Copyright Hillary Johnson 2024. All Rights Reserved
I admit to feeling adulation for the epidemiologists of the twentieth century who studied outbreaks of ME—right up to the point at which the Centers for Disease Control sent two epidemiologists to Incline Village, Nevada to investigate an epidemic in 1985.
A break in the natural order, wherein knowledge accrues and is passed from generation to generation, occurred with the CDC’s Nevada investigation. The agency not only stopped time, it erased a valuable chapter of science as if taking a wrecking ball to a cathedral.
The US government’s denigration of ME, evidenced by its scientists’ decades-long running insults about the ME “personality type,” buttressed by its refusal to spend money to study the disease, is a modern phenomenon.
Prior to 1985, US public health agencies were willing to invest resources and the efforts of its top epidemiologists on ME.
In fact, beginning in 1934, the US government sent top-flight epidemiologists to far-flung locales to investigate reports of suspicious outbreaks of disease—outbreaks that turned out to be ME. I confer on these pioneers a kind of glamor akin to explorers who sailed to the poles in the late nineteenth and early twentieth centuries for the sheer thrill of discovery.
The epidemiologists I’m thinking of —starting with the NIH’s A.G. “Sandy” Gilliam who wrote a 90-page monograph on the 1934 outbreak in Los Angeles—left behind a body of scientific literature that provides a rational counterbalance to the government’s debacle of 1985 and beyond.
As promised, I’m offering a comparison of two CDC investigations of ME outbreaks separated by thirty-one years. The first is a remarkable story because it’s emblematic of a government agency performing at peak competence in the realm of ME.
I know—hard to imagine.
I’m drawing from two sources. The first is my own original reporting on the CDC’s Incline Village, NV investigation, which was one of the major story lines in my 1996 book, Osler’s Web. My second source is the work of journalist Berton Roueche, who wrote about a CDC investigation in Punta Gorda, Florida in 1956. He published his story in The New Yorker under the headline In the Bughouse in 1965. His account describes an effort headed by the agency’s top epidemiologist, Donald Henderson. In the Bughouse was one among several accounts of medical puzzles included in Roueche’s book, The Orange Man, (1967).
Roueche wrote twenty books, frequently medical detective stories in which he featured epidemiologists who cracked, or attempted to crack, disease outbreaks and medical oddities. The New Yorker created The Annals of Medicine department specifically to showcase Roueche’s work. Reportedly, episodes of TV’s House were drawn from Roueche’s New Yorker stories.
I described Henderson’s Florida inquiry in Osler’s Web in a chapter called “Antecedent Epidemics.” I obtained permission to quote portions of In the Bughouse from Roueche’s literary executors, Harold Ober Associates. Subsequently, I thanked Harold Ober for kindly granting me that permission on the first page of Osler’s Web. When you read material within quotation marks below, it is directly quoted from Roueche’s In the Bughouse.
After reading Roueche’s account of Henderson’s Punta Gorda investigation, one would hardly be surprised that the young epidemiologist was poised for historic achievements in public health. Soon after Punta Gorda, Henderson left the CDC, joined the World Health Organization and launched an ambitious plan to rid the world of small pox. It was a successful effort, a feat that won Henderson his place in the pantheon of public health giants. It’s the achievement for which he is best known.
Henderson was twenty-eight when he became chief of the agency’s Epidemic Intelligence Service, which had been established in 1951 to investigate the possibility of bioweapons in the Korean war. At the time, the CDC was called the Communicable Disease Center of the U.S. Public Health Service. The agency’s EIS unit served two purposes, first as a place to teach people of all backgrounds how to perform epidemiology and second, to actually undertake epidemiology.
When I interviewed EIS administrators, I learned that they envisioned their staff as the agency’s shock troops, teams of disease detectives that were ready to race to outbreaks of disease anywhere on earth. In his 1987 book about the AIDS crisis, And the Band Played On, Randy Shilts breathlessly described the EIS as “a rapid deployment force that could be relied upon to pounce on a crisis and establish a beachhead.”
In 1956, under Don Henderson’s leadership—yes. In 1985? You decide.
