The Reemergent 1977 H1N1 Strain and the Gain-of-Function Debate (2015)

Here's the 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.

And a Twitter thread from 2021:

[....] the Soviets employed tens of thousands to make biological weapons, but this wasn't yet known to the western world. They def didn't have the greatest safety record-- a couple years later in Sverdlovsk an anthrax accident killed at least 66 people.

However, flu vaccine manufacturing was more typically used as a cover for biological weapons research. For example, Omutninsk Chemical Factory manufactured flu vaccine and crop production bacteria aboveground, while plague and tularemia worked on in underground facilities.

Vaccine trial possibility: Two big factors support the 1977 flu being caused by a vaccine/challenge trial. 1. live attenuated influenza virus (LAIV) research was big at the time and 2. a 1976 H1N1 swine flu outbreak was feared to have pandemic potential, and the 1977 flu was H1N1

In early days, LAIV often reverted to being infectious. Many 1977 H1N1 isolates were temperature sensitive, suggesting lab manipulation to make a vaccine. The Soviets and Chinese had done LAIV flu trials with tens of thousands of children, and even did challenge studies (!!).