The Gutenberg press disseminated ideas to a wider society. But in the clinical world, much information is still on "lockdown." (Wikimedia Commons)
The best things in life are free: friends, sunny days, beautiful vistas. Wouldn’t it be nice if knowledge were also free? Historically, libraries promulgated knowledge sharing because it was for the public good. We see this spirit increasingly embraced on the Internet – take the recent announcement of a collaboration between Harvard and MIT to make their courses freely available to users around the world via the edX platform.
But have we made all useful knowledge available in a way that allows for the greatest societal advancement? Not really. According to Ken Mandl, MD, MPH, director of the Intelligent Health Laboratory at the Children’s Hospital Informatics Program (CHIP), one important source of information still on lockdown is clinical trial data. In an article called, “Learning from Hackers: Open-Source Clinical Trials” published this month in Science Translational Medicine (not currently available in full text), Mandl and his coauthors call for making raw, de-identified clinical trial data free to the public. Full story »
David Williams wants to turn cells from Fanconi anemia (FA) patients into stem-like iPS cells. To do that, though, he needs to get the patients' cells to reboot properly. (_rockinfree/Flickr)
About a decade ago, David Williams, MD, set out to solve a problem. The chief of Dana-Farber/Children’s Hospital Cancer Center’s Hematology/Oncology division wanted to treat Fanconi anemia (FA)—a rare, inherited bone marrow failure disease—using gene therapy. In the process, he’d be able to replace patients’ faulty bone marrow cells with ones corrected for the genetic defect that causes FA.
There was one big problem though. “The main bar to attempting gene therapy in FA is that you need to be able to collect a certain number of blood stem cells from a patient in order to be able to give enough corrected cells back,” he says. “In our early clinical trials, we were unable to provide enough corrected stem cells to reverse the bone marrow failure we see in these patients.”
One way around the supply issue would be to create the necessary blood stem cells from FA patients’ own cells by first reprogramming skin cells into what are called induced pluripotent stem (iPS) cells. Using one of several methods, scientist can reboot mature skin cells into an immature, stem cell-like state—essentially turning the cells’ biological clocks back to a time when they could grow into anything the body might need. Full story »
Manipulating the enzymes that turn genes on and off could help make the process of reprogramming cells into iPS cells a lot more efficient and safer.
There are several ways to reprogram skin cells into induced pluripotent stem (iPS) cells – cells that behave like embryonic stem cells, and which could help better understand the genetic basis of and develop new treatments for different diseases.
The major methods scientists use now include using viruses to deliver reprogramming genes or using RNAs to produce the necessary proteins without the genes. Different methods have different advantages and disadvantages, and some are more efficient than others.
What’s common across all of the methods is that they rely on four proteins to turn back the cellular clock – c-Myc, Klf4, Oct4, and Sox2. Less understood is whether enzymes that modify chromatin (the DNA-plus-protein package that constitutes our genome) play any role in the reprogramming process. These enzymes manage and control the cell’s epigenetic code – the layer of control that helps cells fine-tune gene expression by adding and removing small chemical tags to genes and proteins.
“During iPS reprogramming, a cell’s epigenetic code gets completely rewritten,” says George Q. Daley, director of the Stem Cell Transplantation Program at Children’s Hospital Boston. “But how the cell’s epigenetic enzymes influence the reprogramming process has been a mystery.” Full story »
Eight percent of Americans name apples as their favorite fruit. About 5 percent of the world population owns a computer and 7 percent are on Facebook. Nine percent own a car. Only 2 percent of adults are natural blondes.
Yet 10 percent of people on this planet have a rare or “orphan” disease. In the U.S., that’s almost 30 million people.
Approximately 7,000 medical conditions have been identified as “rare” – defined by the Orphan Drug Act, passed in 1983, as affecting fewer than 200,000 people in the U.S. Some of these are relatively well known and well studied, such as sickle cell disease or amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease); each affects roughly 30,000 patients in the U.S. Others – like multiminicore myopathy, Diamond Blackfan Anemia or galactosemia – you’re unlikely to have heard of, because they affect only a few hundred or thousand people.
Most of these diseases affect children, often from birth, so at pediatric hospitals, patients suffering from something rare and understudied are actually very common. Full story »
Lorraine Sweeney in 1963, on the 25th anniversary of her historic heart operation. (Children's Hospital Boston Archives)
When the first fetal cardiac surgery was performed at Children’s Hospital Boston in 2001 – entering Jack Miller’s heart through his mother’s abdomen and opening blood flow – the world was stunned. But more than 60 years earlier, another operation was equally game-changing.
