Top Docs 2011

From face transplants to computerized glasses that help blind people "see" to a groundbreaking development in the fight against Lou Gehrig’s disease, here are 14 stunning medical breakthroughs.

By Janelle Nanos | Boston Magazine |

Edited by Janelle Nanos


Illustration Peter Crowther

Illustration Peter Crowther

Here in Boston, we’re surrounded by world-class medical schools and hospitals. So it really means something to be considered the very best. Which brings us to this year’s list of Top Doctors. Beginning on page 87, we present the city’s 650 finest physicians in 57 specialties. How do you make our list? Your peers choose you. In other words, these are the doctors that other doctors recommend to friends and family. Before we get to that, though, we look back on an amazing year of medicine in Boston. From face transplants to computerized glasses that help blind people “see” to a groundbreaking development in the fight against Lou Gehrig’s disease, here are 14 stunning medical breakthroughs.

Transcendental Operation

Photograph by Michael Warren

Photograph by Michael Warren

Richard Mangino, 65, lost his arms and legs in 2002 after contracting a blood infection from an undetected kidney stone. In October, Bohdan Pomahac supervised a double hand transplant for Mangino. The Revere native can now open and close his fingers. “I look at the other person’s eyes when they see my hands for the first time,” he says. “It’s like they’re looking at magic.”

It gives you a cold sweat when you’re taking a face off the donor,” Bohdan Pomahac says. He should know. As the head of the plastic surgery transplant team at Brigham and Women’s Hospital, Pomahac this year oversaw three separate procedures in which a patient received a brand-new face. Oh, and he also supervised a transplant that resulted in an amputee getting two new hands.

Pomahac is a man of science, of course, but he gets a little mystical when describing the intricate process. First he has to cut away the donor’s tissue. After the face is removed, it’s transferred to a preservative solution that makes it appear ghostlike. “It’s pale, there is no color in the lips; it’s almost gray,” Pomahac says. “And then we bring it over here to the hospital and connect the vessels that provide the inflow and outflow of blood. That’s the magical moment. You see the blood rushing in, and suddenly a wave of pigment spreads through the face from one side to the other. You can’t believe it’s happening.”

After seeing successful face transplants in Europe, Pomahac became convinced that he could do the procedure here. The biggest challenge, he says, was proving to the hospital that these non-lifesaving surgeries were a worthy endeavor. Yes, the patients may be alive, he argued, but what kind of lives were they living? “There is no functional prosthetic for the face. These are the aspects of human life that we can restore,” he says. And “no matter what prosthesis you have, the hand is not just something that’s mechanical. You want to touch your family or loved ones.”

After convincing the teaching hospital to develop the plastic surgery transplant program, Pomahac had to persuade the transplant-organ community to allow him to harvest donor tissues. He then raised millions of dollars and worked with healthcare providers to get his patients covered for the immunosuppressant drugs they’d need to prevent rejection.

Photographs by Michael Warren

Photographs by Michael Warren

James Maki, 61, suffered disfiguring burns to his face after falling on the T’s electrified third rail in 2005. After the accident, he kept largely to himself, until he saw Bohdan Pomahac on television talking about face transplants. “Right then, I started wondering, Is my face going to be saved because of this?” he now recalls. “I said to myself, There have to be some lucky people in this world.” 

Pomahac performed his first partial face transplant on James Maki in 2009. Then, this past March, he oversaw the very first full face transplant ever done in the U.S. He and his team did the procedure on two more patients in April and May. Then in October, Pomahac led the hospital’s first double hand transplant, performed on Richard Mangino, a 65-year-old quadruple amputee who lost his limbs to a blood infection. While his work has drawn international acclaim, Pomahac seems most gratified by what the transplants will do for future clinical research. “We will learn how the brain reintegrates the tissues and relearns how to use parts that were lost,” he explains. “It’s moving forward our knowledge about the human body and physiology,and all that goes along with it.”— Janelle Nanos

 

The Grow-Your-Own Organ

Photograph by Bruce Peterson

This decellularized pair of rat lungs can be reseeded with new cells to build a functional organ (Photograph by Bruce Peterson).

