Category: Protoscience/ Frontier Medicine
Major news about one of my favorite molecules, l-fucose. In addition to being part of the antigenic structure of the H antigen found in blood group O, fucose is now garnering attention as an important component in learning. Although neurophysiology spends quite a bit of time looking at the neurosynaptic junction (the gap between two nerve cells, where nerve conduction occurs) most of the emphasis is on the neurotransmitters (such as serotonin and dopamine) that can jump the gap.
However, what goes into holding the synapse together may be as important a factor in cognition and learning as what jumps across the synapse. And that appears to be lectin-like receptors on one side of the nerve synapse which bind to fucose as a ligand on the other.
In other words your nerves have a sweet tooth for fucose.
Reaction in the brain involving fucose skyrocket during periods of intense learning. And human milk is a very rich source of the sugar, with amounts far higher than all other species. The sugar content of human milk varies by ABO blood type and secretor status which makes me want to do a study looking at learning differences along blood group and secretor status in breast fed and bottle fed children.
The fucosyltransferase enzymes FUT1, FUT2 and FUT3 are very intimately involved in determining ABO, secretor and Lewis blood types and recent research has linked serum B12 levels (another important player in proper nerve function) to the FUT2 (secretor) gene.
Fucose and fucosylation have a big role in ontogeny (the origin and the development of an organism from the fertilized egg to its mature form) via it's role in the development of the Lewis X antigen (FUT9) which supports cell-to-cell-adhesion in embryos. Lewis X expression in the brain is in turn controlled by the PAX6 gene, which regulates many elements of nerve growth in addition to forming the architecture of the iris.
The link between PAX6 and Lewis X (FUT9) may explain why a recent study showed that at least some aspects of personality were determined by the genetics of iris formation. Close-up pictures were taken of the study participants' irises, and they also filled out a questionnaire about their personalities. The researchers looked at crypts (pits) and contraction furrows (lines curving around the outer edge of the iris), which are formed when pupils dilate. It was found that those with more crypts were likely to be tender, warm and trusting, while those with more furrows were more likely to be neurotic, impulsive and give in to cravings.
PAX6 is gene that helps regulate embryonic differentiation. PAX6 also has some interesting effects on adrenal and pancreatic function as well as norepinephrine expression in the gut via the enteric nervous system. Maybe there's a future in medicine for the iris after all.
Going forward, I predict that soon the best thing to use in kids who are learning-challenged will not be the usual suspects like Ritalin or SSRIs, but rather glycomic agents from the diet that enhance fucosylation. These drugs do enhance the function or persistence of neurotransmitters, but fucosylation enhancers seem to enhance the stability of the entire neural network. It makes no sense to up-regulate neurotransmitters if you haven't insured that the nerves are holding to each other in the first place.
Of course, most of the old blood typers know that Bladderwrack (Fucus vesiculosis) is a decent source of fucose.
Schizophrenia, gluten, and low-carbohydrate, ketogenic diets
We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.
Previously, Dohan (Acta Psych Scand 1966, 42(2):125-152) observed a decrease in hospital admissions for schizophrenia in countries that had limited bread consumption during World War II, which suggested a possible relationship between bread and schizophrenia. Early work with lectins clearly showed that the brains of schizophrenics bind lectins differently than the brain tissue of non-schizophrenics, which appears to make sense in that the carbohydrate content of schizophrenic brain tissue (in addition to dementia and a few other illnesses) revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate; many of these blood group active carbohydrates with known lectin binding affinities (link).
Over the years some of the most stirring letters I've received from book readers have centered around improvements in family members with schizophrenia. Almost all of these letters have been from or about blood type O schizophrenics, which may mean that the nutritional approach to schizophrenia might necessarily differ by foods and blood type. We are now only beginning to understand the effects of tissue glycosylation on the development and maintenance of brain neural networks.
The class I currently teach in generative medicine uses a content system called Blackboard. Blackboard allows me to upload material and pose questions to a forum-like discussion area. One of my students, upon reading the assignment in the textbook made the following comments:
You talk about the division between classical science and naturopathic science, which you equate, respectively, with reductionism and emergence (p. 30). Do they necessarily have to oppose one another and can they not coexist. And does not naturopathic medicine incorporate some degree of reductionism and classical science some degree of emergence?
I guess this goes back to the old question of: can't we all just get along but, further, isn't it sort of imperative that we not categorize conventional versus naturopathic medicine in such black and white terms? Or maybe it is a more useful distinction than I'm discerning?
