A DNA Test Pushes the Envelope.
This chip can test your DNA.
by Danielle Jacobs
Eddie Vedder wrote the lyrics to “Yellow Ledbetter” on his used cocktail napkin. Emmett “Doc” Brown conceived of the flux capacitor on a scrap of paper after hitting his head on a toilet bowl. Holden Thorp, Kenan professor and chair of the UNC chemistry department, scribbled the foundation of electrochemical DNA diagnostics on the back of an envelope.
The transfer of an electron between an electron donor and an electron acceptor creates electricity. Thirteen years ago, Thorp, along with his first postdoctoral student, Dean Johnston, sought to take advantage of this fact to develop an electrochemical technique to measure the electricity conducted by nucleic acids such as DNA.
Johnston soon found that guanine, one of the four repeating molecules that comprise DNA, was a good electron donor by “basically burning the hell out of a piece of DNA and just getting tons of electricity,” as Thorp puts it. Thorp was doubtful at first, but further investigations allayed his skepticism, and he hastily jotted down a scheme for electrochemical DNA detection on the first piece of scrap paper he could find.
Over time, the scribble developed into a tangible target—DNA diagnostics, the testing of DNA for genetic mutations and their related diseases. Thorp realized that it would be much cheaper to build and operate an electrochemical detector than one for fluorescence, the most prevalent diagnostic method employed today. Fluorescence, which works by measuring the light emission of fluorescently tagged genes, relies on the use of expensive microscopes and optical lasers, and the data have to be further interpreted and resolved to yield any useful information. Thorp’s patented electrochemical technique, on the other hand, is extremely inexpensive and requires the use of less biological sample. The electrical readout is more direct and is easily quantifiable on an instrument called a potentiostat, which, according to Thorp, can be made cheaply in, well, Doc Brown’s basement.
Osmetech, a California-based health-care firm, is the first company to take advantage of Thorp’s electrochemical technique, which currently forms the basis of their genetic testing for carriers of recessive cystic fibrosis (CF) genes. It works by simply hybridizing—or attaching—an amplified DNA sample to a cheap metal electrode, and comparing the electricity released to that of known CF gene mutations.
Various mutations of the CF gene are responsible for causing the disease. Fluorescence technology can only sense one mutation at a time. Thorp’s electrochemical technique allows for an array of DNA, which scientists can test for several mutations simultaneously.
But Thorp believes that electrochemical DNA detection will be most promising in the realm of personalized medicine. For instance, the genetic makeup of cytochrome P450 (CP450), the enzyme responsible for the metabolism of many medications, differs from one individual to another. Since drug efficacy, potency, and toxicity are inherently dependent on this genetic profile, electrochemical CP450 prescreening could make it safer and cheaper to qualify good drug candidates. Thorp uses his own positive reaction to the asthma drug Singulair to explain: “If you had a genetic test to find the people like me who could take Singulair and have it work for them, then when you did your trial you’d only try it out on those folks. You would not only be using less drug when you got it to market, but you’d have the chance of getting drugs that only work on specific subsets of people to market much more easily. You’d have more successful drugs, and safer ways to give them to people.”
You might also one day test your DNA at home. The promise of anonymity and privacy, without the knowledge or involvement of a health insurance company or hospital, makes home diagnostics attractive for testing for genetic diseases. “This is the first step that will make it cheaper to get genetic information,” Thorp says. The next step is to overcome the “minor problem of getting DNA out of the cell and amplifying them.” It’s hard to figure out how you would do that at home, he says. “You never know. It’s possible.”
Danielle Jacobs is a doctoral student studying organic chemistry at Carolina.
