The science behind a rapid paradigm shift
When the first human genome was decoded, popular thinking went: “If we know the genes, we know the person.” Today, barely 15 years later, science is in the middle of an exciting new area of research, which is entertaining interested members of the public with exciting, if not always serious, headlines. The field alleges that traumatic experiences can be passed down through the generations and even significantly affect the lives of grandchildren. As it turns out, the reality is that genes not only control, but are also controlled. And that is what epigenetics is all about – how are genes controlled and what factors can influence them?
Epigenetics refers to the meta-level of genetic regulation. Under the influence of external factors, epigenetic mechanisms regulate which genes are turned on and off. This helps our fixed genetic material to be more flexible. At the biochemical micro level, epigenetic regulators are responsible for how closely packed individual genomic regions are and therefore how accessible or not they are. This works by small adhered or detached chemical groups. The resulting marking of the genome is read by specialised enzymes that then cause the switching on or off of the genes.
As reasonable as this appears, one consequence is that we will have to say goodbye to a long-established dogma: the idea that genes are immutable in the creation of a living being. And, looking back through the history of science: was Lamarck right, after all? The 19th-century French biologist had claimed that organisms acquired traits to pass on to future generations . It is precisely this mechanism that epigeneticists are on the trail of today. Laboratory experiments with mice have demonstrated that a particular, targeted encoding of individual genes results in the changes being passed on to the offspring. Epigenetic changes, however, are so-called soft changes, as they can be undone. And that is medicine’s great hope – to be able to intervene in the control mechanism from the outside in order to be able to work against, for example, senile dementia.
At this point, the level of possible tension around this new field of research becomes clear. On the one hand, the idea that our human condition can be so strongly “manipulated” by environmental influences can be very disturbing. And rightly so. Previously, we may have had the upbeat expectation that although we are experiencing suffering, the next generation will have it better. However, today we must assume that if our generation is suffering hardship, violence or the like, not only will we struggle to forget these difficult periods ourselves but our genes too will remember them, carrying traces to be passed on to the next generation or even several generations.
A study often mentioned in this context is based on the analysis of data collected in the Netherlands over the years of hunger in 1944-45, during which the population there suffered particularly difficult conditions. The children born at this time were not only smaller, but, as adults, had an increased risk of obesity, cardiovascular problems and neuropsychiatric disorders. In turn, their offspring were again smaller than average – despite food being in ready supply and living conditions having greatly improved.
The Göttingen neurologist André Fischer explains it like this: “One possible cause is an altered DNA methylation of the insulin-like growth factor 2. Investigations by my own working group showed that IGF2 is important for cognitive functions and plays a key role in anxiety disorders.” In February this year, Scientific American finally reported on a study that deals with the descendants of Holocaust survivors: “Their latest results reveal that descendants of people who survived the Holocaust have different stress hormone profiles than their peers, perhaps predisposing them to anxiety disorders.“
Elizabeth Blackburn, who received the 2009 Nobel Prize in Medicine for her research on telomeres, had, in 2013, already warned that stress can alter genetic material. She and her colleague Elissa Epel ascertained that violence, abuse and poverty reduce the “protective cover” of the genome.
The question now arises as to what evolutionary sense an epigenetic inheritance mechanism actually has. Does the inheritance of negative experiences only cause additional damage in the next generation? In recent studies the focus has shifted towards finding out whether it could lead to a higher resilience to stress in following generations. Such regulation processes may well have arisen precisely because they modify the rigid concept of inheritance of the same genes to a sensible, where necessary, inter-generational adaptation to varyingly difficult environmental conditions. However, before we can think about drugs for tackling chronic stress, for example, the underlying processes of inherited stress regulation must be further investigated. In this respect, therapeutic agents are the long-term goal here and not the next step.
In one other area, faster therapeutic success is expected: in Alzheimer’s research. In Alzheimer’s patients the genes responsible for learning are suppressed. Animal studies have demonstrated that medication can inhibit the suppression of these cognitive abilities. Not only did the medication prevent neurons from being destroyed, but fresh neurons were actually formed. Another promising fact is that there are already approved ‘epigenetic’ drugs for cancer therapy, which could also turn out to be suitable for neurodegenerative diseases.
Whatever the outcome, we can certainly be curious about the great potential for gaining new insights that epigenetics promises and the impact they will have on our thinking and our lives!
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