If, indeed, scientific reductionism is dead (p. 20) and the biomedical community is unaware, how do you best suggest we, as NDs (or future NDs), start to make inroads into that community to convince them that the idea of emergence/holism/a generative approach is worth substantively incorporating into the larger paradigm of "modern" medicine?
I would argue that there is a global groundswell of desire among consumers of healthcare for this generative approach, but it might be up to us as practitioners of naturopathic medicine to bring it mainstream. But the path to that end is not clear. At the end of the day, not only do we have to all get along, but we need to understand what the other is saying.
To which I replied:
If we define 'dead' as having lived a life with purpose, and perhaps even being so lucky as to exhaust that purpose, then reductionism is quite dead in the sense of being 'not alive'. [Which leads to the question: if an idea has no purpose, hence no life, does it even get to die?]
There will always be a reason to think in reductionist terms when the facts do indeed fit the scenario. IMHO there will always be opportunities for non-complex thinking (and indeed one should seize them whenever one can).
My position is that, as a profession, we are perhaps running the risk of being overly seduced by the simplicity of fitting our oeuvre to the existing allopathic framework. In essence we will be moving into a neighborhood in which the prior occupants have already sucked out the life and are themselves moving on to new areas.
Moreover in doing so we may well be creating a nascent culture of new dogmatists, apparatchiks who insist on only dealing with issues on these terms. If that was not bad enough, this then runs the risk of creating its own response element, its own duality, such that a second subculture results that does the exact opposite, accepting facts a priori.
So, what about this generative medicine idea? As you so astutely point out, the goal is to blend both the complex-systems approach with the mechanistic-reductionist approach, point being that we, as naturopaths, should have a pretty good feel for where the work needs to be done and how to go about doing it. Perhaps this duality is itself a power law: we may be using an 80% reductionist formula to discern 20% of our total causalities. Certainly systems-complexity-network (SCN) medicine comprises only a small fraction of current biomedical information analysis. Generative Medicine, as I see it, should resolve that duality.
No matter what, the informational chasm does indeed lay which complexity, as well as any future potential for understanding and treating the life process itself.
Like they say, if you really want to learn something, teach it.
I write a weekly email to the ND students on my shift at the University of Bridgeport Health Science Center. If in the course of working with a patient a concept arises that appears to require more in-depth knowledge I often specify certain research articles for the students to read in preparation for the next shift. This is not typical of clinic shifts and my shift is thought to be among the more demanding. Despite (or perhaps because of) this, a place on the shift rotation is always in high demand.
Recently the discussion came round to two concepts related to both cancer and inflammation: endoplasmic reticulum stress (ER stress), which results in poorly manufactured proteins; and the subsequent unfolded protein response (UFR), which occurs as a result of the dangerous aspects these improperly folded proteins pose to the cell.
After providing the students with 6-7 key studies, I began to suspect that they might need some cheering-up. So I appended this little ditty to the email:
A polymath is someone who is interested in everything, and nothing else.'
A polymath (Greek πολυμαθής, polymathēs, "having learned much") is a person whose expertise spans a significant number of different subject areas. In less formal terms, a polymath (or polymathic person) may simply be someone who is very knowledgeable. Most ancient scientists were polymaths by today's standards.
How do YOU propose to become a polymath? What might you need or observe?
Firstly, and this might be obvious, there must occur a huge leap in self-confidence. If you are easily intimidated by learning new things, or think you are somehow less smart than others, becoming polymathic will not be easy.
The learning-intimidated state is overcome by taking the first few baby steps in developing a new appreciation of just what you are capable of being aware of. This might be as simple as arriving at the conclusion that, since you are (at the very least) in control of your own life, who else is better capable?
I once had to do an interview with
Well of course I got all bent out of shape. The guy is like one of the smartest people on the planet. etc. etc. etc. string theory, etc. etc. etc. skeptic, etc.etc. etc.
As I got more twisted and twisted, I went to dinner at an old friend's house. These people were once our next door neighbors and we've kept in touch over the years, despite (or perhaps because) we don't have very much in common. On hearing my lament, the husband listened and simplified the whole thing for me by identifying the one basic truism:
'He may be smart, but he don't know what you know.'
Anyway, we couldn't get a time that worked for both of us and the interview never took place, but I did learn something about myself.
