Scientists use new techniques but face tough old obstacles
George Church, director of the Lipper Center for Computational Genetics and professor of genetics at Harvard Medical School, looks at amplified single molecules of DNA with fluorescent computer imaging at his lab.
A THOUSAND DOLLARS is the price considered essential for giving scientists the thousands of sequenced samples they need to understand how genes work, and giving patients access to a personalized DNA snapshot at the doctors office that could show the diseases they are at risk of developing.
Some scientists believe the old methods of sequencing DNA, though improving, will never produce a $1,000 genome, and they are exploring radically different ways to map the blueprint of human life.
Their methods remain far from proven. But there have lately been signs of headway on several fronts.
Its not clear which of these things will be the ultimate success, but I think these are all pieces of the puzzle moving us in the direction we need to go, said Jeff Schloss, program director for technology development at the National Institutes of Healths National Human Genome Research Institute.
THE STARTING POINT
The human genome project yielded the first complete sequence of the 3.2 billion base pairs that comprise the DNA molecule of a person (actually, it sequenced a composite of a few people). Each base is one of four chemicals, their order governing a human beings development.
But that was only a starting point.
While the DNA of one person is 99.9 percent identical to anothers, it is the 0.1 percent of variation that interests many scientists, because the differences may answer questions like why some people develop certain diseases and others do not.
To answer those questions, scientists must compare the DNA sequences of thousands of people. To get them, they must find a way to sequence DNA that, unlike the first sequencing, doesnt require thousands of lab technicians and dozens of supercomputers.
To actually deliver everybodys genome, you cant apply that kind of brute force strategy, said George Church, a researcher at Harvard Medical School.
Meanwhile, in an article published in the journal Science last month, Churchs lab reported progress on bathing DNA in different frequencies of light to produce a color-coded snapshot revealing the order of a DNA sequence.
Daniel Branton, a Harvard colleague of Churchs, is working on a method Schloss considers among the most promising: shooting DNA through a tiny hole called a nanopore and measuring the electric signals each base pair emits.
And in another recent development, a Branford, Conn., company called 454 Life Sciences announced it had sequenced the genome of a virus about 30,000 base pairs long by dropping DNA into tiny wells and is now working on bacteria, with 2 million to 8 million base pairs. The company hopes to work its way up to humans.
Other technologies can compare one strand to a reference, like that provided by the human genome project, and highlight differences. That could help scientists identify the 99.9 percent of identical base pairs, and allow them to focus on the remaining 0.1 percent.
Woburn-based U.S. Genomics, for example, tags certain sequences then shoots them past a laser, which detects the tags as they go by.
Many of these techniques solve some shortcomings of electrophoresis, but none solves them all. Knotty obstacles remain, like blurring of the base pairs fluorescence, or finding computers that can crunch all the numbers these methods produce.
One skeptic, Elaine Mardis, a genetics expert at Washington University in St. Louis, worries that too many labs are releasing data by press release rather than subjecting the information to scientific review. She isnt convinced that scientists are solving problems such as how to read longer DNA snippets or in developing precise instruments to perceive fluorescent light.
Honestly, its going to take us 10 or 15 years to get there, she said of the $1,000 genome. The non-scientific public is hearing this and saying that sounds really great, and people must be at that goal because theyre talking about it. Thats totally not the case. This is the plan for the future, and the future is not now.