THE MYSTERIOUS DEATHS OF VETERANS
In 1976, the year of America’s Bicentennial, Norman Cousins, the gifted political journalist and author, asked, in an editorial for the Saturday Review, “What is the greatest gift the United States has given the world in 200 years?” His answer: the demonstration that it is possible to plan a rational future.
Such a belief is indeed compelling. And it is one to which most public health practitioners subscribe. Optimistic by nature, they believe exerting some control over pathogens, diseases, even behavioral traits can have profound health benefits. Such a belief is the genesis of everything from vaccines to seat belt usage. Logic, carefulness, hard work, and mastery of one’s field—these are the tools for planning.
But the Bicentennial year was to challenge that optimistic belief with a difficult, frustrating outbreak: Legionnaires’ disease. This outbreak occurred at one of the worst times imaginable—on the heels of the nation’s swine flu outbreak and vaccination program.
Swine Flu
A new influenza virus was isolated in January 1976 with many of the same characteristics as the flu virus that had killed 20 million people worldwide sixty years before. No specimens were available from that pandemic, but in the laboratory, the virus looked much as the experts expected the 1918 virus to look.
The CDC had found the 1976 influenza virus disturbing. It was a new influenza virus; it had demonstrated the ability to be transmitted from person to person during an outbreak at Fort Dix, New Jersey, and the population had no antibodies or evidence of immunity to this strain. All previous experience had shown that when these three things were documented, a pandemic would occur. Although it was possible that this could be the first time those elements came together without a pandemic, it certainly was not the way to bet.
CDC Director David Sencer held an emergency meeting of the Advisory Committee on Immunization Practices and other experts, on Saturday, February 14, 1976, which I attended. Participants agreed that a vaccine needed to be developed as fast as possible. Some disagreement arose on whether the vaccine, when manufactured, should be stored in refrigerators or in people. Phrased another way, should vaccine be stored until there was evidence of spread or should an immunization program be started in anticipation of the epidemic?
A case could be made for either side, but previous experience had raised serious doubts about the ability to respond in time to abort an outbreak if the vaccine were simply refrigerated. Once the vaccine is administered, it takes two weeks for an individual to develop immunity. A vaccine that requires the use of needles and syringes cannot be given as easily as a smallpox vaccine, for which untrained people can be trained in ten minutes on how to vaccinate. It would take some weeks to mount an adequate response with flu vaccine. Previous experience had also shown that a new strain of influenza virus could spread rapidly across the nation within weeks.
Dave Sencer realized the hazards of either decision. He listened to the arguments but did not call for a vote. He then made the decision to begin an immunization program, the Swine Flu Program. Later, to secure the necessary political support, a roomful of scientists, including Jonas Salk, inventor of the inactivated polio vaccine given by needle and syringe, and Albert Sabin, inventor of a live polio vaccine given by mouth, met in the Oval Office to make the case and to show their support for the idea when it was presented to President Gerald Ford.
But there were problems. Insurance companies would not insure vaccine producers for liability in the event the vaccine caused unforeseen morbidity or mortality, and manufacturers said they could not accept this risk without insurance. The government debated the issue, and publicity was intense. In July, with vaccine production in place, negotiations between the insurance companies and the manufacturers were breaking down.
A New Public Health Emergency
Now a second difficult outbreak hit. In Philadelphia, site of much of the Bicentennial celebration, people were already somewhat anxious. There was concern that terrorists might target the city in an attempt to disrupt the celebration. Extra security had been imposed.
On Wednesday, July 21, 1976, Legionnaires and family members from around Pennsylvania began to arrive in the city. They came first by the hundreds. Eventually, more than 4,000 arrived for the fifty-eighth convention of the American Legion. More than 600 of them would check into the Bellevue Stratford Hotel, headquarters for the convention.
The Bellevue Stratford had a rich history and a reputation for elegance. The hotel had served as the headquarters for the Republican Party at the 1936 National Convention and for both Democratic and Republican parties at the national conventions in 1948. It entertained royalty and presidents through decades of name changes and remodeling. It prided itself on being able to handle large, important gatherings.