2. Rush/ Don't rush.
How often do we use time to avoid something? To just get 'it' over? However, far from telling you to slow down, I'm suggesting that you rush with a purpose. Not just to 'get it over with ', but rather to 'just to get to the end of it.' Then, instead of just moving on, going back and revisit that notion that caught your eye. Getting to the end of something lets the brain 'pin the four corners' of the concept and set aside space for conceptualization and context.
This observation has an important metaphor about disease and health buried within it.
Health is often like a car speeding down the highway: scenery flying by, but just barely noticed. Windows up. AC on. Favorite tunes playing. The conversation centering on some arcane subject. However, the timing belt breaks. So now we are going zero miles per hour, perched aside a forlorn stretch of highway. Initially we can only think about getting out of here ASAP. But soon other senses intervene and we begin to mesh with this new reality. Perhaps a tall copse of Shepherd's Purse. The sound of a small stream heard but not seen. The alluring shade of a nearby tree.
Disease as metaphor, disease as teacher.
3. Quantity has a quality all of its own.
Think of it like this: if you were pouring a concrete floor, it would be rather silly to start in one corner, pour a one-foot-square area, wait for it to cure and dry, and then move on to the next square. Not only would it be inefficient, but the floor itself would have very little structural integrity.
What should we do instead?
We'd pour 'skim coats' over the entire area, perhaps in several layers, trying to cover as much of the entire area as possible. Now, if I were insecure about my 'footing', and had to make the choice between standing on a one by one-foot-square of concrete or the first layer of a thin skim coat covering the entire area I might opt for the apparent security of the fully-completed one-foot square (and indeed, most testing is done on a person's ability to make the 'most perfect' one-foot square). Trouble is, I'm on a square of concrete that doesn't allow me to move anywhere else.
That's the problem with developing polymathic knowledge: there is an initial 'awkward stage' that many people find troubling, especially if they are insecure, or have been led to believe that all things taught to them must have immediate 'meaning'. However, there is a fix for this and a few of you have already figured it out:
Wonder is often compared to the emotion of awe but unlike awe wonder inspires joy rather than fear or respect.
So you might say that wonder is curiosity tinged with the prospect of potential joy.
Thus we have two choices with this week's assignments. We can moan about the amount of reading on what (after all) is just a clinic shift; start with the first article, tediously plow through it in workmanlike fashion, and then move onto the next, and the next.
This will take hours.
Or we can isolate the key concepts (in this instance I've supplied them: molecular chaperones and the process of n-glycation) gain a cursory understanding of these concepts and then skim through the articles, 'wondrously' luxuriating in areas that catch our attention and/or fit our model of the big picture. Each iteration (or skim coat) deepens knowledge and allows for the creation of more and more interconnectedness.
So, as you might gather, far from being onerous, polymathic behavior is a labor-saving device.
An interesting lecture on biomimicry got me thinking: With these new ways of analyzing intent by the study of naturally occurring shapes, functions and forms, we may be witnessing the 'naturopathization' of imagination in other arts and sciences.
"Now how does one know what is best? There needs to be a decent, well-developed, and endlessly exercised sense of taste for quality, of making strong choices between the excellent and the rest. An open mind but not an empty head: an intense willingness to see things and an intense willingness to make judgements about quality. "
-Edward Tufte ('Beautiful Evidence')
We need more of this 'comparative-reflective' thinking.
Someplace in the Talmud (a Jewish holy book) there is a commentary to the effect that God does not allow illness to exist until the solution or cure has first been created. What a marvelous take on time-space.
But how would we find that cure? We'd look to nature. To my way of thinking, over the course of his or her career, the good physician becomes increasingly comfortable visiting this invisible world, but only if fortified with a deep knowledge of the natural workings of things.
These excursions (really thought experiments) cannot but produce the most creative solutions to suffering, especially when guided by principles similar to those such as Tufte's (a statistician and sculptor-- not a physician-- again testifying to a certain conceptual universality.)
I'd paraphrase it as all knowing and all trusting, but also realizing that when we know very little, we should probably trust very little as well. Just contrast human intuition (usually a leap of faith) with animal intuition (genomic knowingness).
The British biologist Conrad Hal Waddington conceived of genotype (your genetic plan) passing through environment into phenotype (the physical you) as a walk through an 'Epigenetic Landscape'. He conceived a mode of visualizing this process, in which phenotype development is seen as marbles rolling downhill. In the beginning development is plastic, and a cell can become many fates. However, as development proceeds, certain decisions cannot be reversed. This Landscape has hills, valleys, and basins and marbles compete for the grooves on the slope, and eventually coming to rest at the lowest points, which represent the eventual types of tissues they become.
