The Dark and Light Side of Food As Information (Dietary RNAs Directly Impact Gene Expression)


 

New insights in biology show that food is informational and can directly impact and even control the expression of your genes. The implications of this discovery are profound, and have both a light and dark side in need of deeper exploration…

A new study published in the journal BMC Genetics entitled, “Plant miRNAs found in human circulating system provide evidence of cross kingdom RNAi,” reveals that powerful little diet derived nucleic acids known as microRNAs (miRNAs), from commonly consumed plants, are present within the human circulatory system in what appear to be physiologically significant quantities. MiRNAs are comprised of ~ 22 nucleotide single strand non-coding RNAs, which regulate protein coding gene expression by interfering with messenger RNA’s ability to transcribe DNA into protein. This is why miRNAs are sometimes called RNA interference molecules.

The study found,

“…abundant plant miRNAs sequences from 410 human plasma small RNA sequencing data sets. One particular plant miRNA miR2910, conserved in fruits and vegetables, was found to present in high relative amount in the plasma samples. This miRNA, with same 6mer and 7mer-A1 target seed sequences as hsa-miR-4259 and hsa-miR-4715-5p, was predicted to target human JAK-STAT signaling pathway gene SPRY4 and transcription regulation genes.”

This discovery has profound implications, as the human JAK-STAT signalling pathway has a wide range of potential downstream effects. In fact, JAK-STAT transmits information from extracellular chemical signals to the cell nucleus resulting in DNA transcription and expression of genes involved in immunity, differentiation, proliferation, apoptosis — all of which relate to cancer risk and oncogenesis. But this is just the tip of the miRNA iceberg. There have, in fact, been hundreds of these miRNAs identified in commonly consumed foods in the agrarian diet, and they appear to have the ability to match up with hundreds of human gene targets. The implications of this are profound, if not possibly devastating when it comes to GMO food technology.

It is now widely accepted among conventional biologists that miRNAs regulate most of the protein coding genes in mammals. In fact, the profound difference in complexity between higher life forms such as humans relative to, say, earthworms, is attributable to the higher level of RNA complexity within the so-called ‘dark matter of the genome’ (the ~ 98.5% of the human genome that does not code for proteins).

But what research like this brings to the table is the even more provocative possibility that our genetic and epigenetic wellbeing may be wholly dependent on miRNAs existing outside of us within the gene-regulatory miRNAs embedded within our diet.

Can you imagine the difference between an evolutionarily conserved ancestral diet and a modern one comprised of synthetic components and highly processed GMO cereal grasses?

The New Epigenetic/Nutritional Paradigm: Cross-Kingdom Communication

The idea that the plants and animals we eat contribute to modulating the expression of our genome is known as cross-kingdom or inter-species genentic communication, and represents a significant departure from the classical view that the genetic infrastructure of species were closed off, hermetically sealed within the cell nucleus, and could not be accessed epigenetically from the outside in. We’ve moved from this atomistic, monadistic view to an open access one, where miRNAs operate like software upon the hardwired protein-coding sequences within a species’ genome, making for a much more complex and interdependent web of relationships, reminiscent of the Gaian concept of a biospheric interconnectivity between all the biotic elements of the Earth. As I discuss in another article,

“…this more “open access” model would permit species to alter and affect another’s phenotype in real-time, along with potentially altering its long-term evolutionary trajectory by affecting epigenetic inheritance patterns. This speaks to a co-evolutionary and co-operative model, with all areas of the tree of life, co-developing in a highly complex and seemingly highly intelligent, carefully orchestrated manner.”

And so, if plant derived miRNAs can survive cooking and digestion, as appears to be the case, and can accumulate in physiologically significant quantities, they will therefore alter gene expression, introducing the novel concept that mammalian genomes may have, in fact, evolved to outsource some of their regulation to nutrigenomic dimensions within their dietary milieux.

This, of course, has profound implications, such as validating the concept that an evolutionarily appropriate diet —  e.g. Paleo diet — would help to assure the optimal expression of the human genome. Conversely, the use of RNA interference technology by biotech corporations, such as Monsanto/Dow’s newly EPA approved RNAi corn, could have biologically devastating consequences to the health and wellbeing of those fed or exposed to its altered miRNA profiles. To learn more about this concerning possibility, read (and please share) my report: The GMO Agenda Takes a Menacing Leap Forward with EPA’s Silent Approval of Monsanto/Dow’s RNAi Corn

 

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We Might Have Been Wrong About What Makes People Left- or Right-Handed


Scientists have long been intrigued by why people tend to naturally favour the use of one hand over the other. We still don’t fully understand what causes people to be left or right handed, but for decades researchers have assumed that the origin lies inside our brains.

But a study published in 2017 provides early evidence that it’s not only the brain that determines handedness – the spinal cord could also play an important role.

An international team of biopsychologists led from the Ruhr University Bochum in Germany has now shown that genetic activity in the spinal cord is already asymmetrical in the womb, and could be linked to a preference for either the right or left hand.

“These results fundamentally change our understanding of the cause of hemispheric asymmetries,” the researchers wrote in the journal eLife.

To be clear, this is nothing more than a hypothesis in its very early stages for now – we need a lot more independently verified research to come out before we throw out decades of work on handedness and the brain.

But it suggests an intriguing possibility – what if handedness starts to be determined before our brains are even involved in controlling our movements?

Ultrasound scans back in the 1980s provided evidence that left- or right-handedness develops in the womb from as early as the eighth week of pregnancy, and can be easily detected by the 10th week.

 

Research has also shown that from the 13th week of pregnancy, unborn children in the womb tend to preference either sucking their left or right thumb.

Because arm and hand movements are initiated by the motor cortex in our brains, scientists had always looked to asymmetric gene expression in the motor cortex and other parts of the brain to explain why this preference happens so early on.

But in the developing embryo, the motor cortex isn’t always functionally connected to the spinal cord. In fact, when the earliest indications of hand preference appear, the spinal cord hasn’t yet formed a connection with the brain.

“Human foetuses already show considerable asymmetries in arm movements before the motor cortex is functionally linked to the spinal cord, making it more likely that spinal gene expression asymmetries form the molecular basis of handedness,” the team wrote.

Because of this, the team decided to investigate whether perhaps something happening independently in the spinal cord might influence handedness.

They looked at the gene expression in the spinal cords of five human foetuses between the eighth and 12th week of pregnancy.

The researchers detected differences between the amount of genes being expressed on the right or left side of the spinal cord in the eighth week. Interestingly, this difference was seen in the segments of the spinal cord that control the movements of arms and legs.

The team also looked into what was causing the asymmetric gene activity, and showed that it was environmental factors that seemed to be controlling whether spinal cord activity was greater on the left or right side.

Environmental factors can control gene expression through something known as epigenetics – a layer that sits above our genome and determines which genes are switched on and off.

The study suggests that it’s through epigenetics that environmental factors can cause more gene activity on one side of the spinal cord compared to the other.

“Our findings suggest that molecular mechanisms for epigenetic regulation within the spinal cord constitute the starting point for handedness,” the researchers concluded.

