Dr. Les Simpson – Rethinking the Pathogenesis of CFIDS
By Craig Maupin at http:///www.cfidsreport.com
Resting on the bookshelf of Dr. Les Simpson is the book, 'The Structure of Scientific Revolutions', by Thomas Kuhn. In its pages, Kuhn lays out a model for scientific progress. He shows how the entrenched views of medical experts have often slowed progress towards understanding many diseases. Kuhn’s book, and the ideas therein, provide a backdrop to Simpson’s career -- a career that has sought to challenge those entrenched views, while seeking answers to the mysteries of CFS.
Well-traveled, Dr Les Simpson speaks in New Zealand. Dr. Simpson's interest in the disease was preceded by the "Tapanui Flu" outbreak in New Zealand in the early 80's. Today, many researchers are interested in the role of the circulatory system in CFIDS. SPECT scans have revealed impaired blood flow to the brain, research on orthostatic intolerance in PWCs has provided additional clues, and low circulating blood volume has been postulated as a contributor to the illness. However, Simpson was convinced that impaired blood flow played a major role in CFS long before the current increase in awareness on the issue. He believes blood viscosity and reduced rates of capillary blood significantly affect the disorder, providing a unifying model for many of the distinct and disabling symptoms.
The NZ biologist’s research career began in 1964, studying the New Zealand black mouse as a model for human illnesses such as systemic lupus erythematosus. Shortly after an outbreak of ME (Myalgic encephalomyelitis – the name for CFS most frequently used in New Zealand) in the early 80’s, his attentions began to focus more on the role of blood rheology in ME. He explains, “In the early 1980s, a percipient country doctor recognized an unusual pattern of sickness in his region - which became known as "Tapanui Flu”. About that time, I became interested in blood rheology [the study of blood flow] using blood filtration and blood viscometry. I was using a filtration technique to assess red cell stiffness. When Dr. Campbell Murdoch was appointed Professor of General Practice, he was soon involved with ME and through his good offices was able to assess ME blood filterability.”
Simpson continues, ”I found that ME blood filtered poorly - implying that they had a problem with blood flow, particularly at capillary level. In a paper published by New Jersey Medicine, I suggested that ME people might have the anatomical feature of smaller than usual capillary diameters. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people.”
Other models for the illness have struggled to fit the distinct features of CFIDS, such as exertion intolerance and circulatory dysfunction. Simpson feels impaired blood flow offers a unifying thesis that can explain many of these distinct symptoms. He vividly recalls the unique response to exercise of a patient referred to him. “Two scans were done [SPECT scans] -- pre and post exercise. While the pre-exercise scan showed reduced cerebral blood flow, this was much worse in the post-exercise scan. At that time, the effects of physical activity on red cell shape had not been reported. This shows the extent of ignoring blood rheology factors as determinants of blood flow.”
“When you crank up activity levels, symptoms re-surface. Physical activity changes the shape populations of red cells in an additive fashion.” We published a controlled study of the effects of pulling the trigger of a model pistol on red cell shape in ME and controls. The study showed that ME people could not pull the trigger as long as controls before the onset of fatigue - and this was associated with a greater change in the shape populations of red cells. "
While shape changes of red blood cells occur in healthy controls, Simpson says it is the proportion of different types of red blood cells, as well as lower capillary diameter in subsets of patients that may play a large role in undermining proper blood distribution. He does not believe CFIDS is an anemia (a lack or deficiency of red blood cells). “Red cell number is the major determinant of blood viscosity - the main feature of blood rheology. In polycythaemia rubra vera, the high value for red cells is recognized clinically as a cause of the associated increase in blood viscosity.”
“ I never use the word "misshapen" with regards to red cells. The red cells in normal blood fall into 6 different shape classes, and alteration in the cell environment leads to shifts in the proportions of the different cell shapes. Biconcave discocytes (the textbook "normal" red cell) are the most deformable of cells due to the "spare" membrane of the biconcavities. The loss of the concavities when other shapes occur is associated with a reduction in deformability.”
Differing proportions of different shapes of red blood cells can affect blood flow and viscocity. Higher proportions of flat cells ( F-above) may contribute to the high viscocity of blood in CFIDS. Permission Dr. Les Simpson
He continues, “Because many capillaries are much smaller than the diameter of the red cell, red cells must change shape to pass through the capillary bed. But shape-changed red cells are stiffer than usual and poorly deformable and they will pass through small capillaries very slowly, or even block the capillary.”