CDC 1956:
Henderson was alerted to an unusual outbreak of disease in Punta Gorda, Florida on May 9, 1956, when a letter from the Florida state epidemiologist, a man auspiciously named James Bond, landed on his desk. Henderson immediately dispatched a bright young EIS colleague, the epidemiologist David Poskanzer, to Florida. The latter remained in Punta Gorda for a week, then returned to report his findings to Henderson and other epidemiologists at the agency.
CDC 1985:
Incline Village, NV internal medicine specialists Dan Peterson and Paul Cheney first alerted scientists at the Atlanta agency to an outbreak of unusual disease in their town in June of 1985. Over one-hundred people were horribly ill with a disease neither doctor had learned about in medical school or encountered in practice.
Paul Cheney engaged that summer in a series of phone calls with a brand new EIS recruit named Gary Holmes. Cheney tried to convey the dramatic aspects of the disease, but Holmes, in Cheney’s words, “didn’t know very much—he never knew very much.” Holmes, a recent med school grad, had been with the EIS less than four months.
By the end of July, 120 people were sick. “I just kept calling up the CDC and saying, ‘Now we’re up to one-hundred and twenty. And then another week would pass and I would call and say, ‘Now we’re up to one-hundred and thirty-five.” By September, the doctors’ hopes that CDC would send investigators to the lake began to fade.
Cheney and Peterson were increasingly alarmed: the malady was behaving like an infectious disease. Clusters within the larger cluster included members of a girl’s high school basketball team and their coach; a prostitute with the disease—and several of her clients; black jack dealers who worked together at a local casino; and staff who worked in the doctor’s offices and interacted with sick patients every day.
CDC 1956:
Upon his return to Atlanta, Poskanzer presented his observations about “Punta Gorda fever,” as locals were calling the malady, at the agency’s annual Epidemic Intelligence Service conference. (Three decades later, another young EIS officer, Gary Holmes, would present his observations about “chronic EBV” in Incline Village at this same annual in-house meeting.)
“Poskanzer’s report was a feature of the meeting,” Henderson told Roueche. “One thing that particularly struck him about the disease was its enormous and confusing array of symptoms. They were protean—absolutely protean. He stressed that over and over again. I thought I knew what he meant. That is, the point had been emphasized in all the literature that I’d read. But I was mistaken. The symptomatology of epidemic neuromyasthenia is extremely hard to picture. You really have to see it for yourself. Well, I got to see it a few days later.”
Henderson was excited. He had been on the look out for an opportunity to investigate this elusive, hydra-headed disease. He recruited a team of three epidemiologists besides himself, including Poskanzer, to accompany him to Punta Gorda for what he promised would be a “comprehensive clinical and epidemiological study.”
The team arrived on May 27, 1956, staying four days. They returned twice, five months later and then a year later. On their first visit, the team undertook a door-to-door survey in an effort to measure the breadth of the disease in this bayside town of 2,000 people. Aided by neighborhood volunteers, they talked to nearly half the population.
CDC 1985:
One steamy morning in mid-August Federal Express delivered twelve samples of Tahoe blood to the CDC herpes virus lab. Paul Cheney had sent the samples in a last ditch effort to capture the agency’s attention. It took about ten days to run tests. Just as Cheney had promised, CDC bench researchers found abnormally high levels of Epstein-Barr virus in the blood. Thus, Larry Schonberger, head of the division of viral diseases, was presented with a major piece of evidence supporting Cheney’s claims.
After having given up on the CDC, the doctors received word that two epidemiologists were coming to investigate. The doctors were relieved.
“I thought,” Paul Cheney told me, “Now we’re going to finally get some help.”
In mid-October, two young EIS officers flew to Reno, rented a car and drove to the top of Mt. Rose, the 8,000 foot mass that looms between Reno and Incline Village. On a clear day, the continent’s largest alpine lake, twenty-two miles long, twelve miles wide, is starkly visible at the top.
Holmes and Kaplan stopped to stare.
“It was like seeing the promised land,” Holmes told me later about the unforgettable moment.
