Accidental release of virus may have triggered mysterious 1977 pandemic: ScienceAlert

On February 5, 1976, nineteen-year-old U.S. Army Private David Lewis set out from Fort Dix with his unit on a 50-mile hike. On that bitterly cold day, he collapsed and died.

Autopsy samples unexpectedly tested positive for the H1N1 swine influenza virus.

Viral disease surveillance at Fort Dix identified an additional 13 cases among recruits hospitalized for respiratory illnesses. Additional serum antibody testing revealed that over 200 recruits had been infected with the new H1N1 swine virus strain but had not been hospitalized.

Alarm bells immediately began ringing in the epidemiological community: Could Pvt. Lewis' death from H1N1 swine flu be a harbinger of another global pandemic similar to the horrific H1N1 swine flu pandemic of 1918, which killed an estimated 50 million people worldwide?

The US government reacted quickly. On March 24, 1976, President Gerald Ford announced the plan to “vaccinate every man, woman and child in the United States.”

The mass immunization campaign began on October 1, 1976.

Meanwhile, the initial small outbreak at Fort Dix quickly subsided, and there have been no new cases at the base since February.

As Army Colonel Frank Top, who led the investigation into the virus at Fort Dix, later told me, “We had demonstrated pretty conclusively that (the virus) didn't go anywhere else but Fort Dix… it disappeared.”

Nevertheless, biomedical scientists around the world were concerned about this outbreak and saw the massive crash vaccination program in the United States. They began research and development programs for vaccines against H1N1 swine flu in their own countries. By the beginning of the winter of 1976-77, the world was waiting for – and preparing for – a pandemic of H1N1 swine flu, which never came.

But that wasn't the end of the story.

As an experienced infectious disease epidemiologist, I argue that these seemingly prudent but ultimately unnecessary preparations had unintended consequences.

What was strange about the Russian H1N1 flu pandemic?

In an epidemiological twist, a new pandemic influenza virus did indeed emerge, but it was not the expected H1N1 swine virus.

In November 1977, Russian health authorities reported that a human (not swine) strain of H1N1 flu had been discovered in Moscow. By the end of the month, the virus had been reported throughout the USSR and soon worldwide.

Compared to other influenza viruses, this pandemic was strange.

First, the fatality rate was low, about one-third of that of most influenza viruses. Second, it regularly infected only people under the age of 26. Finally, unlike other newly emerged pandemic influenza viruses in the past, the virus failed to displace the already dominant H3N2 subtype, which was the seasonal flu this year.

Instead, the two flu viruses – the new H1N1 and the long-known H3N2 – circulated side by side.

Here the story takes a different turn. Microbiologist Peter Palese used a then-novel technique called RNA oligonucleotide mapping to study the genetic composition of the new Russian flu virus H1N1.

He and his colleagues grew the virus in the lab and then used RNA-cutting enzymes to chop the viral genome into hundreds of pieces. By distributing the chopped RNA in two dimensions based on size and electrical charge, the RNA fragments created a unique, fingerprint-like patch map.

To Palese's great surprise, when he compared the spotting pattern of the 1977 Russian H1N1 flu with a number of other flu viruses, he found that this “new” virus was essentially identical to older H1N1 human flu strains that had become extinct in the early 1950s.

So the 1977 Russian flu virus was actually a strain that had disappeared from the planet a quarter century earlier and then somehow came back into circulation. This explained why it only affected younger people—older people had already been infected and become immune when the virus was circulating in its earlier form decades ago.

But how could the older variety become extinct again?

Refining the timeline of a resurrected virus

Despite its name, the Russian flu probably did not begin in Russia. The first published reports of the virus came from Russia, but later reports from China suggested that it had first been detected months earlier, in the Chinese port city of Tientsin, in May and June 1977.

In 2010, scientists used detailed genetic studies of several samples of the 1977 virus to determine the date of their earliest common ancestor. These “molecular clock” dates suggest that the virus first infected humans a full year earlier, in April or May 1976.

So the best evidence is that the Russian flu of 1977 actually occurred – or rather “reoccurred” – in or near Tientsin, China, in the spring of 1976.

A frozen laboratory virus

Was it just a coincidence that within a few months of Private Lewis' death from swine flu H1N1, a previously extinct strain of influenza H1N1 suddenly reappeared in the population?

Influenza virologists around the world had been using freezers for years to store flu viruses, including some that had become extinct in the wild. Fears of a new H1N1 swine flu pandemic in the United States in 1976 had led to a worldwide surge in research into H1N1 viruses and vaccines.

The accidental release of one of these stored viruses would have been entirely possible in any country conducting H1N1 research, including China, Russia, the United States, the United Kingdom, and probably other countries.

Years after the disease resurfaced, microbiologist Palese reflected on personal conversations he had had with Chi-Ming Chu, China's leading flu expert.

Palese wrote in 2004 that “the introduction of the H1N1 virus in 1977 is now attributed to vaccine trials in the Far East in which several thousand recruits were infected with live H1N1 viruses.”

Although it is not known exactly how such an unintentional release could have occurred during a vaccine trial, there are two main theories.

First, scientists could have used the resurrected H1N1 virus as a starting material to develop a live, attenuated vaccine against H1N1. If the virus had not been sufficiently attenuated in the vaccine, it would have been transmissible from person to person.

Another possibility is that researchers used the resurrected, live virus to test the immunity provided by conventional H1N1 vaccines and that the virus accidentally escaped from the research setting.

Whatever the precise mechanism of release, the combination of the precise location and timing of the pandemic's origin and the status of Chu and Palese as highly credible sources strongly suggests that the Russian flu virus originated from an accidental release in China.

A sobering history lesson

The resurgence of an extinct but dangerous human-adapted H1N1 virus occurred as the world was desperately trying to prevent the looming outbreak of a swine flu pandemic. People were so worried about the possibility of a new pandemic that they inadvertently triggered one.

It was a pandemic that was a self-fulfilling prophecy.

I am not attempting to assign blame here; my main argument is that in the epidemiological fog of 1976, when fear of an impending pandemic was mounting around the world, a research unit in any country could have inadvertently released the resurrected virus that would later be called the Russian flu.

In the global race for research and vaccinations, a possible new pandemic of swine flu H1N1 was to be prevented from Fort Dix. Accidents could have happened anywhere.

Of course, biosafety facilities and policies have improved dramatically over the past half century. But at the same time, there has been an equally dramatic increase in high-security laboratories around the world.

Overreaction. Unintended consequences. Making the situation worse. Self-fulfilling prophecy. There are a variety of terms to describe how the best intentions can go wrong.

The world is still reeling from the effects of COVID-19 and now faces new threats from the cross-species spread of avian influenza, MPOX and other viruses. It is critical that we respond quickly to these new threats to prevent another global wave of disease.

Fast, but not too fast, as experience shows.

Donald S. BurkeDean Emeritus and Distinguished Professor Emeritus of Health Science and Policy and Epidemiology at the School of Public Health, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.