As we mentioned above, this is a very small and early study, and it’s too soon to throw out our current assumptions about handedness just yet. But it’s definitely intriguing new evidence that scientists will need to investigate further.

With so many questions remaining about how and why people are right- or left-handed – and how this affects them later in life – the more we can learn about why we favour certain limbs, the better.

A Revolution In Genetics & Medicine: Body Cells Transfer Genetic Info Directly Into Sperm Cells


No Sex Required: Body Cells Transfer Genetic Info Directly Into Sperm Cells, Amazing Study Finds

A revolutionary new study reveals that the core tenet of classical genetics is patently false, and by implication: what we do in this life — our diet, our mindset, our chemical exposures — can directly impact the DNA and health of future generations.

A paradigm shifting new study titled, “Soma-to-Germline Transmission of RNA in Mice Xenografted with Human Tumour Cells: Possible Transport by Exosomes,” promises to overturn several core tenets of classical genetics, including collapsing the timescale necessary for the transfer of genetic information through the germline of a species (e.g. sperm) from hundreds of thousands of years to what amounts to ‘real time’ changes in biological systems.

In classical genetics, Mendelian laws specify that the inheritance of traits passed from one generation to the next can only occur through sexual reproduction as information is passed down through the chromosomes of a species’ germline cells (egg and sperm), and never through somatic (bodily) cells.  Genetic change, according to this deeply entrenched view, can take hundreds, thousands and even millions of generations to manifest.

The new study, however, has uncovered a novel mechanism through which somatic-to-germline transmission of genetic information is made possible.  Mice grafted with human melanoma tumor cells genetically manipulated to express genes for a fluorescent tracer enzyme (EGFP-encoding plasmid) were found to release information-containing molecules containing the EGFP tracer into the animals’ blood; since EGFP is a non-human and non-murine expressed tracer, there was little doubt that the observed phenomenon was real. These EGFP trackable molecules included exosomes (small nanoparticles produced by all eukaryotic cells (including plants and animals), which contain RNA and DNA molecules), which were verified to deliver RNAs to mature sperm cells (spermatozoa) and remain stored there.  The authors of the study pointed out that RNA of this kind has been found in mouse models to behave as a “transgenerational determinant of inheritable epigenetic variations and that spermatozoal RNA can carry and deliver information that cause phenotypic variations in the progeny.”

The researchers concluded that their study’s findings strongly suggest, “exosomes are the carriers of a flow of information from somatic cells to gametes,” and that their “results indicate that somatic RNA is transferred to sperm cells, which can therefore act as the final recipients of somatic cell-derived information.”

Breaking Through Weismann’s Genetic Barrier

These findings overturn the so-called Weismann barrier, a principle proposed by the German evolutionary biologist August Weismann (1834 – 1914), that states hereditary information can only move from genes to body cells, and not the other way around, which has long been considered a nail in the coffin of the Lamarkian concept that an organism can pass on characteristics it has acquired during its lifetime to its offspring.

Over the past decade, however, the seeming impenetrability of the Weismann barrier has increasingly been called into question, due to a growing body of evidence that epigenetic patterns of gene expression (e.g. histone modifications, gene silencing via methylation) can be transferred across generations without requiring changes in the primary DNA sequences of our genomes; as well as the discovery that certain viruses contain the enzyme reverse transcriptase, which is capable of inscribing RNA-based information directly into our DNA, including germline cells, as is the case for endogenous retroviruses, which are believed responsible for about 5% of the nucleotide sequences in our genome. Nonetheless, as the authors of the new study point out, until their study, “no instance of transmission of DNA- or RNA-mediated information from somatic to germ cells has been reported as yet.”

The researchers further expanded on the implications of their findings:

“Work from our and other laboratories indicates that spermatozoa act as vectors not only of their own genome, but also of foreign genetic information, based on their spontaneous ability to take up exogenous DNA and RNA molecules that are then delivered to oocytes at fertilization with the ensuing generation of phenotypically modified animals [35][37]. In cases in which this has been thoroughly investigated, the sperm-delivered sequences have been seen to remain extrachromosomal and to be sexually transmitted to the next generation in a non-Mendelian fashion [38]. The modes of genetic information delivery in this process are closely reminiscent of those operating in RNA-mediated paramutation inheritance, whereby RNA is the determinant of inheritable epigenetic variations [16][17]. In conclusion, this work reveals that a flow of information can be transferred from the soma to the germline, escaping the principle of the Weismann barrier [39] which postulates that somatically acquired genetic variations cannot be transferred to the germline.”

The implications of research on exosome-mediated information transfer are wide ranging. First, if your somatic cells, which are continually affected by your nutritional, environmental, lifestyle and even mind-body processes, can transfer genetic information through exosomes to the DNA within your germline cells, then your moment-to-moment decisions, behaviors, experiences, toxin and toxicant exposures, could theoretically affect the biological ‘destinies’ of your offspring, and their offspring, stretching on into the distant future.

Exosome research also opens up promising possibilities in the realm of nutrigenomics and ‘food as medicine.’ A recent study found common plant foods, e.g. ginger, grapefruit, grapes, produce exosomes that, following digestion, enter human blood undegraded and subsequently down-regulate inflammatory pathways in the human body in a manner confirming some of their traditional folkloric medicinal uses.  If the somatic cells within our body are capable through extrachromosomal processes of modulating fundamental genetic processes within the germline cells, or, furthermore, if foods that we eat are also capable of acting as vectors of gene-regulatory information, truly the old reductionist, mechanistic, unilinear models of genetics must be abandoned in favor of a view that accounts for the vital importance of all our decisions, nutritional factors, environmental exposures, etc., in determining the course, not only of our bodily health, but the health of countless future generations as well.

Plant-Derived Exosomes as Cross-Species Messengers and Beacons of Epigenetics


Cross-talk between plant and animal cells may be accomplished via microRNA-carrying exosomes, gene-regulating elements contained in plants which reinforce that food is information and suggests an inextricable co-evolutionary relationship between these two disparate kingdoms

Science has recently recognized that multicellular organisms use exosomes as a form of communication. Released from many different types of cells, exosomes are specialized membrane-enclosed nanoparticle-sized vesicles which are produced when budding occurs from the membrane of cellular sorting compartments (Zomer et al., 2010). Exosomes contain a host of proteins, bioactive lipids, and non-coding RNA, a type of nucleotide that that is transcribed from DNA but not translated into proteins, interrupting the central dogma of biology. Non-coding RNA consists of both microRNA (miRNA) and small RNA, both of which are intimately involved in gene expression (Zomer et al, 2010).

It has been demonstrated that the cargo harbored by exosomes can serve as an extracellular messenger to transmit information in between cells. Conventional wisdom was that cells exchange messages through the secretions of proteins such as hormones, cytokines, and neurotransmitters, which are liberated from the sending cell and bind to receptors on neighboring receiving cells to evoke physiological effects. However, with this newly discovered form of exosome-mediated communication, the cargo transported by exosomes is transferred to recipient cells (Ju et al., 2013).

