Research in a Land in Conflict

Despite the hostilities, life — and international study — goes on

Photo: PictureQuest

For a Pennsylvania Catholic and an Israeli Jew, Steve Gruber and Gad Rennert have a lot in common. They are both cancer geneticists with active research programs and physicians who treat patients with colorectal cancer. Both are married and raising young families. Steve Gruber has three children, ages 11, seven and one. Rennert has 12- and 15-year-old daughters.

“Not only do our professional lives overlap completely, our personalities are similar, too,” says Gruber, M.D., Ph.D., the director of clinical cancer genetics at the U-M Comprehensive Cancer Center and an assistant professor of internal medicine and epidemiology. “The only difference is that I’m not nearly as talented as Gadi.”

Steve Gruber and Gad Rennert Photo: Gregory Fox

Gadi is Gad Rennert, M.D., Ph.D., the chair of community medicine and epidemiology at the Technion Faculty of Medicine and Carmel Medical Center in Haifa, Israel. Rennert directs the National Cancer Control Center for Clalit Health Services, Israel’s largest HMO. He also speaks five languages and is, according to Gruber, “one of the most amazing people I have ever met.”

The two scientists met about a year after Steve Gruber joined the U-M Medical School faculty in 1997. Fresh from a fellowship at Johns Hopkins, with a medical degree from Penn and a Ph.D. from Yale, Gruber wanted to study how genes, diet, exercise and other factors interact to produce colon cancer.

He was looking for a research partner. Along the way, he found a friend and discovered that even science is not immune to the world’s troubles.

Gruber knew that descendants of Ashkenazi Jews — a closely related ethnic group that formerly lived in Eastern Europe — have unusually high rates of colon cancer. He thought they would be the ideal study population. But finding them, along with organizing and managing a complex field study, is expensive and a big job for a young scientist early in his research career.

That’s when Dean Brenner, M.D., a professor of internal medicine and pharmacology in the Medical School, entered the picture, Gruber recalls. “Dean said, ‘There’s no question you should do this study in Israel, and I know the perfect person to talk to. In fact, I’m going there in two weeks. Why don’t you come with me?’ So I flew to Israel with Dean, who introduced me to Gadi, and it just clicked.”

So a new international research collaboration — the Molecular Epidemiology of Colorectal Cancer (MECC) Study — was born, and funded in 1999 with a $4.8 million grant from the National Cancer Institute and additional funding from the Irving Weinstein Foundation.

Today, the study includes 4,200 people living in northern Israel — half who have been diagnosed with colorectal cancer and half who haven’t. Gruber’s lab handles DNA and molecular profiling of blood and tumor tissue samples from people in the study. Rennert manages 12 field researchers who visit study subjects in their homes to take blood samples and administer an 800-question survey on diet, physical activity, medical history and other lifestyle factors.

“We understand genes aren’t the whole story, because some people with a genetic susceptibility develop the disease, while others do not,” says Gruber. “This is why Gadi’s field research is so important. Without it, we would have no way of understanding the role of diet and other environmental factors.”

Rennert selects his study subjects with painstaking care to eliminate sample bias. “First, we include every person in our defined geographic area with colorectal cancer. Then we find a control subject without cancer who matches each patient’s demographics as closely as possible,” Rennert explains. “Let’s say I have an 82-year-old male patient with colon cancer who is an Ashkenazi Jew living on a certain street in Haifa. To find a matching control subject, we go to the same street and find an 82-year-old male Ashkenazi Jew who does not have cancer. This is not easy to do, but it’s the only way to ensure reliable data.”

As the research developed, so did the friendship. Rennert and Gruber stayed in constant touch by e-mail and telephone, and visited each other’s laboratories several times a year. With their wives, they went to concerts and picnics together, and their children became trans-Atlantic pen pals.

But in September 2000, after several years of relative peace between the Jewish and Palestinian populations in Israel, hostilities began again. The U.S. State Department issued a travel advisory and, for the first time, Steve Gruber had to postpone a planned visit to Israel.

“We had to figure out new ways to keep data flowing back and forth, but we were able to continue with minimal interruptions,” Gruber says. “The biggest change for me is that I worry about him. Whenever I see in the news that there’s been another bombing, I pick up the phone to see if everyone is OK. When Gadi’s daughter had her Bat Mitzvah, I was really nervous for her.

“There was a bus bombing near Haifa not long ago, so I called Gadi’s office and spoke to Ronit Almog, one of the study coordinators,” Gruber adds. “She was bringing samples back from a hospital near the West Bank and had driven past that same intersection just an hour before the bombing.”

Gruber and Rennert find it ironic that conflict in the Middle East could interfere with research designed to benefit the entire population. “In our study, we have Arabs, we have Sephardic Jews, we have Ashkenazi Jews, we have everybody,” Rennert says. “Our results definitely will make a major contribution to understanding how colorectal cancer develops and progresses in the Arabic, as well as the Jewish, population.”

“What’s so wonderful about this collaboration is the fact that we can learn how genetic and environmental contributions differ among ethnic groups living in the same geographic area,” Gruber says. “Colon cancer isn’t as common in the Arab population, but we still need to learn how to care for everyone who suffers from this disease.”

Rennert is proud of the fact that not one member of his field research team has left the project, even though travel to and from their site visits is much more dangerous now. “It’s already a way of life for us,” Rennert says. “We use public transportation less; we consider the safest way to travel. There’s a higher level of awareness. It’s not foolproof, but it’s how we’ve learned to behave, because otherwise we’d never go anywhere.”

Gruber still travels to Israel, but now he stays in a different hotel away from Haifa’s central commercial district. “The crisis does influence every element of daily life, but everyone refuses to have their lives dictated by conflict. Despite the hostilities, life goes on.”

No matter what happens in the Middle East, Gruber says he and Rennert are determined to continue their work. In fact, Gruber has applied for an extension to his research funding, so the study can continue for several more years.

—SFP