In late 2011 two groups,working independently, announced that they had created strains of the H5N1 virus that were transmissible in ferrets, the preferred model for studying airborne disease transmission (Evans, 2012). As they prepared to publish, the National Science Advisory Board for Biosecurity (NSABB)and recommended partial censorship of the articles. In response, conferences were convened in the USA and Geneva in order to discuss the issue in greater detail.
At the heart of the question was the idea of Dual Use Researchof Concern (DURC) (NIH, 2014). According to the NIH,
Dual Use Research of Concern (DURC)is life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security (NIH, p. 7).
In the work by Ron Fouchier of the Erasmus Medical Center and Yoshihiro Kawaoka of the University of Wisconsin, genetic engineering was used to introduce mutations into separate strains of the H5N1 virus in order to make them transmissible between humans(Resnik, 2013). Previously, the only known strains of H5N1 virus were incapable of direct human to human transmission.
Publication of the two articles would confirm the possibility of creating such an H5N1 virus, and in the hands of an unscrupulous actor, the methodological insights provided could lead to the production of anew bioweapon. This forced the NSABB to make their initial recommendation for censoring the articles.
The H5N1 work highlighted two key ethical issues: the value/risk ratio of performing the work and the decision whether to publish or censor the work. Dealing first with the issue of censorship, it is, of course, not uncommon for research to be carried out under the cover of secrecy and the results censored. The Manhattan Project is one such example. However, in this case, due to the multiple projects coming to fruition within the same time frame, it is clear that the work on the flu virus was being carried on in multiple locations. What value, then, is there to be gained by censoring the papers? Is it not better to report the work in order to prevent unnecessary duplication and research missteps? Clearly the genie is out of the bottle and won’t be put back in.
Is there value to this type of research though? Clearly in the case of the H5N1 work, the investigators were able to gain a better understanding of the virus function. In addition, it may enhance global monitoring programs by indicating key mutations for which to watch, though Bennett (2013)argues that such results are of limited utility as they may not represent the only mutations which could cause pandemic conditions. Carrying out the work in the light of day,allows for open discussion of regulatory and ethical issues related to viral research. Finally, advancement of vaccine work was also possible, though in this specific case, David Relman, MD.,had this to say:
We already know enough to push full out for a broadly protective H5 vaccine. What more do we need? Do we really want to wait for a mammalian respiratory transmissible H5 to show up in nature?The general public appears to be largely opposed or at least highly concerned.A real moratorium should continue for the foreseeable future(Roos, 2012).
This highlights the need to balance actual research benefit against risks.
What then of the risks? Careful consideration of the risk is key to the decision to carry out any DURC work. In our case study, the work carried a number of significant risks. First was the possibility of accidental release of a replication-competent mammalian virus into the environment. Though the researchers attempted to mitigate release risks via use of an ABSL3+ environment and prophylactic vaccination(Roos, 2012), a negative outcome was still a distinct possibility. As mentioned above once the work became known, it is possible that a bad actor would have staged a non-accidental release of the virus in order to create a pandemic situation. Publication of the work also carries the risk of advancing the research of other labs that are well-meaning but are not truly prepared to carry on research at this high a risk level.
How then is the community to proceed? In the words of Evans
This is a distinctly ethical decision-making process. Moreover, it is unlikely that such a process is one that should be governed exclusively by scientists. There are detailed technical issues involved in dual-use dilemmas that those scientists in the field (in the H5N1 studies, influenza research)can and should bring their expertise to. But considerations of value will require other expert (eg, public health, ethics and economics) and community participation. Scientists may approach their research with the best of intentions and the good of society in mind, but it would be a mistake to assume that they could know what is best for the world - and a tragedy to foist that burden on them (Evans, p. 212).
In response to the NSABB recommendation, Fouchier and Kawaoka along with other researchers in the field voluntarily instituted a temporary moratorium on such research so that the scientific community and appropriate governing bodies could catch up with and develop the appropriate guidelines for carrying out such work (Keuhn, 2012). During this moratorium, scientific bodies and governmental organizations were able to meet to discuss the path forward. In the case of the United States, the Policy for Oversight of Life Sciences dual-use research of concern (NIH, 2014) was developed and put into place. This policy did not ban such work or call forits outright censorship. Rather, it called for institutions receiving federal funding to institute internal review and risk assessment boards to approve and monitor any such work. Many other countries used the opportunity to institute similar policies (Fouchier et al., 2012). In addition, the virus has been reclassified as Risk Group 4 due to potential induced transmission which carries significant environmental and handling restrictions.
Once these safeguards were put into place and the appropriate guidelines were disseminated, the original papers were published in full, and the moratorium was lifted.
Finally, what light can this case study shed on the ethical and regulatory issues associated with the human germline issue?