Tue, Jan 15, 2013 - Page 9 News List

Epigenetics may show root causes of many diseases

By Timothy Spector

Fifty-one years ago, James Watson, Maurice Wilkins and Francis Crick were awarded the Nobel Prize in Medicine for their discovery of DNA’s structure — a breakthrough that heralded the age of the gene. Since then, the field of genetics has advanced significantly, particularly as a result of the global Human Genome Project, which in 2003 identified all of the roughly 23,000 genes and 3 billion chemical base pairs in human DNA in order to screen for many rare diseases.

However, despite evidence that most diseases have a clear genetic component, only a fraction of the genes that explain them have been found. And scientists in the field remain puzzled by the fact that most identical twins (who share 100 percent of their genes) do not die from the same diseases. As a result, many in the scientific community are beginning to predict a decline in the role of the gene in pinpointing the root causes of diseases.

CLONING

However, it is too soon to discount genetics because the science of “epigenetics” — the study of mechanisms for turning genes on and off, thus changing the way a cell develops without altering the genetic code — is gaining traction. Indeed, the Nobel Prize in Medicine was last year awarded to John Gurdon and Shinya Yamanaka for revolutionizing scientists’ understanding of how cells develop by reprogramming DNA and cells without altering their genetic structure.

In 1962, Gurdon’s finding that almost any cell in the body contains the complete DNA code enabled him to create a tadpole by cloning an adult frog. More than four decades later, in 2006, Yamanaka discovered a way to trick complex adult cells in mice into regressing to their immature state, forming stem cells. Before this, stem cells — which can potentially be reprogrammed to develop into replacements for lost or damaged tissue — could be taken only from early-stage embryos, a practice that fueled ethical controversy.

The true promise of epigenetics has become apparent only in the last few years, as scientists’ ability to assess the epigenetic mechanisms in DNA — which can now be measured at roughly 30 million points across the human genome — has dramatically improved. Epigenetics can potentially be used to explain the root causes of many diseases that scientists have so far struggled to understand, from asthma to allergies to autism.

Consider lung cancer. Six decades ago, when most men smoked, British doctors linked smoking to lung cancer, making it the first disease to be causally linked to smoking. (In fact, lung cancer kills one in 10 smokers.) However, the incidence of certain kinds of lung cancer continues to rise — particularly in women — making it one of the most prolific killers worldwide, despite the general decline of smoking over the last 30 years.

Indeed, nowadays, many lung cancer patients have no history of smoking. These “blameless” patients seem to develop a different kind of lung cancer from those who report a history of smoking — one that is more responsive to new medications and has better, albeit still poor, outcomes.

Epigenetic processes that cause key anti-cancer genes, such as the tumor suppressor P16, to be switched off could explain the increased prevalence of lung cancer. A recent study showed that a few years of smoking can have this effect, making smokers more susceptible to a variety of cancers.

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