Dr. Ohad Birk takes a self portrait: We’re combining basic research using the latest scientific technologies, with practical applications and deeply human concerns. Wearing two hats – he’s both a clinician and a researcher – Dr. Ohad Birk is treating genetic disorders while hunting down the genes that cause them.

While serving the entire population of some 500,000 in southern Israel, the main focus of his work is with the nearly 140,000 Bedouin of Israel’s Negev region, who suffer a particularly high incidence of genetic disorders.

And while relieving their suffering, the work of Birk’s multidisciplinary team also has applications well beyond the country’s southern desert.

The Negev Bedouin are a relatively isolated population, and they have a very high proportion of consanguineous marriages, with some two-thirds of individuals married to first or second cousins. As an unfortunate consequence, the Bedouin show a high rate of genetically-determined neurological, skeletal, eye, cardiac, gastro-intestinal, skin and eye diseases. There’s even “hereditary infertility” – not a contradiction in terms, explains Birk, acting director of the Genetics Institute at Soroka Medical Center in Beersheva and head of the Ben-Gurion University’s Human Molecular Genetics Lab, but a matter of statistics, since if both
parents carry the defective gene, perhaps a quarter of their children will suffer the defect.

Some abnormalities result in stillbirths. An additional portion of human pain and family dislocation comes with live births burdened by such genetically linked illnesses as: congenital glaucoma and blindness; nasal hypoplasia, a condition in which the baby’s nostrils are blocked; aplasia cutis, in which no skin covers the newborn’s skull; craniosynostosis, a fusing of the rear skull plates that forces the brain to expand upward, elongating the skull; and neurological-spastic diseases, which “most babies” don’t survive for more than six months. Birk also identifies a doubly tragic, still-unnamed syndrome in which an apparently healthy 1-year-old starts to decline, losing mental and physical functions until it dies, usually by age four.

While treating these diseases, Birk, at the head of a combined research and clinical team of 45 people, offers the Bedouin pre-marital carrier testing and pre-natal diagnosis, as well as support in educational programs for high school and religious teachers that increase awareness and prevention of genetic problems. An increasing number of Bedouin now request pre-natal diagnosis, because their religious practice allows abortion through the first four months of pregnancy. There is also growing interest in this community in pre-marital genetic testing, similar to that done in the ultra-orthodox Jews.

However, some illnesses show up too late for abortion, notes Birk, while mental retardation does not reveal itself until after birth. While much progress has been made, he adds, continued inbreeding (and a birth rate of more than 7 children per family) increases the incidence of common defects and creates new ones. Birk notes that changing traditional marriage and family patterns is a slow process.

Beyond treatment and education, Birk’s research group is aimed at long-term prevention by hunting down the genes responsible for these illnesses – painstaking work that requires first characterizing the physical condition, then preparing a DNA “workup” in tandem with a complete history of the affected individual’s extended family. A “genetic linkage analysis”
then aims to identify which group of genes (out of tens of thousands in the human genome) harbors the specific defect responsible for each specific condition. That search generally yields a “locus” of 10-100 genes, Birk says. Further investigation, including comparison of the sequencing of the target genes to normal sequencing, allows Birk’s team to determine if the patient has a gene “miscoding” – an actual mutation of the gene.

While offering carrier testing to the extended family as a clinical option, Birk’s research then continues with the creation of lab mice with the same condition. “Human genes are 97 percent identical to mouse genes,” Birk points out. “If a child is born, for example, without eyes, we create the same phenotype in mice. Such mice allow further studies of the genes, and serve as models for novel treatment modalities in the future.”

The Bedouin total mutation rates are not higher than in any other population, Birk takes care to explain. “We all have mutations in our genes. But in the inbred Bedouin community, individuals meet and marry carriers of the same diseases more frequently, so the rate of genetically
sick infants is higher.”

In some 15 years of genetic studies on Negev Bedouin, Professor Rivka Carmi, the founder of this project (currently Dean of the BGU Faculty of Health Sciences), in collaboration with laboratories in the United States, identified the genes for ten diseases. In the past three years, Birk has taken over, setting up a very effective research laboratory doing all the research “in-house.” State of the art biotechnology tools that emerged in the past few years and a generous support by the MK Humanitarian Foundation have enabled rapid progress: within a couple of years, the team has enabled novel carrier testing for some 15 severe diseases, applicable to more than 20,000 individuals.

In fact, working in close collaboration with many physicians both in southern Israel and throughout the country, Birk’s laboratory has now become a center for research of genetic diseases in inbred communities throughout Israel.

This tremendous effort of prevention, treatment and investigation is sure to bring benefits not only to other Arab and Bedouin communities in the Middle East but also to Europe, with its large Muslim populations. Moreover, studies of this inbred population allow a unique opportunity also in identifying novel drug targets for complex common diseases such as epilepsy and morbid obesity. In fact, Birk is now expanding the focus of his genetic research to include diabetes, whose increase in the Bedouin community mirrors a significant worldwide spike in incidence.

Does he like his work? “We’re nailing down the precise molecular basis of diseases while dealing with intense human situations,” enthuses Birk, who is armed with an M.D. and Ph.D. from Israeli universities plus post-doctoral stints, both clinical and research, at the National Institutes of Health in the USA. “We’re combining basic research using the latest scientific technologies, with practical applications and deeply human concerns. Altogether, it’s amazing, and I love it.”