The same capillaries that moved blood past the alveoli delivered this attack. The capillaries dilated, pouring out fluid, every kind of white blood cell, antibodies, other elements of the immune system, and cytokines into the lung. Then these cytokines and other enzymes virtually obliterated the capillaries. Even more fluid poured into the lung. The cells that line the alveoli were damaged, if they survived the virus itself. Pink glassy membranes, called hyaline membranes, formed on the insides of the alveoli. Once these membranes formed, 'surfactant' (a slippery, soap-like protein that reduces surface tension and eases the transfer of oxygen into red blood cells) disappeared from the alveoli. More blood flooded the lungs. The body started producing fiberlike connective tissue. Areas of the lung became enmeshed in cell debris, fibrin, collagen, and other materials. Proteins and fluid filled the space between cells.
Macfarlane Burnet, the Nobel laureate, described what was happening inside the lungs: 'acute inflammatory injection' very rapid necrosis of most of the epithelial lining of the bronchial tree down to and especially involving the smallest bronchioles' . Essentially toxic damage to alveolar walls and exudation of blood and fluid' [C]ontinued exudation of fluid in areas where blocking of smaller bronchi had occurred would produce eventually airless regions.'
The immune system changes with age. Young adults have the strongest immune system in the population, most capable of mounting a massive immune response. Normally that makes them the healthiest element of the population. Under certain conditions, however, that very strength becomes a weakness.
In 1918 the immune systems of young adults mounted massive responses to the virus. That immune response filled the lungs with fluid and debris, making it impossible for the exchange of oxygen to take place. The immune response killed.
The influenza outbreak in 1997 in Hong Kong, when a new virus jumped from chickens to humans, killed only six people and it did not adapt to man. More than a million chickens were slaughtered to prevent that from happening, and the outbreak has been much studied. In autopsies pathologists noticed extremely high cytokine levels, discovered even that the bone marrow, lymphoid tissue, spleen (all involved in the immune response) and other organs were themselves under attack from an immune system turned renegade. They believed that this proved 'syndrome [was] not previously described with influenza.' In fact, investigators in 1918 had seen the same thing.
This was still influenza, only influenza.
*
In the 1970s physicians began to recognize a pathological process in the lungs that could have many causes but, once the process began, looked the same and received the same treatment. They called it ARDS, which stands for Acute Respiratory Distress Syndrome. Almost anything that puts extreme stress on the lung can cause ARDS: near drowning, smoke inhalation, inhaling toxic fumes (or poison gas)' or influenzal viral pneumonia. Doctors today looking at pathology reports of lungs in 1918 would immediately designate the condition as ARDS.
One pulmonary expert describes ARDS as 'a burn inside the lungs.' It is a virtual scorching of lung tissue. When viral pneumonia causes the condition, the immune system toxins designed to destroy invaders are what, in effect, flame in the lung, scorching the tissue.
Whatever the causes of ARDS, even today there is no way of stopping the process of disintegration in the lung once it begins. The only care is supportive, keeping the victim alive until he or she can recover. This requires all the technology of modern intensive care units. Still, even with the best modern care, even with for example dramatically more efficient and effective administration of oxygen than in 1918, the mortality rate for ARDS patients in different studies ranges from 40 to 60 percent. Without intensive care (and hospitals have few beds in intensive-care units) the mortality rate would approach 100 percent.
(In 2003 a new coronavirus that causes SARS, 'Severe Acute Respiratory Syndrome,' appeared in China and quickly spread around the world. Coronaviruses cause an estimated 15 to 30 percent of all colds and, like the influenza virus, infect epithelial cells. When the coronavirus that causes SARS does kill, it often kills through ARDS, although since the virus replicates much more slowly than influenza, death from ARDS can come several weeks after the first symptoms.)
In ARDS, death can come from many causes. Organs outside the lungs fail because they get too little oxygen. The lungs can so fill with fluid that the right ventricle of the heart cannot empty it so the victim drowns. The strain of trying to pump blood out of the lung can cause heart failure. Or the victim can simply die from exhaustion: he or she must breathe so rapidly to get enough oxygen that muscles become exhausted. Breathing just stops.
*
ARDS by no means accounts for all the influenza deaths in 1918 and 1919, or even for a majority of them. It explains only those who died in a few days, and it explains why so many young healthy people died. Although influenza almost certainly killed some people in ways that had little to do with the lungs (for example, someone whose already weak heart could not stand the additional strain of fighting the disease) the overwhelming majority of non-ARDS deaths came from bacterial pneumonias.
The destruction of the epithelial cells eliminated the sweeping action that clears so much of the respiratory tract of bacteria, and the virus damaged or exhausted other parts of the immune system as well. That gave the normal bacterial flora of the mouth unimpeded entry into the lungs. Recent research also suggests that the neuraminidase on the influenza virus makes it easier for some bacteria to attach to lung tissue, creating a lethal synergy between the virus and these bacteria. And in the lungs, the bacteria began to grow.
Bacterial pneumonias developed a week, two weeks, three weeks after someone came down with influenza, including even a seemingly mild case of influenza. Often influenza victims seemed to recover, even returned to work, then suddenly collapsed again with bacterial pneumonia.
