“Peter Stys has agreed to allow us to reproduce his train crash analogy that he uses to propose an alternate interpretation of the pathology of MS. It makes a lot of sense to those of us close to the field. I hope you enjoy it.”
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| photograph: Ingo Wagner |
Because we know how trains work, we know that a loose rail very quickly results in a stereotyped response of derailed train, bystander damage (overpass taken out), infiltration of rescue elements (that may cause additional damage or injury to passengers if they’re not careful)
you come upon the scene and probably the last thing you think of is digging thru the rubble to examine the rails (even if you did, they’re probably destroyed by the derailment)
you wonder about the guys in red: are they helping or here to cause further damage to the train? There’s a guy with a cutting torch and a piece of metal in his hand, another guy running around smashing in all the windows: they really are hell-bent on destroying what’s left of the train! (if all you have is a static snapshot). Maybe the guys in red assembled before the train arrived and sabotaged it? You consider making a recommendation to confine the guys in red to their stations from now on, this should prevent future train wrecks, problem solved.
you’re perplexed scratching your head, pondering the scene, then a guy comes up and taps you on the shoulder, says he was standing nearby, heard the oncoming train, something didn’t sound right, took out his iPhone and snapped a pic just as the train was passing, what a coincidence that we have a witness at the earliest moment of the crash you think to yourself
shows you the photo, you look closely: front wheels of the locomotive have left the track, and underneath you think you see a bad joint in the rail
curious, and no red guys in sight yet, very odd, very unlike the previous train wrecks you visited. The guy says the red guys only rushed in 10 min after the wreck. This turns your whole concept and conclusions on its head.
so you can go one of both ways:
a) the last 20 train wrecks looked just like this pic above, so the iPhone photo can’t be right, and is an oddity that has little to do with most train wrecks, so you dismiss the witnesses’ account, OR
b) you might wonder whether most train wrecks start like what’s on the iPhone photo, and you got lucky only after the 21st wreck you were called to because of the guy happened to be in the nearby street, so maybe rails are important, and the red guys rush in quickly, but only after the wreck occurs. Maybe they are good guys after all.
This is brilliant. In your opinion, what is the MS equivalent of the bad joint?
Re: "…what is the MS equivalent of the bad joint?"A virus.
That the underlying cause of MS is illusive is understood. Probably multiple triggers lead to the inflammatory cascade that lead to MS symptoms. Controlling inflammation after the insult leads to less neurological deficit. T-cell induced damage to "clean up" the initial insult logically has to be addressed. Just as immune reconstitution inflammatory syndrome occurs in HIV patients whose T-cell count is rebounding, leading to robust cell mediated response to HIV, so may be the case in MS. Agreed, to find the trigger(s) is the holy grail.
Sure this may be a good analogy if the observer at the train wreck was a caveman. You have to ignore all accumulated evidence of physics and science to have this view.I guess this is the same as MS research. If you ignore all previous work that has been done (which would be a collosal waste of time by the way) you could come to new conclusions such as what happened witht the CCSVI hysteria. But does this advance the understanding of MS and treatment development?
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If EBV is the culprit causing the cascade of events leading to inflammation why is it so difficult to detect in MS lesions? Also, how does it effect the BBB? HIV can lead to BBB disruption. Maybe other neuro-inflammatory diseases can provide clues.
The analogy is brilliant! But I thought the dispute of inflammation versus degradation had been settled a couple of years ago in favour of the inflammatory theory? i) a strong immune suppression such as HSCT led to a complete stabilization of clinical progression in early patients. ii) genome wide screening suggested genes involved in the immune system, iii) evidence from the mouse model
The dispute is ongoing and alive as ever. I anticipate a black swan flying in soon.
Dear Dr Giovannoni, I think you have an excellent researchers mindset, keeping the eyes open in all directions and questioning anything that seems to be scientific fact. However, from a patients perspective, the degradational theory of MS has not yet resulted in any help for the patients affected so far. Wouldnt you, if affected, not want to have a bone-marrow transplant as soon as possible after diagnosis, or at least a very lymphocyte-ablative treatment? Your presentation on "early and aggressive" at least suggests that?