The phone is already ringing. Many rooms are still empty as Terry Melton's staff attempts to run the first set of tests without the Automated Sequencer that was supposed to arrive weeks ago.
"We're about a month behind schedule," says Melton, a 1996 Ph.D. graduate in genetics and president of a new company. She rushes through the metal doors of a room sized evidence locker (needed to secure the lab's samples from contamination) to answer the phone.
Her company, Mitotyping Technologies, will work for law enforcement, lawyers, and citizens. By sequencing the mitochondrial DNA (mtDNA) in hair shafts, bones, old blood stains, and teeth, Melton can support or disprove claims about a person's identity. She recently helped solve a three-year-old murder case, for instance, by analyzing a blood stain on a watchband.
Most DNA fingerprinting uses DNA from the nucleus of a cell. Mitochondrial DNA offers two advantages. "First, it is only inherited through the mother's side,"Melton explains. "All of a woman's children will inherit her type, but her sons will not pass it on. So any maternally related individuals can be expected to share the same mtDNA sequence." This fact makes mtDNA analysis easier for juries and other non-scientists to understand. "It is also useful in cases where a long dead or missing individual is not available to supply a reference sample. Any living maternal relative can do so."
Also, mtDNA can be recovered from old, small, or degraded samples in which no nuclear DNA can be found. "The mitochondria are the energy powerhouses of the cell," Melton explains. Every cell can have hundreds or even thousands of copies of the short mtDNA strands (containing 32 genes), as opposed to only two copies of the much longer nuclear DNA (about 100,000 genes).
"You can run a test using only a two-centimeter-long hair fragment," Melton says. Though when she was once sent several hairs believed to belong to Napoleon, she couldn't find any usable DNA. "A 200-year-old hair is kind of a long shot."
In another case using hair, however, she was able disprove the identity of Anna Anderson, who claimed to be the Grand Duchess Anastasia, daughter of the last Tsar of Russia. In 1994, Melton did mtDNA analysis on five of Anderson's hairs. Though excited about solving this famous case, Melton was also a little disappointed. "I grew up in Charlottesville, where Anderson lived at the end of her life. She was a local character in my hometown."
The Anderson case was one of several that Melton undertook as a graduate student in the genetics lab run by anthropologist Mark Stoneking, known for his work on the "Mitochondrial Eve" theory. Since mtDNA is inherited only through the mother, Melton says, "if we look at all the mtDNA sequences and link them together through time, we can say that there is an ancestral sequence common to all humans."
For her dissertation Melton studied the mtDNA of 40 populations around the world to see if there was enough diversity to make mtDNA sequencing useful for forensic analysis. She found it to be an excellent tool. As a postdoc, she began processing requests for mtDNA analysis as a community service. Soon she decided to make the switch to president of her own business.
The stalls and setbacks to setting up Mitotyping Technologies—like waiting for the Automated Sequencer to arrive—have been only minor annoyances, Melton says, thanks to the Penn State Gateways Program.
"We helped Terry identify the issues surrounding this business opportunity," says research commercialization specialist Dan Leri, "and determine what was a fact, what was a myth, and what was a critical assumption. Then we proceeded to capitalize on the facts and manage the assumptions." The program found Melton business mentors and identified potential investors for her company. "They've allowed me to focus on the science. They have really done a lot of the leg work," Melton says.
Lab space in the Zetachron Center for Science and Technology Business Development came about through Nina Fedoroff, director of Penn State's Life Sciences Consortium. When Zetachron, a company that developed drug delivery technologies, was sold in 1996 to Watson Pharmaceutical, co-founder Wally Snipes and his wife agreed to donate the $1.2 million building to Penn State. (Snipes is a former professor of biophysics.)
Says Melton. "Everything came together at once. It almost seemed fated." Now, instead of merely dealing with the challenges of precise lab analysis, Melton is learning to run a business, along with the four other companies taking root in the Zetachron Center. "We're all buying equipment. We're all swearing constantly," she says, as she hangs up on another caller who's promised to ship out an Automated Sequencer ASAP.
Terry Melton, Ph.D., is president of Mitotyping Technologies, LLC, 1981 Pine Hall Dr., State College, PA 16801; 814-861-0676; twm107@mitotyping.com. Dan Leri directs Penn State's Research Commercialization Office, Research Park Technology Center Suite 101, University Park, PA 16802; 814-863-6301; danleri@psu.edu.