"Morphostasis and Immunity”

1995

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
Malignancy
The changing susceptibility to various diseases with ageing
The renewal of sick cells and tissues

Basic pathological mechanisms
Immunity:

Innate
Anamnestic
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.

It concludes:-

"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. I have ceased to believe people who insist it is worthless. It may be cavalier in approach: it may be too speculative in places; it may annoy immunologists and biologists who review it; people may consider it is not appropriate to publish the hypothesis of a person who has simply parasitised other's efforts. But plain wrong it is not.
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.