Competition in gene analysis heats up

A race is shaping up in the genomic-instruments business.

Until now, the market for the equipment drug researchers use to analyze human or bacterial DNA has been dominated by California's Applied Biosystems Group.

But recently three New England companies have begun promoting new methods to speed up the analysis of genetic information. That could lead to cheaper drugs and eventually let doctors offer customized treatments based on a patient's DNA. The companies all have the same goal: more orders for their equipment from drug developers and academic researchers.

A paper published earlier this month by the online version of Science magazine described a faster-paced method to analyze the genome using common laboratory instruments, which researchers at Harvard University have licensed to Agencourt Bioscience of Beverly. The authors say the technique could lower the cost of mapping a human genome to $2.2 million, from $20 million.

Scientists hope machines could one day scan a human genome for just $1,000, which would make such mapping commonplace and allow more drugs to be personalized for individual patients. One of the idea's originators, Harvard University genetics professor George Church, said that even a $20,000 scan would be economically viable in the US healthcare system.

In a scientific paper published July 31, 454 Life Sciences of Branford, Conn., described its own faster sequencing method. Applied Biosystems said it also is working on next-generation sequencing technologies, as is Helicos BioSciences Corp. of Cambridge.

Jonathan Rothberg, 454's chairman, estimates the market is worth $1 billion a year and could generate up to $2 billion in business if faster equipment were available.

Now it's a matter of which company can commercialize its product fastest, said Chad Nusbaum, co-director of the genome sequencing and analysis program at Broad Institute in Cambridge. The faster the analysis, the less expensive the process.

''It's definitely a case where more competition is going to drive down the costs," Nusbaum said.

Nusbaum and others say that is already starting to happen. ''Ten years ago some of these ideas were just floating around, and now they're actually turning into machines," said Hemchand Sookdeo, a technology director at the Cambridge laboratories of drug maker Wyeth Pharmaceuticals.

DNA, or deoxyribonucleic acid, is a chemical mainly found in the nucleus of cells that carries instructions for making the body's structures and materials. The ''human genome" refers to all the DNA strands in a body.

The new techniques all have in common the ability to ''read" shorter strands of DNA than traditional methods. An assembly of chemical trays, computers and microscopic instruments is used to analyze DNA samples.

By using genome sequencing to find genes associated with particular diseases, scientists aim to develop drugs that treat those ailments.

The best-known work in the field is the Human Genome Project, a $3 billion, federally sponsored effort that mapped out the 3 billion chemical base pairs that make up human DNA.

The project was mostly done using $350,000 machines supplied by Applied Biosystems, a California unit of Applera Corp. They are based on what is known as the Sanger method, named after Frederick Sanger, the British winner of the 1980 Nobel Prize in Chemistry, and automate a process known as ''gel electrophoresis." It uses an electrical charge to break DNA apart into its four nucleotides, which are then analyzed through radiography. The nucleotides pair off to encode genetic information. But even at speeds of 20 base pairs per second, it can still take months to fully analyze the DNA of even a bacterial organism, which might have about 5 million base pairs. The authors of the paper published by Science magazine's website, describe a faster process in which a common type of laboratory microscope can be used, with an error rate of less than one per million base pairs scanned.

The paper describes how researchers replicated millions of DNA fragments from the bacteria e. coli and attached them to tiny plastic beads just one micron across. Researchers packed 14 million beads into an area the size of a dime and marked them with fluorescent dyes to be read by a digital camera, sidestepping the slow electrophoresis process. The results can be compared to a known genomic map of the DNA, said Harvard's Church, one of the paper's authors. ''We're looking for mutations," he said. ''It's like looking for a needle in a haystack."

It could be a while before the technique is perfected for human DNA molecules. But Church said the technique should still be useful for biotechnology companies. For example, it could help them create bacteria to produce a certain type of protein. It could also allow drug companies to better understand how their drugs affect certain bacteria.

In April, Agencourt's principals sold the company to Beckman Coulter Inc. of Fullerton, Calif., for $100 million, plus up to $40 million in future payments. Agencourt's operations were not affected and it now has more than 100 employees. Neither Harvard nor Agencourt would disclose the terms of their licensing agreement.

Ross Kerber can be reached at kerber@globe.com.