The Epigenetic Landscape. (After Waddington, C. H., 1956, Principles of Embryology)
Waddington was a big thinker. Not only did he visualize development as passing through the peaks, slopes and valleys of the Epigenetic Landscape, he considered this process one of increasing constraint, or as being "canalizedâ€? as he referred to it: That the early choices influence the later options. If we think of the canals of Venice, the analogy works even better; our little gondola floats from one canal into another and then another. Each choice leaves it fewer options than before, and since gondolas need water, so we can't just pick it up and put plunk it into another canal.
Now just for a moment visualize a newly fertilized egg. It already contains all the wisdom and information needed to eventually go on to produce a completely formed human being in its DNA, but over time it must develop various cell lines (called germ layers) that can then go off and further distinguish themselves as arteries, nerves and organs. Its unfolding is stochastic (a process that is non-deterministic in the sense that the current state state does not fully determine its next state.).
"Stochastic" is one of those great words that is more often misunderstood than understood. It is often quoted as being synonymous with random, but the actual Greek seems to imply something closer to "unknowable." It's often used in the arts (very often in music composition.)
In short: We know it's going to happen; we just don't know what is going to happen.
Your journey from genetic imprinting (the genes that were determined at conception) to full phenotype (the physical you) is to a great degree a stochastic process. which is why Waddington's metaphor is so great. Any architect will tell you that a house almost never winds up like that original plans. Environmental variables (cost of materials, availability) alter reality as the construction project moves from one stage to the other. We cannot always predict the eventual outcome, but we can describe and learn about the landscape in which it takes place and that, to a degree allows us to understand things.
Hindsight is always 20/20, because the outcome almost always describes the process.
That journey started long before your conception, since epigenetic gene control is hereditable.
You are in essence, not what you eat, but rather what your parents, grand parents and even great grandparents ate. Unlike defective genes, which are damaged for life, epigenetically controlled genes can be repaired. And, activation and silencing tags that are knocked off can be regained via nutrients, drugs, and enriching experiences. (1)
Conceivably the cancer you may get today may have been caused by your grandmother's exposure to an industrial poison 50 years ago, even though your grandmother's genes were not changed by the exposureâ€¦ or the mercury you're eating today in fish may not harm you directly, but may harm your grandchildren (2)
These inherited traits can continue to influence the onset of diseases like diabetes, obesity, mental illness and heart disease, from generation to generation.
All in all, the next few years should prove most interesting...
The post-genomic era, which is fueled by automation and other technologies, provokes a change in our grossly naive view of genetic determinism (that single genes govern complex traits) to the obvious reality that most human diseases are complex entities. Gene(s), although necessary, contribute only partially to disease, while environmental factors, lifestyles, epigenetics and epistasis significantly influence pathophysiology and, eventually, the expression of transient biomarkers that can be utilized for diagnosis and prognosis. Human osteoarthritis and rheumatoid arthritis are multifactorial, complex diseases. The genetic inheritance of these diseases remains elusive, although they tend to run in families wherein some siblings have a two- to tenfold increased risk of developing the diseases.
From: Future of genomics in diagnosis of human arthritis: the hype, hope and metamorphosis for tomorrow
Ashok R Amin?, Seth D Thompson? & Shailey A Amin
August 2007, Vol. 2, No. 4, Pages 385-389
Epigenetic alterations have been known to be of importance in cancer for ~2 decades. This has made it possible to decipher epigenetic codes and machinery and has led to the development of a new generation of drugs now in clinical trials. Although less conspicuous, epigenetic alterations have also been progressively shown to be relevant to common diseases such as atherosclerosis and type 2 diabetes. Imprinted genes, with their key roles in controlling feto-placental nutrient supply and demand and their epigenetic lability in response to nutrients, may play an important role in adaptation/evolution. The combination of these various lines of research on epigenetic programming processes has highlighted new possibilities for the prevention and treatment of metabolic syndrome.
From: Nutritional Epigenomics of Metabolic Syndrome
Catherine Gallou-Kabani, and Claudine Junien
Diabetes 54:1899-1906, 2005
1. Asim K. Duttaroy Evolution, Epigenetics, and Maternal Nutrition 2006 Darwin Day Celebration.
2. Montague T. A New Way to Inherit Environmental Harm. Synthesis/Regeneration 39 (Winter 2006)