I like this article. It seems to give a very frank amd honest story as to how and why Dr Angela Christiano began her interest and research into Autoimmune Alopecia. I commend this lady. There is one part in the article which explains to me clearly that people who have never suffered this disease have absolutely no idea what the full psychological effects of it are. Researchers thought Dr Angela Christiano’s research had turned “trivial”……. So still the medical professionals see Autoimmune Alopecia as “just hair”…… Her colleagues asked her,
“How could you go from working on this life-threatening thing to hair?”
It seems in order to get somewhere we may have to come together as a community an push for this since only WE know how drastically this affects our lives, noone else 😦
Farther from when this article was printed Dr Angela Christiano found Autoimmune Alopecia to be genetically linked with Rheumatoid Arthritis, Celiacs Disease and Diabetes Type I. From these common genetic links it seems very sensible for us to be looking down the lines of diet to perhaps manage this condition, or at least ruling it out. Celiacs Disease is very much gut related which inturn is causing the immune reaction in the body. Definitely something to be considering. Dermatology is not helping Autoimmune Alopecia.
By Barry Yeoman
Originally published in
Discover, February 2006
WHEN A WOMAN GOES BALD
ON A FRIDAY MORNING LAST JUNE,
Efrat Fadida threw a denim jacket over her white summer blouse and
caught a ride with her father from the small Israeli town of Gedera east to
Jerusalem. Walking into Hadassah University Medical Center, the 25-year-old cut
a striking figure: high cheekbones, a square jawline, and a scalp as bare as the
day she was born. Fadida suffers from alopecia universalis, a genetically
influenced autoimmune disease that can strike at any age, causing all the body’s
hair to fall out. She had come to Hadassah to meet a team of gene hunters.
“I’ve had this disease a year,” Fadida told the researchers, speaking in
simple declarative sentences and using her fingers to draw quotation marks
around the word disease. “It started in small bald spots. It became
very big, so I decided to shave my head. The only thing that bothers me is that
I don’t have any eyebrows or eyelashes. I’ve learned to love myself.” What she
didn’t say was that she hadn’t always been so accepting, although four others in
her family have the same disorder. As Fadida’s hair began to disappear, she grew
skittish about shampooing. She worried that her boyfriend would leave her. For
the first month she cried constantly. Today, living with supportive parents, she
no longer dates her boyfriend and remains wary of others’ reactions. “I put
makeup on, but I still look like an ill person,” she says. “When people see me,
they think automatically that I have cancer.”
Recently, geneticists have
started closing in on clues that might lead to treatments for Fadida’s disease.
Their efforts are part of a larger push to study more than 300 known genetic
hair disorders, which range from rare diseases detected in a few dozen families
to male-pattern baldness, which affects hundreds of millions. What all these
diseases likely share is a disruption somewhere in the complicated growth cycle
of the hair follicle.
As Fadida spoke, one scientist in the group
listened with particular interest. Angela Christiano, a molecular geneticist at
Columbia University in New York City, presented a dramatic contrast to Fadida,
mostly because of her hair. A veritable fountain of it rises high above
Christiano’s skull and cascades past her shoulders in bursts of onyx and bronze.
Elaborately colored and curled, it is more sculpture than hairdo, and
inescapably the first thing anyone notices about her.
appearances, Christiano knew exactly what the young Israeli was feeling.
Diagnosed in 1996 with alopecia areata, the geneticist lost 10 large clumps from
her magnificent mane before symptoms finally abated.
Christiano has cracked the genetic code of three hair diseases. Now she wants to
pin down the mutations that caused Fadida’s hair loss, and in doing so, figure
out what caused her own.
ALTHOUGH TWO OF HER RELATIVES CUT
HAIR for a living, some of the women in Christiano’s family had trouble
retaining their own. As they reached menopause, both Christiano’s mother and
grandmother began going bald. They wore wigs in public and shied away from any
activity like swimming that might blow their cover. And they were hirsute
compared with Christiano’s second cousin, whose alopecia universalis left her
without a single hair anywhere on her body.
