The Great Influenza
Page 17
Gorgas's army superiors ignored the advice. As a result, the army soon suffered a taste of epidemic disease. It would be a test run, for both a virus and medicine.
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The winter of 1917-18 was the coldest on record east of the Rocky Mountains, barracks were jam-packed, and hundreds of thousands of men were still living in tents. Camp hospitals and other medical facilities had not yet been finished. An army report conceded the failure to provide warm clothing or even heat. But most dangerous was the overcrowding.
Flexner warned that the situation 'was as if the men had pooled their diseases, each picking up the ones he had not had,' greatly assisted by the faulty laying out of the camps, poor administration, and lack of adequate laboratory facilities.' Vaughan protested impotently and later called army procedures 'insane' . How many lives were sacrificed I can not estimate' . The dangers in mobilization steps followed were pointed out to the proper authorities before there was any assembly, but the answer was: 'The purpose of mobilization is to convert civilians into trained soldiers as quickly as possible and not to make a demonstration in preventive medicine.''
In that bitterly cold winter, measles came to the army's barracks, and it came in epidemic form. Usually, of course, measles infects children and causes only fever, rash, cough, runny nose, and discomfort. But like many other children's diseases (especially viral diseases) when measles strikes adults, it often strikes hard. (Early in the twenty-first century, measles is still causing one million deaths a year worldwide.)
This outbreak racked its victims with high fever, extreme sensitivity to light, and violent coughs. Complications included severe diarrhea, meningitis, encephalitis (inflammation of the brain), violent ear infections, and convulsions.
As infected soldiers moved from camp to camp, the virus moved with them, rolling through camps like a bowling ball knocking down pins. Vaughan reported, 'Not a troop train came into Camp Wheeler [near Macon, Georgia] in the fall of 1917 without bringing from one to six cases of measles already in the eruptive stage. These men' distributed its seeds at the encampment and on the train. No power on earth could stop the spread of measles under these conditions.'
Camp Travis outside San Antonio held 30,067 men. By Christmas, 4,571 men had come down with the disease. Funston had an average troop strength of over fifty-six thousand; three thousand were sick enough to require hospitalization. At Greenleaf in South Carolina, Devens in Massachusetts, the numbers were comparable. The 25,260 troops at Camp Cody in New Mexico were free of measles until soon after the arrival of men from Funston. Then measles began roaring through Cody, too.
And some young men began to die.
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Investigators could develop neither a vaccine to prevent measles nor a serum to cure it, but most deaths were coming chiefly from secondary infections, from bacteria invading the lungs after the virus had weakened their defenses. And investigators at Rockefeller and elsewhere struggled to find a way to control these bacterial infections. They made some progress.
Meanwhile the army issued orders forbidding men from crowding around stoves, and officers entered barracks and tents to enforce it. But especially for the tens of thousands who lived in tents in the record cold, it was impossible to keep men from crowding around stoves.
Of all the complications of measles, the most deadly by far was pneumonia. In the six months from September 1917 to March 1918, before the influenza epidemic struck, pneumonia struck down 30,784 soldiers on American soil. It killed 5,741 of them. Nearly all these pneumonia cases developed as complications of measles. At Camp Shelby, 46.5 percent of all deaths (all deaths from all diseases, all car wrecks, all work accidents, all training mishaps combined were a result of pneumonia following measles. At Camp Bowie, 227 soldiers died from disease in November and December 1917; 212 of them died of pneumonia after measles. The average death rate from pneumonia in twenty-nine cantonments was twelve times that of civilian men of the same age.
In 1918 the Republican-controlled Senate held hearings on the Wilson administration's mistakes in mobilizing the military. Republicans had despised Wilson since 1912, when he reached the White House despite winning only 41 percent of the vote. (Former Republican president and then third-party candidate Teddy Roosevelt and incumbent Republican president William Howard Taft split the GOP vote, and Socialist Eugene Debs also won 6 percent.) Mobilization failures seemed a perfect opportunity to embarrass him. And there was personal bitterness in the attacks: Congressman Augustus Peabody Gardner, son-in-law of Senate Majority Leader Henry Cabot Lodge, had resigned from Congress and enlisted, only to die of pneumonia in camp.
