Essay by Stavroula Piliou
Have you ever wondered why identical twins, who share the same genetic blueprint, can end up leading vastly different lives? Or why specific traits, illnesses, or behaviours appear to deviate from the anticipated inheritance patterns prescribed by our genetic code? The answer lies in epigenetics, a field of study that has not only debunked the age-old myth of genetic determinism, but has also unveiled the intricate ways in which our environment and experiences influence the expression of our genes.
Since the 1950s, we have linked certain inherited conditions, like cystic fibrosis, to genetics, setting the stage for the belief that all diseases are genetically predetermined. The 'Human Genome Project', initiated in 1990, was hailed as a game-changer in our battle against chronic diseases. The idea was simple: identify the genes causing chronic diseases, develop drugs to target them, and voila! Cancer, autoimmunity, obesity, all under control. It was thought that our genes dictated everything, and that our destiny was essentially pre-written in the language of DNA. Reality, however, took an unexpected turn. While specific genes may increase the risk of certain conditions, they don't guarantee them. Individuals carrying high-risk genes may sail through life without encountering anticipated diseases, while those with seemingly low-risk genetics may face unexpected health challenges.
Therefore, genes are often cast as villains or heroes: life, however, is never that straightforward. Polymorphisms or SNPs can't simply be labelled as 'bad' or 'good', as they may even confer opposite effects depending on underlying environmental or other contexts. Take the APOE4 polymorphism - linked to increase risk in cardiovascular disease and cognitive decline in Western populations, yet overall protective in developing countries, or populations facing high parasitic loads. Hence, genes are just a piece of the puzzle; context is the key.
This is where epigenetics kicks in. If DNA is the recipe, dictating how our cells create us, epigenetics is the chef determining which recipe to follow. More specifically, epigenetics explores molecular modifications occurring on the DNA molecule, and its associated proteins. Unlike our fixed DNA sequence, which remains relatively stable throughout our lifetime, epigenetic modification adorn our genomic blueprint like colourful post-it notes, influencing which genes are turned on or off. These modifications can be influenced by various environmental factors: diet, stress and chemical exposure to name a few, leading to changes in gene expression that can affect our health and susceptibility to diseases. Try picturing DNA as a tightly wound script, and epigenetic marks as the director's notes, indicating which scenes to emphasise or reduce. The primary players are chemical compounds like methyl groups, histone proteins and non-coding regions of the genome, either 'silencing' genes or influencing the accessibility of their material. Basically, epigenetics highlights our dynamic genetic makeup, and the centrality of lifestyle in shaping our biological destiny.
BUT HOW EXACTLY DOES LOOKING THROUGH THE LENS OF EPIGENETICS CHALLENGE MYTHS THAT HAVE TRADITIONALLY INFLUENCED OUR ADOPTION OF GENETIC DETERMINISM?
Firstly, epigenetics challenges the idea that our genes are a fixed blueprint and reveals that, instead, they are a dynamic and highly adaptable landscape, shaped by environmental factors throughout our lives. For example, research has shown that exposure to air pollution during pregnancy can discrupt epigenetic regulation of genes involved in lung development. Yet, epigenetics also shows that our genes do not dictate our destiny, given we have the contrasting power to influence our gene expression and health outcomes through lifestyle modification. Studies have shown that dietary supplements and lifestyle changes can affect change in situations of obesity and diabetes - this offers hope, demonstrating we are not powerless, and can alter our health trajectories. Stress management techniques, such as yoga and meditation, have been found to target the same genes responsible for stress, reversing and mitigating its effects - regular practice also reduces cytokines and other transcription factors responsible for inflammation, limiting the negative effects stress has on health and wellbeing.
The power of epigenetics doesn't stop there, though. Changes made to gene expression through epigenetic may not be permanent due to changes in behaviour or environment. For example, even though smoking tends to decrease DNA methylation at certain parts of the gene called AHRR, quitting smoking conversely increases AHRR methylation. This observation is particularly important as dysregulations in the AHRR pathway have been associated with various health conditions: cardiovascular, reproductive, and multiple types of cancer. But there's more - even germ infections can utilise epigenetics to weaken the host's immune system: infection with the bacterium Mycobacterium tuberculosis causes histone modification in some immune cells, resulting in the switching off of the IL-12B gene, important for immune system activation. Epigenetic modifications are particularly interesting in cancer, because they make this genetic disease ever more complex. Certain DNA mutations and epigenetic changes can greatly influence cancer risk. A well-tracked example is mutations to the BRCA1 gene, normally functioning as a tumour suppressor gene responsible for repairing DNA damage. DNA mutations that prevent this gene from properly functioning increase the risk of breast cancer. All these examples prove that epigenetic research has the potential to open new revolutionary avenues for personalised medicine and disease prevention, as it allows us to target the mechanisms that regulate gene expression, rather than simply focusing on DNA sequence alterations.
ONCE-IN-A-GENERATION RESEARCH, AND GENERATIONAL IMPACT
By this point, you may be thinking that all this information is overwhelming. However, it gets even more interesting when you consider epigenetics' generational impact. Have you ever wondered if the experiences shaping your life today could have leave a lasting impact on not just you, but also your descendants? Epigenetic modifications create a biological memory, which can pass on and impact future generations, through a phenomenon known as 'trans-generational epigenetic inheritance.'
While the mechanisms behind it are still not fully understood, it suggests that the impact of our experiences may echo across generations, challenging the traditional view of genetics which assumes that only DNA changes pass on. A study led by New York's Mount Sinai Hospital showed that the children of Holocaust who had experienced trauma were more likely to have epigenetic changes associated with post-traumatic stress disorder (PTSD). According to the study leader, "gene changes in the child... [are] only attributable to parental trauma." Another study highlighting the cross-generational impact of "biological trauma" is the Dutch Hunger Winter study, conducted in post-WWII Netherlands. Researchers found that individuals exposed to the famine in-utero exhibited increased susceptibility to obesity, diabetes and cardiovascular diseases later in life, suggesting that epigenetic changes induced by famine early in life have lasting effects on gene expression and disease risk.
In closing, even though our genes are non-negotiable, they don't dictate our destiny. We have the power to change the trajectory of our genetic story - every choice we make, from the food we eat to the way we manage stress, leaves a mark on the epigenetic landscape not only affecting our life, but also those of future generations.
"Our genes lay the foundation, but our experiences and choices ultimately choreograph the highly individual trajectory of existence."
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