Want to hack something in medicine? Vendors are increasingly eager to contribute their tools to problem-solving teams, like those who will gather November 14 for Boston Children’s Hospital’s Hacking Pediatrics. Seeing an array of tools presented at a showcase at Boston Children’s last week, I felt excited about the possibilities ahead.
Here are a few tools that can help innovators improve health care for patients, caregivers and providers.
Neurons are more like snowflakes–no two alike–than anyone realized.
Walt Whitman’s famous line, “I am large, I contain multitudes,” has gained a new level of biological relevance in neuroscience.
As we grow, our brain cells develop different genomes from one another, according to new research from Harvard Medical School and Boston Children’s Hospital. The study, published last week in Science, provides the most definitive evidence yet that somatic (post-conception) mutations exist in significant numbers in the brains of healthy people—about 1,500 in each of the neurons they sampled.
The finding confirms previous suspicions and lays the foundation for exploring the role of these non-inherited mutations in human development and disease. Already, the researchers have found evidence that the mutations occur more often in the genes a neuron uses most. And they been able to trace brain-cell lineages based on mutation patterns.
“This work is a proof of principle that if we had unlimited resources, we could actually decode the whole pattern of development of the human brain,” says co-senior investigator Christopher Walsh, MD, PhD, the HMS Bullard Professor of Pediatrics and Neurology and chief of the Division of Genetics and Genomics at Boston Children’s. “These mutations are durable memory for where a cell came from and what it has been up to. I believe this method will also tell us a lot about healthy and unhealthy aging as well as what makes our brains different from those of other animals.”
The afterbirth has generally been an afterthought, but that’s about to change.
This week, 19 research centers were awarded grants from NIH’s Human Placenta Project, which is seeking to learn more about the intricate organ that sustained us in the womb, the interface between us and our mothers.
When 2015 MacArthur “genius” grant winner Beth Stevens, PhD, began studying the role of glia in the brain in the 1990s, these cells—“glue” from the Greek—weren’t given much thought. Traditionally, glia were thought to merely protect and support neurons, the brain’s real players.
But Stevens, from the Department of Neurology and the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, has made the case that glia are key actors in the brain, not just caretakers. Her work—at the interface between the nervous and immune systems—is helping transform how neurologic disorders like autism, amyotrophic lateral sclerosis (ALS), Alzheimer’s disease and schizophrenia are viewed.
In early 2014, controversy erupted when two papers in Nature indicated that exposing ordinary cells to stress—an acid bath or mechanical stress—could quickly and efficiently turn them into pluripotent stem cells, capable of developing into virtually all the tissues in the body.
The technique, called “stimulus-triggered acquisition of pluripotency,” or STAP, was lauded for its simplicity compared to other methods like nuclear transfer into egg cells or cellular reprogramming with a set of transcription factors.
The 20th century saw great strides in curing childhood cancer, thanks primarily to the discovery that broadly toxic chemotherapy agents could kill malignant cells. Once virtually incurable, pediatric cancer now has an overall long-term survival rate topping 80 percent.
Gastroesophageal reflux disease (GERD), in which stomach acids back up into the esophagus, is increasingly diagnosed in children. One study based on insurance-claims data found that GERD diagnoses in infants more than tripled between 2000 and 2005 (from 3.4 to 12.3 percent). In addition to heartburn and chest pain, GERD has been implicated in cough, wheezing and pneumonia.
To reduce such acid-related symptoms, doctors increasingly prescribe acid suppression medications such as proton pump inhibitors (PPIs). They’re among the most-prescribed drug classes in the U.S. But clinicians in the Aerodigestive Program at Boston Children’s Hospital noticed that a large number of their GERD patients had lung cultures positive for bacteria, and that a strong predictor was the amount of non-acid reflux the child had.
“We then had to ask the question, ‘are acid suppression medications, which are being prescribed to treat respiratory symptoms, actually worsening the problem?’” says program director Rachel Rosen, MD, MPH. “What are these medications doing to change the bacteria composition in children?”
The twists and turns of Stephen Friend’s career are both dizzying and thrilling. In the early days, Stephen Friend, MD, PhD, CEO and co-founder of Sage Bionetworks, spent many a late night as a resident in the emergency room at Children’s Hospital of Philadelphia with Gary Fleischer, MD, current pediatrician-in-chief at Boston Children’s Hospital.
Friend later wound up at Boston Children’s as well, where he did his pediatric hematology-oncology fellowship and later, as part of the faculty, helped co-lead the team that identified the first tumor suppressor at Boston Children’s. A few years later, Friend left academia to pursue his passion in a startup and later engineered a landing at Sage Bionetworks, a nonprofit focused on patient engagement and open science in the research process. The Resilience Project, one of Sage’s research initiatives, analyzes DNA from healthy volunteers to discover rare mutations that protect resilient people from serious childhood illnesses.
Prospects are looking up for patients who have no explanation for their symptoms despite extensive investigations and testing. There’s a growing revolution in DNA diagnostics (see yesterday’s example) and ongoing work to bring clarity and meaning to sequencing data. Patients with similar symptoms can find each other like never before, and are increasingly empowered to lead in research and discovery.
Another small but important development was announced yesterday by the National Institutes of Health. The NIH’s Undiagnosed Diseases Network (UDN) has opened up a one-stop online portal called the UDN Gateway where patients and families can apply for access to expert team analysis and testing. (A referral letter from a provider is required.)
Some 7,500 rare disorders are known to be caused by single-gene mutations. Most of these disorders first appear at birth or in childhood, and for about half, the responsible gene has been identified. Yet, on average, families with rare disorders spend 12 years searching before getting a correct diagnosis.
Jackie Smith, a 35-year-old mother of two, searched for 32 years for the cause of her muscular weakness. Her parents knew something was wrong soon after she was born. At first, because her ankles turned in, they thought she was bow-legged.