Most existing DNA sequencers (including the 454 machine) do their reading by attaching light-producing molecules to DNA, taking pictures and analyzing the resulting image. This optical technology requires all sorts of complicated cameras and robotics, along with huge data files to handle the images.
Rothberg's elegant contribution was to come up with a sensor that directly reads telltale electrical signals produced as DNA copies itself. This vastly simplifies the process and allows engineers to make machines for far less. He founded Ion Torrent with an undisclosed amount of his own money in 2007 and later took in $23 million in venture capital. Still smarting from the loss of 454, he made sure this time to retain a supervoting share majority so he couldn't be forced out.
At the heart of the personal genome machine is a silicon chip with 21 million transistors on it--the equivalent of a desktop computer circa 1995. On top of the chip is a tiny channel the width of two human hairs into which DNA is fed. Each DNA molecule in the body contains two long strands of chemical letters, or bases--A,T, C and G--that come together like a twisted ladder (a.k.a. the double helix). The machine takes a single DNA strand and uses an enzyme to attach bases to it. Every time the enzyme connects two bases--an A to a T or a C to a G--an electrically charged ion is released and detected by sensors on the machine. By exposing the DNA sample to only one letter at the time, the machine can reconstruct the entire sequence.
"It is an absolutely beautiful machine," says Randy Scott, chairman of the cancer-gene tester Genomic Health. He adds that his company may switch to the Ion Torrent machines if they live up to their potential. "Jonathan has done a great job at staying ahead of the curve."
That curve is arcing toward guiding cancer treatment. Illumina's Flatley has had his own genome sequenced and learned that he has a gene for a condition that causes people to get a rash when they are cold. His company is seeing "a stream of infants and cancer patients" who want their genomes sequenced. Life Technologies has signed up a network of cancer centers to probe tumors with its current mainframe system. If a DNA scan of a tumor can predict which treatment will work best, insurers will likely pay up, even though treating cancer patients can be hugely expensive.
But existing machines from Illumina and Life Technologies can take up to eight days to return any data--an eternity for cancer patients who need treatment right away. Moreover, the current technology forces cancer pathologists to wait that entire time, even if they just want to analyze a few genes. It's almost like the difference between waiting for a letter and a text message.
Right now all DNA sequencers are only approved for research use, but scientists are trying to move them into clinical practice anyway. Gordon Mills, chairman of the department of molecular therapeutics at MD Anderson Cancer Center in Houston, says such use is "imminent." He is starting a project to sequence 1,000 genes that might serve as targets for cancer drugs in 10,000 patients. He hopes to figure out if this improves the odds for sick patients, as well as to find ways to get and store tumor samples, save data afterward--and leap over barriers set up by Medicare and the Food & Drug Administration.
Rothberg sees potential health care applications for the PGM. Doctors already use genetic mutations in HIV to predict which drugs a patient's virus will be able to fight off. They are always looking for better ways to do this, and the PGM could help, he says.
He says his next machine, due within six months, will data mine 200 or more genes at a time, and that's what oncologists need right now to make diagnoses and pick drugs. That's just what Massachusetts General Hospital pathologist John Iafrate, who received a free sequencer as part of a contest Ion Torrent held to drum up interest in the technology, is hoping to prove.
posted on January 09, 2011