Epigenetics in Perspective.

There is a lot of controversy and mis-interpretation with regard to epigenetics, both with conventional and alternative scientists and health practitioners. Before analyzing how epigenetics is being used by scientists and abused  others, however, it’s necessary to explain briefly what epigenetics is.

In brief, epigenetics is the study of heritable traits that do not depend upon the primary sequence of DNA.  P.Z. Myers when he laments that this definition is unsatisfactory in that it is rather vague, which is perhaps why quacks have such an easy time abusing concepts in epigenetics. As P.Z. puts it, the term “epigenetics” basically “includes everything. Gene regulation, physiological adaptation, disease responses…they all fall into the catch-all of epigenetics.” Processes that are considered to be epigenetic encompass DNA methylation (in which the cell silences specific genes by attaching methyl groups to bases that make up the DNA sequence) and wrapping the primary DNA sequence around protein complexes into nucleosomes, which are made up of proteins called histones. Indeed, in eukaroytes, the whole histone-DNA complex is known as chromatin, and the “tightness” of the wrapping of the DNA into chromatin is an important mechanism by which the cell controls gene expressions, and this “tightness” can be controlled by a process known as histone acetylation, in which acetyl groups are tacked onto histones (or removed from them). Acetylation removes a positive charge on the histones, thereby decreasing its ability to interact with negatively charged phosphate groups elsewhere on the histones. The end result is that the “tightness” of the condensed (more tightly packed) histone-DNA complex relaxes into a state associated with greater levels of gene transcription. (I realize that this model has been challenged, but for purposes of this discussion it’s adequate.) This process is reversed by a class of enzymes known as histone deacetylases (HDACs).

Suffice to say that epigenetic modifications can be viewed as mechanisms that can ensure accurate transmission of chromatin states and gene expression profiles over generations. We now recognize many epigenetic processes and mechanisms that can regulate the expression of genes, and their number seems to grow every year. It’s become a hideously complex field

In my own field of biogerontology and cancer HDAC inhibitors are a hot area of research as “targeted” therapies, although I must admit that I have a hard time figuring out how a drug that can affect the expressions of hundreds of genes by deacetylating their histones can be considered to be tightly “targeted.”

The above is just a small part of epigenetics, but for now, it is sufficient for the purpose of this paper. Suffice to say that epigenetic modifications can be viewed as mechanisms that can ensure accurate transmission of chromatin states and gene expression profiles over generations. We now recognize many epigenetic processes and mechanisms that can regulate the expression of genes, and their number seems to grow every year. It’s one of the preferred aging pathways or hallmarks as well (See      ).

The Alternative Interpretation of Epigenetics

Creationists who are against the Darwinian interpretation of Evolution appear to have  been the first to invoke epigenetics as a proof of concept demonstrating that Evolution is a fiction.  In epigenetics and the observation that there are traits that are heritable that do not directly depend on the primary DNA sequence they saw what they thought was a “fatal flaw” in Darwin’s theory of evolution. (Darwin didn’t even know what DNA was and nothing in his theory says what the mediator through which traits are passed from one generation to the next is.) Some even thought epigenetics as “proof” of Lamarckian evolution; i.e., the theory that existed before Darwin that postulated that acquired traits could be passed on to offspring. The most common example used to illustrate the Lamarckian concept of evolution is the giraffe, in which successive generations of primordial giraffes stretching their necks to reach higher branches of trees to feed on each passed on to their offspring a tendency to a slightly longer neck, so that over time this acquired trait resulted in today’s giraffe’s with extremely long necks. In any case, to be fair, one can hardly blame creationists for leaping on this particular concept of epigenetics as support for a form of neo-Lamarckian evolution, as several respectable scientists also argued basically the same thing, encouraging credulous journalists to label epigenetics to be the “death knell of Darwin” using breathless headlines. I even saw just such an article last week, which has the advantage of both touting arguments used to link epigenetics to CAM and arguments used linking epigenetics to the “consternation of strict Darwinists.”  It’s an argument that Jerry Coyne has refuted well on more than one occasion.

