The ethics of biosafety considerations in gain-of-function research resulting in the creation of potential pandemic pathogens: Table 1

Abstract

This paper proposes an ethical framework for evaluating biosafety risks of gain-of-function (GOF) experiments that create novel strains of influenza expected to be virulent and transmissible in humans, so-called potential pandemic pathogens (PPP). Such research raises ethical concerns because of the risk that accidental release from a laboratory could lead to extensive or even global spread of a virulent pathogen. Biomedical research ethics has focused largely on human subjects research, while biosafety concerns about accidental infections, seen largely as a problem of occupational health, have been ignored. GOF/PPP research is an example of a small but important class of research where biosafety risks threaten public health, well beyond the small number of persons conducting the research. We argue that bioethical principles that ordinarily apply only to human subjects research should also apply to research that threatens public health, even if, as in GOF/PPP studies, the research involves no human subjects. Specifically we highlight the Nuremberg Code’s requirements of “fruitful results for the good of society, unprocurable by other methods,” and proportionality of risk and humanitarian benefit, as broad ethical principles that recur in later documents on research ethics and should also apply to certain types of research not involving human subjects. We address several potential objections to this view, and conclude with recommendations for bringing these ethical considerations into policy development.

The Silver Lining in Gain-of-Function Experiments with Pathogens of Pandemic Potential

“…A number of critics have argued that the risk of inadvertently creating a global pandemic through accidental release of an engineered, human-transmissible pathogen with high virulence and case fatality rate vastly outweighs any benefits that might be obtained from such research [e.g., 34]. Thus, one source claims a 0.01% to 0.1% probability per year of research in a BSL-3 lab of an accidental release of highly transmissible influenza virus that would kill between 200,000 and 16 million people [35,36].…”

“…Similarly, comparisons of the risks of GOF research to the events leading to the development of the Nuremberg Code do not serve a useful purpose in the discussion [34]. The use of the word "Nuremberg" connotes an association with war crimes that is simply inappropriate for use in a rational discussion about experiments that are ostensibly being done by well-meaning scientists trying to prepare humanity for confronting a potential pandemic.…”

Gain-of-Function Research: Ethical Analysis

“…Despite this debate regarding the magnitude of biosafety risks posed by GOFR, there appears to be fairly widespread agreement that, other things being equal, research risks should be minimized (Casadevall et al 2014a, b; Casadevall and Imperiale 2014; DHHS 2013; Duprex et al 2015; Evans et al 2015; Imperiale and Casadevall 2015; Lipsitch and Galvani 2014; Lipsitch and Inglesby 2014). It has been suggested that GOFR risks might be reduced via:

Employment of safer pathogen strains

of low virulence,

for which there is immunity,

for which there are existing vaccines, and/or

which have been modified to inhibit replication outside of laboratories;

Development/use of vaccines against experimental pathogen strains;

Development/use of broad spectrum vaccines (e.g., pan- or universal influenza vaccine);

Vaccination of laboratory workers to create a ring of immunity; and/or

Ongoing improvement of biosafety practice and infrastructure.

…”

“…In reaching this conclusion, they appeal to Nuremburg Code and Belmont Report requirements that research should “be done only if it benefits society, if the same benefits could not be procured through less risky means, and if the anticipated benefits exceed the anticipated risk” (Evans et al 2015). Though they acknowledge that the Nuremburg Code and Belmont Report were explicitly designed to govern research involving human subjects, they argue that (in light of the general ethical considerations upon which such guidelines are based) these requirements have broader applicability to risky research more generally.…”

“…29The need for additional biosafety research (and associated funding) in particular is also suggested by Evans and colleagues (2015). I here additionally have in mind research that helps determine whether GOFR (as opposed to other kinds of less risky research) is needed to answer key scientific questions.…”