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Where Are We, a Century After the “Spanish Flu”?

2018; Wiley; Volume: 32; Issue: 5 Linguagem: Inglês

10.1096/fj.180501ufm

1530-6860

Thoru Pederson,

Experience-Based Knowledge Management

The FASEB JournalVolume 32, Issue 5 p. 2317-2318 EditorialFree Access Where Are We, a Century After the "Spanish Flu"? Thoru Pederson, Thoru PedersonSearch for more papers by this author Thoru Pederson, Thoru PedersonSearch for more papers by this author First published: 13 April 2018 https://doi.org/10.1096/fj.180501ufmCitations: 1AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL The year 2018 marks 100 years since the onset of the infectious disease outbreak with the highest morbidity and mortality in the history of America, still a relatively young country at age 142, and one that had already survived a civil war of horrific proportions and was just entering another war, on a world scale, that would be of even greater tragic dimensions. Those respective enemies were slavery and intra-European malaise, but meanwhile, in 1918, a different stealth warrior took to arms. Now we come to the centennial, a time to reflect as in Ecclesiastes. We can look to John Barry's (1) superb book for all of the history. The current epidemiologic data are staggering. In the United States, over the period 2010–2016, there were from 9,200,000 to 60,800,000 cases annually, 140,000 to 710,000 hospitalizations, and 12,000 to 56,000 deaths (2). These extraordinary disease-burden data are all the more perplexing because so much has been learned about influenza virus and all of the other orthomyxoviruses, with vaccine efforts having progressed to a considerable degree in the past decade or so. And yet, we know that around the corner each season, pandemics are potentially at hand and that even another "great influenza" lurks as a genuine possibility. A conundrum of the flu is the relative ease of making hopeful vaccines for a given seasonal strain vs. the extraordinary power of the virus to mutate in the meantime. (It is not really an actual "power" of the virus as much as just a default outcome from its very error-prone genome replication machinery.) Many exceptional scientific minds and some companies' fortunes have been put to play on this stage. Gilead Sciences, a company whose origin I once described on these pages (3), came out with Tamiflu, branded as a "smarter" flu vaccine. A small Connecticut company, Protein Sciences Inc., took a different approach and came up with FluBlok. Meanwhile, big pharma has devoted massive resources to outwit the seasonal variation that the flu virus deals in this poker hand. Others in the field have gone back to the drawing board. We might bear in mind that pioneers, such as Jenner (smallpox) and Pasteur (anthrax) were dealing with an infectious agent less variable than influenza virus, and thus a better platform for an immunization strategy. In his engaging biography of Pasteur, René Dubos (4) has a wonderful passage about how Pasteur ruled over the salons and public lecture theaters of Paris, displaying an artful rapport with nonscientists. We can admire Pasteur for this, as communicating biomedical science to the public is of vital importance (5), perhaps more so now than then. But, we can also bear in mind that, with all respect, he was dealing with an infectious agent more readily trained than flu. So what to do now? There are basic principles in virology, molecular biology, and immunology that open the possibility of a new frontier of influenza vaccinology. One idea is to harvest all of the structural biology information on the influenza viral proteins, get a foothold on the variable vs. constant regions that have shown up each season, and tune this information into a broadly reactive antigen that immunologically anticipates every possible variant that might emerge. A promising example of this "universal vaccine" approach is one led by Peter Palese (6), who is one of many accomplished road warriors in this endeavor. Other related ideas are in play. We might think of Hamlet's line, "There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy," as the metaphor for an open mind about how to make the perfect flu vaccine. We have conquered so many of the infectious diseases that changed history in the human era. Let us hope that we are on the cusp of doing so once again, both for the seasonal flu distress that afflicts so many, sometimes just a bad two weeks and other times lethal, and even more hopefully to be able to contravene this dangerous sleuth at our door waiting to launch another 1918. We can smile at Yogi Berra's famous quip, "It's déjà vu all over again," but not when it is an annual cycle impacting and devastating human health throughout the world. This virus has no homing antennae for including or avoiding its infected hosts' country, ethnicity, and citizenship vs. displaced person/immigrant status. In the ethos of medicine, we have another set of antennae that disregards all of those other criteria. These were taught by Hippocrates, at his school in Cos, and by Mamon, which is why their oaths are taken by physicians all these centuries later. Let us applaud all who push flu vaccinology forward, combining the encyclopedic knowledge accumulated with new ideas. One senses that new ideas are what will make the breakthrough, and I am buoyed to see them coming. The opinions expressed in editorials, essays, letters to the editor, and other articles comprising the Up Front section are those of the authors and do not necessarily reflect the opinions of FASEB or its constituent societies. The FASEB Journal welcomes all points of view and many voices. We look forward to hearing these in the form of op-ed pieces and/or letters from its readers addressed to [email protected]. REFERENCES 1Barry, J. M. (2004) The Great Influenza, Viking, New York 2 Centers for Disease Control and Prevention. Disease burden of influenza. Accessed March 9, 2018, at: https://www.cdc.gov/flu/about/disease/burden.htm 3Pederson, T. (2012) Sense and antisense in biotech: the first antisense DNA company. FASEB J. 26, 3594– 3601 4Dubos, R. (1950) Louis Pasteur. Free Lance of Science, Charles Scribner's Sons, New York 5Pederson, T. (2011) Found in translation: crossing the corpus callosum to explain science. FASEB J. 25, 2093– 2097 6Palese, P. (2017) Influenza: a broadly protective antibody. Nature 551, 310– 311 Citing Literature Volume32, Issue5May 2018Pages 2317-2318 ReferencesRelatedInformation