How scientists broke the genetic code of a killer

PUBLISHED : Thursday, 17 April, 2003, 12:00am
UPDATED : Thursday, 17 April, 2003, 12:00am

A Canadian team sets a record pace in identifying the makeup of the coronavirus

A coronavirus specimen - weighing just one-millionth of a gram and taken from the lungs of a patient who died in Toronto - has played a key in the global fight against the deadly Sars.

A crack team of 20 scientists at the Genome Sciences Centre of the British Columbia Cancer Agency in Vancouver worked round the clock and, in a record five days, broke the virus' genetic code on Saturday. The US Centers for Disease Control and Prevention on Monday produced a second gene draft, and yesterday both the University of Hong Kong and the Chinese University announced their own draft sequences.

The speed with which the Canadians sequenced the virus owed much to techniques developed in the past decade in the human genome project - in particular, to the so-called shotgun approach to gene-decoding.

The shotgun technique makes gene-sequencing a fully automated process. It involves blasting the gene samples into fragments and then using supercomputers and sequencers to decode the broken pieces and reassemble them.

What used to take months or even years of manual sequencing can now be done in weeks or even days, said the British Columbia Cancer Agency's molecular biologist and vice-president for research, Victor Ling. 'The sequencing [of the coronavirus] took just one day. The difficult part was converting the virus' RNA into DNA at the beginning,' Dr Ling said.

Coronaviruses belong to a virus family that use only RNA to carry genetic material, instead of the DNA found in most life forms.

Because gene sequencing only works with DNA, the virus' RNA first must be translated into DNA.

'RNA is much less stable and difficult to handle. Converting it to DNA [for sequencing] took up most of our time, about four days,' said Dr Ling.

Fragments from copies of the original virus sample containing representative genes are decoded by automated gene sequencers. The Canadian gene maps detail the sequences of the virus' 29,727 nucleotides - or genetic units - while the Hong Kong maps cover about 30,000.

The sequenced fragments are compared to each other to place them in the correct order along the chain of nucleotides. Known members of the coronavirus family typically contain 29,000 to 31,000 nucleotides.

But the Canadian scientist cautioned the gene mapping itself did not prove that the virus was the main cause of Sars. Armed with the genome, researchers hope to reveal clinching evidence that a coronavirus is the sole cause of Sars: whether monkeys injected with the new coronavirus fall sick.

If it proves to be the culprit, the next step is a vaccine using the virus' proteins to trigger an immune response instead of a viral invasion and sickness.