Seen from the outside, the process of scientific exploration of diseases seems chaotic and confusing. Indeed, from within, it is tempting to deduce that clinical academics are chaotic and confused.

To be fair, that is an appropriate deduction. Einstein famously said, ‘If we knew what we were doing, it wouldn’t be called research.’ The vast majority of medical research can be compared to solving a particularly complex crossword puzzle. We start with the ‘easy answers’, then progress to the deducible, before staring endlessly at the problems that don’t make sense to us. The hope is that the pieces we already have will enable us to fill the gaps and produce a semblance of sense.

Practising medicine often does not allow this freedom of thought. If the CRP is falling, the antibiotics are working; if it is rising, they’re not; fracture is a fracture; air under the diaphragm represents burst viscera.

Where, then, do we place conditions that we don’t as yet have diagnostic tests for?

Myalgic encephalomyelitis – otherwise known as chronic fatigue syndrome or post-viral fatigue – was first defined in 1984, but its existence had been described as far back as in Pompeii. It affects around 250,000 people in the UK, with a preponderance of younger females and those with atopic conditions.

Today marks the first global awareness day for those suffering with this condition. However, the diagnosis itself still provokes controversy among healthcare professionals. To some, it evokes an emotive response – ‘functional’, ‘psychological’ or ‘somatisation’ – for others it is ‘debilitating’, ‘life-changing’ or ‘catastrophic’.

This juxtaposition of opinion, for the same condition, is held for very few conditions. Fibromyalgia, irritable bowel syndrome, functional neurological disorders, similarly create controversy. Hypothyroidism, type 2 diabetes, multiple sclerosis and polymyalgia rheumatica, however, do not face the same stigma despite their initial presentation similarly having non-specific symptoms.

The difference: investigations, tests and results.

Breakthroughs

For diabetes, we have the HbA1c or fasting glucose. We can measure plaque burden on an MRI scan for people with multiple sclerosis. In those with PMR, plasma viscosity correlates with symptoms and disease progression. Each in turn triggers treatment decisions. An elevated HbA1c may suggest escalating medications by including GLP-1 analogues, SGLT-2 inhibitors or insulin. In MS, the use of monoclonal antibodies may be indicated. Increased steroids will resolve the symptoms of a person with PMR and raised plasma viscosity.

However, these are relatively new innovations. It is only 100 years ago this year that insulin was first used to treat Leonard Thompson with his life-threatening type 1 diabetes. The first MRI scan in the UK was performed in 1980 and it was 1984 before the Royal Brompton inaugurated their first scanner for the NHS. Erythrocyte sedimentation rate, the precursor of plasma viscosity for monitoring inflammatory diseases, was first described by Biermacki in 1897 and moved into regular practice less than 100 years ago.

150 years ago all of these conditions, ME and PMR, FND and MS, fibromyalgia and diabetes, would be regarded the same – no proven underlying cause, no treatment, no interest.

So where does that leave us? We believe we are at the pinnacle of medical innovation. A similar position that our peers were in 100, 200 or even 300 years ago. Indeed, the publication of Isaac Newton’s Principia Mathematica in 1687 was seen by his colleagues as the culmination of the scientific revolution, and the beginning of the Age of Enlightenment.

If the last two years have taught us anything, however, it is how much we don’t know. We have learned that a respiratory disease may present as a vascular disease. We have established that up to 10% of the population who contract a coronavirus may be left with ongoing symptoms that are disproportionate to their initial disease burden.

Long COVID defies understanding

Long COVID currently affects 2.8% of the UK population, yet there are more uncertainties than facts. There are multiple hypotheses to account for these symptoms: residual viral infection, mitochondrial dysfunction, micro-emboli or auto-immune disease. People suffering with this condition have highlighted the reality of their condition and inadequacies of conventional medicine.

It instigates a global research priority, and highlights a more important issue. Today’s medical knowledge is not comprehensive; we do not know everything. Long COVID defies our current medical knowledge. There are no diagnostic tests, we do not know the prognosis of the condition and there are no proven treatments. The description and acceptance of long COVID has broadened our acceptance of these medically unexplained diseases.

Currently, 1 in 36 people in the UK have a condition that we can’t measure. We must now return to our medical texts, and re-evaluate other diseases that similarly do not have diagnostic confirmatory tests. A quarter of a million people in the UK living with ME have been telling us for decades about their symptoms. Many have received support, but almost as many feel they have been ignored or told that all of their tests were ‘normal’, therefore it’s all in their head. They have been stigmatised with terms such as ‘yuppie flu’; indeed, even ‘chronic fatigue syndrome’ undermines the severity of the disease.

‘Normal’ test results do not mean there is nothing wrong. It means we don’t have the right tests.

Measuring glucose will not help us diagnose multiple sclerosis, whereas an MRI of the brain will be unhelpful for a patient with hypothyroidism.

Now, more than ever, we need to listen to our patients and start exploring more diseases that don’t yet have an explanation. By working together, patients, healthcare practitioners and researchers can help bring resolution to the millions of people globally who have ME, and other currently unexplained diseases, so we can get to a stage where we can diagnose and treat.

As good as our medical knowledge is, as impressive as the technology we use to support us, we need to accept that we do not yet have all of the answers. When a patient presents with a condition that we cannot explain, the problem is ours, not theirs.

David Strain is chair of the BMA board of science