THE husband-and-wife team who first genetically engineered a copy of an enzyme found in horseshoe crabs' blood is set to profit from their creation, which is being marketed commercially as the diagnostic tool PyroGene.

Until now, the crab had been the only source of the enzyme Factor C, which is used to test for contaminants in every drug and vaccine, every artificial limb, and every dialysis and intravenous drip.

Now, Factor C's new substitute will earn royalties for the National University of Singapore (NUS), where Professor Ding Jeak Ling works in the biological sciences, and Associate Professor Ho Bow, in microbiology.

Factor C, extracted from the crab's sapphire-blue blood, can detect the bacteria that causes cholera, gonorrhoea and flu.

In their presence, the crab's blood clots and turns jelly-like because of Factor C.

Each year, up to 300,000 of the crabs are caught, bled for the enzyme by the biomedical industry, and returned alive to the sea.

The substitute, introduced to the world recently by United States-based life-science company Cambrex Corporation, opens the door to a market said to be worth up to US$100 million (S$176 million) a year.

But it is only now, 12 years after their research yielded results, that it is being translated into dollars through PyroGene.

PyroGene is short for PyroGene Recombinant Factor C Endotoxin Detection System.

The product is the culmination of research work that Prof Ho started back in 1979. His wife joined him five years later. They replicated the enzyme in 1991, and had it ready for use by 1998.

He said: 'At one point, we said, 'Somebody just take it and market it', because in the old days it was so slow-moving and we were very frustrated.'

NUS Enterprise, the university's entrepreneurial arm, then went looking for a business partner in 2000.

It got offers from three major biotech firms and, in 2000, finally licensed the technology to BioWhittaker to produce a diagnostic tool for worldwide distribution. BioWhittaker is now part of Cambrex.

Said Prof Ding: 'We feel comfortable that Cambrex will be the best company to bring this baby to its full potential. We're very gratified and it really encourages us to continue with our research.'

The royalties that PyroGene will earn NUS are in addition to a 'significant' upfront fee that the university has already received.

Both researchers, who are in their late 40s and have two teenage sons, will receive part of the proceeds.

Mr Robert Blumenthal, a director of Cambrex, described PyroGene as a collaborative effort: 'With this, we can get a much better consistency in results and move away from animal testing at the same time.'

Said NUS Enterprise's head, Professor Jacob Phang: 'This is probably the biggest licence the university has given out - and the greatest success.'

The research has led to a spin-off project - a potential antidote for antibiotic-resistant bacteria.

Prof Ho said it will be a long journey to get the drug to the point where it could be used by people.

'And we need somebody to pick it up from there, to provide the grants, because the cost is so huge.'