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Global Health Matters > From Our Grantees—Science and Friendship

From Our Grantees—Science and Friendship

By Cathy Kristiansen

Two scientists from regions of the world where people are deeply hostile toward each other found a way to collaborate on research designed to unlock the mysteries of inherited deafness. Children in certain Palestinian and Israeli Arab families are unusually prone to inherited hearing loss, and identifying the responsible genes helps prospective parents know the risks and speeds potential discovery of a cure.

In 1996, Israeli geneticist Karen Avraham, Ph.D., of Tel Aviv University in Israel, and Palestinian geneticist Moien Kanaan, Ph.D., of Bethlehem University, found they were interested in the same themes of genetic research and decided to combine their expertise. Their funding breakthrough came from the Fogarty International Center (FIC) through grants that would help pay for their initial research and pave the way for them to write proposals for further awards. Dr. Avraham received her 3-year Fogarty International Research Collaboration Award (FIRCA) grant from FIC in 1999; Dr. Kanaan received his FIRCA in 2000. Geneticist Mary-Claire King, Ph.D., of the University of Washington in Seattle, was the U.S. collaborator for both. All FIRCA grants are given jointly to an NIH-funded U.S. investigator and a foreign collaborator, with all support going to the foreign collaborator.

Together, the three scientists launched a gene-mapping and cloning project, collecting clinical data and volunteered DNA samples from 59 Israeli and 74 Palestinian families. Their studies have thus far discovered four genes associated with inherited deafness and led to an understanding of how mutations in these genes lead to inherited hearing loss. (List of published findings below.)

Childhood deafness was more prevalent around the world before widespread distribution of the German measles vaccination greatly curbed incidence of viral damage to hearing in utero. Deafness rates are relatively high in the populations the scientists studied, however, because endogamy—related persons marrying—is traditional among some families and has led to the appearance of recessive genetic traits. Some families in the region have higher occurrences of inherited blindness and beta thalassemia. The large size of many families is helpful in gene mapping projects.

Through their published work, seminars, and teaching, Drs. Kanaan, Avraham, and King have educated the public of the region about hearing loss. This has been useful for the families, and they have worked with an international charitable organization that distributes hearing aids to the needy. "Our work has enabled families to know, in many cases, the genetic basis, or cause, of the deafness in their family," Dr. Avraham said. "The right to know is powerful and provides families with a sense of control."

Many challenges face scientists in such areas torn by strife. For example, exchanging students to train and work in each other's labs requires permits that are difficult to obtain and need frequent renewal. And, because Israeli firms will not make deliveries to Bethlehem, Dr. Kanaan spends valuable time collecting lab supplies. Dr. King said the research collaboration's success thus far has involved "an enormous amount of goodwill" from both the Israeli government's defense forces and the Palestinian authorities.

Today, 31 joint projects between Israeli and Palestinian scientists are active, according to Ziad Abdeen, M.P.H., M.Sc., Ph.D., Dean of Research and Graduate Studies at Al-Quds University in East Jerusalem. Dr. Kanaan feels a strong personal drive to continue his work. "I need to keep the lab going," he said. "It's my way of saying we are still free to think and do, away from prejudices enforced on us by the nature of any occupation."

Fogarty's FIRCA grants that launched Drs. Avraham and Kanaan's project are designed to facilitate joint research between NIH-supported U.S. biomedical scientists and investigators in developing countries. FIRCA awards, which amount to $32,000 per year for up to 3 years, seek to extend and enhance the research interests of U.S. and collaborating scientists and help increase the research capacity of foreign scientists and institutions. FIC launched FIRCA awards in 1992 and makes about 50 awards per year.

"That is exactly what happened with this collaboration," said Dr. King, who is a former FIC Advisory Council member. "The FIRCA grants succeeded scientifically, in public health, and in technology transfer in both countries," said Dr. King. "Bethlehem University now has the capacity for molecular genetics and genomic analysis, and we have been able to bring Palestinian students into Israeli labs to work on the project. It's a real tribute to the NIH, and Fogarty in particular, that our work is respected by people on both sides of the Middle Eastern conflict."

At the end of their FIRCA support last year, the three geneticists won a prestigious R01 grant from the NIH's National Institute on Deafness and other Communication Disorders to continue their work. "I think the investments in Fogarty are the best investments the NIH makes, dollar for dollar," Dr. King said. "People who use these funds are the cream of the cream of the crop."

FIC Program Director Kathleen Michaels also hailed the success of the FIRCA awards to Drs. Avraham and Kanaan. "Both awardees and Dr. King moved this area of research on deafness along," she said. "FIRCA served the purpose of jumpstarting the three-way collaboration and allowing them to write an outstanding competitive application to continue the collaboration through an NIH R01."

The three collaborators are linked by friendship and the continuing hunt for hearing-loss genes, which, Dr. King said, "is going fabulously." The researchers are also pursuing separate research projects.

Dr. Avraham is deciphering the molecular basis of sensory diseases and disorders, using genetic, developmental, biochemical, and cell biological tools. Her research, much of which involves mouse models, focuses on understanding how hearing is maintained through the delicate balance of protein expression in sensory hair cells. Dr. Kanaan is investigating epidermolysis bullosa, a skin abnormality caused by defects in extracellular matrix proteins in the skin's dermis and epidermis layers. Dr. King, who is American Cancer Society Research Professor of Genetics and Medicine at the University of Washington School of Medicine, discovered BRCA1 and has investigated inherited breast and ovarian cancer for 28 years.

Publications: Walsh T, Walsh V, Vreugde S, Hertzano R, Shahin H, Haika S, Lee MK, Kanaan M, King MC, Avraham KB. From flies' eyes to our ears: mutations in a human class III myosin cause progressive non-syndromic hearing loss DFNB30. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7518-23.

Shahin H, Walsh T, Sobe T, Lynch E, King MC, Avraham KB, Kanaan M. Genetics of congenital deafness in the Palestinian population: multiple con-nexin 26 alleles with shared origins in the Middle East. Hum Genet. 2002 Mar;110(3):284-9.

Weiss S, Gottfried I, Mayrose I, Khare SL, Xiang M, Dawson SJ, Avraham KB. The DFNA15 deafness mutation affects POU4F3 protein stability, localization, and transcriptional activity. Mol Cell Biol. 2003 Nov;23(22):7957-64.