But an organism, unknown to scientists at the time, had also checked into the Bellevue Stratford. That organism is now known as Legionella pneumophila. The public health community was destined to learn a great deal about this bacterium. It is found around the world. It is now easily isolated from ponds and streams, and it lives a symbiotic relationship with other organisms, often in one-celled organisms, such as amoebas. The genome has been determined; the eating habits and the methods of causing disease have been studied. It is inhaled directly into the small sacs in the lung, without being picked up by defense mechanisms in the bronchi, and it enters macrophages in the alveoli, or air sacs, of the lung.
The organism has probably been around as long as humans and has probably been in most, if not all, clinical laboratories, but it had never been recognized. Like the childhood fantasy of walking around invisible to others, this bacterium could go anyplace and not be recognized because no one had discovered how to stain it to make it visible nor how to prepare a food that it would consume and thus grow in the laboratory. The organism had also adapted to the modern technology of the twentieth century. It appears to enjoy the atmosphere of warm or hot water. It is especially fond of sediment and organisms found in air-conditioning and hot-water pipes. While it does not spread from person to person, it is easily transmitted through aerosols, such as those formed when air leaves an air-conditioning unit or water leaves a showerhead. People have likely been getting pneumonia from this organism forever, and it has accounted for perhaps 3–4 percent of all pneumonias, but because it could not be isolated in the laboratory, the genesis of the pneumonia was listed as unknown or atypical.
None of this was known in 1976. But now a large number of people were about to be exposed to a particularly deadly aerosol, and the secret of this bacterium was to be revealed.
But it would not be disclosed without much time, agony, and hard work. A spectacular chapter was about to be played out in the history of public health, right under the gaze of William Penn’s statue, who once said, “Healing the world is true religion.”
As with previous conventions, the American Legion convention had hospitality suites, social events, and meetings—to conduct business, to honor veterans who had died in the last year, and to demonstrate the patriotism of this group brought together in defense of the country. Although it was not that different from many conventions, the veterans themselves were known to be heavy smokers and drinkers. Some have related these observations to veterans’ war experiences, where cigarettes were distributed (indeed, cigarettes were included in the souvenir packages offered to attendees of the convention) and drinking became a stress reducer. The Bellevue Stratford actually ran out of ice on Thursday, the first day of the meeting, and the attendees began to bring in their own supplies of ice.
The beginning of an epidemic is not always sudden or dramatic. Who could imagine the illness of an air-conditioner repairman the day before the convention was a harbinger of what was to come? In a gathering of more than 4,000 people, it is expected that some will be sick at any given time. So when some attendees stayed in their rooms on Friday because they were not feeling well, it was not necessarily a cause for alarm. The only unusual part of the story was that Friday was a big day, with the annual parade in the afternoon and a dance at night. But some conventioneers were so ill that they actually went to bed that afternoon.
The closing session was held the next morning, and people began to drift home. Some began having respiratory symptoms and contacted their physicians. Rumors of influenza began to circulate, and suddenly Congress became concerned that this could be an outbreak of swine flu and quickly passed the Tort Claim Act, which would indemnify pharmaceutical companies against claims that might come from the Swine Flu Immunization Program. This swift action allowed the Swine Flu Immunization Program to proceed … but this was not swine flu.
Soon information was coming back from clinics and hospitals to local and state health authorities of conventioneers who developed pneumonia after returning home from the convention. The CDC officially became involved on Monday, August 2, when Bob Craven, an EIS officer with the Respiratory and Special Pathogens Branch, received a call from a nurse at the Veterans Administration Hospital in Philadelphia, who reported two cases of pneumonia in attendees of the convention; one of the patients had died.
A flurry of phone calls throughout the day soon revealed eighteen known deaths of attendees, most from pneumonia, and an additional seventy-one case-patients in hospitals throughout Pennsylvania. That is an unusual number of deaths in a short period. The immediate thought that this could be due to influenza was understandable.