Exosomes may have originally evolved in plants as a means of communication between plant cells and as a way of modulating the first-line innate immune defenses that plants deploy upon pathogen invasion (Ju et al., 2013). These exosomes liberated from digested edible plants, however, may also serve as a means through which our digestive tract communicates directly with the external environment (Ju et al., 2013). Scientists go so far as to speculate that exosomes may be a mode of cross-species communication (Ju et al., 2013). In a recent mouse experiment, exosome-like nanoparticles from grapes were used as proof-of-concept to test the validity of this revolutionary concept (Ju et al., 2013).

Grape-derived Exosomes Prevent Gut Pathologies

When administered to mice, these grape exosome-like nanoparticles (GELNs) penetrated the mucosal lining of the intestine and stimulated a biochemical pathway known as Wnt/β-catenin. which induces intestinal stem cells (Ju et al., 2013). Stem cells are multipotent progenitor cells, which means that they can differentiate into specialized cells in order to replace them as part of an internal repair system through a process called mitosis, or cell division. In effect, when one stem cell divides into two, the daughter cells can either remain a stem cell or differentiate into a cell with a specialized function. In contrast, terminally differentiated cells such as cardiac cells of the heart, blood cells of the circulatory system, and neurons of the nervous system do not normally proliferate—or replicate themselves—and also differ from stem cells in that only the latter is capable of long-term self-renewal.

In this mouse study, administration of the grape-derived exosomes protected mice from development of chemically-induced ulcerative colitis, an autoimmune disorder of the colon, due to activation of these stem cells (Ju et al., 2013). Impressively, when GELNs were given to mice twice in two milligram doses daily, “a striking improvement of the wasting disease became apparent” despite administration of the known colitis inducing agent dextran sulfate sodium (DSS) (Ju et al., 2013, p. 1354). The mice in the GELN-fed group survived nearly twice as long as those that did not receive these grape-derived exosomes (Ju et al., 2013).

GELNs also helped preserve normal histology, or microanatomy, of the intestines of mice given the toxic chemical agent (Ju et al., 2013). Not only that, but GELNs led to the expression of genes that control growth and replication of stem cells (Ju et al., 2013). The authors state, “In the DSS-induced mouse colitis model, GELNs promoted dramatic proliferation of intestinal stem cells and led to an intense acceleration of mucosal epithelium regeneration and a rapid restoration of the intestinal architecture throughout the entire length of the intestine” (Ju et al., 2013, p. 1354).

The grape-derived exosomes activated several subtypes of stem cells, many of which are involved in reparative mechanisms and intestinal homeostasis (Ju et al., 2013). Not only that, but the GELNs exhibited zero toxicity (Ju et al., 2013). These results are especially encouraging because exosome-like nanoparticles are not limited to grapes, but are present in a whole host of plants we consume and may exert additive or synergistic effects in course-correcting our gut biology (Ju et al., 2013).

Implications for Gut Disorders and Autoimmune Disease

The regenerative capacity of the intestinal epithelium, or the one cell thick lining of the gastrointestinal tract which delineates the outside world from our internal body, confers protection against insults such as food-derived antigens, toxic chemicals, commensal and pathogenic microbes, and endotoxins such as lipolysaccharide (LPS) which is a component of gram-negative bacteria swimming in our guts. This single layer of cells—designated “enterocytes” in the small intestine and “colonocytes” in the large intestine—dictates whether the contents in the tube that runs from mouth to anus are excreted or absorbed. Therefore, when compromised due to toxins, medications, stress, dysbiosis, or a nutrient-poor diet, the integrity of the gut barrier is violated, inviting development of autoimmune disease and other pathological conditions.

This so-called intestinal permeability, or leaky gut syndrome, can be corrected with the multiplication of progenitor cells residing in intestinal crypts, the cavernous dips between the villi where intestinal cells are localized. As villi are degraded due to passage of food, stem cells burrowed in the crypts migrate up the villi to replace lost epithelial cells. Therefore, stem cells constitute a repair mechanism and the defense of our body against abnormalities in intestinal integrity (Ju et al., 2013).

That these grape-derived exosome-like nanoparticles can migrate through the intestinal mucus, be incorporated into mouse stem cells, and promote their cell division, constitutes a natural means of healing not only pathologies of the intestine but autoimmune disorderswhere intestinal permeability is a prerequisite for the underlying disease process (Ju et al., 2013). The applications of exosomes to healing are immense, since dysfunctional intestinal permeability has been found to be a prerequisite for the development of every autoimmune disease in which it has been examined, including ankylosing spondylitisceliac diseaseCrohn’s diseasemultiple sclerosisrheumatoid arthritis, insulin-dependent diabetesulcerative colitis, and atopic disorders such as allergy and asthma (Fasano, 2012; Drago et al., 2006; Westall, 2007; Edwards, 2008; Yacyshyn & Meddings, 1995; Martinez-Gonzalez et al., 1994; Schmitz et al., 1999; Hijazi et al., 2004). Given their unique ability to travel in the gut, navigate through the intestinal mucus, and promote a remarkable increase in intestinal stem cells, exosomes may be an especially promising therapeutic avenue for inflammatory bowel disease (IBD) and other severe gastrointestinal epithelial injuries.

Exosomes as the Vehicle of Communication between Plants and Animals

Because exosomes are synthesized by all plants and animals, researchers hypothesize that exosomes may serve as a form of inter-species communication, enabling cross-talk between the plant and animal kingdoms. This concept is biologically plausible since billions of digested plant-derived exosome nanoparticles traverse our gut on a day to day basis, interfacing with the mucosal lining of our gastrointestinal tracts (Ju et al., 2013).

The aforementioned study was paradigm-shifting, therefore, as it provides proof-of-concept that there is a bidirectional communication network between plants and animals facilitated by exosomes (Ju et al., 2013). In essence, the plant-derived exosomes talked to the mammal-derived stem cells of the gastrointestinal tract. Previous studies have also highlighted that non-coding microRNAs (miRNAs) carried on exosomes have the potential to influence our gene expression and therefore human physiology, and that exogenous plant microRNAs derived from food are found to reside in the blood sera and tissues of animals (Zhang et al., 2012). Because these single-stranded RNAs found within foods resemble human RNAs, they are said to share molecular homology and are able to silence or activate mammalian gene expression, and thus have potential applications in a variety of disease states, aging, and development (Yu-Chen et al., 2017; Zhao et al., 2017).

Exosomes Ubiquitous in Plant Foods Exhibit Therapeutic Effects

Exosomes are not limited to grapes, and in fact have been isolated and characterized from other edible plants including carrotsgrapefruit, and ginger root (Groux & Cottrez, 2003). In one study, edible plant derived exosome-like nanoparticles (EPDENs) from these botanicals were found to escape enzymatic digestion and modulate biochemical pathways (Groux & Cottrez, 2003). For instance, exosome-like nanoparticles from the fruits activated a pathway known as Wnt/TCF4, which is instrumental in the anti-inflammatory response, whereas exosome-like nanoparticles from ginger increased interleukin (IL)-10, an anti-inflammatory signaling molecule crucial to prevention of autoimmune reactions (Groux & Cottrez, 2003).