Need a new heart? Or kidney? Or liver? Within a decade it may be possible to simply give a blood sample and two months later receive a custom-grown organ that’s a perfect match. No waitlist, no possibility of rejection, no drugs. In September, Harald Ott and his organ bioengineering team at Mass General’s Center for Regenerative Medicine managed to transplant a specially grown lung into a rat, which survived for a week. That’s a pretty significant development for the team, which is using a technique called “perfusion decellularization” to customize almost any suitable donor organ and create a patient’s perfect match.

The technique involves “washing” a donor organ of its cells,until it becomes what’s known as a scaffold — a colorless organ blueprint. The scaffold is then placed in a bioreactor and repopulated with the patient’s blood cells, which have been reprogrammed to behave as stem cells. Right now, more than 110,000 people in the United States are on the organ transplant list and have to wait anywhere from six months to several years for an organ. Once they get one, they’re forced to down a costly daily cocktail of immunosuppressants for the rest of their lives to prevent rejection. Though bioengineered organs have yet to get to clinical stages, they have the potential to change the way the entire transplant system works.  — Leah Mennies

 

Of Mice and Man-Made Livers

Illustration by Adam McCauley

Illustration by Adam McCauley

All hail the lab mouse. Scientists routinely use the critters to test the safety and efficacy of treatments for humans, but unfortunately, because their liver cells act differently than ours, it’s a challenge to use them for testing new drugs. Scientists have tried to work around the problem by injecting human liver cells into mice, but that’s never really worked. So about 90 percent of drug trials fail because of liver toxicity in humans. But all that began to change earlier this year, when MIT doctoral grad Alice Chen figured out how to put a human liver inside a mouse. The 2011 Lemelson Prize winner was trying to create artificial livers for transplant patients when she developed a hydrogel polymer in which human liver cells could thrive. The polymer (which looks like a soft contact lens) can be easily implanted into a healthy mouse, where the cells can then metabolize drugs just as they would in humans. The transplants have a 90 percent success rate, and can be formed and embedded in just two weeks.— Anne Vickman

 

The End of the Common Cold

It’s the holy grail of medical breakthroughs, and it just may be at hand. We’re talking about the cure for the common cold, and with it the end of influenza, stomach bugs, polio, hemorrhagic fevers, and quite possibly every other viral infection in the world. The miracle compound: double-stranded-RNA-activated caspase oligomerizer — or DRACO, which was announced this summer by Todd Rider and his team at MIT’s Lincoln Labs in Lexington. At heart, DRACO is shockingly simple — just three combined molecules that search the body to find and destroy any cell that dares host a virus. The first molecule helps the group slip in and out of cells; the second detects long strings of double-stranded RNA (the calling card of almost every virus); and the third causes the virus cell to self-destruct. If the drug clears the testing hurdles ahead, this could be it. Bigger than penicillin and, reportedly, with far less chance of resistance. — Shannon Fischer

 

Drug Addition

Photograph by Bruce Peterson

Photograph by Bruce Peterson

The city’s biotech community community cranked out a number of promising new treatments this year. Here’s a look at groundbreaking medications for four serious ailments.

Hepatitis C

Drug: Incivek

Company: Vertex, Cambridge

Incivek represents a less-complicated, more-effective treatment plan for the four million Americans with hepatitis C. The drug works as a protease inhibitor, blocking the proteins that the virus needs to copy itself in the body. Taken three times a day for 12 weeks, it produces recovery times that are twice as fast as previous treatments. It’s estimated that Incivek, which was approved in June, will do $750 million in sales this year.

Multiple Sclerosis

Drug: BG-12

Company: Biogen Idec, Cambridge

BG-12 is one of the first oral medications for multiple sclerosis, an affliction of the nervous system that affects more than 350,000 Americans. The drug reduces brain inflammation and protects neurons that have been attacked by the disease. In the third stage of clinical trials, it’s been found to reduce the rate of annual relapse in patients by 53 percent. Biogen Idec hopes to submit BG-12 to the FDA for approval next year.

