54 THE SCIENTIST | the-scientist.com
PROFILE© AGAPITO SANCHEZ, JR.I
n 1976, Huda Zoghbi (then Huda El-Hibri) was an eager first-
year medical student at the American University of Beirut, Leb-
anon, her hometown. Halfway through that year, a civil war
broke out. “Bombs were falling all around the medical campus,”
the neuroscientist recalls. “I couldn’t commute 500 feet, let alone
the two miles it took me to get home every da y.” She and the other
62 students in her class decided that they, along with their pro-
fessors, would live on campus—mostly underground, in double-
walled rooms—to finish the school year.
Although the medical school was considered a safe zone, as
both warring factions would send their wounded there for care,
an occasional bullet or piece of shrapnel still pierced the cam-
pus. One afternoon, Huda had ventured out for a walk on cam-
pus with her boyfriend, William Zoghbi, a fellow medical stu-
dent. They were holding hands and for no particular reason let
go. In those few seconds, a bullet flew between them. Neither
was hurt, but the young couple realized in an instant how close
and serious the war really was.
Later, shrapnel wounded Huda’s younger brother while he
was walking home from high school, so their parents decided to
send them and another sibling to Texas, where their oldest sister
was a professor of philosophy. The move was supposed to be tem-
porary. But when the 1977 school year was to start in Lebanon,
the civil war was still raging, and neither Huda nor her siblings
could return home.
She was devastated that she could not continue medical
school, and she worried about her parents, living in Beirut sur-
rounded by war. But Huda was also resolute in continuing her
education. She found a medical school, Meharry Medical College
in Nashville, Tennessee, that allowed her to join even though its
academic year had already begun.
Despite the tenuousness of her situation, Huda made do.
She excelled academically. By this time, William had joined
her for medical school in Nashville, and after graduation, they
moved to Houston, Texas. There, Huda began a residency in
pediatrics at the Baylor College of Medicine in 1979. She was
initially fascinated by cardiology, but a rotation in neurol-
ogy opened her eyes to the ways that neurodevelopment can
go awry during childhood. “I kept being drawn back to these
patients, thinking how fascinating the brain is and how as cli-
nicians, we had to use logic to figure out which part of the
brain’s anatomy has a problem and is driving the symptoms,”
she says. She switched her specialty. She and William, a cardi-
ologist, married soon after.Since then, Huda Zoghbi has uncovered the molecular mech-
anisms of normal neurodevelopment and neurodegeneration by
probing the complexities of rare neurological diseases, including
Rett syndrome and spinocerebellar ataxia.LITERATURE, THEN RESEARCH
Zoghbi was born in Beirut in 1954. Her mother raised her and
her siblings while her father ran their family’s olive oil–based
natural soap company. She recalls a simple and happy childhood
by the Mediterranean Sea, playing outdoors, studying, and read-
ing. She devoured Jane Austen, Shakespeare, and Fyodor Dos-
toevsky, as well as Arabic literature. She wanted to be a writer,
but her mother convinced her that, with her excellent grades in
math and the sciences, she should plan to go to medical school.
Zoghbi entered the American University of Beirut as an under-
graduate in 1973, majoring in biology.
“My love of literature has helped my research career,” she says.
“My colleagues tell me that when I give scientific talks or write a
paper, I always tell a story. So I ended up channeling my passion
for writing into my science career.”
After her pediatric residency at Baylor, Zoghbi stayed at the
Houston-based institution, starting a pediatric neurology fellow-
ship in 1982. She was frustrated by the fact that medical science
could only ease the symptoms of the many children she worked
with who suffered from untreatable neurological disorders. It was
then that a patient caught her attention: a girl with Rett syn-
drome, a rare, poorly characterized disorder that leads to severe
learning disability and motor impairments, including ataxia—
balance and coordination problems—loss of speech, seizures, and
some autism-like behaviors, most distinctively repetitive hand-
wringing movements.
“The children are born normal, acquire milestones, and then
gradually lose them,” she says. “I saw two Rett patients in the
same week, and this is a rare disease affecting about 1 in 10,000
girls.” In the scientific literature, there was no reporting of Rett
patients in the US, so Zoghbi set out to find additional indi-
viduals with the disease. She studied six of them to understand
the pathogenesis of the disorder and found that the girls had
decreased circulating metabolites of key neurotransmitters, nor-
epinephrine and dopamine in particular.
Those results, and Zoghbi’s work over the next few years,
helped Baylor become a major Rett syndrome referral center.
The disorder mostly afflicts female offspring of healthy parents,
making it 99.5 percent sporadic from an epidemiological stand-Driven to find ways to help patients with rare nervous system disorders, Huda Zoghbi has spent
her career understanding the genetic and molecular basis of neurodevelopment.BY ANNA AZVOLINSKYGenetic Neurologist