The Cryptic Virus – Determining the Origins of Pandemic H1N1

The term “swine flu” is often used to describe the virus causing the current pandemic of influenza. This is unfortunate because it implies that we know that this virus originated in pigs.

We don’t.

How can we tell where pandemic H1N1 came from? The most definitive answers will come from comparing its sequences with those of other flu viruses. I recently did this with pandemic H1N1, specifically, the A/California/04/2009 isolate. This isolate was collected from a 10 year old boy on April 1, 2009. It is one of the first isolates with sequences from all 8 genomic segments of the virus. It is also one of the best studied isolates.

To determine the most likely origin of pandemic H1N1, it is important to approach sequence analysis without bias. By this I mean, to consider all possible sources for the virus and to see which hypothetical explanation best fits the available data. There are three main possibilities:

1. Evolution from existing virus or viruses. This may be due to reassortment, recombination, mutation or a mixture of the three. If this hypothesis is correct, segments of pandemic H1N1 should match very closely sequences from existing viruses.

2. “Bad vaccines”. It is possible that a live vaccine or an improperly prepared killed vaccine was administered incorrectly and thus a lab-created virus escaped “into the wild” and ultimately infected people. If this hypothesis is correct, pandemic H1N1 viral sequences should match vaccine sequences very closely. They would also expected to match currently circulating viruses that are causing human or animal disease.

3. Gene synthesis. In the year 2009, it is possible to create viruses from scratch based on sequence alone. This hypothesis is difficult to prove because the sequences of such a virus could be made to mimic naturally occurring viruses. The only positive evidence would be subtle sequence anomalies, possibly involving codon optimisation.

Many observers noted early in the pandemic that sequence comparisons did not reveal a good match with any known virus. Because some of the genomic sequences most closely resembled viruses found in pigs and because pigs are thought to be good candidate animals for reassortment of viral genomes, an intense search was launched for “the smoking pig”, an animal harboring the virus that crossed the species barrier to cause the current pandemic in humans. Contrary to the popular media story line, no such pig was ever found. To this date, there is no evidence that pandemic H1N1 arose in pigs. Hence, the term “swine flu” is premature, at best.

Even a cursory examination of the available sequences raises many difficult questions for those who suggest a natural origin for the new H1N1 virus. Sequences from different genomic segments most closely resemble viruses that infect: North American birds, European pigs,  North American pigs, Chinese pigs,  and a man in Wisconsin who had been infected by a pig. And some pandemic H1N1 sequences seem about equally similar to viruses that infect birds and pigs. How could a virus naturally evolve from avian, pig and human influenzas that are only found in North America, Europe and China?

The current hypothesis advanced by proponents of natural evolution is that there has been cryptic spread of the antecedents of the current virus in pigs, perhaps for years. Further, pigs from Europe and Asia are suggested to have been smuggled into North America, bypassing normal quarantine and testing procedures. These “secret pigs” then are supposed to have mixed with North American pigs to create the pandemic strain. Although possible, this is not a very convincing scenario.

Dr. Adrian Gibbs has noticed many of the difficulties associated with the natural evolution of pandemic flu and proposed an alternative hypothesis: that an improperly prepared vaccine was somehow released into the wild and ultimately infected a human. As noted above, the main problem with this idea is that pandemic H1N1 does not match the sequences of any known vaccine. Nor does it match any known disease for which a vaccine would be useful. It is possible that there is a “secret disease” and a “secret vaccine” that we are not aware of. But at this point, no evidence has been provided to support this hypothesis.

The final possibility is gene synthesis. If there was any convincing evidence that either of the first two hypotheses were true, there would be no reason to consider an artificial virus. Unfortunately, we don’t have any supporting evidence for either a naturally evolving virus or a “bad vaccine”. Hence we are left with our third hypothesis: gene synthesis. This is a difficult one to prove. The only evidence will be subtle anomalies in nucleotide and protein sequences.

Whatever the origin of the pandemic H1N1, at this point, we can say it involves one of these three secrets:

a secret pig

a secret vaccine

a secret synthesis

In an attempt to distinguish between these “secret” alternatives, I will consider the function and sequences of each of the 8 genomic segments, and their proteins, in an upcoming series of blogs.


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