The Great Influenza

by John M. Barry

  The fact that the 1918 pandemic likely began in the United States makes a difference because it warns investigators where to look for a new virus. They must look everywhere.

  *

  The World Health Organization tries to do just that. Its surveillance system quickly identified a new H7N7 virus that appeared in the spring of 2003 in European poultry farms. This virus infected eighty-three people and killed one, a veterinarian. To prevent it from adapting to people, public health authorities in the Netherlands, Belgium, and Germany slaughtered nearly thirty million animals (most of them poultry but some swine.) The simultaneous SARS outbreak buried information on this occurrence in American news media.) WHO also quickly jumped on the 1997 Hong Kong outbreak. But the 1997 virus still survives in chickens and in 2003 killed one of two people it infected.

  This same surveillance system also helped lead to the quick identification and containment of SARS, which was initially thought to be, and feared as, a new influenza virus. SARS offers both a historic public health success story and a warning. The success is obvious. Once WHO officials learned of it, it brought enormous resources to bear. Investigators around the world collaborated (entirely unlike the French and Germans in their search for the causes of cholera and plague a century earlier) and quickly identified the virus. At the same time world and national public health officials, except in China, moved rapidly and ruthlessly to quarantine and isolate anyone with or exposed to the disease. What once threatened to become a worldwide scourge was contained and may have been eliminated entirely. Even if it reemerges, close monitoring should keep it in check.

  But before the first notification of WHO, the disease existed for months in China. For political and commercial reasons mainland Chinese authorities kept the disease secret and then initially lied about it. Once they did recognize the threat they moved aggressively and successfully to contain it, but had it been a new influenza virus, the months of silence would have made it impossible for public health authorities to have any chance either to contain the virus or develop a vaccine before a pandemic exploded across the world. Possibly the Chinese government (and other governments) learned a lesson they will not forget; possibly they will be both open and aggressive in the future whenever any indication of a new disease surfaces. One hopes so.

  But even if Chinese authorities do change their approach to epidemic disease, even if SARS taught them and other governments around the world the same lesson, the fact that SARS killed people for several months before it attracted WHO's attention demonstrates the vulnerability of the influenza surveillance system. If the 1918 virus crossed into humans in Haskell County, influenza can cross into man anywhere. Although eighty-two countries participate in WHO's surveillance effort, more than one hundred do not. One Latin American physician at Tulane University involved in public health warns that at least as late as 1985 (and probably later than that) the national medical school of Honduras taught its students that influenza was a bad cold. Those former students now practice medicine with that attitude.

  It takes time to manufacture and distribute vaccines, and vaccines are the most effective defense. Early warning can make an enormous difference.

  In the meantime the World Health Organization and individual countries continue to monitor influenza viruses, and continue to refine plans on how to respond to another epidemic or pandemic.

  If one erupts, whether we want the knowledge or not, we will learn how good a job these planners have done.

  *

  Finally comes the question of how to apply lessons from 1918 to a new pandemic, and how these lessons relate to bioterrorism.

  The use of biological weapons has a history going back at least to the Romans, who catapulted sick animals into enclaves of their enemies. The British and Americans likely used smallpox against Native Americans, and in 1777 British Major Robert Donkin recommended using smallpox against 'American rebels' in a book on military strategy - but his recommendation was physically removed, the pages referring to it torn out of, nearly every copy of his book.

  Yet in only three verified modern instances has disease been used as a weapon. During World War II Japan spread bubonic plague in China, and Japanese scientists also infected prisoners of war with other pathogens in experiments. In 1984 in Oregon a cult infected salad bars with salmonella (no deaths, 751 became ill). And in 2001 an unknown terrorist sent anthrax through the United States mail.

  The threat of bioterror is nonetheless real. The World Health Organization believes forty-three different infectious organisms could be used as weapons. It considers the three most serious infectious threats anthrax, plague, and smallpox. It also considers botulinum toxin, a pure poison that can paralyze and kill, a bioterror threat.

  All can be countered. Vaccines can prevent smallpox, anthrax, and plague (antibiotics also work against anthrax and plague) and antitoxin can neutralize botulinum. Also, neither anthrax nor botulinum toxin can spread from person to person. The ability to counter these weapons, however, does not mean their use would not cause mass terror even if their use was isolated. The reaction across the country to the anthrax attacks demonstrates that. And more than isolated use is possible.

  The WHO has studied what it called a 'worst case' scenario of an attack with pneumonic plague, the most lethal and contagious incarnation of bubonic plague, on a city of 5 million, and concluded it would make 150,000 ill and kill 36,000. Adjusted for population, these numbers represent considerably less than what influenza did to Philadelphia in 1918.

  The 1918 pandemic, then, provides a case study of the public health and government response to a major bioterrorism attack, and it teaches two main lessons. The first involves threat assessment, planning, and allocating resources. It applies to both epidemics and large-scale bioterror attacks.

