Thread by @sambit_dash

A story about a pandemic.
“That’s one small step for man, one giant leap for mankind”. In the summer of 2005, these immortal words of Neil Armstrong was emailed by Dr Terrence Tumpey to his colleagues.

Working alone in a high security laboratory with biometric fingerprint, iris scan for his eyes alone, he had been the first man to resurrect an old demon – the 1918 Spanish Flu virus. #SpanishFlu

The Spanish Flu (or 1918 H1N1 flu to be politically/scientifically correct) killed 50 million people in the world. About 18 million in India alone. Unlike #COVID19 the virus killed maximally in 15-34 years age range.

For decades after the deadliest pandemic. What made it so deadly after all? The question perplexed researchers! Among several theories was that human beings were less immune (#BCGvaccine was only given 4 years later), healthcare facilities were poor (no #ventilators) and so on.

Enter – a virus hunter. 25 year old Swedish microbiologist Johan Hultin in hope to find the virus went to an obscure village Brevig Mission in Alaska where 72 of the village of 80 inhabitants dies in 1918 flu and were buried there.

Hultin found a little girl’s body preserved in the frozen earth in her blue dress and collected lung specimen.

But it was in 1951. Despite best efforts, the tissue could not be preserved well and when back in the lab, he injected the tissue in chicken embryos. It did nothing. A dead end. For the next four-and-a-half decades, nothing would happen to the virus.

In 1997, a young molecular pathologist Jeffery Taubenberger would publish a paper in journal Science on initial genetic characterization of Spanish influenza virus. But what was his source?

His team had extracted the RNA of the virus from preserved lung tissue of a US serviceman who had died on September 26, 1918.

It was after this sequencing that the virus was understood to be a novel influenza A (H1N1).
Re-enter a 72 year old Hultin. Another mission to Brevig Mission village in Alaska.

‘Lucy’, a 20 something woman, obese, was found with perfectly frozen lungs. These lungs tissue would give genetic material of the 1918 virus.
The name 'Lucy' was given by Hultin.

Two years later in 1999, the hemagglutinin gene of the virus would be sequenced using “Lucy’, serviceman and another human sample. Hemagglutinin protein lets the virus enter respiratory tract cells and flu vaccines target specifically this.

But all this could not yet answer the question – why was 1918 influenza virus so deadly.

Numerous studies were published on this in the next 5 years. 8 genes of the virus were enough to enough of them. By 2005, all of the genes were sequenced.

Centre for Disease Control (CDC) did not have an easy time deciding whether the virus, the deadliest pandemic flu of 20th century, was to be recreated. After much consideration, it decided to go ahead.

With highest safety standard possible at that time (today there are many BSL-3 labs even in India) in 2005, Dr Tumpey started work, who took antiviral drug as precaution and was well aware of the risks it involved.

Once the virus grew they had to be injected in mice. Now, mice are rarely get sick by human influenza strains. The mice died within just few days after being infected with the 1918 virus.

To check which of the 8 gene was causing this rapid viral reproduction, mice were infected with individual genes. None of them produced the virulence by itself.

Spanish Flu spread in the world with the soldiers of World War I. Today while facing a #COVID19 pandemic, unprecedented in all our lives, it is sobering to think about the H1N1 influenza virus of 1918.

What made the virus it so deadly?
It was “the constellation of all 8 genes together” which made it an exceptionally virulent virus.
End of Story.

Those who might be interested in this science history: @vishuguttal @zeusisdead @AnantBhan @patralekha2011 @SonaliVaid @epigiri @TheNaikMic @oommen @d_extrovert @ChandnaHimani @shashikiranu @amitvarma @ajumathew_ @TheRealDoctorT @anubhutivishnoi