Our DNA need not necessarily decide our destiny. Geneticists are now putting together concrete evidence to show that the environment we live in influences our heredity as much as it does our health. The air we breathe, the water we drink and the food we eat contain a variety of unwanted substances such as diesel and petrol fumes, tobacco smoke, pesticides, germs, and other pollutants. These contaminants, along with basic nutrients, trigger certain biochemical changes in the body that can modify the hard wiring of our genetic code.

This is dangerous, geneticists warn, because the modified genes in an organ like the kidney or the liver may start overproducing or not at all producing the desired proteins under the influence of external factors, thus hampering the organ’s natural functioning. The study of these chemical triggers and the genetic modifications, which is broadly classified as “epigenetics”, can therefore yield clues as to how lifestyle and the environment affect our predisposition to many dreaded diseases, including several types of cancers, mental disorders and hypertension.

One of the most convincing demonstrations of the influence of epigenetics was reported by a team of US researchers in the journal Science. Led by Michael Skinner, a professor of molecular biosciences at Washington State University, the scientists showed that pregnant rats briefly exposed to high levels of the insecticide methoxychlor and the fungicide vinclozolin produced male pups with a 90 per cent decrease in sperm production for at least four generations.

Among the major epigenetic changes is a process known as DNA methylation. This is a chemical alteration to the nucleic acid that occurs when a methyl chemical tag is either added or removed from DNA bases in a gene. Researchers think that such changes play a critical role, particularly in cancer, either by switching on genes that promote uncontrolled cell growth or turning off other genes that would normally suppress a tumour. They also believe that mapping all DNA methylation sites in the 23 pairs of human chromosomes will give a better understanding of the biological basis of a disease and may allow diagnosis at a later stage.

Currently, two separate research groups in Europe and the US are trying to map different parts of the overarching human epigenome.

Epigenetics

The European group — comprising the Wellcome Trust Sanger Institute and a private German biotech firm, Epigenomics AG — recently announced the results of the first phase of their project, which intends to cover about 10 per cent of the human chromosomes. For their work, the scientists measured levels of DNA methylation across the chromosomes number 6, 20 and 22 in tissues from 12 different human organs. The study, published in the November 2006 issue of the journal Nature Genetics, reported that at least one in every six genes the researchers studied was vulnerable to such external modifications. The European team also found that the influence of epigenetic factors was the maximum in the case of reproduction. “Analysis of the global epigenetic landscape revealed methylation specific to male reproductive tissues and cells show greatest difference (up to 20 per cent) as compared with other cell types,” says the European project leader, Stephan Beck, of the Wellcome Trust Sanger Institute.

The role of epigenetic factors in human diseases was first shown in 1983 when two scientists from Johns Hopkins University School of Medicine, Dr Bert Vogelstein and Dr Andrew Feinberg, brought to light their links with cancer. Since then, there have been many studies linking a number of chemical substances such as pesticides to tumours.

However, epigenetics as a subject gained the attention of the medical fraternity and researchers only in the aftermath of the successful completion of the Human Genome Project, which mapped the blueprint of the human genetic makeup. “Even though the Human Genome Project provided invaluable insights to what man is made of, it failed to yield tangible benefits in terms of new therapies or drugs. This is one of the main reasons the medical fraternity turned its attention to epigenetics,” says Dr Jacob Peedicayil, an associate professor at Christian Medical College, Vellore.

There are others reasons too. Scientists think that having the human DNA sequenced (through the Human Genome Project) is just the first step in our quest to understand the complexities of the biological systems in the human body. Once one knows the basic workings of the DNA, it is easier to explore the external influences.

Epigenetic effects undoubtedly are the single most important external influence and learning more about these effects is essential to deciphering the mysteries of human diseases.

More importantly, epigenetic studies have clinical significance too. Studies have shown that several of these epigenetic changes can be reversed. “Epigenetic defects are thought to be more easily reversible with pharmacological intervention,” says Dr Peedicayil. This would mean that several of the incurable diseases of the day can easily be treated or prevented if medical science can trace their epigenetic roots, he adds.

Obesity link

Scientists believe the study of the epigenome may also throw light on the increasing obesity levels in developing countries. Dr Mark Hanson of Southampton University says epigenetic programming in the womb is leading to the health problems associated with rapid industrialisation, especially in developing countries such as India and China. According to him, the foetus gets a massive amount of information from its mother about the external environment. This information would prepare the foetus’ cells to cope with the external environment after birth.

For instance, a child born in rural India would have received certain information from its mother in the womb about the types of food and their availability in the village (external environment). Armed with the information received in the womb, the child readily adapts to the food habits of the rural people.

However when the child attains adulthood, he may move to a city, take an office job and have ready access to larger quantities of food. Quite often, the human body reacts to such mismatch through obesity.