It is impossible to know what percentage of the dead were killed by a viral pneumonia and ARDS and how many died from bacterial pneumonias. Generally speaking, epidemiologists and historians who have written about this pandemic have assumed that the overwhelming majority of deaths came from secondary invaders, from bacterial pneumonias that can be fought with antibiotics.
The conclusion of the army's pneumonia commission, however, is chilling in terms of implications for today. This commission, comprised of half a dozen of the finest scientists in America, both conducted autopsies and reviewed pathology reports of others; it found signs of what would today be called ARDS in almost half the autopsies. A separate study limited to the pathology of the disease, conducted by Milton Winternitz, a Welch protegé and later dean of the Yale Medical School, reached the same conclusion.
That overstates the proportion of victims who died from ARDS (in effect from influenzal viral pneumonia) because the army study looked only at deaths among soldiers, men who were young and otherwise healthy, the group most likely to have been killed by their own immune systems. In the total population, viral pneumonias and ARDS would not account for as high a percentage of the deaths. Most deaths almost certainly did come from secondary bacterial infections, but probably not quite so many as has been assumed. That should, however, be small comfort for those who worry about the next influenza pandemic.
The 1957 pandemic struck in the golden age of antibiotics, but even then just 25 percent of the fatalities had viral pneumonia only; three-quarters of the deaths came from complications, generally bacterial pneumonia. Since then bacterial resistance has become a major problem in medicine. Today the mortality rate for a bacterial pneumonia following influenza is still roughly 7 percent, and in some parts of the United States, 35 percent of pneumococcal infections are resistant to the antibiotic of choice. When staphylococcus aureus, a bacterium that has become particularly troubling in hospitals because of its resistance to antibiotics, is the secondary invader, the death rate (today) rises to as high as 42 percent. That is higher than the general death rate from bacterial pneumonias in 1918.
Part VII
> THE RACE
CHAPTER TWENTY-TWO
NATURE CHOSE to rage in 1918, and it chose the form of the influenza virus in which to do it. This meant that nature first crept upon the world in familiar, almost comic, form. It came in masquerade. Then it pulled down its mask and showed its fleshless bone.
Then, as the pathogen spread from cantonments to cities, as it spread within cities, as it moved from city to town to village to farmhouse, medical science began moving as well. It began its own race against the pathogen, moving more rapidly and with more purpose than it ever had.
Scientists did not presume to think that they would or could control this rage of nature. But they did not abandon their search for ways to control the damage of this rage. They still tried to save lives.
Worldwide their struggle, their race, commenced. In the United States that struggle would be fought by Welch, Gorgas, Cole, and their colleagues, as well as by the institutions they had built and the men and women they had trained. Neither these institutions nor these men and women had ever been tested like this. They had never imagined they would be tested like this. But any possibility of affecting the course of the disease lay in their hands.
*
To save lives they needed the answer to at least one of three questions. It was possible that even a single rough approximation of an answer would give them enough knowledge to intervene, to interrupt the disease at some critical juncture. But it was also possible they could learn detailed answers to all three questions and still remain helpless, utterly helpless.
First, they needed to understand the epidemiology of influenza, how it behaved and spread. Scientists had already learned to control cholera, typhoid, yellow fever, malaria, bubonic plague, and other diseases by understanding their epidemiology even before developing either a vaccine or cure.
Second, they needed to learn its pathology, what it did within the body, the precise course of the disease. That too might allow them to intervene in some way that saved lives.
Third, they needed to know what the pathogen was, what microorganism caused influenza. This could allow them to find a way to stimulate the immune system to prevent or cure the disease. It was also conceivable that even without knowing the precise cause, they could develop a serum or vaccine.
The easiest question to answer for influenza was its epidemiology. Although some respected investigators still believed in the miasma theory (they thought influenza spread too fast for person-to-person contact to account for it) most believed correctly it was an airborne pathogen. Breathing it in could cause the disease. They did not know the exact, precise details, that for example when the virus floats in the air it can infect someone else for anywhere from an hour to a day after it is exhaled (the lower the humidity, the longer the virus survives). But they did know that it was 'a crowd disease,' spread most easily in crowds.
They also had an accurate estimate that someone with influenza 'sheds' the virus (can infect others) usually from the third to the sixth day after he or she is infected.
They also believed, correctly, that people could catch influenza not only by inhaling it but by hand-to-mouth or -nose contact. They rightly thought, for instance, that a sick person could cover his mouth with his hand when he coughed, then several hours later shake hands, and the second person could then rub his chin in thought or touch his nose or stick a piece of candy in his mouth and infect himself. Similarly, someone sick could cough into a hand, touch a hard surface such as a doorknob, and spread it to someone else who turns the doorknob and later brings a hand to face. (In fact, the virus can remain infectious on a hard surface for up to two days.)
Knowledge of influenza's epidemiology, then, was of little use. Only ruthless isolation and quarantine could affect its course. No scientist and no public health official had the political power to take such action. Some local authorities might take some action, but no national figure could. Even within the army Gorgas's urgent and desperate calls to end the transfer of troops were ignored.
