Truman Green's science rumours

July 11, 2010

Epigenetics

Filed under: Uncategorized — trugreen1 @ 4:13 am

                                                               Epigenetics  by  Truman Green

The human body is comprised of approximately ten-fifty trillion cells, and ten times as many bacterial cells, each containing recipies or blueprints, known as genes, not only for the physical assembly of the entire organism, but also for determining how the offspring of the organism will be assembled, and how similar it will be to the parent.

This assembly is governed by the rules mysteriously mandated in the genetic code which require that certain chemical bases will always combine with the same base. The mandatory pairing of these bases in DNA (adenine with thymine and cytosine with guanine, except in RNA where thymine unites with uracil), and the sequencing mechanisms within the nucleus and cytoplasm of the cell are essentially the same in all forms of life on this planet, including humans, bacteria and viruses.

The pairing and bonding of chemicals in the DNA molecule result in a long helix chain which carries the information in sequences, the composition of which determines how it will be used to construct the proteins necessary for the final manifestation of the organism, known as the phenotype. The precise sequencing of the chemicals known as nucleotide bases results in the formation of building blocks known as amino acids, and it is the assembly of amino acids into proteins which direct the composition, function and structure of cells, tissue and organs of living organisms.

A very informative illustration of how the DNA bases are organized into proteins can be found at internet sites which offer the viewer the opportunity to practice constructing proteins by lining up nucleotide bases according to the genetic code–known as “transcription,” and then organizing them into amino acids by passing them through the ribosome outside of the cell nucleus where they are “read”–three bases or codons at a time–and “translated” into proteins.

To view this process and to practice making proteins go to: http://learn.genetics.utah.edu/content/begin/dna/transcribe/

The complete genomes of several organisms have been sequenced in recent years, including that of humans, and several genomes are available online. The human genome has 3 biillion nucleode bases and 30,000 genes, but a smaller genome comprised of 9 genes and approximately 9000 bases, the Simian Immunodeficiency Virus, can be found here: http://www.ncbi.nlm.nih.gov/nuccore/1220519?report=genbank.

                                                     Epigenetics–over and above genetics

The sequences of nucleotides and amino acids form the genotype of every organism, but the emerging field of epigenetics examines alterations of the genotype which do not directly involve alterations of the sequences achieved in the nucleus and ribosomal mechanism of the cell. Narrowly defined, the term applies to mechanisms which affect how the bases and amino acids will be transcribed and translated, but more broadly, it refers to inheritable factors which  result in changes to the apearance, function and structure of the organism which have not been dirived from changes in DNA sequences. The “epi” prefix is used to describe factors which are “over and above” or “in addition to” genetic sequences.
                                               

                                                       Evolutionary Theory and Epigenetics
Charles Darwin’s theory of the origin of the assembly of organisms into “species” is based upon the idea that because there is competition among individuals within a species, those individuals which continually win will be more likely to have their genetic information inherited by succeeding generations. This is the concept of “the survival of the fittest,” and Darwin proposed that this competition results in a “natural selection” of the most successful individuals. An example presented in his “The Origin of Species,” was that of a male wolf which could run faster than his comrads, thereby having greater success in predation and greater access to females with whch to produce offspring. The idea was that whatever specific phenotypical variations were present in this individual would begin the slow process of species alteration and result in the emergence of new species.

The famous, but debunked, Spotted Moth story regarding white moths in Britain which supposedly evolved to black   because of the soot from coal-based industries is a good example of Darwin’s speciation theory. It was later proved that both varieties of moth–white and black–belonged to the same species, therefore no speciation had occurred. Similarly, the lack of speciation among dogs which have been selected for required traits for thousands of years, and the failure in identifying “transitional species,” such as the missing link between apes and humans, continues to provide serious grounds for doubt that “natural selection” has ever or will ever lead to speciation. All dogs–from Chihuahuas to Alaskan Malamutes– are members of the same species and can produce fertile offspring if mated, and no amount of selection–natural or otherwise–has been able to initiate speciation.

As controversy regarding the viability of such “natural selection” increased during and after Darwin’s time, evolutionists added “mutations” to the mix, by which accidental changes in sequences would occur, and when mutations and natural selection were questioned, so-called “genetic drift”–stochastic or random changes in gene sequences–were added to take up the slack in the Darwinian species origination mechanism.

During the decade between l935 and l947 evolutionists developed the Modern Synthesis, the main thrust of which is that natural selection is the prime engine of evolution and that research in all branches of biology, including Mendelian laws of inheritance, confirm the basic tenents of Darwinism.