None of this history,
however, led Christiano to her studies. That happened with remarkable
serendipity. After she earned her Ph.D. from Rutgers University in 1991, she
began an emotionally wrenching postdoctoral fellowship: hunting down the genetic
basis of epidermolysis bullosa, a childhood disease that causes disfiguring and
even fatal blisters. Every few months, Christiano collected blood samples from
children at Rockefeller University Hospital in New York City to analyze their
DNA. “These kids are covered from head to foot with blisters that are like
third-degree burns. They have to be bandaged constantly. And to take those
bandages off, you have to soak the children in warm water because if you just
took the gauze off, you would take their skin off.”
powerless because scientists knew so little about the disease. But over the next
five years she isolated one gene, then another, and another, until more than 50
mutations on several genes associated with epidermolysis bullosa had been
nailed. Not only did her research lay the groundwork for effective genetic
counseling, but she also developed the first prenatal test for the disease. She
Riding on success, she accepted an appointment at Columbia
University in 1995. In her new job, she was expected to break away from her old
postdoctoral studies and establish herself as an independent scientist with new
research interests. In her first academic year, she seemed to be spinning
without direction. Then one day she got her hair cut.
It was May 9,
1996. Christiano was at her favorite salon in Metuchen, New Jersey, when the
beautician casually mentioned a small bald spot: “What happened? Did you have a
biopsy back here?” Christiano assumed she had merely tied her hair too tight,
but later that day she asked a colleague for a second opinion. With the office
door closed, immunologist Monica Peacocke parted Christiano’s hair. When
Peacocke saw a bald patch the diameter of a coffee cup, she let out a scream.
“It’s not small!” she cried.
Doctors diagnosed the problem as alopecia
areata, a genetically determined autoimmune disease in which the body’s T cells
identify hair-follicle cells as foreign invaders and try to destroy them.
Healthy scalp hair follows a staggered process through three phases: a growth
period, which can last up to eight years; a two- to three-week degeneration
period; and a two- to four-month resting period, during which the follicle
weakens and the hair falls out. The periods can vary in length in different
people, but in patients with alopecia areata, all the hair in a single area
enters the phases of degeneration and resting at the same time, causing hairs to
fall out all at once.
Doctors told Christiano the only
treatment was to undergo a series of painful cortisone-derivative shots in her
scalp to blunt the immune-cell attack. Over the next year and a half, she
developed nine more bald spots. As soon as hair in one corticosteroid-injected
patch began growing back—as colorless as rice noodles at first—another would
Christiano lived with perpetual fear: “You wake up every morning
and before you lift your head off the pillow, you think, ‘Is it all there? Is it
gone?’ And then you get angry at yourself for being so vain. You think, ‘I just
spent five years working on these lethal skin diseases. I should count my
blessings that this is all I have.’ And that doesn’t work.” The answer, she
decided, was to throw herself into figuring out what was happening to her.
As she learned more, she was surprised that so little was known about a
condition that plagues 5 million Americans. What genes are responsible for
normal hair, she wondered. And what at the molecular level causes those cycles
to go awry?
Because alopecia areata was believed to result from more
than one altered gene, Christiano knew it would be daunting to decipher. The
completion of the Human Genome Project was almost a decade away. Instead, she
decided to seek out a simpler form of the disease, one regulated by a single
gene. She knew what to look for: a family in which a large number of people had
extreme hair loss but whose other members had perfectly normal hair. That
pattern of inheritance would suggest the strong effect of a single gene
mutation, and it would most likely crop up in families that had a lot of shared
genes through the intermarriage of first cousins.
