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Mark D. Uehling

February 10, 2003 | The cliché is that no one ever gets fired for buying gene sequencing equipment from Applied Biosystems Inc (ABI). But Sandra Talbot wouldn’t buy from ABI even if you quadrupled her tiny DNA sequencing budget.

Talbot is a research geneticist at the U.S. Geological Survey in Fairbanks, Alaska, where she runs Li-Cor Biosciences DNA sequencing equipment 24/7, helping field biologists in the U.S. and abroad track the genetic makeup of 40 species of wild birds, mammals, and plants. “The Li-Cor is cheaper and more reliable,” Talbot says. “We’ve never had those machines down for more than half a day.”

ABI remains the Intel of DNA sequencing. Its machines are ubiquitous and highly respected. Most of its sophisticated customers are satisfied. But there are other companies in the DNA sequencing field, and they say they are surviving on the margins of ABI with better software, better service, or technological advantages.

Survival on the Margins
For its part, the mighty ABI, with a 78 percent market share, is hardly threatened by these small fry. But like the science they support, makers of sequencing equipment are evolving -- and sufficiently focused to thrive. These companies say that as sequencing technology becomes more of a commodity, some customers are doing comparison shopping.

Competitors don’t see a monolith -- an IBM circa 1980 -- but a leader with a few vulnerabilities. “I can make a career out of Applied Biosystems leftovers,” says Paul Newman, director of sales and marketing at SpectruMedix LLC, a niche DNA sequencer company. “A lot of smaller customers have had had less than stellar support from Applied Biosystems, and we hope to capitalize on that.”

For its part, ABI says that attentive support is a key reason -- after high performance -- that customers select it. Large numbers of its customers, the company says, are individual researchers. “If we didn’t take care of them, we’d be in big trouble,” says Marianne Hane, director of genetic analysis business management at ABI. “Support is a priority for us. We do really try to put what we need to support all customers in place.”

Despite ABI’s dominance, there is plenty of competition for the rest of the pie. Last May, BioInformatics LLC, a consulting firm, surveyed 230 scientists and life science executives actively engaged in DNA sequencing. The Avis of DNA sequencing -- Amersham Biosciences -- controls only 11 percent of the market with its MegaBACE line, according to BioInformatics. Most of those surveyed are using such equipment for tasks other than traditional sequencing: mutation detection was the common alternative, with more than half of all respondents citing it.

Customers have other reasons to give other brands a chance. In Alaska, geneticist Sandra Talbot says has heard incidents of ABI equipment being down for weeks. There were general scientific concerns about the quality of the data coming off the ABI machines. And there were ease-of-use issues. “I want something that doesn’t break, that high school students can run,” she says, noting her frugal lab uses such students as a part-time labor force

‘Lots of Platforms’
The BioInformatics survey found that while DNA sequencing instrument buyers tend to use the software that comes with their machines, they also rely on a variety of other software packages for isolated, specific tasks. “I find it amazing that these little guys get in there,” says Robin Rothrock, marketing director at BioInformatics. “You may labor under the illusion that there is one mother platform, but there are lots of platforms being used.”

For some companies, software is key. Li-Cor has a small slice of the overall DNA sequencing market, but is benefiting from a few key tasks for which ABI and other machines are not so well suited. “These are niche markets where Li-Cor is the best instrument,” says Jeff Harford, team leader for genomics at Li-Cor. In general, he says, science is shifting away from traditional sequencing per se. “We’re more interested in gene function and where the genes are,” Harford says. “We used to go head to head against ABI a lot more. We had to force ourselves not to worry about getting into the national genome centers.”

Beyond Sequencing
What Li-Cor instruments can handle, Harford says, are chores like analyzing microsatellites (short, repetitious sections of DNA) or amplified fragment length polymorphisms (AFLPs), a method that looks at patterns of individual differences in DNA. Another hot technique of late is called tilling (targeting induced local lesions IN genomes), and Li-Cor is getting word-of-mouth endorsements from bench scientists about its equipment being especially well-suited for this.

Uniquely among its competitors, Harford says, Li-Cor can also do diagnostics and repairs online. “We can log on to the Internet, take a look at [a customer’s] instrument, their data, and diagnose it here in Nebraska.” Even so, according to the BioInformatics survey, Li-Cor has just 2 percent market share.

One rung above Li-Cor, with a 4 percent market share, Beckman Coulter acknowledges the big dog on the block -- but not much fear. Jeff Chapman, the company’s strategic marketing manager, says Beckman Coulter’s broad mission in diagnostics and throughout the various ecosystems of the biomedical landscape -- beyond large sequencing centers -- led it to start from scratch when designing the CEQ 8000 Genetic Analysis System.

The company says the key was to automate and simplify the sequencing work so that non-experts could do it, without spending years to master the intricate details. “It’s an easy system to use,” Chapman says. “The more you automate things that are manual and tedious, the less the scientist has to intervene.” For Chapman, there’s an analogy to mass spectrometry -- once arcane , it is now routine in many labs. He predicts DNA sequencing instruments will someday be just as unremarkable in small labs and hospitals.

Chapman adds that market research -- and the company’s expertise in microfluidics and workflow -- allowed Beckman to come up with DNA sequencing solutions for labs of all sizes. “Genetic analysis is now an integral part of all mainstream research. We’ve made DNA sequencing available to the majority of labs out there.”

‘This Is Good DNA’
In the end, of course, what matters is the data coming off the machine. Beckman is trying to let nonexperts get as much good data as they can without twisting the knobs. Says Chapman: “We’ve integrated quality values automatically. The system will tell you, ‘This is good DNA.’ If you like, it will trim away sequence of low confidence. It will also trim away contaminants.”

At Amersham Biosciences, meanwhile, Trevor Hawkins, Amersham’s senior vice president of genomics, has the benefit of formerly running the U.S. Department of Energy’s Joint Genome Initiative. So he’s quite familiar with the competition, even if he can’t be coaxed into direct comparisons -- or into uttering its name. Hawkins says one Amersham advantage is in its consummables: “Amersham has done a tremendous job providing novel reagents, novel enzymes, novel dye sets,” he says.

But software is also integral to the company’s strategy, he says, citing Amersham’s Scierra laboratory information management system (LIMS), which can pump data into an Oracle database. Scierra modules, he says, can unite not only genotyping data but also information flowing off microarrays and proteomic systems. “It is critically important to us as an organization that we provide the same look and feel of software on all of our systems, and that we allow people to tie together data from all those systems.”

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