"Gain-of-function” research designed to make pathogens deadlier or more transmissible in order to develop treatments and countermeasures has been given a green light by the National Institutes of Health (NIH).

The NIH pulled the plug on such research on Oct. 17, 2014, after several incidents that could have led to public health threats, not the least of which were breaches in working with anthrax and bird flu in the prestigious labs at the CDC.

“During the funding pause, the U.S. government undertook a deliberative process to assess the potential benefits and risks associated with these types of studies,” the NIH stated in a Dec. 19, 2017, announcement.1 “The purpose of this guide notice is to notify applicants that in accordance with the December 2017 issuance of the Department of Health and Human Services’ ‘HHS Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens,’2 the National Institutes of Health is removing the funding pause on the provision of new or continuation funding for gain-of-function research projects.”

The research could enhance pathogenicity and/or transmissibility of a potential pandemic threat. The pathogens likely targeted include MERS coronavirus or H5N1 avian influenza, both of which could cause considerable human suffering and mortality if they mutated to improve virulence or transmissibility. Enhancing these deadly pathogens in high containment labs could anticipate such a mutation in nature, allowing for the development for treatments and vaccines if the viruses eventually mutate in the wild or through the efforts of bioterrorists. Of course, the risks include an enhanced pathogen escaping the lab and the possibility that the methods used could fall into the hands of those wanting to weaponize the microorganisms.

One study reviewed a framework to access the ethics of such research, but concluded that “difficult judgments will need to be made. … There might not always be clear right answers regarding whether a given case of gain of function research should proceed (or be funded). Like risk-benefit assessment, ethics involves inevitable uncertainty.”3

Safeguards

To prevent accidents and incidents and ensure the work is conducted under controlled conditions, HHS calls for the following criteria for research on a potential pandemic pathogen (PPP):

• the research has been evaluated by an independent expert review process (whether internal or external) and has been determined to be scientifically sound;

• the pathogen that is anticipated to be created, transferred, or used by the research must be reasonably judged to be a credible source of a potential future human pandemic;

• an assessment of the overall potential risks and benefits associated with the research determines that the potential risks as compared to the potential benefits to society are justified;

• there are no feasible, equally efficacious alternative methods to address the same question in a manner that poses less risk than does the proposed approach;

• the investigator and the institution where the research would be conducted have the demonstrated capacity and commitment to conduct it safely and securely, and have the ability to respond rapidly, mitigate potential risks, and take corrective actions in response to laboratory accidents, lapses in protocol and procedures, and potential security breaches;

• the research results are anticipated to be responsibly communicated, in compliance with applicable laws, regulations, and policies, and any terms and conditions of funding, in order to realize their potential benefit;

• the research will be supported through funding mechanisms that allow for appropriate management of risks and ongoing federal and institutional oversight of all aspects of the research throughout the course of the research;

• the research is ethically justifiable. Nonmaleficence, beneficence, justice, respect for persons, scientific freedom, and responsible stewardship are among the ethical values that should be considered by a multidisciplinary review process in making decisions about whether to fund research involving PPPs.

Though this will probably be determined on a case-by-case basis, it remains to be seen if possible bioterror agents would be approved for enhancement. For example, smallpox has been eradicated from nature, and thus may not be “judged to be a credible source of a potential future human pandemic.” However, frozen stores of smallpox — to which much of the Earth’s population is now susceptible — are still held by the United States and Russia. In addition to smallpox, the Department of Homeland Security lists other agents that meet the “material threat determination” as threats to national security if weaponized. These pathogens include anthrax, glanders, melioidosis, botulism toxin, hemorrhagic fever, tularemia, MDR anthrax, typhus, and plague.4

REFERENCES

1. NIH. Announcing the Removal of the Funding Pause for Gain-of-Function Research Projects. Dec. 19, 2017. Available at: http://bit.ly/2z6aG5Q. Accessed Jan. 11, 2018.

2. HHS. Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens. 2017. Available at: http://bit.ly/2EoC41J. Accessed Jan. 11, 2018.

3. Selgelid MJ. Gain-of-Function Research: Ethical Analysis. Sci Eng Ethics 2016; 22(4): 923–964.

4. Trust for America’s Health. Ready or Not? Protecting the Public’s Health From Diseases, Disasters, and Bioterrorism. 2017. Available at: http://bit.ly/2FpqZif. Accessed Jan. 11, 2018.