She found what she was
looking for in a remote part of
LESS THAN TWO WEEKS AFTER HER
ALOPECIA was diagnosed, Christiano read a clinical report about a
family in a small Punjabi village. Many of its babies were born with hair, but
they soon lost it, even their eyelashes. The problem did not appear to be
related to more complex skin disorders: Their teeth were fine. Their nails were
fine. They sweated normally. “It was exactly what we were looking for,” she
Christiano sent a letter to researchers in Islamabad, suggesting a
collaboration and enclosing a snapshot of her own bald spot. Five months later,
30 blood samples arrived, followed by Pakistani researcher Wasim Ahmad, who
remained at the New York laboratory for two years. Christiano and her team chose
several of the samples, analyzed the DNA, then compared the bald patients with
relatives with normal growth. She identified a region on chromosome 8 where the
affected family members had distinctly different genes.
ecstatic: “Oh, my God, it was like heroin.” But she was still a long way from
isolating a gene. “Let’s put it in simple terms: We went from the whole of the
United States down to a zip code. Maybe a county,” she says. Within that region,
there were hundreds of genes, few of them mapped. When it came to further
narrowing, the Columbia team was stalled.
A photograph of a young family
member finally helped crack the problem. Typically, the family followed the
Muslim practice of shaving the heads of its infants. Once the hair was shaved,
it never grew back. One mother, however, did not shave her daughter’s head.
Ahmad obtained a picture of the girl at age 6. Partway through the balding
process, she retained a fringe on the back of her head, much like a 50-year-old
man with male-pattern baldness.
Shortly afterward, Christiano attended a
lecture at a meeting of the Society for Investigative Dermatology. She heard
about a mouse with a mutation on a recessive gene nicknamed hairless. A slide
show illustrated how, over the course of four days, the mouse’s hairline
migrated from its nose toward its tail, until the animal was nearly bald. As
Christiano viewed the slides, she realized the pattern resembled that of the
young Pakistani girl. She decided to explore whether the mouse and the girl had
the same condition. Because mice and humans share many of the same genes,
Christiano’s lab was able to isolate the human equivalent of the hairless gene.
To everyone’s delight, it was located on chromosome 8. Then the team compared
the DNA sequence of an affected patient with that of a healthy control. Sure
enough, the hairless gene from the bald Pakistani family contained a mutation.
“This was a landmark achievement,” says Ralf Paus, a professor of
dermatology at the University of Lübeck and an expert on hair-follicle biology.
The matching of human and rodent phenotypes—observable characteristics—to find
human mutations was a novel idea among hair researchers. “We had been pestered
by clinicians saying, ‘What does the mouse say about human hair growth?'” Paus
says. “This proves that what you can do with mice you can extrapolate to the
Christiano’s paper, published in the journal
Science in 1998, did, however, contain one notable misnomer. Using the
original Pakistani diagnosis, she suggested that the family was suffering from a
form of congenital alopecia. It turned out that the patients had a much rarer
disorder called papular atrichia, which destroys the hair follicle. That made
her discovery “biologically fascinating but clinically of limited relevance,”
Paus says. (Worldwide, there are only about 30 documented families with papular
atrichia.) Still, by identifying the human hairless gene as an important master
switch in regulating cell death in a hair follicle—a discovery that could lead
to gene therapies for unwanted hair growth—Christiano emerged as a new star in
the field, and a glamorous one.
“The first talk she gave, people
thought: ‘Who the hell is this? How did she get in here?’ ” Paus recalls. “With
her flamboyant hairdo, no one could believe this was one of the world’s foremost
skin researchers. But she has vitalized the hair field like no one before her.
Some people get a little taken aback by her flamboyance. I just love it—and if
you look at her work, no one can compete with that.”
CHRISTIANO MADE THE SWITCH to hair research from skin blisters, some of
her colleagues in the epidermolysis bullosa field wondered if her research had
turned trivial. “Hair?” she remembers their asking. “How could you go from
working on this life-threatening thing to hair?” But as the news of her research
spread, Christiano was deluged with correspondence from people suffering from
all sorts of hair abnormalities. Some wrote that they never left their homes.
Others had considered suicide. “I am frustrated and scared and feel hopeless,”
wrote a midwestern woman with little hair left. “I don’t know what it will do to
me if I keep losing my hair.”
