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EDITIONS
Monday, 7 October, 2002, 11:34 GMT 12:34 UK
What did the Nobel Winners do?
Breast cancer tumour
The winner's work could yield cancer treatments
Three scientists have been jointly awarded the Nobel Prize for Medicine for their discoveries - but what did they actually do?

All three made discoveries which will prove vital in the understanding of the life of the human cell - be it healthy or cancerous.

Their finest work concerns an organism with fewer than 1,000 cells - the nematode worm.

Between them, and cell by cell, they have mapped the development of this worm from the egg, and, on the way, helped tell the scientific community more about the key genetic processes which govern its fate.

Professor Sydney Brenner

When doctors wanted to learn more about what happens to cells in the human body, they soon realised that humans themselves were far too complex to allow doctors to study every single division and differentiation.

It was Professor Brenner's brainchild to use the nematode, which, at only 1mm long, and completely transparent, allows easy viewing of every cell division.

In 1974, he showed that by adding a chemical compound, gene mutations could be induced in the worm - and that these mutations could have profound impacts on the development of the creature.

Nematode
Nematode worm: Success story
This is the bedrock of much genetic science today - demonstrating the principle that our genes, if somehow mutated, might have a radical knock-on effect.

This is the basis of the Nobel Prize award, but by no means the only discovery of Professor Brenner's distinguished scientific career.

He is also credited with the discovery of "messenger" RNA - a key element in the method by which the genetic code in every cell is "transcribed" to produce body chemicals called proteins - which pass on chemical messages to cells and tissues.

Professor Sir John Sulston

Professor Sulston took Sydney Brenner's work and went further with it.

He managed to develop a way of study every single cell division in the nematode worm.

On the way he mapped out the sequence of cell changes and divisions in the developing nervous system of the worm, finding out that this was the same in every single worm.

His key find, however, was the fact that certain cells, rather than keeping on dividing forever, simply died at a certain point in the development of the creature.

This cell death appeared to be programmed.

By looking at a cell on the point of this "apoptosis", or programmed cell death, he was able to map out exactly which genes were involved in this necessary biological process.

In particular, he found a gene called nuc-1 which seemed to be vital to the whole process.

He found a mutation of nuc-1, in which the cell died - but without the DNA within it being broken down - a key part of the process.

This is important because it is the failure of cells to die "properly" at the correct point that it is at the root of many cancers - and the "overenthusiasm" of cells to die which maximises the damage from strokes, Alzheimer's disease or heart attacks.

If apoptosis could be initiated within a tumour, or halted around the site of a stroke, then this would be a massive medical breakthrough.

Sulston's first sequence of the nematode was in fact the first ever complete genome produced of an animal, and as head of the Sanger Centre near Cambridge, he oversaw the production of a "rough draft" of the entire human code by 2000.

Professor Robert Horvitz

Once again, Professor Horvitz built further on the foundations laid by Brenner and Sulston.

He found two proper "death genes" - if these were not present, then cells did not die when they should.

In addition, he found a third gene which interacted with the other two to protect against cell death.

And he made a jump to humans, identifying a gene on the human genome which appeared similar to one of the two "death genes".

Further work has discovered that most of the genes involved in cell death in the nematode have their counterpart in the human genome.

It is this progression into the human genome which offers promise for treatments which either encourage or protect against cell death.

See also:

08 Oct 01 | Health
09 Oct 00 | Health
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