www.washingtonpost.com Open in urlscan Pro
104.64.160.155  Public Scan

Form analysis
0 forms found in the DOM

Text Content

Accessibility statementSkip to main content

Democracy Dies in Darkness
SubscribeSign in
ScienceSpace Animals Health Environment
ScienceSpace Animals Health Environment


THIS BOY WAS BORN WITHOUT AN IMMUNE SYSTEM. GENE THERAPY BUILT ONE.


THE INNOVATION MAY HELP PAVE THE WAY TOWARD TREATMENTS FOR HUNDREDS OF OTHER
RARE DISEASES

By Carolyn Y. Johnson
November 27, 2023 at 6:00 a.m. EST

Hataałii Tiisyatonii "HT" Begay, 5, rides a toy horse next to his brother
Hastiin, 7, at the family ranch on the Navajo Nation. (Adriana Zehbrauskas for
The Washington Post)

Listen
16 min

Share
Comment on this storyComment93
Add to your saved stories
Save

TUBA CITY, Ariz. — Hataałii Tiisyatonii “HT” Begay, a Native American boy who is
Diné, or Navajo, rolls toy trucks around in the dirt. He chases chickens into
their coop. He pauses to watch his dad deftly gut a sheep for a ceremonial
feast. Then he climbs onto a picnic table with his brother and cousins, chanting
“Lava!” while pretending the ground has turned into molten rock.



To his family, HT is a typical 5-year-old — a smiling, curious, busy blur who
roams across his family’s ranch, where the land seems to stretch all the way to
the sky.

To his doctors, he is a marvel.

HT was born with a form of severe combined immunodeficiency, or SCID, which
meant he had virtually no immune defenses. About 70 children are born with SCID
each year in the United States and Canada, though only two or three will have
the same type as HT. Without treatment, children with SCID typically die in the
first two years of life.

On the sixth day of HT’s life, he and his family returned to the hospital where
he’d been born in Tuba City, Ariz., a community on the Navajo Nation about 50
miles east of the Grand Canyon. A pediatrician told them HT would need to be
isolated and airlifted to Phoenix Children’s Hospital. Joy turned to shock. His
paternal grandmother, Laverna Shorty, recalls scrubbing her arms down before she
could enter the room in Phoenix, which was filled with the sound of HT’s coarse
cough.

Two and a half months later, at the University of California at San Francisco
Benioff Children’s Hospital, HT became the first person in the world to receive
an experimental gene therapy designed to build his immune system, cell by cell.
The outcome of this experiment was far from certain — a big leap of trust for
his family members, who were relying on Western medicine and traditional
knowledge to find a path for HT to come home.

“We just prayed for him,” Laverna said. “You know, you overcome things with
prayers, and you have to have faith. So I had faith in the Western medicine and
my own cultural beliefs.”

HT was the trailblazer for a successful gene therapy that has now been given to
13 infants. His recovery highlights the power of treatments that aim to fix the
roots of a disease inside a patient’s own cells, offering long-lasting outcomes
that, doctors hope, may turn out to be cures. It is also one piece of a deeper
story about how doctors and families navigated cultural differences and learned
from each other to save children’s lives.

The next step won’t be easy: Drug companies so far have shown little interest in
turning HT’s experimental therapy into an approved medical treatment. It’s a
reflection of a broader challenge that threatens to limit the profound potential
of gene therapies for ultrarare diseases. But HT’s doctors are determined to
find a path forward, one that could become a model for other rare conditions to
follow.


BUBBLE BOY DISEASE

SCID is more famously known as “bubble boy disease,” after a high-profile case
in the 1970s in which a boy in Texas lived to the age of 12 inside a sterile
chamber. Today, it is known to be caused by mutations in at least 20 different
genes.

Most pediatricians may never see a child with SCID. But during her medical
residency at the University of Colorado, Diana Hu cared for a child with SCID
from the Navajo Nation who had been sent to Denver for a bone-marrow transplant
to treat the condition. In 1985, shortly after she began practicing medicine in
Tuba City, she cared for two local babies with SCID. The next year, she saw two
more cases.



The alarming number of sick babies spurred doctors to scour medical records and
interview families, searching for infants who may have died without being
diagnosed. They estimated that among Diné people, 1 in 2,000 babies are born
with SCID. In the general population, by contrast, SCID affects about 1 in
58,000 babies.

