mBio: “The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate”

The 1977-1978 influenza epidemic was probably not a natural event, as the genetic sequence of the virus was nearly identical to the sequences of decades-old strains. While there are several hypotheses that could explain its origin, the possibility that the 1977 epidemic resulted from a laboratory accident has recently gained popularity in discussions about the biosafety risks of gain-of-function (GOF) influenza virus research, as an argument for why this research should not be performed. There is now a moratorium in the United States on funding GOF research while the benefits and risks, including the potential for accident, are analyzed. Given the importance of this historical epidemic to ongoing policy debates, we revisit the evidence that the 1977 epidemic was not natural and examine three potential origins: a laboratory accident, a live-vaccine trial escape, or deliberate release as a biological weapon. Based on available evidence, the 1977 strain was indeed too closely matched to decades-old strains to likely be a natural occurrence.

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While the use of the 1977 influenza epidemic as a cautionary tale for potential laboratory accidents is expedient, the relevance to GOF research is greatly diminished if the 1977 epidemic was the result of a vaccine trial or vaccine development gone awry; these are both more plausible explanations than a single laboratory accident. In addition, in 1977, influenza research was performed without modern biosafety regulations and protective equipment, making the lab accident hypothesis much less relevant to the modern GOF debate. While the events that led to the 1977 influenza epidemic cannot preclude a future consequential accident stemming from the laboratory, it remains likely that to this date, there has been no real-world example of a laboratory accident that has led to a global epidemic.

Michelle Rozo & Gigi Kwik Gronvall

Interesting research into the origins of another pandemic, much less severe than the current one. The authors conclude the more likely explanation is a faulty vaccine trial that allowed the virus to spread again among the general population. While this is only circumstantially related to the ongoing, and growing, discussion about the possibility of a coronavirus lab leak, it provides another solid reason why human challenge trials are a bad idea: if the vaccine on trial is ineffective, you risk spreading the very pathogen you were trying to combat.

Fig 2 Explanations for the origin of the 1977 influenza epidemic have changed over time. Timeline of the 1977 H1N1 epidemic and relevant modern influenza events (left) correlated with explanations of the origin of the 1977 viral strain (right). A comprehensive search was performed using PubMed, searching for “1977 AND H1N1”, which produced 159 results, published between 1977 and 2015. Additionally, “1977 H1N1” was placed in Google search engine, and the first 100 results were examined. Non-English publications were excluded. Out of these results, 41 publications that listed a conclusion regarding the reemergence of the 1977 H1N1 strain were identified. The 41 publications are listed in the Appendix. The conclusion was subcategorized into six types, and the frequencies of these were plotted over time. Both the number of mentions (y axis) and the conclusion (“most likely lab accident”) increased in prominence over time. MERS, Middle East respiratory syndrome; SARS, severe acute respiratory syndrome.