What’s next from Longwood? Advancements for eyes, hearts, cancer, children’s mental health, diabetes, and more
Anthony Russo for The Boston Globe
If you live here, this has probably happened to you.
You or someone you know is sick, very sick. A radical surgery is needed, or an aggressive treatment, or a specialist to diagnose a rare disorder. And it turns out the person who happens to be the foremost expert, or the surgeon who invented the required procedure, or the leading specialist, isn’t in Chicago or New York or Los Angeles or Denver or San Francisco. They’re in Boston. And it’s very likely they’re in Longwood.
It’s where we go with routine bruises, broken bones, and feverish children, for the milestone moments from birth to death, and for the miracles of science we hope will extend life for a week, a month, a year, or a decade.
So what do the next few years hold for this medical mecca? Here are just a few of the advances to look for in the coming months or years out of the Longwood Medical Area.
Innovation: Doctors work hard to help people with serious long-term or even terminal illnesses get better; but often they are reluctant to ask patients how they feel about the possibility that that might not happen. “These are tough, emotionally demanding conversations,” says Susan Block, director of the Serious Illness Care Program at Ariadne Labs. She’s been working with colleagues Dr. Atul Gawande, the labs’ executive director and prominent author, and Rachelle Bernacki, associate director of the care program, on a way to encourage more meaningful talk about patients’ futures. Block and her colleagues have developed the seven-question Serious Illness Conversation Guide, which helps put doctors, patients, and family members on the same page in dealing with illnesses like cancer, chronic lung disease, heart failure, and advanced diabetes. The team hopes the structured question list, being tested at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, will one day be the standard of care worldwide. “The best decisions are made,” Block says, “when the physician can make a recommendation based on the medical situation and also the values of the patient.”
How soon: Within five years.
Innovation:Late in 2013, Feroze-Ud-Din Mahmood and his colleagues tried 3-D printing of mitral valves using high-resolution echocardiographic data, giving surgeons a true, tangible picture of each individual’s heart valves before making the first incision. “It’s like looking at a car onscreen versus going to the showroom to see the car for yourself,” says Mahmood, director of vascular anesthesia and perioperative echocardiography at Beth Israel. “Now there’s no guessing involved, no surprises. With this technology, you can display the internal anatomy before you open the patient, so you can plan: ‘I’ll put a stitch here or I’ll cut this much.’ ” The technique promises to increase precision, shorten operating times, and ease training, particularly in minimally invasive techniques. The next step: create a surgical task trainer that will allow surgeons to actually practice on a replica of each patient’s valve. “The more you can image and practice before going into the patient the better,” says Mahmood. “It will be a revolution.”
How soon: Within the year.
Innovation: “We use local anesthesia every day for dental work, surgery, lots of things,” says Charles Berde, division chief of pain medicine at Children’s. “If you go to the dentist, you want it to wear off fast, but in many parts of the body you want it to last longer for prolonged pain relief.” In the early 2000s, Berde and Daniel Kohane, an anesthesiologist and director of the Laboratory for Biomaterials and Drug Delivery, showed that a compound called neosaxitoxin held promise for this purpose. Next, researchers at a Chilean biotech company found a way to produce large quantities of the injectable toxin. The compound is well-tolerated by nerve and muscle tissue and very safe to the heart, even in large quantities. Also, it means post-surgery patients will need less morphine and oxycodone, which have undesirable side effects. Preliminary studies have been done in Chile and the drug is now moving through the FDA’s approval process. “We think it will dramatically alter the way pain is controlled after surgery,” says Berde, “allowing patients to recover faster and have fewer side effects. It will have a huge impact for a 75-year-old or a 1-year-old undergoing a big operation.”
How soon: Four or five years.
Innovation: Hypertrophic and dilated cardiomyopathy are two forms of heart disease that seem dissimilar: The former strikes young people suddenly; the latter causes progressive heart failure in the middle-aged. But researchers have long believed both shared a genetic component. Christine Seidman, a senior physician at the Brigham and a geneticist at Harvard Medical School, and her husband, Jonathan Seidman, a researcher at the Brigham and a professor of cardiovascular genetics, led a team that discovered gene mutations that disrupt the functioning of the sarcomere — a component of muscle tissue that is involved in contractions — were responsible for both types of heart disease. They’re now collaborating with colleagues to find drugs that target the sarcomere and will lead to the first treatment advances for these diseases in 50 years. “It’s a much more direct intervention than has been feasible for all sorts of heart diseases, where we’re generally treating symptoms and not targeting the actual problem,” says Christine Seidman. “It’s very exciting.”
How soon: Within six years.
Innovation: Oncologists often must try various treatments, wasting valuable time and exposing cancer patients to dangerous side effects, before finding the precise one that’s most effective. Dana-Farber researchers are aiming to speed that process. They’ve developed “mouse avatars” — mice implanted with tumor cells from a single patient — to help them quickly identify the most effective drug to treat that individual’s sarcoma or ovarian, stomach, breast, or blood cancer. Using several of the mice for each patient, doctors will be able to test multiple drugs simultaneously. “We’ve created almost 50 mouse avatar models for ovarian cancer, for example,” says pathologist Ronny Drapkin, the lead investigator, “and the cancers are much more faithful to the patients’ original tumors than are ovarian cancer cells grown in the laboratory, so they respond to chemotherapy much the way patients do. This might help us find the right drug for a patient in as little as eight to 12 weeks, which in many cases should lead to more successful outcomes.”
