"Are you saying that you know of a disease who's distribution in a given geography looks like an unending power law increasing to the right instead of a gaussian distribution with a peak and decline?"
Getting to the root of this polio problem is very important I believe and I’m looking forward to your upcoming posts. However I’m getting rather lost in the details and couldn’t explain your work to someone else! When finished would you consider producing a video summary of everything that could be shown to others, or explaining it all to someone on a podcast? DocMalik is a very friendly orthopaedic surgeon, now out of work due to speaking against the covid narratives, who has all sorts of interesting guests on his podcast and he allows them to speak freely.
Just the problem itself is difficult to convey. I can give the Turtles polio chapter credit for doing this well, at least. I'll think about what a video presentation would look like in terms of structure. But as an interview it would probably be difficult to tackle the problem efficiently. (More interesting and easy would be my argument for why polio can't really go away - conversely it is difficult as a post because it risks making the series look gimmicky.)
The probability of developing paralytic disease is oddly small that it seems there should be an explanation for vast communities with existing antibodies that did not suffer disease outbreaks. The provocation poliomyelitis theory is still interesting. I wonder if there is any merit to the possibility that disease development could be linked to toxins/viruses/etc. that are chronically demyelinating and/or inflammatory but not necessarily to an extent of presenting other acutely recognizable degeneration. It seems key that polio can pass the BBB and attack the anterior horn. How does it get there? The body first needs a red carpet to be able to roll one out.
There are certainly other mimics (AFP, Guillain-Barré, etc) where demyelination is a paramount mechanism to symptoms, as well as other enteroviruses that have similar presentation. Guillain-Barré handshakes with pneumoniae; perhaps there is a similar synergy/comorbidity for polio. There have been some polio comorbidity studies, but all seem rather shotgun spray (ie laundry list of generally poor health markers), or they focus on sequelae.
Your work is always thought-provoking and interesting. Thank you.
If you want the definitive mechanistic study it's Bodian's 1955 work, which consolidates everything including provocation. The only limitation is that he doesn't think the virus is traveling from peripheral nerve to spine, and the reasons he gives are not really good - as I mention in Explaining Pt 1. doi: 10.1111/j.1749-6632.1955.tb42545.x. is the summary.
Among many very important insights, he is convincing (it may be more in his 1949 paper doi: 10.1016/0002-9343(49)90130-8.) that nerve cell destruction is not inflammatory. I thought so for a long time per my original Injection Theory mechanism, he changed my mind. You can have total nerve destruction without inflammatory response but not vice versa - so the inflammatory response follows nerve destruction. Essentially (Elliott is also convincing on this point https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934079/) the virus just eats the spine from inside out. As for where it gets in, Bodian is convincing that it's from viremia and I think through peripheral nerves due to provocation.
I think the question thus is not BBB perforation - let's assume the virus doesn't have a problem here - but infection and transit from nerve to nerve, which is (ostensibly) regulated by CD155.
The CD155 receptor is then the missing link in explaining everything. It's not normally expressed in nerve cells affected by polio, I have read, but only in embryogenesis. So this seems a big clue, though I need to verify the expression point. If someone can show experimentally that CD155 is re-expressed by peripheral nerves after insult - as part of some sort of healing response - then the whole mechanism of paralysis is solved.
Without that CD155 mediated change, would the virus ever be able to breach the membrane? And would it theoretically _always_ be able to breach once it loses its capsid? I’m also wondering if cellular pH might have an affect on this process.
What I’m reading regarding CD155 leads me to believe those with most risk of polio disease development may have had _something_ (existing tumor burden or other increased cytotoxic activity?) precipitating CD155 upregulation. Maybe this is just a rabbit hole though, or I’m missing/misinterpreting something.
If cancer rates in children 0-4 in 1950 was 11.1 per 100,000 (seer.cancer.gov mortality trends), could this track? Perhaps another good question would be what changed in the 40’s that could have led to an increase in both cancer and polio rates in the US? Other than nuclear warfare, smoking, and “once we start tracking tornadoes, there are many more tornadoes”. (I apologize if you’ve addressed this already; I have not yet finished reading the vast amount that you have written.). Cancer rates data are proving difficult to unravel as far as mortality vs incidence, as focus seems to be heavily on the former, and data pre-Dorn is proving difficult to find.
At any rate, it seems like there’s a Nobel prize in there somewhere re:CD155 upregulation and role in tumorigenesis.
If so then you would expect extreme rates of post-polio cancer (presuming most cancers detected later on). I doubt such an association would have gone missed e.g. even oncologists should have noticed it without trying from frequent encounters.
So the things that were noticed (as far as I am aware the only things) were the links with tonsillectomy and recent vaccines, but in the latter case it wasn't until England first took up diphtheria vaccination in 1941 and then had polio resurgence in late 40s, and then maybe pregnancy and definitely exercise. The latter two are quite interesting as presumably people got pregnant and exercised before 1880, but where was epidemic polio. (And as always the age distribution of the earliest epidemic cases demands concluding that in 1880 most Western adults were immune to the virus, it didn't get reintroduced from the global south or anything like that.)
So I still want to tackle the mathematical question of whether another X factor besides injection is needed (in pt. 3 of explaining series), before speculating what that other X factor would be. But if there is one, it should have been noticed if unique, but wasn't so it was probably semi-universal in West, and actually here you could speculate some rare susceptibility (nerve reaction such as increased CD155) from very sub-toxic levels of lead or other metals, sure.
