Constable: Scientist sees genomes as 'blueprint' for treatment

Ten years ago, 4-year-old Nicholas Volker of Wisconsin had exhausted treatment options for his digestive issues.

"Nic was dying, and no one knew why," remembers Howard Jacob, a scientist who was in charge of the genomics center at Medical College of Wisconsin at the time. Jacob, who grew up in Lake County and graduated from Carmel High School in Mundelein, made the bold decision to have the boy's genome sequenced to see if his DNA provided any clues.

Doctors found a mutation, which they thought was causing his condition, and the genome sequencing indicated a bone-marrow transplant of cells taken from umbilical cord blood would help. Nic, who made a miraculous recovery, still has other health issues, but the Milwaukee Journal Sentinel chronicled the groundbreaking treatment in a series titled, "One in a billion: a boy's life, a medical mystery," which was awarded a Pulitzer Prize in 2010.

"I always believed reading genomes would change medicine," says Jacob, 58. "That case convinced me."

Now the vice president and head of genomic research at AbbVie, the large biotech company in North Chicago, Jacob is pushing the value, and boundaries, of genome sequencing.

"The technology is changing so fast, and so is the speed with which we do things," Jacob says as he stands in his AbbVie laboratory. The Genomic Research Center's high-performance computers used for analyzing sequencing data would have filled half the space in Willis Tower, and used energy equal to a year's worth of production for a nuclear power plant if the system had been built when the human genome project was launched in 1993. That first human genome sequence cost $1 billion. Today's AbbVie lab has two high-throughput sequencing machines that can sequence 24 human genomes every three days, Jacob says. The cost is about $1,000 a person, and it costs another $2,000 to have doctors analyze it, he adds.

When Jacob got his genome sequenced nine years ago, it cost him $9,000 and showed some interesting results. Looking at the 6 billion nucleotides in the DNA he inherited from his mother and father, Jacob discovered about 32 million results (about 0.5% of his genes) that were not typical. One indicated he had a slightly higher risk of developing diabetes, another showed that he "chewed up morphine" three times faster than most people, and another showed that he carried a gene linked to breast cancer.

As a result of this information, Jacob improved his diet to prevent diabetes, asked for a pain medicine other than morphine after a knee surgery, and has talked with his wife, Lisa, a medical technician, and their daughters Shelby, 25, and Julia, 22, about the breast cancer gene.

"We give doctors our family history," Jacob says, explaining how people list relatives they think died of cancers or heart disease. "What if we actually had real data?"

Genome sequencing, while it worked for Nic Volker, won't answer all of today's questions.

"It's not to a point where it's accurate enough to say you're definitely going to get that disease," Jacob says. Identifiable genes, including BRCA1 and BRCA2, have been shown to increase a person's chance of developing breast cancer. Another gene mutation nullifies the effectiveness of a popular heart drug. But doctors don't understand what every gene mutation means. And diet, lifestyle and environment can play a role in whether an increased risk results in a disease.

Dystopian depictions of the future sometimes show a world where people use genome sequencing to develop a fetus that will grow up to be smart, athletic or musical. Other times, genome sequencing is depicted as a way to separate the good from the mutated, or to allow employers, insurance companies and others to discriminate against people with an increased risk of disease.

"With any technology, there's a risk people will abuse the information," Jacob says. "But we're trying to be as responsible as we can."

Scientists at AbbVie and around the globe are working to develop a collection of a million genome readings, but the donors are anonymous, and the DNA is for research, not treatment. In 1990, the National Institutes of Health founded the Ethical, Legal, and Social Implications (ELSI) program as part of the Human Genome Project.

"It's genetics. It's our kids, our families. It makes people uncomfortable," Jacob says. "Do you want to know something or not know something?"

Jacob says patients should know in advance if a medicine won't be effective. "When do you want to find out?" he says, noting a heart-attack patient can rule out an ineffective drug, or his survivors can discover the problem with that drug after his second heart attack.

Jacob first worked at Abbott as an intern during college when his father, a retired Navy officer, worked as a corporate engineer at the medical company. Jacob competed in his first science fair in sixth grade, and credits his science teacher, Darlene Strysic, at Holy Family grade school in North Chicago, for inspiring his interest.

"I've been a dork about science all my life," says Jacob, who was just 5 years old when he started telling people that he would get his doctoral degree. After graduating from Iowa State University, Jacob earned his Ph.D. in pharmacology at the University of Iowa and then did postdoc work at MIT, Harvard and Stanford. He speaks about genome sequencing at conferences around the world.

"When we read someone's genome, we're really trying to develop their blueprint," Jacob says. "What if we read your genome from the day you are born? Medicine is fundamentally going to change. How do we make better drugs, and get them to the right people?"