Education

For Aziz Sancar, long hours in lab lead to triumph

Tar Heels of the Year: Aziz Sancar and Paul Modrich

Tar Heels of the Year Aziz Sancar of the University of North Carolina and Paul Modrich of Duke University share stories of receiving the 2015 Nobel Prize for Chemistry.
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Tar Heels of the Year Aziz Sancar of the University of North Carolina and Paul Modrich of Duke University share stories of receiving the 2015 Nobel Prize for Chemistry.

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The News & Observer’s Tar Heel of the Year

The News & Observer recognizes North Carolina residents who have made significant contributions in the last year and beyond. This year, we asked readers to tell us about people who have made a difference in our state. Here are our stories.

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Aziz Sancar’s first career plan was to play soccer for the Turkish national team.

Born in the rural Savur region in southeast Turkey in 1946, he spent his youth hoping to be the next Turgay Seren, the former goalkeeper for the Istanbul-based team whose heroic saves during a 1951 game against West Germany earned him the nickname “Panther of Berlin.”

“He was my hero,” Sancar said.

But Sancar – pronounced “SAN-jar” – was born with a cold analytical eye that helps him separate emotion from fact. In his senior year of high school he realized, “I was not tall enough to be a goalkeeper,” and decided on a career in medicine or chemistry instead.

The seventh of eight children born to illiterate parents, Sancar was nonetheless pushed to get an education. He worked hard in school, he says, and scored well enough on college entrance exams to enroll in the Turkish university of his choice. He chose Istanbul Medical School.

In many ways, he says, leaving his village for the teeming city of Istanbul was like moving to a foreign country. It was a difficult transition. But he thrived in the academic setting, and planned to become a research biochemist – until one of his professors advised him to practice medicine for a while first.

He finished at the top of his class of 625 students, he says, and spent two years as a physician in rural Turkey.

“Those were probably the happiest years of my life,” said Sancar, who felt beloved by his patients and gratified by the work. Many of those he treated had never seen a doctor and were grateful for any help.

“A shot of antibiotics could save a kid’s life,” he said. But it bothered him that he didn’t understand, at a molecular level, why an antibiotic worked against one type of infection and not another.

For Sancar, practicing medicine felt like being a highly trained technician. “You are presented with a set of symptoms, and you prescribe certain tests. You make a certain diagnosis, and you use certain prescriptions for treatment,” he said.

A practicing physician does not necessarily advance human understanding, Sancar said. For him, practicing medicine wasn’t enough. He wanted to know how it worked.

Mentors and heroes

So he went back to school, this time at the University of Texas at Dallas. There, DNA pioneer Claud S. Rupert taught and ran a lab that Sancar regarded as the center of the universe for the study of a certain kind of DNA repair, in which bacteria recover from deadly doses of ultraviolet radiation if they are exposed to a blue light.

A new place, a new hero for Sancar, who went to work in Rupert’s lab. It was there in 1976 that Sancar made his first major contribution to the field: He cloned the gene for photolyase, the enzyme that repairs the UV-damaged DNA in bacteria, though at the time, he didn’t understand how it worked.

Shortly afterward, he got a notice ordering him to return to Turkey for an obligatory four months of military service.

When he got back to Texas, he planned to take the next step with his newly cloned gene, but Rupert pushed him to write his doctoral thesis, get his degree and pursue new research.

Besides his tutelage under Rupert, Sancar had launched another partnership while in Dallas, with a fellow molecular biology doctoral student named Gwendolyn Boles, with whom he sometimes competed for late-night access to lab equipment.

“I just thought he was really interesting,” Gwen Sancar said. “He had a different sort of outlook from a lot of American men I had run into. And he was very accepting of a woman who was dedicated to a career.”

On the seventh day, he didn’t rest. He just didn’t work as hard.

Gwen Sancar

Though Sancar believes he was the first person east of the Rockies to clone a gene, the accomplishment didn’t result in immediate offers of postdoctoral positions. He had three applications turned down. Then, Gwen landed a post in New York, and Sancar was hired on as a technician in a lab at Yale’s School of Medicine that was one of several at the university doing DNA repair research. The couple moved east. They married in 1978.

While both worked long hours, Gwen Sancar says her husband was intensely focused.

“I have never seen a single individual in my life who was so determined to make his experiments work,” she said. “It was not unusual to work until 3 a.m. and go back at it at 9 a.m., six days a week. On the seventh day, he didn’t rest. He just didn’t work as hard.”

