Cancer Initiation: The 6th Generation of Medical Science: One Carbon Metabolism and its connection to the Immune System

Sunday, January 22, 2017

The 6th Generation of Medical Science: One Carbon Metabolism and its connection to the Immune System


   In an earlier post, for the sake of classifying medical knowledge by my self-defined generations, I defined a system of scientific epistemologies, or paradigms numbered 1 through 5. Unfortunately, the reason for doing this is because the current system is proving to be insufficient. In particular, there has been a large number of medical conditions that are classified as "auto-immune", or the result on attack by ones own immune system. There are many theories as to why these medical conditions come about, but conclusive evidence has proven to be elusive.
   Medical data that is Generation 1 and Generation 2, that is correlations and chemical analysis, has shown clearly that there is a strong relationship between stress in the single carbon metabolism system autoimmune disease. Unfortunately, further reasoning behind this relationship is "all over the place". For example, one theory promoted [1] is that maternal antibodies affect their male offspring disproportionately. There are potential physiological flaws with this argument. The brain is known to be isolated from the rest of the body to cross the blood brain barrier. Ok. Further discussions on the connection between autoimmune response and autism relate to alterations that allow permeability to intestinal barriers and the blood-brain barrier.[2] At this point, all proposed connections remain conjecture.

Innate cancer defenses and autoimmunity

 We have proposed other possible connections between oxidative stress ( failure in the single carbon cycle ) and the immune system. Specifically, we have identified a class of epigenetically suppressed antigens that we refer to as wingspans antigens, which are though ( by me ) to be a cancer defense. On the other hand, if epigenetic suppression fails for some reason other than cancer ( for example, failure in the single carbon cycle ) then these antigens would erroneously trigger the immune system. A short discussion of this is here.

A larger cancer defense framework

 We have proposed that wingspans antigens are part of a system that we have called the Rattlesnake Hypothesis. In very brief, higher organisms ( such as us ) have multiple levels of defense against cells that have lost control of the cell cycle ( cancer ) . The first is that the telomeres of the cells DNA strands ( chromosomes ) shorten with each cellular division. When the telomeres are gone, the cell is senescent, and can no longer divide. In cancer, in most all cases, the cell clone is immortalized through the expression of telomerase, or a group of enzymes that can perform the same action.  (extending the telomeres ) . Thus there needs to be another line of defense. If a cell line is undergoing global hypomethylation, suppressed antigens will be expressed erroneously. Their proposed function is to signal the immune system that cell cycle regulation has been lost. We call this conceptual system the rattlesnake hypothesis.

Clinical Status

To my knowledge, clinical auto-immune conditions have not been been tested for the presence of wingspans antigens. Thus, Generation 6 is hypothetical.


[1]  MOISES VELASQUEZ-MANOFF  An Immune Disorder at the Root of Autism Retreived from The New York Times, Aug. 25, 2012 [NYT]

[2] Fiorentino M, Sapone A, Senger S, Camhi SS, Kadzielski SM, Buie TM, Kelly DL, Cascella N, Fasano A. Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism. 2016 Nov 29;7:49. [PubMed]

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