Influenza pandemics often occur due to gene mixing from different strains causing an especially virulent strain to appear. Scientists from the U.S., U.K., and Japan have shown that avian influenza viruses circulating the world right now contain all the same or very similar genes that make up the incredibly virulent and deadly human strain that caused the 1918 pandemic, killing 3-5% of the world’s population which at that time meant about 40 million deaths.
Animal influenzas including bird or avian flu are thought to be the reservoir for deadly human strains like one which caused the 1918 pandemic. Scientists have noted recently that the genes of the avian flu viruses are very similar to the 1918 strain. Professor Yoshihiro Kawaoka of the University of Wisconsin-Madison followed this hunch by generating a strain call “1918-like” through combining genes from 8 current circulating avian flu virus strains.
Alarmingly, he found in testing that it has high potential to infect and cause transmission in humans Further, a mere seven genetic changes is sufficient to generate a strain that is airborne transmissible.
To focus their attention on the genes that contribute mostly to the enhanced infectivity of the “1918-like” strain and the normal avian strains, the researchers went gene by gene. They created systematically strains that had only one gene from the 1918 strain against the genetic background of an otherwise typical avian influenza strain, and were able to show that the genes hemagluttinin (HA) and an RNA polymerase (PB2) are the strongest contributors to the pathogenicity of the human generated “1918-like” strain. The HA gene is what the flu virus uses to latch onto the exterior of a human cell. The PB2 gene is what the flu uses to manufacture copies of itself. Both were found to be more efficient in the 1918 and 1918-like strains.
At first the researchers found that the “1918-like” strain was not transmissible. But with these two important genes in hand, they found that by adding them from the original 1918 strain give rise to transmission. This led them to try generating slight variations of “1918-like” to see whether it was quite easy to make a transmissible strain.
The researchers again focused on the HA and PB2 genes, making just a few mutations. Remarkably, one of their resulting strains, a “1918-like” with a mere 7 genetic changes across 3 genes, could infect and be transmitted to their test subjects.
One bright spot in the research is that blood from people who were vaccinated against the more normal, 2009 seasonal flu strain, also react to the dangerous 1918-strains generated in Kawaoka’s laboratory, giving rise to hope that perhaps the population has some protection already. Influenza research of this type requires high level of safety procedures and precautions. The work carried out by Kawaoka required what is called Biosafety Level 3. This entails the use of negative pressure hoods, proper safety attire, and restricted access during experimentation. The highest level is Biosafety Level 4 which is reserved for Ebola and other fast, deadly public health disease agents.
Despite the safety precautions, many people are fearful of the consequences of recreating a strain of influenza that even resembles the deadly one that struck the world in 1918. In 2012, Kawaoka came under heavy scrutiny for related work. The National Science Advisory Board for Biosecurity (NSABB) debated whether Kawaoka’s work was too dangerous to release even as a scientific publication to the public. Kawaoka vigorously defended the research by pointing out that it answers important questions demanded by the National Institutes of Health of the U.S. In the end NSABB permitted his 2012 research to be published in the journal Nature. The work reported here was published in Cell Host and Microbe, a sister journal of Cell.