The Great Influenza (61 page)

Every major laboratory in the United States continued to focus on the disease. Lewis in Philadelphia kept after it, as did others at the University of Pennsylvania. Rosenau in Boston led a team of Harvard researchers. Ludwig Hektoen and Preston Kyes at the University of Chicago stayed after it. Rosenow at the Mayo Clinic in Minnesota continued to work on it. Every member of the army's pneumonia commission returned to civilian research and continued to investigate influenza. The Metropolitan Life Insurance Company gave grants to university scientists and actually subsidized both the city of New York and the federal government, giving grants for research by Park and Williams in their New York laboratories and by George McCoy of the Public Health Service's Hygienic Laboratory.

The army also made 'every effort to collect' specimens representing pulmonary lesions due to the present influenza epidemic,' not only from army camps but from civilian sources. These specimens would prove enormously important more than three-quarters of a century later, when Jeffrey Taubenberger would extract the 1918 influenza virus from them and successfully sequence its genome.

At the Rockefeller Institute, Cole put 'every available man' to work on it. He also put Martha Wollstein on it. When Captain Francis Blake, who had been part of the army's pneumonia commission, visited his old colleagues at the institute at Christmas, he found everyone 'working tooth and nail on this influenza business with monkeys and everything else.' A week later, out of the army and back at Rockefeller, he said, 'I shall be so glad when we can get all this business off our hands and finished up and I can to something else for a change, as it seems as though I have done nothing but work on, and eat, and dream about and live with pneumonia and influenza for six months.'

He would not be free of it any time soon.

* 

Slowly, over a period of months, a body of knowledge began to form. Investigators began to learn about the firestorm that had roared around the world and was continuing to smolder.

First, they confirmed what they had suspected: the lethal fall disease was a second wave of the same disease that had hit in the spring. They based their conclusion on the fact that those exposed to the spring wave had substantial immunity to the later one. The army had the best records. These records involved chiefly young men, so they were not useful in answering some questions. But they could speak to immunity, and clearly demonstrated it. Camp Shelby, for example, was home to the only division in the United States that remained in the United States from March through the fall. In April 1918 influenza sickened 2,000 of 26,000 troops there enough to seek treatment, many more probably had lesser or subclinical infections, and all 26,000 men were exposed to the disease. During the summer, 11,645 new recruits arrived. In October influenza 'scarcely touched' the old troops but decimated the recruits. In Europe in the spring, influenza hit the Eleventh Regiment Engineers, making 613 men out of a command of 1,200 ill and killing two, but protecting them from the lethal wave: in the fall the regiment suffered only 150 'colds' and a single death. Camp Dodge had two units of seasoned troops; influenza had struck one group in the spring, and only 6.6 percent of this organization caught influenza in the fall; the other group escaped the spring wave, but 48.5 percent of them had influenza in the fall. And there were many other examples.

Statistics also confirmed what every physician, indeed every person, already knew. In the civilian population as well, young adults had died at extraordinary, and frightening, rates. The elderly, normally the group most susceptible to influenza, not only survived attacks of the disease but were attacked far less often. This resistance of the elderly was a worldwide phenomenon. The most likely explanation is that an earlier pandemic (later analysis of antibodies proved it was not the 1889-90 one), so mild as to not attract attention, resembled the 1918 virus closely enough that it provided protection.

Finally, a door-to-door survey in several cities also confirmed the obvious: people living in the most crowded conditions suffered more than those with the most space. It also seemed (although this was not scientifically established) that those who went to bed the earliest, stayed there the longest, and had the best care also survived at the highest rates. Those findings meant of course that the poor died in larger numbers than the rich. (Questions about race and the epidemic yielded contradictory information.)

But nearly everything else about the disease remained unsettled. Even the interplay between the germ theory of disease and other factors was at issue. As late as 1926, a respected epidemiologist still argued a version of the miasma theory, claiming 'a correlation between' influenza and cyclic variation in air pressure.'

