One Mutation Away?
It’s almost like a mantra
“But scientists fear H5N1 could mutate into a form easily passed between humans and spark a human flu pandemic.” (@IrelandOn-Line, 17 Feb 2006)[1]
“Should it adapt to be able to be transmitted from human to human, international health experts warn, bird flu could spark a global pandemic, infecting as much as a quarter of the world's population and killing as many as 180 million to 360 million people ... ” (Zuckerman, 2005)[2]
When you read reports about bird flu, you will find a lot of statements like these. Some commentators claim that adaptation of the bird virus to us humans is inevitable. Especially on the Web, you will also find claims that “The avian flu is only one mutation away from spreading from person to person.”[3]
A probable source for such claims is the testimony on influenza preparedness before Congress by the Director of the National Vaccine Program at the Department of Health and Human Services: “… many scientists believe that it may be one mutation away from developing the ability to efficiently transmit from person to person.”[4]
Others researchers and commentators say that the virus will not mutate to this fearsome form, since it has not done so in the more than ten years in which it had the opportunity. So, who is right and how can we find out?
Really only one mutation?
The short answer is that nobody knows which way the H5N1 virus will mutate, and that we only have crude ways of estimating how close H5N1 is to a pandemic strain. One way to get at an approximate answer is to compare the genetic sequence of present-day H5N1 strains with the H1N1 strain that has killed so many humans in 1918.
If you are interested and willing to invest a bit of time and are not afraid of unfamiliar words, you can check up on the validity of such claims yourself. A great tool for comparing sequence information on different strains of influenza viruses is the “Influenza Virus Resource”[5] of the National Center for Biotechnology Information (NCBI) at NIH. You can download the sequences of amino acid building blocks that are expressed by the genes of particular H5N1 virus isolates, and count the positions that match or don’t match the 1918 H1N1 strain.
A diligent poster on a Web site has done just that, and here is an example of what he found:
Gene segment |
Number of amino acids |
Number of differences | |
H1N1, 1918a |
H5N1, 2005b | ||
PB2 |
759 |
759 |
20 |
PB1 |
757 |
757 |
14 |
PA |
716 |
716 |
13 |
HA |
566 |
--- |
-- |
NP |
498 |
498 |
14 |
NA |
469 |
469 |
75 |
M2 |
97 |
97 |
8 |
M1 |
252 |
252 |
12 |
NS2 |
121 |
121 |
6 |
NS1 |
230 |
225 |
20 |
Total number of differences |
182 | ||
a The H1N1 virus sequence is that of the A/Brevig Mission/1/1918 virus (the HA sequence is from A/South Carolina/1/1918)
b The H5N1 virus sequence is that of the A/human/Thailand/676/2005 virus.
At least in this comparison, the H5N1 virus isolated from an infected human in Thailand is not very close to the 1918 virus. Admittedly, this is a rather crude way of looking at it, because the H5N1 virus may become more dangerous by mutating in ways not found in the 1918 strain, but it’s one way in which one can track how H5N1 virus changes.
The need for sequence information
In the hands of competent researchers, analyzing sequence information from individual virus isolates is our best chance of reducing uncertainty. Relating sequence data to virus behavior, and tracking changes in virus sequences over time and as it spreads geographically, can help us determine whether it is time to stock up and prepare or keep a watchful wait.
What researchers need urgently to do this work is timely access to complete sequence information of H5N1 viruses as they are isolated from animals and especially humans. Unfortunately, some countries are unable or unwilling to report sequence information to international agencies, and parochial attitudes within such agencies stand in the way.
We’ll discuss this pressing issue further. Stay tuned.
[5] http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/select.cgi
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