Photo: PTI
Photo: PTI

The curious case of the H1N1 mutation

India's rejection of an MIT study on swine flu reveals a transcontinental trail of unanswered questions about the genetic data involved

From culture to disease, the global swirl of things in this era of jetliners and the Internet is limitless—olives, jihad, Kim Kardashian and swine flu. So it was last month that I reached out to Ram Sasisekharan, a professor of biological engineering at the Massachusetts Institute of Technology (MIT) in Boston, to talk about the growing dread in India about H1N1, popularly called swine flu.

Why, you might ask, am I talking to someone on the other side of the world in one of the world’s most advanced countries, when H1N1 is raging here in chaotic, overpopulated India with its dramatically different circumstances? Swine flu, as the name suggests, has some porcine origins, but it is a variety of influenza spread by a virus with a globalized mix of swine, bird and human genes. Like its mother virus, H1N1 is a global genetic puzzle, with scientists in various countries monitoring bits and pieces and trying to see the big picture, as the virus evolves, mutates and changes, alternating a benign life within humans with killing them in droves.

The column I wrote in this paper on 19 February explored why the virus was continuing to kill people when it should have been—as Indian scientists had predicted—dying out with the coming of warmer weather. After all, this was the same virus that flared up mildly each year, killing an average of less than 700 Indians every year over the last six years. Yet, in less than three months of 2015, it has killed 1,731 people (as of 15 March), closing fast on its highest toll—1,763 killed in 2010.

These events threw up many questions: Had the virus mutated? Had it followed its evolutionary imperative again and swapped genes to transform from mild concern to serious threat? Is India in danger of facing a pandemic, an epidemic spread across a wide area, striking a vast swathe of the population? Varieties of flu kill between 250,000 and 500,000 people every year, the World Health Organization says, the toll soaring in pandemic years.

Sasisekharan was particularly well placed to provide some answers because over the years he had closely examined H1N1’s evolution by tracking its genetic sequence, the virus’ DNA code. In 2011, Sasisekharan and his colleagues at MIT revealed the virus to be a quick-change artist. A simple two-letter change in H1N1’s code, the scientists found, let the virus bind better to human cells, in other words, mutate and become more virulent.

Had a mutation occurred in India to explains H1N1’s greater virulence? When I spoke with him last month, Sasisekharan said it was hard to tell because there was little or no “sequence information" on the Indian H1N1 strain circulating in global, genetic databases. This was frustrating, he said, because such information-sharing allowed collaborative efforts, which were key to surveillance, management and predicting the spread of the virus. Back in India, the only information made available by unnamed scientific sources in a couple of newspapers was that H1N1 genetic sequences with the National Institute of Virology (NIV) in Pune showed no mutations.

On 6 March, MIT public relations alerted me—one of many heads-up that I get from scientific institutions around the world; in India, I get none—to a forthcoming paper from Sasisekharan. As is the practice, worldwide, I got access to the paper on the routine condition that it would not be released before a specified time on the embargo date of 11 March.

My story (for the data-driven public-interest journalism nonproft, IndiaSpend, of which I am the editor) was out at midnight. By the next morning, Sasisekharan was inundated by calls and emails from India. His paper—published in Cell Host and Microbe, a global scientific journal—essentially said that the Indian H1N1 virus, a genetic sample of which he had obtained from a global database, showed changes in a gene called heammaglutinin, known to mark virulence. In other words, the Indian virus may have mutated, which might explain the unexplained virulence and unprecedented death toll (although the infection rate, compared to 2010, is not particularly worrying for a flu outbreak). The paper also noted that India ranked a low 14th in a global list of contributors of complete H1N1 genetic sequences.

An MIT professor is hard to ignore, and as the story went, well, viral, and the media asked a normally reticent NIV for reactions, the government—within 24 hours—put out a press release. It denied there were any mutations.

“Our experts have carefully examined the findings mentioned in the above-mentioned publication (Cell Host and Microbe)," the release said. “We found that the strain analyzed in the said publication and the sequence data of the original H1N1 virus...as available with NIV did not show any of these mutations." Neither did an analysis of the virus by the US Centers for Disease Control and the World Health Organization report genetic changes or resistance to oseltamivir, the main anti-H1N1 drug, the release said.

For the Indian media, the story mostly ended there. I continued a back-and-forth with the scientists involved in both countries. To me, the Indian government’s stand only threw up more questions.

If there were no mutations, as the NIV insisted, then where did Sasisekharan get his genetic data from? It had to have come from India.

When I asked Sasisekharan, he sent me a screenshot of the genetic sequence as it appears on the Global Initiative on Sharing Avian Influenza Data (GISAID), a leading depository of such information.

“Anyone can log on and verify the information at www.platform.gisaid.org," he wrote in an email.

The name and address of the originating laboratory: NIV, Pune.

Contacting NIV isn’t quite as easy as emailing or calling Boston. But an email—obtained after a couple of calls to NIV—to Mourya led to a quick response, through his secretary. “The commentary by MIT scientists in Cell Host & Microbe is based on the analysis of a single HA (heammaglutinin) gene of a H1N1 virus A/India/6427/2014 strain that was submitted to GISAID by CDC Atlanta USA (screenshot below) and not National Institute of Virology Pune India which was the originating lab," Mourya’s email said. “Hope this clarifies the issue."

It did not. The screenshot was the same one I got from Sasisekharan. Curiously, it showed the same user logged in, Kannan Tharakaraman, Sasisekharan’s colleague, which meant that Mourya was sending me the same screen shot he had received from the media, who obviously got it from Sasisekharan!

As Mourya said, the CDC did sumbit the genetic sample, but it originated from NIV.

I emailed Mourya again, pointing this out. His response: “I think you can have a look on passage level C1 & C2 also." The GISAID database did have that entry. I asked him what he meant. He never replied, but his implication was that the genetic sequence that the MIT scientists used was not original and hence unreliable.

This kind of a defence--if you can call it that--only raises more questions:

Since NIV has samples of the H1N1 virus panicking India, why does it not release the genetic sequences? The H1N1 virus’ proclivity to mutate is now common scientific knowledge, so--instead of running down warnings--does it not make sense to share its current and evolving genetic profile? Given the dangerous global history of influenza, should not worldwide collaboration be a preferred option to bland, unconvincing denial?

The quicker NIV and India’s government start answering these questions, the better.

Samar Halarnkar is editor of IndiaSpend.org, a data-driven, public-interest journalism non-profit. He also writes the column Our Daily Bread in Mint Lounge.

Comments are welcome at frontiermail@livemint.com. To read Samar Halarnkar’s previous columns, go to www.livemint.com/frontiermail

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