Gorgas was summoned to explain the measles fiasco. His testimony and his report on the epidemic to the chief of staff made front-page news. Like his mentor Sternberg during the typhoid debacle twenty years earlier, he lacerated his War Department colleagues and superiors for rushing troops to cantonments under living conditions that failed to meet minimum public health standards, for overcrowding, for exposing recruits to measles who had no immunity, for using untrained 'country boys' to care for desperately sick men in poorly equipped hospitals and sometimes without hospitals at all. And he stated that the War Department seemed to consider the Medical Department of the army unimportant. 'I was never in their confidence, no,' he said in response to one senator's question.
He had hoped his testimony would force the army to give him more power to protect troops. Perhaps it did; the army initiated courts-martial at three cantonments. But his testimony also isolated him. He confided to his sister that, in the War Department, 'All my friends seem to have deserted me and everybody is giving me a kick as I pass by.'
Meanwhile, Welch visited one of the worst-hit camps, a camp where measles itself had left but where victims with complications still lingered. He told Gorgas that the mortality rate for troops developing pneumonia after measles 'is stated to be 30% but more now in hospital will die. A good statistician needed in hospital - registrar not competent.' To give the men in the hospital a better chance to survive, he continued, 'Have Colonel Russell send directions for Avery's medicine for pneumococcus type work.'
He was referring to the Rockefeller Institute's Oswald Avery, one of the Canadians there who had been inducted into the army as only a private. Private or not, he soon would be, if he was not already, the world's leading investigator of pneumonia. And conclusions Avery would reach would have import far (very, very far) beyond that subject. His findings would create a scientific revolution that would change the direction of all genetic research and create modern molecular biology. But that would come later.
Osler called pneumonia 'the captain of the men of death.' Pneumonia was the leading cause of death around the world, greater than tuberculosis, greater than cancer, greater than heart disease, greater than plague.
And, like measles, when influenza kills, it usually kills through pneumonia.
CHAPTER TWELVE
MEDICAL DICTIONARIES define pneumonia as 'an inflammation of the lungs with consolidation.' This definition omits mention of an infection, but in practice pneumonia is almost always caused by some kind of microorganism invading the lung, followed by an infusion of the body's infection-fighting weapons. The resulting inflamed mix of cells, enzymes, cell debris, fluid, and the equivalent of scar tissue thickens and leads to the consolidation; then the lung, normally soft and spongy, becomes firm, solid, inelastic. The disease kills usually when either the consolidation becomes so widespread that the lungs cannot transfer enough oxygen into the bloodstream, or the pathogen enters the bloodstream and carries the infection throughout the body.
Pneumonia maintained its position as the leading cause of death in the United States until 1936. It and influenza are so closely linked that modern international health statistics, including those compiled by the United States Centers for Disease Control, routinely classify them as a single cause of death. Even now, early in the twenty-first century, with antibiotics, antiviral drugs, oxygen, and intensive-care units, inf
luenza and pneumonia combined routinely rank as the fifth or sixth (it varies year to year, usually depending on the severity of the influenza season) leading cause of death in the United States and the leading cause of death from infectious disease.
Influenza causes pneumonia either directly, by a massive viral invasion of the lungs, or indirectly (and more commonly) by destroying certain parts of the body's defenses and allowing so-called secondary invaders, bacteria, to infest the lungs virtually unopposed. There is also evidence that the influenza virus makes it easier for some bacteria to invade the lung not only by generally wiping out defense mechanisms but by specifically facilitating some bacteria's ability to attach to lung tissue.
