Re: The Rosennean Modelling project

----- Original Message -----

To: ***

Sent: Wednesday, April 07, 2004 3:39 PM

Subject: Re: The Rosennean Modelling project

There is a set of ideas about immune system function and how it relates to autoimmune diseases (among other things) that my father developed in the late 1980's. He referred to it as "The Immunological Shadow Theory". As I considered the three areas of interest that I have for the list's "modeling project", I realized that all three are connected in this one theory.

A brief sketch of the basic theory is as follows:

Robert Rosen theorized that certain things have to be true in human reproductive physiology order for a human embryo to survive gestation. One is that the developing immune system of the embryo must learn to recognize the body's own proteins as "self". Another is that the immune system must be able to deactivate itself in relation to those "self" proteins. My father said this would naturally create an "immunological shadow" such that any protein similar enough to "self" would not be recognized as foreign by the immune system. This would also create a category of proteins that "outline the silhouette of this shadow", i.e.; are close enough in similarity to the "self" proteins to almost qualify, but are at the edge of what the immune system can recognize as foreign. Members of the same family will have genetic similarities in "self" proteins and therefore will have similar "immunological shadows". The similarity in "self" proteins in a family would explain why transplants from a close relative tend to pose less risk of rejection by the immune system.

My father then considered the fact that many autoimmune diseases are known to have "viral triggers". I actually know several people who have had a bad case of influenza and six months later went into either kidney failure or developed some other chronic form of autoimmune dysfunction (such as fibromyalgia and lupus). My father considered his own situation of being struck with type 1 (juvenile) diabetes at the age of 45... he was pretty sure it was a case of Asian flu that brought about his type 1 diabetes, because he got sick while in Japan for three months and never felt well again. Within six months, he was diagnosed with raging diabetes. It is also known that new cases of type 1 diabetes are heaviest in the cold&flu season of the areas of the planet with temperate climates and much lower during warm seasons. It is also known that incidence of type 1 is lowest at equatorial areas.

Thus, my father postulated that this kind of immune activity may be due to a battle against pathogens whose proteins are similar enough to lie on the edge of the shadows; once the immune system is finally "switched on" and the foreign protein is vanquished, the immune system remains confused about "self" proteins and does considerable damage before finally deactivating. The fact that viruses "hide" inside cells may give them an edge (over bacteria and other pathogens) which can be further magnified by the immunological shadow effect.

My father also believed that the shadow itself must play a role in situations where certain cancers and/or diseases run in families such that foreign organisms/pathogens which are well camouflaged by the "self" similarity can live undetected in a host's body and eventually create a disease state via unusual channels. Ordinarily the immune system acts so speedily to destroy foreign pathogens that these channels don't have time to develop, so they are little known and generally not recognized for what they may actually be.

This theory should be testable and if it proves to be valid, there should be many therapeutic potentials to use it as a means of protecting whole families from the various effects of this immunological shadow effect. For example, a database could be created where the proteins of known pathogens are mapped. This could be utilized in several ways. In the case of an autoimmune disease that runs in a family, their "immunological shadow" can also be mapped and cross checked with the database of known pathogens. Any which come up as positive for similarity can be combatted with vaccine for all new and/or unaffected members of the family. Indeed, the mapping for each individual's "immunological shadow" could be routinely ascertained at birth and a vaccination program instituted to protect individuals would then be a routine addition to other vaccine programs of childhood.

The potential worldwide benefit of being able to prevent type one diabetes alone is enormous.

Potential applications:

Medical testing/mapping of human protein profiles.

Medical testing/mapping of pathogen protein profiles.

Database of all protein profiles/Program for running comparisons.

Protocols for determining risk of all pathogens that fall within an
individual?s ?immunological shadow.

Protocols for determining risk of the subgroup of pathogensthat fall on outer edge of similarity (risk of auto-immune consequences of infection by those pathogens.

Development of vaccines for pathogens whose proteins are similar to human proteins such that they will be targeted by the genetic mapping of human proteins for this purpose.

Research on immune function with regards to new facets illuminated by the discovery of the human ?immunological shadow?.

Research on human embryonic immune system development with regards to new facets illuminated by same.

I'm interested to hear what the group has to offer on these ideas.

