DNA Sequencing Becomes Cheaper

The cost of decoding the blueprint of life on Earth may drop dramatically, thanks to recent research conducted at the Harvard Medical School.

The Harvard research team—led by Professor of Genetics George M. Church, M.D.-Ph.D. student Jay A. Shendure, and fourth-year genetics graduate student Greg Porrec—announced last week, in the journal Science, that it has developed a faster and less expensive way to sequence DNA.

Compared with previous technologies, which suspended DNA fragments in gel and decoded them using electrophoresis, the new procedure attaches thousands of DNA fragments onto tiny one-micron beads. Four different-colored dyes bind at specific locations, depending on which of the four DNA bases is present, allowing scientists to scan the sample with an epifluorescence microscope to determine its base sequence.

The new procedure can be used to compare differences with a previously sequenced genome, making it useful to determine how the 0.1 percent genetic variation among humans is expressed. It cannot be used to sequence an entirely new genome.

The new procedure is both faster and cheaper than electrophoresis, because the epifluorescence microscope is less expensive and more widely available, the process can be conducted using “off-the-shelf instruments and chemical reagents,” and the epifluorescence scanning process is much faster than electrophoresis.

“Electrophoresis is slow. You can’t really speed it up,” Church told Reuters News Service this month. “But with a digital camera, you can go as fast as electronics can go.” Church did not return requests for further comment.

Cost is important because the potential applications for sequencing human genomes—such as identifying the genes responsible for cancer or other diseases—are only valid if the price of the procedure falls. The most expensive element of the process is currently the $140,000 epifluorescence microscope.

Scientists would need ultimately to lower the cost of sequencing a human genome to $1,000. The electrophoresis method, however, costs about $20 million, while the Harvard researchers’ epifluorescence method, which processes thousands of bases at the same time, currently costs about $2.2 million. By speeding up the process, the new method reduces lab time and, consequently, cost. Researchers say they hope it can be decreased even more.

“We’re estimating that we can lower the price point by roughly ninefold. Things are going very well, so we anticipate this can go down even further,” Shendure said. “This is the first iteration of the technology working.”

The Harvard technology has been licensed to Agencourt Bioscience Corporation in exchange for royalties.

Benefiting from a spate of National Institutes of Health grants, work in the cutting-edge field is moving quickly, as researchers swap ideas while competing to make potentially lucrative innovations first.

“We’re collaborating all over the place,” Shendure said. “This field will move a lot quicker if there’s a lot of cross-pollination between labs with different ideas. One of the things we try to do is develop a general framework that other people can substitute their different technologies into and move even quicker.”

454 Life Sciences of Branford, Conn., also announced that it had devised a faster way to sequence DNA. It is selling a $500,000 machine that it claims is equivalent to a $50 million sequencing center.

That compnay’s machine uses luminescent chemicals as well, but the bases are recorded by setting off luciferase, a bioluminescent.

While this machine is more expensive than the Harvard technique, it could be used to sequence a genome from scratch.

—Staff writer Samuel C. Scott can be reached at sscott@fas.harvard.edu.