  In 1999 the CDC issued a formal call for each of the fifty states to prepare plans for pandemic influenza and laid out suggested guidelines. The same plans would apply to an outbreak of nearly any epidemic disease or use of biological weapons. Since then, and more importantly since September 11, 2001, most states have begun to develop plans. But clearly epidemiologists, scientists, public health officials, and ethicists will have to join with the professionals who handle disasters to have sets of alternative recommendations in place (actual decisions will likely be up to elected officials) and ready to implement.

  Some of the issues are obvious and simple, such as making sure health care workers are the first to get vaccinated. If they become sick, they can care for no one else. Emergency rooms need to recognize symptoms that can raise red flags, although the best clue will probably be a rush of cases. Investigators must be prepared to identify a pathogen, and epidemiologists must know the best ways to contain each likely pathogen. Legislation has to be in place to indemnify manufacturers and health care providers in the event of well-defined emergency circumstances. Production facilities have to be ready to manufacture vaccines and drugs; others should be stockpiled and distributed around the country, conceivably even in a form that individuals can administer to themselves to lessen the strain on professionals. (A study published in 2003 drives home how important logistics can be. It warned that under existing plans to distribute antibiotics, a small plane spraying anthrax spores over New York City could, under theoretically perfect conditions, kill 120,000 people, while improving distribution of antibiotics alone would slash the death toll from an identical attack to 1,000.)

  Other questions also involve logistics and risk assessment. Influenza and most biological weapons attack the respiratory system. An outbreak would quickly fill beds in intensive care units, so resources need to be available to help huge numbers of people breathe. Public health officials also have to know the risks of side effects of vaccines, and based on the risk assessment they will have to know under what circumstances they would recommend vaccination and for whom.

  Some elements of any plan, however, involve questions of power and ethics. Public health officials will need the authority to enforce
decisions, including ruthless ones. If, for example, unvaccinated individuals threaten not only themselves but others by providing a reservoir in which pathogens can breed, officials might decide to order mandatory vaccination. Or, if there is any chance to limit the geographical spread of the disease, officials must have in place the legal power to take extreme quarantine measures. A centralized system should exist to allocate all resources including professionals as well. The utter waste of resources in 1918 in New York City (when doctors repeatedly crossed each other's paths entering and leaving the same building because no centralized system was used to dispatch them) should not be tolerated.

  Questions about who will have the authority to make and enforce such decisions, and under what circumstances, must be settled in advance. Neither an epidemic nor an attack will leave time for debate.

  Some of the issues are almost purely ethical ones. If, say, containment of a pathogen is possible, but doing so requires isolating a building entirely, possibly saving many lives but at the cost of those in that building - what then? Medical ethics require physicians to do their best for each individual patient, but a military commander may ethically sacrifice a patrol, a platoon, a company to save a larger group. What ethic applies?

  Another ethical question involves the free flow of scientific information. An investigator will probably at some point discover what made the 1918 virus so lethal. The influenza virus can be created to design in the laboratory, so publishing the information would give it to terrorists. A weaponized influenza virus could be the equivalent of a worldwide nuclear holocaust. But publishing would also give the information to researchers who could find a way to block whatever mechanism made the virus deadly, conceivably both countering any made-to-order killer virus and preventing any future natural outbreak on that scale. Should the information be published?

  Scientific journals have already developed voluntary guidelines on what to publish, but these are not simple questions. Some go to the heart of medical or societal ethics, others to limits on freedom.

  And some of these issues, such as stockpiling vaccines or training workers, simply cost enormous sums of money. So does paying nurses enough to escape the current nursing shortage, which may soon approach that of 1918.

  What to do depends upon the assessment of the risk. Just as there was disagreement over the threat from the Soviet Union during the Cold War and how large the defense budget had to be to handle that threat, there will be disagreement over how real and how severe the threat from biological weapons is and how much must be spent (in money and in the erosion of values) to defend against it.

  But there is another lesson from 1918 that is clear. It is also less tangible. It involves fear and the media and the way authorities deal with the public.

  *

  There was terror afoot in 1918, real terror. The randomness of death brought that terror home. So did its speed. And so did the fact that the healthiest and strongest seemed the most vulnerable.

  The media and public officials helped create that terror - not by exaggerating the disease but by minimizing it, by trying to reassure.

  Terror rises in the dark of the mind, in the unknown beast tracking us in the jungle. The fear of the dark is an almost physical manifestation of that. Horror movies build upon the fear of the unknown, the uncertain threat that we cannot see and do not know and can find no safe haven from. But in every horror movie, once the monster appears, terror condenses into the concrete and diminishes. Fear remains. But the edge of panic created by the unknown dissipates. The power of the imagination dissipates.

  In 1918 the lies of officials and of the press never allowed the terror to condense into the concrete. The public could trust nothing and so they knew nothing. So a terror seeped into the society that prevented one woman from caring for her sister, that prevented volunteers from bringing food to families too ill to feed themselves and who starved to death because of it, that prevented trained nurses from responding to the most urgent calls for their services. The fear, not the disease, threatened to break the society apart. As Victor Vaughan (a careful man, a measured man, a man who did not overstate to make a point) warned, 'Civilization could have disappeared within a few more weeks.'

