We may be on the verge of collectively knowing just how much we don't know. Biology stands on the brink of a shift in the understanding of inheritance. The discovery of epigenetics -- hidden influences upon the genes -- could affect every aspect of our lives.
The picture of a genetic makeup that fluctuates by the hour and minutes seems at odds with the public perception: That genes determine everything from our physical characteristics all the way to our behaviour. Many scientists seem to think that our geners form an immutable blueprint that our cells must forever follow. British research scientists and Oxford Susan Greenfield says "the reductionist genetic train of thought fuels the currently highly fashionable concept of a gene for this or that"
Niles edridge in his book why we do it, says "genes have been the dominant metaphor underlying all manner of human behaviour, from the most basic to animalistic, like sex, up to and including such esoterica as the practise of religion, the enjoyment of music, and the codification of laws and moral strictures... The media are besotted with genes... genes have for over half a century easily eclipsed the outside natural world as the primary driving force of evolution in the minds of evolutionary biologists."
The tools of our consciousness, including our beliefs, thoughts, intentions and actions, often seem to correlate much more strongly with our health, longevity, and happiness than our genes do. Larry dossey, MD, observes in his much cited publication health perceptions and survival: do global evaluations of health status really predict mortality? "Several studies show that what one thinks about ones health is one of the most accurate predictors of longevity ever discovered". Studies show that a committed spiritual practice involving mindfulness can add many years to our lives, regardless of our genetic mix.
As we think our thoughts and feel our feeling our bodies change and respond with a complex array of shifts, each thought releases a particular mixture of biochemicals in our organs and triggers genetic changes in our cells. Psychologist Ernest Rossi explores in his text the psychobiology of gene expression "how our subjective states of mind, consciously motivated behaviour, and our perception of free will can modulate gene expression to optimize health" Nobel prize winner Eric Kandell MD believes that in future treatments "social influences will be biologically incorporated in the altered expressions of specific genes in specific nerve cells of specific areas of the brain"
Brain researchers Kemperman and Gage envision a future in which the regeneration of damaged neural networks is a cornerstone of medical treatment, and doctors prescriptions include "modulations of environmental or cognitive stimuli", and "alterations of physical activity", in other words, doctors in the future will prescribe, instead of (or in addition to) a drug, a particular therapeutic belief or thought, a positive feeling, an affirmative social activity.
In Laymans Terms
At the heart of this new field is a simple but contentious idea -- that genes have a memory. This is not the same as 'water memory' or homeopathy; this has empirical scientific foundations. Suppose that the lives of your grandparents -- the air they breathed, the food they ate, even the things they saw -- can directly affect you, decades later, despite your never experiencing these things yourself. And that what you do in your lifetime could in turn affect your grandchildren.
The conventional view is that DNA carries all our heritable information and that nothing an individual does in their lifetime will be biologically passed to their children. To many scientists, epigenetics amounts to a heresy, calling into question the accepted view of the DNA sequence -- a cornerstone on which modern biology sits.
Epigenetics adds a whole new layer to genes beyond the DNA. It proposes a control system of 'switches' that turn genes on or off -- and suggests that things people experience, like nutrition and stress, can control these switches and cause heritable effects in humans.
In a remote town in northern Sweden there is evidence for this radical idea. Lying in Överkalix's parish registries of births and deaths and its detailed harvest records is a secret that confounds traditional scientific thinking. Marcus Pembrey, a Professor of Clinical Genetics at the Institute of Child Health in London, in collaboration with Swedish researcher Lars Olov Bygren, has found evidence in these records of an environmental effect being passed down the generations. They have shown that a famine at critical times in the lives of the grandparents can affect the life expectancy of the grandchildren. This is the first evidence that an environmental effect can be inherited in humans.
In other independent groups around the world, the first hints that there is more to inheritance than just the genes are coming to light. The mechanism by which this extraordinary discovery can be explained is starting to be revealed.
Professor Wolf Reik, at the Babraham Institute in Cambridge, has spent years studying this hidden ghost world. He has found that merely manipulating mice embryos is enough to set off 'switches' that turn genes on or off.
