Gain of Function Research of Concern

Advances in molecular genetics have enabled the development and creation of genetically modified organisms. A consequence of work in this area has been controversy as to whether the products of genetic modification represent beneficial scientific advances, as their advocates argue, because they increase human knowledge or whether, as the opponents of such research argue, genetically modified organisms represent a serious potential threat to the environment. A particular facet of the controversy has developed because of studies with severe respiratory viral pathogens which have the potential to cause pandemics. The initial concern arose from work with the highly pathogenic avian influenza virus H5N1. The virus has a high mortality rate in chickens, is spread by wild fowl, and has an apparent mortality rate of about 50% in humans who are infected. The virus does not normally infect humans because human respiratory cells do not have the surface receptor required by H5N1; however, some people who came into close contact with infected fowl were infected with the mortality rate noted above. In 2011 two papers were submitted for publication which reported that modification of the viral hemagglutinin, the attachment protein, enabled H5N1 virus to be transmitted by respiratory droplets between ferrets, the best laboratory model for human influenza. The work was done to enhance surveillance of H5N1 which might present a serious threat to humans and to enhance the development of vaccines. Opponents raised concern that escape of such modified viruses from the laboratory could lead to a pandemic in which millions might die, because no vaccine existed, flu vaccines are of variable efficacy, and it was uncertain whether current antivirals would be effective and of sufficient availability. Papers were published, letters written, and symposia held to argue the issue. After lengthy consideration by the US National Scientific Advisory Board for Biosecurity (NSABB), it was recommended that the papers be allowed to be published. However, the controversy continued on an international level. Work with two additional respiratory viruses with high mortality, SARS and MERS, was also of concern. The controversy was exacerbated by the highly publicized mishandling of microbial pathogens by the CDC and the NIH/FDA. Consequently, the executive office of the US President enacted a moratorium on so-called gain of function research of concern. The NSABB was charged with developing a recommendation to the US government concerning the regulation of the research. A working group was constituted and external studies of risk assessment and bioethics were commissioned. Two symposia sponsored by the US National Academy of Sciences were also commissioned. The input from all of these and from the comments of numerous individuals were synthesized into a report by the NSABB working group which was accepted unanimously by the full NSABB May 24,2016 for transmission to the US government.

This proposal is for a Research Topic of Frontiers in Science in Biosafety and Biosecurity to solicit 5-10 articles from senior scientists, representing a diverse set of viewpoints, on the perceived risks, approach of regulation of the research, international synchrony in oversight and scientific cooperation, as well as the adequacy of current efforts to safeguard human health.