Moreover, all of the foods tested induced translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) to the nucleus, where it presides over the expression of an array of antioxidant response element (ARE) genes (Mu et al., 2014). In other words, all foods tested promoted activity of pathways crucial to reducing inflammation (Mu et al., 2014). In another study, a microRNA derived from broccoli was found to be present in human sera and to inhibit growth of breast cancer through its effect on the gene TCF7 (Chin et al., 2016).

Furthermore, flavonoids known as berry anthocyanidins delivered via milk-derived exosomes significantly suppress both the growth and proliferation of chemotherapy-resistant ovarian cancer cells, supporting the notion that the exosomal nanoparticles on which microRNAs are carried are a highly effective way of enhancing the therapeutic efficacy of phytonutrients (Aquil et al., 2017). While berry anthocyanidins exhibit anti-cancer effects in a dose-dependent manner on their own, their bioavailability, or the proportion ingested that enters systemic circulation and elicits an active effect, is poor (Aquil et al., 2017). They also demonstrate inherent instability unless attached to exosomes (Aquil et al., 2017). Exosomes therefore may be mother nature’s delivery service or packaging mechanism for these potentially healing non-coding RNAs (Aquil et al., 2017).

In the experiment with ginger, grapefruit, and carrots, the plant-derived exosome-like nanoparticles communicated with mammalian immune cells and stem cells in the gut, facilitating “such interspecies mutualism between a plant-derived diet and the mammalian gut” (Mu et al., 2014). Importantly, the exosome-mediated effects of fruits and vegetables lend credence to recommendations that emphasize dietary diversity and eating the rainbow, as researchers state, “Ingesting EPDENs from a variety of fruits and vegetables daily would be expected to provide greater beneficial effects for maintaining gut homeostasis than ingesting EPDENs from single edible plant” (Mu et al., 2014). These food-derived exosome-like nanoparticles also support the notion that the value of fruits and vegetables extends far beyond their vitamin, mineral, and bioactive phytonutrient content and may also include their governance over genetic and epigenetic phenomena.

Exosomes Suggest Co-Evolution Between Plants and Mammals

The mechanism whereby exosomes change human physiology is that, “Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells” (Mu et al., 2014). Thus, exosomes may provide a viable explanation for the intimately woven interdependence of humans and plants, and the far-reaching therapeutic effects of eating a predominantly plant-based diet.

This research fundamentally reinforces the old adage “you are what you eat,” demonstrating the multifaceted effects that plants exert on human physiology. It moreover has implications for a co-evolutionary symbiosis between angiosperms, or seed-producing plants, and metazoa, multicellular animals which constitute the evolutionary lineage to which humans belong. The quarter million species of flowering plants that supply the dietary constituents in the modern human diet, angiosperms co-evolved with mammals for at least two hundred million years, rising to the pinnacle as two of the most dominant life forms on planet earth.

This sentiment is echoed by researchers, who state, “Certain miRNA species, such as miRNA-155, miRNA-168, and members of the miRNA-854 family may be expressed in both plants and animals, suggesting a common origin and functional selection of specific miRNAs over vast periods of evolution” (Zhao et al., 2017). In other words, both plant and animal microRNAs may have arisen from a common ancestor following the evolutionary divergence of plants and animals (Zhao et al., 2017).

Further, certain herbal constituents, such as curcumin, the component of turmeric which imparts a golden hue to curry, have been shown to restore the normal expression patterns of numerous human microRNAs that are dysregulated in multiple sclerosis (MS) and known to be involved in regulation of the immune system (Dolati et al., 2017). Therefore, not only do plants transfer microRNAs via exosomes to human cells, but they can also elicit health benefits through their effects on human microRNAs.

This elegant symmetry between the molecular machinery of plants and animals illustrates that human health is quintessentially predicated on inclusion of bioactive plant constituents—and further illuminates why the post-industrial age of irradiated, genetically modified, processed and refined foods has occurred with a concomitant explosion in chronic illness. This research flies in the face of the prevailing reductionistic philosophy that food is merely caloric content and that the body resembles a mechanistic body-as-machine, and highlights that food is a form of biologically meaningful information upon which our genetic and epigenetic machinery is contingent.

No Sex Required: Body Cells Pass Genetic Information Directly Into Sperm Cells

Could exosomes be the messengers through which plant cells and animal cells interact? It is biologically plausible, since “certain sncRNAs (as miRNAs) of plants and animals have persisted in their size, biogenesis, form, and function throughout many hundreds of millions of years of evolution as discrete information-carrying entities” (Zhao et al., 2017). Scientists further speculate that microRNA-carrying exosomes may not only be one of the health-conferring constituents of medicinal plants (Xie et al., 2016), but they also may serve as an essential supplier of gene regulatory information (Zhao et al., 2017).

In addition, novel scientific data on exosomes is overturning the conventional postulate that limits genetic change to the elongated time scale of hundreds of thousands or even millions of years. In particular, a study of xenotransplantation, where living cells from one species are grafted into a recipient of another species, shows that this time scale can be dramatically accelerated with exosomes (Cossetti et al., 2014). In the study, researchers engineered human melanoma cells to express genes for a fluorescent tracer enzyme called EGFP-encoding plasmid and transplanted the cancer cells into mice (Cossetti et al., 2014). Among the EGFP trackable molecules found to be released into the animals’ blood were exosomes (Cossetti et al., 2014). Most surprising, however, was that exosomes delivered RNAs to mature sperm cells (spermatozoa) and remained stored there (Cossetti et al., 2014).

These findings suggest that microRNA, therefore, can transmit information to future generations and alter the resultant phenotype of the progeny—by modifying gene expression in a way that changes the observable traits and disease risk of the offspring as well as its morphology, development, and physiology. This study was the first to prove RNA-mediated transfer of information from somatic (body) to germ cells (egg and sperm) (Cossetti et al., 2014), poking holes in the principle of the Weisman barrier, a previously forgone conclusion which posited that the information transmitted by egg and sperm to future generations remains independent of somatic cells and parental experience.

Thus, exosomes may be the medium through which epigenetic insults, such as chemical exposures, nutrient-poor diets, stress, smoking, and a sedentary lifestyle are conveyed to future generations—and the vehicle through which our lived experiences will persevere in our descendants and exert trans-generational effects. This confirms a long-discarded hypothesis of French naturalist Jean-Baptiste Lamarck, who proposed that the features acquired over the life of an organism are transmitted to offspring. Thus, consuming a diet rich in plant-derived microRNAs may protect your unborn child from devastating diseases. Because of microRNA-harboring exosomes, our experiences—the foods we consume, the air we breathe, the thoughts we imagine, the traumas we endure, and the toxic burdens we accumulate—may leave a lasting footprint upon our descendants and become imprinted in our progeny long after we expire.

UA researcher wins grant to study cancer and epigenetics


UA researcher Keith Maggert wants to change the way you think about epigenetics.

With a recent grant from the National Institutes of Health (NIH), he plans to further investigate a theory that has the potential to redefine the way scientists study epigenetics. The grant is a five-year Transformative Research Award totaling $1.7 million, according to UA News.