For mothers like Stephanie Mullins, who had her first child by in vitro fertilisation, this has profound implications. It means it is possible that the IVF procedure caused her son Ciaran to be born with Beckwith-Wiedemann Syndrome -- a rare disorder linked to abnormal gene expression. It has been shown that babies conceived by IVF have a three- to four-fold increased chance of developing this condition.
And Reik's work has gone further, showing that these switches themselves can be inherited. This means that a 'memory' of an event could be passed through generations. A simple environmental effect could switch genes on or off -- and this change could be inherited.
His research has demonstrated that genes and the environment are not mutually exclusive but are inextricably intertwined, one affecting the other.
The idea that inheritance is not just about which genes you inherit but whether these are switched on or off is a whole new frontier in biology. It raises questions with huge implications, and means the search will be on to find what sort of environmental effects can affect these switches.
After the tragic events of September 11th 2001, Rachel Yehuda, a psychologist at the Mount Sinai School of Medicine in New York, studied the effects of stress on a group of women who were inside or near the World Trade Center and were pregnant at the time. Produced in conjunction with Jonathan Seckl, an Edinburgh doctor, her results suggest that stress effects can pass down generations. Meanwhile research at Washington State University points to toxic effects -- like exposure to fungicides or pesticides -- causing biological changes in rats that persist for at least four generations.
This work is at the forefront of a paradigm shift in scientific thinking. It will change the way the causes of disease are viewed, as well as the importance of lifestyles and family relationships. What people do no longer just affects themselves, but can determine the health of their children and grandchildren in decades to come. "We are," as Marcus Pembrey says, "all guardians of our genome."
The mechanics of epigenetics
For the materialistically predisposed, adding small methyl groups to specific points of DNA is one of the main ways of turning a gene off. This short video and news report gives you a Laymans view understanding.
Due to the limited data available in the gene structure epigenetic changes were needed for things such as plasmodium falciparum genes. Epigenetic changes are more flexible than genetic changes, and permit rapid yet reversible adaptation, so determining which proteins can be turned off, via release of the usual hormones/endorphins/neurochemicals that relate to particular states of mind, is very important.
Epigenetic changes determine which proteins are transcribed. So far theres three systems which intertwine with each other to silence genes: histone modifications (histone proteins that are the primary components of chromatin responsible for forming DNA that makes up chromosomes), RNA-associated silencing and DNA methylation.
5-methylcytosine is a is a methylated form of the DNA base cytosine that is involved in the regulation of gene transcription, old perspectives on it's role in this (that did not consider biofeedback and psychosomatic cause of the chemicals in question at the time) while still true have been shown to not be holistic enough; it's now known to be a main epigenetic mechanism, with many 5MC patterns being inherited epigenetically.
Epigenetic changes are an ideal target for disease control, because they are natyurally reversable, whereas sequence mutations in DNA are not. Which would shut a lot of the anti-genetic modification people up. But also likely just move the issue they have to scrutinising epigenetics; unless they actually understand the reversible ramifications it has that have before been a matter of contention.
DNA Is Not Destiny (source)
"The new science of epigenetics rewrites the rules of disease, heredity, and identity. [.....]
It was a little eerie and a little scary to see how something as subtle as a nutritional change in the pregnant mother rat could have such a dramatic impact on the gene expression of the baby," Jirtle says. "The results showed how important epigenetic changes could be."
Jirtle continues "The tip of the iceberg is genomics.... The bottom of the iceberg is epigenetics"
Dr Moshe Syf from McGill university in Montreal has studied the relationships between rats and their offspring. Some of the mother rats groomed and nurtured their young, and some hardly did at all. Rats that had been groomed as infants showed marked behavioural changes as adults, they were "Less fearful and better adjusted than the offspring of the neglectful mothers" (Epigenetics, The Economist*) They then acted in similar nurturing ways towards their own offspring, producing the same epigenetic behavioural results in the next generation. This shows that epigenetic changes, once started in one generation, can be passed on to the following generations without changes in the gene themselves.
