Two papers were submitted to the journal Nature in August 2011 that dealt with
influenza. One came from the University
of Wisconsin-Madison lab of Yoshihiro Kawaoka; the other from a team at the
Erasmus Medical Center in Rotterdam, the Netherlands, and was headed by Ron
Fouchier. To say that this research
caused a stir would be an understatement.
A “pause” was placed on this research in both countries due to fears
from the community about viral release (the original letter and a note about it was found on my other blog, Dr. Amedeo).
Meanwhile, the papers themselves were heavily discussed by Nature editors, the World Health
Organization, the general public and the US National Science Advisory Board for
Biosecurity (NSABB). The initial
position was that, in the interest of public security, these papers should only
be made available to certain people who applied for the information or published
without their methods and certain key results hidden. In a land of peer-reviewed work and
government red-tape, these options were not well received. After much discussion, the NSABB backed off
and left Nature to make the final
publication decision. Nearly nine months
after the papers were first received, the Kawaoka paper was published in the
journal Nature, appearing online
ahead of print on May 2nd, 2012.
The Fouchier group paper will be published in the journal Science in the next few weeks.
What
was the hub-bub all about? Pandemics. Bioterrorism.
Freedom of information.
I
covered the influenza virus, and the Spanish influenza in particular, in an
earlier series of posts on this blog, which you can find here. Three key pieces of information from those
posts are important to explaining the above papers:
One. Two proteins
exist on the outside of an influenza virus that are very important to viruses
being able to bind a cell and then get inside.
They are called hemaglutinin (HA) and neuraminidase (N). Several versions of each protein
exist and each version is given its own number.
An influenza virus is named for the versions of HA and N that are found
on the outside. For example, most people
remember the H1N1 scare. That particular
strain of influenza had version 1 of HA and version 1 of N.
Two. Influenza
viruses are specific for certain species.
Human influenza viruses exist; avian influenza viruses exist; even swine
flus exist. In each of these viruses,
the HA protein is specialized for binding to the cells in that particular
animal. The number 5 in H5 is telling
you the version of HA in the influenza, and species specific nature of the
virus tells you what cells that particular H5 is specialized to bind.
Three. The
specialization of each HA is not static.
Viruses quickly infect cells, replicate inside, and move on to infecting
other cells and replicating again. This
is a lot of DNA replication and virus generation in a short time. Mutations happen. Influenza viruses gain mutations (aka evolve)
quickly. Sometimes these mutations allow
for a previous version of H5 that could only bind to birds now suddenly being able
to bind humans. When these types of
sudden shifts happen, pandemics can result.
The Spanish Influenza was an example of this sudden host change from
birds to humans and resulted in a pandemic that swept through World War I
America.
Currently,
a form of influenza called H5N1 is circulating in Indonesia, Vietnam, and Egypt
among other places. This virus is able
to infect birds and has resulted in the culling of millions of birds. 578 humans have been infected by H5N1
resulting in 340 deaths. Interestingly,
there is little evidence for human to human transmission of the virus. The virus only infected a human from direct
human-bird contact. The virus gained the
ability to infect a human but not to be easily transmitted between humans. This keeps the H5N1 virus somewhat contained
and low risk to the public. However…
what if, just like the Spanish Influenza of the early 20th century,
H5N1 suddenly gained the ability to infect humans and transmit easily between
them? Well, we could possibly have a pandemic on
our hands that could result in the deaths of thousands or millions of people throughout
the world.
The labs of Kawaoka and Fouchier wanted
to know what changes could occur in the H5 protein that would allow it to
reliably infect humans and allow for easy human to human transmission. The Kawaoka paper highlights two areas of the
protein and how they could be mutated to potentially switch H5N1’s ability to
easily infect humans. The Fouchier paper
is still unpublished, but I know its focus is similar. The concern about these papers arose from two
things: 1. These labs made viruses that could infect humans. Did these labs have regulations in place to
safeguard escape of the virus from the laboratories? 2. These papers outline, in detail, how to
switch the strictly avain H5N1 virus into a potential deadly human weapon. Should that information be made public? In the end, it was decided so.
Kawaoka published an impassioned
editorial explaining the reasoning for his research and the importance it holds
to staving off future pandemics. The WHO
asked for higher safety standards, with which both labs complied and those
standards will be published by the WHO in the coming weeks. The journals wanted the option for
peer-reviewed quality work (something that would not happen if these papers were only released
to certain people or without methods).
In a Nature editorial, the
reason for publication was outlined as thus:
Having now considered these matters in depth, the editors of
this journal have decided that we will not consider either alternative for
papers in Nature in the forseeable future.
A paper that omits key results or methods disables subsequent research
and peer review. Furthermore, after much
internal and external deliberation, we cannot imagine any mechanism or
criterion by which to sensibly judge who should or should not be allowed to see
the work. Nor do we believe that any
restricted information distributed to university laboratories would stay
confidential long.
If you are curious to the contents of
the Kawaoka paper, see my most recent post on Dr. Amedeo. When the Fouchier paper becomes available, I
will post a similar summary there, as well.
REFERENCES:
Kawaoka Editorial: Kawaoka et al. "Flu transmission work is urgent." Nature
Nature Editorial: "Publishing Risky Research." Nature (2012) 485, pg 5
Kawaoka Paper: Imai et al. "Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets." Nature (2012), published online ahead of print
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