Monthly Archives: September 2014

The Hygiene Hypothesis, How Our Overprotective Nature is One of the Leading Causes of Allergies

The Hygiene Hypothesis, How Our Overprotective Nature is One of the Leading Causes of Allergies

The Hygiene Hypotheses and Causes of Allergies

I was young once. Now, I am a boomer. When I was growing up, I never knew any child with a food allergy. Allergies of any kind seemed rare. Yet now, allergic concerns are frequently encountered? Just a few weeks ago, I was on a flight from Phoenix to Philadelphia. Shortly after the flight began, the flight attendant announced that no nut snacks would be passed out with in-flight drink service since there was a passenger on the plane with a peanut allergy. After I got over my shock that there might have been any snack at all, I reflected with surprise on the notion that the allergy of this person was so severe that any peanuts anywhere in the cabin was a threat. I had come into contact with thousands of children while growing up both as classmates and friends and I had never ever seen any allergic reactions. We all ate the same foods and there were no dietary rules. What is happening? What is different? After all, just think of it,…. how many boomers ever had a friend with a gluten allergy?

The answer to this apparent disconnect may lie in the emerging science of the hologenome and our contemporary fastidious cleanliness. Current research has suggested that the surge of allergic symptoms is related to our attempt to distance ourselves from our ubiquitous microbial companions. This has been dubbed the “hygiene hypothesis.” In theory, as we seek to protect our young from dirt and disease, we are inadvertently causing an imbalance in our vital exposure to microbial companions that are imperative for our optimal health. New research is showing that we live in an exquisitely intimate association with a vast collection of microbial life. This partnership can directly affect our response to allergens. There is epidemiological evidence that supports this new perspective. Some studies strongly suggest that immunological diseases such as asthma and autoimmune diseases are less common in countries considered to be underdeveloped compared to wealthier nations. Interestingly, this same pattern sees to also hold for a variety of other chronic illnesses.

These microbial partnerships are essential to our metabolism, reproduction, longevity, and well being. This is now known as the new science of the hologenome. The concept of the hologenome re-envisions all organisms as a deeply interlinked complex partnerships between the cells that make us ourselves and our indispensable microbial partners. This has lead to a concept called the ‘old friends hypothesis’. As proposed in 2003, this theory asserts that there needs to be a requisite exposure to a variety of diverse microbes with which we were associated during our evolutionary journey. Therefore, our metabolism is dependent upon certain microbes, as ‘old friends’, and they have become absolutely necessary for our optimal immunological development.

In our zeal to protect against harmful infections, we have inadvertently shielded our children from the typical exposure to a diverse array of microbial life that had characterized all prior generations. The consequence of this exclusion from these vital exposures is experienced as a significant increase in allergic reactions such as hay fever, food intolerance and asthma. In theory then, a substantial increase in the incidence of allergy is a result of this restricted exposure to the microbial domain. All of these problems are thought to be an expression of a decrease in immune tolerance related to a significant change in how our children encounter the environment compared to previous generations.

It currently appears that allergic reactions of all sorts may be directly related to the inadvertent exclusion of critical microbes that co-evolved with us and are required for our personal microbial and cellular ecological balance. Medical practitioners are learning that our health depends on this striking balance of microbial forces. For example, recent research suggests that infants that are not fully exposed to an extensive group of microbes have a less diverse gut microbiome ( microbial species in the gut) and are at increased risk of allergies and asthma. A recent Canadian study provided evidence that exposure to pets and a large number of siblings influenced the early development of gut microbial community of an infant. Less exposure was directly implicated in the subsequent development of allergic disease.
Some scientists believe that the lack of exposure of children to the normal distribution of microbial interchanges can have additional implications. Research studies suggest a potential association between this generational change in childhood experience and the increasing incidence of chronic diseases beyond asthma, food allergies or allergic rhinitis. Many immune centered diseases are potential related to this dynamic such as diabetes, multiple sclerosis, some cancers and even psychological entities such as depression or autism.

What then is an appropriate response to these concerns? Actually nothing special at all. If your child has been vaccinated, simply be willing to let your child share in reasonable unrestricted play with other children and share toys. And also, just let them roll in the dirt with a pet.

