The Science of Epigenetics

| March 31, 2010 | 0 Comments

by Assad Meymandi, MD, PhD, DLFAPA
Dr. Meymandi is in private practice as a psychiatrist and neurologist and serves as an adjunct professor of psychiatry at the University of North Carolina at Chapel Hill. He is a noted physician, editor, and philanthropist who frequently speaks and writes on diverse topics that relate to his interests in medicine, the arts, religion, and philanthropy. He lives in Raleigh with his wife Emily.

Psychiatry (Edgemont) 2010;7(3):40–41

It seems a bit odd to start a discussion about a cutting-edge, up-to-the-minute science with an ancient Biblical story, yet the passages in Genesis chapters 41 through 47, which describe the Egyptian Pharaoh’s dream of “seven years of plenty and seven years of famine,” prove to be relevant to the science of epigenetics. Epigenetics, a 21st century science, is the study of changes in gene activity that does not involve alteration to the genetic code but gets passed down to successive generations.

In the 19th century, a province in northern Sweden called Norrbotten literally experienced seven years of famine followed by good harvest and abundance of food. The feast and famine period that occurred in this sparsely populated province (only six people per square mile) has offered astonishing epidemiologic and scientific data that have given birth to the science of epigenetics. The years 1800, 1812, 1821, 1836, and 1856 (the year of potato famine in Ireland) were years of total crop failure and famine for the people of Norrbotten. But in 1801, 1822, 1828, 1844, and 1863, there was excellent harvest and an abundance of food. Scientists of the renowned Karolinska Institute, Stockholm, Sweden, have undertaken the painstaking work of evaluating this history of famine and feast to see how it affected the lives of the children. With these studies, they have found that “life conditions could affect your health not only when you were a fetus, but also well into adulthood,” concluding that parents’ experiences early in their own lives change the traits they pass on to their offspring. The result of the study shows that the years the children were well fed, their own subsequent offspring grew up to be healthier and physically bigger.

In 1966, when I was director of Cumberland County Mental Health Center applying for a grant for the Head Start program, I used a study by Karolinska Institute published in the Acta Physiologica Scandinavica and Lancet, which demonstrated that fetus and fetal central nervous systems (CNS) exposed to excess secretion of maternal catecholamines, especially metanephrines, vinyl mandellic acid, and 3-methoxy 5-hydroxy methylgleycol (MHPG), produces babies that are more irritable, scrawny, cranky, susceptible to attention deficit hyperactive disorder (ADHD), and prone to anxiety, phobia, and social maladjustment. The project, titled “Intrauterine Head Start,” was funded and our findings were published. So, the knowledge of environmental influence on the fetus is not new. What is new, however, is the epidemiologic studies from Norrbotten and their defiance of Darwin’s assertion in his seminal work On the Origin of Species (1859) that evolution takes place over millions of years. The Norrbotten studies suggest that evolution and environmental influence affect genes within one or two generations. It does not take millions of years. This is heretical. Suddenly, we have evidence that Darwin was wrong. It takes only 25 to 75 years, 1 to 3 generations, not millennia, for evolution of genes to take place.

A switch

The exciting science of epigenetics is very much like a switch on the outside of the genetic circuits and genome that influences the behaviors of a gene. The very prefix epi, which means to lie outside of the root structure, helps explains that, while not an integral part of an organism’s genetic code, epigenetics can influence the gene’s activites from the outside. Flipping the switch enhances (turns a gene on) or inhibits (turns a gene off) DNA activity.

In-Utero Cell Differentiation

Cells in the kidney and the cells in the brain have the exact same deoxyribonucleic acid (DNA). The nascent cell can differentiate only when crucial epigenetic processes turn on or turn off the right gene in utero. This is why studies of identical twins show that while one sibling might develop asthma, bipolar disorder, or even schizophrenia, the other can be perfectly normal. The studies from Norrbotten clearly show that because of the epigentic switch, one can pass down epigenetic changes in a single generation.

Epigenetic Drugs

Cutting-edge scientists want to discover how to enhance the activities of the good genes and how to silence and discourage the activities of the bad genes. The task is not very difficult. To chemically flip the “good” switch on, one must introduce a methyl group (CH3) to the side chain of DNA—a very simple procedure; or vice versa, to flip it off, introduce a demethylate compound to suppress the activities of the bad genes.

There are several epigenetic drugs on the market. For example, the drug 5-aza-cytidine (Celgene Corporation, Summit, New Jersey) is an epigenetic drug that prolongs the life of patients afflicted by severe myelodysplastic syndromes. In recent years, the United States Food and Drug Administration (FDA) has approved three other epigenetic drugs that are thought to stimulate tumor-suppressing genes. It is hoped that we will find drugs that turn off expression of genes in many diseases, including cancer, autism, schizophrenia, alcoholism, and Alzheimer’s.

With the instrument and knowledge of epiginomics, it is conceivable to find the switch (the epigenome) that turns off the dumping of amyloid in the synaptic cleft that causes the devastating dementia of Alzheimer’s. Currently, the National Institute of Health is investing heavily in better understanding and codifying epigenomics. The Human Genome Project, completed in March 2000, found that the human genome contains 25,000 genes. Private enterprise along with Craig Venter, who won the Nobel Prize in Medicine or Physiology in 2005, beat government bureaucracy by completing the project two years before the government. Venter has already published his autobiography, A Life Decoded: My Genome—My Life, where he recounts his role in the Human Genome Project.

Now, we need a massive project to identify the epigenome and compile the human epigenomic book. The number of epigenomes far exceeds 25,000, and the cost of completing the project will cost hundreds of billions of dollars. It will also cause a bad case of “Darwinitis.” We will keep you posted as the science of epigenetics further develops.

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Category: Commentary, Genetics, Meymandi at Large, Past Articles, Psychiatry

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