In the laboratory, however, the fog remained dense. The pathogen remained unknown. Enormous resources were being poured into this research everywhere. In Australia, Macfarlane Burnet lived through the epidemic as a teenager, and it burned itself into his consciousness. As he said soon after receiving the Nobel Prize, 'For me as for many others interested in bacteriology and infectious disease, the outstanding objective in medicine for years was' influenza.'

Yet all this work had not penetrated the fog.

The problem did not lie in any lack of clues. The problem lay in distinguishing the few clues that led in the right direction from all those that led in the wrong direction. This was not bubonic plague. That was among the easiest pathogens to discover: the bacteria that caused it swarmed in the buboes. This was only influenza.

As the second wave of influenza had broken upon the world, thousands of scientists had attacked the problem. In Germany and France they had attacked it, in Britain and Italy, in Australia and Brazil, in Japan and China. But as 1919 wore away, then 1920, as the disease drifted toward mildness, one at a time these thousands began to peel off. They found the problem too difficult to conceptualize (to figure out a way to address it) or the techniques seemed too inadequate to address it, or it lay too far from their old interests or knowledge base. After two years of extraordinary (and continuing) efforts by many of the world's best investigators, in 1920 Welch made a frustrating prediction: 'I think that this epidemic is likely to pass away and we are no more familiar with the control of the disease than we were in the epidemic of 1889. It is humiliating, but true.'

Hundreds of investigators did continue to pursue the question but they could agree on little. Everything was in dispute. And central to those disputes were the old team of William Park and Anna Williams on one side, Paul Lewis and many of those at the Rockefeller Institute on another.

Lewis's research would end in irony and tragedy. The Rockefeller Institute would discover most of its own investigators in error.

But Oswald Avery would not be in error. Avery would make the most profound discovery of them all.

CHAPTER THIRTY-FIVE

T
HE GREATEST QUESTIONS
remained the simplest ones: What caused influenza? What was the pathogen? Was Pfeiffer right when he identified a cause and named it
Bacillus influenzae?
And if he was not right, then what did cause it? What was the killer?

The pursuit of this question is a classic case of how one does science, of how one finds an answer, of the complexity of nature, of how one builds a solid scientific structure.

All through the epidemic bacteriologists had had mixed results looking for
B. influenzae
. People as skilled as Park and Williams in New York, Lewis in Philadelphia, and Avery had all been unable to isolate it from the first cases they studied. Then they adjusted their techniques, changed the medium in which they grew it, added blood heated to a particular temperature to the medium, changed the dyes used for staining, and they found it. Park and Williams soon found it so consistently that Park assured the National Research Council it was the etiological agent - the cause of the disease. The Public Health Service believed it to be the cause. Lewis, despite initial misgivings, thought it the cause.

At Rockefeller, Martha Wollstein had studied Pfeiffer's bacillus since 1906. After several years of work she still had not considered her experiments sufficiently 'clean cut and stable to signify Pfeiffer's is the specific inciting agent.' But she had continued to study the bacillus, and in the midst of the pandemic she had become convinced
B. influenzae
did cause the disease. She had been so confident that the vaccine she prepared included
only
Pfeiffer's bacillus. Her work convinced her Rockefeller colleagues as well; they all took her vaccine, even though they were among the few in the country with access to the Rockefeller antipneumococcus vaccine, which had proven itself effective.

Midway through the pandemic, failure to find Pfeiffer's seemed a mark not of good science but of incompetence. When one army bacteriologist failed to find it on 'blood agar plates from 159 of the first patients,' the army sent another scientist to the camp to undertake 'an investigation of the bacteriologic methods employed in the laboratory of the base hospital.' Typical of the institution Gorgas had built, it was a true investigation, not a witch-hunt, and it concluded that this particular laboratory had done 'a splendid piece of work. If the influenza bacillus had been present' it would have been found.' But that conclusion did not come out until long after the epidemic had passed.

