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Gene Array Give Away: Stanford Scientists Put Instructions, Software for Chips on Net

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Scientists looking to analyze which genes are active in which cells can either pay a company like Affymetrix to provide the technology or they can now put together the equipment themselves, using instructions and software freely available off the Internet. David Botstein and Patrick Brown at Stanford University head one of the world’s most prolific bioinformatics labs in academia, and they’re giving away the manual.

When microarrays first came on the scene a few years ago, they offered a breakthrough for biologists looking to analyze the expression of thousands of genes at once. Much of this technology, which uses robots to place specks of genes onto glass chips to study how cells work, was originally created by scientists at Stanford and commercialized through private companies. Botstein and Brown have decided to stop the flow of information from Stanford into the pockets of commercial entrepreneurs. By creating a website dedicated to sharing Stanford’s knowledge of microarrays, they’ve given academics the option to put together the technology themselves without paying industry prices.

The Botstein-Brown lab functions without any industry backing, Botstein proudly noted at the inaugural meeting of the European Life Science Organization, held September in Geneva. Labs can reproduce the technology found in his lab for about $100,000, he said, encouraging others to get into the game.

“You too can do genomics in the comfort of your own lab,” joked session chairman Jonathan Knowles from Basel, Switzerland upon hearing Botstein’s presentation.

The new Stanford Functional Genomics lab uses a chip-based, two-color fluorescent-hybridization array technology to categorize the gene expression of different cancer cell types. Botstein reported that he and his colleagues have matched the gene expression patterns to patient survival and cancer submission rates. “This will be important in terms of understanding the biology of cancers and deciding treatment,” Botstein noted.

Five years ago, Stanford graduate student Dari Shalon developed the original microarray technology that incorporated a robot-controlled quill-pen-like device to spot DNA onto glass slides. When Shalon graduated, he took the technology and started his own company, Synteni, which he later sold to Incyte Pharmaceuticals. Other companies followed suit with competing models.

Later, Joe DeRisi – then a graduate student at Stanford – created the next-generation system. He took Shalon’s basic design and improved the robot-control program among other things. The improvements allowed the Stanford scientists to do more arrays at a quicker pace and resulted in what can be considered a new product. Brown and his colleagues decided to make the information freely available on the Internet.

“Pat Brown wanted to make sure the [latest] technology didn’t get locked up, so they’ve worked to make sure the information is as widespread as possible,” Mike Fero, director of Stanford’s functional genomics facility, told BioInform.

All you need is about $33,000 for the robot parts, money for the PC, and a motivated student or postdoc, Fero said. A commercially available product costs around three times that much. Stanford’s website provides instructions on where to buy the parts (from companies like Western Technology, Teco, McMasters, Die-Tech, Majer Precision, and Newark Electronics), how to assemble the pieces, and how to program the robot. “It’s a no brainer,” Fero said.

“The added value that companies like Affymetrix offer are fairly small in terms of hardware,” he added.

Some labs that analyze relatively small numbers of genes may find gene-array packages sold through various companies attractive, Fero said. One former Stanford student started a company called GeneMachines that offers an almost exact copy to the robot whose instructions can be found online. But GeneMachines’ microarrays only print 100 slides at a time and use proprietary software. For labs looking to run large exploratory gene-expression studies, the costs quickly run up.

Using Stanford’s homegrown technology, the Stanford group analyzes about 50,000 genes at a time for about $120, including the cost of the array, the database support, and exploratory analysis. “That’s a pretty low-cost way to take a gene expression level snapshot of what is going on inside a cell,” Fero said.

But Fero keeps his eyes on advances coming out of industry. “The big players are involved now,” he commented. “Some very strong technology companies like Corning and Agilent have gotten into this field and have announced that they will have technologies that will drive costs way down,” he notes.

Will companies in industry supercede their homegrown efforts with faster and cheaper gene-array equipment? “I hope so,” Fero said. “But for the short-term, this works.”

The Brown Lab’s complete guide to microarraying for the molecular biologist is available at http://cmgm.stanford.edu/ pbrown/mguide/index.html.

—Melissa Mertl

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