Viral Metagenomic Studies

Viral MetagenomicsViral genomics is the study of the full composition of viral genetic source material in the environment. Studies utilizing new technologies are identifying an enormous range of viral diversity that is typically invisible to standard studies. The hologenomic participants in an ecology cannot be fully understood unless these entities are identified. The metagenomic approach has improved our understanding of viral epidemiology, the impact of viruses on our evolutionary transit and has impacted and accelerated the discovery of previously unsuspected viral participants.

Part of the difficulty in identifying viral strains is that many viruses are difficult to amplify in cell cultures. However, there are now numerous molecular techniques to genetically characterize and identify new viruses without the limitations of prior techniques requiring targeted reagents. The range of ecologies to which these new techniques have been applied is quite far reaching. For example, seawater, feces, shore sediments, plasma, or respiratory secretions are only a few. The product of these investigations is a new understanding of the profound variety and influences of viral loads on every ecology. 

Among other things learned to date, unbiased characterization of viral loads on various populations is challenging our prior notions of ‘sterile’ environments. Such studies need not apply to just viral load however. In 2013, a new species of bacteria was discovered in the ‘clean’ rooms used by NASA to build their spacecraft. It had been previously assumed that these specialized rooms were sterile. However, as it has been discovered, this was an unwarranted assumption. In 2007, an unusual bacterium was identified that had eluded all known and repeated sterilization methods. Two years later, this same bacterium was identified inside a clean room at the European Space Agency’s launch site in South America, nearly 2500 miles distant from the site at which it was first discovered. Analysis showed that it should be considered not only a new species, but also an entirely new bacterial genus with a unique molecular composition of its cell wall and other differentiating properties. 

Metagenomic studies based on new techniques beyond outdated cell culture methods allow researchers to identify a wide variety of microbial life that has been hidden from our purview. Some of this previously invisible life as already hitched a ride to any place in space that we have attempted to explore. Surely this is unintentional, but the implications are as yet unknown. 

Hologenomic evolution theory asserts that all multicellular organisms are highly complex and largely specific united co-dependent ecologies. We are only now beginning to understand how profound and varied this partnership can be. As abundantly documented in The Microcosm Within, we are all the current products of hologenomic forces that are only just beginning to be comprehended through the new types of investigations, such as metagenomic analysis, that are only now commonly employed.

Part 5: Epigenetics & Homosexuality

epigenetics homosexuality

Homosexuality and Epigenetics

It is now well established that same sex attraction is not volitional. In The Microcosm Within, the incompatibility of any adequate theory for the persistence of homosexuality within the standard Darwinian construct of natural selection is fully discussed. The evidence points to same sex attraction as a genetic event representing the conservation of an original cellular capacity for self-reproduction brought forward over time as a conserved core process and expressed throughout the animal kingdom as same sex attraction.

More recently, there has been consideration that same sex attraction might be under epigenetic influences. A relationship between epigenetics and homosexuality have been cued from a 2012 study that proposed an experimental model in which epigenetic markers relate to same sex orientation.  This theory was offered as an explanation for some interesting well known observations; the tendency for homosexuality to run in families, the fact that only 20% of identical twins express same sex attraction, and the fact that no ‘homosexuality’ gene has ever been identified. 

The proposal of the research scientists in that study is that epigenetic markers are shaped by androgen signaling and become a factor in gonad development thereby molding sexual orientation. In effect, the underlying genes are modified by epigenetic factors based on the differential experience of the fetus to the stress of maternal hormonal levels. These markers can then be transferred to successive generations accounting for the familial tendency. It is not merely the absolute level of the androgen signals that might matter, but the underlying sensitivity of the developing cells to these signals. This might differ from individual to individual based on genetic architecture or there may be an inherent difference between males and females. The effects of these transmitted epi-marks need not be specific to the gonads, instead affecting areas of the brain, so that there is no difference in the gonads themselves. 

Not everyone feels that this type of theorizing is particularly important since it is clear that same sex attraction is simply part of the human condition and our inherent variability. Yet, this sort of investigation and speculation does serve to emphasize that same sex attraction, what ever its causes, is not subject to the simple rules of natural selection that underpins Darwinism. Further too, if such a trait with its consequential impact on reproduction escapes natural selection, then a theory of evolution as impelled by natural selection needs to be reexamined. 

