They were a happy but slightly nervous group of scientists16 handpicked lab chiefs, one of whom had come all the way from New Zealand to Long Island, New York, for the experience. They would build DNA microarrayers from off-the-shelf parts under the eyes of the machine's inventors, Pat Brown and his associate Joseph DeRisi, and learn how to use the machines efficiently.
They met in a new building at Cold Spring Harbor Laboratory, which hosted the two-week program. "People shouldn't have to wait for years and years for this new technology," declared James Watson, codiscoverer of DNA's structure and president of the laboratory, as he wandered through the messy room early in the session. "If you can look at 15,000 genes at one time, instead of 3, you can make so much more progress.... After I heard Pat Brown speak at a meeting recently, I thought, 'You have to have a course!'"
Eight times more scientists had applied for this training than could be admitted. Now the chosen few12 men and 4 womenwere faced with mounds of crates and boxes full of bewildering parts that they were expected to assemble into four working machines. Clearly uneasy, they formed small groups around piles of equipment.
Many of them kept consulting their copies of the "MGuide," a loose-leaf book that had been printed off Pat Brown's Web site. Brown had posted the step-by-step instructions for making DNA microarrayers on the Web so that his techniques would be freely available to all researchers. Nevertheless, the visiting scientists seemed glad to have Brown and DeRisi right beside them as they started their work.
DeRisi, in particular, knew most of the pitfalls. He had actually built a prototype of this arrayer himself a few years earlier, during three months of intensive work. "I got the parts from various manufacturers, but not a lot of literature gets shipped with these parts," he recalled. "Eventually I figured it all out and kept a big notebook." Since then, he has made five more arrayers, improving and simplifying the procedure on each pass.
The parts for an arrayer cost around $25,000. Brown and DeRisi had sent four sets to Cold Spring Harbor Laboratory from Stanford. They also brought a container of yeast genomic DNA so that each visiting scientist could amplify (make multiple copies of) it and learn how to print it onto glass microscope slides in the new arrayers.
The early morning chaos of wires, cables, motors, odd-shaped parts, and wrappings on tables and on the floor slowly cleared up. By 2 p.m. on the first day, most of the arrayers' foundationsthree servomotor-powered linear rail tables over an antivibration tablehad been laid and the participants seemed a little less lost. Brown was impressed. "Things are running amazingly smoothly," he remarked. "There have been no glitches! Usually there are some. I kinda wish we had some, because it's a great troubleshooting experience to find out what went wrong."
His wish was soon granted. Suddenly a loud, ominous grinding noise brought everything to a standstill. "Ooh, what did I do?" exclaimed a male voice. Another scientist immediately pushed a red button in a square yellow box on the table and the sound stopped. DeRisi jumped into the fray. "If you need to hit the emergency-stop button, you must power down the amplifier and turn down the program before you release this button," he warned loudly. "Remember that!" He quickly identified the problem and took care of it, reassuring the perpetrator that there had been no serious damage.
The scientists picked up where they had left off. At one table, four of them spent more than three hours doggedly aligning and realigning the printhead until it fit correctlyan essential step. The whole group seemed increasingly determined to keep going. After dinner they returned to the lab for more work. By 12:30 a.m. that night, three of the arrayers were up and running (the last one turned out to have a few missing parts, which would arrive shortly.)
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