Children’s has always embodied a culture of innovation and scientific
discovery, with the goal of improving the lives of children and families. This
legacy continues today as we lead the world in pediatric research, empowering
our clinicians and scientists to challenge the status quo and seek better
answers for children everywhere.
about some of our proudest moments and see what breakthroughs we’re working
Before the benefits of pasteurization were discovered and widely practiced, milk was a major source of deadly diseases — particularly for young children. During Boston Children’s first 50 years, bad milk was a constant concern for clinicians. This led Physician-in-Chief Thomas Morgan Rotch, MD, to begin the world’s first milk lab in 1891. By combining research and personalized clinical care, Rotch increased patient safety. His commitment to advocacy for children has made him widely considered to be one of the fathers of pediatrics.
Fast forward: Promising studies for kids with allergies
While milk today is much safer for children, it can still be a danger to kids with allergies. Boston Children’s allergists — led by Lynda Schneider, MD, — have combined desensitization treatments with a drug that quiets the immune system in studies that show promise for treating children with milk and peanut allergies.
While spending a beautiful summer day gazing out at the ocean, James Gamble had the sudden realization that the fluid in our blood and surrounding our cells may have a similar composition to seawater. His resulting research measuring electrolyte concentrations in different body fluids formed the basis of fluid replacement therapy. This was critical at the time. Dehydrating diarrheal diseases were common and extremely dangerous, especially for infants, as 90 percent of severely dehydrated babies died. Fluid replacement therapy continues to save countless lives around the world.
Boston Children’s gastroenterologist Michael Docktor partnered with alongside Klick Health to use virtual reality as a patient education tool for kids with inflammatory bowel disease (IBD). By taking a virtual tour of their gastrointestinal tracks, children may be able to better understand their condition and be more motivated to follow their treatment.
Before pediatric anesthesia was ever an established specialty, children were anesthetized with ether, using one-size-fits-all equipment. Nurse anesthetist Betty Lank took it upon herself to design child-sized masks and blood-pressure cuffs and became the first person in the US to use cyclopropane — an improved anesthetic — with children. Alongside Robert M. Smith, Boston Children’s first full-time physician anesthesiologist-in-chief, Lank helped greatly improve the monitoring and safety standards for children during surgery.
Boston Children’s physicians and researchers have spent years looking for alternatives to opioids, and promising replacements may be on the horizon. Three new pain management approaches in development: a safe anesthetic derived from an algae toxin, light- or ultrasound-activated pain blockers, and a highly-selective pain medication that infiltrates pain fibers.
On an August morning in 1938, Chief Surgical Resident Robert Gross made the decision to go against his boss’s wishes and perform the first patent ductus arteriosus repair. This bold decision allowed his patient, then 7-year-old Lorraine Sweeney, to become the world’s first survivor of surgery for a congenital heart defect. The procedure also opened the door for the new field of heart surgery around the world. Back in Boston, Gross and his successors continued to make history with contributions like the first aortic graft and the first open-heart surgery on a newborn.
Because children’s hearts are still growing, any artificial valve or graft will eventually need to be replaced. Cardiac surgeon Pedro del Nido, along with colleagues at Brigham and Women’s Hospital are designing a valve with a braided outer rim, inspired by Chinese finger puzzles, which will elongate as a child grows. Surgeon Heung Bae Kim is using tissue expanders to activate a natural growth process in one of the heart's major arteries. He then uses the newly grown tissue to replace a narrowed portion of the vessel.
Building a new esophagus for children with esophageal atresia
Millie was rushed to Boston Children’s as the day she was born, when it was discovered she couldn’t eat or swallow. A gap in her esophagus — known as tracheoesophageal fistula — left her drowning in her mother’s milk. No infant with this condition had ever survived, but Millie did, thanks to surgeon William E. Ladd, who developed a three-step procedure that created Millie’s new esophagus.
Boston Children’s is the world center for the “Foker process,” developed by John Foker. During this procedure, surgeons stimulate growth of the esophagus by putting small amounts of tension on the disconnected ends. One day, the Foker process may be performed by an implantable robot.
When William Lennox established the world’s first pediatric Seizure Unit at Boston Children’s in 1944, 16 states barred people with epilepsy from marrying. The stigma surrounding seizures was unimaginable, but by including social workers and psychologists in treatment teams, Lennox spearheaded seizure advocacy as well as treatment, training and research. Through the Seizure Unit and his groundbreaking epilepsy research, Lennox paved the way for improved treatment and understanding of these conditions.
Boston Children’s is still carrying the torch for epilepsy research, as researchers like Annapurna Poduri and Alexander Rotenberg study genetic forms of epilepsy through zebrafish models. As anti-seizure medications only help a minority of patients, the hope is that continued research using these models will lead to better treatments.
Sidney Farber was the chief of pathology at Boston Children’s at a time when a leukemia diagnosis was a death sentence. But his hunch that antifolate could potentially be a cure for acute lymphoblastic leukemia led to the first clinical trials to show that a drug could treat cancer. Farber’s work helped establish the field of chemotherapy, and brought us a future were 80 to 90 percent of children with leukemia are cured.