Scientists were also learning too well about the pathology of the disease and its natural course. They were learning chiefly that they could do almost nothing to intervene in serious cases, in the cases that progressed to viral pneumonia and ARDS; even administering oxygen seemed to have no effect.
They believed they could, however, possibly save lives if they could prevent or treat the slower moving pneumonias caused by what they were fairly quickly suspecting to be secondary invaders. Some preventive measures involved only giving proper guidance, such as to rest in bed after influenza infection, or giving good care, which was becoming more and more impossible as the numbers of the sick rose, as nurses and doctors themselves succumbed.
But if they could find the pathogen' They had tools, they could manipulate the immune system, they could prevent and cure some pneumonias - including the most common pneumonias. The conquest of bacterial pneumonias seemed tantalizingly within the reach of science, tantalizingly at the very edge of scientists' reach - or just beyond it. If they could just find the pathogen'
All the energies of science rose to that challenge.
*
William Welch himself would not rise to it. From Camp Devens he had returned directly to Baltimore, neither stopping in New York City nor going on to report to the surgeon general's office in Washington. Others could perform that duty, and on the phone he had said what he had to say.
In the meantime Welch wasn't feeling very well. No doubt he tried to shrug off the discomfort. He had, after all, had an exceedingly difficult trip. Just before going to Devens he, Cole, and Vaughan had concluded their latest round of camp inspections and had just begun to relax for a few days in Asheville, North Carolina. He had even contemplated resigning his commission. Then they had been abruptly ordered to the surgeon general's office on a Sunday, gone straight on to Devens, and there discovered this terrible disease.
So he had every reason to be tired and out of sorts. Likely he told himself something akin to that. The rattling of the train would have disturbed him, exacerbating the first signs of a headache. Large a man as he was, he had difficulty getting comfortable on a train anyway.
But as the train moved south he felt worse and worse, perhaps suffering a sudden violent headache and an unproductive cough, cough in which nothing came up, and certainly with a fever. He would have looked at himself clinically, objectively, and made a correct diagnosis. He had influenza.
No record exists of his precise clinical course. All of Baltimore, all of the East Coast, was erupting in flames. The virus struck the Hopkins itself so hard that the university closed its hospital to all but its own staff and students. Three Hopkins medical students, three Hopkins nurses, and three Hopkins doctors would die.
Welch did not go to the hospital. Almost seventy years old, forty years older than those who were dying in the greatest numbers, having just left the horror at Devens and knowing the enormous strain on and therefore the likely poor care even at the Hopkins facility, he later said, 'I could not have dreamed of going to a hospital at that time.'
Instead, he went to bed immediately in his own rooms, and stayed there. He knew better than to push himself now: pushing oneself after infection with this disease could easily open the path for a secondary invader to kill. After ten days in bed at home, when he felt well enough to travel at all, to recuperate more he withdrew entirely to his beloved Hotel Dennis in Atlantic City, the odd tacky place that was his haven.
In the midst of the chaos that was everywhere, he returned to this familiar place that gave him comfort. What had he always liked about it? Perhaps the life that roared through it. Quiet resorts bored him: he described Mohonk, a mountain resort ninety miles above New York City, as 'a kind of twin-lakes-resort with Miss Dares sitting in rockers on the broad piazza,' where it seems as if nine o'clock will never come so that one could go decently to bed' [C]olored neckties are not allowed.' But Atlantic City! and 'the most terrifying, miraculous, blood-curdling affair called the Flip-flap railro
ad' just built on a long pier out over the ocean' [Y]ou go down from a height of about 75 feet' with the head down and the feet up, so that you would drop out of the car, if it was not for the tremendous speed. As you go round the circle the effect is indescribable' . Crowds stand around and say they would not try it for $1000.'
Yes, the life that roared through Atlantic City (the young men and women and their frolicking, the sensuality of sweat and surf and salt, the vibrancy and thrust of flesh about the ocean and boardwalk, all that) made one feel as if one were not merely observing but partaking. But now Atlantic City was quiet. It was October, off-season, the resorts quiet. And here, as everywhere, was influenza. Here, as everywhere, there was a shortage of doctors, a shortage of nurses, a shortage of hospitals, a shortage of coffins, its schools closed, its places of public amusement closed, its Flip-flap railroad closed.
He stayed in bed for several more weeks, recuperating. The disease, he told his nephew, 'seems to have localized itself in my intestinal, rather than the respiratory tract, which is probably fortunate.' He also insisted that his nephew, later a U.S. senator, make certain if any symptoms of influenza appeared at all in his family that the victim stay in bed 'until the temperature has been normal for three days.'
He had planned to attend a meeting on the disease at the Rockefeller Institute, but almost two weeks after arriving in Atlantic City, a month after first becoming ill, he canceled; he had not recovered enough to attend. He would play no further role in medical science for the course of the epidemic. He would not participate in the search for a solution. He had of course done no laboratory work in years, but he had often proved an extraordinarily useful conduit, knowing everyone and everything, a cross-pollinator recognizing how the work of one investigator might complement the work of another, and directly or indirectly putting the two in touch. Now he would not play even that role.
The Great Influenza Page 28