Perhaps the best-known of the twentieth-century Darwin supporters was Stephen Jay Gould who famously noticed that there seemed to be sudden leaps in the fossil record, and devised the hypothesis of  Punctuated Equilibrium to explain such apparent anomalies. Jean Baptiste Lamarck, a contemporary of Darwin believed that evolution could proceed as individuals were able to inherit characteristics which resulted from the behaviour of their parents. This theory of “Acquired Characteristics,” or “Lamarkianism” bears considerable similarity to the emerging hypotheses of epigenetics, and in many instances provides an exact template.

The “survival of the fittest” and “natural selection” were inevitably adopted by social theorists–even racists– who wanted to use evolutionary theory to confirm their beliefs that the world was unfolding as it should, with the naturally “fittest” race in its naturally-mandated positions of superiority, power and wealth, selected by none other than Darwin’s “natural” selection. If Darwinism provided the agar for such ideas, epigenetics supplies an entire theoretical empiricism with endless examples of how the behaviour of parents can be genetically inherited by their children.

It is universally accepted that all humans originated in Africa, but epigenetics logically implies that blacks, who remain in African today, or who left in the last four hundred years as slaves, have in common that their ancestors never experienced the early diaspora into Europe and Asia, and so have never benefitted genetically from the inheritable learning achieved by Caucasians or Asians who are both genetically related to Neanderthals.

In an article by Brandon Keim  published by Wired Magazine May 6, 2010 Svante Paabo of the Max Planck Institute, comments on the lack of Neanderthal genes in black people:

“For people of African descent, dissappointed by the lack of Neanderthal ancestry, Paabo gave solace:

‘It is totally possible that inside Africa, there was a contribution from other archaic humans that we don’t know about. We shouldn’t take these results as saying that only peoople outside Africa have cavemen biology.”‘

Just as Social Darwinism–buttressed by Darwinian evolution–provided a rationale for racial superiority in the century after Darwin, those wishing to exploit epigenetics for evidence that certain inheritable learning opportunities improved the intellectual capacities of certain groups and left others far behind will find a fertile ground in the inheritance hypotheses of epigenetics.

                                                         Fast evolution in Tibetans

The July, 2010 announcement of the results of a study regarding the Tibetan peoples’ more efficient use of oxygen in their high-altitude homeland furnishes an excellent backdrop against which the differences in genetic and epigenetic hypotheses may be illustrated.(1) Researches found that variations in two genes enable present-day Tibetans to survive in an oxygen-poor environment which would make breathing difficult for non-Tibetans. Darwinian evolutionists would interpret the new findings as being derived from accidental mutations which provided a benefit to those whose genotype included this sequencing error. Such accidentally-adaptive individuals would be more suitable to the low-oxygen atmosphere and therefore more likely to assume an advantage in parenting offspring. In this manner it would be theorized that eventually the entire population would acquire the beneficial genetic makeup which included random errors in nucleotide sequences and amino acid and protein production.

Contemporary theoretical epigeneticists such as Bruce Lipton might have a different interpretation. Lipton writes the following in his book, The Biology of Belief:: “Single cells are also capable of learning through their environmental experiences and are able to create cellular memories which they pass on to their offspring. For example, when measles virus infects a child, an immature immune cell is called in to create a protective protein antibody against that virus. In the process, the cells must create a new gene to serve as a blueprint in the manufacturing the measles protein.”(2)

In Lipton’s theory, evolution can happen not only in one generation but also in one individual, with the “cellular memory” of infection constructing new genes which become permanent and heritable sequences in the genotype.

In this fashion, viral immunity could be inferred upon entire populations merely by the function of “cell memory,” with no necessity for the individual to come into contact with the offending viral antigens in order for the immune system to create protective antibodies, which it accomplishes by providing blueprints and creating new genes. In essence, a child would inherit viral immunity from whatever antigens its parents happened to come into contact with. While Lipton fails to provide a precise explanation and illustration of his non-empirically-deduced “cell memory,” his ideas are similar to those of other theorists who believe that immediate offspring may inherit the repercusions of the behaviour or experience of their parents.
                                                                 
                                                                   Twin Studies

Reseachers in many fields have used identical and fraternal twins in order to determine which characteristics, behaviours and diseases can be attributed to genetic sequence and which can be attributed to other or “epi” factors. Indentical, or monozygotic twins, result from the splitting of a zygote into two embryos in the womb, and will therefore have identical gene sequences in their genome, while fratermal, or dizygotic twins, which are no more genetically similar than siblings, result from two separate, fertilized eggs .

Results of comparisons between monozygotic twins raised apart and those raised together, in most instances, confirm that most human characteristics are strictly dependent upon DNA sequences, or genetics, but recently several studies have shown that even identical twins can have significant differences in the incidence and progression of disease.

