Publish and Perish?
In late 2011, the National Science Advisory Board for Biosecurity (NSABB) made an unprecedented recommendation that details of two H5N1 bird flu studies by researchers from the Netherlands and the University of Wisconsin be withheld from publication because they could potentially be used to start a deadly pandemic. In March, following months of controversy and additional review, the board reversed that recommendation. Michael Imperiale, Ph.D., Arthur F. Thurnau Professor and associate chair of the Department of Microbiology and Immunology, has served on the NSABB since its inception in 2005 and explains what’s at stake in the debate.
Q: What makes the H5N1 flu so dangerous?
A: There have only been a small number of human cases of H5N1 — just over 600 to date — but the mortality rate is incredibly high, nearly 60 percent. So, while we’ve been seeing it transmitted from bird to human, rather than human to human — primarily in populations with direct contact with animals, like poultry workers — we’ve come to know it as a highly lethal virus in humans. In contrast, the mortality rate associated with the 1918 influenza pandemic was around 2 to 3 percent and it killed up to 40 million people; a quarter of the world was infected.
Q: Where does the research at the heart of the controversy fit in?
A: The unanswered question is, “Could this virus start spreading from human to human?” There’s been a lot of debate in the influenza community as to whether this is going to happen.
Q: What did the two research teams find?
A: They introduced mutations into the virus based on the fact that avian viruses use different receptors to get into cells than human viruses. They changed the virus so that it would be able to recognize human receptors, and then they took the engineered virus and passaged it through ferrets. When they introduced this virus to ferrets within sneezing distance of non-infected animals — a well-established model for influenza transmission — they found that the passaged virus can be transmitted from ferret to ferret through an airborne route.
Q: What is the scientific value of this type of research?
A: There are three potential benefits. The first is simply confirming that mammal-to-mammal transmission is possible. Another is that it may be useful for vaccine development. And finally, if public health authorities know certain mutations can cause transmissibility, they can watch out for them. Now there are two caveats to that: Presumably these aren’t the only mutations that can cause transmissibility, so you don’t want to get a false sense of security; and influenza surveillance is not that great. It’s been argued that by the time you’ve seen a particular sequence, it may already be too late.
Q: Why did the board make its initial recommendation?
A: This is the first time we’ve seen papers and said, “Whoa, this is potentially really dangerous.” We had reviewed a couple of papers previously that described the reconstruction of the 1918 influenza virus. In that case, we deemed that publishing wasn’t of concern because the sequence of that virus and how to reproduce the virus from that sequence were already known. Now you could argue with the H5N1 research that someone could also go into the literature and figure out how to do it, but our thinking here was, “Why give them the actual template?”