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State-Funded Lab At Harvard Medical Aims To Reinvent Drug Discovery

Jerry Lin and Sharon Wang at the not yet one-year-old Laboratory of Systems Pharmacology at Harvard Medical School. The two are studying the effects of cancer treatment drugs on the heart. (Robin Lubbock/WBUR)

Jerry Lin and Sharon Wang at the not yet one-year-old Laboratory of Systems Pharmacology at Harvard Medical School. The two are studying the effects of cancer treatment drugs on the heart. (Robin Lubbock/WBUR)

Jerry Lin makes a few adjustments on his microscope and grins.

“Wow, it’s beating,” Lin says as a white cell floating across an inky black background begins to pulse. “That’s cool.” A few colleagues, including Lin’s lab partner, Sharon Wang, murmur approvingly.

“We want to take a real-time video to look at the pattern of how cells beat over time,” Wang says, explaining this stage of the experiment.

Once Lin and Wang understand the morphology of these heart muscle cells, they’ll test how the cells respond to various cancer treatments.

“Later on, we can look at how that frequency of beating responds to different drugs,” Wang says.

The experiment is important, says lab director Peter Sorger, because heart problems can be a side effect of a drug that stops the spread of breast cancer.

“On the one hand, it’s a marvelous magic bullet,” Sorger says. “On the other hand, it does damage on its way in. So the purpose of these studies is to understand precisely why that happens.”

Sorger and his team at the Laboratory of Systems Pharmacology are focused on cancer and on analyzing the ways cancer drugs affect the whole body. They aim to reinvent the drug development process through this systems approach, by going much deeper than would scientists supervising a typical clinical trial and by establishing a new model of collaboration. Continue reading

Mass. General Launches Trial Of Old TB Vaccine For Type 1 Diabetes

A blood test to check glucose levels (Alden Chadwick/Flickr Creative Commons)

A blood test to check glucose levels (Alden Chadwick/Flickr Creative Commons)

Type 1 diabetes, the autoimmune form that usually strikes young people, is big and getting bigger: As many as 3 million Americans may have it, and their numbers are growing quickly and mysteriously.

So any promise of potential progress is a big deal, and it was splashy news back in 2012 when Dr. Denise Faustman, director of the Immunobiology Laboratory at the Massachusetts General Hospital, reported positive results for a test of a tuberculosis vaccine called BCG — Bacillus Calmette-Guerin — in a tiny trial of three longtime diabetes patients. Of particular appeal: BCG has been around for nearly a century, has been shown to be safe and, long since generic, is also cheap.

Now, Faustman has just announced the launch of a far bigger human clinical trial, aiming for 150 patients from ages 18 to 65. Though BCG is known as a vaccine, the trial will use it not to prevent diabetes but to try to reverse the disease — at least partially — in patients who already have it.

Dr. Faustman’s research, funded mainly by the Iacocca Foundation, has been considered somewhat controversial, so the results of the new trial — which is expected to last five years and is a “Phase II” trial to assess how effective the treatment is — could lay that debate to rest.

Our conversation, lightly edited:

So how do you see the headline here? And should it begin ‘This is not a cure’? What’s your main message to the public?

I think the main point of what we’re doing is: These are the first trials trying to intervene immunologically in people with long-standing autoimmunity and trying to reverse the disease, but doing it with a cheap, inexpensive, hundred-year-old drug.

Dr. Denise Faustman, director of the Immunobiology Laboratory at Massachusetts General Hospital (Courtesy MGH)

Dr. Denise Faustman, director of the Immunobiology Laboratory at Massachusetts General Hospital (Courtesy MGH)

But how would you calibrate the promise, or hope, of how well this might work for people?

It’s interesting because these trials, although we were kind of the first in the world to start in Phase I, they’ve caught on, on a global basis — using repeat BCG in diverse autoimmune diseases, such as multiple sclerosis, such as Sjögren’s disease. So, although we were kind of lonely to begin with, suggesting this hundred-year-old drug might have major therapeutic impacts, we’re not so lonely anymore. In fact, in Europe, there are Phase III trials going on in multiple sclerosis.

