First published in The Lupus Magazine By Kim Nault ©
Tyler Malcolm is a retired commercial diver who lives in a small suburban town in Pennsylvania.
He is an animal enthusiast who provides year-round food for the wildlife that frequents his backyard and has made accommodations for the flying squirrels that have taken up residence in the Christmas storage boxes in his attic. You may be wondering who Tyler is and what role does he have with lupus?
I met Tyler while he served on the Lupus MCTD Foundation of America board of directors, as the scientific/research advisor from 2008-2009. I am among several who regard Tyler as a witty and gifted man, though he will neither confirm nor deny this.
Over the phone the wildlife aficionado sighs, “SLE/ Tissue Catabolism is a simple theory and I believe it fits. If it will help people, what can it hurt? Twenty-five years of wondering if my idea could help people is too long, Kim.”
In 1985 Tyler Malcolm, a twenty-something granite contractor read an article about SLE in the New York Times. He was intrigued as to why this serious autoimmune disease population was 90% female. He did not have a family member or loved one diagnosed with lupus. He had no scientific background, nor a medical degree; he was puzzled as to what the cause of the debilitating disease was. Tyler maintains that his ignorance of the disease better placed him in a position of objectivity and served as a powerful tool for hypothesis testing.
Having an investigative mind, he began to frequent local public libraries combing through research articles on the subject of lupus. Making notes on 3X5 inch index cards, he collected scientific data, biological mechanisms of the human body and medical terminology and reasoned out his theory based on the collected data.
A few months later, his brainchild, the theory ‘Systemic Lupus Erythematosus/Tissue Catabolism’ was born. He also authored several other theories during that same time line, each having a copyrights for their authenticity with the United States Library of Congress.
Tyler believes that effective problem solving requires only relevant facts.
He says this cautiously, “I think that it is a thoughtless reflex to generalize the lupus population by just saying that SLE must have something to do with female hormones.”
He looks askance at studies focusing only on the female hormonal as an influence in SLE.
“The studies are weak, inconclusive and sometimes contradictory. After reading that New York Times article, I wondered, what else could it be? I looked at the whole biology, not just hormone levels, not just cells, not just age statistics, but everything at once.”
Tyler’s conclusion was that the higher female incidence in SLE is that females have more cell turnover than males; that estrogen drives cell turnover, which could explain - if nothing else - the higher incidence of lupus in females.
Giving me an anatomy lesson, “Did you know that the kidneys process about 200 quarts of blood a day ? This creates a prime filter for cell turnover to migrate through the body. What’s also interesting is that one of the major organs that get damaged by SLE are the kidneys.”
Tyler also ascertains, “A cure for lupus won’t be made until science uncovers the exact cause of the disease. I see a big surprise coming in the future of lupus research. The cancer people are jumping on the apoptosis (a fancy word for cell turnover) bandwagon like crazy and once they realize that their disease is linked to SLE through the same fundamental process it will trigger a huge shift in research dollars. In many areas of study, it will be impossible to do cancer research without - at the same time - producing results that are also meaningful for lupus. “
A quarter of a century ago Tyler was personally unaffected by the disease of lupus. Years later, lupus has become personal to him.
“The complexity of a person's lupus ordeal is something that I am just learning to appreciate. Back in the 1980’s when I pondered SLE, it was just as a distant and abstract puzzle. Now it's close and real - but - it's not a puzzle anymore, is it?”
Through his service position at the Lupus MCTD Foundation, he has developed relationships with lupus patients; he worries about one friend’s declining kidney function and another’s central nervous system. It does not satisfy him that there are no new advances with lupus, and that every day people are suffering and some are dying. As a patient, I understand Tyler’s frustrations and have often contemplated the disproportional injustice of science being able to put man on the moon, versus science having yet to discover the cause or cure for lupus.
Could the cause of lupus could be a malfunction in the actual cell turnover process? Tyler’s hypothesis has left me to ponder that the very mechanism that initiates the entire autoimmune response in lupus is a hyper-reaction in the cell turnover process. He suspects that if his theory is true, that cell turnover is indeed the cause of lupus, then scientists could target and counteract cell turnover, and thereby cure lupus. Twenty-five years ago, his original objective was to uncover the reason for the higher female incidence in SLE. Through the years, he has silently wrestled with the unanswered question to whether his theory could stop the anguish that people are suffering from. Indeed, Tyler, twenty-five years of wondering whether your theory could help people is too long.
