IT SOUNDS like science fiction: simply swallowing a pill, or eating a specific food supplement, could permanently change your behaviour for the better, or reverse diseases such as schizophrenia, Huntington鈥檚 or cancer.
Yet such treatments are looking increasingly plausible. In the latest development, normal rats have been made to behave differently just by injecting them with a specific amino acid. The change to their behaviour was permanent. The amino acid altered the way the rat鈥檚 genes were expressed, raising the idea that drugs or dietary supplements might permanently halt the genetic effects that predispose people to mental or physical illness.
It is not yet clear whether such interventions could work in humans. But there is good reason to believe they could, as evidence mounts that a range of simple nutrients might have such effects.
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Two years ago, researchers led by Randy Jirtle of Duke University Medical Center in Durham, North Carolina, showed that the activity of a mouse鈥檚 genes can be influenced by food supplements eaten by its mother just prior to, or during, very early pregnancy (快猫短视频, 9 August 2003, p 14). Then last year, Moshe Szyf, Michael Meaney and colleagues at McGill University in Montreal, Canada, showed that mothers could influence the way a rat鈥檚 genes are expressed after it has been born. If a rat is not licked, groomed and nursed enough by its mother, chemical tags known as methyl groups are added to the DNA of a particular gene.
The affected gene codes for the glucocorticoid receptor gene, expressed in the hippocampus of the brain. The gene helps mediate the animal鈥檚 response to stress, and in poorly raised rats, the methylation damped down the gene鈥檚 activity. Such pups produced higher levels of stress hormones and were less confident exploring new environments. The effect lasted for life (Nature Neuroscience, vol 7, p 847).
Now the team has shown that a food supplement can have the same effect on well-reared rats at 90 days old 鈥� well into adulthood. The researchers injected L-methionine, a common amino acid and food supplement, into the brains of well-reared rats. The amino acid methylated the glucocorticoid gene, and the animals鈥� behaviour changed. 鈥淭hey were almost exactly like the poorly raised group,鈥� says Szyf, who announced his findings at a small meeting on environmental epigenomics earlier this month in Durham, North Carolina.
鈥淭his opens up new ways of thinking about treating and preventing diseases caused by how our DNA is expressed鈥�
Though the experiment impaired well-adjusted animals, the opposite should be possible, and Szyf has already shown that a chemical called TSA that is designed to strip away methyl groups can turn a badly raised rat into a more normal one.
No one is envisaging injecting supplements into people鈥檚 brains, but Szyf says his study shows how important subtle nutrients and supplements can be. 鈥淔ood has a dramatic effect,鈥� he says. 鈥淏ut it can go both ways,鈥� he cautions. Methionine, for instance, the supplement he used to make healthy rats stressed, is widely available in capsule form online or in health-food stores 鈥� and the molecules are small enough to get into the brain via the bloodstream.
Rob Waterland from Baylor College of Medicine in Houston, Texas, who attended the meeting, says Szyf鈥檚 ideas are creating a buzz, as they suggest that methylation can influence our DNA well into adulthood. A huge number of diseases are caused by changes to how our DNA is expressed, and this opens up new ways of thinking about how to prevent and treat them, he says.
But Waterland points out there is still much work to be done. Substances like methionine and TSA are, he says, a 鈥渟ledgehammer approach鈥�, in that they are likely to demethylate lots of genes, and we don鈥檛 even know which they will affect. But he speculates that techniques such as 鈥淩NA-directed DNA methylation鈥�, so far tested only in plants but theoretically possible in mammals, may allow us to target such methylation much more precisely.
