Saturday, December 17, 2011

The Biosecurity Debate On H5N1 Research



BSL-4 Lab Worker - Photo Credit –USAMRIID

# 6016



Three months ago, one of the best known researchers in the world - Ron Fouchier of Erasmus Medical Centre in Rotterdam - announced at a scientific conference that he’d managed to turn H5N1 into a virulent, and easily transmissible (among ferrets, anyway) pathogen.


(You can read about this work in Katherine Harmon’s Sci-Am article and in a follow up to this story in New Scientist: Five Easy Mutations.)


Halfway across the world, Yoshihiro Kawaoka, a highly respected virologist at the University of Wisconsin-Madison School of Veterinary Medicine announced the creation of a comparable H5N1 super flu at roughly the same time.


At issue is whether scientists should even be tinkering with this particularly lethal flu strain, and whether (or how) those results should be published.


Some fear that this knowledge could be used by bioterrorists to engineer a bio-weapon (see NPR: Bio-Terrorism Concerns Over Bird Flu Research).


Erasmus University provided their side of this discussion late last month, which I blogged on in The Bird Flu Research Debate Continues.


On Thursday I highlighted an opinion piece (see Laurie Garrett On The Bird Flu Research Controversy) that appeared in Foreign Policy, that essentially argued that in many ways the genie was already out of the bottle, and that if we didn’t figure out this virus, nature could very well do it for us. 


The Center For Biosecurity at UPMC, on the same day, released a strongly worded editorial advising against these types of H5N1 research projects, and lobbying against the publication of the methods and results.


The link to the Biosecurity Blog follows:



Editorial: The Risk of Engineering a Highly Transmissible H5N1 Virus.

Thomas V. Inglesby, Anita Cicero, D. A. Henderson. Scientists recently have announced that they genetically modified H5N1 in the laboratory and that this mutated strain spread through the air between ferrets that were physically separated from each other. This is ominous news . . . Read editorial now [Posted December 15, 2011]


The Center’s director - and one of the authors of this editorial - Thomas V. Inglesby appeared on NBC Nightly News Thursday night in a short segment on this controversy.


I don’t know how long this link will be active, but for now you can Watch this clip from the December 15 broadcast.



I confess to having mixed feelings over all of this, but I suspect that ultimately, some sort of redacted version of these research projects will make it into print.


The fact that two scientists – half a world apart –independently created a virulent and transmissible H5N1 flu suggests that the basic knowledge on how to do so is already in the ether.


The work of Fouchier and Kawaoka are under intense scrutiny right now because those experiments yielded unexpected success.


But they aren’t the only scientists following these controversial avenues of research.


And in the case of the Fouchier experiment, it wasn’t sophisticated genetic engineering that produced this super flu, it was the low-tech (and well known) serial passage method that ultimately succeeded.


Last July, in H5N1: A Rite Of Passage I looked at another bird flu research project that looked at increases in pathogenicity (in mice) of two H5N1 viruses after six serial passages in quail.



Simplified Illustration of a Serial Passage Experiment



Similarly, last September we saw a study that appeared in The Journal of Virology called:


Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin

J. Virol. doi:10.1128/JVI.05582-11

Troy D. Cline, Erik A. Karlsson, Pamela Freiden, Bradley J. Seufzer, Jerold E. Rehg, Richard J. Webby, and Stacey Schultz-Cherry


Using reverse genetics, researchers at St. Jude Children’s Research Hospital created several reassortant 2009 pH1N1 viruses with individual genes borrowed from a 1997 H5N1 virus, and then tested them for replication and virulence.


They found that one of these lab-created viruses, with the HA gene from the H5 virus, increased replication over the parental strain and produced virulence in mice comparable to the parent H5N1 strain.


They also report that serial passage through human lung epithelial cells (in Vitro) "resulted in increased pathogenicity, suggesting that these viruses may easily adapt to humans and become more virulent."


And while not (currently) in the same league as H5N1 when it comes to pathogenicity, similar experiments are being performed on the H9N2 avian flu virus as well.


Last February in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.


In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.


And in July of this year, another H9N2 reassortment study appeared in PNAS, where scientists combined the H9N2 virus with the 2009 H1N1 virus, and generated 4 reassortants (PNAS: Reassortment Potential Of Avian H9N2). 


Three of these hybrid viruses showed efficient respiratory droplet transmission, suggestive that if this reassortment can be induced in the lab, it has the potential of occurring in nature.


These are but a few examples of the kind of reverse genetics research being performed on flu viruses in laboratories all over the world. 


While all of this may be more than a little unnerving, quashing the publication of Fouchier’s or Kawaoka’s research isn’t going to stop other scientists, in hundreds of labs around the world, from pushing forward with their research.


Added to that, nature’s laboratory is open 24/7, working to solve the puzzle of how to make the highly lethal H5N1 virus a more `biologically fit’ pathogen. 


And for a virus, that means transmissibility.


Something which research scientists hope they can mitigate or even halt, if they can figure out – in advance – how nature will go about it.


Which, if they are right, could bring  a whole new meaning to the phrase `Publish or Perish’.