Genetics and stem cells

The history of swine flu

The Independent says that “the swine flu pandemic might not have happened had it not been for the accidental release of the same strain of influenza virus from a research laboratory in the late 1970s.” The news comes from a medical article which analysed the history of the influenza A H1N1 virus, including the recent development of swine flu seen around the world.

The reports say that the H1N1 influenza strain was responsible for a flu pandemic in 1977, but before this it had not been found in humans for more than 20 years. By looking at the genetic makeup of the 1977 virus, researchers have found that it was similar to a strain that was circulating in 1950. This 1950s strain would have been stored in labs and researchers have suggested that the re-emergence of the virus in 1977 “was probably an accidental release from a laboratory source”, possibly through laboratory workers becoming infected.

Professor John Oxford of the Royal London Hospital is reported as saying that the theory is “plausible”, but that “it may have been a good thing as it would have given many older people alive today some measure of immunity to the current pandemic.” The newspapers have concentrated on the possibility of an accidental reintroduction of the H1N1 virus during the 1970s. However, this is only one aspect of the complex history of the current pandemic swine flu virus discussed in the article. The current swine flu virus has developed over time by natural exchange of genetic material between human, bird and pig strains of the influenza virus. This review does not suggest that the current form was created in or leaked from a laboratory.

Where did the story come from?

The news story is based on a scientific article in the peer-reviewed New England Journal of Medicine by Dr Shanta M Zimmer and Dr Donald S Burke from the University of Pittsburgh. It was funded by the National Institute of General Medical Sciences in the US and the Bill and Melinda Gates Foundation.

What kind of scientific study was this?

The study was a narrative review which described the history of the current swine-origin influenza A virus (H1N1) strain, commonly known as swine flu. The authors discussed the evolutionary and epidemiologic events that led to the emergence of the swine flu strain that caused the current pandemic.

What were the results of the study?

The authors describe the first appearance of influenza in pigs in 1918, when there was a pandemic of human influenza A (H1N1). Pigs also developed respiratory symptoms resembling those of people with the virus, which led scientists to believe that the influenza virus was also infecting pigs.

The authors of this review describe various laboratory experiments in pigs and other animals that supported the theory that the influenza virus seen in pigs had come from the 1918 human pandemic strain. This includes a 1930s study that showed that human antibodies against the 1918 strain of human influenza A (H1N1) could prevent mice from being infected with swine influenza.

After 1918, the rapid changes in the human influenza virus meant that it became different to the influenza virus seen in pigs. The authors say that genetic studies of samples of the human H1N1 virus taken between 1918 and 2006 from 17 countries have shown that the virus gradually mutated over time, exchanging genetic material between different subtypes of the virus. However, it has not gained new genetic material from birds or other sources.

The disappearance of the human H1N1 virus
The authors say that from 1957, influenza A (H1N1) was no longer circulating in humans and that it was replaced by the H2N2 virus. This virus contained genetic material from both the H1N1 strain and a bird virus. The influenza A (H1N1) virus was not identified in humans again until 1977. The authors report that the reasons for this disappearance are not clear, but it may be because an increased immunity against the H1N1 strain, along with the immune reaction against the H2N2 strain, was enough to wipe out the H1N1 strain.

The authors describe evidence of sporadic transfers of swine flu infection to humans over the past 50 years. The first evidence of such transmission was documented in 1958. They say that swine influenza infection in humans may often go undetected because the symptoms were similar to those of human influenza. The sporadic cases of transmission were reported to be through work-related and environmental exposures, including family members of people in high-risk groups (such as those who worked with pigs).

The authors mention an outbreak of a new H1N1 strain of swine influenza in soldiers at an army base in New Jersey in 1976, which resulted in 230 confirmed cases and one death. The virus had a low person-to-person transmission rate and, although it spread within the army base due to close social contact, it did not spread outside the base. A mass immunisation programme against this outbreak immunised 40 million civilians.

*The re-emergence of the human H1N1 virus
In 1977, the H1N1 virus also re-emerged in China, Hong Kong and the former Soviet Union. This virus had relatively mild effects and affected mainly young people. This strain was closely related to the strain that circulated in 1950, but not to those seen in 1947 and 1957.The authors say that this suggests that the strain had been “preserved since 1950” and that the re-emergence “was probably an accidental release from a laboratory source” that had managed to take hold due to the waning immunity to this strain in the population.

They say that since this time, the H1N1 virus has been circulating with another influenza A subtype (H3N2, the subtype that is more often dominant) during outbreaks of seasonal flu.
The authors discuss changes in the swine influenza virus since 1979. They report that, although swine influenza was detected in pigs in the US as early as 1930, it only spread to Europe in 1976 in a shipment of pigs from the US to Italy. A few years afterwards, the strain was replaced by another H1N1 strain, which was passed onto pigs from wild ducks. There were also reports of events occurring in China.

A new strain was also identified in North American pigs in 1998. This virus had a complex genetic makeup, with parts of its genetic sequence from the original H1N1 swine virus but other parts from bird influenza and human influenza viruses. As the genetic material was combined from three different sources, this was called a “triple reassortant” virus.

The first case of human infection with the triple reassortant virus occurred in Wisconsin in the US, where a 17-year-old became infected after being exposed to pigs at a slaughterhouse. Eleven further cases were reported between 2005 and 2009, with most of those infected having been exposed to pigs. However, the authors note that it is likely that more cases have occurred, as generally people with influenza symptoms do not have their virus isolated and tested to determine its origins.

The swine flu pandemic
The first two cases of the current strain of pandemic swine influenza (called the S-OIV strain) in the US were reported in April 2009. The US Centers for Disease Control and Prevention (CDC) found that these cases were caused by a swine virus that had not previously been identified in the US. Genetic analysis of the virus showed that it contained some genetic material from the triple reassortant swine virus and some from the Eurasian influenza A (H1N1) swine virus lineage.

The authors report that the newly emerged pandemic swine flu virus (S-OIV) has some weak genetic similarity with the circulating seasonal H1N1 virus within parts of their genetic makeup that are descended from the original 1918 strain. They say that how these two strains will compete is uncertain and that it is unknown whether immunity against the seasonal strain might offer some protection against the newly emerging virus.

What interpretations did the researchers draw from these results?

The authors conclude that the emergence of the swine flu pandemic highlights the importance of greater understanding and study of viruses that can affect both animals and humans. They also stress the “critical importance of international collaboration in efforts to predict and control future pandemic threats”.

What does the NHS Knowledge Service make of this study?

This review discusses the history of the influenza A (H1N1) viruses, leading up to the current swine flu pandemic. This history includes the original transmission of the H1N1 strain from humans to pigs during a 1918 pandemic, the divergence of the human and swine flu strains, the disappearance and re-emergence of the human H1N1 strain and genetic changes in the swine and human H1N1 strains.

The newspapers have concentrated on the probable reintroduction of the H1N1 strain into the human population from a laboratory during the 1970s. However, this was only one small aspect of the complex history of the swine flu virus, which has now become a pandemic.

The current swine flu virus has developed over time by natural exchange of genetic material between human, bird and pig strains of the influenza virus, and this review does not suggest that the current virus has been leaked from a laboratory.

NHS Attribution