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“I hope to show that transgenerational epigenetic effects are actually caused by genome damage—it’s not epigenetic, it’s actually uncharacterized genome damage,” Maggert, an associate professor of cellular and molecular medicine and a member of the Cancer Biology Program at the UA Cancer Center, said.

What exactly are epigenetics, though?

Cells have the ability to respond to their environment, Maggert said. If a stimulus such as temperature is applied to the environment, the cell will induce itself to change, turning on a set of genes to cope with the input. These genes sometimes, though, remain turned on after the stimulus has been removed. In some cases, these genes can transcend generations, a concept known as transgenerational memory.

“There’s these ideas that this epigenetic memory can be transgenerational—that is, it can affect a generation but then the children are the ones who also share in that increased disease risk or increased susceptibility to all sorts of things,” Maggert said.

Maggert’s research challenges a fundamental belief in epigenetic study. For years, the majority of scientists have believed that an additional layer of information on top of the chromosomes directed whether the genes turned on or off, Maggert said. But in the course of his studies, Maggert realized that may not be the case. Maggert believes there is no layer on top of the DNA—instead, his research has shown that epigenetic changes in cells cause damage to the genome.

“We just thought that these areas of the genome were totally quiet or didn’t do anything interesting,” Maggert said. “What my work is showing is that when a cell is stressed in a way to induce transgenerational inheritance, those regions of the genome are also damaged.”

This is a bold step for Maggert, whose research enters uncharted territory in the study of epigenetics. Before, scientists focused their research on the idea that epigenetics had three phases: establishment, maintenance and interpretation. He argues that if researchers continue to work under this model, they will never be successful.

“This idea of establishment, maintenance and interpretation is totally wrong, and if we go into the experiments with this in mind, then we’re not even looking at the most obvious explanation,” Maggert said.

Continuing down this line of research may even have detrimental effects, according to Maggert. If scientists develop drugs that affect epigenetics at those genes, they could actually end up doing more harm than good. He said that while epigenetic drugs have experienced some positive results in the treatment of diseases such as leukemia, the majority of the results are underwhelming.

According to an article in UA News, many illnesses, including metabolic diseases such as cancer and diabetes, are thought to be caused by epigenetics. If Maggert’s research is correct and epigenetic defects do originate in the genome, then detecting epigenetic effects may become much easier.

“First of all, we need to avoid doing things that could cause more damage, but then we could also focus on what the actual contributors to those diseases are,” Maggert said.

For Maggert, the timing was right. Many scientists in the field had become dissatisfied with the ineffectiveness of the existing models, he said.

The first few times he proposed his ideas, they were largely unaccepted by the scientific community. But now, after 20 years, scientists are beginning to seriously consider his theories. Researchers are now at the point where the existing mindset is just not working, Maggert said.

The majority of NIH grants are awarded to researchers studying the traditional model of epigenetics, making Maggert an exception to the norm.

“This kind of grant is very unusual and pretty hard to get,” Maggert said. “NIH doesn’t expect there are many fields of study that are as mature as epigenetics that are going to have somebody come in and say, ‘This is very different than the way we’re thinking of it.’ ”

Maggert plans to test his ideas using experiments on fruit flies and human cells. He will spend the next five years using the grant to further his research in demonstrating his theories.

Falling for This Myth Could Give You Cancer


How much control do you really have over your own life in general, and your health in particular? These questions have puzzled many since the beginning of time. Now, the emerging science of epigenetics is offering some answers that put true control within your reach.

Falling for This Myth Could Give You Cancer

Story at-a-glance

  • Science has shattered the Central Dogma of molecular biology, proving that determinism—the belief that your genes control your health—is false. You actually have a tremendous amount of control over how your genetic traits are expressed, by changing your thoughts and altering your diet and your environment
  • In 1988, the experiments of John Cairns demonstrated even primitive organisms can evolve “consciously,” as DNA changes in response to its environment. The cell’s “consciousness” lies in its membrane, which contains receptors that pick up various environmental signals. This mechanism controls the “reading” of the genes inside the cell
  • The work of Dr. Bruce Lipton and other epigenetic researchers shows that the “environmental signals” also include thoughts and emotions—both of which have been shown to directly affect DNA expression
  • Contrary to the Newtonian belief in your body as a biological machine, epigenetic science reveals that you are an extension of your environment, which includes everything from your thoughts and belief systems, to toxic exposures and exposure to sunlight, exercise, and, of course, everything you choose to put onto and into your body. Epigenetics shatters the idea that you are a victim of your genes, and shows that you have tremendous power to shape and direct your physical health

According to some scientists, changing your health may be as “simple” as changing your thoughts and beliefs.

“Contrary to what many people are being led to believe, a lot of emphasis placed on genes determining human behavior is nothing but theory and doctrine,” writes Konstantin Erikseni . “We are free to make decisions that impact our lives and those of others. … Our beliefs can change our biology. We have the power to heal ourselves, increase our feelings of self-worth and improve our emotional state.”

Epigenetics Shatters “The Central Dogma”

Eriksen goes on to discuss something called “The Central Dogma” of molecular biology, which states that biological information is transferred sequentially and only in one direction (from DNA to RNA to proteins).

The ramification of buying into the central dogma is that it leads to belief in absolute determinism, which leaves you utterly powerless to do anything about the health of your body; it’s all driven by your genetic code, which you were born with.

However, scientists have completely shattered this dogma and proven it false. You actually have a tremendous amount of control over how your genetic traits are expressed—from how you think to what you eat and the environment you live in.

You may recall the Human Genome Projectii , which was launched in 1990 and completed in 2003. The mission was to map out all human genes and their interactions, which would than serve as the basis for curing virtually any disease. Alas, not only did they realize the human body consists of far fewer genes than previously believed, they also discovered that these genes do not operate as previously predicted.

In the featured article, Eriksen describes the experiments of John Cairns, a British molecular biologist who in 1988 produced compelling evidence that our responses to our environment determine the expression of our genes. A radical thought, for sure, but one that has been proven correct on multiple occasions since then.

Eriksen writesiii :

“Cairns took bacteria whose genes did not allow them to produce lactase, the enzyme needed to digest milk sugar, and placed them in petri dishes where the only food present was lactase. Much to his astonishment, within a few days, all of the petri dishes had been colonized by the bacteria and they were eating lactose. The bacterial DNA had changed in response to its environment. This experiment has been replicated many times and they have not found a better explanation than this obvious fact – that even primitive organisms can evolve consciously.

So, information flows in both directions, from DNA to proteins and from proteins to DNA, contradicting the “central dogma.” Genes can be activated and de-activated by signals from the environment. The consciousness of the cell is inside the cell’s membrane. Each and every cell in our bodies has a type of consciousness. Genes change their expression depending on what is happening outside our cells and even outside our bodies.”

Your Emotions Regulate Your Genetic Expression

As if genes changing expression in response to environmental factors such as nutrients wasn’t enough, other researchers have demonstrated that this “environment” that your genes respond to also includes your conscious thoughts, emotions, and unconscious beliefs. Cellular biologist Bruce Lipton, PhD., is one of the leading authorities on how emotions can regulate genetic expression, which are explained in-depth in his excellent books The Biology of Belief, and Spontaneous Evolution.