There were numerous chemical changes detected in the rats brains and major differences had developed between the nurtured group and the neglected group, especially in the area of the hippocampus involved in stress. A gene that dampens our response to stress had a greater degree of expression in the well nurtured rats. The brains of the nurtured rats also showed higher levels of a chemical (acetyl groups) that facilitates gene expression by binding the protein sheath around the gene, making it easier for the gene to express. They also had higher levels of an enzyme that adds acetyl groups to the protein sheath.
In the non nurtured rats the changes were quite different, they were anxious and fearful. The same gene repressing substance that Randy Jirtle found in her work (that I cited above), the methyl groups, were much more prevalent in the hippocampi. It bonded to the DNA and inhibited the expression of the gene involved in dampening stress. To test the hypothesis that these two substances were causing epigenetic changes in the Rats they injected the fearful rats with a substance that raised the number of acetyls in the hippocampus. Sure enough, the behaviour of the rats changed and they became less fearful and better adjusted.
Determining Nature vs. Nurture
Molecular evidence is finally emerging to inform the long-standing debate
Psychologists, psychiatrists and neuroscientists have jousted for years over how much of our behavior is driven by our genes versus the environments in which we grow up and live. Arguments have persisted because there has been little hard evidence to answer basic questions: How exactly do genes and environment interact to determine whether someone will become depressed, say, or schizophrenic? And can environmental interventions such as drugs or psychotherapy really alleviate disorders that are largely determined by genes?
The article goes on to note that depressed and anti social behaviour in mice is accompanied by methyl groups sticking to genes, and also extends this research to humans, as the brains of schizophrenics also show changes in the methylation of genes, or acetylization of their protein sheaths.
Experiments have shown a striking link between our state of mind, such as childhood stress, and later disease. ACE (adverse child experiences) conducted detailed social, psychological and medial examinations of some 17,000 people over a five year period. The study showed a strong inverse link between emotional wellbeing, health and longevity on the one hand, and early life stress on the other. People in a dysfunctional family were five times more likely to be depressed, three times more likely to smoke, thirty times more likely to commit suicide, and ailments were much more common in the dysfunctional families, increased rates of obesity, heart disease, lung disease, diabetes, bone fractures, hypertension, and hepatitis. The genetic link between nurturing and gene expression in children is also now being traced; "One recent study suggests that children with a certain version of a gene that produces an enzyme known as MAO-A (which metabolizes neurotransmitters such as serotonin and dopamine) are significantly more likely to become violent—but only if they were mistreated as children. In this way, an aspect of human behavior might be a bit like the body of the Bicyclus butterfly, driven to one form or another by genes that switch in response to environmental cues, one genotype yielding two different phenotypes for two different environments." (why we have misunderstood the nature nurture debate - Professor Gary Marcus)
And there are many more examples of our beliefs causing epigenetic changes, the most researched is how our perceptions effect disease progression. Gail Ironson, MD, has shown that there were two factors that are interesting predictors of how fast HIV progressed in the research subjects. The first was the view of the nature of god. Some believed in a punishing god, while other believed in a benevolent god. She observes that, “People who view god as judgemental god have a CD4 (T-helper) cell decline more than twice the rate of those who don’t see god as judgemental, and their viral load increases more than three times faster. For example a precise statement affirmed by these patients is ‘god will judge me harshly one day’ This one item is related to an increased likelihood that patient will develop and opportunistic infection or die. These beliefs predict disease progression even more strongly than depression” (From: View of God is associated with disease progression in HIV. Paper presented at the annual meeting of the Society of Behavioral Medicine, March 22–25, 2006, San Francisco, California. Abstract published in Annals of Behavioural Medicine 2006)
“Spirituality may be viewed as another type of coping. Men and women with HIV studied during the HAART era who endorsed more spirituality after their HIV diagnosis had a slower decline in CD4+ cell counts and better control of VL over 4 years (18). Fitzpatrick et al. (19) followed 901 HIV infected persons for 1 year and found that participation in spiritual activities (e.g., prayer, meditation, affirmations, visualizations) predicted reduced risk of dying, but only in those not on HAART. Another HAART era study found significantly lower mortality over 3 to 5 years for those with HIV who had a spiritual transformation (20). Furthermore, the spiritual belief that "God is merciful" was protective of health over time, whereas the belief that "God is judgmental and punishing and is going to judge me harshly some day" was associated with a faster deterioration of CD4+ cells and poorer control of the HIV virus (21). Thus, view of God may be either helpful or harmful, depending on the nature of that belief.”