Psychologist John Rooney of La Salle
University in Philadelphia has found that women so prize their hair that most
students surveyed during a classroom exercise said they would not shave their
heads for even $1 million. The roots of such a strong emotional attachment may
well lie in natural selection, says evolutionary psychologist David Buss of the
University of Texas: “Hair quality—fullness, texture, color, and even length—are
strong correlates of youth and health. They signal high mate value. Loss of hair
signals loss of mate value, hence it is psychologically upsetting.”
wasn’t until those letters started pouring in that I realized that, even though
people didn’t die from this disease, a part of their soul died,” Christiano
Not long after her discovery, Christiano was giving a lecture at
Harvard University when a dermatologist approached to tell her about two sisters
in Acerno, a mountaintop village outside Naples, Italy. Both girls were born
with compromised immune systems. One had died around her first birthday. The
other had received a bone-marrow transplant at five months, enabling her to
survive into childhood, but without scalp hair, eyebrows, or eyelashes. “I think
this might be related to the nude mouse,” the Harvard scientist suggested. Mice
with mutations in what is called the nude gene don’t fully develop the thymus, a
small organ in the chest cavity that plays a key role in the maturation of
infection-fighting T cells. For reasons unrelated to the thymus, the rodents
also have immature follicles and are completely bald.
contacted Claudio Pignata of Federico II University of Naples, who informed her
that a handful of children in Acerno die each year of the same immunodeficiency.
In most cases, the children are so ill and die so young that their baldness goes
unnoticed. Pignata sent blood samples to New York. Christiano’s lab found that
the sisters had a common mutation on chromosome 17, right in the area of the
human nude gene. A deeper analysis confirmed her hunch, linking nude to the
sisters’ condition. Pignata now offers genetic counseling based on blood tests
of prospective parents in the Italian village, where one resident in 15 carries
Meanwhile, more letters arrived. Christiano heard from a
Texas pediatrician whose Pakistani-American family had sparse hair that broke
easily and sometimes coiled beneath the skin because it was too weak to
penetrate the surface. By now she had set up a system: Find a mutant mouse with
a similar phenotype and see if the human patient had a mutation on the
equivalent gene. “This is our hat trick,” she thought. But when she tested one
candidate mouse with a known mutation, the trick failed.
Christiano turned to a colleague, who suggested she look at a lanceolate mouse,
a rodent with sparse, stubbly hairs but no identified mutation. It took five
years of gene hunting to find the source of the mouse’s strange hair patterns.
In 2002 a student in Christiano’s lab was studying the Human Genome Project
database and noticed an unnamed region where Christiano had predicted the human
version of the lanceolate gene would reside. The gene proved to be severely
mutated in both the Texas family and some lanceolate mice. “This one took a
little bit longer,” Christiano says, “but only because we had to wait for the
genome project to catch up and point us in the right direction.”
UNLIKE A DISEASE SUCH AS HYPERTENSION, which
follows a similar course in most sufferers, hair diseases come in many types.
And while the most common disorders involve the absence of hair, some people
grow too much. Christiano turned to a rare condition called hypertrichosis,
whose sufferers are sometimes called wolf people. Instead of growing normal
facial hair, they develop thick, pigmented scalp hair called terminal hair all
over their faces. So unusual is their appearance that some people with
hypertrichosis work as circus performers. The syndrome has different causes, but
it can be inherited in families, and Christiano suspects it involves a single
The problem of studying hypertrichosis is that so few people have
the genetic form. So for the past six years, Christiano has been scouting
research subjects all over the world. In 1998 she located two families in
Europe. Then, in 2001, she flew to Monterrey, Mexico, where a colleague drove
her to a rural open-air clinic. There she met a family with a quirky phenotype:
those with excessive hair were also deaf and unable to speak. Many of them lived
in shame, remaining inside and shaving constantly.
family—especially an uncle and his young nephew—touched Christiano. “The uncle
was just amazingly beautiful,” she says. “I mean, I’ve never seen so much hair
on one person. Others in the family were not as out about their disease, but he
was very proud of his. He couldn’t wait to take his shirt off and show me his
“We could tell that the nephew looked up to this uncle as a guide
to what his life was going to be like. In turn, the uncle looked at this kid as
his responsibility. And they didn’t even do sign language with each other. Even
though they couldn’t vocalize or hear each other, they had this bond that was
Christiano took blood samples. She has not turned up
any genetic clues yet, but if she succeeds, the impact could be staggering.