  So the final lesson, a simple one yet one most difficult to execute, is that those who occupy positions of authority must lessen the panic that can alienate all within a society. Society cannot function if it is every man for himself. By definition, civilization cannot survive that.

  Those in authority must retain the public's trust. The way to do that is to distort nothing, to put the best face on nothing, to try to manipulate no one. Lincoln said that first, and best.

  Leadership must make whatever horror exists concrete. Only then will people be able to break it apart.

  Acknowledgments

  THIS BOOK was initially supposed to be a straightforward story of the deadliest epidemic in human history, told from the perspectives of both scientists who tried to fight it and political leaders who tried to respond to it. I thought it would take me two and a half years to write, three at the most.

  That plan didn't work. Instead this book took seven years to write. It has evolved (and, I hope, grown) into something rather different than originally conceived.

  It took so long partly because it didn't seem possible to write about the scientists without exploring the nature of American medicine at this time, for the scientists in this book did far more than laboratory research. They changed the very nature of medicine in the United States.

  And, finding useful material on the epidemic proved remarkably difficult. It was easy enough to find stories of death, but my own interests have always focused on people who try to exercise some kind of control over events. Anyone doing so was far too busy, far too overwhelmed, to pay any attention to keeping records.

  In the course of these seven years, many people helped me. Some shared with me their own research or helped me find material, others helped me understand the influenza virus and the disease it causes, and some offered advice on the manuscript. None of them, of course, is responsible for any errors of commission or omission, whether factual or of judgment, in the book. (Wouldn't it be entertaining to once read an acknowledgment in which the author blames others for any mistakes?)

  Two friends, Steven Rosenberg and Nicholas Restifo at the National Cancer Institute, helped me understand how a scientist approaches a problem and also read parts of the manuscript and offered comments. So did Peter Palese at Mount Sinai Medical Center in New York, one of the world's leading experts on the influenza virus, who gave very generously of his time and expertise. Robert Webster, at St. Jude Medical Center, like Palese a world leader in influenza research, offered his insights and criticisms as well. Ronald French checked the manuscript for accuracy on the clinical course of the disease. Vincent Morelli introduced me to Warren Summers, who along with the entire pulmonary section of the Louisiana State University Health Sciences Center in New Orleans helped me understand much of what happens in the lung during an influenza attack; Warren was extremely patient and repeatedly helpful. Mitchell Freidman at the Tulane Medical School also explained events in the lung to me.

  Jeffrey Taubenberger at the Armed Forces Institute of Pathology kept me abreast of his latest findings. John Yewdell at the National Institutes of Health also explained much about the virus. Robert Martensen at Tulane made valuable suggestions on the history of medicine. Alan Kraut at American University also read and commented on part of the manuscript.

  I also particularly thank John MacLachlan of the Tulane-Xavier Center for Bioenvironmental Research, who very much helped make this book possible. William Steinmann, head of the Center for Clinical Effectiveness and Life Support at the Tulane Medical Center, gave generously of his office space, knowledge of disease, and friendship.

  All of the above have M.D.s or Ph.D.s or both. Without their assistance I would have been lost trying to understand my own cytokine storm.

  People who write books are al
ways thanking librarians and archivists. They have good reason to. Virtually everyone at the Rudolph Matas Medical Library at Tulane University was extraordinarily helpful to me, but Patsy Copeland deserves truly special mention. So do Kathleen Puglia, Sue Dorsey, and Cindy Goldstein.

  I also want to thank Mark Samels of WGBH's American Experience, who made available all the material collected for its program on the pandemic; Janice Goldblum at the National Academy of Sciences, who did more than just her job; Gretchen Worden at the Mutter Museum in Philadelphia; Jeffrey Anderson, then a graduate student at Rutgers, and Gery Gernhart, then a graduate student at American University, both of whom generously offered me their own research; and Charles Hardy of West Chester University, who gave me oral histories he had collected; and Mitch Yockelson at the National Archives, who gave me the benefit of his knowledge. Eliot Kaplan, then the editor of Philadelphia Magazine, also supported the project. I also want to thank Pauline Miner and Catherine Hart in Kansas. For help with photos I want to especially thank Susan Robbins Watson at the American Red Cross, Lisa Pendergraff at the Dudley Township Library in Kansas, Andre Sobocinski and Jan Herman at the Bureau of Navy Medicine, Darwin Stapleton at the Rockefeller University archives, and Nancy McCall at the Alan Mason Chesney archives at Johns Hopkins. I also want to thank Pat Ward Friedman for her information about her grandfather.

  Now we come to my editor, Wendy Wolf. Although this is only my fifth book, counting magazine articles I've worked with literally dozens of editors. Wendy Wolf very much stands out. She edits the old-fashioned way; she works at it. On this manuscript she worked particularly hard, and working with her has been a pleasure. It is a true statement to say that, for better or worse (and I hope better), this book wouldn't exist without her. I'd also like to thank Hilary Redmon for her diligence, reliability, and just general assistance.