Another day in bed as Greg’s Spanish Flu, aka Merville Fever, continued. Still no flying for him. But what was the origin of Spanish Flu?
Diary
Saturday June 22nd. Stayed in bed all day.
Origin of Spanish Flu
After yesterday’s excursion into epidemiology, here’s a bit of a voyage into virology. (We’ll return to aviation soon enough.)
Let’s get one thing out of the way first: the origin of Spanish flu is probably not Spain. It is generally thought that the name came about because Spain’s neutrality in the First World War merely permitted more extensive reporting of the pandemic. See Trilla et al. Clinical Infectious Diseases 47(5) 668–673 (2008) (https://doi.org/10.1086/590567) for more.
We now know – but in 1918 they didn’t – that the causative agent of flu is a virus. At the time, it was thought to be caused by a bacterium, Haemophilus influenzae, which is now known to be the cause of various other conditions, including some cases of bacterial meningitis.
Viruses
Like all viruses, influenza virus isn’t really a living entity. It’s a package of genetic material (in this case RNA rather than DNA) wrapped up in a protein-studded lipid (fatty) coat. It can’t reproduce on its own. It can only replicate by infecting a host cell and hijacking the cell’s replication machinery. The infected host then churns out vast quantities of progeny virus, and the cycle begins again.
Today we know what the virus looks like. Here is an electron micrograph of a recreated form of the 1918 Spanish Flu virus:
Surface Proteins and Subtypes
Among the proteins studding the lipid coat of the virus particles (which are in the order of 100 nm in diameter), two that are important for the way that the virus infects its host cells are haemagglutinin (abbreviated HA or H) and neuraminidase (NA or N). Haemagglutinin is involved in the virus binding to the host cell, and neuraminidase assists in viral trafficking. Here’s a schematic picture of a flu virus particle:
Although there are three kinds of influenza virus, A, B and C, it is only influenza A that poses a serious threat to public health. The 1918 so-called Spanish Flu was an example of influenza A. We now know (see below) that it was a subtype known as H1N1, so called because it contains haemagglutinin of subtype 1 (of 16 known subtypes) and neuraminidase of subtype 1 (of 9). Formally, the Spanish Flu virus is therefore known as 1918 A(H1N1) influenza.
Reassortment
When a flu pandemic arises, it is often because of genetic reassortment of the virus. This arises when two different viruses infect the same individual (human or another susceptible species such as pigs or birds). Because the RNA in the nucleus is in different segments, these segments can reassort to give a new genetic combination. In this way, an H1N1 virus might reassort with an H5N3 virus to give an H5N1 virus, say (not a random example, but that is another story). And the human immune system might not have ‘seen’ this reassortment before – at least in the recent past – and therefore have no effective immunity against it.
And the Origin of Spanish Flu is…
…actually not clear. It seems that the reassortment mechanism just discussed did not give rise to the Spanish Flu virus in 1918. Taubenberger and colleagues, working in the mid-1990s with archival influenza autopsy materials collected in the autumn of 1918, sequenced the RNA of the virus and determined it to be an H1N1 subtype and similar to a bird flu virus from an unknown source. (For a review, see Taubenberger & Morens “1918 Influenza: the Mother of All Pandemics” Emerg Infect Dis. 2006;12(1):15-22 (https://dx.doi.org/10.3201/eid1201.050979)). Similar to a bird flu virus, that is, but not exactly the same: it had a mutation, or mutations, that enabled it to infect humans – and pigs. So this proposed bird flu-like virus seems to have been new – immunologically speaking – both to us and to pigs.
It has to be said that not everyone goes along with the Taubenberger bird virus origin theory. A lively debate in the pages of Nature testifies to that. And even Taubenberger says that it is not just a question of a single mutation arising in a pre-existing H1N1 bird flu. That theory is discounted by the large number of mutations found between the 1918 virus and known bird flu viruses. For the moment, the answer to the question “what is the origin of Spanish Flu?” is the unsatisfactory “we don’t really know”. But the bird flu theory is still a contender.
A Live Issue
Intriguingly, this is not merely a question of historical interest. The legacy of the 1918 Spanish Flu is still with us today. The reason that Taubenberger & Morens called the Spanish Flu pandemic in 1918 “the mother of all pandemics” in the title of their 2006 review article is that, in their words :
All influenza A pandemics since that time, and indeed almost all cases of influenza A worldwide…, have been caused by descendants of the 1918 virus.
Yet another long shadow cast from the years of the Great War.