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September 07, 2012

Soon science could enable us all to run as fast as Usain Bolt

One of the biggest scientific research projects in recent years has just unveiled its results. The Encode consortium, consisting of 442 researchers working in 32 institutes around the world, has spent the last five years studying a representative 1% of our genome. The findings may help to revolutionise medicine, but could also provide us with novel ways of tinkering with our minds and bodies.

One of the puzzles the researchers hoped to solve was why we have so much DNA. We've known for decades that only a tiny fraction of it, about 2%, are codes for conventional genes (protein-coding segments), the supposed movers and shakers of our cells and bodies. Many scientists thought that the remaining 98% was mostly junk, a bit like all the deleted fragments of documents that clog up your hard disk. The researchers found that it was instead packed full of genetic switches that tell each cell in your body which genes must be switched on or off to make a muscle, skin or nerve cell.

The results are likely to have major implications for our understanding of common diseases, such as diabetes, obesity, heart disease, cancer and even the debilities of old age, such as Alzheimer's disease. These were previously thought to bechiefly caused by defective genes (together with environmental influences, such as smoking), but decades of research have has failed to findenough defects that could account for their prevalence. Today, scientists believe that these diseases are caused not by defective genes, but defective switching: a liver cell may be genetically tripped to stop absorbing blood sugar, thereby causing diabetes; a lung cell may be tripped into generating mutagens that attack its own DNA, causing cancer.

That's potentially good news for sufferers because, although it's hard to fix a faulty gene, it may be much easier to flip a genetic switch and return a diseased cell back to its healthy state. Scientists have already developed novel forms of drugs, based on DNA's molecular cousin, RNA, that act like our own genetic switches to manipulate the control panel of our cells. A few of these gene-switch drugs are already in the market, but the Encode project suggests that thousands more await discovery.

A new era of gene-switch medicine may be on the horizon, but there are many problems that still have to be overcome. The first is getting the RNA-based gene-switch drugs safely inside the target cells and not into others where they might cause adverse side-effects. But even more of a challenge is to accurately predict the effect of flipping a genetic switch. The thousands identified by Encode are unlikely to work like simple light switches; instead, each switch is connected to many others in a vastly complicated gene circuitboard. Flipping one switch will be more like dropping a stone into a pool: the effects will reverberate through the entire network, and the eventual outcome will not be easy to predict. Systems biology, a new science, is simultaneously trying to unravel the circuit boards to make better predictions.

Few doubt that gene switching will provide the medicine of the future, but no one is sure when that future will be realised. When it comes, it will provide opportunities that go well beyond curing disease. Just as the difference between healthy and sick people may be down to gene switching, it seems likely that many of the differences between one person and another – between us and Usain Bolt, for example – may be due, similarly, to different patterns of gene switching. The kind of gene-switch medicines that will cure diseases may then be turned to therapies that will allow us all to run sub-10 second 100 metres. Physiology, mood, intelligence, libido, anxiety, appetite may all be fair game for the gene-switch therapeutics of the future.

Even the signs and frailties of old age may be kept at bay by a careful manipulation of our gene switches to return them to their youthful state. And what about the differences between us and our closest relatives, which many scientists believe are mostly due to differences in gene switching? Could gene-switch therapy be developed that would allow a chimp to talk? Planet of the Apes may not be so far away.

Five years of the Encode project has revealed just 1% of the human gene switches, but the pace of genetics is accelerating so fast that it seems likely that we will know most of them within a decade. That will be far too late to be any threat to Usain Bolt's dominance on the track, but the doping authorities in sport may face significant new challenges in the future.

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