The Gene Dilemma: Researchers take lead in battle with disease: Ethics borne in mind amid laboratory progress

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The Independent Online
TURN RIGHT at the top of the first-floor stairs inside the rather old-fashioned brick building that is St Mary's Medical School in London and you will find a hunt going on. There are detectives. A suspect. And the prospect of a whodunit ending.

The intensive hunt in the biochemistry department is to isolate the gene responsible for the rare inherited disease of Friedreich's ataxia, a condition in which degeneration of nerve fibres causes loss of co-ordination, balance and early death through heart failure. There is no cure. The hunt is not for a cure, but for the foundation knowledge that could bring that day closer.

A multi-national team of 10 genetic 'detectives' in the ataxia laboratory is headed by Dr Susan Chamberlain. She has been 'on the case' for eight years. Suspects have been rounded up and discarded. But this year she is 'hopeful'.

The process of investigation does not look particularly hi- tech. As Dr Mark Pook, a molecular geneticist, explained: 'The basic material in gene hunting is blood samples.'

The search for the gene (the unit of inheritance that consists of a specific sequence of deoxyribonucleic acid, or DNA - the 'building blocks' that carry all genetic information - begins with identifying a large number of families with more than one affected individual. The St Mary's team has used two very large families, one from Thailand, one from Cuba. Those who have suffered from or escaped ataxia are mapped on a family tree, allowing the investigators to trace the suspected defective gene to a single individual.

The white cells of the blood samples contain the DNA. To collect the DNA, the cell walls are broken by using detergent. The DNA is then formed into a globular substance by precipitating it with ethanol and spinning it in a centrifuge.

Any real genetic hunt begins with the chromosomes, the structures containing DNA. The human genetic blueprint is written out in the chemistry of DNA and consists of a message 3 billion 'letters' long. Humans have 23 pairs of chromosomes, one of each from either of their parents.

In Friedreich's ataxia, a recessive genetic disorder, both parents would have to pass on the defective gene to their offspring. For dominant forms of ataxia, where only one defective gene needs to be inherited, the defective genes have already been located on chromosome 6, 12, 14 and at least one other is yet to be identified.

The St Mary's team has narrowed the search for the Friedreich's ataxia gene to a small region of the ninth chromosome. But that is only the beginning - the fine analysis is in locating the precise 'culprit' pattern within the region of 500,000 genetic 'letters' on chromosome 9 where they believe the gene to lie.

'It is like looking in a large library of unmarked books for something as small as a specific letter in one word, in one sentence, on one page, within one book, or even the dot on one i,' Dr Pook said.

The chemical letters of the genetic code are known as 'bases'. There are four: adenine (A), thymine (T), guanine (G) and cytosine (C). But by using certain enzymes, applied to pure DNA, certain sequences of A,T, G and C can be identified.

The St Mary's team look up lengthy tables of enzymes which cut up DNA into handy segments for study. The collected 'bits' can then be placed on a gel capable of conducting electricity. A current is then passed through the gel. The result is a marked pattern, like a supermarket bar code, which can be studied to show the sequence present.

The results are sent to the Human Genome Project computer centre at Northwick Park Hospital. Correlations and comparisons are made with previously reported gene sequences. The point is to identify an alteration in the pattern on the gels within a specific area within the genome unique to those suffering from the recessive ataxia.

Dr Chamberlain went on: 'We know the defective gene is located in the 9th chromosome. And we think we have narrowed down the options to within 500,000 of the sequence.'

Narrowing the options further is the task for 1994. Amid the ordinary looking laboratory, sporting its collection of chemical jars, electrical equipment of a none too impressive nature, and a jungle of 'post- it' notes, lies the potential identification of yet another of the hidden codes of mankind.

The research, funded by the Ataxia charity, the Medical Research Council and other bodies, costs pounds 250,000 a year.

The team knows the potential effects of 'success'. Dr Chamberlain said: 'Ethics in genetics is a subject that is discussed in everything we do.'

The pictures of patients on the pinboard behind her desk are a reminder of her work's clinical aim - even if success is some way off.

(Photograph omitted)