Is it any wonder that a couple of years ago, Der Spiegel did a ten page feature on epigenetics? The cover of the issue in which this feature was published touted it with a nude blonde (and oh-so-Nordic) female emerging from the water with a DNA double helix-like twist of water covering up her naughty bits, with the headline proclaiming, “The victory over the genes. Smarter, healthier, happier. How we can outwit our genome.”

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Then we have books like Happiness Genes: Unlock the Positive Potential Hidden in Your DNA by James D. Baird and Laurie Nadel, in which we are told, “Happiness is at your fingertips, or rather sitting in your DNA, right now! The new science of epigenetics reveals there are reserves of natural happiness within your DNA that can be controlled by you, by your emotions, beliefs and behavioral choices.”

I’m not sure how epigenetics will make you happy, but I’m sure Baird and Nadel are more than happy to explain if you buy their book. Not surprisingly, naturopaths are jumping on the bandwagon, claiming that epigenetics is at the root of how naturopathy “works”:

Generally speaking, if we want to express a gene and turn it into a protein, we would express certain DNA machinery (through histone proteins, promoters, regulators, etc) to make that happen, and vice versa to turn a gene off. So speaking from a naturopathic viewpoint, what we put into our bodies, the type of water that we drink, the way that we adapt to stress influences whether or not a certain gene is going to be turned on. For a more personal example, what I put into my body is going to influence my genetic code to promote or stop transcription and translation of the BRCA1 or BRCA2 genes, which could eventually result into cancer.

 

Critique

Their arguments are unconvincing for a number of reasons. Epigenetic inheritance, like methylated bits of DNA, histone modifications, and the like, constitute temporary “inheritance” that may transcend one or two generations but don’t have the permanance to effect evolutionary change. (Methylated DNA, for instance, is demethylated and reset in every generation.) Further, much epigenetic change, like methylation of DNA, is really coded for in the DNA, so what we have is simply a normal alteration of the phenotype (in this case the “phenotype” is DNA) by garden variety nucleotide mutations in the DNA. There’s nothing new here—certainly no new paradigm. And when you map adaptive evolutionary change, and see where it resides in the genome, you invariably find that it rests on changes in DNA sequence, either structural-gene mutations or nucleotide changes in miRNAs or regulatory regions. I know of not a single good case where any evolutionary change was caused by non-DNA-based inheritance. Indeed. Moreover, epigenetic changes are not very stably heritable, rarely persisting anywhere near enough generations to be a major force in evolution.

In addition, a fair amount of alternative health physicians look to epigenetics as a way to  reprogram  one’s own DNA (and all without Toby Alexander and the need to mess with all those messy etheric strands of DNA) and thereby heal yourself of almost anything or even render yourself basically immune to nearly every disease that plagues modern humans. Consequently, you see articles on Mercola.com and similar outlets with titles like How Your Thoughts Can Cause or Cure Cancer (through epigenetic modifications of one’s genome which  can purportly control consciouslyness).

 

Text under construction.more later

 

the central dogma of molecular biology in which genes make RNA, which make proteins…

 

Cancer and Epigenetics

Cancer biologist Robert Weinberg was, after all, quoted in an article entitled Epigenetics: How our experiences affect our offspring as saying that the evidence that epigenetics plays a major role in cancer has become “absolutely rock solid.” And so it has. If it weren’t, HDAC inhibitors wouldn’t be viewed as such a promising new class of drugs to use to treat cancer. Some, however, take a good idea a bit too far and claim that cancer is an “epigenetic disease”; it’s probably likely that it’s a combination of epigenetic and genetic changes that lead to cancer and that the relative contribution of each depends on the cancer. Even so, cancers virtually all have what I like to call (using my favorite scientific term, of course) “messed up genomes” so complicated that it’s no wonder we haven’t cured cancer yet.

More later

 

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