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Dr. Wysong's Blog - 6/6/2011

EPIGENETICS

Throughout history humans have pondered the question of why creatures are what they are. Is the answer nature or nurture?

Up until the discovery of genetics (nature), it was commonly thought that what we did in life and how we behaved (nurture) determined what our children would be. The "original sin" of Adam and Eve is an example of this. Jean-Baptiste Lamarck (1744-1829) developed the theory of "inheritance of acquired characteristics," which argued that a dad who worked hard and grew big muscles would have young boys with big muscles. This idea was soon dislodged by Gregor Mendel (1822-1844) who demonstrated that traits are quite strictly controlled by predictable genetics.

The discovery of DNA further solidified Mendelian genetics by explaining heredity with mechanistic molecular detail. Thus we have come to believe that we are simply the expression of a blueprint that is a combination of packets of DNA, half from mom, and half from dad. But…

The only thing that does not change is change.

The new science of epigenetics now shows that DNA is only part of the puzzle. How we eat, live and love helps determine how our genes behave and what our children will be like. We are returning to the ideas of Lamarck.

The following paragraph touches on the molecular complexity of epigenetics, the understanding of which is still in its infancy. Try not to let your eyes glaze over reading this, which is only a primer.

All cells in the body contain the same DNA blueprint. Epigenetics explains how the 200 cell types in a fully formed body emerge from the one DNA and then steadfastly remain what they are. Chromosomes contain DNA, as you know, but not that alone. Chromatin fibers consist of subunits known as nucleosomes made up of DNA wrapped around histones, like thread on spools. Genes that are tightly wound and buried on the histone do not activate. Those exposed do. Other important elements in this genetic matrix include histone tails, chromatin remodeling proteins, non-coding RNA, remodeling complexes, gene promoters, CpG islands, master regulatory genes, and more. Chemical modification (methylation, phosphorylation, acetylation) of histone tails, and methyl marks on DNA determines how, when, and what genes are "exposed" on the histone spools and expressed. For more detail--enough to make your head spin--do an Internet search on epigenetics.

Although all the mechan ics may seem overwhelmingly complicated (which they are), the takeaway is simple and very important: We, to a large extent, control our own destiny. Although we cannot break free from the store of information in our DNA, we can affect how it is expressed. (Another peripheral point to keep in mind with all this mechanistic detail that gives the naïve the presumption of "knowing," is that nobody has a clue as to where it all came from in the first place. Not even one element of this biochemistry can be explained by a step by step evolutionary process, let alone the myriad elements and processes that are occurring with lightning speed every moment as we go about this thing called life.)

Environmental factors beyond (epi) the mere sequence of bases on DNA (genetic) determine what we are and become. What we do day to day, and what we are exposed to in our environment, can change which genes are or are not expressed. For example, leaf and flower genes in a tree turn off for winter dormancy, and then turn on in the spring. Some changes that cause methylation of DNA itself can create more permanent genetic expressions that are passed to offspring. In contrast to the previous view that we are only DNA determined, both adaptation and heritability can occur in the course of a lifetime.

Gene behavior is now found to be quite malleable and scientists are mining the genome with new tools. No longer are mutant genes sought as the sole cause of disease. The dramatic rises in obesity, heart disease, diabetes and other modern conditions are increasingly pegged as epigenetic in nature, and may well claim their origins in embryonic development due to nutritional and other environmental factors. Even suicide can be linked to childhood trauma that caused a methylation to DNA.

In one experiment, four common nutritional supplements – B12, folic acid, choline and betaine from sugar beets – fed to pregnant mice actually altered the coat colors of offspring. By methylating certain genes, the supplements also lowered the offsprings' adult susceptibility to obesity, diabetes and cancer as compared to the unsupplemented offspring.

Nutrition isn't a fleeting affair having to do with just mouth feel and recreation. We become, quite literally, what we eat as well as what our parents and even grandparents ate. Seismic shifts in food sources, geographic locations, chemical exposures and even weather patterns can alter gene expression through epigenetic changes.

Our heritage, from the time we lived off the land, is under-nutrition. In utero we expect to find scarcity. But then we are born into a land of plenty where unlimited (and perverted) food is just a refrigerator or fast food outlet away. This departure from our natural context can have disastrous epigenetic effects.

The notion that heart disease is genetic or about middle-aged men's behavior is obsolete (see my book, The Cholesterol Myth - Believe it to Your Peril). A huge body of evidence now supports the notion that heart and other chronic degenerative diseases are linked to poor fetal growth followed by adequate or even an excess of food in childhood. While we are not doomed by our prenatal and early nutritional exposures, they do make us more vulnerable to disease.

Nutrition is only one player in an epigenetic repertoire that encompasses climate, sunshine, exercise, chemical exposure, stress, creative challenge, freedom, and even love. We and our children will bear either the consequences of a life lived by the irrationality of belief and faith, or the gifts of a life well reasoned and well lived.