In strictly molecular investigations of epigenetics biology, researchers limit their investigations to enzyme alterations of genetic sequences, predominantly the roles played by mechanisms such as methylation, which apparently results in gene silencing, and covalent modificatins of DNA-bound histones, which result in gene activation. George M. Martins, a biogerontologist, in a study published in The Proceedings of the National Academy of Sciences in 2005, found significant evidence that the elderly are more susceptible than the young to such enzymatic alterations of their genotype.

Another study entitled, “Epigeneteic differences Arise During the Lifetime of Monozygotic Twins,”(3) confirms the increased susceptibility of the elderly to epigenetic changes. From the study:

“Monozytotic twins share a common genotype. However, most monozygotic twins asre not identical. Several types of phenotype discordance may be observed such as differences in susceptibilities to disease and a wide range of anthropomorphic features. We found that, although twins are epigenetically indistinquishable during the early years of life, older monozygotic twins exhibited remarkable differences in the overall content and genomic distsribution of 5-methylcytosine DNA and histone acetylation, affecting their gene expression portrait. These findings indicated how an appreciation of epigenetics is missing from out understanding of how different phenotypes can be originated from the same genotype.”

                                                     Beyond 80 years, genetics trumps epigenetics

In July, 2010 researchers at Boston University (4) announced the discovery of 150 gene variations which are significantly more common in centenarians than in octogenarians. These findings would appear to suggest that the best assurance of living beyond 80 is to be fortunate enough to have these gene variations. While healthy lifestyles, including good nutrition and exercise, probably help to determine who will reach 80 years, beyond that genetics appears to trump epigenetics. Researchers claim that they can predict with 77% accuracy which genotypes will allow their bearers to become centenarians. 

Coincidental with the new findings is the strong indication that, even though centenarians may possess genetic indications of serious disease before they reach the age of 80, the existence of the gene variations provides protection from the expression of disease genes, and allows the fortunate to remain healthy well into their nineties and even beyond 100 years. Strictly speaking, the existence of protective gene variations is a purely genetic circumstance, but if scientists are able to develop drugs which mimic the activity of these genes, their participation can be perceived as an epigenetic intrusion into a genotypical eventuality.

As might be predicted by experienced watchers of new “medical breakthroughs,” the researchers also announced that the new findings will likely result in the development of new drugs which will mimic the activity of the newly-discovered gene variations. It’s not debatable that any drug which appears to mimic genes which offer increased longevity will be fantastically marketable.

                                                             Marketing Epigenetics

Besides “ripe old age,” epigenetics–at least in theory–offers endless marketing possibilities. Ill-advised behaviour such as overuse of opiate analgesics, alcoholism, lack of sufficient sleep, smoking, poor nutrition, and high-stress lifestyles are all known to take their toll on the health, well-being and longevity of the individual. The new revelations regarding epigentics is that children can become the genetic beneficiaries of their parents’ ill-advised lifestyles and numerous environmental circumstances, such as residential proximity to chemical carcinogen-producing plants or serious poverty. Epigenetic pharmaceuticals apparently offer the possibility of affecting the genes which control susceptibility to detrimental environments and behaviour.

According to an article by Alla Katsnelson, Can Drugs Based On Epigenetics Spark a New era in Cancer Treatment?, published in New Scientist on April 7, 2010:  “Almost every pharma company has an internal program in epigenetics or a strong interest in partnering in epigenetics research.”  In this article Katsnelson outlines the activities of several companies and provides this cautionary epilogue:

“Despite the field’s optimism researchers and companies realize how little they still know about pulling therapies out of epigenetics. ‘There’s a great deal of work to be done to biologically characterize these targets and understand the consequences of selectively inhibiting gene modifying enzymes,’ stresses Goldsmith.  It’s hard not to wonder whether the promise of epigenetic drugs is as overhyped as the promise of drugs based on genomics.”(5 )

                                                                Complexity problem

Thanks to the proliferation of television crime shows and the emergence of real life progress in the field of criminal forensics, it is now well known that every individual can be identified by unique nucleotide sequencing markers. Intuition suggests that each individual might also harbour a unique response to epigenetic influences. It is widely apparent that for every environmental or behavioural influence on genetic molecules, there will be vast individual variation in how these influences will be expressed.

Many, if not all, complex phenotype variations result from equally complicated and probably unknowable interactions among the 3 billion nucleotide base pairings and 30,000 genes in the human genome. And, as if the variability is not sufficient to produce inviduality in each human, the deck is shuffled one last time at the uniting of sperm and egg in sexual reproduction, in which it is selcom possible for geneticists, doctors or theoreticians to predict how genes will be expressed and how the unique epigenome of each child will be constructed.

