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Prof. Works for Your Cheap DNA

Genome sequencing has already dropped in price from $3 billion to about $10 million since 2003, when the Human Genome Project was first completed, and now Harvard Medical School (HMS) Professor of Genetics George M. Church is spearheading a project that aims to make personal genome sequencing affordable within two years’ time.

“There’s two aspects of it...chronological and economic,” Church said. “We will try to drive [the price] down by another factor of 10 within the next year or two.”

This means the millions that it now costs to sequence one person’s genome will drop to $10,000 to $20,000—what Church said he sees as a reasonable price for a complete personal data set.

“People pay $35,000 to clone their cats,” he said.

He explained that the cost of the process has decreased because of technological improvements and miniaturization. Thanks to microchemistry and microtechnology, he said, previously unwieldy and inefficient technology has been outphased.

“Now we can get 100 million base pairs on little glass microscope slides,” he said. The complete human genome contains about 3.2 billion base pairs.

Jeffrey Schloss, program director of technology development coordination at the National Human Genome Research Institute (NHGRI), said Church is a leader in genomic development.

“George’s idea of essentially shattering the genome and then amplifying each of those different pieces in situ...has really stimulated the field of single fragment sequencing,” he said. “[He] has been a leading thinker in pushing forward to develop new genomic technologies.”

Church’s team has a “Centers of Excellence in Genomic Sciences” grant from the NHGRI. His research team is one of about 20 groups in the program that are working on genome sequencing.

The human genome carries encoded in it all the genetic information that determines biological traits. So far, though, not enough individuals’ genomes have been decoded for researchers to be able to compare the 0.1 percent of DNA that differentiates the traits of one person from those of the next. To do so would enable researchers to pinpoint the particular genes that relate to a specific characteristic, such as a disposition toward a certain disease or physical attribute like blond hair.

Church and his team are beginning to gather genetic information from volunteer test subjects, as costs of doing so decrease, in order to amass a data pool that would have further applications.

Traditionally, researchers have had to promise these volunteers that the information in their DNA would be kept secret, leaving the researchers vulnerable to lawsuits if this data was accidentally made public. Church’s lab, however, is using only those volunteers who do not care about the release of their genetic data for one reason or another.

“They self-identify as being at lower risk,” he said. “It’s kind of an experiment inside an experiment.”

At the moment, Church and his team are working on the sequencing of three subjects’ genomes, which they say they hope to have the data from in March.

Church said that, since the project was the cover story in Scientific American this month, his team has received hundreds of e—mails from people who want to have their genomes sequenced and placed in the public domain.

However, there are potential problems with a future of widespread genome sequencing, according to Church and Schloss.

These range from the possibility that people might assume that their futures were set if they knew their genome, discounting the importance of environment and “nurture,” to more practical issues of genetic discrimination by employers and insurance companies.

Church said that much discrimination is already based on genetics, as when insurance companies charge young men more than young women for car insurance, which he said was essentially discriminating against the “Y” chromosome.

Both Church and Schloss said that the emergence of legislation to combat genetic discrimination was vitally important.

“There are drawbacks to almost every technology,” Schloss said. “The question is, what are the risks and what are the benefits? Where do you come out on that seesaw?”

If all goes according to plan in Church’s lab, he said he expects to finish on top.

—Staff writer Alexandra C. Bell can be reached at acbell@fas.harvard.edu.

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