A 50 Year Journey in Medicine

Dr Graham Exelby Updated June 2026

As I pass more than fifty years in medicine, including over forty-five years in general practice, one lesson has remained constant:

We never stop learning.

Medicine continually reminds us that certainty is often temporary. What is accepted today may be revised tomorrow. The most important question I have learned to ask is not "What is the diagnosis?" but rather "Why is this happening?"

That question has guided much of my professional life. Early in my career I became interested in conditions that were often dismissed as difficult, poorly understood, or untreatable. The work of Dr Merv Garrett demonstrated how diet could profoundly influence conditions such as eczema and irritable bowel syndrome. It was one of the first examples I encountered showing that many chronic illnesses could not be adequately explained by simple disease labels alone.

Over subsequent decades my focus increasingly turned towards patients with fibromyalgia, chronic fatigue syndrome, dysautonomia, migraine, connective tissue disorders, mast cell activation syndromes and eventually Postural Orthostatic Tachycardia Syndrome (POTS). These patients frequently presented with complex symptoms affecting multiple organ systems, yet traditional medical models often treated each symptom in isolation.

The arrival of COVID-19 accelerated this journey dramatically.

COVID provided a unique opportunity to observe the development of complex chronic illness in real time. Many of the questions that had remained unanswered for years suddenly became clearer. We began to see how infections, trauma, mould exposure, sustained stress, surgery, hormonal changes and other environmental insults could activate innate immune threat pathways, including Toll-like receptors (TLRs), leading to persistent inflammatory signalling, mast cell activation, central sensitisation and autonomic dysfunction.

At the same time, advances in genetic analysis, particularly through the work of Dr Valerio Vittone, revealed recurring patterns involving oxidative stress pathways, methylation pathways, mast cell regulation, COMT, inflammatory signalling, mitochondrial resilience and immune regulation. These findings helped explain why some individuals appear particularly vulnerable to developing chronic illness following a physiological stressor while others recover completely.

As our understanding expanded, it became clear that these illnesses were not simply immune disorders, vascular disorders, neurological disorders or psychological disorders. They represented an interaction between all of these systems.

Over the past several years this work has evolved into a broader model integrating four major contributors to chronic illness:

1. Genetic Predisposition

Our genes influence how we respond to inflammation, infection, oxidative stress, trauma and environmental exposures. Genetic variations involving inflammatory signalling, mast cell regulation, methylation pathways, oxidative stress pathways and autonomic regulation appear to create varying levels of vulnerability.

2. Immune and Metabolic Dysregulation

Persistent activation of innate immune pathways, including TLR and RAGE signalling, may lead to ongoing inflammation, altered energy production, mitochondrial dysfunction, central sensitisation and impaired physiological recovery.

3. Microvascular and Pericyte Dysfunction

Increasing evidence suggests that pericytes—specialised cells that regulate capillary blood flow and tissue perfusion—may play a critical role in many chronic illnesses. Dysfunction of these cells may contribute to impaired oxygen delivery, autonomic dysfunction, neuroinflammation, abnormal RAAS signalling, exercise intolerance and post-exertional malaise.

4. Mechanical and Hydraulic Dysfunction

Perhaps the most unexpected area of discovery has been the role of biomechanics and fluid dynamics.

Advanced imaging and dynamic ultrasound studies have demonstrated high rates of thoracic outlet syndrome, jugular outlet obstruction, internal jugular vein compression, vertebral venous dysfunction, lymphatic obstruction and altered cranio-cervical mechanics in patients with POTS, Long COVID and related disorders.

These findings suggest that impaired venous, lymphatic and cerebrospinal fluid drainage may contribute significantly to autonomic dysfunction, brainstem hypoperfusion, head pressure syndromes, fatigue, cognitive dysfunction and chronic illness progression.

Rather than existing as separate diseases, many conditions appear to represent different expressions of the same underlying physiological disturbances.

This understanding has transformed how we investigate and manage these patients.

The use of dynamic imaging, brain SPECT scanning, advanced ultrasound, retinal imaging, orthostatic echocardiography, heart rate variability analysis, amino acid profiling and genetic assessment has allowed us to move beyond symptom-based medicine towards identifying the underlying drivers of disease.

Perhaps the most rewarding aspect of this work has been seeing patients recover after years of being told that nothing could be done.

Many patients who were previously disabled, housebound or unable to work have regained significant function once the contributing factors were identified and addressed. While there remains much to learn, these experiences reinforce the importance of continuing to question established assumptions.

Medicine is entering an extraordinary era.

Emerging research into neuroinflammation, microvascular regulation, lymphatic function, autonomic control, mitochondrial biology, genetics and immune signalling is beginning to connect previously unrelated diseases. Conditions such as Long COVID, POTS, ME/CFS, migraine, autoimmune disease, neurodegenerative disorders and even cancer may ultimately prove to share common biological pathways.

The journey is far from complete.

Every year raises new questions, challenges old assumptions and reveals new possibilities. The greatest lesson from fifty years in medicine is not how much we know, but how much remains to be discovered.

That ongoing search for understanding continues to inspire me every day.

Acknowledgements

No medical journey occurs in isolation.

I am deeply grateful to the many patients who have trusted me with their stories, often in circumstances where conventional explanations were inadequate.

I also acknowledge the many researchers, clinicians, physiotherapists, osteopaths, sonographers, radiologists, surgeons, scientists and colleagues who have contributed to this evolving understanding. In particular, I thank Dr Merv Garrett, Dr Valerio Vittone, Professor Peter Smith, Professor Jon Jenkins, Dr Kevin Lee, Dr Vini Nascimenco, Dr Zane Sherif, Rylee White and her team, Dr Raymond Perrin, Kjetil Larsen and the many others whose expertise and willingness to challenge accepted thinking have helped shape this work.

Most importantly, I remain grateful to the patients themselves. Their perseverance, courage and determination continue to drive the search for better answers and better outcomes.