Judith Rosen

April 8, 2004

Copyright (All rights reserved)

----- Original Message -----
From: Ayten Aydin
To: ***
Sent: Monday, April 05, 2004 11:12 AM
Subject: Re: [ROSEN] The Rosennean Modelling project

Judith,

If adequate number of people show interest in the area of Immune System, you may include me into the list. I do not know how much I can contribute into the research you have in mind, but the paper I am presently working is on the food connection of diseases and is primarily dealing with the Immunity-related diseases. My understanding is that the immune system is the host of an incredible number of disorders. A passage from my draft is below:

"Auto-immune diseases are usually chronic and cause slow, progressive damage to organs and tissues. These may be organ specific or multi-system diseases involving variety of body systems and producing complex pattern of symptoms and signs. Organ-specific disorders may involve thyroid, adrenaline gland, spleen, pancreas, stomach, liver, kidney, nerves and muscles, skin, hair, ovaries, reproduction organs etc. Among possible triggers, certain infections, particularly viruses, vaccinations and environmental factors can cause subtle changes in lymphocyte function that lead to a breakdown in self-recognition by the immune system. In normal circumstances, the immune system is a protective shield and is able to distinguish clearly between ?self? and ?non-self?. For reasons not yet clearly understood, immune system?s safety mechanisms sometimes breakdown, resulting in an auto-immune disease. Thus, the protection we enjoy from the immune system carries a cost. The following are important conditions caused by immune system activity:
Heart- alveloitis and asthma; Digestive system- Gastrointestinal and liver-coelic disease, ulcerative colitis and some form of hepatitis; Skin- contact dermatitis, pemphigus, pemphigoid and dermatitis herpetiforms; Endocrine- Addison?s disease, thyroiditis and Type I ?insulin dependent (early onset) diabetes mellitus; Ear, nose and throat- hay fever, otitis media (glue ear); Eye- uveiris, allergic conjunctivitis and keratoconjunctivitis sicca; Children diseases- atopic eczema, milk allergy, juvenile chronic arthtitis and Henoch-Schonlein purpura; Blood- pernicious anamemia, autoimmune hoemolytic anaemia and blood transfusion reactions; Reproductive- rhesus disease of newborn and infertility; Kidney- glomerulonephritis; Joints- rheumatoid arthritis, SLE and dermatomyositis; Nerves- multiple sclerosis, myasthenia gravis, polyneuritis, polymyositis, post-vaccination/post-infection, eucephalitis; Infections- immune activity is responsible for a variety of syndromes associated with tuberculosis, malaria, Chagas? disease and leprosy; General- anaphylaxis, graft rejection and serum sickness."
Good luck,
Ayten

----- Original Message -----
From: Judith Rosen
To: ***
Sent: Monday, April 05, 2004 5:31 PM
Subject: The Rosennean Modelling project

I've been cooking some of these ideas over the weekend. I'm going to "think out loud" as it were and see what comes together on the ideas raised so far towards creating new medical models based on Robert Rosen's Complexity Theory approach:

So far, the focus has been narrowed down to the area of medicine and I'd like to continue in this direction (particularly as no one else has voiced any objections or counter-suggestions). Here are my potential areas to focus our modeling exercise on:

One of my curiosities has been mitochondria and the role they play in genetics of human beings and in metabolism. I have done quite a bit of research on this subject and the subject is getting bigger all the time. Mitochondrial DNA has been implicated in scores of metabolic and genetic diseases, and is jointly implicated in such familiar diseases as Alzheimer's, Parkinson's, and Type 1 Diabetes, along with several types of cancers... stuff I would never have thought could be associated with mitochondrial DNA. The subject also plays a role in cloning, because the host egg's mitochondria stay intact when a new nucleus is inserted, Thus Dolly the sheep had "a stranger's" mitochondria. What role did that fact play in the success/failure of the project? Cells have a unique version of an internal immune system that can attack mitochondria, and I am very curious about what kinds of research have been done on mitochondrial gene therapy and whether transplanting foreign mitochondria can induce the cell's immune system to attack or if that is only a property of the larger immune system. The NIH has begun a huge funding effort to support research in this area, so it sounds to me as though my curiosity has pretty good timing. Anyone on the list want to continue down this road?

Another area of interest which is apparently related is that of immune system. My father had some theories on the nature of the immune system which I would like to pursue further. His ideas are in the direction of understanding autoimmune diseases, in particular. I'm willing to share his theories with the list as long as I can protect the copyright issue (I can't "patent" a theory, apparently, but if we generate something that is patentable, I want to make sure that my father's name is included, etc). This particular subject might have to be conducted "off-list" amongst interested subscribers if the legalities specify that by posting these theories, I give up copyright of them. (Tim, do you know anything about this issue?).

A third area that my father had a lot of ideas in was embryology and differentiation of cells, etc. So I would be interested in pursuing research into that area with an eye towards seeing what kind of modeling protocols we can generate using Rosennean approaches.

A final one is apropos the recent discussions on Anticipation. I want to delve deeper into what this "internal predictive model" consists of and how it is encoded into an organism. I see that the implications of this have a lot to say about everything from aging to ecosystem management, etc. Anticipation is one of the basic concepts connected to complexity at the dimension of living organisms, so I don't see how ecologists can hope to model ecosystem behavior in the light of climate change, etc, without a better understanding of this feature of organisms.

Any ideas from the group? Preferences? Suggestions?

Judith