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Biomedicine

Gene Sequencing for the Masses

A genomics pioneer’s sequencing machine comes to market.

An inexpensive new gene-sequencing machine is due to hit the market next month, and its creators hope that it will make sequencing more common, ultimately giving a boost to personalized medicine. The machine is the brainchild of George Church, a genomics pioneer who developed the first direct sequencing technology as a graduate student in the 1980s and helped initiate the Human Genome Project soon after.

Commodity genomics: The Polonator, at top, is an inexpensive sequencing machine developed by George Church’s lab at Harvard Medical School and by Danaher Motion, an instrument company in Salem, NH. At bottom are genetic markers with fluorescent tags that glow red, green, yellow, and blue. Each marker is bound to a single base on a fragment of DNA. During a sequencing run, the Polonator captures and analyzes 5.7 million such images to generate the sequence of each fragment.

Church sees greater access to sequencing as a vital component in the drive toward personalized medicine, in which treatments and preventative medicine are tailored to an individual’s genetic makeup. The new machine, which was developed with an “open source” philosophy, was commercialized by Danaher Motion, based in Salem, NH, with the specific intent of keeping costs low. “It seems like the biomedical-instrument field in general tries not to commoditize,” says Church, who heads the Center for Computational Genetics at Harvard Medical School, in Boston. “It tries to keep profit margins high and slow the inevitable decrease in cost.” The Danaher device will cost roughly $150,000, a third to a tenth of the cost of systems currently on the market.

The technology will become an integral part of Church’s other brainchild, the Personal Genome Project, an effort to enable personalized medicine by providing a test bed for new genomics technologies and analytic tools. Church and his collaborators are using the new device to sequence the genomes of the project’s first 10 volunteers, who will share their genome sequences, medical records, and other personal information with both scientists and the public. Church hopes that, ultimately, thousands of people or more will have their genomes sequenced as part of the project, and that the result will be a huge compendium of data that is useful to both the volunteers themselves and to the research community. “Part of the goal of this project is as a bridge between the research market, which is small, and the consumer market,” says Church.

Church’s group has spent the past several years developing prototypes of the sequencing device–known as the Polonator–from off-the-shelf components. Church originally planned to create an instruction manual for building a Polonator from scratch and post it on the Internet, but he ultimately decided that it would be more effective to develop a commercial device. His team partnered with Danaher Motion, a precision-instrument maker that built movable microscope stages for earlier versions of the technology. Over the past year, Danaher has worked with Church to develop the cheapest and most robust system possible.

The device is a commercial version of the polony sequencing approach developed in Church’s lab over the past 10 years. Millions of beads coated with small fragments of the DNA to be sequenced are spread on a glass slide. Next, a series of fluorescently labeled DNA bases bind to the fragments. Finally, a standard fluorescence microscope reveals which base is at each position on a fragment. (The commercial version of the technology can accommodate a billion beads and has a more sophisticated imaging instrument.)

While the scientists don’t yet have the final figures on the Polonator’s accuracy and throughput, they expect that it will sequence 10 billion base pairs in a single 80-hour run, a capacity equal to or greater than that of currently available technologies. Harvard and MIT’s jointly run Broad Institute for genomic medicine, in Cambridge, MA, and the Max Planck Institute, in Germany, have already purchased devices at the $150,000 sticker price, and the machines should be delivered within the next week or two. General availability is expected by mid- to late May.

Despite almost no marketing, the Polonator has already created a buzz in the research community. McCarthy brought a prototype to a sequencing conference in Florida earlier this year and says that people were lined up to see it until the early hours of the morning. Last week, scientists at a genome-sequencing conference in San Diego, where McCarthy gave his first public presentation on the technology, found the concept intriguing. One of those in attendance was Vladimir Benes, head of the genomics core facility at the European Molecular Biology Laboratory, in Heidelberg, Germany. “It’s definitely in the spirit of George Church to make technology as accessible as possible and let the community do what they like,” Benes said at the time.

Patrice Milos, chief scientific officer at Helicos BioSciences, a company based in Cambridge, MA, that has just released its own sequencing machine, had a more muted reaction. “As with any technology, it’s seeing what they can deliver that matters,” Milos said.

The Polonator embodies an open-source philosophy. It was designed so that users can tinker with it in any way they wish. All the parts can be swapped out, and scientists can use enzymes and chemicals other than those sold by Danaher for the sequencing process. Church and others are already working on alternative chemical processes that could make the instrument more efficient. “The fact that it’s open source is great,” says Andrew Barry, supervisor of process development at the Broad Institute. “It’s going to be a community-driven instrument.”

Church believes that sequencing will ultimately be a more effective personalized-medicine tool than the microarray technologies currently on the market. (Several companies now offer chips studded with small pieces of DNA that can be used to detect specific genetic variations linked to disease.) By looking at the entire genome, sequencing is able to identify mutations that microarrays cannot. “Sequencing is turning out to be as cost effective at most things as chips are now,” Church says. “And you can do things with sequencing you can’t do with chips.”

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