70th Anniversary of Royal Free outbreak - Why was it so hard to identify the cause, and what were the consequences of this?

14th July, 2025

Although there was much overlap in the symptoms recorded in the different outbreaks, especially fatigue, pain, and ‘flare ups’ - a tendency to relapse following exertion, scientists at the time were not able to identify the cause of the illness.  

What were the symptoms at the Royal Free and earlier outbreaks? 

Across all outbreaks, there appeared to be an initial ‘acute’ phase of the illness, often charactersised by a sore throat, nausea and vomiting, headaches, dizziness, enlarged and tender lymph nodes, muscle and back pain, and fatigue. 

Following this, there were ongoing symptoms which displayed evidence of the involvement of the central nervous system - this CNS involvement was said to be ‘characteristic’ of the outbreak at the Royal Free (The medical staff at the Royal Free Hospital., 1957). A report from the outbreak in Los Angeles in 1934 stated that following the initial infection, there was a tendency for people - especially women - to relapse, or experience ‘flare-ups’ (Gilliam,1938). 

Evidence from the outbreaks in Iceland (1948-1949), and in New York (1950) showed the long-term impact of the illness:  

• For some who became ill in Iceland, neurological symptoms - including muscle tenderness, muscle weakness, and loss of muscle (muscle atrophy) – were still present 7-10 months after the illness began (Sigurdsson et al., 1950).  

• In New York, 9 cases were followed up until 1952 - 2 years after the start of the outbreak in the city. Notably, the course of the illness was characterised by “remarkable fluctuations in intensity, variety, and type of symptoms” (White et.al., 1954).  

Poliomyelitis (attributed to Polioviruses) - why linked, and why discounted? 

In many of the outbreaks, the symptoms of the ‘mystery illness’ were initially attributed to poliomyelitis - a serious infectious disease which, although now very rare due to a vaccination programme introduced in 1955, is caused by a virus that spreads easily from person to person.  

In fact, even when differences in the clinical presentation of the disease were noted, the diagnosis given in many instances - such as during the 1934 outbreak in Los Angeles - was ‘atypical poliomyelitis’.  

Differences

Despite similarities in symptoms, key differences were observed between outbreaks of poliomyelitis and outbreaks of the mystery illness. 

These included:  

• Inconsistencies in timing of outbreaks:

Shaw and Thelander - who wrote about the 1934 outbreak of ‘suspected poliomyelitis’ in San Francisco - noted that while episodes of poliomyelitis typically occur during periods when other epidemic diseases are not present, this outbreak occurred at a time when measles incidence was decreasing, and there was a great deal of respiratory infection and acute illness.  

• Atypical age and sex distribution.

In the Iceland epidemic of 1948 to 1949, the predominance of spread in schools was not typical of poliomyelitis, neither were the age and sex distribution - scientists explained that polio is usually higher in males than females, but this unknown illness was higher in young females (Sigurdsson. et al.,1950). 

• Differences in symptoms.

Similarly to the outbreak in Iceland, the outbreak in New York was initially thought to be linked to poliomyelitis and named ‘acute anterior poliomyelitis’. However, the symptoms observed meant that the doctors at the time became ‘increasingly convinced’ the disease was neither polio nor any other virus known to them (White et al., 1954). 

The polio vaccine

Another factor which decreased the likelihood that the illness was soley due to the polio virus was the introduction of a polio vaccine in 1955. Although the introduction of this vaccine did appear to have some protective effect against the unknown virus, it did not prevent cases of M.E. developing. 

Notably, Dr. Byron Hyde stated that while many pre-1955 ‘M.E. patients’ were paralysed and in wheelchairs, post-1955 ‘patients’ commonly had severe muscular failure but did not display paralysis - Hyde concluded by stating that “clearly the introduction of the polio vaccine had an effect on the prevention of paralysis in ‘M.E.’” (Hyde, 1990). 

Additionally, while Polio is thought to be eradicated in Europe today, cases of M.E. are still emerging meaning that there must be other cause(s) of the disease. 

Why was it so hard to identify the cause of the illness? 

Gaps in knowledge at the time of the outbreaks further hindered identification of the cause of the illness. 

These were:  

• Incomplete records  

1. Routine reporting of the early stages of the illness was not carried out due to the mild symptoms often present at the beginning of the infection, and the similarity in symptoms between the unknown illness and the flu (Ovenden, 2004) . Additionally, many mild cases – especially those in rural areas – may not have been reported, and as routine testing was not carried out for the illness, there is no record of asymptomatic cases which may have also occurred.  