How soon: Within five years.
Innovation: When you go to the doctor, the doctor talks with you and suggests a diagnosis, a treatment plan, and a prognosis. It’s recorded in your medical record. When you go to the dentist, it’s more casual. “Dentistry is 100 percent focused on the procedure that is being done that day,” says Elsbeth Kalenderian, chair of the department of oral health policy and epidemiology. Kalenderian and her colleagues are out to shift that thinking. They created a standardized nomenclature for dental diagnostics consisting of 17 categories, 106 subcategories, and more than 1,500 diagnostic terms, hierarchically organized and linkable to other terminologies. Their goal is to make it the industry standard, expecting it will enhance communication between specialties, facilitating research, and between doctors and patients, as well as allowing dentists to track what works over time both for a particular patient and for their practice as a whole. It can even help forensic dentists identify human remains. “There is no such thing as a dental record that is too complete,” says Kalenderian, who is working to make sure “every dentist in the world is using it eventually.”
How soon: In the next two years.
Innovation: Epidemiologists trying to track, say, the next Ebola outbreak have traditionally run into a major problem: lack of data regarding how people move — and potentially spread disease — around their communities or regions. Caroline Buckee, associate director of the school’s Center for Communicable Disease Dynamics, has figured out a way to use cellphones to get that data, potentially allowing for early interventions that can head off crises. “Even in poor rural areas now, more people own cellphones than don’t,” Buckee says. “We can’t identify individuals, but for each subscriber you have an approximate location each time they use the phone. So over time you can build up a longitudinal map for millions of people, and suddenly you have the population dynamics for an entire country so that massive data gap is filled.” Her group has set up an NGO to work out the political and bureaucratic logistics, but once they do, the next “exciting possibility,” she says, is integrating mobile phone data with that from satellites and pathogen genomics to allow on-the-ground health practitioners virtually real-time monitoring.
How soon: In the next year or so.
Innovation: Not that long ago, diabetes patients diagnosed in childhood were expected to become infertile, have nerve, eye, and kidney damage, and live short lives. In 1948, Elliott P. Joslin, a diabetes specialist, began giving medals to those who’d defied the odds for 25 years as incentive to others to manage their disease carefully. In 1970 he expanded the program and began awarding a 50-year medal. Today those long-term survivors — there are about 10,000 nationwide — are the subject of research by the Joslin Diabetes Center’s chief scientific officer, George King, and Hillary Keenan. They’re looking at the patients’ genetics, proteins, family history, and stem cells to isolate protective factors that might help other sufferers. “The question is what’s neutralizing the toxic effect of high glucose in these medalists?” he asks. “We’re starting to see results.” He’s identified behaviors that can help lower heart disease in diabetic women (the key is in increasing HDL cholesterol) and is hoping to start human trials for a vision-sparing treatment in the next year. He’s also working to develop therapies that will target kidney complications. “If we can address these things now we can make sure there are many more medalists in the future,” he says.
How soon: Within five years.
Innovation: Though in the past couple of decades researchers have learned specific interventions in children’s mental health, including help for anxiety, depression, trauma, and behavior problems, they are frequently not seen in clinical settings. “The average mental health professional in the community often isn’t trained in those effective, evidence-based models of care,” says Robert Franks, president and CEO of the center. “We really need to improve access to training and the kind of supervision and support they need to make sure they’re delivering this type of mental health care with quality.” The center’s Mental Health Improvement Initiative will be training and coaching staff at schools and community-based providers around Greater Boston for several years.
How soon: Starting this year.
Innovation: Descemets Membrane Endothelial Keratoplasty, or DMEK, came out of Holland about six years ago and is the thinnest, most advanced form of corneal transplantation available. Dr. Peter Veldman, a cornea and refractive surgeon at Mass. Eye and Ear (which opened a Longwood outpatient surgical center in 2012) who recently returned from a year-long fellowship at a high-volume DMEK center in Portland, Ore., is bringing this technique back to New England. It is work that helped correct a problem that had been vexing doctors: Up to 10 percent of the time, the transplanted tissue — which is about a hundredth of a millimeter, or one cell layer, thick — was put onto eyes upside-down, causing it to fail. Veldman collaborated with an eye bank to develop a way to stamp the transplants to eliminate this complication, making surgery safer. “We need to train other doctors in these techniques,” Veldman says. “I plan to host visiting surgeons so they can observe DMEK surgery at Longwood and do simulated surgeries with whole eyes and transplant tissue in a lab setting.”
How soon: In the next year.
Innovation: Part of the reason drug development is so expensive is that clinical trials take years to complete and sometimes don’t work in the end anyway, since the countless animals that are sacrificed don’t necessarily prove to be good models for human physiology. Donald Ingber, a Harvard biologist and founding director of the Wyss Institute, and his colleagues have developed “organs on a chip” — thumbdrive-sized flexible polymer devices that mimic the microarchitecture and functions of living organs. The lung chip, for example, “breathes,” and the gut chip simulates peristaltic action so that researchers can actually grow a microbiome on it. “The level of our ability to recapitulate organ forms and functions and motions is just astounding to people and it’s even astounding to me,” Ingber says. “We never expected we’d get the level of functionality we have.” Perhaps most exciting, the chips corresponding to various systems can be linked to “build a human body on chips,” he adds, potentially replacing animal testing altogether. “If we can test for drugs in human systems, it’s really a game-changer.”
How soon: Two to three years.
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