Fraser in Charge
The subsequent investigation was to be one of the largest ever undertaken by the CDC. It was headed by Dr. David Fraser, an intense, clear-thinking epidemiologist who reveled in the complex and mysterious world of newly discovered pathogens. His team would demonstrate the value of the CDC’s history of training a group that might be needed if the country ever faced bioterrorism. Some were former members of the EIS, including Dr. Bob Sharrar, now chief of communicable disease in Philadelphia. Some were current EIS officers who would go on to other public health positions in the future, including Dr. Steve Thacker, who later became head of the program to train these “disease detectives,” and Dr. David Heymann, who would later head up the communicable disease programs of the WHO. They were only a few of the dozens of CDC epidemiologists assigned to Fraser, supplementing dozens of state employees. Scores of others were involved in testing specimens from patients and the environment and supporting the huge logistic needs of the investigators.
The large team instituted intense surveillance, contacting hospitals and clinics. They sought help on cases by establishing a hotline to immediately provide information to the public. As the cases and deaths mounted, attempts were made to culture an organism, and specimens were collected for testing for toxic agents.
In a surprising development, tests for influenza were negative, as were cultures for known causes of pneumonia. By noon of August 3, a case definition had been developed and approximately 100 persons fit the category. An EIS officer visited each person, a chart review and physical exam were completed, and cases were excluded or included based on this review. By the evening of August 5, the list included 140 persons.
There was no clue of an etiological agent. However, an important finding had been established—there had been no secondary spread from these patients, a fact that provided some reassurance to the public. This was important because family members were understandably concerned that they might be next, and some people were shunning those who had attended the convention. The lack of an influenza virus in cultures and of secondary spread was sufficient to eliminate influenza as a possible cause.
Among attendees, visiting the Bellevue Stratford Hotel was strongly associated with illness. Although only about 15 percent of the attendees had actually stayed at this hotel, many had visited it for the meetings.
Because thousands of phone calls came in to the CDC investigators, a triage system was developed so that EIS officers could concentrate on what investigators hoped would be the most productive leads. First, to characterize the illness, each patient was contacted for follow-up information. While incubation periods varied, and some attendees were sick by the end of the convention on July 24, the average person’s symptoms developed six days after arrival at the convention. Few cases developed after August 1. The illness was characterized by fever and cough, severe enough that 80 percent of patients were hospitalized. Fevers over 104°F, rapid pulse, and rapid breathing were more common in those who died.
But still no agent could be identified. Organic and inorganic toxic agents were also sought in environmental samples and tissue samples at autopsy. Every test ended in frustration.
The analysis suggested higher attack rates in persons who actually stayed at the Bellevue Stratford than those who did not. In addition, persons who developed symptoms but had not stayed at the hotel were found to have spent more time at the hotel for meetings than did those who did not get sick. Finally, the highest rates of illness seemed to be related to time spent in the hotel’s lobby. The lack of illness in hotel employees was noted, but the employees tended to be much younger than the guests, so they did not provide a true comparison group. These were all good clues, but they did not add up to an answer.
The investigation continued through the fall, the team always hoping for new information that would explain what was not making sense. It seemed clear to the investigators that this was an infectious agent, but the science was failing them.
No investigation is complete without red herrings, and while public health investigations don’t require such problems, sometimes they appear. The red herring came from a respected scientist, F. William Sunderman. Dr. Sunderman was exceptional in many ways. He was a first-class pathologist, musician, globalist (and survivor, living to the age of 104), as well as a world authority on the toxic effects of nickel carbonyl. He suggested that the epidemic was due to nickel carbonyl. CDC-gathered specimens were not adequate for the analysis required, and the early autopsy specimens supported the theory. It was then discovered that the pathologists had gathered the specimens by using metal instruments and that they were the possible sources of the nickel. Sunderman himself did the retesting and found the evidence wanting. The theory was discarded, and the investigation continued.
Cyril Wecht, coroner of Allegheny County, Pennsylvania, was politically ambitious, outspoken, controversial, and a magnet for journalists. He was publicly critical about what he thought was being done wrong in the Legionnaires’ disease investigation, and, consequently, both Pennsylvania and the CDC health officials were placed on the defensive. Outspoken critics can be helpful in setting priorities and making decisions. If they are on your team, it is useful to enlist them in exploring their theories and making midcourse corrections when appropriate. But if they aren’t on your team and instead act as outside commentators, with no responsibility to test their suggestions, they require an inordinate amount of energy and time just to answer their charges. It is far easier to be disruptive than helpful.