Rethinking 'the selfish gene' as more a cultural icon
"genes have been the dominant metaphor underlying all manner of human behaviour, from the most basic to animalistic, like sex, up to and including such esoterica as the practise of religion, the enjoyment of music, and the codification of laws and moral strictures... The media are besotted with genes... genes have for over half a century easily eclipsed the outside natural world as the primary driving force of evolution in the minds of evolutionary biologists." (Dawson Church, the genie in your genes)
To fully accept the arguments of Richard Dawkins (author of The Selfish Gene) and his acolytes, one would be forced to conclude that "we do it" solely because our genes are telling us to reproduce more genes; but genes don't drive evolution, argues Eldredge (curator, American Museum of Natural History), especially in social creatures such as humans. In this popular science work, he discusses a "human triangle" of sexual, reproductive, and economic behavior that has increasingly been guided by culture over the past two-and-a-half million years. Furthermore, Eldredge says, Dawkins' gene-centric view "has profoundly bad implications for social theory and its political implementation."
Unexamined beliefs in this or that gene causing this or that condition are part of the foundation of many scientific disciplines. Such assumptions can be found in various publications, like this one aired on NPS; "Scientists today announced that they have found a gene for dislexia. Its a gene on choromozone six called DCDC2", the new york times picked up on this and ran a story entitled "Findings support that dislexia disorder is genetic" Other media picked up the story, and the legend of the primacy of DNA was reinforced.
The main issue, in the case of Dawkins selfish gene material and related theories, is that it locates the ultimate power over our health in the untouchable realm of molecular structure, rather than in our own conscious actions and descisions.
Dorothy Nelkin in her much cited book entitled "The DNA mystique: The Gene as a Cultural Icon" sums up the point by stating "In a diverse array of popular sources, the gene has become a supergene, an almost supernatural entity that has the power to define identity, determine human affairs, dictate human relationships, and explain social problems. In this construct, human beings in all their complexity are seen as products of a molecular text...the secular equivalent of a soul—the immortal site of the true self and determiner of fate."
Swaying the skeptics
Many people have come up with ways to test epigenetic ideas, and the general trend is supportive. Some of the strongest evidence comes from the 9/11 attacks effects on people subsequently suffering PTSD and how this has made similar PTSD symptoms more likely in their offspring (Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy - ref2 - ref3). Some studies done on hunger and lack of food during historical food shortages in war times can still be evident in offspring a hundred years later in subsequent generations first became apparent in Sweden after a world war.
The remote, snow-swept expanses of northern Sweden are an unlikely place to begin a story about cutting-edge genetic science. The kingdom's northernmost county, Norrbotten, is nearly free of human life; an average of just six people live in each square mile. And yet this tiny population can reveal a lot about how genes work in our everyday lives. In the 1980s, Dr. Lars Olov Bygren, a preventive-health specialist who is now at the prestigious Karolinska Institute in Stockholm, began to wonder what long-term effects the feast and famine years might have had on children growing up in Norrbotten in the 19th century — and not just on them but on their kids and grandkids as well. So he drew a random sample of 99 individuals born in the Overkalix parish of Norrbotten in 1905 and used historical records to trace their parents and grandparents back to birth. By analyzing meticulous agricultural records, Bygren and two colleagues determined how much food had been available to the parents and grandparents when they were young.
Around the time he started collecting the data, Bygren had become fascinated with research showing that conditions in the womb could affect your health not only when you were a fetus but well into adulthood. In 1986, for example, the Lancet published the first of two groundbreaking papers showing that if a pregnant woman ate poorly, her child would be at significantly higher than average risk for cardiovascular disease as an adult. Bygren wondered whether that effect could start even before pregnancy: Could parents' experiences early in their lives somehow change the traits they passed to their offspring?
