Last month, researchers announced that they would resume
work with potentially dangerous avian flu strains that had been modified in a
way that allowed transmission between mammals. The initial discovery of the
mutations leading to increased transmissibility caused an uproar among both
scientists and the general public. The outcry reached such a pitch that the
scientists agreed to a voluntary moratorium
on their research. The stated reasons for the moratorium were twofold: to give
enough time to explain the importance of the research to the public and to
allow governmental agencies to assess if future work with the modified strains
required additional security or protective gear. In some ways, the controversy
over the modified H5N1 virus was a sequel to the outcry that occurred over the resurrection
and sequencing of the 1918
influenza strain which, though dormant for many years, had been highly
pathogenic and was responsible for a terrible pandemic both in the US and
abroad. In 2005, researchers
isolated fragments of the virus from a frozen specimen in Alaska, and used
these pieces to reconstruct the viral genome. Many of the questions being asked
today were also topics of discussion in 2005, leading one to wonder how many
times this debate must surface before it is addressed in a systematic fashion.
Since certainly research will surely continue on these and other highly
contagious diseases, the US government must develop comprehensive guidelines to
protect both the researchers and the public before the research is undertaken,
rather than asking questions after the fact.
Such regulations
should cover the following points at a minimum:
- Should
research funded by the NIH be subject to review to determine if the potential
benefits of the work outweigh the risks before its undertaking? Without a
doubt, this is a difficult question, as both the risks and benefits can hardly
be accurately ascertained until the research is completed. Many researchers
have lofty goals but research can fall short of actual concrete benefits.
Officials in both the CDC and the National Institute of Allergy and Infectious
Diseases signed
off on the resurrection of the 1918 virus, but it is not clear if this was the
case for the modified H5N1 virus, though the researchers must have been
aware of the some of the concern that would arise by modifying an existing,
virulent strain of the virus. Even now that the work has been completed, it is
hard to address the resulting benefits. The authors of the study have argued
that identifying mutations that make the virus transmissible will be useful
because it is possible to monitor mutations as they arise in the wild and if
these particular mutations occur, their potential for destruction will be
immediately identified and steps can be taken to contain those strains.
However, criticism of the work with modified H5N1 virus has centered on the
argument that the authors have merely determined a subset of the mutations that
could cause the H5N1virus to become transmissible between mammals, and it is
unknown how many other mutations or combinations of mutations could have a similar
effect. Partial knowledge could actually lead to a false sense of security
with regard to our understanding of the H5N1 virus.
- If
such work is determined to be worth its potential risks, how can those risks be
minimized? In other words, what precautions should be taken when working with
the modified virus, particularly before a mutant virus is fully characterized?
These precautions should aim to both protect laboratory workers and but also to
prevent outside contamination or theft. Interestingly, even now that the risks
have been partially assessed for the modified H5N1 virus, this issue is proving
controversial. The US has not yet offered its guidelines for working with the
virus, despite the passage of a year and resumption of work with the virus in
other countries. For now, it appears that researchers in the US are willing to wait for these
guidelines before resuming research, but they are losing time compared to their
international counterparts. One can only hope that whatever guidelines are
given will be broad enough to cover at additional research for the foreseeable
future so that additional year long pauses will not be needed each time a new,
more dangerous strain is created
- How widely should the identity of mutations that lead to greater virulence be shared? In the case of both the 1918 virus and the modified H5N1 viruses, the full extent of the genetic information was published in peer reviewed journals. Interestingly, in the case of the modified H5N1 viruses, the National Science Advisory Board for Biosecurity (NSABB) initially recommended withholding publication of the specific mutations that increased transmissibility, a decision that broke with their previous decision to recommend publication of the 1918 flu sequence. However, the panel reversed their decision a few months later, recommending the publication of the identity of mutations go forward. Again, though the issue certainly merited careful consideration, it seems the lack of a comprehensive policy caused a delay in sharing useful information.
As the knowledge of these
and other dangerous infectious agents grows, so does the potential for harm
that accompanies some lines of research. At some point a line will have to be
drawn on one or more of the issues listed above. That line should be determined
before the work is performed, rather than forcing researchers to close
Pandora’s box after it has been opened.
Irene Reynolds Tebbs
6th year, Molecular Biophysics and Biochemistry
