The Great Influenza (37 page)

The epidemiology of this pandemic was
interesting.
The unusual symptoms were
interesting.
And the autopsies (and some symptoms revealed themselves only in autopsy) were
interesting.
The damage this virus caused and its epidemiology presented a deep mystery. An explanation would come - but not for decades.

In the meantime this influenza, for it was after all only influenza, left almost no internal organ untouched. Another distinguished pathologist noted that the brain showed 'marked hyperemia' (blood flooding the brain, probably because of an out-of-control inflammatory response) adding, 'the convolutions of the brain were flattened and the brain tissues were noticeably dry.'

The virus inflamed or affected the pericardium (the sac of tissue and fluid that protects the heart) and the heart muscle itself, noted others. The heart was also often 'relaxed and flabby, offering strong contrast to the firm, contracted left ventricle nearly always present in post-mortem in patients dying from lobar pneumonia.'

The amount of damage to the kidneys varied but at least some damage 'occurred in nearly every case.' The liver was sometimes damaged. The adrenal glands suffered 'necrotic areas, frank hemorrhage, and occasionally abscesses' . When not involved in the hemorrhagic process they usually showed considerable congestion.'

Muscles along the rib cage were torn apart both by internal toxic processes and by the external stress of coughing, and in many other muscles pathologists noted 'necrosis,' or 'waxy degeneration.'

Even the testes showed 'very striking changes' encountered in nearly every case' . It was difficult to understand why such severe toxic lesions of the muscle and the testis should occur' .'

And, finally, came the lungs.

Physicians had seen lungs in such condition. But those lungs had not come from pneumonia patients. Only one known disease (a particularly virulent form of bubonic plague called pneumonic plague, which kills approximately 90 percent of its victims) ripped the lungs apart in the way this disease did. So did weapons in war.

An army physician concluded, 'The only comparable findings are those of pneumonic plague and those seen in acute death from toxic gas.'

Seventy years after the pandemic, Edwin Kilbourne, a highly respected scientist who has spent much of his life studying influenza, confirmed this observation, stating that the condition of the lungs was 'unusual in other viral respiratory infections and is reminiscent of lesions seen following inhalation of poison gas.'

But the cause was not poison gas, and it was not pneumonic plague. It was only influenza.

CHAPTER TWENTY-ONE

I
N
1918
IN PARTICULAR,
influenza struck so suddenly that many victims could remember the precise instant they knew they were sick, so suddenly that throughout the world reports were common of people who toppled off horses, collapsed on the sidewalk.

Death itself could come so fast. Charles-Edward Winslow, a prominent epidemiologist and professor at Yale, noted, 'We have had a number of cases where people were perfectly healthy and died within twelve hours.' The
Journal of the American Medical Association
carried reports of death within hours: 'One robust person showed the first symptom at 4:00
P.M.
and died by 10:00
A.M.
' In
The Plague of the Spanish Lady: The Influenza Pandemic of 1918-1919,
writer Richard Collier recounted this: In Rio de Janeiro, a man asked medical student Ciro Viera Da Cunha, who was waiting for a streetcar, for information in a perfectly normal voice, then fell down, dead; in Cape Town, South Africa, Charles Lewis boarded a streetcar for a three-mile trip home when the conductor collapsed, dead. In the next three miles six people aboard the streetcar died, including the driver.

Lewis stepped off the streetcar and walked home.

* 

It was the lungs that had attracted attention from pathologists first. Physicians and pathologists had many times seen lungs of those dead of pneumonia. Many of the deaths from influenzal pneumonia did look like these normal pneumonias. And the later in the epidemic a victim died, the higher was the percentage of autopsy findings that resembled normal pneumonia, bacterial pneumonia.

Those who died very quickly, a day or even less after the first symptoms, however, most likely died of an overwhelming and massive invasion of the virus itself. The virus destroyed enough cells in the lung to block the exchange of oxygen. This alone was unusual and puzzling. But the lungs of the men and women who died two days, three days, four days after the first symptom of influenza bore no resemblance to normal pneumonias at all. They were more unusual, more puzzling.