It was a heretical idea. After all, we have had a long-standing deal with biology: whatever choices we make during our lives might ruin our short-term memory or make us fat or hasten death, but they won't change our genes — our actual DNA. Which meant that when we had kids of our own, the genetic slate would be wiped clean.
What's more, any such effects of nurture (environment) on a species' nature (genes) were not supposed to happen so quickly. Charles Darwin, whose On the Origin of Species celebrated its 150th anniversary in November, taught us that evolutionary changes take place over many generations and through millions of years of natural selection. But Bygren and other scientists have now amassed historical evidence suggesting that powerful environmental conditions (near death from starvation, for instance) can somehow leave an imprint on the genetic material in eggs and sperm. These genetic imprints can short-circuit evolution and pass along new traits in a single generation.
For instance, Bygren's research showed that in Overkalix, boys who enjoyed those rare overabundant winters — kids who went from normal eating to gluttony in a single season — produced sons and grandsons who lived shorter lives. Far shorter: in the first paper Bygren wrote about Norrbotten, which was published in 2001 in the Dutch journal Acta Biotheoretica, he showed that the grandsons of Overkalix boys who had overeaten died an average of six years earlier than the grandsons of those who had endured a poor harvest. Once Bygren and his team controlled for certain socioeconomic variations, the difference in longevity jumped to an astonishing 32 years. Later papers using different Norrbotten cohorts also found significant drops in life span and discovered that they applied along the female line as well, meaning that the daughters and granddaughters of girls who had gone from normal to gluttonous diets also lived shorter lives. To put it simply, the data suggested that a single winter of overeating as a youngster could initiate a biological chain of events that would lead one's grandchildren to die decades earlier than their peers did. How could this be possible? What does it all mean practically?
Meet the Epigenome
The answer lies beyond both nature and nurture. Bygren's data — along with those of many other scientists working separately over the past 20 years — have given birth to the new science of epigenetics. At its most basic, epigenetics is the study of changes in gene activity that do not involve alterations to the genetic code but still get passed down to at least one successive generation. These patterns of gene expression are governed by the cellular material — the epigenome — that sits on top of the genome, just outside it. It is these epigenetic "marks" that tell your genes to switch on or off, to speak loudly or whisper. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next.
Epigenetics brings both good news and bad. Bad news first: there's evidence that lifestyle choices like smoking and eating too much can change the epigenetic marks atop your DNA in ways that cause the genes for obesity to express themselves too strongly and the genes for longevity to express themselves too weakly. We all know that you can truncate your own life if you smoke or overeat, but it's becoming clear that those same bad behaviors can also predispose your kids — before they are even conceived — to disease and early death.
The good news: scientists are learning to manipulate epigenetic marks in the lab, which means they are developing drugs that treat illness simply by silencing bad genes and jump-starting good ones. In 2004 the Food and Drug Administration (FDA) approved an epigenetic drug for the first time. Azacitidine is used to treat patients with myelodysplastic syndromes (usually abbreviated, a bit oddly, to MDS), a group of rare and deadly blood malignancies. The drug uses epigenetic marks to dial down genes in blood precursor cells that have become overexpressed. According to Celgene Corp. — the Summit, N.J., company that makes azacitidine — people given a diagnosis of serious MDS live a median of two years on azacitidine; those taking conventional blood medications live just 15 months.
Since 2004, the FDA has approved three other epigenetic drugs that are thought to work at least in part by stimulating tumor-suppressor genes that disease has silenced. The great hope for ongoing epigenetic research is that with the flick of a biochemical switch, we could tell genes that play a role in many diseases — including cancer, schizophrenia, autism, Alzheimer's, diabetes and many others — to lie dormant. We could, at long last, have a trump card to play against Darwin.
