**1. Introduction**

Controversy exists over whether myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS) and as ME/CFS, is an organic disease, a psychosomatic illness, or even exists as a disease entity. ME/CFS usually occurs as sporadic cases, but epidemics (outbreaks) have occurred worldwide [1,2]. In the summer of 1955, an illness, that had not been described in existing medical textbooks, affected more than 300 members of the medical, nursing, and ancillary staff at the Royal Free Group of hospitals in London [2–4]. The hospital medical staff reported that "this was an outbreak of an obscure, highly infectious illness with evidence of involvement of lymphoreticular structures and the central and peripheral nervous systems" and called it an encephalomyelitis [3,4]. The outbreak lasted from July to November and resulted in the main hospital being closed for three months. In spite of intensive investigation, no causal pathogen was identified [2–4]. No evidence was found that contaminated water, milk, or food was the source of infection and no toxins were found [3,4]. The illness was initially named Royal Free disease but the following year the name benign myalgic encephalomyelitis was coined to describe this and several other

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Organic Disease or Psychosomatic Illness? A Re-Examination of the Royal Free Epidemic of 1955. *Medicina* **2020**, *57*, 12. https://dx.doi.org/10.3390/ medicina57010012

**Citation:** Underhill, R.; Baillod, R.

Received: 20 November 2020 Accepted: 22 December 2020 Published: 26 December 2020

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similar outbreaks [5]. The name chronic fatigue syndrome (CFS) was introduced in 1988 to describe a comparable disease, in Nevada, USA [6].

Fifteen years after the Royal Free outbreak, two psychiatrists (McEvedy CP, and Beard AW) published a hypothesis stating: "From a re-analysis of the case notes of patients with Royal Free disease, it is concluded that there is little evidence of an organic disease affecting the central nervous system and that epidemic hysteria is a much more likely explanation. The data which support this hypothesis are the high attack rate in females compared with males; the intensity of the malaise compared with the slight pyrexia; the presence of subjective features similar to those seen in a previous epidemic of hysterical over-breathing; the glove-and-stocking distribution of the anesthesia; and the normal findings in special investigations. Finally, a deliberate attempt by one of the authors to produce an electromyographic record similar to that reported in Royal Free disease was successful" [7]. They based their hypothesis on a study of 198 case notes selected from 255 hospitalized patients [3,7]. McEvedy and Beard also reviewed 14 other outbreaks identified as ME and proposed that they were psychosocial phenomena caused by mass hysteria on the part of the patients or altered medical perception of the community [8]. The concept of hysteria as the cause of the Royal Free outbreak was strongly opposed by the Royal Free medical staff on the grounds that there were characteristic physical signs, the disease was endemic in North London at the time of the outbreak, the disease course was prolonged, and epidemics had occurred worldwide [9,10].

The publication of the McEvedy and Beard papers ignited controversy over whether ME was an organic disease or a psychosomatic illness [2]. The following factors have been employed to support a psychosomatic hypothesis. The etiology is uncertain. There is no biomarker. Diagnostic criteria are based on clinical symptoms and the exclusion of other fatiguing illnesses. There are no pathognomonic physical signs. Patients frequently do not look ill even when severely affected by the disease. There is no curative medication. The concept that ME/CFS is a psychosomatic illness is widespread [11–13] and has resulted in the stigmatization of patients and patient complaints of sensing hostility from their health care providers [14,15].

Research studies in patients with ME/CFS have shown multiple pathophysiological differences between patients and healthy controls in the immune system, the nervous system, and metabolic processes including energy metabolism [16–18]. Although no causal pathogen has been identified, studies have shown that patients harbor a variety of infectious agents and have pointed towards a possible aetiological role for infectious organisms [19,20]. The psychosomatic hypothesis does not explain these pathophysiological changes. Mathematical modeling of the Royal Free outbreak also validates an infectious disease aetiology and refutes the epidemic hysteria hypothesis [21].

The question of hysteria or psychoneurosis as a possible cause was raised in the Royal Free outbreak [2,3], the 1934 Los Angeles county general hospital outbreak [22], and in three other outbreaks classified as ME [23]. Manifestations of psychoneurosis were seen in a few cases in all these outbreaks, but the authors concluded that hysteria did not explain the observed clinical features. Psychogenic anxiety reactions, evidenced by non-specific symptoms have been described in people exposed to outbreaks of organic disease, or people present during a disaster [24–26] and have been labeled "reactive psychological disaster syndrome" [26]. Reactive psychological disaster syndrome might account for some patients showing hysterical manifestations in various outbreaks of ME.

Our objective was to obtain first-hand observational accounts of the 1955 outbreak of ME from ex-Royal Free hospital staff and patients who had experienced it and to review evidence for the underlying cause being an organic infectious illness versus psychogenic epidemic hysteria. No other follow-up studies have been published.

Etymology: ME/CFS has been labeled psychosomatic, psychosocial, somatoform, and a biopsychosocial illness. This paper uses the term psychosomatic.

#### **2. Materials and Methods**

Statements were placed in the 'Royal Free Association' newsletter and the 'Royal Free Nurses League' magazine. These organizations were established for doctors and nurses respectively who trained or worked at the Royal Free Group of hospitals. The statements invited anyone who had experienced the Royal Free disease outbreak of 1955 to contact the authors to provide information about their experiences. We asked for information from both those who became ill and those who remained healthy. Volunteers contacted us by email and letters. Those who supplied a telephone number were interviewed using a semistructured interview. Telephone participants were asked for their age and occupation at the time of the outbreak and were asked what they remembered about the event. Participants were included in the study if they had personally experienced the outbreak. The authors of this study were medical students at the Royal Free medical school and as such, were not permitted to enter the hospital at the time of the outbreak. Therefore, we did not meet the inclusion criteria for the study group. To avoid individual identification, descriptions of the outbreak in this paper are a compilation of individual accounts. Evidence for the outbreak being an infectious encephalomyelitis versus epidemic hysteria was evaluated by comparing the study group's accounts and the original published medical staff reports [3,4] with data given for the epidemic hysteria hypothesis [7].