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Although many bacteria, viruses, and fungi can invade the lung, the single most common cause of pneumonia is the pneumococcus, a bacterium that can be either a primary or secondary invader. (It causes approximately 95 percent of lobar pneumonias, involving one or more entire lobes, although a far lesser percentage of bronchopneumonias.) George Sternberg, while working in a makeshift laboratory on an army post in 1881, first isolated this bacterium from his own saliva, inoculated rabbits with it, and learned that it killed. He did not recognize the disease as pneumonia. Neither did Pasteur, who discovered the same organism later but published first, so scientific etiquette gives him priority in the discovery. Three years later a third investigator demonstrated that this bacteria frequently colonized the lungs and caused pneumonia, hence its name.
Under the microscope the pneumococcus looks like a typical streptococcus, a medium-size elliptical or round bacterium usually linked with others in a chain, although the pneumococcus usually is linked only to one other bacterium (and is sometimes called a diplococcus) like two pearls side by side. When exposed to sunlight it dies within ninety minutes, but it survives in moist sputum in a dark room for ten days. It can be found occasionally on dust particles. In virulent form, it can be highly infectious - in fact it can itself cause epidemics.
As early as 1892 scientists tried to make a serum to treat it. They failed. In the next decades, while investigators were making enormous advances against other diseases, they made almost no progress against pneumonia. This was not through lack of trying. Whenever researchers made any progress against diphtheria, plague, typhoid, meningitis, tetanus, snake bite, and other killers, they immediately applied the same methods against pneumonia. Still nothing even hinted at success.
Investigators were working at the very outermost edge of science. Gradually they improved their ability to produce a serum that protected an animal, but not people. And they struggled to understand how this serum worked, advancing hypotheses that might eventually lead to therapies. Sir Almroth Wright, who was knighted for developing a typhoid vaccine, speculated that the immune system coated invading organisms with what he called 'opsonins,' which made it far easier for white blood cells to devour the invader. His insight was correct, but he was wrong in the conclusions he drew from this insight.
Nowhere was pneumonia more severe than among workers in South Africa's gold and diamond mines. Epidemic conditions were virtually constant and outbreaks routinely killed 40 percent of the men who got sick. In 1914 South African mine owners asked Wright to devise a vaccine against pneumonia. He claimed success. In fact he not only failed, his vaccinations could kill. This and other errors earned Wright the mocking nickname 'Sir Almost Right' from competing investigators.
But by then two German scientists had found a clue to the problem in treating or preventing pneumonia. In 1910 they distinguished between what they called 'typical' pneumococci and 'atypical' pneumococci. They and others tried to develop this clue.
Yet as the Great War began so little progress had been made against pneumonia that Osler himself still recommended venesection (bleeding: 'We employ it nowadays much more than we did a few years ago, but more often late in the disease than early. To bleed at the very onset in robust, healthy individuals in whom the disease sets in with great intensity and high fever is, I believe, a good practice.'
Osler did not claim that bleeding cured pneumonia, only that it might relieve certain symptoms. He was wrong. The 1916 edition of his textbook also stated, 'Pneumonia is a self-limited disease, which can neither be aborted nor cut short by any known means at our command.'
Americans were about to challenge that conclusion.
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When Rufus Cole came to the Rockefeller Institute to head its hospital, he decided to focus most of his own energies and those of the team he put together on pneumonia. It was an obvious choice, since it was the biggest killer.
To cure or prevent pneumonia required, as with all other infectious diseases at the time, manipulating the body's own defenses, the immune system.
In the diseases scientists could defeat, the antigen (the molecules on the surfaces of invading organisms that stimulated the immune system to respond, the target the immune response aimed at) did not change. In diphtheria the dangerous part was not even the bacteria itself but a toxin the bacteria produced.
The toxin was not alive, did not evolve, and had a fixed form, and the production of antitoxin had become routine. Horses were injected with gradually increasing doses of virulent bacteria. The bacteria made the toxin. In turn, the horse's immune system generated antibodies that bound to and neutralized the toxin. The horse was then bled, solids removed from the blood until only the serum remained, and this was then purified into the antitoxin that had become so common and lifesaving.
