Kawaoka of the University of Wisconsin-Madison first searched online databases in order to find out if any close relatives to the 1918 viral proteins exist in current the avian influenza virus pool. They identified eight genes which produced proteins that were highly similar to proteins produced by the 1918 virus.
The team then used a technique called reverse genetics to generate an influenza virus containing these eight viral segments and assessed its pathogenicity. The virus, which shared 97% amino acid (the building blocks of proteins) similarity with the 1918 pandemic influenza virus, had an intermediate pathogenicity; it was more pathogenic than circulating “authentic” avian influenza viruses but less pathogenic than the 1918 strain in mouse and ferret models. Ferrets are used to study influenza virus infection because they exhibit similar symptoms to humans infected with influenza A virus.
Influenza viruses have the capability of initiating a pandemic if they can be efficiently spread between humans. In order to deduce whether the engineered virus was highly transmissible, the team compared transmission in ferrets with the 1918 virus. They found that the new virus did not transmit among ferrets via respiratory droplets, which is how influenza viruses are predominantly spread, but the 1918 virus did.
The scientists then investigated the number of changes that would be required for this novel virus to become as transmissible as the 1918 virus. They found that a mere 7 mutations in 3 genes resulted in a virus with similar transmission efficiencies to the 1918 virus. According to Kawaoka, these data suggest that the genetic ingredients for a potentially pandemic virus exist in nature and could combine to form such a virus.
“The point of this study was to assess the risk of avian viruses currently circulating in nature,” said Kawaoka in a news-release. Furthermore, Kawaoka explained that studies such as this will help scientists concoct strategies to counter pandemic viruses.
Another interesting finding of the study was that sera from individuals vaccinated against the current seasonal influenza strain reacted strongly with the new virus, which could insinuate that this vaccine offers some protection.
Not everyone agrees that this research is necessary, however. Although the studies were conducted in containment facilities, the study has been labeled foolish by some. “The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous,” said Lord May, former president of the Royal Society. “Yes, there is a danger, but it’s not arising from the viruses out there in the animals, it’s arising from the labs of grossly ambitious people.”
Marc Lipsitch, professor of epidemiology at Harvard School of Public Health also expressed concerns: “I am worried that this signals a growing trend to make transmissible novel viruses willy-nilly, without strong public health rationale. This is risky activity, even in the safest labs. Scientists should not take such risks without strong evidence that the work could save lives, which this paper does not provide.” He also argues that the chances of a virus similar to the one created in this paper emerging in nature are remote.
But Kawaoka defends his work and says that others underestimate the importance of studies such as this which could eventually help scientists to reliably identify viruses with pandemic capabilities.