Autobiography of Huda Y Zoghbi
I was born and brought up in Beirut, Lebanon. My father owned a business making olive oil and olive oil soap, and my mother was a housewife. My parents loved learning and I grew up in a house that had an enormous library stocked floor to ceiling with books.
For college, I attended the American University of Beirut (AUB). After a brief but intense flirtation with literature, I decided to major in biology at my mother’s insistence and continued on to medical school at AUB. Medical school changed the course of my life. I met the love of my life, William Zoghbi, who has been my greatest joy for the past 40 years and father to our two precious children, Roula and Anthony. It also brought me to the United States. In 1975, half way through my first year, civil war broke out, forcing those of us determined to continue our studies to sleep in double-walled rooms and basements on campus. That summer, my parents sent my brothers and me away with the full expectation that the war would end quickly and I’d return to Beirut for the next term.
However, the war worsened, leaving no way to come home safely. I applied to transfer to an American medical school, and was fortunate that Meharry Medical College agreed to take me even though school had already been in session for two months. I was terribly homesick and coped by studying constantly and dreaming of returning to Lebanon. But the war continued. Fortunately, William transferred to Meharry the next year, easing my loneliness.
We completed fourth year rotations at Stanford, Emory, and Baylor College of Medicine (BCM). I fell in love with BCM because of the nurturing collegial environment and Ralph Feigin, chair of the pediatrics department, who took me under his wing. When William and I graduated, we both matched at Baylor for residency. During that time, Ralph taught me clinical scholarship and became like a second father to me. I initially had my heart set on pursuing pediatric cardiology. However, on my pediatric neurology rotation, I met Marv Fishman, a fantastic clinician and teacher who helped me appreciate the beauty of taking a history and solving the puzzle of the patient through logic and physical exam. By the end of this rotation, Marv had inspired me to become a child neurologist.
In 1983, the course of my life changed again. At Texas Children’s Hospital, I met a five-year-old girl with Rett syndrome—a new clinical entity that I had just learned about from a paper by Hagberg and colleagues. A week later, I encountered a second girl with Rett. The girls are born apparently healthy, but around 12-18 months they begin wringing their hands continuously and lose their acquired motor and language skills. The Rett presentation was so unusual and consistent that I thought it had to be genetic. I began searching for similar cases and within days I identified six more girls with Rett syndrome. Not only was this a puzzling constellation of symptoms, but the mechanism of disease was enigmatic, too: there was no apparent defect at birth, nor was there degeneration of the brain. I felt compelled to pursue research to understand the cause and be able to offer parents some kind of hope for treatment.
I was fortunate to join, as a post-doctoral fellow, the lab of Art Beaudet, who mentored me in molecular genetics despite my lack of experience. He steered me towards a project involving an adult ataxia syndrome that promised to be more tractable to genetic methods than a sporadic disorder like Rett. I started my own lab studying spinocerebellar ataxia type 1 in 1988, and in 1993, Harry Orr and I discovered that CAG repeat expansions were the culprit. Our continued collaboration has been one of the longest-running and most joyful of my career.
I had not forgotten Rett, though. I had been collecting data and had samples from over 200 families. Many scientists doubted a sporadic disease could be genetic and funding dried up. Thankfully, in 1996, I became a Howard Hughes Medical Institute investigator and the Rett families agreed to support a postdoc in my lab—two critical events that provided the funding that helped us to finally find, in 1999, that mutations in MECP2 cause Rett. Many ask what kept me going all those years. The answer is the girls and a strong intuition that their symptoms had to be caused by a specific molecular defect.
The discovery of the Rett syndrome gene remains the most hard-won and personally important to me. I am forever grateful to the Rett families who trusted in me and for the tireless trainees who took a huge risk working on this project, especially Ruthie Amir, who persevered to discover the mutations despite three years of negative data. I am thankful that my clinical experiences guided me to the lab where I discovered how much I enjoy research and solving biological puzzles, how important basic science is to advance medicine, and the joy of mentoring students and fellows. I am deeply honored to share the Shaw Prize with Adrian Bird, who has done so much to reveal the workings of MeCP2.
27 September 2016 Hong Kong