Science has indeed taken us far beyond Newtonian physics, which says you live in a mechanical universe. According to this belief, your body is just a biological machine, so by modifying the parts of the machine, you can modify your health. Also, as a biological machine, your body is thought to respond to physical “things” like the active chemicals in drugs, and by adjusting the drugs that modify your machinery, doctors can modify and control health. However, with the advent of quantum physics, scientists have realized the flaws in Newtonian physics, as quantum physics shows us that the invisible, immaterial realm is actually far more important than the material realm. In fact, your thoughts may shape your environment far more than physical matter!

According to Dr. Lipton, the true secret to life does not lie within your DNA, but rather within the mechanisms of your cell membrane.

Each cell membrane has receptors that pick up various environmental signals, and this mechanism controls the “reading” of the genes inside your cells. Your cells can choose to read or not read the genetic blueprint depending on the signals being received from the environment. So having a “cancer program” in your DNA does not automatically mean you’re destined to get cancer. Far from it. This genetic information does not ever have to be expressed…

What this all means is that you are not controlled by your genetic makeup. Instead, your genetic readout (which genes are turned “on” and which are turned “off”) is primarily determined by your thoughts, attitudes, and perceptions!

The major problem with believing the myth that your genes control your life is that you become a victim of your heredity. Since you can’t change your genes, it essentially means that your life is predetermined, and therefore you have very little control over your health. With any luck, modern medicine will find the gene responsible and be able to alter it, or devise some other form of drug to modify your body’s chemistry, but aside from that, you’re out of luck… The new science, however, reveals that your perceptions control your biology, and this places you in the driver’s seat, because if you can change your perceptions, you can shape and direct your own genetic readout.

This new science also reveals that you are in fact an extension of your environment, which includes everything from your thoughts and belief systems, to toxic exposures and exposure to sunlight, exercise, and, of course, everything you choose to put onto and into your body. As Dr. Lipton is fond of saying, the new biology moves you out of victimhood and into Mastery—mastery over your own health.

It is a supreme confirmation of my favorite saying, “You Can Take Control of Your Health.”

How Nutrition Alters Genetic Expression

Two years ago, a study performed by the Linus Pauling Institute at Oregon State University was showcased at the annual Experimental Biology convention. The study demonstrated how “histone modifications” can impact the expression of many degenerative diseases, ranging from cancer and heart disease to biopolar disorder and even aging itself. According to Rod Dashwood, a professor of environmental and molecular toxicology and head of LPI’s Cancer Chemoprotection Program, as quoted in a press releaseiv:

“We believe that many diseases that have aberrant gene expression at their root can be linked to how DNA is packaged, and the actions of enzymes such as histone deacetylases, or HDACs. As recently as 10 years ago we knew almost nothing about HDAC dysregulation in cancer or other diseases, but it’s now one of the most promising areas of health-related research.”

In a nutshell, we all have tumor suppressor genes, and these genes are capable of stopping cancer cells in their tracks. These genes are present in every cell in your body, but so are proteins called “histones.” As Dr. Jean-Pierre Issa at the M.D. Anderson Cancer Center explainsv , histones can “hug” DNA so tightly that it becomes “hidden from view for the cell.” If a tumor suppressor gene is hidden, it cannot be utilized, and in this way too much histone will “turn off” these cancer suppressors, and allow cancer cells to proliferate.

Now here’s where epigenetics comes in … certain foods, such as broccoli and other cruciferous vegetables, garlic, and onions contain substances that act as histone inhibitors, which essentially block the histone, allowing your tumor suppressor genes to activate and fight cancer. By regularly consuming these foods, you are naturally supporting your body’s ability to fight tumors.

Certain alternative oncologists also tap directly into the epigenetic mechanism, such as Dr. Nicholas Gonzalez, who uses a three-pronged approach to cancer based primarily on nutrition and detoxification, and Dr. Stanislaw Burzynski, who treats cancer with a gene-targeted approach. His treatment uses non-toxic peptides and amino acids, known as antineoplastons, which act as genetic switches that turn your tumor suppressor genes “on.”

A Healthy Lifestyle Supports Healthy Genetic Expression

So the good news is that you are in control of your genes … You can alter them on a regular basis, depending on the foods you eat, the air you breathe, and the thoughts you think. It’s your environment and lifestyle that dictates your tendency to express disease, and this new realization is set to make major waves in the future of disease prevention — including one day educating people on how to fight disease at the epigenetic level. When a disease occurs, the solution, according to epigenetic therapy, is simply to “remind” your affected cells (change its environmental instructions) of its healthy function, so they can go back to being normal cells instead of  diseased cells.

You can begin to do this on your own, long before you manifest a disease. By leading a healthy lifestyle, with high quality nutrition, exercise, limited exposure to toxins, and a positive mental attitude, you encourage your genes to express positive, disease-fighting behaviors.

This is what preventive medicine is all about. It’s not about taking any one particular nutrient as a supplement to fix one specific “part” of your biological machinery… The more people become willing to embrace this simple truth, the healthier everyone will get.

It’s also worth pointing out that epigenetic effects begin before birth.

Epigenetic research from 2009 showed that rat fetuses receiving poor nutrition in the womb become genetically primed for a nutrition-poor environment. As a result of this genetic adaptation, the rats tended to be smaller. They were also at higher risk for a host of health problems throughout their lives, such as diabetes, growth retardation, cardiovascular disease, obesity, and neurodevelopmental delays. Again, while some are tempted to blame such “predispositions” on bad genes, the KEY factor is nutrition, i.e. the cellular environment.

If you’re ready to address your dietary choices, read through my comprehensive nutrition plan, which will give you tips and tools for eating healthy, dealing with stress, and living a lifestyle that will support your epigenetic health.

You can also turn your genes off and on with your emotions too. Many, if not most people carry emotional scars; traumas that can adversely affect health. Using techniques like energy psychology, you can go in and correct the trauma and help regulate your genetic expression. My favorite technique for this is the Emotional Freedom Technique (EFT), but there are many others. Choose whichever one appeals to you, and if you don’t sense any benefits, try another, until you find what works best for you.

Please, remember that ‘You CAN Take Control of Your Health.’

Pesticides found to cause trans-generational mental disorders and obesity … Harmful traits are inherited for THREE generations


From an early age, we are inundated with the helpless belief that our genes are set in stone – a fixed code – a destiny that we cannot control. The study of epigenetics debunks this mythical mindset, revealing how external factors change our gene expression throughout our lifetime.

Pesticides

The field of epigenetics examines more closely the relationship between our genes and our environment, and how man-made chemicals influence cellular processes, ultimately changing the expression of our genes. Some chemicals may inactivate genes that are normally active. Other chemicals may activate genes that would typically lay dormant. These chemically-induced changes in gene behavior can initiate health problems, especially in the womb, during childhood development and puberty.

