Gain of Function or Gain of Risk?: The Problem Behind Research On Enhanced Pathogens

Gain of Function or Gain of Risk?: The Problem Behind Research On Enhanced Pathogens

In the world of viral research, the study of pandemic diseases is a risky, if not dangerous, field of research. A subset of these studies is called gain-of-function research, and is the subject of many heated debates among members of the scientific community. The debates are understandable, as the consequences of mishandling viruses with pandemic potential are near-devastating for the safety of the country. With movies like Contagion (2011), it is hard to not be afraid of a nationwide pandemic caused by an accident in a lab. However, arguments of the necessity for understanding pandemic diseases are equally supported. The big question regarding research on enhanced pathogens stands: is deeper knowledge about pandemic disease worth the risk of accidentally spreading them?

In order to decide whether or not research on pandemic diseases is too risky to carry out, it is important to understand the core experimental procedure used in these studies. Scientists use gain-of-function research (GOF) to study how an entity gains a new property or function. In the case of the influenza (H5N1) virus, it was found  to have gained a new function of mammalian transmission. This was observed in the passage of the virus in ferrets and how that allowed selection for variants with ferret-to-ferret transmissibility. This discovery was significant because of H5N1’s newfound capacity to become transmissible in mammals by changing just a few amino acids.

However, GOF research also gave rise to beneficial discoveries, such as vaccines. In the case of certain human pathogenic viruses, such as poliovirus, attenuation occurred through passage in cells of another species. The gain-of-function observed was replication in another species, which in turn weakened its ability to replicate in human cells. This reduced ability to replicate in human cells made it a viable choice to be used as a vaccine against poliovirus.

Through practice of GOF experiments, the search for deeper understanding of potentially pandemic viruses yields useful results. The discovery of a new vaccine as well as a possible danger of the influenza virus is knowledge that reduces the mystery behind enhanced pathogens. Though these benefits seem worth it, the risks are also very concerning. Two main risks with pathogenic research that the National Science Advisory Board for Biosecurity (NSABB) were concerned with while reviewing the H5N1 GOF studies were biosafety and biosecurity, with more focus on biosecurity. While a biosafety risk is the likelihood of an accident that would cause an outbreak or an epidemic, a biosecurity risk is the likelihood that someone would use the viruses with the intention of harming the human population. Biosafety risks are more predictable and have a recorded history of occurrences. An example of a biosafety breach in the past would be the reintroduction of H5N1 into the population in 1970, which was caused by an accidental release of a laboratory strain. On the other hand, biosecurity risks are much harder to measure. Since the nefarious nature of humans is not easy to immediately detect, there is no way in knowing the likelihood of someone committing an act of bioterrorism. For these reasons, biosafety hazards are more dependable when assessing the potential risks of a certain laboratory procedure, and more specifically, procedures done in gain-of-function research.

Despite the many risks coupled with gain-of-function research, the new information on pandemic diseases and their capabilities are too important to neglect. Studying the possible mutations of enhanced pathogens is vital to the deeper understanding of the possible risks these pathogens may pose for society. Even though biosafety risks can occur, they should not stop revolutionary viral research from happening. It would be in everyone’s best interest if safe lab procedures were followed more thoroughly, thus minimizing the threat of biosafety breaches and allowing a movement towards fully comprehending the complexity of pathogens with pandemic capabilities.

The risk-reward dilemma presented by the gain-of-function research in enhanced pathogens is constantly being debated within the scientific community. Though the discoveries made through these experiments are valuable advancements in the understanding of pandemic disease, the risks are ever-present and extremely concerning. In October 2014, the White House enforced a mandatory moratorium on all gain-of-function research in response to the two Texan health-care workers getting infected with Ebola. Whether or not gain-of-function research is worth the risks, seems to have been decided for us.

Sources:

http://mbio.asm.org/content/5/4/e01730-14.full

http://blogs.nature.com/news/2014/10/white-house-suspends-enhanced-pathogen-research.html

 

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