While circulatory dysfunction and post-exertional muscle fatigue are hallmarks of the illness, the symptom set of neurological dysfunction varies widely among sufferers. Simpson believes impaired blood flow can provide a reasonable explanation for the widely varied neurological set of symptoms among individuals with CFIDS/ME. “As blood flow with normal rates of delivery of oxygen to nerves is essential for normal nerve function, it is very likely that dysfunction of autonomic nerves (as in orthostatic intolerance) could be expected in conditions with changed populations of red cell shapes. In a 1992 paper published by New Jersey Medicine, I suggested that ME people might have smaller than usual capillary diameters in those parts of the body expressing symptoms. Such a proposal would help to explain the great variety and variation in distribution of the symptoms reported by ME people. ”
When speaking to Simpson, you can quickly come to the conclusion that he is a man who has an independent mind. He questions much of what has transpired over the past 20 years with regard to the illness government agencies refer to as a “fatigue syndrome”. Many have questioned whether the term has fomented public apathy and slowly obscured the definition of illness. According to Simpson, the word “fatigue” is too broad for medical use and cannot adequately describe what happens in ME/CFIDS. “My rooted objection to CFS concerns the term ’fatigue’. And, the situation is not clarified by dictionary definitions stating that fatigue is the consequence of long term physical activity.”
Simpson is also concerned that more needs to be done to educate the medical and scientific communities about the role blood flow and viscosity play in many diseases. At the moment, no education institutions have dedicated programs on haemorheology (study of blood viscosity). He would like to see courses on haemorheology taught at medical schools. “There is a very large medical literature concerning haemorheology - yet the topic is not taught at medical schools - nor is the published information utilized clinically.” Simpson believes that a body of new ideas on how to more effectively study red blood cells has been published, but this information is yet to be applied properly. Haematologists, he says, “have failed to make the transition from light to electron microscopy. When they use electron microscopy, they do not use immediately fixed red cells - and the textbook concept of a red cell simply shows the effects of treatment prior to fixation.”
Since retiring in 1985, Simpson has sacrificed a large amount of his own time and personal resources to uncover more information about CFIDS/ME. “Since my earliest days with ME, my objective has been to try and improve the well-being of patients.” An attempt by Simpson to establish a clinic to test red blood cells did not survive due to lack of funds, a problem experienced by many researchers interested in CFIDS. If Simpson’s ideas are correct, agents which improve blood viscosity/flow may relieve symptoms in CFIDS patients. He hopes to someday see placebo-controlled studies conducted “with the primary objective of determining which agent [haemorheological], if any, has the ability to improve patient well-being.” He continues, “Because it is not possible to increase the diameter of a capillary, treatments should be aimed at increasing red cell flexibility. There is published information which reports that TRENTAL (pentoxifylline), fish oil, and oil of evening primrose taken in sufficient amounts (4000mg) improved red cell flexibility.”
Simpson concedes there is much to be learned about blood flow and its effect on CFIDS. He is very modest about the limitations of his research. “I recognized that identifying the cause or causes of the problem could be well beyond my resources.” While he feels red blood cells and blood rheology can explain the distinct features and variablity of the illness, he adds, “Both the immune response and biochemical activity may change the internal environment sufficiently to alter the shape populations of red cells.”
Finally, Simpson says that entrenched views about the pathology of CFIDS must eventually concede the strong role that blood flow plays. He is deeply concerned that closed minds and personal agendas are keeping knowledge of the illness from progressing,-- as if Kuhn's ideas are being played out in a real-time drama. Researchers, he feels, seem more interested in promoting their own fields of expertise and presumptions, rather than working collaboratively to defeat a disabling illness. “Despite the efforts of the psychiatrists, the English Parliamentary study accepted that ME is an organic disorder. Yet, even the parliamentary recognition of ME as an organic illness has done little for patients. In the USA, there have been more than 2000 papers on the topic published since 1988, yet the well being of patients has not improved. Sooner or later, authorities may learn that possibly they need to rethink their concept of pathogenesis.”
The CFIDS Report would like to thank Northern Rivers ME/CFS/FM Support Association and Merle Fullerton for their assistance.