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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)
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