“The hotel was right across from the lake,” his senior partner Jon Kaplan said. “We didn’t have a view, but that didn’t keep us from getting out and seeing the area. Gary and I climbed a mountain one day—Mount Talac. We took a whole day and climbed up there. It was gorgeous.”
Later, Gary Holmes revealed to me that had the locale not been Lake Tahoe, he and Kaplan would have been less inclined to make the trip.
CDC 1956
By the time Henderson and his team arrived in Punta Gorda, sixty-five cases had already been diagnosed. Henderson and his colleagues turned up an additional sixty-two cases of the disease by going door-to-door. As Henderson explained to Roueche, “Medical records are only an indication of the scope of an epidemic. There are always a number of victims who can’t or won’t see a doctor. This was especially true in Punta Gorda.”
CDC 1985
In a letter to Nevada health officials in October 1985, Gary Holmes wrote that he and his partner had examined sixteen patients. One year later, when he presented his report about Incline Village to the annual in-house EIS meeting, Holmes reported seeing ten patients. When I interviewed him two years after the fact, he again used the figure ten.
“We figured that with ten people we could get a pretty good idea of whether there was something that we really wanted to bite down on and and do a thorough investigation,” Holmes explained, “or whether we should back off and take it kind of easy.”
For his part, Kaplan, reaching back into his memory, estimated in our interview that the two had examined “a dozen—fifteen—something like that. We asked to see patients they thought were most likely to have the disease. So they picked,” Kaplan told me, disdain entering his voice. “We didn’t pick.”
What Cheney recalled was his frustration at trying, and failing, to convey to the CDC investigators the alarming nature of the problem. He and his partner desperately wanted the federal researchers to grasp the dimensions of the calamity, and not only its epidemic aspects.
“Dan and I were saying, ‘Gosh, look at this one…and this one.’ And, ‘This is an interesting case,” the doctor said. “We were imparting—trying to impart—the sense of what we were dealing with.
“As I remember,” Cheney told me, “they weren’t excited. They wouldn’t say anything. It remined me of many bureaucrats. You know—it was just a job.”
CDC 1956
Henderson and his companions were stymied by the multiplicity of symptoms among patients.
As Henderson later recalled, “The principal presenting symptoms were recurrent sharp pains in the muscles of the back and neck, severe headache, disturbances of coordination, and some transient motor and sensory dysfunction. Plus a strong emotional overlay—tension, anxiety, depression.”
Recent disturbances in memory were also prominent, Henderson noted. He described one memorable case to Roueche:
“I was in on several of the interviews, and I can testify that we managed to get the facts—one way or another. I remember one case in point. It was a preacher—white, middle-aged, married. He had been sick, and his symptoms were generally provocative. Except on the emotional side. He insisted that there was nothing wrong with his mind or his memory. As we rose to go, the interviewer asked him if she could have a glass of water. Of course, he said, and left the room. But almost at once, he was back. The interviewer had asked him for something—what was it? She told him. Oh, yes. He started out of the room again, and then stopped and called upstairs to his wife. Where did they keep the ice cubes? She told him, and he went on into the kitchen. But a moment later he called her again. This time he wanted to know just how many cubes should go into the glass. We added him to the case list.”
CDC 1985
“No detailed histories were taken,” Cheney told me. “We dragged Gary and Jon upstairs (the doctor’s private offices were on a lower floor) and had them feel a spleen here or a lymph node there, but they engaged in no systematic examination of even a subset of these patients.”
Both CDC investigators were put off by the patients’ claim they were ill.
“I was impressed that the patients thought there was something wrong with them. I mean, you can’t minimize that,” Kaplan told me. “They knew why they were there and they were there to tell us about it…I got the impression that there was a kind of collusion going on between the patients and the doctors.
“Their symptoms were really quite different,” Kaplan continued. “Some people had been laid out for months and others hadn’t been as severe. The other symptoms were incredibly varied. It wasn’t like an episode of shigella [dysentery], where everybody comes in and they have exactly the same thing…
“It was pretty apparent early on that the illness just wasn’t cut and dried. It wasn’t simply that you could diagnose it,” Kaplan said.
