THE HUMAN DNA IS A BIOLOGICAL INTERNET and superior in many aspects to the artificial one. Russian scientific research directly or indirectly explains phenomena such as clairvoyance, intuition, spontaneous and remote acts of healing, self-healing, affirmation techniques, unusual light/auras around people (namely spiritual masters), mind’s influence on weather patterns and much more. In addition, there is evidence for a whole new type of medicine in which DNA can be influenced and reprogrammed by words and frequencies withoutcutting out and replacing single genes.
The Great DNA Data Deficit: Are Genes for Disease a Mirage?
Jonathan Latham and Allison Wilson
Just before his appointment as head of the US National Institutes of Health (NIH), Francis Collins, the most prominent medical geneticist of our time, had his own genome scanned for disease susceptibility genes. He had decided, so he said, that the technology of personalised genomics was finally mature enough to yield meaningful results. Indeed, the outcome of his scan inspired The Language of Life, his recent book which urges every individual to do the same and secure their place on the personalised genomics bandwagon.
So, what knowledge did Collins’s scan produce? His results can be summarised very briefly. For North American males the probability of developing type 2 diabetes is 23%. Collins’s own risk was estimated at 29% and he highlighted this as the outstanding finding. For all other common diseases, however, including stroke, cancer, heart disease, and dementia, Collins’s likelihood of contracting them was average.
Predicting disease probability to within a percentage point might seem like a major scientific achievement. From the perspective of a professional geneticist, however, there is an obvious problem with these results. The hoped-for outcome is to detect genes that cause personal risk to deviate from the average. Otherwise, a genetic scan or even a whole genome sequence is showing nothing that wasn’t already known. The real story, therefore, of Collins’s personal genome scan is not its success, but rather its failure to reveal meaningful information about his long-term medical prospects. Moreover, Collins’s genome is unlikely to be an aberration. Contrary to expectations, the latest genetic research indicates that almost everyone’s genome will be similarly unrevealing.
We must assume that, as a geneticist as well as head of NIH, Francis Collins is more aware of this than anyone, but if so, he wrote The Language of Life not out of raw enthusiasm but because the genetics revolution (and not just personalised genomics) is in big trouble. He knows it is going to need all the boosters it can get.
What has changed scientifically in the last three years is the accumulating inability of a new whole-genome scanning technique (called Genome-Wide Association studies; GWAs) to find important genes for disease in human populations1. In study after study, applying GWAs to every common (non-infectious) physical disease and mental disorder, the results have been remarkably consistent: only genes with very minor effects have been uncovered (summarised in Manolio et al 2009; Dermitzakis and Clark 2009). In other words, the genetic variation confidently expected by medical geneticists to explain common diseases, cannot be found.
There are, nevertheless, certain exceptions to this blanket statement. One group are the single gene, mostly rare, genetic disorders whose discovery predated GWA studies2. These include cystic fibrosis, sickle cell anaemia and Huntington’s disease. A second class of exceptions are a handful of genetic contributors to common diseases and whose discovery also predated GWAs. They are few enough to list individually: a fairly common single gene variant for Alzheimer’s disease, and the two breast cancer genes BRCA 1 and 2 (Miki et al. 1994; Reiman et al. 1996). Lastly, GWA studies themselves have identified five genes each with a significant role in the common degenerative eye disease called age-related macular degeneration (AMD). With these exceptions duly noted, however, we can reiterate that according to the best available data, genetic predispositions (i.e. causes) have a negligible role in heart disease, cancer3, stroke, autoimmune diseases, obesity, autism, Parkinson’s disease, depression, schizophrenia and many other common mental and physical illnesses that are the major killers in Western countries4.
For anyone who has read about ‘genes for’ nearly every disease and the deluge of medical advances predicted to follow these discoveries, the negative results of the GWA studies will likely come as a surprise. They may even appear to contradict everything we know about the role of genes in disease. This disbelief is in fact the prevailing view of medical geneticists. They do not dispute the GWA results themselves but are now assuming that genes predisposing to common diseases must somehow have been missed by the GWA methodology. There is a big problem, however, in that geneticists have been unable to agree on where this ‘dark matter of DNA’ might be hiding.
If, instead of invoking missing genes, we take the GWA studies at face value, then apart from the exceptions noted above, genetic predispositions as significant factors in the prevalence of common diseases are refuted. If true, this would be a discovery of truly enormous significance. Medical progress will have to do without genetics providing “a complete transformation in therapeutic medicine” (Francis Collins, White House Press Release, June 26, 2000). Secondly, as Francis Collins found, genetic testing will never predict an individual’s personal risk of common diseases. And of course, if the enormous death toll from common Western diseases cannot be attributed to genetic predispositions it must predominantly originate in our wider environment. In other words, diet, lifestyle and chemical exposures, to name a few of the possibilities.
The question, therefore, of whether medical geneticists are acting reasonably in proposing some hitherto unexpected genetic hiding place, or are simply grasping at straws, is a hugely significant one. And there is more than one problem with the medical geneticists’ position. Firstly, as lack of agreement implies, they have been unable to hypothesise a genetic hiding place that is both plausible and large enough to conceal the necessary human genetic variation for disease. Furthermore, for most common diseases there exists plentiful evidence that environment, and not genes, can satisfactorily explain their existence. Finally, the oddity of denying the significance of results they have spent many billions of dollars generating can be explained by realising that a shortage of genes for disease means an impending oversupply of medical geneticists.
