"Morphostasis and Immunity”
This page includes a brief synopsis of this article, published in 1995
Here are the links to a reproduction of the article:
Synopsis and main points
- Morphostasis (tissue homeostasis) is discussed.
- Morphostasis must encompass:
- Intracellular and molecular biology
- Cell-to-cell communication and co-operation (gap junctions in particular)
- Within the embryo
- Development from zygote to mature animal
- Evolution from simple metazoans to mammals
- The general scheme of morphostasis including:-
- The surveillance for sick cells
- Cell and animal senescence
- The changing susceptibility to various diseases with ageing
- The renewal of sick cells and tissues
- Basic pathological mechanisms
- Immune ontogeny
- Immune phylogeny (from simple metazoans to mammals)
- It should also highlight how metazoan homeostasis and defence diverged as plants split from animals.
- It outlines the importance of the "zygote derived colony"
- It introduces the concept of healthy-self-cells and other-than-healthy-self-cells and their discrimination
- It explores the role of gap junctions in healthy-self expression
- It explores internal cell surveillance, apoptosis, necrosis and inflammation
- It explores the (probable) step by step evolution or morphostasis
- It introduces the concept of evolutionary shells
- It explores the pivotal role of natural killer cells in the switch to an anamnestic (memorising) immune process.
- It explores the "clinical consequences" of these points.
- "The general principles of morphostasis are discussed. I have made a committed assumption that gap junctions are the most important intracellular junctions (ICJs) in maintaining healthy self identity. Other ICJs may contribute a larger part than I have credited here. This idea has been constructed using a cycle of speculative hypothesis followed by falsification leading to new hypothesis. By experience, many of its more precise conclusions will prove to be not quite as conceived but they will prove to be closer than the current paradigm permits. If well founded, the hypothesis should prove to be a useful framework for a more focused investigation of the biochemical processes of morphostasis."
- I have put B-cells ... (whatever I was about to continue writing here has been eclipsed by time). I suspect that I was intending to say that I had earlier assumed B-cells came after the evolution of T-cells. However, the precursor B-cell was probably just a fastidious phagocyte that specifically attached to and ingested developmental ligands to clear apoptosisng tissues – like the tadpole tail, etc, using just an IgM like effector. The IgG, IgA, IgE embellishments probably followed the evolution of T-cells .
Submission to Medical Hypotheses: 14th August 1994
Will you consider this article for publication?
I have peddled earlier versions of this around numerous journals and have been generally greeted with dismissal. No one seems to see the need for a paradigm shift. It is due. Polly Matzinger has now published an article supporting one of the main conclusions of my hypothesis. I had certainly reached her point (and beyond) before I read that paper. Equally, the core importance of elective suicide was constructed in my mind long before the flurry of interest in apoptosis. Then there is the inversion of TNK and TC function. That was realised and incorporated into the hypothesis long before I was aware of supporting literature. The idea that N-CAM constant like regions evolved to promote highly permeable gap junctions led to a literature search for supportive evidence and this was found. And there are more fulfilled predictions.
All in all, it is falling together quickly. So many observations fit into the hypothesis so very comfortably that it is impossible to reach any other conclusion than that this "falsificationist" approach has eventually come up trumps.
It is unbelievably frustrating not to be able to penetrate this curtain of resistance!
Perhaps you, too, will support the conventionalists.
Reply from Medical Hypotheses: 28th September, 1994
Many thanks for your fascinating paper submitted to Medical Hypotheses. We have read this with considerable interest or would be happy to have it in the journal. A reprint order form will be sent to you direct from the publishers.
I am interested in resistance to innovation and I would be most grateful if you could provide me with a summary of the history of this concept and some of the letters of rejection that you have received from the journals.