In the meantime the existence of such an investigation told other army bacteriologists that inability to find
B. influenzae
meant they did not know their job. Simultaneously, Avery published the new techniques he had developed that made it much easier to grow the organism. Bacteriologists began to find what they were looking for. At Camp Zachary Taylor, bacteriologists had been unable to find Pfeiffer's bacillus. Now they reported, 'More latterly Avery's oleate medium was used with very gratifying results.' They found the bacteria everywhere: in 48.7 percent of samples of blood taken directly from the heart, in 54.8 percent of lungs, in 48.3 percent of spleens. At Camp Dix, 'in every case studied the influenza bacillus was found either in the lungs or in the upper respiratory tract or nasal sinuses.'

In camp after camp, bacteriologists fell into line. Bacteriologists at Camp MacArthur in Texas were not alone in their determination 'to obtain the highest possible incidence of B. influenzae,' and they found it in 88 percent of lungs. But they did so not through any irrefutable laboratory tests; they simply looked through a microscope and identified the bacteria by appearance. Such observations are subjective and not proof, only indications.

At Camp Sherman, where the mortality rate had been the highest in the country and the reputations of camp doctors had been called into question, the final report on the epidemic exemplified the tension. In a section written by the bacteriologist, the report said, 'The persistent absence of influenza bacilli in the diverse materials examined militated against attributing the epidemic to the Pfeiffer organism.' But the section written by the pathologist in effect accused the bacteriologist of incompetence. The pathologist said he had observed pathogens through the microscope that he believed
were
'Pfeiffer's organism' and that 'all the bacteria which were present in this epidemic were not discovered as a result of the cultural methods used.'

Civilian investigators isolated Pfeiffer's with similar regularity. Yet even with all the findings of Pfeiffer's
B. influenzae,
the picture remained confusing. For rarely (even though Avery's medium inhibited the growth of pneumococci and hemolytic streptococci, both of which had often been found in influenza cases) was Pfeiffer's found alone.

And sometimes
B. influenzae
was still not being found at all. Investigators were especially failing to find it in the lungs of victims who died quickly. In at least three camps (Fremont in California and Gordon and Wheeler in Georgia) the failure to find Pfeiffer's in an overwhelming majority of cases simply meant that the bacteriologists, instead of exposing themselves to possible criticism, diagnosed victims of the epidemic as suffering from 'other respiratory diseases' instead of influenza. In some cases even the most experienced investigators found the bacillus rarely. In Chicago, D. J. Davis had studied Pfeiffer's for ten years, but found it in only five of sixty-two cases. In Germany, where Pfeiffer himself remained one of the most powerful figures in medical science, some researchers could not isolate the bacillus either, although he continued to insist it caused the disease.

These reports created increasing doubt about the Pfeiffer's influenza bacillus. Scientists did not doubt the word of those who found it. They did not doubt that the bacillus could cause disease and kill. But they began to doubt what finding it proved.

* 

There were other questions. In the midst of the epidemic, under the greatest pressures, many bacteriologists had compromised the quality of their work in the hope of getting quick results. As one scientist said, 'It requires at least three weeks of concentrated labor to investigate and identify the various species of streptococci from a single drop of normal sputum smeared on one plate of our culture medium. How then is it possible for two workers to investigate the bacteriology of the respiratory tract of, say, 100 cases of influenza and of 50 normal individuals in one year, except in the most slipshod manner?'

Park and Williams were anything but slipshod. They had been among the first to proclaim
B. influenzae
the likely cause of the epidemic. In mid-October, Park still held to that position, declaring, 'The influenza bacilli have been found in nearly every case of clear-cut infectious influenza. In the complicating pneumonias, they have been found associated with either the hemolytic streptococcus or pneumococci. In one case the bronchopneumonia was due entirely to the influenza bacillus. The results of the Department of Health of the City of New York have closely agreed with those reported from Chelsea Naval Hospital.'