Student blog posts: Dangerous H5N1 strain made airborne

A few weeks ago This week my students wrote short essays about the infamous  Hersft et al 2012 paper on airborne Influenza A in ferrets. For months, this paper was not published (even though it was accepted for publication) because it was unclear whether the results should be published at all, for fear that terrorist groups would use it to create a dangerous flu strain (see here). In my class, all students read the same paper, but they each have a different assignment. 

Figure 4 of Herfst et al 2012 Science.

Peter Manzo: My opinion

I thought this paper was a little slow but it was very interesting. The idea of an airborne virus has plagued mankind for centuries and according to the article, there is a possibility for viruses to mutate enough to become airborne. I liked how the article explained in detail what influenza is and its nomenclature. I thought it was interesting that the research group was able to produce an airborne virus but I do not understand why they would help a virus evolve to that state. I think the results are important but I wonder if the experiment will be redone.

Eduardo Lujan: The main conclusion of the paper

The main conclusion of the paper was that A/H5N1 influenza virus has the capability to become airborne transmissible in ferrets. Studies such as the one conducted in the paper are denoted as “gain of function” and the authors used this approach to genetically modify A/H5N1 virus and then used the modified virus during serial passage in ferrets. The authors concluded that four amino acid substitutions in the hemagglutinin protein and one mutation in the polymerase complex were all present in airborne-transmitted virus isolates. This paper is extremely relevant to health and medicine because it holds the potential to provide insight into a virus’s capacity to become airborne and cause explosive disease, and this information will allow scientists to begin developing therapeutics to alleviate such a situation. I do not believe that this paper will have an impact on current patients because the research carried out in this study did not lead to any novel treatments.

Graham Larue: The data that were used in the paper

In this paper, the authors wanted to investigate the possible mutations in avian influenza A/H5N1 which could lead to the possibility of airborne transmission between humans. In order to test this, the investigators performed targeted mutagenesis and serial virus passage in ferrets to determine whether the mutations made provide a sufficient substrate to allow for development of airborne transmission. The primary source of data for the experiment(s) came from throat and nasal swabs, as well as nasal washes which were then tested for viral load via end-point dilution in canine kidney cells. For the serial passage experiments, such samples were collected for each individual in the transmission chain. Viral quasi-species from each sample were characterized using 454 pyrosequencing, and viral genomes obtained using Sanger sequencing for experiment 4. In total, this paper used a variety of genetic, immunologic, molecular and bioinformatic (sequencing analysis) techniques to address the question of airborne transmission acquisition in avian influenza. There is scant detailed discussion about any of the individual analyses used in this paper, but clearly some amount of basic statistics must have gone into the generation of significance values and the like.

Student blogpost: on bad-small-things and small animals

Nicolas Cole (MSc student at SFSU) does a great job explaining the Hersft et al 2012 paper on airborne Influenza A in ferrets using only the 1000 most common words of the English language. Enjoy!  

Figure 2 from Herfst et al 2012 Science

There is a “bad-small-thing” that goes from one flying animal to another flying animal, causing death. It can also go from a flying animal to a human, if a human touches that flying animal while it is dead. This causes the human to get sick. Does this “bad-small-thing” go from human to human through the air? A group of doctors studied the “bad-small-thing” in “small animals” that do not fly. The “small animals” can also die because of the “bad-small-thing” being in their bodies.

First, the doctors changed the “bad-small-thing” in small ways that could make it go from “small animal” to “small animal” through the air. At first, the “bad-small-thing” and the “changed-bad-small-thing” did not move through the air from one “small animal” to the next.

Then they passed the “bad-small-thing” from one “small animal” to the next, to change it more. They did this ten times with both the “bad-small-thing” and the “changed-bad-small-thing”. They found that the “changed-bad-small-thing” grew easier and more often after passing from “small animal” to “small animal”.

Next, they wanted to see if the “passed-changed-bad-small-thing” could pass from “small animal” to another “small animal” through the air. The doctors put the “small animals” in boxes that did not let the “small animals” touch, but air could pass between them. They put small animals with the normal “bad-small-thing” next to boxes of not-sick “small animals” and they put the “small animals” with the “passed-changed-bad-small-thing” next to not-sick “small animals”.

So, if the “passed-changed-bad-small-thing” could be passed, it could not pass by touch but could pass by air. Sure enough, the doctors found that the “passed-changed-bad-small-thing” passed from sick “small animals” to not-sick “small animals” but the “normal-bad-small-thing” did not pass through the air. However, none of the not-sick “small animals” that became sick through the air died.

The doctors took a closer look at the “air-passed-changed-bad-small-thing” and the “changed-bad-small-thing” and found that the “bad-small-thing” only needs 5 changes to be able to pass through the air from “small animal” to “small animal”. The doctors also say that even though the “small animals” were able to get sick from the “air-passed-changed-bad-small-thing” through the air, this does not mean that humans can change the “bad-small-thing” in the same way as the “small animals” so that it could pass through the air.

Finally, the doctors studied “man-made-human-good-stuff” that is meant to stop “bad-small-thing” from passing from humans to humans. They put the “man-made-human-good-stuff” in the “small animals” that were sick from the “air-passed-changed-bad-small-thing”. The “man-made-human-good-stuff” was able to stop the “air-passed-changed-bad-small-thing”!!!!!!!!!!!!!!!!!!!! (because happy points are free).

For the first time doctors were able to show that a “bad-small-thing” can pass from animal to animal enough that it can become a “air-passed-changed-bad-small-thing” and that can be bad for humans.