The funny thing is, scientists have known about epigenetic marks since at least the 1970s. But until the late '90s, epigenetic phenomena were regarded as a sideshow to the main event, DNA. To be sure, epigenetic marks were always understood to be important: after all, a cell in your brain and a cell in your kidney contain the exact same DNA, and scientists have long known that nascent cells can differentiate only when crucial epigenetic processes turn on or turn off the right genes in utero.
More recently, however, researchers have begun to realize that epigenetics could also help explain certain scientific mysteries that traditional genetics never could: for instance, why one member of a pair of identical twins can develop bipolar disorder or asthma even though the other is fine. Or why autism strikes boys four times as often as girls. Or why extreme changes in diet over a short period in Norrbotten could lead to extreme changes in longevity. In these cases, the genes may be the same, but their patterns of expression have clearly been tweaked.
Biologists offer this analogy as an explanation: if the genome is the hardware, then the epigenome is the software. "I can load Windows, if I want, on my Mac," says Joseph Ecker, a Salk Institute biologist and leading epigenetic scientist. "You're going to have the same chip in there, the same genome, but different software. And the outcome is a different cell type."As Terence Mckenna first said "culture is your chosen operating system, not a reality"
Other recent studies have also shown the power of environment over gene expression. For instance, fruit flies exposed to a drug called geldanamycin show unusual outgrowths on their eyes that can last through at least 13 generations of offspring even though no change in DNA has occurred (and generations 2 through 13 were not directly exposed to the drug). Similarly, according to a paper published last year in the Quarterly Review of Biology by Eva Jablonka (an epigenetic pioneer) and Gal Raz of Tel Aviv University, roundworms fed with a kind of bacteria can feature a small, dumpy appearance and a switched-off green fluorescent protein; the changes last at least 40 generations. (Jablonka and Raz's paper catalogs some 100 forms of epigenetic inheritance)
Can epigenetic changes be permanent? Possibly, but it's important to remember that epigenetics isn't evolution. It doesn't change DNA. Epigenetic changes represent a biological response to an environmental stressor. That response can be inherited through many generations via epigenetic marks, but if you remove the environmental pressure, the epigenetic marks will eventually fade, and the DNA code will — over time — begin to revert to its original programming. That's the current thinking, anyway: that only natural selection causes permanent genetic change.
And yet even if epigenetic inheritance doesn't last forever, it can be hugely powerful. In February 2009, the Journal of Neuroscience published a paper showing that even memory — a wildly complex biological and psychological process — can be improved from one generation to the next via epigenetics. The paper described an experiment with mice led by Larry Feig, a Tufts University biochemist. Feig's team exposed mice with genetic memory problems to an environment rich with toys, exercise and extra attention. These mice showed significant improvement in long-term potentiation (LTP), a form of neural transmission that is key to memory formation. Surprisingly, their offspring also showed LTP improvement, even when the offspring got no extra attention.
All this explains why the scientific community is so nervously excited about epigenetics. In his forthcoming book The Genius in All of Us: Why Everything You've Been Told About Genetics, Talent and IQ Is Wrong, science writer David Shenk says epigenetics is helping usher in a "new paradigm" that "reveals how bankrupt the phrase 'nature versus nurture' really is." He calls epigenetics "perhaps the most important discovery in the science of heredity since the gene."
Geneticists are quietly acknowledging that we may have too easily dismissed an early naturalist who anticipated modern epigenetics — and whom Darwinists have long disparaged. Jean-Baptiste Lamarck (1744-1829) argued that evolution could occur within a generation or two. He posited that animals acquired certain traits during their lifetimes because of their environment and choices. The most famous Lamarckian example: giraffes acquired their long necks because their recent ancestors had stretched to reach high, nutrient-rich leaves.
In contrast, Darwin argued that evolution works not through the fire of effort but through cold, impartial selection. By Darwinist thinking, giraffes got their long necks over millennia because genes for long necks had, very slowly, gained advantage. Darwin, who was 84 years younger than Lamarck, was the better scientist, and he won the day. Lamarckian evolution came to be seen as a scientific blunder. Yet epigenetics is now forcing scientists to re-evaluate Lamarck's ideas.
