One of the most controversial fields of study relevant to public health and pandemic prevention is that of infectious agents with the potential to incite widespread outbreaks in humans, referred to as pandemic potential pathogens (PPPs). As established in the resources provided during Week 1, there is no single perfect candidate identifiable as the next ‘Disease X’ - but there are a number of properties which increase the likelihood of a pathogen to cause infection on such a vast scale. For example, a prion is unlikely to be considered a ‘pandemic potential pathogen’ as transmission rates are typically low and relatively exceptional circumstances are required for an outbreak to occur (e.g. mass consumption of contaminated meat, or a communal event of human cannibalism). On the other hand, an RNA virus with a high replication rate, high adaptability and virulence, zoonotic potential and a means of airborne transmission would traditionally be considered high-risk and a likely target for biosurveillance initiatives.
Whilst research into such an RNA virus could potentially be beneficial, providing insight into processes of pathogenesis (the process by which a disease develops), allowing for improved understanding of zoonotic disease progression in animal models (which, in turn, enables the development of more reliable treatment plans should spillover occur) and facilitating the production of recombinant viruses which can be utilised to identify specific genes related to virulence or immune evasion (research which could serve as the basis for vaccine development), the risk associated with possible lapses in biosafety practices is extremely high. Furthermore, ‘gain of function’ (GoF) PPP research results in the production of enhanced pandemic potential pathogens (EPPPs), which have been genetically altered to produce recombinant pathogens with enhanced biological functions (e.g. increased virulence, transmissibility or immunogenicity).
The term ‘gain of function research’ stems from two 2011 research experiments utilising the H5N1 strain of the avian influenza virus, that which is associated with a mortality rate of around 60%. Working separately, virologists Yoshihiro Kawaoka and Ron Fouchier managed to mutate the viral strain such that it became easily transmissible between ferrets - mammals whose immune response to influenza viruses is considered most similar to that of humans - where airborne transmission had previously proven extremely inefficient. Fouchier later declared that his team had likely created “probably one of the most dangerous viruses you can make”, with the National Science Advisory Board for Biosecurity (NSABB) chairman Paul Keim stating that he couldn’t think of “another pathogenic organism that is as scary as [the engineered H5N1 virus]”. Kawaoka and Fouchier were subsequently required by international advisory boards to halt their experimentation and delay the publication of their findings, for fear that malevolent actors could seek to replicate their research experiments and produce a viral strain of such enhanced pathogenicity that anthrax could be said to pale in comparison. Whilst the virologists were later allowed to resume their research, the associated risk remains almost unfathomably high. Just a eight years later, during further experimentation involving ferrets and the H5N1 EPPP, the air-purifying respirator hose of a trainee member of Kawaoka’s fell loose, allowing for the inhalation of contaminated air. The University of Wisconsin-Madison, with which this research was associated, failed to report this incident to the public, or to relevant public health officials, with a relevant laboratory compliance official curtailing the trainee’s quarantine period without undertaking any official consultation.
As EPPPs have been deliberately engineered to enhance the biological functions associated with heightened pathogenicity, there is an inherent risk of dual use associated with their creation. As historical analysis of warfare indicates, the bioweapon is an increasingly attractive prospect to those intending to cause mass incapacitation of enemy populations. For example, the British government purchased Gruinard Island during the Second World War with the intention of trialling the usage of anthrax spores as a means of infecting the German opposition. Dozens of sheep were deployed to Gruinard, wherein they were subject to experiments involving anthrax “explosions” and the provision of anthrax-laced linseed cakes. The government’s anthrax distribution plan was eventually abandoned in favour of the development of nuclear weapons programmes, but ‘Operation Vegetarian’ remains a stark reminder of the potential of a particularly virulent pathogen to become a bioweapon. It is also worth noting that the contamination of the local ecosystem led to the death of livestock on the mainland, for which the government offered compensation - insisting that the deaths had occurred as a result of diseased Greek sheep falling into the local waterways.
As the examples of Gruinard Island and the H5N1 laboratory safety breach suggest, the organisational bodies responsible for laboratory leaks and environmental contamination are often loath to admit culpability. This negligence could place the public at increased risk of exposure to PPPs and EPPPs and impede the biosurveillance efforts forming the backbone of early warning pandemic preparation systems - and this risk isn’t even comparable to that presented by malevolent actors working in invisible biolabs, with the very intention of engineering the next ‘Disease X’ and causing mass destruction.
❓A prion is a transmissible misfolded protein - and therein not considered a living organism, as it contains no genetic data encoded via nucleic acids. When a protein in the brain folds abnormally - becoming a prion - it can induce further abnormalities in the tertiary structure of other proteins, triggering a chain reaction which can result in the development of a neurodegenerative disease. One example of a large-scale disease event caused by the transmission of prions is the series of kuru outbreaks experienced by tribal populations in Papua New Guinea between the 1950s and 1960s - incited by the ritualistic consumption of the brain tissue of the deceased, as enacted by the Papua New Guinean Fore people.
Mandatory Resources 🦠
A WIRED Article Explaining How New Technologies Identify Bioengineered Pathogens
A Short Article Exploring Biosafety Concerns in ePPP Research
“Dangerous Lab Leaks Happen Far More Often Than The Public Is Aware”: A Guardian Article