Pesticides of the past alter gene expression from one generation to the next

Now the field of epigenetics is discovering a disturbing new trend. Man-made chemical pesticides (such as the persistent pollutant DDT), are altering gene expression through multiple generations, destroying the inherent health of entire bloodlines. This means pesticides are silently changing the expression of genes, generation after generation, and the damage is being carried on, restricting future generations’ ability to live harmoniously with their environment. The pesticides are interfering with people’s natural relationship with their bodies and the world around them. The damage of past pesticides (such as DDT) is being carried out and expressed in the genes of new generations of people who may not even consider the banned pollutant to be a threat.

When a parent’s gene expression has been manipulated by pesticides, those changes can be inherited by the next generation. The pesticide poisons of the past century are literally rewriting the gene expression of future generations, victimizing the next of kin from the start. The trans-generational damage has now been recognized across three generations. The damage can be observed in childhood cancer cases that are linked directly back to parental pesticide exposure. Lymphoma risk increases two-fold for children whose parents were pesticide applicators. Pesticide applicators who applied pesticides without proper protection give birth to children who are at greater risk of developing childhood cancers.

In 2012, biologists experimented with pesticides on mice. The genetic changes that occurred were passed down through three generations, eliciting mental disorders and obesity in the offspring. Through the same genetic mechanisms, these effects are observed in humans.

2,4-D herbicide initiating changes in cell cycle control, human stress response, and DNA repair

The commonly-used herbicide 2,4-D damages cellular DNA. Medical researchers discovered the herbicide’s genotoxic effects in 2004, showing how it causes chromosomes to break apart in human blood cells. In 2005, “environmentally realistic levels,” of 2,4-D were found to change gene expression for important functions of the body, including immunology, stress response, cell cycle control and DNA repair.

Egyptian geneticists found that the bone marrow cells of mice were being deconstructed in the presence of 2,4-D, as the chromosomes broke apart.

University of Minnesota researchers couldn’t deny the fact that 2,4-D was causing severe changes in men who worked with the herbicide and had high levels of the chemical metabolites in their urine. The researchers found that the men were silently enduring chromosome aberrations and hormonal fluctuations that would ultimately affect their mental state, metabolism, homeostasis and sex drive.

Glyphosate is a catalyst for disease processes

Glyphosate herbicide alters genetic expression of humans by destroying the microbiome of the exposed persons. MIT researchers documented the role of glyphosate in damaging the gastrointestinal tract of humans, and depleting good species of bacteria that the body needs to detoxify and stimulate immune response. Glyphosate is a catalyst for disease processes, and is behind the widespread epidemics of heart disease, diabetes, obesity, autism, infertility and cancer that are ravaging people stuck on the Western diet of glyphosate-infested food products.

The more we eliminate pesticides from our lives, the quicker we allow our cellular processes to normalize and self regulate, allowing our genes to express health and vitality.

Learn more: http://www.naturalnews.com/053340_pesticides_genetic_expression_transgenerational_effects.html#ixzz43nuYg3NQ

Epigenetics 101: a beginner’s guide to explaining everything


The word ‘epigenetics’ is everywhere these days, from academic journals and popular science articles to ads touting miracle cures. But what is epigenetics, and why is it so important?

DNA methyltransferase 1, from www.enzymlogic.com.
DNA methyltransferase 1, from http://www.enzymlogic.com.

Epigenetics is one of the hottest fields in the life sciences. It’s a phenomenon with wide-ranging, powerful effects on many aspects of biology, and enormous potential in human medicine. As such, its ability to fill in some of the gaps in our scientific knowledge is mentioned everywhere from academic journals to the mainstream media to some of the less scientifically rigorous corners of the Internet.

  • Wondering why identical twins aren’t actually, well, identical? Epigenetics!
  • Want to blame your parents for something that doesn’t seem to be genetic? Epigenetics!
  • Got a weird result from an experiment that doesn’t seem to make sense? Epigenetics!
  • Want to think yourself healthy? That’s not epigenetics! (Sorry ‘bout that).

But what exactly is epigenetics – and does the reality live up to the hype?

The basics

The incidence of the word ‘epigenetics’ in published books, 1800-2008. Bringing this graph up to date and including other publication types would send that line right off the top of your screen.

Epigenetics is essentially additional information layered on top of the sequence of letters (strings of molecules called A, C, G, and T) that makes up DNA.

If you consider a DNA sequence as the text of an instruction manual that explains how to make a human body, epigenetics is as if someone’s taken a pack of highlighters and used different colours to mark up different parts of the text in different ways. For example, someone might use a pink highlighter to mark parts of the text that need to be read the most carefully, and a blue highlighter to mark parts that aren’t as important.

There are different types of epigenetic marks, and each one tells the proteins in the cell to process those parts of the DNA in certain ways. For example, DNA can be tagged with tiny molecules called methyl groups that stick to some of its C letters. Other tags can be added to proteins called histones that are closely associated with DNA. There are proteins that specifically seek out and bind to these methylated areas, and shut it down so that the genes in that region are inactivated in that cell. So methylation is like a blue highlighter telling the cell “you don’t need to know about this section right now.”

The DNA double helix wrapped around four histone proteins, in a structure called a nucleosome.
The DNA double helix wrapped around four histone proteins, in a structure called a nucleosome. By Richard Wheeler (Zephyris) [CC-BY-SA-3.0]]/Wikimedia Commons

Methyl groups and other small molecular tags can attach to different locations on the histone proteins, each one having a different effect. Some tags in some locations loosen the attachment between the DNA and the histone, making the DNA more accessible to the proteins that are responsible for activating the genes in that region; this is like a pink highlighter telling the cell “hey, this part’s important”. Other tags in other locations do the opposite, or attract other proteins with other specific functions. There are epigenetic marks that cluster around the start points of genes; there are marks that cover long stretches of DNA, and others that affect much shorter regions; there are even epigenetic modifications of RNA, a whole new field that I’m simultaneously fascinated by and trying to ignore because it’s bound to create a lot of extra work for me in both the project manager and the grant writing parts of my role. There are no doubt many other marks we don’t even know about yet.

Even though every cell in your body starts off with the same DNA sequence, give or take a couple of letters here and there, the text has different patterns of highlighting in different types of cell – a liver cell doesn’t need to follow the same parts of the instruction manual as a brain cell. But the really interesting thing about epigenetics is that the marks aren’t fixed in the same way the DNA sequence is: some of them can change throughout your lifetime, and in response to outside influences. Some can even be inherited, just like some highlighting still shows up when text is photocopied.

Epigenetics and our experiences

Any outside stimulus that can be detected by the body has the potential to cause epigenetic modifications. It’s not yet clear exactly which exposures affect which epigenetic marks, nor what the mechanisms and downstream effects are, but there are a number of quite well characterized examples, from chemicals to lifestyle factors to lived experiences:

  • Bisphenol A (BPA) is an additive in some plastics that has been linked to cancer and other diseases and has already been removed from consumer products in some countries. BPA seems to exert its effects through a number of mechanisms, including epigenetic modification.
  • The beneficial effects of exercise have been known for generations, but the mechanisms are still surprisingly hazy. However, there’s mounting evidence that changes to the pattern of epigenetic marks in muscle and fatty tissue are involved.
  • Childhood abuse and other forms of early trauma also seem to affect DNA methylation patterns, which may help to explain the poor health that many victims of such abuse face throughout adulthood.