CDC 1956
Henderson’s defining criteria “fell a bit short of scientific excellence,” he admitted in his conversations with Roueche.
“Epidemic neuromyasthenia is a most ungrateful disease in that respect. Its manifestations are subjective rather than objective…There was practically nothing that we could see or touch or measure. I mean, there were no lesions to examine, no big livers or tender spleens to feel, no jaundice, no classically paralyzed limbs, no laboratory data to analyze. We used to sit in my room at the motel after dinner and puzzle it over and over. None of us had ever seen anything like it. We just couldn’t put it together. It was bizarre…I tell you, we began to feel that we were living in the bughouse.” (Slang of the era for psychiatric hospital)
In time, the group began to entertain the notion that the patients, too, might belong in the bughouse.
“Depression, Terrifying dreams. Crying without provocation. Nausea and headache and diarrhea. Back and neck pains. Imaginary fever. Problems of memory and mentation. Vertigo. Hyperventilation. Menstrual irregularities. Difficulty in swallowing. Fatigue. Fast heart. Imaginary swellings. Paresthesia [transient numbness and tingling]. And paresis [extreme muscle weakness]…You can see why the possibility of a psychoneurotic explanation came readily to mind,” Henderson told Roueche.
CDC 1985
As the senior epidemiologist, it fell upon Kaplan’s shoulders to devise a means to elucidate the claims of two doctors and scores of patients along the lake’s perimeter.
“Eventually what I did was say, ‘Let’s pick some clinical definition to work with. What’s the common denominator? Everybody says they’re tired. Okay. Let’s use tiredness as a definition…which ended up being about as nebulous as the whole situation out there to begin with.”
After five days, however, Kaplan returned to Atlanta. His departure compelled his partner to abandon the luxurious lakeside Hilton because now Holmes had only his own parsimonious government per diem to cover expenses. With Kaplan gone, there would be no more jogging on the beach or hiking mountain trails.
“I moved into some little ski-lodge-looking motel,” Holmes told me. “A couple of evenings I went to the casinos. There’s not a whole lot else to do in that town. It was either that or work on the patients’ charts.”
Maintaining a schedule that ended precisely at 4 pm., the hour at which the CDC’s work day ended in Atlanta, Holmes, with the help of a county health department nurse, created a questionnaire that sought to class patients into four categories of “tiredness.” Ultimately, Holmes entirely eliminated the fourth category. It included patients who had symptoms other than tiredness, symptoms like heart failure, thyroid disease, unspecified colitis, chronic low back pain and “similar diseases that might have explained their fatigue,” Holmes said.
Cheney and Peterson believed the simultaneous emergence of heart, thyroid, respiratory, gastrointestinal, bacterial and any number of other ailments was hardly coincidental among epidemic patients. Based on their knowledge of their patients’ histories, they felt these were features of the multi-system constellation of a single entity. It was a perceptual breach that would persist decades into the future, with the government’s bias holding sway and resulting in an egregious distortion of any understanding of ME. It turned ME into a manifestation of one subjective symptom, tiredness, rather than a discrete disease with multiple symptoms and biomarkers.
In the end, after adhering to his partner’s recommended methodology, Holmes had identified what he believed were fifteen patients with “tiredness” and no other confounding symptoms—out of 150 patients who were sick.
“What else could we do?” Gary Holmes asked me later in his liquid Texas dialect, his voice rising. “They were wanting us to go out and do this thorough investigation of everybody that they thought had the disease and it would have yielded no useful information whatsoever. Because there was such a mixed bag of stuff going on…That’s the old garbage-in, garbage-out, basically.”
CDC 1956
The pattern of the epidemic, the apparent absence of any common exposure factors, and the high incidence of the illness among medical and hospital personnel, was consistent only with an infectious disease transmitted from person to person.
Ultimately, Henderson and Co. dismissed the bughouse theory because the facts of the epidemic could not support it. The cases had occurred in scattered, random fashion from February to June rather than simultaneously; additionally, Henderson noted, “Nothing had happened in Punta Gorda that could have excited a mass reaction.” In fact, he pointed out, “there was hardly a ripple of apprehension among the general population in the town…It was just the reverse of a panic situation.