Congress Weighs In
But the biggest nemesis was congressman John M. Murphy, chair of the congressional Subcommittee on Consumer Protection and Finance. Murphy was accomplished and powerful. Born on Staten Island, he had attended Amherst College and West Point. During his twelve years of military service, he was awarded the Distinguished Service Cross and the Bronze Star. He had demonstrated his abilities, but he had also become addicted to the spotlight.
Murphy was determined to have a hearing to show the CDC’s incompetence. The press had been harsh about the CDC’s inability to find a cause for the outbreak, and media attention fed Murphy’s approach. The CDC had quickly ruled out dozens of outbreak possibilities, an astounding accomplishment from a scientific perspective. But it didn’t make up for its failure to find the cause. Congressman Murphy now scheduled two days of hearings in Philadelphia to hammer home the incompetence of the CDC. Dave Fraser would be the major witness at these hearings, but he was joined by Drs. Sencer and Joseph Boutwell, deputy director of the Bureau of Laboratories at the CDC. Dave Sencer was determined to take the heat by actually reading the opening statement on behalf of all three witnesses.
Congressmen generate headlines, and so the anticipation of hearings in Philadelphia again increased the negative stories about the CDC’s inability to solve the outbreak. To make matters worse, Murphy circulated a memo to his committee that indicated that he would label the investigation “a fiasco.” The memo was leaked to Jack Anderson. Anderson was a journalist, radio and TV personality, and a heavyweight in investigative reporting circles. He was unafraid of powerful people and was known for revealing information on J. Edgar Hoover (even going through Hoover’s garbage cans). He was bold in fighting battles but not always right. For example, he sided with Senator Joseph McCarthy in his hunt for communists until the evidence against McCarthy became overwhelming. Anderson published an article on Legionnaires’ disease that denigrated the CDC and its experts as people who had a high regard for themselves—one not shared by the rest of the scientific community. This was going to be a hostile hearing.
On Tuesday, November 23, Congressman Murphy opened the hearing and did not disappoint those looking to find fault. His opening statement was belittling to those who had worked hard for four months to entertain every possibility, seek out every clue, and review every finding. He said, “CDC’s apparent failure to consider all possible causes from the very beginning, no matter what their expectations led them to believe, is questionable.” He believed a toxin was the cause of Legionnaires’ disease and that the CDC was so focused on an infectious cause that it had failed to see the big picture.
The day went on with a variety of witnesses. The CDC’s statement was put off until the next morning. At that time, Dave Sencer read a careful statement that reviewed what had been found and suggested that this was not a human failure but rather a reflection of where the science was at this time.
The questions that followed the opening statement were not so much questions as continuing attacks on the witnesses. Reason was brushed aside, and the three CDC witnesses experienced what many have learned: the power of science is often neutralized by the power of power.
It was a moment of low morale for the CDC. The Legionnaires’ outbreak was a frustrating example of coming up short. There had been outbreaks in the past that were not solved. But usually the reason was understandable. A delay may have made it impossible to get proper samples—or none may have been available (a frequent occurrence in foodborne outbreaks). Sometimes, as in an outbreak of respiratory problems in Pontiac, Michigan, the samples seemed adequate, but no organism was identified. But even with organisms never before seen, as with Lassa fever, green monkey disease, or Ebola, modern laboratory techniques had risen to the occasion and identified, for the first time, an organism not previously known.
The outbreak of Legionnaires’ disease provided sufficient clinical patients, compulsive investigators, and samples of almost everything—but no solution. It was more than frustrating. It was demoralizing. Highly trained investigators were rendered impotent.