You will not, however, gather this from the popular or even scientific media, or even the science journals themselves. No-one so far has been prepared to point out the weaknesses in the medical geneticist’s position. The closest up to now is from science journalist Nicholas Wade in the New York Times who has suggested that genetic researchers have “gone back to square one.” Even this is a massive understatement, however. Human genetic research is not merely at an impasse, it would seem to have excluded inherited DNA, its central subject, as a major explanation of most diseases.
The failure to find major ‘disease genes’
Advances in medical genetics have historically centered on the search for genetic variants conferring susceptibility to rare diseases. Such genes are most easily detected when their effects are very strong (in genetics this is called highly penetrant), or a gene variant is present in unusually inbred human populations such as Icelanders or Ashkenazi Jews. This strategy, based on traditional genetics, has uncovered genes for cystic fibrosis, Huntington’s disease, the breast cancer susceptibility genes BRCA 1 and 2, and many others. Important though these discoveries have been, these defective genetic variants are relatively rare, meaning they do not account for disease in most people2. To find the genes expected to perform analogous roles in more common diseases, different genetic tools were needed, ones that were more statistical in nature.
The technique of genome wide association (GWA) was not merely the latest hot thing in genetics. It was in many ways the logical extension of the human genome sequencing project. The original project sequenced just one genome but, genetically speaking, we are all different. These differences are, for many geneticists, the real interest of human DNA. Many thousands of minor genetic differences between individuals have now been catalogued and medical geneticists wanted to use this seemingly random variation to tag disease genes. Using these minor DNA differences to screen large human populations, GWA studies were going to identify the precise location of the gene variants associated with susceptibility to common disorders and diseases.
To date, more than 700 separate GWA studies have been completed, covering about 80 different diseases. Every common disease, including dozens of cancers, heart disease, stroke, diabetes, mental illnesses, autism, and others, has had one or more GWA study associated with it (Hindorff et al. 2009). At a combined cost of billions of dollars, it was expected at last to reveal the genes behind human illness. And, once identified, these gene variants would become the launchpad for the personalised genomic revolution.
But it didn’t work out that way. Only for one disease, AMD, have geneticists found any of the major-effect genes they expected and, of the remaining diseases, only for type 2 diabetes does the genetic contribution of the genes with minor effects come anywhere close to being of any public health significance (Dermitzakis and Clark 2009; Manolio et al. 2009). In the case of AMD, the five genes determine approximately half the predicted genetic risk (Maller et al. 2006). Apart from these, GWA studies have found little genetic variation for disease. The few conclusive examples in which genes have a significant predisposing influence on a common disease remain the gene variant associated with Alzheimer’s disease and the breast cancer genes BRCA1 and 2, all of which were discovered well before the GWA era (Miki et al. 1994 and Reiman et al. 1996).
Though they have not found what their designers hoped they would, the results of the GWA studies of common diseases do support two distinct conclusions, both with far-reaching implications. First, apart from the exceptions noted, the genetic contribution to major diseases is small, accounting at most for around 5 or 10% of all disease cases (Manolio et al. 2009). Secondly, and equally important, this genetic contribution is distributed among large numbers of genes, each with only a minute effect (Hindorff et al. 2009). For example, the human population contains at least 40 distinct genes associated with type I diabetes (Barrett et al. 2009). Prostate cancer is associated with 27 genes (Ioannidis et al. 2010); and Crohn’s disease with 32 (Barrett et al. 2008).
The implications for understanding how each person’s health is affected by their genetic inheritance are remarkable. For each disease, even if a person was born with every known ‘bad’ (or ‘good’) genetic variant, which is statistically highly unlikely, their probability of contracting the disease would still only be minimally altered from the average.
Scientists Discover Quadruple Helix: Four Strand DNA In Human Cells
The human race knows very little of itself, almost like a race with amnesia. As we continue to move forward through time, new discoveries are made that make old theories obsolete and false. It’s a good lesson that shows us how we can attach ourselves to “truths” and believe them whole-heartedly, often forgetting that truth is constantly changing and new paradigms of perception always lurk around the corner.
Decades after scientists described our “chemical code” of life using the double helix DNA, researchers have discovered four-stranded DNA within human cells. The structures are called G-quadruplexes, because they form in regions of DNA that are full of guanine, one of the DNA molecule’s four building blocks. The others are adenine, cytosine and thymine. A hydrogen bond is responsible for holding the four guanines together. The four stranded DNA usually presents itself right before cell division.
The discovery was published online in Nature Chemistry, and you can take a look at it here. The study was led by Shankar Balasubramanian at the University of cambridge, UK.
The Ghost in our Genes
Our genes carry unbelievable information of our past. And it is this genetic information, that affects our present, because the only way forward is to look into the past. This documentary film explains genetic science and it’s impact on our future life.
A gene is the basic unit of heredity in a living organism. The field of genetics predates modern molecular biology, but it is now known that all living things depend on DNA to pass on their traits to offspring.
Genetics is a discipline of biology and the science of heredity and variation in living organisms. The fact that living things inherit traits from their parents has been used since prehistoric times to improve crop plants and animals through selective breeding.
However, the modern science of genetics, which seeks to understand the process of inheritance, only began with the work of Gregor Mendel in the mid-nineteenth century. Although he did not know the physical basis for heredity, Mendel observed that organisms inherit traits in a discrete manner-these basic units of inheritance are now called genes.
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.
At the heart of this new field is a simple but contentious idea — that genes have a ‘memory’. 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.”