• Low mortality rate  

2. Another way of gathering information about an illness is to carry out autopsies on the bodies of people who died from it. As very few people died from the illness in this instance – it had a low mortality rate – scientists could not investigate disease mechanisms in detail in this way.  

• Inconclusive tests  

3. Notably, although many tests were conducted to try and isolate and identify the unknown pathogen causing the illness at the Royal Free – and during other historical outbreaks – they were not able to shed light on exactly what was causing the complex illness.   

• Limitations of the samples used 

4. Tests commonly used samples of body fluid like saliva, blood, or cerebrospinal fluid (CSF) which may not be able to provide a complete picture. According to Dr. Amy Proal - who is working on research funded by ME Research UK - over time there is a tendency for pathogens to leave the blood where the immune system is often the most robust, and to ‘hide’ in tissues where they are better protected. This means that studying samples of body fluids, such as saliva, blood, or urine, is not enough. Rather, it is essential to additionally examine tissue samples from areas of the body such as the gut, muscles, bone marrow, and lymph nodes. Even today many studies only consider samples of body fluid rather than tissue samples and research has highlighted the need for tissue biopsy studies when considering pathogen reactivation in Royal Free M.E., or Tahoe CFS.

What were the consequences of not identifying the cause of the outbreak? 

Nomenclature - A disease with many names 

Since there was no clear cause for the disease, the ‘mystery illness’ was given many names over the years, these included:  

• Acute anterior poliomyelitis  
• Iceland disease 
• Persistent myalgia 
• Akureyri disease
• Epidemic neuromyasthenia 
• Epidemic malaise 
• Royal Free Disease 
• Benign Myalgic Encephalomyelitis  

Although these are no longer used today, the lack of a consistent name for the disease persists. 

Dismissed as ‘hysteria’ 

Due to the limitations in evidence available at the time, the many different names given to the illness, and the lack of conclusive tests to identify a viral cause for the disease, in 1970, the British Medical Journal published a paper by two doctors - McEvedy and Beard - which described the 1955 outbreak of M.E. (what was termed in The Lancet in 1956 as ‘benign myalgic encephalomyelitis’) at the Royal Free Hospital in London as “epidemic hysteria”. 

McEvedy and Beard reviewed the medical records of those who contracted the illness but published their conclusions on the outbreak at the Royal Free without considering Dr Ramsay’s work or ever talking to a single person who contracted the illness (Ovenden, 2004).  

Drs Ramsay, Dinsdale, Compston and Richardson responded immediately to the article by McEverdy and Beard stating:  

“While the diagnosis of hysteria had been seriously considered at the time of the outbreak, the occurrence of fever in 89%, lymphadenopathy in 79%, ocular palsy in 43%, and of facial palsy in 19%, rendered it quite untenable”  

Devastatingly, despite this reply from Dr. Melvin Ramsay and colleagues clearly stating that hysteria did not explain the symptoms of the outbreak at the Royal Free, the paper by McEverdy and Beard was so influential among medics that the credibility of M.E. has never recovered. Even today, despite evidence clearly showing M.E. is a biological disease, many people - including some health professionals - incorrectly believe M.E. to be psychological in nature (psychosomatic).  

It has been suggested that McEvedy and Beard attributed the 1955 outbreak to psychological factors as most people affected were female nurses, and, historically, many unexplained illnesses in women were viewed as psychiatric, and dismissed as “hysteria”.  

The following article in this series will discuss what the the significance of the outbreak at the Royal Free is today. 

References:

• The medical staff at the Royal Free Hospital. “An outbreak of Encephalomyelitis in the Royal Free Hospital Group, London, in 1955”. British Medical Journal. (1957)

• Dr. B. Hyde, Chapter 12, Section: M.E. : An Historical Perspective, in The Clinical and Scientific Basis of Myalgic Encephalomyelitis and Chronic Fatigue Syndrome (1990)

• Pauline Ovenden, 2004. “A personal account of the outbreak of M.E. at the royal free hospital”

• Gilliam A.G. “Epidemiological study of an epidemic diagnosed as poliomyelitis, occurring among the personnel of the Los Angeles County General Hospital during the summer of 1934. Public Health Bulletin No.240 - April 1938)

• Hart T. M., et al., “Orthopedic Aspect of the Los Angeles County 1934 Poliomyelitis Epidemic” (1934).

• Sigurdsson B. et al., “A disease epidemic in Iceland simulating Poliomyelitis.” (1950).

• White et al., “Iceland disease - A new infection simulating Acute Anterior Poliomyelitis” Neurology, 4, 506-516. (1954).

• Shaw and Thelander “Poliomyelitis in San Francisco” American Journal of Public Health (1934).