While most forms of leukemia are curable, one group is still very deadly. Half of infant patients with a mutation that impairs the mixed lineage leukemia (MLL) gene are never cured. But oncologist Scott Armstrong has discovered the importance of the protein DOT1L in this leukemia’s destruction, and has already brought one DOT1L inhibitor to trial in adults.
Thomas Weller and his boss, the great virologist John Enders, were experimenting with chicken pox when Weller added poliovirus to a few flasks of leftover culture medium. Never has an afterthought done more for humanity. The poliovirus grew opening the door for the development of polio vaccines. The discovery earned Weller, Enders and their colleague Frederick Robbins the Nobel Prize, and led to an explosion of vaccine development.
Fast forward: Continuing the tradition of vaccine development
Boston Children’s continues to pave the way in vaccine research, with a lung cancer vaccine set to begin clinical trials in 2019 at the Dana-Farber Cancer Institute. Other efforts include the Multiple Antigen Presenting System (MAPS), which enhances immune response while reducing the time, cost and complexity of vaccine production and the Precision Vaccines Program, which is developing targeted vaccines for vulnerable populations, such as newborns and the elderly.
While investigating pulmonary edemas, a buildup of fluid in the lungs , Mary Ellen Avery realized that although people with this condition can literally foam at the mouth, very premature babies had the opposite problem: their lungs made no bubbles. Avery discovered that preemies’ lungs lacked surfactant, a foamy substance that allows lungs to inflate after they exhale. Others would develop treatments based on her work, and premature babies now receive surfactant minutes after they’re born.
Fast forward: Helping premature babies see the world
Very premature babies are at risk of retinopathy of prematurity, a condition in which aberrant, leaky blood vessels grow in the retina and cause blindness. In the mid-1990s, ophthalmologist and biochemist Lois Smith found the culprit was vascular endothelial growth factor (VEGF) — a discovery that led to the first treatment. She is now researching safer alternatives and is on the way to finding a promising therapy.
In 1971, Boston Children’s Chief of Surgery Judah Folkman published a paper in the New England Journal of Medicine that was met with skepticism. Eventually it would revolutionize our understanding of cancer. Folkman posited that angiogenesis — the growth of new blood vessels — was the critical event that turned cancer from harmless to potentially deadly. His work isolating the stimulators and inhibitors of angiogenesis would result in life-extending treatments and pave the way for angiogenesis research around the world.
Fast forward: Angiogenesis meets its match in the Vascular Biology Program
Antiangiogenic drugs help fight cancer by blocking blood vessel growth. The Vascular Biology Program’s (VBP) Robert D’Amato discovered three that are now frontline treatments for multiple myeloma. In 2017, another drug from the VBP entered clinical trials. Developed by Randolph Watnick, it significantly inhibited metastases in laboratory studies of numerous cancers. The hope is that soon it will be able to do the same in people.
When Boston Children’s opened its scoliosis clinic in the 1890s, nonsurgical treatment for scoliosis was a rigid jacket made from plaster. By the 1970s, treatment options hadn’t improved much, as the most common brace combined a girdle, metal rod and neck ring. But when a teen patient at Boston Children’s refused to wear the brace, Chief of Orthopedics John E. Hall and orthotist Bill Miller designed a lower-profile, more comfortable brace . This Boston Brace also turned out to be more effective and is now the most widely used brace around the world.
Given that a Boston Brace may be worn for many hours a day, it’s important the brace is customized properly for the specific patient for maximum comfort. Boston Brace manufacturer Boston Orthotics and Prosthetics is now developing a system in consultation with our orthopedists to 3D-print braces for each patient – ensuring a more comfortable fit.
How Massachusetts’s kids helped halt lead poisoning
In the late 1970s, an astounding 70 percent of all first- and second-graders in Chelsea and Somerville donated their baby teeth to Boston Children’s. These teeth were used to study the effects of lead exposure. Researchers correlated lead levels in teeth with children’s IQ, behavior and development. The study showed that children whose teeth had the highest lead levels were far behind those with the lowest on measures including IQ, motor coordination and attentiveness in class. This research influenced federal guidelines for lead exposure. Today, paint and gasoline, historically the largest sources of childhood lead exposure, are lead free.
In 2001, a study by Boston Children’s David Ludwig, MD, was the first to report the link between sugary sodas and childhood obesity. A flood of research soon followed, leading to public policy initiatives and federal regulations prohibiting the sale of sugary drinks in schools.
As a kid, Claudia De Pass was spending more time in the hospital than at school due to sickle cell disease. But then she became the first sickle cell patient to take hydroxyurea. The drug changed her life — and the lives of patients around the world. Hydroxyurea was a blood cancer drug when Boston Children’s Chief of Hematology and Oncology David Nathan advocated trying it for sickle cell disease. It is the primary sickle cell treatment today.
In 2008, Vijay Sankaran and Stuart Orkin ended the 30-year hunt for the gene that controls the switch from fetal hemoglobin, which doesn’t sickle, to adult globin, which does. A team led by David Williams, Chief of Hematology/Oncology at Boston Children’s, then developed a gene therapy to flip the switch. It’s too soon to claim victory, but a clinical trial opened in 2018 and the first patient’s blood was sickle-free six months after treatment.