To date, W. Tyler Malcolm’s, Systemic Lupus Erythematosus/ Tissue Catabolism theory remains disproved.
Systemic Lupus Erythematosus and Tissue Catabolism
Copyright 1985 by William Tyler Malcolm
A 90% female incidence and a diversity of autoantigens are unusual features of the autoimmune disorder systemic lupus erythematosus (SLE). The link between estrogenic metabolites and immune stimulation is far too weak to account for SLE's overwhelming female prevalence (besides, any such causal relationship would make all other autoimmune disorders 90% female as well). The consistent occurrence of the same set of autoantigens and the existence of animal models for SLE suggest that it may be related to a fundamental process.
The immunological aspect of tissue catabolism during necrotic clean up and necrobiotic removal may be this process since most of the autoantigens of SLE are intracellular substances and because female histology is characterized by a high amount of menstrual and pregnancy-related cell turnover in many tissues (endometrium, myometrium, cervical mucus glands, vagina, ovary, mammary epithelia).
Since these processes are driven by sex steroids the studies linking linking these hormones and oral contraceptives to SLE's predisposition or progression make sense when viewed through the steroids' stimulatory or antagonistic effects on the normal hyperplastic processes, rather than through their direct influences on the immune system.
Since tissue catabolism is such a fundamental and certain process it is unlikely that a diverse immune response is generated de novo each time a cell turns over; rather, this complicated response is probably a set of concerted actions narrowly controlled, steadily maintained, and suitably modulated.
The circulating anticoagulants often increased in SLE and the other targets of autoantibody such as platelets, erythrocytes, and lymphocytes fit this hypothesis since one would expect that they function in tissue catabolism, or are normally present at the locus, or are themselves the objects of overly aggressive immune-related turnover mechanisms.
Predictably, complement would function in cell turnover and SLE, unlike most other autoimmune disorders, shows abnormalities in serum complement levels and C3b receptors. Exposure of the T antigenic determinant (MN blood group precursor) is a possible mechanism of cell turnover.
Humans maintain anti-T IgM even in the absence of disease and females have higher IgM levels than males. Normally, the T antigen is masked and the pentameric anti-T IgM is inaccessible to tissue cells. The acidic (trauma environment) or enzymatic unmasking of T followed by its complexing with anti-T IgM at a locus of microtrauma or a site of increased vascular permeability should trigger complement fixation.
It is difficult to imagine why the T antigenic determininant exists and the anti-T IgM is maintained if the resulting complex does not serve some purposeful function, such as initiating cell turnover.
A possible explanation of the reciprocal incidences of breast cancer and SLE between black and white women is that a more active and efficient cell turnover process may reduce the risk of a fully progressed malignancy but increase the chance of SLE. This cell turnover concept is also useful in understanding the gender differences in the incidences of many other malignancies.
When I was reading through the archives of the Lupus Magazine and stumbled across Kim's article on The SLE/ Tissue Catabolism Theory, I was immediately intrigued, as I too, have a hunger for constantly learning more, especially when it is with regards to a subject or topic that affects me or has a personal connection... Obviously a theory that has yet to be disproved and may lead us to many more answers with regards to Lupus research, finding the cause and potentially a cure, struck a particular chord of importance to me! I hope you enjoyed and were just as intrigued by this as I was... Since first stumbling upon this I have done some research myself, and find it to be a truly remarkable idea that Malcolm has proposed...
And on that note, it is time for me to get my Sunday going as there is an empty mug of coffee next to me and as you all know, that is simply unexceptable! Be sure to check out Kim's blog- Redefining Myself with Lupus and MS too as she is constantly sharing wonderful informative articles and ideas and has a great outlook (we're big fans over here at CHRONICLYsILLy!) And as always I will leave you with our usual conclusive information, the page of hope where we have been fundraising and will continue to fundraise for the LFA's grass roots campaign for lupus awareness and crucial research, as well as our CHRONICLYsILLy Designs© Awareness shop where we are rolling out new products left and right to help you rock awareness and support in style, with some prototypes in the making as well! 10% of all sales re being donated to the LFA! I hope you all have a lovely Sunday and enjoy the day with spoonful thoughts to each and every one of you, and of course, our daily Jolt-of-Java!
Jolt-of-Java: "Laugh as much as you can breath, and love as long as you live..." -unknown