The Great Influenza (42 page)

Park instantly wired back, 'Will undertake work.'

* 

It was as if the laboratory had gone to war, and Park was confident of victory. As he reviewed every published and unpublished scrap of data on the disease from laboratories around the world, he was unimpressed and dismissed most of it with near contempt. Certain his lab could do better, believing that others' sloppiness at least partly contributed to their failure to understand the disease, he laid extraordinarily ambitious plans. In addition to finding the pathogen, in addition to finding a vaccine or serum or both, in addition to producing that drug in huge quantities, in addition to communicating to others the precise procedures to follow so they could produce it, he intended still more. He intended to make the most thorough study of any disease outbreak ever, selecting a large sample of people and, as many of them inevitably became ill, monitoring them through the most sophisticated possible laboratory and epidemiological means. The workload would be enormous, but he believed that his department could handle it.

But within days, almost within hours, the disease began to overwhelm the department. Park had already compensated for the loss of labor to the war by analyzing every system and maximizing efficiency (installing, for example, a vacuum pump that in fifteen minutes could fill three thousand tubes with individual vaccine doses), and even changing accounting methods. But now, as influenza struck first one janitor or technician or scientist at a time, then four at a time, then fifteen at a time, the laboratory reeled. Not so long before, when the Health Department had tracked a typhus outbreak to ground, four of his workers had died of typhus - most likely from laboratory infection. Now people in Park's own lab were again sick, some dying.

Influenza had humbled him, and quickly. He abandoned both his arrogance about the work of others and his own ambitious plans. Now he was trying to get just one thing right, the important thing.
What was the pathogen?

Meanwhile, the world seemed to shift underfoot. To Park and Williams and to others in other laboratories racing to find an answer, it must have seemed as if they could see this great catastrophe approaching but had to remain frozen in place, all but incapable of doing anything to defeat or avoid it. It was almost as if one's foot were caught under rocks in a tidal pool while the tide came in - the water rising to the knees, to the waist, one sucking in a deep breath then doubling over to try to pry one's foot loose and straightening to feel the water at one's neck, the swell of a wave passing over one's head' .

* 

New York City was panicking, terrified.

By now Copeland was enforcing strict quarantines on all cases. There were literally hundreds of thousands of people sick simultaneously, many of them desperately sick. The death toll ultimately reached thirty-three thousand for New York City alone, and that understated the number considerably since statisticians later arbitrarily stopped counting people as victims of the epidemic even though people were still dying of the disease at epidemic rates - still dying months later at rates higher than anywhere else in the country.

It was impossible to get a doctor, and perhaps more impossible to get a nurse. Reports came in that nurses were being held by force in the homes of patients too frightened and desperate to allow them to leave. Nurses were literally being kidnapped. It did not seem possible to put more pressure on the laboratory. Yet more pressure came.

* 

The pressure pushed Park to abandon more than his ambitious plans. He had always been meticulous, had never compromised, had built much of his scientific reputation on exposing the flawed work of others, always moving forward carefully, basing his own experiments upon well-established premises and with as few assumptions as possible. 'On the basis of experimental facts,' he had always said, 'we are justified in' '

Now Park had no leisure for justification. If he was to have any impact on the course of the epidemic he would have to guess - and guess right. So those in his laboratory would, he reported, 'study closely only the more dominant types that were demonstrated by our procedure' . We recognized that our methods' did not take into account' heretofore undescribed organisms that might have an etiologic relationship to these infections.'

The laboratory had only two constants. One was an endless supply of samples, of swabbings, blood, sputum, and urine from live patients and organs from the dead. 'We had plenty of material, I am sorry to say,' Williams observed laconically.