Advertisement

Story continues below advertisement



Karen Yazzie’s first child, Brandon Jay Nez, was born in Tuba City in December
1985. He became very sick with diarrhea and pneumonia, and was diagnosed with
SCID. He was transported to Denver, but he died in March 1986, before doctors
could even try a bone-marrow transplant.

“He never got as far as that,” Yazzie said.

Doctors saw that the cases among the Diné followed the pattern of a recessive
genetic disease, though they did not yet know which gene caused it. Such
illnesses can remain hidden in families for generations, because people carry
two copies of each gene, and as long as they have one normal copy, they won’t be
affected. Children like Brandon were tragically unlucky — they inherited two
copies of an errant gene, one from each parent.

Yazzie learned that she and her husband had a 1 in 4 chance of having another
child with the illness. Her next child, Brittney Nez, was healthy. In 1990,
Yazzie had twins. One of them, Courtney Nez, had SCID.



Hu made a call that was by then becoming familiar, reaching out to Morton Cowan,
a pediatric immunologist at the University of California at San Francisco who
had become a partner in caring for such patients.

Brittney, then 5, flew out to San Francisco with her mom and baby sister to
donate her bone marrow cells to Courtney. In the hospital, Courtney celebrated
her first laugh with a traditional Diné ceremony that welcomes the child into
the community.

Doctors were beginning to learn that these children didn’t always do well, even
with a matched bone marrow transplant. Their immune systems didn’t always
reconstitute, leaving them battling persistent infections, and they were slow to
grow, along with other complications.

Courtney was fearless, spunky and strong-willed, Yazzie said. She became
partially paralyzed from a stroke around age 10, and later developed bleeding in
her lungs. Still, she cooked for her family, making fry bread or a simple
breakfast sandwich with toast, eggs and Spam. She bottle fed lambs. She excelled
at school. She never stopped making jokes.

But Courtney was in and out of the hospital her whole life, and she died at age
21.

“There’s not a day that goes by that we don’t think about her,” Brittney said.
“See, Court, you’re never forgotten, you’re always talked about. Everyone
remembers you.”


WORKING TOGETHER TO SAVE CHILDREN’S LIVES

Over Courtney’s short lifetime, doctors began to unravel the disease that
haunted these families.

The children lacked T cells and B cells, critical immune fighters that fend off
infections. In 2002, Cowan and his colleagues identified a mutation in a gene
that codes for a protein called Artemis, which plays a role in DNA repair and is
essential for the development of T and B cells; the disease became known as
Artemis-deficient SCID. It was more common among people with Diné and Apache
ancestry, but it was discovered in other populations, too.

Even with this knowledge, children were still being diagnosed with SCID too
late; the first clue often came when babies were in the grip of unusually severe
infections.

For decades, routine newborn screening has used a few drops of blood from a
baby’s heel to test for many genetic disorders. In 2009, a team led by pediatric
immunologist Jennifer Puck proposed to pilot a SCID screening test at two
hospitals on the Navajo Nation that would analyze an additional drop of blood to
help identify SCID at birth. It is now used across the United States.



The progress was possible because Native American families worked with the
researchers to find ways to save their children — a partnership that required
bridging cultural gaps and mistrust.

“You don’t go in there and say, ‘I’m going to fix your problem.’ You need to be
a listener and be humble,” Puck said.

Western science and medicine have historically ignored and underestimated the
traditional knowledge of Native people, said Katrina Claw, a Navajo geneticist
at the University of Colorado’s Anschutz Medical Campus. Many people in the
community have a deep knowledge of biology and heredity, grounded in expertise
in raising livestock and crops passed down over generations. The Navajo clan
system, a way of identifying oneself that also keeps track of kinship, is a
complex genealogical and cultural system and a form of genetic knowledge, Claw
said.

The Navajo Nation implemented a moratorium on genetic research on the
reservation in 2002, partially in response to an exploitative history in which
researchers retrieved samples or data from Native Americans, often without
proper consent or sharing the results. That ugly practice intersects with
cultural beliefs that every part of a person’s body is sacred, which created
concern about what happened to blood or tissue samples after they were taken.



“We’re still recovering from this whole helicopter research era, when people
took samples and never came back,” Claw said. “In my interactions with cultural
and tribal leaders, people aren’t opposed to cures and treatments. … It’s the
approach and the way it is done that matter to Navajo people.”

The doctors in San Francisco began building ties to the reservation in the
mid-1980s. Hu helped Cowan organize a picnic in Winslow, Ariz., to meet and
interview families to learn their history and gather samples. Over time, that
evolved into an annual tradition — a “SCID clinic picnic” where the doctors
check up on their patients and then hold a barbecue so the families could share
stories, laughter and tears.


