A better prenatal test?

(FSB Magazine) -- Life was proceeding as planned for Ravinder Dhallan, or so it seemed. Having earned doctorates in medicine and biomedical engineering at Johns Hopkins University, he had just started a radiation oncology residency at Massachusetts General Hospital. On the home front Dhallan and his wife, Hejung Christine Chang, had a daughter, and they were eager to see their family grow.

Then things got complicated. Chang suffered two miscarriages. The couple was devastated and had no idea what to do. Only later did they realize that the miscarriages had a genetic basis. The episode left Dhallan struck by how little information was available to women who experienced complications during pregnancy. "It suddenly became personal," he says. And so he resolved to invent a better prenatal diagnostic exam.

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Dhallan had long dreamed of solving a scientific problem and building a business around his discovery. That's an uncommon trait in the highly structured world of modern medicine. Every year enterprising MDs come up with ingenious new therapies. But few doctors are willing to trade their medical careers for the risks of a startup.

Dhallan's venture seemed particularly chancy. His goal was a test to detect fetal abnormalities such as Down syndrome and cystic fibrosis at an early stage in a pregnancy (so there's enough time for the fetus to be treated or aborted safely). It was no easy task. Currently the diagnostic gold standard is amniocentesis, in which a four-inch needle is inserted into the abdomen to extract amniotic or placental cells directly from the womb. The results are 100% accurate, but the test carries a one-in-200 risk of triggering a miscarriage and can't be performed until the pregnancy is 15 to 18 weeks along. An alternative, chorionic villus sampling, can be performed ten to 12 weeks after conception but poses a greater risk of miscarriage.

Meanwhile, today's noninvasive prenatal screenings options rely on a combination of ultrasound imaging and blood samples drawn 11 and 16 weeks into the pregnancy. Accuracy rates range from 60% to 90%, and about 5% of tests produce false positives.

What has made detecting genetic problems in a fetus so difficult thus far is that you need a test that can distinguish fetal and maternal DNA. Think needle in haystack: One vial of a pregnant woman's blood contains billions of copies of her own DNA mixed with just a few hundred copies of her baby's DNA.

Dhallan's patented procedure, called Rapid Analysis of Variations in the Genome, draws 29.5 milliliters (or a mere two tablespoons) of blood from the mother's arm, isolates fetal DNA cells, and checks them for three copies of chromosome 21, the marker for Down syndrome. The test is 99% accurate, according to his published studies, and can be performed after the eighth week of pregnancy. He is now working to extend the test to detect cystic fibrosis.

Dhallan has incorporated a biotech firm called RavGen (ravgen.com), based in Columbia, Md. He has raised $15 million for research and development and has completed two clinical trials of RavGen's prenatal screen. Dhallan is now recruiting clinicians and their patients for the third and last clinical trial. His test will then go up for approval from the U.S. Food and Drug Administration. He hopes to have a test on the market in the next few years.

Dhallan's timing is impeccable. The number of women giving birth after age 35 - the highest-risk group for Down syndrome - is increasing at a rate of 1.5% each year. Last January the American College of Obstetrics and Gyne-cology recommended that all pregnant women be screened for Down syndrome. The occurrence of the syndrome has held steady over the past few years at one in every 800 to 1,000 U.S. births.

How did Dhallan manage the transition from physician to entrepreneur? Part of the answer lies in his medical training. After deciding to launch RavGen, he left oncology for emergency medicine, hoping that a schedule of long-er days and shorter workweeks would free up time to focus on his business. But the emergency room turned out to be great training for the daily high-wire act of running a startup. "You get perspective," says Dhallan. "Once you've dealt with life and death day in and day out, other problems seem trivial." The ER also helped him develop strong leadership skills. "If someone has been shot six times, everyone is looking at the physician's response," Dhallan says. "If I didn't look confident, then everyone would lose confidence."

On free days Dhallan read about prenatal medicine and picked the brains of entrepreneurs in many fields. "One guy had a concrete company," says Dhallan. "Another was a builder. I asked them how they incorporated. Who was their accountant? What law firm did they like?" Like many other successful entrepreneurs, Dhallan surrounded himself with smart people. Most of his 20 employees are scientists. His board includes a Nobel laureate and several medical experts affiliated with Johns Hopkins University in nearby Baltimore. To retain control of his young company, Dhallan raised capital from long-term angel investors, avoiding venture capitalists and strategic partners. One of his first investors was a college buddy; another, a childhood friend.

Dhallan faces stiff competition. Some 15 research teams worldwide are seeking a solution for safe, reliable, noninvasive alternatives to amniocentesis, says Dr. Jacob Canick, director of prenatal and special testing at Women & Infants Hospital in Providence. One rival, Dr. Dennis Lo of the Chinese University of Hong Kong (cuhk.edu.hk), describes Dhallan's research as promising but inconclusive. "I was very excited, but our researchers were unable to replicate his work in the lab," Lo says.

Dhallan isn't fazed. In 2004 he pub-lished his technique in the weekly Journal of the American Medical Association. A second paper appeared in the February issue of The Lancet, a British medical journal. And he is launching his largest random, double-blind study yet. On the business side, Dhallan earned an MBA at the University of Pennsylvania's Wharton School. Rav-Gen will soon announce a partnership with a well-known ultrasound company. "This will help our brand gain traction faster," he says.

The news from home is equally good. After ten years of reproductive challenges, Dhallan's wife gave birth to their second child, a son. Matthew Dhallan is now 2 years old and thriving.