Multiple Sclerosis, micro-organism and the Sun - the link becomes more plausible

West of Scotland: John Lowrie Morrison – Jolomo

Multiple sclerosis (MS) is a well-recognised disabling and often ultimately fatal neurological disease that affects young adults. Its cause is not known. 



The "Cause"

The cause of MS is said to be "auto-immune", which means that inflammatory processes are involved with immune reactions. However "auto-immune" can only be a mechanism of disease and not a true cause.

Figure 1. MRI scan of brain showing multiple deep seated sclerotic lesions as light grey patches

The cause of a disease is its prime mover, the initiator of the disease process. It is invariably identified from the epidemiology of the disease, its distribution within society and the world. Examples are cigarette smoking and lung cancer, aniline dyes and bladder cancer, contaminated water and cholera, family patterns and genetic conditions. In particular, clues arise from changes in the incidence of the disease and its spread in time or geography.

It has been known for many years that the geographical incidence of MS (new cases per year) varies considerably. It is very rare south of the European Alps, and its incidence is much higher in Northern Europe. The world's highest incidence appears to be in the West of Scotland.

Figure 2. Geography of MS, higher incidences in darker colours

We have seen this pattern previously. The epidemiology of MS is remarkably similar to that of coronary heart disease (CHD). The link is likely to be a common susceptibility rather than specific cause.

I have previously stated my contention that CHD is due to one or more micro-organisms, the identity of which we cannot yet be certain, or of which we are completely ignorant. Although a number of micro-organisms are likely to be responsible for background sporadic CHD, a specific single micro-organism must have been responsible for the 20th century epidemic. So it is for influenza: a number of strains can cause the illness over many years, but a specific strain is responsible for an epidemic.

Epidemics

Epidemics give important clues as to causation, whether a micro-organism or a chemical poison. Epidemics are never due to genetic factors.

Figure 3. Location of the Faroe Islands in the North Atlantic

Epidemics of MS have been described in the Faroe Islands in the Northern Atlantic during World War 2. Previously MS was thought to be unknown in the isolated Faroe Islands, but in 1943 there were 23 new cases, in a population of only 25,000. There were subsequently smaller epidemics of 10, 10 and 12 cases.

Figure 4. Faroe Islands

These small but significant epidemics followed the establishment of RAF (Royal Air Force) bases on the Faroe Islands. The purpose of these was to provide air support for war-time shipping convoys crossing the North Atlantic.

In the absence of alternatives, it was thought that the epidemics must have resulted from transmission of a micro-organism from the staff of the RAF who were stationed on the islands. The identity of the micro-organism could not be established at that time, and it has not been stablished subsequently.

Figure 5. RAF Bristol Blenheim bomber as was stationed on the Faroe Islands

The transmission of micro-organisms around the world is well-known. The sea voyage of Christopher Columbus to the West Indies in 1492 made land-fall in what is now known as the Dominican Republic. 90% of the population were shortly to die from smallpox, contracted from the crew. Smallpox was unknown in the Americas and the populations had no immunity (that is inherited or "herd" immunity). 

In return the crew brought syphilis from the Americas to Spain, and thus to Europe. It ravaged the population, which had no immunity, and it was four hundred years before the microbial cause was identified.

MS in the Armed Forces of the UK

New evidence has just become available, supporting the transmissible nature of MS and the likelihood that it is due to a micro-organism. 

It has been identified that the incidence of MS is much higher in former members of the armed forces (military) than in the general population. 

The incidence of MS in this study has been based on deaths, rather than true incidence (new cases per year) or prevalence (number of cases at a moment in time) of the condition. However MS tends to be ultimately fatal and so death rate is a useful measure.


The study was based on 3,688,916 deaths in the UK among men aged 20–74 years. Occupations of the deceased had been recorded and there were 26,507 whose last recorded occupation was "military". There were 7485 deaths from MS, and 129 of these were in the military group.

Therefore in the general population dying during a period of 30 years, 7485 out of 3,688,916 deaths were the result of MS, and in those who had been in the armed forces 129 out of 26,507 their death  was the result of MS. 

These findings can be expressed the Proportional Mortality Ratio (PMR). The PMR standardises the frequency of deaths in the overall population at 100. This is compared to the subgroup under investigation. A PMR in the subgroup greater than 100 indicates that the cause of death is more common, and a PMR less than 100 indicates that it is more rare.

Table. Proportional (Standardised) Mortality Rate of MS in former military workforce

[The mathematical process of standardisation is quite simple. To standardise the population PMR at 100, the mathematical formula is 100 x  0.002029 / 0.002029 = 100. To find the relative PMR of military personnel the formula will be 100 x   0.004867 /   0.002029 = 240.]

We can see in the table that the PMR for MS in former armed forces workers is 240, which is of course two and a half times that of the general population.

This is a major difference in incidence, much higher in people who had been in the armed forces. Why should this be?

Transmission of a biological agent

There appears to be no explanation in terms of chemical exposure, as the difference remained unchanged during each of the three decades included in the study.

The authors felt that the only plausible explanation concerned the fact that members of the armed forces live and work closely together during many years. This implies a transmissible agent as the cause. Person to person transmission is usually a biological agent, a micro-organism.

Is there a reason why MS could not be due to a micro-organism? The answer is "no". There is no competing putative cause, and the experience of the Faroe Islands and the UK military is strong. Direct transmission studies in humans would hardly be ethical and animal inoculations are unlikely to work. Whereas tuberculosis could be transmitted to a variety on animals, this experience does not extend to many other disease–animal experiments.

One of the problems of research into MS is the lack of available pre-mortem biopsy material, the disease being located deep within the brain. The cerebro-spinal fluid (CSF) is readily available for sampling, but it is not as useful as affected brain tissue.

There have been previous suggestions of a micro-organism causing MS, spirochetes and cytomegalovirus, but without transmission studies the identification of a causative organism is unlikely to be conclusive. 

There is the precedent of neuro-syphilis, which leads to the clinical syndromes of the dementing condition general paralysis of the insane (GPI) and also the disabling condition tabes dorsalis (TD). Both manifestations of neuro-syphilis are chronic and ultimately fatal, rarely seen today but a very major health problem a century ago. It was about 350 years before the neurological condition was linked to the primary sexually transmitted infection, and a further 50 years before the causative spirochaetal organism Treponema pallidum was identified. Unethical and effectively criminal human transmission studies were undertaken in the mid-20th century, before medical ethics was established. Such  conclusive studies cannot be undertaken today.

Geography and the Sun

The geography of MS fits in with a microbiological cause. An increasing incidence of disease with increasing distance from the equator (in both hemispheres) indicates a simple latitude factor, the incident sunlight energy at ground level. There is further evidence of the importance of vitamin D in the development of MS. There is a seasonal effect: the highest incidence is in people born in the spring. This means that the later stages of gestation would have been during the winter when sun intensity is at its lowest.

Figure 6. Month of Birth and risk of MS in the UK

It is known that vitamin D enhances immunity. A failure of full immunity results in greater susceptibility to infection. We can therefore appreciate that whereas MS is extremely rare in countries such as Italy and Greece, the world's highest incidence is in the West of Scotland (tuberculosis and CHD are similar). Even further north in the Faroe Islands immunological defence would be low but MS only occurred when the causative micro-organism arrived in 1943.

Links:

MS in the Faroe Islands
https://www.ncbi.nlm.nih.gov/pubmed/371519

MS deaths in UK armed forces
https://academic.oup.com/occmed/article/67/6/448/3872312/Mortality-from-multiple-sclerosis-in-British

Risk of MS and month of birth http://www.bmj.com/content/330/7483/120