With exploding human populations and a globalized economy, the threat of pandemic disease and fear surrounding such pandemics is a pandemic in itself. Human beings have never been so connected, and it has never been easier for an emerging infectious disease to spread across borders and across oceans. Frightening diseases such as high pathogenicity avian influenza and ebola appear regularly in the news and threaten to cause high mortality in the countries where they emerge as well as abroad. How do we as a society deal with the threat of these dangerous, potentially pandemic pathogens? The answer to that question is more controversial than you might think.
Though it may seem obvious that humanity would be better off with vaccines and drugs to prevent and treat emerging, potentially pandemic diseases, research to develop these lifesaving interventions does not come without risk. In order to study a potentially dangerous infectious agent, a scientist needs to be able to work with it in his or her laboratory. If the infectious agent is present in the lab, what is to stop it from escaping and causing the very pandemic that the scientist’s work was aimed at preventing?
Naturally, there are many precautions and regulations in place to prevent such a release. For dangerous, potentially pandemic pathogens, depending on the route of exposure, scientists work at either Biosafety Level 3 (BSL3) or Biosafety Level 4 (BSL4) containment.
Under BSL3 conditions (image below), researchers work in laboratories under positive pressure and keep all work contained to hoods, designed so that air flows only into a contaminated environment and not back out without being thoroughly filtered and sterilized.
Influenza researcher working under Biosafety Level 3 (BSL3) precautions. (CDC Public Health Image Library)
Under BSL4 conditions, all work is contained to highly secure, thoroughly protected spaces, and scientists are only given access to the work area while wearing full biohazard suits, for maximum isolation of pathogenic agents. If you picture the lab scenes from any recent pandemic science fiction movie, Contagion being a prime example, you are probably picturing BSL4.
Unfortunately, biohazard containment is not foolproof, and occasionally potentially dangerous infectious agents are not properly contained. Although no recent laboratory incidents have led to a catastrophic pandemic, newsworthy incidents have occurred.
In one incident in March, high virulence H5N1 avian influenza cross-contaminated a sample of low-virulence flu, which was then transferred to another laboratory not properly equipped to handle high virulence infectious agents.
“occasionally potentially dangerous infectious agents are not properly contained”
In a separate incident in June, anthrax bacteria from a BSL3 laboratory were transferred to a BSL2 laboratory after scientists followed a novel and unapproved inactivation procedure, raising the fear that the transferred anthrax was not fully inactivated prior to its transfer, and resulting in potential anthrax exposure for individuals working in the lower containment BSL2 facility.
Both incidents occurred in laboratories controlled by the Centers for Disease Control and Prevention (CDC). In neither incident did an actual exposure to pathogenic material occur, but these incidents do raise questions about the appropriateness of certain research on dangerous, potentially pandemic pathogens. Indeed, the CDC has faced pressure to improve its biosafety procedures, with some even calling for a moratorium to be placed on conducting research with potentially dangerous pathogens.
Director of the CDC Thomas Frieden has addressed these concerns, saying, “The fact that something like this could happen in such a superb laboratory is unsettling because it tells me that we need to look at our culture of safety throughout all of our laboratories.”
In light of these incidents and additional controversy surrounding gain-of-function influenza research, which triggered a moratorium on such research in 2012, a coalition of scientists called the Cambridge Working Group (CWG) has arisen to challenge the right of scientists to conduct research on potentially pandemic pathogens. Essentially, the CWG is against conducting any research that is not zero risk, for fear of creating the very pandemics infectious disease scientists hope to prevent.
In the mission statement posted to the CWG website, the signatories state that experiments “involving the creation of potential pandemic pathogens should be curtailed until there has been a quantitative, objective and credible assessment of the risks, potential benefits, and opportunities for risk mitigation, as well as comparison against safer experimental approaches.”
The scientists of the CWG have also called for a conference to discuss what is needed to contain and curtail dangerous pathogen research, similar to the Asilomar conference held in 1975 to discuss the safety and permissibility of research involving recombinant DNA technology.
In response to the CWG, a number of scientists have raised their voices in opposition to what some in the scientific community consider to be alarmist and reactionary obstructionism to scientific progress. These “Scientists for Science (SFS)” have posted a mission statement arguing that work on potentially pandemic pathogens is necessary for scientific advancement and protection of the population. In particular, the SFS assert that it is possible to perform research safely and responsibly within the frameworks that have already been established by national and international regulatory bodies.
“a number of scientists have raised their voices in opposition to what some in the scientific community consider to be alarmist and reactionary obstructionism to scientific progress”
The SFS take issue with the CWG’s position that gain-of-function experiments and other work with potentially pandemic pathogens comes at little benefit to society. Instead, the SFS argue that the results of individual experiments are difficult to anticipate, often serendipitously beneficial, and only properly understood in the context of a wide body of experimental work.
Indeed, the SFS emphasize that it is difficult to perform a risk-benefit analysis when the benefits are unknowable but potentially crucial and the risks minimized whenever possible. To this end, the SFS have called for the efforts of researchers and regulators to be focused on maximizing the safety and security of BSL3 and BSL4 facilities, rather than on curtailing potentially dangerous pathogen research in a reflexive way.
The SFS and CWG both agree that an Asilomar-like conference should be held to discuss best practices and potential additional regulation of research on potentially dangerous pathogens. However, these groups disagree on who would best be suited to organize such a meeting.
Whereas the CWG proposes organizing such a meeting itself, the SFS propose a neutral party organize the meeting so that all alternatives are weighed equally, and a problem with research on potentially dangerous pathogens is not presumed to exist; indeed, unlike recombinant DNA work at the time of Asilomar in 1975, the SFS argue that potentially dangerous pathogen work is already highly regulated and extensively monitored. Neutral parties proposed by the SFS to convene such a meeting include the International Union of Microbiological Societies, the American Society for Microbiology, and national academies, such as the U.S. National Academy of Sciences.
This controversy is unlikely to be resolved until such a meeting takes place. Scientists, regulators, and legislators need to weigh the risks of dangerous potentially pandemic pathogen research against the need to develop treatments and vaccinations effective against these pathogens. Do we risk being the instruments of our own destruction, or stand by while dangerous pathogens grow more and more threatening as the human population becomes larger and denser with each passing day? There is no easy answer.
Conflict of interest statement: Michael Schreiber is a PhD student in the laboratory of Vincent Racaniello, a co-organizer of scientistsforscience.org.