Within a couple of years at Yale, Sancar identified several enzymes involved in a kind of DNA repair that happens without exposure to light. The enzymes identify UV damage within the DNA strand, and snip out the damaged section through what’s now known as excision repair. He published those findings in 1983.

That was just a year after Aziz and Gwen Sancar had come to UNC-Chapel Hill, the first university that offered to bring them both in to the same department at a time when many employers considered it risky to hire a scientific couple.

I’m an idea person. I’m not very good with my hands.

Aziz Sancar

Hired as an associate professor, Aziz Sancar had a couple of years to set up his lab and produce enough papers to qualify for tenure. He continued his work on excision repair in bacteria and, working with other researchers, set about figuring out how the process works in human DNA.

Lab work – actual hands-on, at-the-bench, eye-to-the-microscope lab work – is a challenge for Sancar, who said he has to work twice as hard as other researchers to get useful results. “I’m an idea person,” he said. “I’m not very good with my hands.”

For five years, he tried experiments in which he incubated human cell extract with damaged DNA to find evidence of excision repair, but it never showed up. It was frustrating to him and exhausting to others in the lab. He heard that one of his grad students had even considered suicide.

Then he got an application from a young woman Ph.D. candidate who wanted to join his lab, though she knew she didn’t have the proper experience. She had never dealt with DNA. But she promised to work hard. He hired her and put her on the excision-repair experiment with three other post-docs.

“She worked like a maniac,” Sancar said. “And within nine months, she got it.”

It was a huge breakthrough in 1991, for which Sancar says the former student, J.C. Huang, “is my hero.”

A gift for finding talent

The Sancar Lab occupies a bright, busy section of the third floor of the Genetic Medicine Building on UNC-Chapel Hill’s medical campus. In honor of his Nobel win, Sancar was given a modest new office within the suite, to which he promptly relocated his text and reference books. There is no clutter, nothing out of place except several autographed jerseys from the Turkish national soccer team spread across a small settee, sent to him after the Nobel announcement. Next to his desktop computer, Sancar keeps a cup of green tea, steeped with leaves sent to him by a Chinese scientist with whom he has collaborated.

Though he doesn’t like to be hunched over the bench, Sancar, 69, is involved in every aspect of the lab, meeting individually with researchers to discuss how their work is going or to talk about relevant papers published by others. He sits in on weekly lab meetings where discussions include complex science and issues as mundane as how to better handle radioactive trash.

He somehow finds the right people and motivates them to get excited about the work.

Mike Kemp, UNC research assistant professor

Mike Kemp, a research assistant professor who has worked in the Sancar Lab for eight years, says one reason it has produced so much good work is that Sancar has a gift for finding good people.

“He somehow finds the right people and motivates them to get excited about the work,” Kemp said. “It’s a mixture of science and art and management, and it’s very rare to find.”

The Sancars have no children, but are godparents to two. His wife says Sancar has always loved being around kids.

Kemp once had to bring his young son to the lab while he finished work on a project, and Sancar took the boy aside. Next thing Kemp knew, “Aziz was filling up water balloons with him and they were throwing them at me. It was probably a safety violation, and not what you think of when you think of this serious scientist,” he said.

Though he doesn’t like to travel to scientific events because he doesn’t like to give speeches, when he does lecture or talk about his work Sancar is quick to credit others. When Sancar and Paul Modrich got into this line of work, only a few dozen researchers were publishing papers each year in their field. Now, hundreds of new papers come out annually. Every discovery, incremental as it may seem, contributes to the understanding of how DNA gets repaired, Sancar said.

“Research is not done in a vacuum,” he told the audience during his lecture at Stockholm University the day before the Nobel Prize presentation. “We all build on research done by our predecessors and our contemporaries.”

Before the 2015 prize was announced, Sancar had begun to wonder if the Nobel committee would get around to recognizing the field at all. Nearly every year for the past decade, he had nominated Modrich for the award.

Dale Ramsden, a colleague of Sancar’s in biochemistry at UNC and one of two professors who share teaching responsibilities with him in a graduate-level course, says there are two kinds of students who work in a research lab. He can sort them by the way they wait for experiment results, which often come in the form of a gelled image that has be to run through a scanner to be visible.

“One student is watching every scan line, waiting for that image to show up,” Ramsden said. “The other is playing Minesweeper or solitaire and checks the machine when the image is done.”