“If it wasn’t a question of mass hysteria,” Henderson said, “what was the anatomy of the epidemic?”
After eliminating insect-to-man transmission, common exposures to a toxic product, and contamination of food or water supplies, the team arrived at the only remaining possibility: “It was also, of course, the likeliest explanation. “
“The pattern of the epidemic, the apparent absence of any common exposure factors, and the high incidence of the illness among medical and hospital personnel, was consistent only with an infectious disease transmitted from person to person. Just how the microorganism responsible might travel from person to person was not at all clear. It is still wide open to conjecture. We were able, however, to postulate the general nature of the microorganism. It was probably a virus.”
CDC 1985
Just before returning to Atlanta eleven days after he arrived, and after consulting with Kaplan by phone, Holmes decided to collect blood samples from the fifteen people they deemed bona fide.
“This was not something they thought about early or even in the middle of this thing,” Cheney remembered. “Gary almost missed his plane trying to get blood to bring back.”
Holmes also selected thirty patients as controls at the eleventh hour, too. He conscripted office staff from the internal medicine practice and a number of patients who came through the doctors’ offices with minor complaints. Clearly, no one at CDC considered the Tahoe malady might be caused by infectious agent, because if that were true, any number of people could have been infected and asymptomatic. No one in the region would be a suitable control in that case.
Additionally, as the doctors would discover one year later, the Texan had erred and unwittingly conscripted “fatigue” patients into the control group.
CDC 1956
The fact that the team tested Punta Gorda residents for several viruses with negative results hardly dissuaded Henderson. He noted that infection might occur very early in the disease. By the time symptoms arose, the patient might have ceased to excrete the virus, a phenomenon common to many viral illnesses. Further, Henderson explained, viruses “are hard enough to find…in the best of circumstances…They’re extremely numerous, too. Umpteen new ones are discovered every year.”
Having concluded the disease in Punta Gorda was a viral infection, Henderson told Roueche that the solemnity of his conclusion weighed heavily on him. He was worried. At night in his hotel room he often sat, head in hands, wondering whether he should go directly home to his wife and children when his investigation was over, or whether he should quarantine for some period of time.
CDC 1985
One month after his return to Atlanta, Gary Holmes drafted a three-page letter to Nevada’s chief epidemiologist, laying the first brick in the foundation of what would become intractable federal policy on the Nevada epidemic and, in turn, the disease.
If anything untoward had occurred in Nevada, the young EIS officer cynically postulated, it had been an epidemic of a diagnosis.
From that point on, neither Cheney nor Peterson were considered credible reporters, even though their observations about the disease and their increasingly sophisticated understanding of it formed the framework of most of the ensuing scientific discovery around ME.
In 1992, the Institute of Medicine produced a scholarly book called Emerging Infections: Microbial Threats to Health in the United States. Numerous scientists weighed in on how to identify emerging infections as early as possible. The book began by emphasizing the critical, first alert role played by medical doctors in emerging infections. If one were to distill the government's failed handling of the ME epidemic into a singular incident, it would be the CDC's dismissive treatment of Paul Cheney and Dan Peterson in Nevada in 1985. The agency’s EIS officers slandered and stigmatized the two doctors who could have been the most helpful to public health officials.
CDC 1956
I believe our concerns of 1959 are as valid today as they were then and that we were as confidently knowledgeable about the syndrome then as we are today.
In 1959, Don Henderson wrote an article about the disease for the New England Journal of Medicine. Henderson was the author, but he collaborated on the article with Alexis Shelokov, an NIH scientist who had investigated an outbreak of ME among nurses at a psychiatric hospital outside Washington, DC in 1955. He described several similar outbreaks in previous decades and struggled to impose order on the seemingly innumerable symptoms of the disease. The two investigators agreed that the epidemics likely represented the same clinical syndrome and may have shared the same causative virus. They noted the marked susceptibility of nurses and doctors, which they believed was also the strongest evidence for person-to-person transmission. They were particularly impressed by the preponderance of the disease among young and middle-aged adults and by its proclivity for women by a ratio of at least 1.5 to 1. The severity of the disease had been “considerably greater” for women, they noted. They were also struck by the extraordinary attack rates, usually six to seven percent of the population, which were remarkably consistent among epidemics. These rates, they proposed, intimated that the causative pathogen was one to which the communities affected had no previous immunity.