Epigenetic inheritance

This is an area where the hype has advanced faster and further than the actual science. There have been some fascinating early studies on the inheritance of epigenetic marks, but most of the strongest evidence so far comes from research done on mice. There have been hints that some of these findings also apply to human inheritance, but we’ve only just started to untangle this phenomenon.

  • We’ve known for some time that certain environmental factors experienced by adult mice can be passed on to their offspring via epigenetic mechanisms. The best example is a gene called agouti, which is methylated in normal brown mice. However, mice with an unmethylated agouti gene are yellow and obese, despite being genetically essentially identical to their skinny brown relatives. Altering the pregnant mother’s diet can modify the ratio of brown to yellow offspring: folic acid results in more brown pups, while BPA results in more yellow pups.
  • Research on the epigenetic inheritance of addictive behavior is less advanced, but does look quite promising. Studies in rats recently demonstrated that exposure to THC (the active compound in cannabis) during adolescence can prime future offspring to display signs of predisposition to heroin addiction.
  • Studies of humans whose ancestors survived through periods of starvation in Sweden and the Netherlands suggest that the effects of famine on epigenetics and health can pass through at least three generations. Nutrient deprivation in a recent ancestor seems to prime the body for diabetes and cardiovascular problems, a response that may have evolved to mitigate the effects of any future famines in the same geographic area.

“More research is needed”

Epigenetics research continues apace in labs investigating a dazzling variety of topics. One interesting direction is the application of high-throughput sequencing technologies to the characterization of hundreds of ‘epigenomes’ (epigenetic marks across the entire genome). I manage a project that’s part of the International Human Epigenomics Consortium (IHEC), and am also a member of a couple of the consortium’s working groups, so I see for myself every day how fast this field is progressing. The goal of IHEC is to generate at least 1,000 publicly available ‘reference’ epigenomes (patterns of DNA methylation, six histone modifications, and gene activation) from various normal and diseased cell types. These references will serve as a baseline in other studies, in the same way that the original human genome project sequenced a reference genome to which scientists can now compare their own results to identify changes associated with specific diseases.

This is a field that’s guaranteed to keep generating headlines and catching the public’s interest. The apparent ability of epigenetics to fill some pretty diverse gaps in our understanding of human health and disease, and to provide scientific mechanisms for so many of our lived experiences, makes it very compelling, but we do need to be careful not to over-interpret the evidence we’ve collected so far. And we certainly need to be highly sceptical of anyone claiming that we can consciously change our epigenomes in specific ways through the power of thought.

Now that I’ve piqued your interest in this fascinating field (and maybe that of your unborn children. Epigenetics!), in my next piece I’ll explore the role of epigenetic changes in the onset of cancer and other diseases, and what this means for the development of new treatment options.

Epigenetic Cancer Therapy Clears Phase I .


A new therapy designed to treat cancer by regulating gene expression has helped a handful of patients with blood malignancies in a preliminary clinical trial, according to pharmaceutical company OncoEthix. Today (April 7) at the American Association for Cancer Research (AACR) annual meeting in San Diego, California, the Lausanne, Switzerland-based firm presented unpublished data from a Phase I clinical trial of the drug, “OTX015,” a small-molecule inhibitor of the BET-bromodomain proteins BRD2, BRD3, and BRD4, which help to regulate gene expression. Seven of 38 patients for whom sufficient OTX015 trial data were available seemed to have benefited from the drug, OncoEthixannounced. Four of those seven patients have acute myelogenous leukemia (AML), while others enrolled in the trial have other hematological malignancies, including diffuse large B-cell lymphoma and multiple myeloma. One of the four AML patients experienced a complete response—meaning that his or her bone marrow and blood returned to normal—which is ongoing, the company said. The other three are still being treated with OTX015.

“To my knowledge, this is the first reported successful Phase I clinical trial with BET inhibitors targeting AML,” said Lin-Feng Chen, an associate professor of biochemistry at the University of Illinois, who was not involved in the work. “Although it is not completed yet, the results so far are very encouraging.”

“Everybody’s excited about bromodomain inhibition,” OncoEthix Chief Scientific Officer Esteban Cvitkovic said during an AACR press conference.

Pharma giant GlaxoSmithKline (GSK) and the Cambridge, Massacusetts-based firm Constellation Pharmaceuticals are among other drug companies with BET-bromodomain inhibitors in their pipelines. GSK’s I-BET762 is currently in a Phase I clinical trial.

Cvitkovic said that OTX015 has not yet shown cumulative toxicity. The firm is still working to determine the optimal dosing and schedule for the drug, administered as a monotherapy, he added.

“This trial . . . provides a great example for targeting epigenetic regulators for cancer therapy,” Chen wrote in an e-mail to The Scientist, adding that “the promising results from this trial will allow more clinical trials in the near future with BET inhibitors targeting other types of leukemia or cancers.”

Chen added that the study also paves the way for other investigational epigenetic cancer therapies. Targeting epigenetic machinery “provides a promising approach for treating drug resistance and clinical relapse and offers new option for combination therapy,” he said. “The major challenge is how to predict the treatment outcome. There is no clear biomarker to determine which patient would respond and benefit most from the therapy.”

‘Memories’ pass between generations


Generations of a family

Behaviour can be affected by events in previous generations which have been passed on through a form of genetic memory, animal studies suggest.

Experiments showed that a traumatic event could affect the DNA in sperm and alter the brains and behaviour of subsequent generations.

A Nature Neuroscience study shows mice trained to avoid a smell passed their aversion on to their “grandchildren”.

Experts said the results were important for phobia and anxiety research.

The animals were trained to fear a smell similar to cherry blossom.

The team at the Emory University School of Medicine, in the US, then looked at what was happening inside the sperm.

They showed a section of DNA responsible for sensitivity to the cherry blossom scent was made more active in the mice’s sperm.

Both the mice’s offspring, and their offspring, were “extremely sensitive” to cherry blossom and would avoid the scent, despite never having experiencing it in their lives.

Changes in brain structure were also found.

“The experiences of a parent, even before conceiving, markedly influence both structure and function in the nervous system of subsequent generations,” the report concluded.

Family affair

The findings provide evidence of “transgenerational epigenetic inheritance” – that the environment can affect an individual’s genetics, which can in turn be passed on.

One of the researchers Dr Brian Dias told the BBC: “This might be one mechanism that descendants show imprints of their ancestor.

“There is absolutely no doubt that what happens to the sperm and egg will affect subsequent generations.”

Prof Marcus Pembrey, from University College London, said the findings were “highly relevant to phobias, anxiety and post-traumatic stress disorders” and provided “compelling evidence” that a form of memory could be passed between generations.

He commented: “It is high time public health researchers took human transgenerational responses seriously.

“I suspect we will not understand the rise in neuropsychiatric disorders or obesity, diabetes and metabolic disruptions generally without taking a multigenerational approach.”

In the smell-aversion study, is it thought that either some of the odour ends up in the bloodstream which affected sperm production or that a signal from the brain was sent to the sperm to alter DNA.