A DROP OF BLOOD SETS OFF ALARM BELLS

By the time HT was born in April 2018, newborn screening for SCID was routine,
and results from his blood test set off immediate alarm bells.

Share this articleShare

After initial testing in Phoenix, HT was airlifted to San Francisco. A
bone-marrow transplant could save HT’s life, the doctors told his family, but
his older brother, Hastiin, wasn’t a match.

There was another option. Cowan and Puck had developed a therapy that could
insert a corrected version of the gene that codes for Artemis into stem cells
and build the immune system. So far, it had been tested only in cells in a dish
and animals. The doctors knew that the prospect of inserting a gene into a
baby’s stem cells was daunting.

After several lengthy conference calls with HT’s parents and grandparents, the
family agreed.

The medical team in San Francisco first harvested HT’s bone marrow cells. Then,
they used a harmless virus to insert the corrected Artemis gene into his cells.
And on June 23, 2018, they returned the cells to HT.

His father, Darren Shorty, had been hesitant for his son to join the trial. He
went to the family ranch and drew on medicine that he learned from his
grandmother, harvesting some traditional healing herbs.



Darren then brought the herb, called “life medicine,” to the hospital to make a
tea for HT. The care team was unaware of the medicine at first, and Puck tried
to intervene, explaining her worry that it would interfere with the gene
therapy. Darren explained the healing and spiritual value of the herb, and they
reached a compromise. He would make a tea, boiling it for 30 minutes.

Building an immune system from scratch takes time, and HT’s parents had another
son to care for, bills to pay and work to do. They went home, and Laverna
Shorty, who had already raised nine children and fostered more, quit her job in
construction to care for her grandson 24/7 in San Francisco.

Laverna tasted all of HT’s medicines before she gave them to him, devising
strategies to help him to swallow the bitter ones. She cradled him, counting the
raindrops on the window and cars on the street below and singing songs. When she
got too tired of holding HT, she fashioned a pouch out of a bedsheet, wrapping
HT close to her heart.

Laverna asked the doctors and nurses to explain everything to her. She started
looking up immunological terms, learning about T cells, B cells and neutrophils,
the immune warriors that protect people from germs.

“I came thinking that I was just going to change diapers, [give] cuddles. No. I
actually, I took a big responsibility upon myself,” Laverna said.

Everyone rejoiced when, three months after the transplant, a test showed that
HT’s body had made three T cells per microliter of blood. It was a crucial first
step.



Doctors closely monitored HT, watching his immune markers slowly tick up and
giving Laverna permission to do things like take him out in a stroller with a
plastic protective sheet on top.

HT developed various complications — anemia, infections, mouth sores — and he
still needed infusions of antibodies to help shore up his immune system. But
when he finally got home around age 2, he was allowed to play in the dirt and
touch an animal, a crucial milestone, because his family keeps horses, dogs,
sheep and chickens.

Advertisement

Story continues below advertisement



Hu, the Tuba City pediatrician, advocates for these children with a perspective
grounded in the decades she has spent caring for the community. Sometimes, that
means securing emergency housing for a family if they lack electricity or
running water, or finding ways for children to attend school safely despite the
risk of an infection.

“People from here have a connection to the land,” Hu said. “This is the art of
medicine, not the science.”

In spring of 2020, HT developed an infection, and he and Laverna were airlifted
to San Francisco. The pandemic hit the reservation hard, so they stayed in
California for months. When they moved back to the Navajo Nation, they lived in
a travel trailer on the family ranch.

Despite the setbacks, HT’s immune system was getting stronger. Thirty-two months
after his gene therapy, he no longer needed monthly infusions of antibodies.


CURES IN LIMBO

Cowan and Puck’s gene therapy is now a scientific success. Last December, they
published a paper in the New England Journal of Medicine showing that 10 infants
have been treated, including HT. All were healthy after follow-ups that ranged
from 10 months to four years, and four patients no longer needed infusions of
antibodies to bolster their immune systems.

At the end of this month, they will treat their 14th patient.

Now, a new challenge looms: how to guarantee other children will be able to
access the treatment long term.

Gene therapies for rare diseases can command multimillion-dollar price tags, but
even with the potential reward, drug companies’ interest so far has been tepid
for Artemis-SCID, which afflicts just 2 to 3 percent of the already small number
of SCID patients.

