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SCIENCE-FOR-THE-PEOPLE  March 2000

SCIENCE-FOR-THE-PEOPLE March 2000

Subject:

Gene chips, expression profiling and gene therapies

From:

"Mr P.A. Van Heusden" <[log in to unmask]>

Reply-To:

Science for the People Discussion List <[log in to unmask]>

Date:

Mon, 13 Mar 2000 11:09:08 +0000

Content-Type:

TEXT/PLAIN

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Parts/Attachments

TEXT/PLAIN (86 lines)

Hi

Just following on on the discussion arising from the 'Gene chip' article.
Firstly, these kind of gene chips are not new - maybe the most famous
producer of them up to now has been Affymetrix (www.affymetrix.com), who
have used techniques analagous to those used to produce silicon computer
chips to 'array' DNA fragments on chips with a very high density.

Affymetrix (and others') products are similar in purpose to so-called
'micro-arrays', glass or nylon slides with 5,000 or 10,000 'spots' of DNA
each. These are used in 'expression profiling' - i.e. trying to detect
whether (and for some variants, how much) a gene is 'turned on'.

As people might know, while the human body is constantly 'transcribing'
DNA into mRNA molecules, not all genes are being transcribed all the time.
Whether a particular gene is being transcribed or not depends on a complex
gene regulatory network, which involves proteins which bind to the
'promotor region' of genes, causing the transcription of those genes to be
blocked.

The hope is that by examining 'expression profiles' of for instance,
different tissues, or different individuals, an idea can be had of which
genes 'do' what. This is pay dirt for pharmacogenetics, of course. The
silly thing is that the genetic research community seems to have a dual
personality on this issue - on the one hand, everyone who knows anything
realises that the picture is extremely complex - the current statistical
analysis of the genetic basis for various diseases (e.g. using family
studies) suggests that there are often a number of different collections
of genes which underly the same disease.

An example here is 'Celiac disease', aka. gluten intolerance: family
studies suggest that the genetic profile of all people affected with the
disease is not uniform. So with this disease, as in schizophrenia or
bipolar disorder, we might be dealing with a number of different
mechanisms with the same final result. Even if we weren't, at present we
can study gene expression only statistically - understanding the actual
mechanism of gene interaction is way, way beyond us. Even with the
'refined' techniques of micro-array or gene chip based expression
profiling, what we are getting is essentially points on graph - we still
don't know what the graph is, let alone what the gene expression network
which leads to the graph is.

For anyone who feels up to it, a good presentation on the state-of-the-art
in modelling gene regulation networks is at:
http://industry.ebi.ac.uk/~brazma/Genenets/ppframe.htm and note, even this
'state of the art' only takes into account quite simple regulatory events
(gene A switching on causes gene B to switch off), and does not talk about
interaction with environment. The author, Alvis Brazma, makes the point
that trying to find the 'right network' for gene expression data is a
problem which is exponentially hard.

So, we know that we do not know - yet at the same time there is tremendous
pressure, particularly from industry, to pretend that we are a few years
away from all sorts of 'genetic cures'. This pressure pervades science -
particularly when public science is a poorly funded enterprise, oriented
towards supplying trained scientists and other basic necessities for
industry. Journals like 'New Scientist' have a lot on their conscience as
well - they constantly, stupidly, reduce science to flash-bang
reductionism - the kind of science which fills school chemistry classes
with smells and noises, but not much else. Finally, of course, 'science
writers' for newspapers play the same fiddle - today's Independent has a
ridiculous piece on how high testosterone in fetuses (i.e. being male)
leads to long fingers which in turns leads to holding senior positions in
orchestras.

Anyway, my rant will shortly end. Without publically spiriting scientists
- something only possible in the context of public science funded and
supported as a contribution to society, not profit - we're basically
trapped into a downward spiral. And it gets really scary from here on in,
particular when we consider the implications of tampering with genetic
'causes' using gene therapies, when we aren't even close to understanding
the side effects.

As I've said before, the only way forward is for scientists to organise
themselves not just as scientists, but consciously and visibly on the same
side as those who oppose the madness of this capitalist nightmare we live
in.

Peter
--
Peter van Heusden : [log in to unmask] : PGP key available
Criticism has torn up the imaginary flowers from the chain not so that man
shall wear the unadorned, bleak chain but so that he will shake off the
chain and pluck the living flower. - Karl Marx
           NOTE: I do not speak for the HGMP or the MRC.

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