Part 4: Epigenetics and Chromatin – Epigenetic Changes


Epigenetics and Chromatin

Chromatin represents the combination of both the DNA and proteins in a cell nucleus. This combined material can assume specific configurations. This chromatin architecture is currently viewed as having a critical role in controlling gene expression and DNA replication. The primary protein elements of chromatin, or histones, compact DNA and assist in mitosis. Epigenetic changes occur by complex interactions between environmental influences and the underlying protein structure and DNA of a genome, which can alter the configuration of chromatin or change how segments interact in their three-dimensional environment. Examples include DNA methylation and alternations to chromatin architecture through histone modification. It is believed that most epigenetic modifications to underlying DNA sequences, either through promotion of genetic expression or silencing of genetic sequences proceeds through alterations in chromatin architecture.

In general, it is currently considered that epigenetic changes to a genome are less stably heritable than base genetic heritability. That is, if a genetic change occurs to the underlying genetic code it is more likely to be stably transmitted to future generations than epigenetic changes, termed epialleles. These latter modifications are thought to be generally unstable. In addition, the fidelity of transfer if it occurs may not lead to exactly the same degree of genetic expression in a further population, termed variable penetrance. So the genetic expression potentiated by the epigenetic change may still persist, but be lessened or the new trait may entirely disappear in future generations. The process that appears to account for this is that most epigenetic changes are believed to act by modification of underlying chromatin architecture rather than the intrinsic DNA base sequences within that complex assembly. It has even been postulated that the protein histone elements of chromatin may even constitute its own form of code that offer cues and instructions for gene regulation and could then account for differing states of genetic expression and activity.

Yet, according to William Kelly at Emery University in a recent article on transgenerational epigenetics, some things are clear. Complex and overlapping epigenetic mechanisms build changes in chromatin architecture that are heritable. These changes can guide genetic expression in germline cells, and then guide chromatin architecture in the zygote. There is an “initiating event” that triggers these epigenetic processes. Some further maintenance mechanism assures that this altered genetic expression and activity is maintained through successive rounds of replication and reproduction. Further, there appears to be some ability to discriminate at the germline as to which epigenetic processes persist and which are expunged. All of these mechanisms are fully compatible with hologenomic evolution theory, as explored in The Microcosm Within. Importantly, such new scientific findings critically undermine the simplified paradigms of conventional of the Modern Synthesis and its unfaltering allegiance to unfettered natural selection and random genetic mutation.

Part 3: Epigenetics and Cancer | Epigenetic Modification

Epigenetics and Cancer

Epigenetics and Cancer

New research is demonstrating that the etiology of cancer is complex. Epigenetic modifications of the genomes of cancer cells appear to be quite important. These are changes that do not necessarily reflect the exact DNA sequences within a cell, but alter, by various means, the expression of the underlying code. It is increasingly apparent that epigenetic modification may be as important as genetic mutation in the transformation of a normal cell to a cancer cell. This does not change the fact that many cancers are induced by infectious disease which itself can be considered an epigenetic variable. 

Such epigenetic mechanisms are being successfully defined. These include DNA methylation, arguably the most researched marker, by which the methylation profile can be linked to tumorigenesis as promoters of unlicensed cell reproduction. Alternatively, hypermethylated DNA zones can result in consequential gene silencing, which is considered itself to be a form of carcinogenic epigenetic mutation. It is also theorized that hypomethylation in parts of a genome can lead to chromosomal instability and the activation of transposable elements which can increase cancer risk or directly induce it. 

Recent studies have implicated an epigenetic signature that can predict whether a woman may develop breast cancer, even without those BRCA gene mutations that are typically considered a prime risk factor. An epigenetic signature in women with a mutated BRCA-1 gene has been linked to increased cancer risk and lower survival rates in a study conducted at the University College of London. 