Homozygous Familial Hypercholesterolemia

Drug: Mipomersen

Company: Genzyme, Cambridge

Those who suffer from this extremely rare genetic disorder are born without the low-density lipoprotein receptors that pull bad cholesterol out of the blood, which can lead to heart attacks by their teens or twenties. Mipomersen blocks production of the protein that bad cholesterol adheres to in the blood, reducing atherosclerosis. In Phase 3 trials, the drug — submitted to the FDA this year — cut patients’ LDL counts by 25 percent.

Advanced Basal Cell Carcinoma

Drug: Vismodegib

Company: Curis, Lexington

Vismodegib is the first orally administered drug to help treat advanced basal cell carcinoma, the most common skin cancer in the U.S. It works by blocking a common protein that, in rare cases, can mutate and cause the disease. In a second round of trials, it was found to substantially shrink tumors and heal lesions in 43 percent of patients.— J.N.

 

Closing the Door on the Ebola Virus

In August, two groups of researchers from Brigham and Women’s and the Whitehead Institute identified a cholesterol-transporting protein in our bodies that turns out to be the door through which the Ebola virus enters our cells. “We tested six different strains, and all of them were completely dependent on the protein,” says Brigham and Women’s researcher James Cunningham. Block that door in mice and cell cultures, and there is no infection, no death. It’s very early, but should discovery pan out into therapeutics, it could be the key to stopping a human Ebola infection dead in its tracks.— S.F.

Mr. Roboto

Photograph by Bruce Peterson

Photograph by Bruce Peterson

Sometimes having a big mouth can be good for your health. For patients with head and neck tumors, for instance, a spacious oral cavity can be the difference between a massive procedure that cuts through the jaw and throat, opening up the face like a book, or a minimally invasive surgery done with the help of a robot. At Boston Medical Center, otolaryngologists Gregory Grillone and Scharukh Jalisi have redefined the concept of “open wide” by perfecting a technique called transoral robotic surgery (TORS), recently approved by the FDA. When a patient has a relatively large jaw, doctors can remove tumors in hard-to-reach places — behind the tonsils and tongue, say, or deep in the larynx and throat — by using a remote console to maneuver several robotic arms, each outfitted with an HD camera or surgical tool. The robotic precision allows the doctors, who performed more than 30 of the operations this year, to better clean out tumors, and it gets patients home in days rather than weeks.  — J.N.

The 10 Percent Doctrine

Doctors have long known that up to 10 percent of all heart attack patients die within a year; the problem was that they didn’t know which 10 percent were at risk. They do now, thanks to the work of Zeeshan Syed, who discovered the answer while in the joint health sciences doctoral program run by Harvard and MIT. Syed scanned the electrocardiogram readings of nearly 5,000 patients — tens of thousands of hours of recorded heartbeats — and discovered patterns, called biomarkers, that hospitals can now use to identify high-risk patients. “We can tease something out of nothing,” says Syed, who published his findings in September. You just have to look.  —  J.N.

 

 A Current Affair

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Illustration by Adam McCauley

One of the most challenging aspects of treating patients with ALS, or Lou Gehrig’s disease, is figuring out whether the treatments are working at all. That’s because patients are often too weak to endure the strength and breathing tests that measure the deterioration of their muscle function. The problem was maddening for Seward Rutkove, the neuromuscular disease chair at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School. “I was obsessed with the idea that we needed new ways to evaluate muscle health,” Rutkove says. Years ago, he encountered the work of two Northeastern University physicists who were examining how muscle tissue responds to electrodes. Working alongside them, Seward developed a technique, electrical impedance myography (EIM), that determines a muscle’s condition by sending an imperceptible electrical current through it. EIM testing works on almost any muscle in the body, providing doctors with a quick way of knowing whether ALS medications are effective — a benefit that could cut the cost of medical trials in half. In February Rutkove was awarded a $1 million prize for his findings from Prize4Life, an organization that promotes and funds scientific innovation for treating ALS. With the prize money and a team of scientists from MIT, he’s developing a handheld EIM device that will give doctors newfound muscle in treating the disease.  —  J.N.

