Is ME/CFS a Single Case of an Undiscovered Cause?

The history of medicine demonstrates that the identification of disease mechanisms can vary dramatically in duration and complexity. The discovery and confirmation of HIV required only approximately two years, after which the diagnosis became universally accepted. The pharmaceutical industry subsequently developed therapies capable of suppressing viral replication, although no definitive cure has yet succeeded in eliminating the virus entirely from the human body.

In contrast, other diseases required decades before their underlying mechanisms were understood. One notable example is Creutzfeldt-Jakob disease. Although the disease was initially described between 1920 and 1921, its true cause, misfolded proteins known as prions, was not verified until 1982, more than sixty years later. Research into Kuru played a critical role in uncovering the biology of prion diseases.

As described by Robert Sapolsky: 

“It was studied by Carleton Gajdusek, who showed that the condition was transmissible. The route of transmission was deeply unusual: ritual endocannibalism, in which relatives consumed the remains of deceased family members as an act of respect. The infectious material was especially dangerous when raw brain tissue was handled during preparation.

It took 19 years for Dr. Carleton Gajdusek’s discovery of the cause of kuru, meanwhile frequently dismissed by other scientists, to be fully acknowledged. Dr. Carleton Gajdusek was ultimately honored with the Nobel Prize.

What shocked scientists was the incubation period. Unlike ordinary viral infections, which produce symptoms within days or weeks, kuru could remain silent for years or even decades. Some cases appeared more than 50 years after exposure. This led to the concept of ‘slow’ infectious diseases.

But the story became even stranger with the work of Stanley Prusiner, who studied scrapie and eventually identified the infectious agent. Scientists expected to find a virus containing DNA or RNA. Instead, Prusiner found something almost unthinkable: the infectious agent appeared to be made only of protein.

No DNA. No RNA. Just protein.

This was a radical challenge to biology’s central dogma. Viruses replicate by using genetic material. Prions do something different. They are misfolded proteins that force normal versions of the same protein to adopt the abnormal shape.”

A further historical example relevant to ME/CFS research involves Elaine DeFreitas at the Wistar Institute in Philadelphia. Between 1991 and 1992, DeFreitas reported evidence suggesting the presence of a retrovirus-like sequence in patients diagnosed with ME/CFS. The findings generated significant scientific interest because they appeared to support the hypothesis of an infectious or viral component underlying the illness. However, subsequent replication studies failed to consistently reproduce the original findings, leading to controversy and eventual abandonment of the hypothesis by much of the scientific community.

This raises an important scientific question: could the inability to confirm the original observations have resulted from methodological limitations, faulty replication procedures, insufficient technology at the time, or biological complexity not yet fully understood? The history of biomedical research demonstrates that early discoveries are not always reproducible under initial conditions, particularly when dealing with poorly characterized diseases, low-level pathogens, or unconventional biological mechanisms.

Scientifically, it remains plausible that humanity coexists with additional undiscovered pathogens or biological mechanisms that continue to cause chronic illness and suffering before they are fully identified, understood, and verified. The pursuit of scientific clarity may at times be slowed or influenced by political interests, financial incentives, institutional resistance, or competition for recognition within the scientific community. 

Meanwhile, patients affected by Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) frequently endure stigma, inadequate medical care and community support, as well as prolonged uncertainty while awaiting meaningful biomedical advances. Although not all patients necessarily expect a complete cure, many would regard a substantial and sustained reduction in symptoms as a meaningful improvement in quality of life.

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a five-year copyright. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9