And they had their routine. Only the need to keep to discipline saved the laboratory from utter chaos. There was nothing even faintly exciting about this work; it was pure tedium, and pure boredom. And yet every step involved contact with something that could kill, and every step involved passion. Technicians took sputum samples from patients in the hospital and immediately (they could not wait even an hour, or bacteria from the patient's mouth could penetrate into the sputum and contaminate it) began working with it. The steps began with 'washing': placing each small lump of balled mucus in a bottle of sterile water, removing it and repeating the process five times, then breaking up the mucus, washing it more, passing a platinum loop (a thin circle of platinum, like something one uses to blow bubbles) through it to transfer it to a test tube, taking another loop and repeating the step half a dozen times. Each step took time, time while people died, but they had no choice. They needed each step, needed to dilute the bacteria to prevent too many colonies from growing in the same medium. Then they took more time, more steps, isolating each of these growths.

Everything mattered. The most tedious tasks mattered. Washing glassware mattered. Contaminated glassware could ruin an experiment, waste time, cost lives. In the course of this work, 220,488 test tubes, bottles, and flasks would be sterilized. Everything mattered, and yet no one knew who would report to work each day, who would not (and who would suddenly be carried across the street to the hospital) and if someone failed to come into work it was nearly impossible to keep track of such simple jobs as removing growing cultures from incubators.

There were dozens of ways to grow bacteria but often only one way to grow a particular kind. Some grow only without oxygen, others only with it in plentiful supply. Some require alkaline media, others acid. Some are extremely delicate, others stable.

Every step, every attempt to grow the pathogen, meant effort, and effort meant time. Every hour incubating a culture meant time. They did not have time.

Four days after accepting the task from Pearce, Park wired, 'The only results so far that are of real importance have been obtained in two fatal cases, one a man coming from Brooklyn Navy Yard and one a doctor from the naval hospital in Boston. Both developed an acute septic pneumonia and died within a week of the onset of the first infection. In both cases the lungs showed a beginning pneumonia and in smears very abundant streptococci' . There were absolutely no influenza bacilli in either of the lungs.'

The failure to find the 'influenza bacillus' maddened Park. His best hope to produce a vaccine or serum would be to find a known pathogen, and the most likely suspect was the one Pfeiffer had named
Bacillus influenzae.
Pfeiffer had been and still was confident it caused the disease. Park would not hesitate to rule
B. influenzae
out if he did not find good evidence for it, but he had the utmost respect for Pfeiffer. Working in these desperate circumstances, he wanted to confirm rather than reject Pfeiffer's work. He wanted the answer to be Pfeiffer's bacillus. That would give them a chance, a chance to produce something that saved thousands of lives.

B. influenzae
was a particularly difficult bacteria to isolate. It is tiny, even by the standards of bacteria, and usually occurs singly or in pairs rather than in large groups. It requires particular factors, including blood, in culture medium for it to grow. It grows only within a very narrow range of temperatures, and its colonies are minute, transparent, and without structure. (Most bacteria form distinctive colonies with a particular shape and color, distinctive enough that they can sometimes be identified just by looking at the colony in the same way that some ants can be identified by the form of their anthill.)
B. influenzae
grows only on the surface of the medium, since it depends heavily upon oxygen. It is also difficult to stain, hence difficult to see under the microscope. It is an easy target to miss unless one is specifically looking for it and unless one uses excellent technique.

While others in the lab searched for other organisms, Park asked Anna Williams to concentrate on finding Pfeiffer's. Anna Williams found it. She found it constantly. Ultimately, once she perfected her technique, she would find it in 80 percent of all samples from the Willard Parker Hospital, in every single sample from the Marine Hospital, in 98 percent of the samples from the Home for Children.

As much as he wanted Williams to be right, he would not let his desire corrupt his science. He went a step further, to 'the most delicate test of identity' agglutination.'

'Agglutination' refers to a phenomenon in which antibodies in a test tube bind to the antigen of the bacterium and form clumps, often large enough to be visible to the naked eye.

Since the binding of antibodies to an antigen is
specific,
since the antibodies to the influenza bacillus will bind to only that bacteria and to no other, it is a precise confirmation of identity. The agglutination tests proved without doubt that Williams had found Pfeiffer's influenza bacillus.

Less than a week after first reporting his failure to find it, Park wired Pearce that
B. influenzae
'would seem to be the starting point of the disease.' But he was well aware that his methods had been less than thorough, adding, 'There is of course the possibility that some unknown filterable virus may be the starting point.'