Whether one supposes that there is some kind of mysterious intelligence in the origin and design of genetic molecules such as the nucleotide–which must have existed before the DNA helix chain, and even the genetic code itself–or assumes that the assembly of biochemicals into proteins, tissues and organs has a stochastic origin, or occurred due to mutations or natural selection, it can hardly be denied that individuality–at least regarding humans–is a design priority.

The complexity required to provide individuality to each member of our species may ultimately prove to be the undoing of epigenetics’ viability as the provider of  new medicines and treatments, as it was for the over-hyped sequencing of the entire human genome, which resulted in few, if any, efficacious genetically-derived medicines or treatments. Even in the field of oncology, which for decades has been guided by the supposed existence of oncogenes and tumour-suppressor genes, very little, if anything has been accomplished to alter the mortality statistics of cancer.

One fondly remembers the promises of “genetic medicine” in which pharmaceuticals and therapies would be designed specifically for individuals according to their sequenced genome.

Epigenetics would be a wonderful pharmaceutical and therapeutic tool if humans came as clones of each other, or at least as similar as dizygotic twins, but in a species comprised of unique individuals with unique responses to influences of all kinds–chemical, behavioural and environmental–a reality in which epigenetic research will provide medicines and therapies might continue to be beyond the reach of medical science for many decades–perhaps permanently.

If genetic medicine–a field which has only to deal with accurately discernable nucleotide base sequencing–fails to deliver promised benefits, epigenetic medicine–which will be orders of magnitude more complex–will be a formidable challenge indeed, and perhaps only the latest “pet rock” of medical science.
Footnotes

1. Science Daly, July 2, 2010

2. Bruce Lipton, The Power of Belief, Chapter 1.

3. Proceedings of The National Academy of Sciences, edited by Stanley M. Gartler, Jan. 17, 2005

4. Boston University Medical Campus, July, 2010

5. The New Scientist.com, April 7, 2010 Alla
    Katsnelson, Can Drugs Based on Epigenetics Spark
    a New Era in Cancer Treatment?

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3 Comments »

  1. Hi. Yes, the “blueprint” for the offspring doesn’t technically exist until after sex cells have combined but they will be using the genetic information that is present in the nucleus of almost all cells of the parent organisms. I’ll probably alter this sentence to make it clearer, but I did say later on that there’s a “shuffling” of the genes in sexual reproduction.

    Darwinian or Lamarkian evolution implies the slow aggregation of new inheritable traits. In Lipton’s program “cell memory” can somehow create a blueprint for a new gene. This will create a slightly different individual. If genes are created in this fashion the implication is that over thousands or millions of years the experience of the phenotype can produce changes that will lead to speciation. This is basically Lamarkian evolution. My wording here that evolution can happen in one individual is not the best. I’m talking about the implication of this kind of gene manufacturing over thousands of generations.

    If, you’ll recall I’m more into intelligent design and don’t believe that epigenetics, Lamarkian or Darwinian evolution are particularly relevant as methods of deciding which species will survive or even how they change into other species.

    I tend to think of life on earth as some kind of experimental farm. Problem is, I have no idea who’s doing the farm.

    Regarding Tibetans and mutations, I just wanted to show the different approaches to deciding how Tibetans are able to use oxygen more efficiently. Actually, according to the study they have a different complement of red blood cells.

    I think mutations are almost always retrograde so I think that “cell memory” is the better explanation, althought I have no idea how it works. Neo-darwinians would tend to show this change with the mutation model or possibly genetic drift.

    Comment by trugreen1 — July 16, 2010 @ 3:46 pm

  2. Hi. In Darwinian or Lamarkian evolution small genetic changes over thousands of years create new species. The implication regarding Lipton’s cell memory is that over thousands or millions of years it will be the conglomeration of experiences that will lead to genetic changes and ultimately to speciation.

    I’m sure you didn’t think that I was suggesting that a single learning experience in a single individual would cause speciation.

    Comment by trugreen1 — July 16, 2010 @ 4:00 pm

  3. Hi again. Regarding learning being inheritable. If immune cells can create blueprints for genes by way of Lipton’s “cell memory,” why then, can’t neurons (where learning occurs) do the same thing–resulting in slow changes to the organism which is experiencing the learning.

    Thus, in this way learning would be a candidate for cell memory leading to inheritable genetic change..

    I’m not saying I believe this but just included it as a logical progression of the “cell memory” idea.

    Thanks, Truman

    Comment by trugreen1 — July 16, 2010 @ 4:10 pm


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