The Great Influenza: The Epic Story of the Deadliest Plague in History - John M. Barry (2004)
Part III. THE TINDERBOX
EVEN WHEN COLE first tried the new serum on patients it showed promise. He and Avery immediately devoted themselves to refining their procedures in the laboratory, in the methods of infecting horses and producing serum, in the way they administered it. Finally they began a careful series of trials with a finished product. They found that giving large dosages of serum—half a liter—intravenously cut the death rate of Type I pneumonias by more than half, from 23 percent to 10 percent.
It was not a cure. Pneumonias caused by other types of pneumococci did not yield so easily. And, as Avery and Cole stated, “Protection in man is inferior to protection in mice.”
But of all pneumonias, those caused by Type I pneumococci were the single most common. Cutting the death rate by more than half in the single most common pneumonia was progress, real progress, enough progress that in 1917 the institute published a ninety-page monograph by Cole, Avery, Dochez, and Henry Chickering, another young Rockefeller scientist, entitled “Acute Lobar Pneumonia Prevention and Serum Treatment.”
It was a landmark work, for the first time explaining step-by-step a way to prepare and use a serum that could cure pneumonia. And it very much anticipated outbreaks of the disease in army cantonments, noting, “Pneumonia bids fair in the present war to lead all diseases as a cause of death.”
In October 1917, Gorgas told army hospital commanders that, “in view of the probability that pneumonia will be one of the most important diseases amongst the troops,” they must send even more doctors to the Rockefeller Institute to learn how to prepare and administer this serum. Avery, still a private, was already diverting time from his research to teach bacteriology to officers who would be working in cantonments. Now he and his colleagues also taught this serum therapy. His students, rather than call him “Private,” addressed him respectfully as “Professor”—a nickname already occasionally given him. His colleagues shortened it to “Fess,” which stuck with him for the rest of his life.
Simultaneously Cole, Avery, and Dochez were developing a vaccine to prevent pneumonia caused by Types I, II, and III pneumococci. After proving it worked in animals, they and six other Rockefeller researchers turned themselves into guinea pigs, testing its safety in humans by giving each other massive doses. All of them had negative reactions to the vaccine itself; three had severe reactions. They decided that the vaccine was too dangerous to administer in those dosages but planned another experiment with lower doses administered once a week for four weeks, which gave recipients time to gradually build up immunity.
This vaccine came too late for any large-scale impact on the measles epidemic, but at Camp Gordon outside Atlanta, a vaccine against the strain of pneumococcus causing most of the pneumonias there was tested on one hundred men with measles, with fifty men vaccinated and fifty used as controls. Only two of those vaccinated developed this pneumonia, compared to fourteen unvaccinated men.
Meanwhile, Cole wrote Colonel Frederick Russell, who during his own scientific career in the army had significantly improved typhoid vaccine, about “the progress we have already made in the matter of prophylactic vaccination against pneumonia.” But, Cole added, “The manufacture of large amounts of vaccine will be a big matter, much more difficult than the manufacture of typhoid vaccine…. I have been getting an organization together so that the large amounts of media necessary could be prepared, and so the vaccine could be made on a large scale.”
Cole’s organization was ready for a large test in March 1918, just as influenza was first surfacing among soldiers in Kansas. The vaccine was given to twelve thousand troops at Camp Upton on Long Island—that used up all the vaccine available—while nineteen thousand troops served as controls, receiving no vaccine. Over the next three months, not a single vaccinated soldier developed pneumonia caused by any of the types of pneumococci vaccinated against. The controls suffered 101 cases. This result was not absolutely conclusive. But it was more than suggestive. And it was a far better result than was being achieved anywhere else in the world. The Pasteur Institute was also testing a pneumonia vaccine, but without success.
If Avery and Cole could develop a serum or vaccine with real effectiveness against the captain of death…If they could do that, it would be the greatest triumph medical science had yet known.
Both the prospect of finally being able to defeat pneumonia and its appearance in the army camps only intensified Gorgas’s determination to find a way to limit its killing. He asked Welch to create and chair a special board on the disease. Gorgas wanted the board run, literally, out of his own office; Welch’s desk was in Gorgas’s personal office.
Welch demurred and called Flexner. Both men agreed that the best man in the country, and probably in the world, to chair the board was Rufus Cole. The next day Flexner and Cole got on a train to Washington to meet Gorgas and Welch at the Cosmos Club. There they picked the members of the pneumonia board, a board to be supported by all the knowledge and resources of Gorgas, Welch, Flexner, and the institutions they represented.
