The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate

Abstract

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. While the origin of the outbreak cannot be conclusively determined without additional evidence, there are very plausible alternatives to the laboratory accident hypothesis, diminishing the relevance of the 1977 experience to the modern GOF debate.

FIG 1

Phylogenetic tree of late 1950s and 1977 influenza virus strains. Distance was calculated using BLOSUM 62 based on HA amino acid sequence. Black box indicates 1977 strains and the most similar late 1950s strains.

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.