A month after the congressional hearing, David Fraser finished his report and in seventy-nine pages summarized what had been found. The summary of those seventy-nine pages is muted, and it requires some insight to understand the hard work; the countless hours; the political, scientific, and social barriers faced; and the unhappiness and frustration of not being able to find the cause of this outbreak:
SUMMARY—An outbreak of 180 cases of febrile respiratory illness with 29 deaths occurred in Philadelphia in July and August 1976. One hundred forty-nine of the cases were in persons who had attended an American Legion Convention held at Hotel A and the remainder had all entered the hotel. Results of the epidemiologic investigation indicated that continuing common-source transmission occurred during the convention, and that age, delegate status at the convention, and spending time in Hotel A were determined to be risk factors for illness. No mode, place, or vehicle of transmission could be incriminated with certainty. The outbreak terminated spontaneously, and no spread to the City of Philadelphia was found. (Unpublished CDC communication)
Resolution
The story was not over. Restless scientists at the CDC continued to second-guess themselves. Joe McDade, an expert on Rickettsia organisms, attended a party on the evening of December 28 of that year, but he was troubled and returned to his lab to search once again through the slides he had prepared from samples submitted months earlier from the Philadelphia outbreak. He later described the effort as similar to searching for a contact lens on a basketball floor by oneself.
He had been asked to rule out Q fever and had inoculated guinea pigs with material from patients who had died. The guinea pigs died, but no organisms could be found in the guinea pig samples. He had seen occasional inclusions in scavenger cells that looked like bacteria, but they seemed insignificant because if they had caused disease the sample would have been swarming with the bacteria.
This night, however, he noticed something that excited him. He saw a number of bacteria inside a white cell. The next day, he and his team started from scratch. Because the bacteria were not showing up with the usual staining techniques, the lab team tried new ways of staining and new ways of growing the organism.
Within two weeks, McDade, his mentor Dr. Charlie Shepard, and their staffs had located the new organism, figured out how to make it grow, and found a way of staining it so that it could be seen under the microscope. Then they had shown that survivors of the Pennsylvania outbreak had antibodies to this exact organism.
The scientists determined that the newly named Legionella organisms do not grow under typical laboratory conditions. They require a specialized diet of cysteine and iron, low sodium, and activated charcoal. They also thrive in higher temperatures than most bacteria.
The team kept these findings absolutely quiet until they were sure of their results. Even then they had reservations. But it was time to tell.
Roslyn “Robbie” Robinson, director of the CDC Laboratories, asked for an appointment with Dave Sencer. Robinson brought with him Walt Dowdle, head of virology; Dr. Shepard, a world-renowned leprologist; and Dr. McDade, a rickettsiologist, to the meeting with the CDC’s director. After some hemming and hawing, as Sencer later reported it, Robbie said, “I guess we should tell you that Shep and Joe have isolated the organism that causes Legionnaires’ disease.”
“After a minute of stunned silence,” Sencer said, “they explained that the two had been using old microbiological techniques to see if they could recover an organism, and they had. I called Dave Fraser to come down along with Don Berreth [director of the CDC’s Office of Information] … Shep said they wanted to take the weekend to redo the isolation in a room where they had not been working to rule out any possibility of contamination.”
The scientists confirmed the findings over the weekend, and Berreth developed a plan for a special edition of the Morbidity and Mortality Weekly Report (MMWR) to be released on Tuesday, January 18, 1977. The presses were running that day when Sencer said, “Shep came literally running into my office, to tell me that he had retrieved sera from the serum bank of two earlier unresolved outbreaks of pneumonia and they were positive for the identical organism. The presses stopped, the corrections were made, and from then on it moved like clockwork.”
That Tuesday, January 18, there was also a conference call of health officers around the country, and every CDC worker involved in any way with the investigation was on the call. This was followed by a CDC press conference, at which Sencer announced to gathering journalists that the cause of Legionnaires’ disease was now known. It was a time to rejoice over the ability of science to unravel yet another complex problem.
Before the press conference, Sencer contacted his superiors in Washington, DC, so that they would not be surprised by the announcement. He even had the courtesy to call Congressman Murphy to say that, after an exhausting series of tests, McDade and Shepard were confident that they understood the cause of the Philadelphia outbreak. The congressman responded, “Well, it’s about time.”
Three days later, Congressman Murphy issued a newsletter with the banner headline: “CONGRESSMAN MURPHY CONFIRMS THE CAUSE OF LEGIONNAIRES DISEASE.”a
a Less than four years later, in December 1980, the press reported that Congressman Frank Thompson Jr. and Congressman John M. Murphy had been found guilty in the FBI undercover Abscam probe—Thompson for bribery and conspiracy and Murphy for receiving an unlawful gratuity, conflict of interest, and conspiracy.