Great summary, looking forward to Explaining polio, pt 3!
Thanks!
Getting to the root of this polio problem is very important I believe and I’m looking forward to your upcoming posts. However I’m getting rather lost in the details and couldn’t explain your work to someone else! When finished would you consider producing a video summary of everything that could be shown to others, or explaining it all to someone on a podcast? DocMalik is a very friendly orthopaedic surgeon, now out of work due to speaking against the covid narratives, who has all sorts of interesting guests on his podcast and he allows them to speak freely.
Just the problem itself is difficult to convey. I can give the Turtles polio chapter credit for doing this well, at least. I'll think about what a video presentation would look like in terms of structure. But as an interview it would probably be difficult to tackle the problem efficiently. (More interesting and easy would be my argument for why polio can't really go away - conversely it is difficult as a post because it risks making the series look gimmicky.)
The probability of developing paralytic disease is oddly small that it seems there should be an explanation for vast communities with existing antibodies that did not suffer disease outbreaks. The provocation poliomyelitis theory is still interesting. I wonder if there is any merit to the possibility that disease development could be linked to toxins/viruses/etc. that are chronically demyelinating and/or inflammatory but not necessarily to an extent of presenting other acutely recognizable degeneration. It seems key that polio can pass the BBB and attack the anterior horn. How does it get there? The body first needs a red carpet to be able to roll one out.
There are certainly other mimics (AFP, Guillain-Barré, etc) where demyelination is a paramount mechanism to symptoms, as well as other enteroviruses that have similar presentation. Guillain-Barré handshakes with pneumoniae; perhaps there is a similar synergy/comorbidity for polio. There have been some polio comorbidity studies, but all seem rather shotgun spray (ie laundry list of generally poor health markers), or they focus on sequelae.
Your work is always thought-provoking and interesting. Thank you.
If you want the definitive mechanistic study it's Bodian's 1955 work, which consolidates everything including provocation. The only limitation is that he doesn't think the virus is traveling from peripheral nerve to spine, and the reasons he gives are not really good - as I mention in Explaining Pt 1. doi: 10.1111/j.1749-6632.1955.tb42545.x. is the summary.
Among many very important insights, he is convincing (it may be more in his 1949 paper doi: 10.1016/0002-9343(49)90130-8.) that nerve cell destruction is not inflammatory. I thought so for a long time per my original Injection Theory mechanism, he changed my mind. You can have total nerve destruction without inflammatory response but not vice versa - so the inflammatory response follows nerve destruction. Essentially (Elliott is also convincing on this point https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934079/) the virus just eats the spine from inside out. As for where it gets in, Bodian is convincing that it's from viremia and I think through peripheral nerves due to provocation.
I think the question thus is not BBB perforation - let's assume the virus doesn't have a problem here - but infection and transit from nerve to nerve, which is (ostensibly) regulated by CD155.
The CD155 receptor is then the missing link in explaining everything. It's not normally expressed in nerve cells affected by polio, I have read, but only in embryogenesis. So this seems a big clue, though I need to verify the expression point. If someone can show experimentally that CD155 is re-expressed by peripheral nerves after insult - as part of some sort of healing response - then the whole mechanism of paralysis is solved.
Without that CD155 mediated change, would the virus ever be able to breach the membrane? And would it theoretically _always_ be able to breach once it loses its capsid? I’m also wondering if cellular pH might have an affect on this process.
What I’m reading regarding CD155 leads me to believe those with most risk of polio disease development may have had _something_ (existing tumor burden or other increased cytotoxic activity?) precipitating CD155 upregulation. Maybe this is just a rabbit hole though, or I’m missing/misinterpreting something.
If cancer rates in children 0-4 in 1950 was 11.1 per 100,000 (seer.cancer.gov mortality trends), could this track? Perhaps another good question would be what changed in the 40’s that could have led to an increase in both cancer and polio rates in the US? Other than nuclear warfare, smoking, and “once we start tracking tornadoes, there are many more tornadoes”. (I apologize if you’ve addressed this already; I have not yet finished reading the vast amount that you have written.). Cancer rates data are proving difficult to unravel as far as mortality vs incidence, as focus seems to be heavily on the former, and data pre-Dorn is proving difficult to find.
At any rate, it seems like there’s a Nobel prize in there somewhere re:CD155 upregulation and role in tumorigenesis.
If so then you would expect extreme rates of post-polio cancer (presuming most cancers detected later on). I doubt such an association would have gone missed e.g. even oncologists should have noticed it without trying from frequent encounters.
So the things that were noticed (as far as I am aware the only things) were the links with tonsillectomy and recent vaccines, but in the latter case it wasn't until England first took up diphtheria vaccination in 1941 and then had polio resurgence in late 40s, and then maybe pregnancy and definitely exercise. The latter two are quite interesting as presumably people got pregnant and exercised before 1880, but where was epidemic polio. (And as always the age distribution of the earliest epidemic cases demands concluding that in 1880 most Western adults were immune to the virus, it didn't get reintroduced from the global south or anything like that.)
So I still want to tackle the mathematical question of whether another X factor besides injection is needed (in pt. 3 of explaining series), before speculating what that other X factor would be. But if there is one, it should have been noticed if unique, but wasn't so it was probably semi-universal in West, and actually here you could speculate some rare susceptibility (nerve reaction such as increased CD155) from very sub-toxic levels of lead or other metals, sure.