An identical process produced tetanus antitoxin, Flexner's serum against meningitis, and several other sera or antitoxins. Scientists were vaccinating the horse against a disease, then extracting the horse antibodies and injecting them into people. This borrowing of immune-system defenses from an outside source is called 'passive immunity.'
When vaccines are used to stimulate people's own immune systems directly, so that they develop their own defenses against bacteria or viruses, it is called 'active immunity.'
But in all the diseases treated successfully so far, the antigens, the target the immune system aimed at, remained constant. The target stayed still; it did not move. And so the target was easy to hit.
The pneumococcus was different. The discovery of 'typical' and 'atypical' pneumococci had opened a door, and investigators were now finding many types of the bacteria. Different types had different antigens. Sometimes also the same type was virulent, sometimes not, but why one killed and another caused mild or no disease was not yet a question anyone was designing experiments to answer. That lay out there for the future, a sort of undertow pulling at the data. The focus was far more immediate: finding a curative serum, a preventative vaccine, or both.
By 1912 Cole at Rockefeller had developed a serum that had measurable if not dramatic curative power against a single type of pneumococcus. He happened to read a paper by Avery on an entirely different subject - secondary infections in victims of tuberculosis. Although narrow and hardly a classic, the paper still made a deep impression on Cole. It was solid, thorough, tight, and yet was deeply analytical, showing an awareness of the potential implications of the conclusions and possible new directions for research. It also demonstrated Avery's knowledge of chemistry and ability to carry out a fully scientific laboratory investigation of illness in patients. Cole wrote Avery a note offering him a job at the institute. Avery did not reply. Cole sent a second note. Still he received no reply. Finally Cole visited Avery and raised the salary offer. Later he realized Avery rarely read his mail. It was typical of Avery; his focus was always on his experiments. Now he accepted. Soon after the Great War started, but before America's entry into it, Avery also began working on pneumonia.
Pneumonia was Cole's passion. For Avery it would become an obsession.
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Oswald Avery was a short thin fragile man, a tiny man really who weighed at most 110 pounds. With his large head and intense eyes, he looked like someone who would have been laughed at as an 'egghead,' if that word had bee
n in use then, and bullied in a schoolyard as a boy. If that was the case, it appeared to have left no scars; he seemed friendly, cheerful, even outgoing.
Born in Montreal, he grew up in New York City the son of a Baptist minister who preached at a church in the city. He had a good many talents. At Colgate University he tied for first prize in an oratory contest with classmate Harry Emerson Fosdick, who became among the most prominent preachers of the early twentieth century (Fosdick's brother Raymond ultimately headed the Rockefeller Foundation; John Rockefeller Sr. built Riverside Church for Harry). Avery also played cornet well enough to have performed in concert with the National Conservatory of Music (a concert conducted by Antonin Dvorjak) and he often drew ink caricatures and painted landscapes.
Yet for all his outward friendliness and sociability, Avery spoke himself of what he called 'the true inwardness of research.'
René Dubos, an Avery protegé, recalled, 'To a few of us who saw him in every day life, however, there was often revealed another aspect of his personality,' a more haunting quality,' a melancholy figure whistling gently to himself the lonely tune of the shepherd song in Tristan and Isolde. An acute need for privacy, even if it had to be bought at the cost of loneliness, conditioned much of Avery's behavior.'
If the phone rang Avery would talk animatedly, as if happy to hear from the caller, but when he hung up, Dubos recalled, 'It was as if a mask dropped, his smile replaced with a tired and almost tortured expression, the telephone pushed away on the desk as a symbol of protest against the encroaching world.'
Like Welch, he never married, nor was he known to have had an emotional or intimate relationship with anyone of either sex. Like Welch, he could be charming and the center of attention; he did comic impersonations so well that one colleague called him 'a natural born comedian.' Yet he resented any kind of intrusion upon himself, resented even attempts by others to entertain him.