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Authors: John M Barry

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But these alternative hypotheses have problems. After the 1918/1919 pandemic, many scientists searched for the source of the disease. The American Medical Association sponsored what is generally considered the best of several comprehensive international studies of the pandemic, conducted by Dr. Edwin Jordan, editor of the
Journal of Infectious Disease.
He spent years reviewing evidence from all over the world and the AMA published his work in 1927.

Jordan first considered China as the possible source. Influenza did surface in early 1918 in China, but the outbreaks seemed minor and did not spread. Chinese scientists, trained by the Rockefeller Institute, themselves believed there was no evidence connecting any outbreak to the pandemic. Hong Kong had only twenty-two influenza hospital admissions in the first five months of 1918, and in Canton the first case of influenza did not surface until June 4. Recently some medical historians have suggested that one particular outbreak of deadly pulmonary disease in China in 1918 was actually influenza, but contemporary scientists diagnosed it as pneumonic plague and by 1918 the plague bacillus could be easily and conclusively identified in the laboratory. Also, one could not confuse pneumonic plague, with its then nearly 100 percent mortality rate, with even the most lethal influenza. So after tracing all known outbreaks in China, Jordan concluded that none of them 'could be reasonably regarded as the true forerunner of the European epidemic.'

Jordan also considered Oxford's hypothesis of the 1916 'purulent bronchitis' as a possible source. He rejected it for several reasons. At least some members of the British medical corps did not consider the infection contagious. No evidence suggested that it spread rapidly or widely, and a new influenza virus almost always does both. In fact, the outbreak did not seem to spread at all.

Also, we now know a sudden mutation in an existing influenza virus can account for a sudden virulent outbreak. In the summer of 2002, for example, an influenza epidemic with an extremely high death rate erupted in parts of Madagascar and in some towns it sickened an outright majority (in one instance 67 percent) of the population. But the virus causing this lethal epidemic was an old one that normally caused mild disease. (Technically, it was an H3N2 virus of a subtype isolated in 1999 in Panama.) It had simply mutated in a violent direction, then reverted to its normal mild status. The epidemic did not even spread to the whole island before fading away; it affected only thirteen of 111 health districts in Madagascar. Something similar may have happened in the British base.

Jordan also considered as possible sources other eruptions of influenza in early 1918 in France as well as some in India. He concluded that it was highly unlikely that the pandemic began in any of them. They too behaved like local eruptions of endemic influenza.

That left the United States. Jordan looked at a series of spring outbreaks there. The evidence seemed far stronger. One could see influenza jumping from army camp to camp, then into cities, and traveling with troops to Europe. His conclusion: the United States was the site of origin.

A later, equally comprehensive, multivolume British study of the pandemic agreed with Jordan. It too found no evidence for the influenza's origin in the Orient; it too rejected the 1916 outbreak of 'purulent bronchitis' among British troops; and it too concluded, 'The disease was probably carried from the United States to Europe.'

Australian Macfarlane Burnet, quoted earlier on this point, also studied the pandemic closely. He too found the evidence 'strongly suggestive' that the disease started in the United States and spread with 'the arrival of American troops in France.'

More evidence against the 1916 origin comes from scientists Jeffrey Taubenberger and Peter Palese. Taubenberger is sequencing the genome of the 1918 virus after extracting samples of it from Alaska and the army's pathology 'museum.' Based on rates of mutation of the genome, he concludes that the virus emerged a few months prior to the pandemic. Peter Palese states, 'The evidence that the virus was around before 1918 is very flimsy. It's much more likely from all the data I'm aware of that the virus developed in 1918, or no more than six months earlier.'

If the disease did emerge a few months prior to the pandemic, and if the judgments of Jordan and other contemporaries were correct in thinking it started in the United States, then Haskell County, Kansas, seems the most likely origin. First, the outbreak in January and February 1918 was so unusual and so dangerous that even though influenza was not a reportable disease, Loring Miner reported it to the U.S. Public Health Service.

Second, if the virus did not originate in Haskell, there is no explanation for how it arrived there. Someone infected with the virus would have had to travel from an infected area somewhere else while leaving absolutely no trace of the disease in the country through which he or she passed. Given the length of time people with influenza can infect others, without air travel it would be physically impossible for the Haskell virus to have come from Europe. Nor are there other known outbreaks in the United States where someone could have become infected and carried it to Haskell. This strongly suggests that a new virus did emerge in Haskell.

And unlike the 1916 outbreak in France, which did not seem to spread, one can trace with perfect definiteness the route of the virus from Haskell to the outside world. The local paper listed by name people exposed to the disease who traveled to Camp Funston only a few days before the first reported case there; others the paper did not name may well also have gone there. Other than Haskell, Camp Funston was the first known outbreak of epidemic influenza in the United States. Several histories of the pandemic have begun their story there. And, one can easily track the disease from Funston outward - to other cantonments, to Europe, and to the U.S. civilian population.

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.

BOOK: The Great Influenza
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