The one playing solitaire has a job. The other has a passion; that’s the student who will stay with it.

“It’s the joy of discovery. That’s what you want to be in this for,” Ramsden said. That’s what Sancar has.

Not afraid to be wrong

Though he long ago became a U.S. citizen, Sancar loves his native Turkey and travels there at least once a year, usually with his wife, to visit family.

He was on his way back from Turkey in 1996 when, unable to sleep, he flipped through an in-flight magazine and came across a reprint of a journal article about jet lag and the circadian clock, that innate 24-hour cycle in every living thing. Sancar thought back to a gene he had found in humans that looked like the one that aids DNA repair in bacteria. But the gene wasn’t involved in DNA repair in humans, and Sancar had set it aside, not knowing what its purpose was.

“It’s a clock gene,” he said he suddenly realized.

When he has a new idea, or is looking for one, Sancar says he first goes to young people.

“They’re more creative. It’s just a biological fact,” he said. But when he proposed the connection to the circadian clock, only one of his 15 researchers thought it was plausible. Still, he launched experiments that eventually proved him right.

Scientists now know that every cell has a circadian clock, and that among other things, it helps regulate what time of day damaged DNA gets repaired the most efficiently. One implication for humans is that there might be better and worse times to administer chemotherapy, which not only attacks cancerous cells but also damages the DNA of healthy cells.

At regular lab meetings, Sancar watches presentations by his students who are exploring such topics. They click through slides of drawings and charts. They talk in abbreviations. Sancar watches, laser-focused. When he points out errors and asks questions, his speech still is heavily accented and his voice is soft almost to the point of mumbling, but he makes clear that he likes papers that present simple principles and irrefutable facts.

“I am not afraid to be wrong as long as I am honest with my data,” he said of his own research papers. “Only God is right all the time.”

If he publishes a paper and it’s later going to be proved wrong, he wants to be the first to do it.

Just when you figure we know everything, all of a sudden, something comes along, and there is a whole new field to explore.

Aziz Sancar

When he’s not at his lab, a seven-minute walk from his home on the southern side of Chapel Hill, Sancar often can be found in the bleachers watching UNC women’s soccer, basketball or volleyball. After the Nobel Prize was announced, former UNC soccer star Mia Hamm sent him an autographed jersey, which hangs in a frame outside the lab, near a copy of Sancar’s enzyme patent.

The town of Chapel Hill gave Sancar a key to the city to honor his Nobel win, and when he went to accept it, he told town leaders he considers himself “a Chapel Hillian.”

But he remembers from his experiences in Istanbul and Dallas how hard it can be, especially for a young person just leaving home, to adjust to a new place. Eight years ago, Sancar and his wife bought a 1950s-era boarding house on Franklin Street and set it up as a temporary home for up to four Turkish students at a time. It helps them ease into their new surroundings.

Sancar is adjusting, too. Along with Modrich, he’s become a bit of a celebrity. Turkey celebrated as if it were a national holiday when the Nobel announcement was made, and there’s a new postage stamp there bearing his smiling face.

Both men have been inundated with speaking requests, but the travel would take time away from his real work, Sancar says, and there is so much more of it to do.

“Just when you figure we know everything, all of a sudden, something comes along, and there is a whole new field to explore.”

Martha Quillin: 919-829-8989, @MarthaQuillin 

Aziz Sancar

Born: Around Sept. 8, 1946, Savur region, Turkey.

Family: Wife, Gwendolyn Boles Sancar; sisters, Edibe Sancar, Yildiz Sancar and Seyran Sancar of Mersin, Turkey; brothers, Kenan Sancar, Orhan Sancar and Tahir Sancar of Istanbul, Turkey, Hasan Sancar of Alanya, Turkey; goddaughters, Rose Lorraine Peifer and Lillian Claire McCormick of Chapel Hill.

Education: Master’s degree, Istanbul University; Ph.D., University of Texas.

Career: Sarah Graham Kenan Professor of Biochemistry at UNC School of Medicine.

Extracurricular: Die-hard fan of UNC women’s soccer, basketball and volleyball; co-founder of the Aziz and Gwen Sancar Foundation, which operates the Carolina Turkish House in Chapel Hill.

Honors: Nobel Prize in chemistry, 2015; American Society for Biochemistry and Molecular Biology Valee Award; member, National Academy of Sciences; Turkish Koç Award; member, Turkish Academy of Sciences.

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