Epigenetics is a field of scientific research that has seen explosive growth over the past decade or so. It is starting to come to the attention of the general public, featured in numerous publications including The New York Times and now The Oberlin Review. I’ve become convinced that everybody, regardless of background, should have a basic understanding of epigenetics, as it has far reaching consequences for many fields, including biology, neuroscience, medicine, sociology and anthropology, to name a few.

Epigenetics literally means “over-genetics,” and the term was coined in the 1940s to explain how two people with the same genetic background could develop different physical traits or phenotypes. The term is currently defined as heritable changes that do not directly affect the sequence of base pairs in the DNA but affect the expression of certain genes. For example, every cell in your body contains a copy of the genes needed to make bone cells and eye cells. The body uses epigenetic modifications to silence the bone cell genes in the eyes and vice versa, thus creating the thousands of types of highly differentiated cells in the human body.

The nucleus of each cell in our bodies contains approximately two meters of DNA that need to be condensed into an area that is approximately five to ten micrometers, or 10-6 meters in diameter.

This means that DNA needs to be compressed to about one millionth of its full length in each cell and still be able to coordinate all of the activities of said cell. We achieve this by wrapping and coiling DNA around proteins called histones. These histones can be modified in certain ways that can lead to a tightening or loosening of the DNA around the histomes. When DNA is very tightly wrapped, it cannot be expressed, as is the case for the bone cell gene in the eye. When it is more loosely wrapped, cellular machinery responsible for expressing the gene can access the DNA (like with bone cell genes in bone tissue).

Another important type of epigenetic modification is called DNA methylation, which directly affects the DNA structure and is associated with the silencing of genes. When cells divide, these epigenetic changes can be passed on to the daughter cells, which allows differentiated cell types in the body to remain stable over periods of time with many divisions.

Before epigenetics came about, we thought of inheritance of disease as being solely based on genetic mutations, changes in the DNA sequence that could cause disease. Environmental factors were always thought not to interact with gene expression. Even today you hear people talk about nature versus nurture — does the environment or do genes cause a heritable disease? It turns out that these two factors are much less separable than previously thought. Many scientists

have looked at high stress levels, which increase levels of cortisol in the blood stream. This cortisol can act on cells throughout the body, and many studies have shown that chronically high cortisol can lead to epigenetic changes that correlate with depression, reduced immune response, weight gain and other adverse effects. Epigenetic changes have been linked to a plethora of environmental events including childhood abuse, high fat or low protein diets and air pollution.

This may change the way we view and treat many diseases, especially psychiatric diseases that have no known direct genetic cause. Over Winter Term I worked on a project investigating a drug that induces histone modifications, which may normalize expression of genes that are downregulated in depressed patients.

The potential in the field of pharmacoepigenetics, drugs that induce epigenetic changes, is huge and could revolutionize treatments for diseases from depression and anxiety to cancer, diabetes and just about anything that you can think of.

Not only does epigenetics blur the nature versus nurture line,

but recent studies have shown that epigenetic modifications can be inherited across generations. Around the turn of the 19th century, Jean-Baptiste Lamarck proposed a theory whereby organisms could inherit traits that had been acquired during the lifetime of the parent. Then came Charles Darwin and his theory of evolution, which led to biology students around the world being given the example of Lamarck as a classically incorrect scientific theory. It was so opposed to 20th century biological dogma that telling a biologist that some forms of Lamarckian inheritance were possible would have been heretical even as recently as 20 years ago.

Many epidemiological studies were conducted in Sweden during the 2000s, using that country’s access to extensive and centralized medical records for all its citizens. They determined that if a man experienced famine before puberty, his grandchildren would be much less likely to have heart disease or diabetes than those of a man who had been well fed. Of course, this study still leaves a huge black box over the mechanism of inheritance, but it must be something other than traditional genetics because DNA remains relatively stable across generations.

A research group at Emory University performed an experiment in which it exposed male mice to a chemical called acetophenone and paired this exposure with an aversive shock. They found that the offspring of these males born from

normal, untreated females had increased receptors for acetophenone and a corresponding increase in fear response when exposed to the compound. The same effect was observed in the grandchildren of the exposed mice. The researchers involved in this project point to forms of epigenetic inheritance for this change.

However, the complexity doesn’t stop there. We still have very little idea about how these changes are transmitted from the sperm to the fertilized egg and from there to the fully developed progeny and beyond. Most epigenetic changes are removed and reprogrammed following fertilization. DNA is unwrapped from histones and rewrapped around a different type of protein called protamines, which allow it to be more tightly packed. Most methyl groups are removed and laid out again later in development.

In short, there are many theories of why we are observing a seemingly Lamarckian evolution. Hopefully in coming years the scientific community will come to understand how these patterns of epigenetic inheritance are occurring. This cutting-edge research likely challenges many of the concepts that you were taught in high school biology and also challenges many of the ideas that some current researchers have held for most of their careers. It seems that in science, things are always more complicated, and you always need to be prepared to give up what you thought you knew in favor of new research.