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One of the greatest public health fears is an influenza pandemic. Epidemiologists have worried that the avian flu virus, formally known as H5N1, could mutate enough to sicken and pass among humans, who would not have an immunity to it. A universal flu vaccine would prevent such a threat: like some childhood shots, it would confer lifelong protection—and eliminate seasonal flu injections as well. For the Insights story, "Beating the Flu in a Single Shot,"appearing in the June 2008 Scientific American, Alexander Hellemans talked with Walter Fiers of Ghent University in Belgium. Fiers discovered a key protein on the influenza virus that could serve as a target for a universal vaccine; the drug has shown promise in an early clinical trial. Here is an edited excerpt of the interview, translated from Dutch.
Before you started working on the influenza virus, you were actually decoding genomes in the 1960s. Did this then-new technique help you in tackling the influenza virus?
My first research project was the determination of the sequence of nucleotides, a technique which was still in its infancy. The problem we were faced with in 1960-62 was that the determination of the genetic code—and the linking of code words to amino acids was based on synthetic polynucleotides. This did not explain which of the 64 possibilities of combinations occur in nature. This was our first project: the determination of the sequence of a real gene as it occurs in nature, and this was from the genome of the bacteriophage MS2.
Why did you choose this virus?
If you want to resolve a problem, you have to return to the simplest form in which this problem can be solved—this is reductionism. So we looked for a very small virus. We looked for the smallest possible genome: a bacteriophage with RNA. We elucidated the nucleotide sequence of a gene, and this was published in 1972. The bacteriophage MS2 contains four genes, and we published the complete genome in 1976.
So this was the first genome to be sequenced?
This was the first complete genome that we have sequenced. From there, with the technology we developed, at that moment, it was the largest molecule from which the primary structure was determined. Subsequently, researchers have switched to DNA-containing organisms and now have reached humans. But the automation required for this was far beyond our capabilities.
You switched from studies of bacteriophages to the influenza virus in the 1970s. Why?
Because it had an enormous medical relevance and importance. The problem we had then, which we still have today, is the phenomenon of drift and shift. If it were not for drift—the accumulation of point mutations—and shift—the interchange of genes from animal and human strains—we would have had a vaccine based on serological data. Because of drift and shift, the World Health Organization [WHO] makes a prediction every year about the strain that is the most likely to cause an epidemic in the Western world. Based on this information one makes a vaccine the classical way, growing them in eggs, something that was started just after the Second World War, around 1950. And this is still being done the same way.
How do organizations, such as the WHO, predict these mutations?
On the basis of an epidemic that spreads out in other parts of the world. For example, epidemics that happen in the Northern Hemisphere usually mirror what previously happened in the Southern Hemisphere. And if we know against which epidemics our population here has acquired immunity, we can then see whether there are other advancing epidemics that will not be stopped by the local immunity, making it probable that it may cause an epidemic here.