Medicine: Finding Ill-Fitting Genes
Hadassah–Hebrew University Medical Center is welcoming a fresh face— acclaimed physician and researcher Judith Melki, the new head of human genetics.
When Judith Melki, her M.D. newly minted, interned in pediatrics and genetics at hospitals in her native Paris, she found herself faced too often with dying babies whom she was unable to help.
“I would look at a sick infant and know there was nothing that I or any other doctor could do to save it,” she says. “And then I would have to face that baby’s young parents and tell them their child would die, and then tell them their chance of having other children, similarly affected, was high.”
This was 1986. there was no treatment for most of the 4,000 diseases known to be caused by the transmission of mutant genes. For the vast majority of diseases, not even genetic counseling was possible.
“After a couple of years as an intern, I decided to see if I could help these families through the laboratory,” says Dr. Melki.
With characteristic understatement, the diminutive physician and scientist continues: “I found I could be useful there. I identified my first gene, one that is responsible for spinal muscular atrophy, which affects one in 6,000 infants. Then I identified others. When I saw how much this helped afflicted families [by enabling prenatal diagnosis], it was impossible to stop looking for more.”
Dr. Melki, 51, is the new head of human genetics at the Hadassah–Hebrew University Medical Center in Jerusalem. She succeeds Dr. Gideon Bach (himself discoverer of the gene that triggers mucolipidosis IV), who established the department 26 years ago. Dr. Melki, who has a Ph.D. in neurogenetics, tendered her resignation last April to three prestigious Paris institutions: the University of Paris-Sud 11 medical school, where she was professor of medical genetics; the Sud Francilien hospital’s medical genetics unit, which she led; and the Molecular Neurogenetics Laboratory at the French National Institute for Health and Medical Research, of which she was also head.
What makes a woman at the top of her profession uproot herself and start again? “Change isn’t a bad thing,” she says, smiling. “Ten years from now will be too late to make a career move. So I am doing it now.”
In practical terms, Dr. Shlomo Mor-Yosef, director general of Hadassah Medical Organization, made Dr. Melki an offer that was hard to refuse. “He and the medical center administration gave me professionally tempting undertakings that they have kept to the letter,” she says.
“Dr. Melki is a world renowned researcher in human genetics, in particular muscular and neural diseases,” says Dr. Mor-Yosef. “She has published extensively in leading scientific journals and is a highly recognized physician, a combination characteristic of Hadassah’s department heads. We felt she fitted in here, and we’re delighted to welcome her.”
Among the “tempting undertakings” given Dr. Melki was enabling the upgrading of the department. The physical facility was relocated and rebuilt with a larger medical-genetics clinic and a better equipped diagnostic laboratory. Dr. Melki has also been supported in building a genetics-research unit with one of the best platform-technology facilities in the world where she and her team will hunt down mutant genes.
Along with the professional offer, Dr. Melki weighed three more factors in deciding to move. “First, Hadassah is one of the world’s most prestigious hospitals, on a level with the best in Paris,” she says. “Second, the expertise of Hadassah physicians and researchers is widely recognized.” And third, while the career opportunities were a strong draw, they were underpinned by the pull of dormant Zionism.
“I had visited Israel often,” she notes. “I had gone for professional meetings, and I have relatives here. Once I began to think about moving to Israel—and best of all to Jerusalem—and setting up a new research lab, it was no longer something I could pass up.”
The fourth of six children, Dr. Melki is descended from a French Jewish family that lived in Constantine, Algeria, until 1950, counting two generations of war heroes among its members.
“My grandfather was awarded France’s highest decoration, the Légion d’Honneur, for service in World War I,” she says. “My father served with [Charles] de Gaulle and the Free French, who were based in Algeria after 1943 in World War II. He fought in the invasion of Sicily and in the battles at Monte Cassino, which cleared the way to Rome. He, too, received a Légion d’Honneur and a Croix de Guerre for heroism.”
The Melkis had French citizenship (secured for Algeria’s Jews in 1870 by French Jewish lawyer and statesman Adolphe Crémieux). In 1950, with the political situation in the country—and, along with it, the plight of its Jewish community—deteriorating perilously as Algeria battled for independence, the family relocated to Paris.
“My father studied medicine there and became a dermatologist,” says Dr. Melki. “Most of us followed him into medicine or related fields.”
Dr. Melki left for Israel in August 2007. Unmarried, she came on her own and has made friends quickly. With them, she indulges her passion for walking. “Shabbat is my day for getting to know Jerusalem,” she says. “Each week, on foot, we explore one of the city’s neighborhoods or nearby villages…. The more I see and get to know, the more wonderful I find it.”
Dr. Melki speaks as an expert. Among countries through which she has hiked are Scotland, Ireland, Iceland and Indonesia. “I love to walk and I love exploring what’s around me,” she says.
For the six days a week that aren’t Shabbat, Dr. Melki is a research scientist and head of a busy department with a major budget. Barely breaking 5 feet in height with brown curls, a soft voice and an unassuming manner, she looks 20 years younger than her age, but her reputation and ability effortlessly command the respect of colleagues. Hadassah’s humangenetics team is well aware that their new department head is a celebrated scientist whose name appears on close to 100 published research papers, who has identified genes, created genetics-testing tools, generated animal models, registered patents and is developing breakthrough therapeutic approaches.
Dr. melki began at hadassah last September. “I was concerned that the human-genetics team would find it hard to accept a new head after working with Dr. Bach for so many years,” she recalls. “But… I feel I have settled in easily and that we work well together.”
She finds her colleagues able, professional and highly motivated.
“The main difference here in Israel is the mentality,” she says. “The new team works much more independently than my team in France, and they are also far less formal and more direct. Directness has advantages and disadvantages, but overall I appreciate it. It’s sometimes a lot easier when people say what they mean and call a spade a spade.”
With the encouragement of Hadassah and the new research lab in which the estimated three billion chemical sequences of the human genome can be screened in four days, Dr. Melki sees Hadassah becoming a referral center in genetic disease for the entire Middle East.
“The genetics of rare diseases is one main area of our research,” she says. “It’s one that is sometimes simpler to investigate here, where [intra]marriage among many of Israel’s Jewish and Arab communities increases the frequency of some genetic diseases. This helps us track down culprit genes. Identifying these genes allows us to counsel the families that carry them.”
Discovery of mutant genes is also expected to lead the way to therapy. This is the second main research area in Hadassah’s new lab: understanding how mutation wreaks damage so therapeutic strategies can be created. To do this, the team develops animal models that mimic the human disease. While still in Paris, Dr. Melki created a model for spinal muscular atrophy, the most frequent recessive autosomal disorder after cystic fibrosis. This has led to clinical trials with a molecule that alleviates the condition, currently under way outside Israel.
“The more we know about a disorder, the closer we come to treating it effectively,” she says.
The first research projects in Hadassah’s new genetics-research lab began in January, with several more in development.
“This is long-term work,” says Dr. Melki. “Research is like a tree. You plant it and you nurture it. It grows only a little each year, but eventually it bears fruit.”