They chose well. Each person selected would later be elected to membership in the National Academy of Sciences, arguably the most exclusive scientific organization in the world.
Avery would of course lead the actual laboratory investigations and stay in New York. Most of the others would work in the field. Lieutenant Thomas Rivers, a Hopkins graduate and Welch protégé, would become one of the world’s leading virologists and succeed Cole as head of the Rockefeller Institute Hospital. Lieutenant Francis Blake, another Rockefeller researcher, would become dean of the Yale Medical School. Captain Eugene Opie, regarded as one of the most brilliant of Welch’s pathology students, was already dean of the Washington University Medical School when he joined the army. Collaborating with them, although not actual board members, were future Nobel laureates Karl Landsteiner at Rockefeller and George Whipple at the Hopkins. Years later another Rockefeller scientist recalled, “It was really a privilege to be on the pneumonia team.”
On a routine basis—if such urgency could be routine—Cole traveled to Washington to discuss the latest findings with Welch and senior army medical officers in Gorgas’s office. Cole, Welch, Victor Vaughan, and Russell had also been conducting a series of the most rigorous inspection tours of cantonments, checking on everything from the quality of the camp’s surgeons, bacteriologists, and epidemiologists right down to the way camp kitchens washed dishes. Any recommendations they made were immediately ordered to be carried out. But they did not simply dictate; many of the camp hospitals and laboratories were run by men they respected, and they listened to ideas as well.
Late that spring, Cole reported to the American Medical Association one of his conclusions about measles: that it “seems to render the respiratory mucous membrane especially susceptible to secondary infection.” He also believed that these secondary infections, like measles itself, “occur chiefly in epidemic form…. Every new case of the infection adds not only to the extent but also to the intensity of the epidemic.”
On June 4, 1918, Cole, Welch, and several other members of the pneumonia board appeared in Gorgas’s office once more, this time with Hermann Biggs, New York State health commissoner; Milton Rosenau, a prominent Harvard scientist who was then a navy lieutenant commander; and L. Emmett Holt, one of those instrumental in the founding of the Rockefeller Institute. This time the discussion was wide-ranging, focusing on how to minimize the possibility of something worse than the measles epidemic. They were all worried about Gorgas’s nightmare.
They were not particularly worried about influenza, although they were tracking outbreaks of the disease. For the moment those outbreaks were mild, not nearly as dangerous as the measles epidemic had been. They well knew that when influenza kills, it kills through pneumonia, but Gorgas had already asked the Rockefeller Institute to gear up its production and study of pneumonia serum and vaccine, and both the institute and the Army Medical School had launched major efforts to do so.
Then the conversation turned from the laboratory to epidemiological issues. The inspection tours of the camps had convinced Welch, Cole, Vaughan, and Russell that cross-infections had caused many of the measles-related pneumonia deaths. To prevent such a problem from recurring, Cole suggested creating contagious-disease wards with specially trained staffs, something the best civilian hospitals had. Welch pointed out that the British had isolation hospitals with entirely separate organizations and rigid discipline. Another possible solution to cross-infection involved using cubicles in hospitals—creating a warren of partitions around hospital beds.
They also discussed overcrowding in hospitals and isolation of troops. Since 1916 the Canadian army had segregated all troops arriving in Britain for twenty-eight days, to prevent their infecting any trained troops ready to go to the front. Welch advised establishing similar “detention camps for new recruits where men are kept for 10–14 days.”
They all recognized the difficulty of convincing the army to do this, or of convincing the army to end the even more serious problem of overcrowding in barracks.
Still, another army medical officer injected one piece of good news. He said that the problem of overcrowding in the hospitals themselves had been eliminated. Every hospital in the army had at least one hundred empty beds as of May 15, with a total of twenty-three thousand beds empty. Every single epidemiological statistic the army collected showed improved overall health. He insisted that facilities and training were adequate.
Time would tell.
Man might be defined as “modern” largely to the extent that he attempts to control, as opposed to adjust himself to, nature. In this relationship with nature, modern humanity has generally been the aggressor and a daring one at that, altering the flow of rivers, building upon geological faults, and, today, even engineering the genes of existing species. Nature has generally been languid in its response, although contentious once aroused and occasionally displaying a flair for violence.
By 1918 humankind was fully modern, and fully scientific, but too busy fighting itself to aggress against nature. Nature, however, chooses its own moments. It chose this moment to aggress against man, and it did not do so prodding languidly. For the first time, modern humanity, a humanity practicing the modern scientific method, would confront nature in its fullest rage.