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Thursday, December 10, 1998 Published at 21:08 GMT


Hunting down the genes

Automation is aiding genome research

Sequencing the genome of the worm C. elegans and other organisms will have a major impact on human life says BBC News Online Science Editor Dr David Whitehouse.

C. elegans is the most complex creature to have its entire genome sequenced. Scientists have a complete map of the genes in a number of other organisms, but these are all single-celled lifeforms such as bacteria.

Only last month, Swedish and American researchers announced that they had mapped all the genes in the bacterium that causes epidemic typhus.

But the worm sequence marks a significant step upwards. C. elegans is constructed from many cells. We humans are also multi-cellular with a great deal in common with this nematode.

A cure for cancer

For example, it is curious that although worms do not suffer from the same old-age problems we do, they do have similar genes that in humans cause colon cancer and Alzheimer's disease.

[ image: Genes hold the key]
Genes hold the key
Looking at the development of C. elegans could help us understand cancer. As the tiny worm develops and grows, certain cells are deliberately destroyed in a way that is determined by the worm's genes.

Almost all animal cells have a similar self-destruct mechanism. In humans, it is one of the body's leading defences against cells that become cancerous. When this self-destruct mechanism fails, a cancer can occur. So it is by studying the genes that we may learn how to manipulate the processes that take place inside a lifeform - from man to microbe.

Gene hunting

At the moment, perhaps 30 organisms have had their entire genetic code unravelled. By the end of the century, we may have the complete genetic codes for perhaps 40 lifeforms.

[ image: C. elegans heralds a new era in biology]
C. elegans heralds a new era in biology
British scientists are leading an attempt to sequence Streptomyces, an important group of microbes which make almost two-thirds of all known natural antibiotics and which have provided the majority of new antibiotics in the past 50 years.

As well as antibiotics, Streptomyces and their near relatives produce anti-fungal agents such as nystatin, anti-cancer drugs, immunosuppressants for use in transplant surgery, anti-parasitic agents and even a herbicide. A fuller understanding of the genes will lead to the development of yet more useful products.

Fighting disease

Researchers have also unravelled the complete genetic sequence of one of the world's worst scourges, the tuberculosis bacterium. It kills 3 million people in the world each year. Drug companies are thrilled.

Last year, Human Genome Sciences in Rockville, Maryland, determined the entire genetic sequence of the bacterium Enterococcus faecalis. This organism, a normal inhabitant of our intestines, is emerging as a major component of hospital infections.

In the United States alone there are over 800,000 cases of such infections each year costing about $4 billion to treat. Many strains of this bacterium are resistant to most antibiotics and most have acquired resistance to Vancomycin often regarded as the antibiotic of last resort. This dangerous microbe has 4,000 genes, 75% of which bear some relation to known genes, 25% of which seem new and strange.

More food please

It is not just microbes that scientists want to sequence, they want to look at plants as well and for good reason. There is a strong interest among many cereal biologists to sequence the rice genome. Rice, wheat and maize account for approximately half of the world's food production.

[ image: Rice yields need to be increased]
Rice yields need to be increased
Over the past 30 years, world rice production has doubled as the result of the introduction of new varieties and improved technology. However, these improvements are no longer keeping pace with the demand from hungry mouths.

As countries become more affluent there is a greater demand for rice but less space to grow it in. Knowing the rice genome would allow biotechnologists to improve yields.

Safe of dangerous

We also have the complete sequence of the ubiquitous E. coli with its 4,200 genes, one third of which are mysterious. For more than 70 years E. coli, a natural inhabitant of the lower intestinal tract of animals has been one of the most studied of organisms.

[ image: E. coli: The workhorse of biotechnology]
E. coli: The workhorse of biotechnology
In recent years, it has become the workhorse of biotechnology. By introducing genes from other species, it serves as a living factory producing human insulin and other medicines.

The 1996 outbreak in Scotland of toxic strains of E. coli was an example of an increasing number of human food poisonings. Microbiologists want to know why one strain of E. coli is harmless and another strain that can kill. The answer to that question will lie in the genes.

One by one

The sequencing of the genome belonging to C. elegans heralds a new era in biology. For the first time in history we have access to the entire genetic content of a growing number and variety of living creatures. For living things, this is analogous to the discovery of the periodic table in chemistry.

"It's an avalanche" says Daniel Drell project manager for microbial genomes for the US department of Energy. The first genome was sequenced in 1995, many more are on the way. Even the quest to sequence the human genome will be completed very shortly.

Craig Venter of the Institute for Genomic Research in the United States puts this work into perspective: "It's scientific information that will be used for centuries".

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Sanger Centre

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