Resurrection of the 1918 influenza virus

Why Revive a Deadly Flu Virus?

"Inside the freezer were trays and boxes containing "select agents" -- highly pathogenic microbes that under the Patriot Act cannot be handled without special clearance from the Department of Justice. Tumpey wiped the frost off a box. He was the only person in the C.D.C., or anywhere else, authorized to handle this particular agent: a synthesized version of an influenza virus that, nearly a century before, killed between 20 million and 50 million people. He placed the box in a secure container, and after showering and dressing, carried the container through secure corridors to another building at the C.D.C., where he entered another suite of rooms, dressing once again according to Biosafety Level 3+ protocols, the second most stringent level of biosecurity. For the next couple of hours, he squirted the virus into the nostrils of laboratory mice. He was fairly certain they would all soon die."

"In the 20th century, flu pandemics occurred in 1918, 1957 and 1968. The last two killed two million and 700,000 people respectively -- again, claiming most of their victims among the young, the old and the weak."

"In the fall of that year it spread across the planet, perversely striking down healthy young adults. Once ensconced in their lungs, the virus triggered a havoc of inflammation, hemorrhage and cell death. Trying to draw air into such lungs was like breathing through meat. Many of the afflicted died within hours after they first began to feel a little feverish. Others succumbed more slowly to secondary bacterial infections. By the spring of the following year, the virus had disappeared as mysteriously as it had come."

"The second, and in some ways even more remarkable, thing about the 1918 flu virus is that it has literally been brought back to life. In October, a team of scientists, Tumpey among them, announced that they had recreated the extinct organism from its genetic code -- essentially the scenario played out in the movie "Jurassic Park," albeit on a microbial scale."

"Give me $100,000 and two months, and I can recreate it right here in my lab," says Earl Brown, a flu researcher who specializes in the evolution of virulence at the University of Ottawa. "You wouldn't be able to tell it from the real thing that was around a hundred years ago. Would it kill at the same rate as in 1918? Probably. But you really don't want to have to find that out. You don't want to give this thing a second time around."

"Jeffery Taubenberger, the man most responsible for resurrecting the 1918 flu virus, was looking a little sick. His face was pale and his eyes red-rimmed, and he had barely touched the pasta he ordered for lunch. He pulled out a handkerchief and sneezed hard."

"There's not a respiratory virus on earth that I don't seem to want to amplify," he told me. "If I were alive in 1918, I'd be dead."

"Taubenberger is the chairman of the department of molecular pathology of the Armed Forces Institute of Pathology in Rockville, Md."

"The resurrection of the 1918 flu incarnates this turning point. It is not the first virus to be reconstituted from its genetic code. But it is so far the largest, and the meanest, and the only one to be snatched back into existence from a time when we knew so much less and were so much more at its mercy."

"The team did not even have to wait for Taubenberger to finish the whole sequence of the 1918 virus to begin testing its virulence. In 2001, Adolfo Garcia-Sastre and Christopher Basler, also at Mount Sinai, reconstructed the genes for just the two critical surface proteins and sent them on to Tumpey, at that time working at the Southeast Poultry Research Laboratory in Athens, Ga. Taking advantage of influenza's innate ability to mix and match genes from two strains, he combined the two 1918 genes with others from an innocuous laboratory strain to make a complete set. Tumpey infected some lab mice, which are normally not affected much by human flus. Five days later, he came into the laboratory at around 11 at night for a quick check on their progress. All the mice were dead."

"He did not have much longer to wait. It took nearly 50 years to find a trace of the virus in preserved tissue, and nearly 10 years for Taubenberger to sequence its code, finishing the last of three genes driving the virus's replication machinery early last year. From that point, it required just a few months for the Mount Sinai group to transform the code into actual genes, and in Tumpey's lab mere days for the genes to begin assembling themselves into viable virus particles and come bursting out into the surrounding solution.

Tumpey and his colleagues were well aware that bringing such a lethal pathogen back into the world was going to cause controversy. But he was fairly certain that he had laid the groundwork to defend the decision, obtaining approvals from the highest levels at the C.D.C. and the National Institute of Allergy and Infectious Diseases, which had financed the work. He had conducted experiments showing that mice were protected from the virus by the current human flu vaccine and by Tamiflu, the antiviral drug. In any case, because a virus descended from the 1918 one has been circulating in the population since 1977, Tumpey is confident that everyone carries at least partial immunity to the 1918 virus itself."

"Not everyone is as sanguine as Tumpey. "I believe that this was research that should not have been performed," says Richard Ebright, a Howard Hughes Medical Institute investigator at Rutgers University. "If this virus was to be accidentally or intentionally released, it is virtually certain that there would be greater lethality than from seasonal influenza, and quite possible that the threat of pandemic that is in the news daily would become a reality."

"Then again, common sense is not a prerequisite for membership in a terrorist organization. Accidental release of the virus cannot be ruled out, either. While few question the experience and expertise of the C.D.C. in containing dangerous microbes, other labs will be working with the virus, and there is ample precedent for accidents occurring under stringent biosecurity, including release of the SARS virus in the past few years from three separate laboratories in Asia, which led to one death. In fact, the reason those of us who were not around in 1918 still may have some immunity to that pandemic strain is that a relatively innocuous descendant H1 type was reintroduced into the environment in 1977, probably by accident in China or Russia."

Note This actually came from an army base in the US in 1976, not "China or Russia in 1977".


1918 Influenza: the Mother of All Pandemics

"The "Spanish" influenza pandemic of 1918–1919, which caused ≈50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epidemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis."
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By 2020 half a million people had died of this virus and the reasons given to resurrect it - to learn - did not pan out. we learned nothing, other than "let sleeping viruses lie".

If they ever want to bring back the Black Death - just say no.


Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past

"Although the pandemic influenza viruses of 1957, 1968, and 2009 are all descended, via different pathways, from the 1918 virus, only the 2009 pandemic virus expresses an antigenically similar hemagglutinin (HA) (11). All influenza A viruses (IAV), including the 1918 virus, possess a segmented single-stranded RNA genome and can evolve by the accumulation of selected mutations (“antigenic drift”) or through the exchange of gene segments by reassortment with other influenza viruses (“antigenic shift”). Sequencing the 1918 virus provided the basis for the subsequent understanding that the key 2009 virus HA gene, after having apparently been transmitted from humans to pigs in or about 1918, had been maintained in pigs over the past 90 years or so as a separate lineage from the 1918 human pandemic H1N1 virus (11), a lineage that has long been recognized as the “classical” swine H1N1 influenza virus. When the 2009 pandemic virus emerged in humans with a swine H1 HA gene descended from, and still closely related antigenically to, the 1918 pandemic virus, extensive cross-protection between the 2009 and 1918 pandemic viruses was demonstrated in experimental animals (12–16)."




nyt 2006: Why Revive a Deadly Flu Virus?
https://www.nytimes.com/2006/01/29/magazine/why-revive-a-deadly-flu-virus.html


taubenberger 2006: 1918 Influenza: the Mother of All Pandemics
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291398/


taubenberger 2012: Reconstruction of the 1918 Influenza Virus: Unexpected Rewards from the Past
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3448162/