 

Your iPhone Will See You Now

Thanks to the work of Boston-area researchers, your smartphone just might save your life one day. When it comes to the following medical problems, there’s an app for that.

Diabetes

Northeastern University researcher Heather Clark and her team have developed what’s quite possibly the most badass blood test the disease has ever seen. It’s a tiny tattoo packed with a glucose-sensing dye that, when hit with a special light from your handy iPhone attachment, reveals your blood-sugar status. Bye-bye, finger pricks.

Tumors

New this year from Mass General: an app and a tiny machine that will take biopsies of miniscule tumors and analyze and summarize the results within an hour. That means no pathology lab, virtually no wait for results — and no invasive digging for samples. The hospital’s now at work on a smartphone blood test for cancer.

Mental Health

“You seem stressed, is everything okay?” It’s not a text from your mom, it’s a little smartphone counseling courtesy of the Daily Data app from MIT startup Ginger.io. Released this year, the app analyzes accelerometer data and the frequency of your calls, texts, and game-playing to monitor your mood (and even your chronic diseases).

Bogus Meds

Sproxil dealt a major blow to the $200 billion counterfeit-drug industry with a new app that sniffs out fake medicines. The Cambridge tech firm partnered with drug companies to put scratch-off codes on their packaging. Enter the code into the app, and a text will appear a few seconds later verifying the drug’s authenticity.

Cataracts

Last year, MIT’s Media Lab gave us the iPhone app for eyeglass prescriptions. This year, they developed a $5 iPhone app that can detect cataracts — and their spread and severity — earlier than even professionally trained specialists can find them. Oh, and the app can do it all in five minutes or less. — S.F.

 

Putting Doctors on the Clock

Earlier this year, two Harvard Business School professors had a thought. What if, instead of relying on arbitrary estimates from Medicaid or Medicare, hospitals could determine what healthcare procedures actually cost? To find out, they asked two Boston surgeons to introduce a new tool to their medical kits: a stopwatch.

Professor Robert Kaplan’s theory, “Time-Driven Activity-Based Costing,” has been used by businesses across the country to help track efficiency and outcomes. But it’s never been tried in a hospital setting, in part because we prefer our doctors to focus on saving lives rather than worrying about the cost of care. But that’s left a huge gap in understanding, says Kaplan’s colleague, Michael Porter, who has researched healthcare delivery for more than a decade: “It’s not because of how physicians are trained. They’ve just never had any way of knowing or thinking about it.”

The professors launched a pilot program, recruiting John Wright, who performs knee replacement procedures at Brigham and Women’s, and John Meara, who runs the cleft palate unit at Children’s Hospital, to take part. The doctors asked their staffs to help them map out each step in a patient’s treatment, from the moment they’re checked in at the door of the hospital to their final follow-up visit. A per-minute cost was then calculated based on the time that each doctor, nurse, clinician, or assistant spent with the patient. Then all of the overhead costs were factored in — equipment, electricity, cleaning and sanitizing of tools — and were added up to create a full cycle of care.

Mapping the process allowed the doctors to identify inefficiencies, like the amount of time nurses spent filling out paperwork instead of tending to patients. And it enabled them to look at how well their patients fared relative to how much money was spent on their care. In one example, Meara found that when it comes to cleft palates, 40 percent of the costs incurred over 18 months of care stemmed from the few days a child spent in the ICU after surgery. He then determined that the same child could, with just a bit of extra oversight, recover equally well in a less-expensive general wing of the hospital. For his part, Wright learned that an exercise machine used to strengthen the knee after surgery was actually detrimental to patients. So he transferred the cost of the machine to more physical therapy, and his patients wound up recovering faster.