In the meantime, many in the field are watching the halting path of a gene
therapy called Strimvelis, which is aimed at another form of SCID. The therapy
was approved in Europe in 2016.

“That treatment I think you can legitimately say is a cure, and I don’t use that
word very often,” said Philip J. Brooks, the deputy director of the Division of
Rare Diseases Research Innovation at the National Center for Advancing
Translational Sciences.

But last year, biotechnology company Orchard Therapeutics announced that it
would stop its investment in the treatment.



Orchard also stopped development of an experimental treatment for the same type
of SCID that had successfully been used in 50 patients, citing manufacturing
challenges. Strimvelis has been transferred to an Italian biomedical charity,
and Orchard returned the license on the experimental therapy to the academic
groups that began the work.

“We’ve got these transformative, miraculous therapies that don’t fit in anyone’s
business model,” said Donald Kohn, a professor of microbiology, immunology and
molecular genetics at the University of California at Los Angeles who has been
treating patients with the experimental therapy, with dwindling funds. “It’s at
a paradoxical state. It’s hard to get a research grant when you’ve kind of
proven it’s effective.”

Researchers remain hopeful, and are spitballing new models. A nonprofit might be
able to develop such medicines. They’re exploring the steps toward setting up
commercial manufacturing, looking for alternative funding sources and talking to
regulators.

What regulators and scientists agree on is that gene therapies, and eventually
gene editing, will provide an opportunity to target thousands of rare diseases —
if the manufacturing challenges and business model can be worked out.

“We’re at a tender moment for rare-disease gene therapy,” said Peter Marks, who
leads the center that oversees gene therapies at the Food and Drug
Administration.

The urgency comes from seeing children like HT thrive. What’s astonishing to
Cowan and Puck is how much better the Artemis-SCID gene therapy patients are
doing than those who received traditional bone marrow transplants.



The therapy has given these children a way to be children again.

This year, when the doctors came for the SCID clinic and picnic, they got to
visit HT at his home — what Puck calls his “place of belonging.”

Back at the ranch, Laverna mixed dough in a giant bucket for enough tortillas
for 50 people. Her children prepared mutton for a feast. A big pot of potatoes
bubbled on the stove.

HT was out there, too, dashing around with the animals or exploring in the
shade. After he spent years of living in small spaces, under a constant shadow
of worry, his world now stretches as far as the eye can see.



Dana Hedgpeth contributed to this report.

Share
93 Comments

Loading...

Subscribe to comment and get the full experience. Choose your plan →



Loading...
Company
About The Post Newsroom Policies & Standards Diversity & Inclusion Careers Media
& Community Relations WP Creative Group Accessibility Statement Sitemap
Get The Post
Become a Subscriber Gift Subscriptions Mobile & Apps Newsletters & Alerts
Washington Post Live Reprints & Permissions Post Store Books & E-Books Print
Archives (Subscribers Only) Today’s Paper Public Notices Coupons
Contact Us
Contact the Newsroom Contact Customer Care Contact the Opinions Team Advertise
Licensing & Syndication Request a Correction Send a News Tip Report a
Vulnerability
Terms of Use
Digital Products Terms of Sale Print Products Terms of Sale Terms of Service
Privacy Policy Cookie Settings Submissions & Discussion Policy RSS Terms of
Service Ad Choices
washingtonpost.com © 1996-2023 The Washington Post
 * washingtonpost.com
 * © 1996-2023 The Washington Post
 * About The Post
 * Contact the Newsroom
 * Contact Customer Care
 * Request a Correction
 * Send a News Tip
 * Report a Vulnerability
 * Download the Washington Post App
 * Policies & Standards
 * Terms of Service
 * Privacy Policy
 * Cookie Settings
 * Print Products Terms of Sale
 * Digital Products Terms of Sale
 * Submissions & Discussion Policy
 * RSS Terms of Service
 * Ad Choices
 * Coupons








WE CARE ABOUT YOUR PRIVACY

We and our 38 partners store and/or access information on a device, such as
unique IDs in cookies to process personal data. You may accept or manage your
choices by clicking below, including your right to object where legitimate
interest is used, or at any time in the privacy policy page. These choices will
be signaled to our partners and will not affect browsing data.


WE AND OUR PARTNERS PROCESS DATA TO PROVIDE:

Actively scan device characteristics for identification. Use limited data to
select advertising. Store and/or access information on a device. Use limited
data to select content. Personalised advertising and content, advertising and
content measurement, audience research and services development. List of
Partners (vendors)

I Accept Reject All Show Purposes