Hypertrichosis is the mirror image of male-pattern baldness. With balding men,
ordinary scalp hair is replaced by vellus, or peach fuzz. Among people with
hypertrichosis, facial vellus is replaced by scalp hair. Unlocking the secret to
hypertrichosis could lead to gene therapies not just for people with too much
hair but also for some of those with too little.
IS NOT A THEORIST. “Although she’s a Ph.D.-trained scientist, she’s
always looking for the clinical relevance of her findings,” says Hal Dietz, a
researcher at the Institute for Genetic Medicine at Johns Hopkins University.
“She’s very emotionally attached to the patient populations. She’s always looked
for the relevance of her work to prenatal diagnosis of a condition, family
counseling, and the development of new and rational treatment strategies.”
Christiano’s desire to connect with her research subjects was what
brought her to Jerusalem last June. Hadassah University Medical Center claims
the world’s largest collection of patients with genetic hair diseases, including
roughly half the documented cases of papular atrichia, the condition Christiano
linked to the hairless gene. It also has many patients with alopecia, the
disease that triggered Christiano’s own hair loss and which remains unsolved.
“It’s extremely important not just to see the blood or the DNA but to see there
are human beings behind this. And they suffer,” says Hadassah dermatologist
Abraham Zlotogorski, Christiano’s principal Israeli collaborator. “It’s very
important for patients to see there’s an international effort to find a cure for
their problem.” Conditions like papular atrichia are sometimes known as orphan
diseases because they lack the frequency to merit much research. “But for
patients, this is not an orphan disease,” Zlotogorski says. “It’s 100 percent of
When Christiano arrived at the clinic that Friday
morning, the waiting room was already filling with the patients whose DNA she
knew intimately. Several of the papular atrichia families had traveled from the
West Bank and Jordan, braving bureaucracy and highway checkpoints solely for
science’s sake, as the disease still has no treatment. Emerging from the
elevator, the geneticist saw two bald Palestinian girls, ages 3 and 8, who had
come from the West Bank with their fathers, cousins in an intermarried family.
Their heads were covered with kerchiefs. It was the first time Christiano had
ever seen atrichia patients face-to-face. “Oh, my God,” she whispered. “They’re
For the next five hours, the Hadassah conference room was a
buzz of activity. Patients came and were examined. Most who were bald covered
their heads with wigs or kerchiefs; their embarrassment was palpable.
Zlotogorski pointed out the papules (tiny bumps) on the heads, elbows, and knees
of the atrichia patients—subtle manifestations that help clinicians distinguish
the disease from the autoimmune form of alopecia universalis. Questions and
answers were translated into Hebrew, Arabic, and English. As lunchtime came and
went, pastries disappeared from the middle of a long oval conference table.
Researchers took blood samples and skin biopsies and sketched out family
pedigrees on scrap paper. Patients with alopecia universalis were given steroid
shots in their eyebrows in hopes of revving up hair growth. As Zlotogorski
injected a 14-year-old Israeli girl—who held her bald mother’s hand and flinched
at the needle—Christiano watched and winced with her. “It brings back so many
memories,” she said.
“But you’re cured, right?” asked Basel Saad Edin, a
Hadassah physician from the West Bank.
“You’re never cured,” Christiano
said. “You wake up every morning and you feel…” The sentence trailed off as
she patted the back of her head. “Too many memories,” she finally said.
“In Arabic, there’s a saying: If there’s a crisis, sometimes it benefits
other people,” the Palestinian physician said. He reflected on the international
effort fueled by Christiano’s own disease—an effort that has brought scientists
closer than ever before to finding the genetic basis of alopecia areata and its
more extreme variants. “Maybe,” he said, “it’s a good thing you had this
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