Could these results lead to an entirely new financial plan for hospitals? It’s too early to know for sure, but the business professors’ cost-mapping idea has proven to be a valuable start. “We’re spending too much money and we’re not sure whether we’re getting the value for it,” says Wright. “We can’t afford to continue to run the system as we are.” — J.N.

 

HIV-Free

Photograph by David Phillips/Visuals Unlimited

Photograph by David Phillips/Visuals Unlimited

An HIV vaccine has remained elusive for decades, in part because just when researchers think they have it pinned down, the wily virus mutates and slips away. As MIT immunologist Arup Chakraborty observes, HIV is so protean that a single infected person can have as many strains of the virus in his body as there are annual strains of flu in the entire world. But now Chakraborty and Harvard Medical School’s Bruce Walker may be closing in on the virus’s undoing. Chakraborty looked beyond the constantly changing individual proteins in the virus, and instead focused on identifying groups of proteins that weren’t mutating as much. It was there, he reasoned, that you would find HIV’s basic structures. Attack one of those structures at various points, and the virus would actually harm itself when it mutated.

Chakraborty identified one of these “polyproteins” through computational analysis, which Walker then confirmed by testing a group of long-standing HIV patients. They published their findings in June, and animal trials will begin in a few months. Chakraborty began work on HIV just three years ago, after he joined Walker — who has studied the virus since the ’80s — on a visit to South Africa’s AIDS-ravaged KwaZulu-Natal province. The pair now work collaboratively through the Ragon Institute, a consortium formed by MIT, Harvard, and Mass General. Producing a vaccine is not only urgently needed, but it may be the only viable solution, says Chakraborty. “Monitoring and treatment through therapy is difficult in the sub-Saharan region, where you might have one clinic and five nurses for half a million people.” —  Matthew Reed Baker

 

Can You See Me Now?

Photograph by Bruce Peterson

Photograph by Bruce Peterson

If you think Siri and location-based apps make your life easier, just imagine what the technology can do for the sight-impaired. Joseph Rizzo III, the director of neuro-ophthalmology at Mass Eye and Ear, and his team have developed a prototype for “smart” glasses that guide the blind around unfamiliar environments. Here’s how they’ll work.  — Courtney Hollands

1) Audio cues identifying objects around the wearer are sent to an earpiece.

2) Small vibrators placed at the temple and the back of the ear buzz when the patient needs to turn or avoid an object.

3) A camera embedded in the glasses captures and sends images to a small GPS-enabled processor, which identifies objects and people and “reads” signs and text via optical character recognition.

 

It’s All in the Genes

Illustration by Adam McCauley

Illustration by Adam McCauley

Patients have typically had two options for attacking cancer: surgery or chemotherapy. But now, thanks in part to the work of a team of researchers at Dana-Farber Cancer Institute, we may be at the dawn of a new era of treatment. The researchers have come up with “smart medicines,” or molecular-targeted therapies, that attack certain genetic defects in patients that can cause cancerous tumors.

These particular cancers are fed by proteins gone haywire. The smart meds turn off those proteins, cutting off the tumor’s food supply and causing it to die. Success rates in clinical trials have been startlingly high. In one instance, a woman named Beverly was diagnosed with late-stage lung cancer and given six months to live. Then Pasi Jänne, associate professor of medicine at Dana-Farber, discovered that Beverly’s lung cells contained an alteration in a protein called anaplastic lymphoma kinase (ALK), a mutation that produces rapidly growing tumors in 5 percent of non-small-cell lung cancer patients. Jänne enrolled her in a clinical trial of a new drug, crizotinib, that essentially acts as a kill switch for ALK.

Within six weeks, Beverly’s tumors had shrunk by more than half. Where chemo typically has an efficacy rate of 30 to 40 percent for cancers like this, with smart medicines it’s more like 70 to 80 percent. “When they work, they usually work in days,” Jänne says, “not in weeks or months that we see with chemotherapy.” The FDA approved crizotinib in August, and other smart medicines are in the works for certain types of melanoma and leukemia.  —  Casey Lyons

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