Chips with everything

DNA technology is about to reveal your cancer risk - and a lot more besides, says Roger Dobson
  
  


It looks like a run-of-the-mill silicon chip. It's flat, dark grey in colour and no bigger than a thumbnail, almost identical to the millions of chips found in electronic devices as diverse as washing machines and computers. But this is a very special chip. It does not control spin-rinse cycles or carry out Internet searches, its job is to find out whether or not people are likely to get cancer.

Similar chips are being made for other diseases, including AIDS, leukaemia and TB, and eventually there will be chips that will even predict the behavioural traits of unborn babies.

DNA chip technology is a burgeoning new area of medicine and genetics that promises to revolutionise disease diagnosis. But it is also generating growing controversy, with calls for international controls to make sure it is not abused.

Current laboratory techniques for detecting genetic mutations that are responsible for disease are time-consuming and expensive, taking months, even years. In contrast, a DNA chip takes minutes, or at most hours, to seek out disease-causing mutations in genes.

Though the technology is complex, the theory behind the process is simple. Instead of having intricate microelectronic circuits etched onto their surfaces, these tiny chips are coated with DNA sequences, some of which are associated with a healthy gene while others are known disease-causing mutations.

The sequences, up to 400,000 on a single tiny chip, line up in the squares of a grid on the surface of the chip. A sample of the patient's DNA is then put onto the chip and each sequence pairs off with its opposite number. Whether or not they are exactly the same as their partner is then detected by a laser.

A patient whose DNA exactly matches with a known mutation on the chip may be at risk from that particular disease. If the DNA fails to match with a known healthy sequence that can also indicate potential problems.

"It is incredibly rapid. What you are relying on is that you will recognise differences between the DNA on the chip and DNA you are looking at. In terms of a quick screen, it is masterful because it gives you a quick answer and it is cheap," says Dr Gareth Evans, consultant geneticist at Christie's Hospital, Manchester.

Half a dozen companies are now working on producing variations of these chips and California-based Affymetrix has launched three for use by researchers. The jewel in the crown at present is a chip which works on a gene called p53 that is abnormal in more than half of all types of cancers.

At the Houston Advanced Researcher Center, Dr Dat Dao and a team of researchers are working on chips that will be able to pinpoint antibiotic-resistant strains of TB. Another chip detecting mutations linked to breast cancer is in the pipeline, and the centre is also working on one that will take some of the hit and miss out of matching donor tissue for bone marrow transplants.

All the chips developed so far are being used only by researchers in the US and the UK, but the eventual aim is to use them for routine diagnostic purposes.

"This genosensor technology is going to create a host of benefits for the diagnosis of cancer as well as genetic and infectious diseases. It is going to be the diagnostic tool of the future," says Dr Dao.

Dr Mike Ramsay of the Oak Ridge National laboratory of the US Department of Energy, who also works with DNA chips, agrees: "This technology could be used to screen for people carrying genes that predispose them to getting breast cancer, becoming obese, or having children with cystic fibrosis. To make such an analysis we eventually hope to require only a few white blood cells or skin cells." But the rapidly evolving technology is seen by some as a Pandora's box, with almost as many ethical dilemmas as benefits. One of the biggest fears is that the chips will be seen as the ideal tool for the establishment of widespread genetic screening of all types and for all kinds of motives.

"Today's supply of screening for young couples is restricted to cystic fibrosis and a few rare diseases that are confined to specific populations. The chip, however, will broaden the spectrum of analysable parental traits practically ad libitum," says Dr Wolfram Henn, clinical geneticist at the University of Hamburg who raises concerns about the technology in this month's Journal of Medical Ethics.

The chief area for concern is prenatal screening, where DNA chips, the developers claim, will make it possible to test for every disease and trait in an unborn baby.

Dr Henn says that a chip with probes for interesting traits in the foetus has the potential to be a best seller, but warns that it could lead to a world of hi-tech eugenics.

"The subjective choice of genetic traits that are considered as prenatal selection criteria may blur the distinction between preventative medicine and striving for the perfectly designed child," he says.

It may also, he suggests, lead to the removal of diseases which can be detected before birth from health insurance cover: "The exclusion of prenatally testable conditions from insurance cover might serve to sanction a new kind of economically motivated negative eugenics that may well become popular in an era of declining prosperity," he warns.

Of course, not all our behaviour and ill health are down to genes. Some babies may, for example, be born with a predisposition to shyness, but others will have shyness thrust upon them by their early life experiences. Chips that can lead to the correction of nature may have arrived, but the failings of nurture will remain, at least for now.

 

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