It was 1938, a time before heart-lung bypass, when ether and chloroform were only starting to be supplanted by more controllable anesthetics, when tinkering with the heart or even opening the chest were seen as dangerous and taboo.
Tinkering was what Robert E. Gross, chief surgical resident at The Children’s Hospital, liked to do. He was interested in a congenital heart condition known as patent ductus arteriosus, a passageway between the pulmonary artery and the aorta that’s supposed to close after birth — but doesn’t. Full story »
Brian Rosman holds up a tablet app he and a team of Children's and MIT Media Lab staff developed over the past two weeks during the Health and Wellness Hackathon
At 10 a.m. he’s directing two actors on set, at 10:34 a.m. he’s filling up a catheter and at 11:01 a.m. he’s gushing about the importance of pediatric avatars. Brian Rosman, a Robotic Surgery Research Fellow in the Department of Urology at Children’s Hospital Boston, has been working non-stop at the MIT Media Lab’s Health & Wellness hackathon to create a new app for post-operative care. His duties have included directing a video about the app, rounding up realistic props and explaining how the program works to judges and hackathon attendees.
Rosman and his team of coders, clinicians and industry professionals are competing against five other teams for a $10,000 prize awarded to the best open source healthcare application. Full story »
Recently, in the hospital cafeteria, I overheard a group of researchers discussing the upcoming availability of whole-genome sequencing to physicians. “We should devise a way to study how physicians will use this,” said one of them—underscoring the disruptive nature of the transformation that is currently happening in medicine.
The ability to immediately obtain whole-genome sequences from patients holds enormous potential for understanding and treating human disease. The list of studies reporting successful diagnosis of otherwise elusive orphan conditions is already too long to recount—more than 600 articles in PubMed as of the date of this posting—including poignant examples of advancing clinical care. Full story »
There are no best practices for turning patient's genome sequence into information that a doctor can easily understand…and act on. Children's Hospital Boston's CLARITY Challenge calls on the genomics community to come up with those practices, and possibly help three families in the process. (michab37/Flickr)
Personalized medicine, harnessing genomics to improve patient care, is a great idea on paper. But investigators have long struggled to find a smooth route from the bench – where patients’ DNA samples are sequenced – to the bedside, where a doctor can use a genomics report to diagnose illness, prescribe treatments and offer means of prevention.
Looking for innovations, Children’s Hospital Boston decided to use the incentive of competition, launching a contest called the CLARITY Challenge. The winner will be the company or group that can best translate the science of genomics into tools and methods that integrate into and inform everyday care. Full story »
There is no crystal ball to predict what side effects a new drug might cause. But a new mathematical model could help. (Bitterjug/Flickr)
A major challenge in drug development is figuring out what might go wrong. During the development process, a new drug might be given to a few thousand people, maybe fewer if it’s for a rare or orphan disease – just enough to tell whether it does what the researchers think it will and to establish its short-term safety.
Once a drug is approved and available to the public, and out of the controlled laboratory or clinical trial environment, regulators rely on a mix of surveillance, reporting (by doctors and patients) and data mining to catch problems.
But these methods can fall short when it comes to rare side effects, drug-drug interactions or adverse events that arise only after patients have been on a drug for a long time. It can be years before doctors and regulators gather enough data and address safety problems with label warnings, revised prescribing guidelines or, in extreme cases, removal from the market.
So while detection works to a point, wouldn’t it be better if we could predict adverse drug events before a drug even hits the market? Full story »
If you look at the range of research models available to scientists today (from fungi to flies to mice and larger), one little guy stands out – a tropical freshwater fish from the rivers of Bangladesh called the zebrafish. While it may be small, this fish is having a big impact on medical science, especially in genetics, stem cell biology, and drug screening, as covered in today’s Wall Street Journal.
As we’ve mentioned previously on Vector, the zebrafish is swimming its way into many research programs, both here at Children’s Hospital Boston and across the country. As a model, they are quite attractive to researchers, in part due to their small size, their fecundity, and their surprising similarities to us (from a genetic standpoint, that is).
Richard White, who works with Leonard Zon in the Stem Cell Program at Children’s Hospital Boston, offers up an explanation for the fish’s popularity:
