May 2006

Rewriting the Genome

Sequencing and synthesizing DNA keeps getting faster and cheaper. George Church explains the impacts of these advances.

By David Rotman

George Church, professor of genetics at the Harvard Medical School and a pioneer of genomics. (Credit: Mark Ostow.)

The genomic revolution is being driven by advances in analytical and computational techniques, and George Church has been behind many of them. Starting in the late 1970s, Church helped create the tools, including early software and protocols for DNA sequencing, that eventually made possible the Human Genome Project.

These days, Church, a professor of genetics at the Harvard Medical School, and his 50-person lab are still finding ways to synthesize and sequence DNA faster and more cheaply. One of his latest interests is synthetic biology, in which researchers design and synthesize biological "parts" that they then incorporate into microbes or cells.

Some anticipated products of synthetic biology: engineered cells that produce novel types of pharmaceuticals, redesigned biological therapeutics that are more effective and safer, and biosensors that can be built directly into cells.

Technology Review: What is synthetic biology?

George Church: Genetics turned into genomics when you dealt with the whole genome. Biology turns into systems biology when you deal either with the whole of the cell or some fairly large part of it. Genetic engineering turns into synthetic biology when you use what you learn from parts and theory to engineer real systems.

TR: How could synthetic biology help you design more-effective drugs?

GC: Some groups are making cells that sense tumors and respond by producing a toxin. Synthetic biology will help you engineer the cell to home in on the tumor, to recognize the tumor, and, once it is confirmed, to start making a tumor-specific drug.

TR: You and your colleagues recently developed a new way to synthesize DNA. What are the benefits?

GC: It's about reducing cost at a reasonable accuracy. Right now the cost of synthesizing a base [using conventional technology] is about 10 cents. That's the current street price for raw oligonucleotides. For synthesizing simple genes, it's more like $1.30 a base. [Our method] can manufacture oligonucleotides at .01 cent per base.

TR: How will getting the cost down aid synthetic biology?

GC: It means you're willing to make many more [genetic] constructs. Making more constructs means you're much more likely to make something that works or something useful.

TR: The new method also allows you to make longer stretches of DNA, right?

GC: Longer stretches are certainly enabled. The implications are that we are getting closer to being able to arbitrarily "program" the millions of base pairs in microbes or billions of base pairs in plants and animal genomes similar to the way that we program computers.

TR: There has been a lot of buzz about a $1,000 personal genome.

GC: That's sequencing. So we're off synthesis now.