“To date, there is no agreement upon a name, almost every epidemic receiving a different designation….this creates a chaotic problem.”
Henderson and Shelokov concluded their paper by predicting more epidemics were likely, an assumption based on the plethora of outbreaks already reported.
“Although…these illnesses do not appear numerically important on a national scale, the long-term morbidity among those who are ill and the very large percentage involved in a single outbreak indicate a need for intensive, comprehensive investigation and surveillance of outbreaks as they occur.”
Henderson never investigated another epidemic of the disease, but he described to Roueche his optimism about studying the disease in the future.
“We’ll know it the next time we see it. And we’ll have some new approaches to employ…We’re ready and waiting. But Punta Gorda happened quite a few years ago, and I must say I’m beginning to wonder if there will ever be a next time. The last reported outbreaks occurred in Athens [Greece] in 1958, and in a convent up in New York State in 1961. Neither of them was recognized for what it was until it had almost run its course. We haven’t heard a decent rumor of it since then. It seems to have disappeared.”
Before he left the CDC, Henderson wrote a detailed protocol for CDC epidemiologists to follow whenever the next outbreak occurred, but his protocol languished somewhere inside the CDC. In response to my question, Gary Holmes, assigned to what became known as “chronic Epstein-Barr syndrome” in the late 1980s, told me he searched the agency for Henderson’s protocol in 1987, but was unable to find it.
Did someone throw it away? Or does the protocol remain tucked away in a dusty file cabinet in the recesses of the Epidemic Intelligence Service offices in Atlanta to this day? Most probably written in 1957, Don Henderson’s protocol, if it exists, is sixty-seven years old. Henderson’s battle plan likely would have more value as an academic document than as a practical one. Given that the US federal agencies and governments around the world have allowed ME to become endemic, isolated outbreaks are likely over.
One outstanding question that remains unanswered, of course, is what was the “new dynamic,” as Cheney once characterized it, of the 1980s that allowed ME to explode into the general population? A question for another day.
Coda
In 1992, Henderson was working as a scientific advisor to President George H. Bush. I wrote him a letter about ME. In his letter to me, Don Henderson expressed dubiousness that the disease that by then seemed so widespread could possibly be the same illness he, Shelokov, Poskanzer, Gilliam and others had investigated with such vigor thirty years before.
In a follow up phone conversation soon after, I pressed Henderson on why he believed the disease of the 1980s, and by then the 1990s, could not be the same disease he investigated in Punta Gorda.
He replied that it simply strained credulity.
Why? I asked him again.
Once more, he could offer only his opinion: it simply was unimaginable that so many people could have ME.
Nevertheless, Henderson continued, “What is disturbing to me is to discover how little progress has been made in achieving even a primitive understanding of the pathophysiology, let alone the etiology…I believe our concerns of 1959 are as valid today as they were then and that we were as confidently knowledgeable about the syndrome then as we are today.”
Copyright 2024 Hillary Johnson. All Rights Reserved.
Thank you for sharing this valuable history.
Thank you from me also. It's like having a 'mini dive' back into Osler's Web, leaving me wondering how on earth I managed to read it many years ago, and more impressed than ever that you should have written such a detailed history.
I'm going to raise something from my own ponderings having read this article, especially this passage, although I'm not necessarily expecting an answer:
" They were also struck by the extraordinary attack rates, usually six to seven percent of the population, which were remarkably consistent among epidemics. These rates, they proposed, intimated that the causative pathogen was one to which the communities affected had no previous immunity."
What occurred to me, as an alternative to and/or a compounding problem with, the "no previous immunity" hypothesis, was the potential for the 'attack rate' to reflect a genetic aberration making only those sufferers more likely to succumb to the causative pathogen. Ie a DNA aberration which tends toward 6% prevalence in populations generally. Just a thought?