* 

The report had consequences. Park's laboratory began the struggle to produce an antiserum and vaccine to Pfeiffer's bacillus. Soon they were culturing liters and liters of the bacteria, transporting it north, and injecting it into the horses on the Health Department's 175-acre farm sixty-five miles north of the city.

But the only way to know for certain that
B. influenzae
caused the disease was to follow Koch's postulates: isolate the pathogen, use it to recreate the disease in an experimental animal, and then re-isolate the pathogen from the animal. The bacillus did kill laboratory rats. But their symptoms did not resemble influenza.

The results, suggestive as they were, did not fully satisfy Koch's postulates. In this case the necessary experimental animal was man.

Human experiments had begun. In Boston, Rosenau and Keegan were already trying to give the disease to volunteers from a navy brig.

None of the volunteer subjects had yet gotten sick. One of the doctors conducting the study did. In fact he died of influenza. In a scientific sense, however, his death demonstrated nothing.

CHAPTER TWENTY-FOUR

W
HILE
P
ARK TRIED
to produce an antiserum or vaccine against the disease in New York, Philadelphia was already approaching collapse. Its experience would soon be echoed in many cities around the country.

There Paul Lewis was searching for the answer as well. Few, including Park, were more likely to find it. The son of a physician, Lewis grew up in Milwaukee, went to the University of Wisconsin, and finished his medical training at Penn in 1904. Even before leaving medical school he knew he intended to spend his life in the laboratory, and he quickly acquired both a pedigree and a well-deserved reputation. He started as a junior investigator working on pneumonia under Welch, Osler, Biggs, and several others who comprised the Rockefeller Institute's Board of Scientific Advisers. Lewis impressed them all. Most impressed was Theobald Smith, one of the world's leading bacteriologists, for whom Lewis then worked in Boston. Later Smith recommended Lewis to Simon Flexner, saying that Harvard lacked the resources to allow Lewis to develop fully and that '[h]is heart lies in research.'

From Smith there could come no higher compliment. Lewis deserved it. He seemed born for the laboratory. At least that was the only place where he was happy; he loved not only the work itself but the laboratory environment, loved disappearing into the laboratory and into thought. 'Love' was not too strong a word; his passions lay in the lab. At Rockefeller, Lewis had started off pursuing his own ideas but when a polio epidemic erupted Flexner asked him to work with him on it. He agreed. It was a perfect match. Their polio work was a model combination of speed and good science. They not only proved that polio was a viral disease, still considered a landmark finding in virology, but they developed a vaccine that protected monkeys from polio 100 percent of the time. It would take nearly half a century to develop a polio vaccine for humans. In the course of this research Lewis became one of the leading experts in the world on viruses.

Flexner pronounced Lewis 'one of the best men in the country,' a very gifted fellow.' That may have been an understatement. Richard Shope worked closely with him in the 1920s, knew many of the world's best scientists (including Flexner, Welch, Park, Williams, and many Nobel laureates) and himself became a member of the National Academy of Sciences. He called Lewis the smartest man he ever knew. Joseph Aronson, a prize-winning University of Pennsylvania scientist who had also done research at the Pasteur Institute, named his son after Lewis and, like Shope, said Lewis was the brightest man he had ever met.

When the war began, Pearce, the National Research Council official, told Lewis what he told only four or five other scientists in the country: to expect to be asked 'for special service in connection with epidemic disease.'

Lewis was ready. He received a navy commission and told Flexner he had 'no onerous routine duties.' His laboratory abilities were far more important. He was still cooperating with Cole and Avery on the development of pneumonia serum, and he was also, as he told Flexner, experimenting with dyes 'as regards their capacity to inhibit the growth' of the bacteria that cause tuberculosis. The idea that dyes might kill bacteria was not original with him, but he was doing world-class work in the area and his instincts were right about its importance. Twenty years later a Nobel Prize would go to Gerhard Domagk for turning a dye into the first antibiotic, the first of the sulfa drugs.