Hypoplastic left heart syndrome (HLHS) constricts blood flow into the left ventricle of a baby’s developing heart, leaving infants with one pumping chamber, many risky surgeries and a lifetime of limitations. So when Jennifer and Henry Miller’s baby was diagnosed prenatally with a condition that would lead to HLHS, they contacted Wayne Tworetzky, director of the Fetal Cardiology Program. Tworetzky proposed a daring solution: correct the defect in utero. On November 21, 2001, Jack Miller was born with a healthy heart. His was the first successful fetal correction of HLHS. Jack is now a high school junior who surfs and plays baseball, just like any other kid.
Fetal imaging may soon help cardiologists identify patients at risk for an all too common complication of congenital heart disease: learning and developmental difficulties. The hospital’s fetal heart team has joined forces with neuroradiologist Ellen Grant to develop imaging techniques that reveal when the brain, as well as the heart, is developing abnormally. Early studies have detected slower brain growth and irregular brain folding in fetuses with congenital heart disease compared to normal, establishing the potential for this method. The goal is a future in which genetics and imaging guide prenatal treatment.
In the United States, hydrocephalus (“water” on the brain) is easily treated with a shunt that diverts the excess fluid from the brain to the abdomen. But in rural Africa, where hydrocephalus is much more common, shunting is not a viable option because it requires too much follow-up care and medical facilities are scarce. But if left untreated, hydrocephalus can be fatal. While working in Uganda, neurosurgeon Benjamin Warf devised a life-saving shuntless solution. He has since brought the procedure, called ETV/CPC, back to Boston, where he continues to see positive results.
Benjamin Warf and neuroimaging expert Ellen Grant have brought a powerful brain-imaging technology called near-infrared spectroscopy (NIRS) to the bedsides of Ugandan hydrocephalus patients. Their goal is to determine why some patients benefit from treatment while others don’t and to develop a brain imaging profile that can both predict whether a child is likely to respond and monitor progress.
The first U.S. clinic for transgender youth, the Gender Management Service (GeMS), was started at Boston Children’s in 2007 by endocrinologist Norman Spack and urologist David Diamond. GeMS is modeled after a Dutch program, providing counseling and resources in the years before medical intervention is appropriate, along with psychological support and a stepwise approach to medical treatment.
Fast forward: The final stage of gender affirmation
Zack Hogle had his gender affirmation surgery in 2018 at Boston Children’s Center for Gender Surgery. It was the first phalloplasty performed at a U.S. pediatric hospital, and gave Zack the chance to finally become his complete self.
Anterior cruciate ligament (ACL) reconstruction replaces a patient’s torn ACL with either a tendon graft or a cadaver ligament, and carries a high chance of re-tear and osteoarthritis. After discovering the ACL doesn’t self-repair due to its inability to form a blood clot, Boston Children’s orthopedic surgeon Martha Murray invented bridge-enhanced ACL repair (BEAR®). BEAR uses a blood-infused sponge to bridge the torn ends of the ACL. In clinical trials, BEAR patients have shown increased knee function and muscle strength.
The National Institutes of Health recently funded a $6 million, five-year, multisite trial of the BEAR procedure. The study will follow more than 200 patients with ACL tears and compare outcomes to standard reconstruction at six months, one year and two years post-surgery. Researchers expect results to show BEAR leads to earlier improvement and fewer side effects.
Synaptic pruning—whittling down the connections between neurons—is critical for healthy brain development. But in the mature brain, abnormal synaptic pruning can cause disease. It is an early contributor to Alzheimer’s. In a pioneering 2016 study, Boston Children’s neuroscientist Beth Stevens and team determined which cells destroy synapses in Alzheimer’s: microglia, a type of immune cell Stevens had earlier discovered was responsible for normal synaptic pruning. Her insight that microglia are reactivated in Alzheimer’s could lead to new treatments for the disease.
Fast forward: Crossing the barrier to treat brain disease
Like all immune cells, microglia are born in the bone marrow. But they have the special ability to cross the blood-brain barrier and thus hold promise as vehicles for delivering gene therapies into the brain. Alessandra Biffi, director of Boston Children’s Gene Therapy Program, is exploiting this unique characteristic to develop treatments for a handful of devastating genetic brain disorders.
At Boston Children’s, a team of researchers led by Chief of Genetics Christopher A. Walsh has discovered that inherited mutations are not the sole genetic causes of autism. In a 2017 study, Dr. Walsh’s team analyzed the genomes of nearly 6,000 families, including autism patients, their parents and siblings. Their results showed that somatic mutations — which occur after conception — might play an important role in the disease. These findings could lead to further answers about the causes of autism.
Boston Children’s neurologist Mustafa Sahin was among the first to demonstrate that brain circuit development is disrupted in tuberous sclerosis complex (TSC) — a rare neurological disorder with similarities to autism. Sahin saw these abnormalities could be reversed in animal models, and is now using this knowledge to discover new ways to treat autism.