Interestingly, a new epigenetic therapy designed to treat cancer by regulating gene expression has been cleared for Phase I trials. A recent clinical trial of a small molecule inhibitor drug of a particular class of proteins helps to control gene expression. This epigenetic control mechanism has shown initial promise in the treatment of refractory carcinomas. As the researchers note, the success of this initial trial, albeit limited, points the way for other investigational epigenetic cancer therapies. Thus, our emerging understanding of epigenetics if offering profound clues to both the causes of cancer and its cure. 

Part 2: Epigenetics and Evolution – Transgenerational Epigenetic Inheritance


Transgenerational Inheritance

New scientific findings involving epigenetics are having a profound impact on our understanding of evolutionary mechanisms. It is becoming increasingly apparent that epigenetic modifications play a critical role in the regulation of gene expression. In so doing, they produce phenotypic changes. It is becoming abundantly clear that these influences are an important factor in our own human experiences, influencing life span, mood disorders, immunological status, obesity or tendencies towards the variety of chronic illnesses that have afflicted our human experience. Although it has until recently been assumed that these epigenetic marks are cleared in each generation and then re-established by reiteration of similar environmental influences, it is now manifest that this is not always the case. The term ‘transgenerational epigenetic inheritance’ has been applied to this phenomenon.

Epigenetics is now an established discipline. Examples abound. For example, one of the first fully documented instances was the transgenerational epigenetic inheritance of flower symmetry from bilateral to radial in Linaria vulgari. This results from a change in DNA status, a process of methylation, rather from any change in the underlying DNA sequence. In essence, a different form of gene expression and its phenotypic trait correlates to either an active or silent state of underlying genetic code based on environmental experiences. This has been shown to be heritable over multiple generations and might be permanent. Obviously, there remain difficulties in ascertaining with certainty what might be an ‘epigenetic’ change and what could be an underlying genetic mutation, yet the concept seems robust. There is a means for the experiences of an organism within its environment to affect its genetic expression and that change can be either meiotically transferred to the next generation or through RNA transcripts in germ line cytoplasm to progeny. Importantly, in hologenomic evolutionary theory, the targets of these kinds of transfers and their influences are extensively available to organisms that are pictured as vast inter-related ecologies of innate and microbial cellular life… a microcosm within. We, and all hologenomes are subject to a vast array of both internal and external environmental influences in an exquisite, complicated and co-dependent interplay.


Part 1: Definition of Epigenetics and Acquired Characteristics

What is epigenetics?

Jean-Baptiste Lamarck

This is the first of a five part series discussing epigenetics.

In science, what is old can once again become the new. To better understand the definition of epigenetics, we must look back at the time before Darwin. Charles Darwin proposed his version of natural selection and heritable descent by gradual modification in 1859, but before that, many theories had been considered before creationism. One leading evolutionary proponent was Jean-Baptiste Chevalier do Lamarck. He was the protégé of the Comte de Buffon who had believed that living organisms can vary over time and their experiences in the environment may affect them and their progeny. Lamarck proposed the concept of the inheritance of acquired characteristics as just this sort of mechanism. He believed that evolution can be effected by the manner in which a body part is used or altered during the lifetime of an organism and that this acquired character was then heritable. For example, a blacksmith using upper body strength for work would be more likely to produce children with greater upper body strength. Although carrying considerable weight as a scientific theory in its era, scientists were rather easily able to point out the many apparent contradictions to it. Ultimately, it was eclipsed and discredited. Indeed, Lamarckism has often been used as a specific example of fallibility of belief systems in scientific progress.

However, it seems that Lamarck was not entirely incorrect. Prior to our genetic era, C.H. Waddington developed the term epigenetics as a means of naming a process in which heritable factors might interact with the environment to produce the phenotypes and forms that we can observe. Although it was firmly believed until relatively recently that genes are fixed in an individual and that only random mutation can affect them, current scientific information has revealed that genes and genetic expression can be affected in a variety of consequential ways by environmental factors. Currently, epigenetics is established to mean the heritable phenotypic changes that an organism can express without specific alteration to the relevant underlying DNA sequences. It is becoming increasingly apparent that this type of inheritance is consequential and multi-generational, and may be permanent in particular instances. So, Lamarck’s derided notions have been unexpectedly revived as our understanding of the fuller complexity of genetic variation has deepened.