In April a Chicago pathologist had sent lung-tissue samples to the head of a research institute and asked him 'to look over it as a new disease.' British pathologists in France had commented on strange autopsy findings in the spring. Capps had mentioned unusual findings in the lungs to Welch, Cole, and other members of the inspection party in June. The lungs Welch himself had seen in the Devens autopsy room had made him fear that the disease was a new one.

The respiratory tract serves a single purpose: to transfer oxygen from the air into red blood cells. One can picture the entire system as an inverted oak tree. The trachea (the windpipe) carries air from the outside world into the lungs and is the equivalent of the tree trunk. This trunk then divides into two great branches, each called a 'primary bronchus,' which carry oxygen into the right and left lungs. Each primary bronchus subdivides into smaller and smaller bronchi, smaller branches, as they enter the lungs until they become 'bronchioles.' (Bronchi have cartilage, which helps give the lung a kind of architectural structure; bronchioles do not have cartilage.)

Each lung itself subdivides into lobes - the right lung has three, the left only two. The lobes subdivide into a total of nineteen smaller pockets. Within these pockets, sprouting like leaves from the smaller bronchi and the bronchioles, are clusters of tiny sacs called alveoli. They are much like tiny but porous balloons, and the average person has 300 million of them. The alveoli play a role comparable to that which leaves play in photosynthesis. In the alveoli, the actual transfer of oxygen into the blood takes place.

The right side of the heart pumps blood without oxygen into the lungs, where it passes into capillaries, the smallest blood vessels, so small that individual blood cells often move in single file. Capillaries surround the alveoli, and oxygen molecules slip through the membrane of the alveolar tissue and attach to the hemoglobin of the red blood cells as they circulate past them. After picking up oxygen, the blood returns to the left side of the heart, where it is pumped through arteries throughout the body. (The body's entire blood supply moves through the lungs each minute.)

In arteries, red blood cells carry oxygen and are bright red; in veins, such as those visible on one's wrist, the same cells without oxygen are bluish. When the lungs fail to oxygenate the blood, part of the body, and in some cases the entire body, can turn blue, causing cyanosis. Lack of oxygen, if extended for any length of time, damages and ultimately kills other organs in the body.

Healthy lung tissue is light, spongy, and porous, much lighter than water, and a good insulator of sound. A physician percussing the chest of a healthy patient will hear little. When normal lung tissue is manipulated, it 'crepitates': as the air in the alevoli escapes, it makes a crackling noise similar to rubbing hairs together.

A congested lung sounds different from a healthy one: solid tissue conducts breathing sounds to the chest wall, so someone listening can hear 'rales,' crackling or wheezing sounds (although it can also sound either dull or hyperresonant). If the congestion is dense enough and widespread enough the lung is 'consolidated.'

In bronchopneumonia, bacteria (and many kinds of bacteria can do this) invade the alveoli themselves. Immune-system cells follow them there, and so do antibodies, fluid, and other proteins and enzymes. An infected alveolus becomes dense with this material, which prevents it from transferring oxygen to the blood. This 'consolidation' appears in patches surrounding the bronchi, and the infection is usually fairly localized.

In lobar pneumonia, entire lobes become consolidated and transformed into a liverlike mass - hence the word 'hepatization' to describe it. A hepatized lobe can turn various colors depending on the stage of disease; grey hepatization, for example, indicates that various kinds of white blood cells have poured into the lung to fight an infection. A diseased lung also includes the detritus of dissolved cells, along with various proteins such as fibrin and collagen that are part of the body's efforts to repair damage. (These repair efforts can cause their own problems. 'Fibrosis' occurs when too much fibrin interferes with the normal functioning of the lung.)

Roughly two-thirds of all bacterial pneumonias and an even higher percentage of lobar pneumonias are caused by a single group of bacteria, the various subtypes of the pneumococcus. (The pneumococcus is also the second leading cause of meningitis.) A virulent pneumococcus can spread through an entire lobe within a matter of hours. Even today, in 20 to 30 percent of the cases of lobar pneumonia, bacteria also spread through the blood to infect other areas of the body, and many victims still die. Some cyanosis is not unusual in lobar pneumonia, but most of the lung often still looks normal.

