DNA sequencers speedread human blueprint makeup


June 11, 2000,

Mercury News


DNA sequencers are speedreaders of the long string of chemical letters, called bases, that make up the human blueprint.


On a computer screen, each base appears in a color -- red, blue, green, yellow -- that paints a picture of the genetic code that is the fundamental basis of everything that we are as a species: physically, emotionally, mentally. If a machine read 3 billion bases per second, it would take 100 years just to read the genetic information inside your cells; fortunately, these machines are much faster.


Until the mid-'80s, biologists had to tag DNA fragments with radioactivity, place them in gels squeezed between two pieces of glass, zap them with electricity, then photograph and interpret a long-patterned stripe. A total of 15,000 bases a year was considered a good year.


PE Biosystem's first sequencer, the ABI Prism 377, set the standard in DNA sequencing and genetic analysis, analyzing 15,000 bases a day. More than 10,000 of these devices, which sell for $115,000, can be found in life science labs around the world, from Harvard to tropical rain forests and above the Arctic Circle.


Competing sequencers, such as the Amersham ALF Express and the Li-Cor IR2, do not offer the efficiency, flexibility, third-party applications or user network afforded by the 377, according to analyst Winton Gibbons.


The emergence of more ambitious sequencing endeavors like the Human Genome Project revealed that something more was needed. While the Prism 377 is adequate for small-scale projects, it could not meet the demands of industrial-scale projects.


So Perkin-Elmer Biosystems developed the ABI Prism 3700 for production-scale life science research. Fully automated, the $300,000 machine offers researchers the ability to work on a massive scale with minimal labor, allowing 1,456 samples to run unattended. More than 1,000 of these machines were placed in labs last year.


The machine doesn't do anything particularly novel; rather, it automates the process on a far larger scale than the 377, cutting sequencing time by 60 percent and labor costs by 90 percent.


The capillaries replace tray-sized racks of toxic Jello-like material used in previous models. Other tasks, such as data collection and analysis, also are automated, allowing 24-hour unattended operation, said PE Biosystems applications manager Nathan Caffo.


Each machine has 96 glass capillaries, hair-thin tubes filled with DNA samples. Pulled along by an electric current, DNA fragments move through the tubes quickly, separating out because small stretches of DNA move faster than large ones. The new machines, stocked with chemicals and more than a thousand DNA samples, can run for more than a day without human intervention.


At full capacity, dozens of machines can churn out an astounding 100 million letters of DNA sequence every day.


Competitor Nycomed Amersham Pharmacia offers the MegaBACE 1000, a rival production scale sequencer. But analysts say it has failed to dominate the market because of smaller output than the PE Biosystem's 3700.


Although PE Biosystems produces the vast majority of sequencers, there is no monopoly of the market, according to Elaine Heron, vice president and general manager of AppliedBiosystems, the division that manufactures the genetic tools.


``We have licensed (our technologies) to a lot of other companies. We have not done any thing to discourage competition. And we try to do what's best for customers,'' said Heron.


``Its a hard system to put together,'' she concedes. ``You need chemists and biologists and engineers and software experts. . . This is a challenge for a variety of companies.''