Tag Archives: avian flu

Evolving Avian Flu for Enhanced Transmission

Avian influenza (H5N1) infections have about 60% mortality rate. Only around 600 people are known to have been infected, so it is still a very rare but certainly deadly disease. Those infected are individuals who have direct contact with infected birds. Although some cases of human-to-human transmission have been suspected, good evidence for this is lacking. Its an important virus in agriculture too. When H5N1 is identified in domestic birds, the usual response is a massive cull, resulting in millions of birds killed and farmers left in great financial difficulty.

The question of whether such a virus could mutate to cause a human pandemic is an important one. In the history of flu pandemics, only H1, H2, or H3 viruses have been involved. Is it impossible for H5 to cause a pandemic, or has it simply not happened yet? If it could, would it retain the same level of pathogenicity, or in adapting to human-to-human transmission, would it become less virulent?

To answer the question of the possibility of human-to-human transmission, some researchers in the Netherlands performed some experiment to evolve H5N1 to become more transmissible. They infected ferrets, and over several passages (moving the virus from one animal to the next) managed to encourage transmission between ferrets. The virus adapted to transmission between ferrets, changing slightly from the original virus. The changes are minor, only 5 mutations in 2 genes. However, this research has caused some significant concern: they have generated a transmissible form of a highly pathogenic virus. Is this a good idea?

Importantly, the results have not been published so all this information is from news reports and interviews. Few people have seen the data.

This is what scientists call “dual-purpose” research. On the one hand, it can answer important questions. On the other, it can lead to the development of biological weapons, ideas for biological weapons, or seriously bad accidents. The best science writers are having a hard time not sensationalizing this. Even the researcher who did it seems to be playing up the drama. What if it gets out? Millions will die! But is there a real risk from this virus?

Its hard to know the facts without the published data.

How well does the ferret model the pathogenicity and transmissibility in humans? It is commonly used and generally accepted to be quite good, but it seems a stretch to assume a human pandemic can occur based on transmission between ferrets in the lab. We need to be careful not to over-extend the findings of the study (this is especially the case since the data is not available). The experiment presumably shows that the virus can be transmitted between ferrets. It does not demonstrate that this virus can cause a human pandemic.

How pathogenic is the new virus? Does it cause the same disease as the original virus or did the mutations that allow transmissibility also decrease virulence? Maybe it can spread human-to-human, but its not clear how sick they would get. Further, usually when a virus is passaged several times through a different host species, it adapts to that species and results in attenuation in the original host. This has been observed many times, and has even led to the development of several attenuated vaccines.

Related to this, many evolutionary biologists believe that virulence and transmission are closely tied. That is, a virus that is too deadly will cause outbreaks that fizzle out (Ebola is a good example). Viruses that don’t cause enough disease might have a hard time transmitting too (coughing, sneezing or diarrhea are good examples – a little bit of disease helps get the virus out of your bod and into the next one). Paul Ewald argued that the high mortality rate of the 1918 influenza was in part due to the fact that the conditions at the time allowed for a more deadly virus to evolve. Due to WWI, factors such as overcrowding and troop movements may have allowed a highly virulent virus to be successful. Conditions today may not favor a pandemic by a highly virulent virus. So would a transmissible and pathogenic H5N1 cause a major epidemic or would it fizzle out?

There is also the issue of publication. There is debate on whether the research should be published or kept secret. Does publication provide a roadmap for someone who wants to do this for evil purposes to repeat the experiment and create a biological weapon? It seems to me that even without details of the experiment, enough information is already available to repeat it. Withholding publication would also prevent other researchers from understanding and extending the findings. Any benefits from having done the experiments would be significantly less without publication.

I have seen stories like this one before. Several years ago, an highly pathogenic ectromelia virus (causes mousepox, related to the smallpox virus) was made by adding the gene for Interleukin-4. The researchers did not intend to make a highly pathogenic virus, it was rather a surprise to see this effect. There was much debate about whether they should publish, that perhaps this was a roadmap for building a highly pathogenic poxvirus in humans. They published and we have since learned more about the virus, including the observation that the virus does not transmit effectively, and that doing the same thing in other viruses doesn’t have the same effect. The more we know, the better.

I’d make the same argument here. I’d like to see the research published. The information from this study is probably valuable, addresses an important question, and is only one small step in understanding H5N1 influenza.