In 1918 pathologists did see at autopsy the normal devastation of the lungs caused by the usual lobar and bronchopneumonias. But the lungs from those who died quickly during the pandemic, the lungs that so confused even Welch, those lungs were different. Said one pathologist, 'Physical signs were confusing. Typical consolidation was seldom found.' And another: 'The old classification by distribution of the lesions was inappropriate.' And another: 'Essentially toxic damage to alevolar walls and exudation of blood and fluid. Very little evidence of bacterial action could be found in some of these cases.'

At a discussion reported in the
Journal of the American Medical Association,
several pathologists concurred, 'The pathological picture was striking, and was unlike any type of pneumonia ordinarily seen in this country' . The lung lesions, complex and variable, struck one as being quite different in character to anything one had met with at all commonly in the thousands of autopsies one had performed during the last 20 years.'

Normally when the lungs are removed they collapse like deflated balloons. Not now. Now they were full, but not of air. In bacterial pneumonias, normally the infection rages inside the alveoli, inside the tiny sacs. In 1918, while the alveoli were also sometimes invaded, the spaces between the alveoli were filled. This space, which makes up the bulk of the volume of the lung, was filled with the debris of destroyed cells and with every element of the immune system, from enzymes to white blood cells. And it was filled with blood.

One more observer concluded that 'the acute death' he saw evidence of in the lungs 'is a lesion which does not occur in other types of pulmonary infection. In influenza it is the lesion of characterization.'

* 

Victims' lungs were being ripped apart as a result of, in effect, collateral damage from the attack of the immune system on the virus. Since the respiratory tract must allow outside air to pass into the innermost recesses of the body, it is extremely well defended. The lungs became the battleground between the invaders and the immune system. Nothing was left standing on that battleground.

The immune system begins its defense far in advance of the lungs, with enzymes in saliva that destroy some pathogens (including HIV, which makes its home in most bodily fluids, but not in saliva, where enzymes kill it). Then it raises physical obstacles, such as nasal hairs that filter out large particles and sharp turns in the throat that force inhaled air to collide with the sides of breathing passageways.

Mucus lines these passageways and traps organisms and irritants. Underneath the layer of mucus lies a blanket of 'epithelial cells,' and from their surfaces extend 'cilia,' akin to tiny hairs which, like tiny oars, sweep upward continuously at from 1,000 to 1,500 beats a minute. This sweeping motion moves foreign organisms away from places they can lodge and launch an infection, and up to the larynx. If something does gain a foothold in the upper respiratory tract, the body first tries to flush it out with more fluid (hence the typical runny nose) and then expel it with coughs and sneezes.

These defenses are as physical as raising an arm to block a punch and do no damage to the lungs. Even if the body overreacts, this usually does no serious harm, although an increased volume of mucus blocks air passages and makes breathing more difficult. (In allergies these same symptoms occur because the immune system does overreact.)

There are more aggressive defenses. Macrophages and 'natural killer' cells (two kinds of white blood cells that seek and destroy all foreign invaders, unlike other elements of the immune system that only attack a specific threat) patrol the entire respiratory tract and lungs. Cells in the respiratory tract secrete enzymes that attack bacteria and some viruses (including influenza) or block them from attaching to tissue beneath the mucus, and these secretions also bring more white cells and antibacterial enzymes into a counterattack; if a virus is the invader, white blood cells also secrete interferon, which can block viral infection.

All these defenses work so well that the lungs themselves, although directly exposed to outside air, are normally sterile.

But when the lungs do become infected, other defenses, lethal and violent defenses, come into play. For the immune system is at its core a killing machine. It targets infecting organisms, attacks with a complex arsenal of weapons (some of them savage weapons) and neutralizes or kills the invader.

The balance, however, between kill and overkill, response and overresponse, is a delicate one. The immune system can behave like a SWAT team that kills the hostage along with the hostage taker, or the army that destroys the village to save it.