So, we’re seeing clinical effects in patient populations where people thought it wasn’t possible to reverse or partially reverse a disease. So we’re pretty hopeful that this inexpensive way might make a significant dent on the clinical course of a disease and do it at incredible cost savings to the public.

So, does that go as far as possible ‘cure’? Continue reading

You Are When You Eat: Study Explores Body Clock Effects On Blood Sugar

(Macro Mondays/Flickr Creative Commons)

(Macro Mondays/Flickr Creative Commons)

You know the old saying (or maybe you should): “Eat breakfast like a king, lunch like a prince and dinner like a pauper.”

A new study in the journal PNAS looks into some of the underlying biology: that our bodies tend to regulate blood sugar better after breakfast than after dinner.

Led by researchers at Brigham and Women’s Hospital, it also helps explain why night shift workers tend to be at heightened risk for Type 2 diabetes.

Says the study’s senior author, Frank A. J. L. Scheer of the Brigham, on Radio Boston today: “What we wanted to explore was whether the biological clock — the internal clock — is playing an important part in this day/night variation, or that it might just be due to the sleep/wake and feeding/fasting cycle.”

The study pinpoints two separate mechanisms at work:

• Our basic body clocks, also known as circadian rhythm, have major influence on our blood sugar regulation: our glucose tolerance is naturally higher in the morning than the evening.

• And, independently, when our clocks are misaligned — when we’re forced to flip our days and nights — that, too, lowers our glucose tolerance.

Bottom line, for those of us who are not shift workers: The same exact meal can lead to more of an increase in blood sugar when eaten at night than when eaten in the morning (and higher blood sugar is considered a risk factor for developing diabetes.) Chalk one up for the writers of old sayings.

On the study: Continue reading

Why To Exercise Today: Protection (In Mice) From Diabetes Effect On Heart

Screen shot 2015-02-25 at 10.33.10 AM

You’ve probably seen those scary maps showing a wave of obesity engulfing the country over the last generation, as state after state converts to more-overweight-than-not. The map above comes from a similar animation, only the wave is diabetes. Watch the states turn alarming colors over time here.

For many of us as we age, Type 2 diabetes is not so much a question of “if” as “when.” So even if you don’t have diabetes now, here’s a bit more inspiration to help fend it off with exercise: Researchers report that — in mice, at least — exercise appears to protect powerfully against a potentially fatal heart complication of diabetes.

The complication is called diabetic cardiomyopathy, and it can lead to heart failure. It may not be first on your list of fears (especially if you’ve never heard of it before, as I hadn’t), but these new findings serve as yet another demonstration of the countless ways that exercise may defend you against health harms.  From the University of Virginia Health System’s press release:

“This is a proof of concept. It shows that an antioxidant coming from skeletal muscle that can be induced by exercise training can provide profound protection against an important detrimental disease condition,” said UVA researcher Zhen Yan, PhD. “The implication is if we can come up with a strategy to promote [this effect] in people who are vulnerable to, or already developing, diabetes, that could prevent the development of diabetic cardiomyopathy.”

Yan and his team used genetically modified mice to show that enhancing the production of a molecule called EcSOD – which is produced in skeletal muscle and promoted by regular exercise – would prevent the damaging effects of diabetic cardiomyopathy. These effects include stiffening and enlargement of the heart, which can lead to heart failure.

While the work amplified the expression of the molecule to levels beyond what normal exercise would produce, Yan said it’s an important demonstration of the concrete benefits of regular exercise in people. “Our studies show that even as little as two weeks of exercise could significantly elevate the level in the blood and the heart,” he said.

Yan says he’s also hoping to develop a pill that could help patients who can’t exercise, or boost the effect in people who can. Ah, yes, the eternal search for the exercise pill. Don’t hold your breath — better to huff and puff instead.

Boundary Crossing: When Doctors And Patients Get Personal For Better Health

A diabetes patient and her doctor sit down to talk as part of a novel program aimed at improving the patient-provider relationship.

A diabetes patient and her doctor sit down to talk as part of a novel program aimed at improving the patient-provider relationship.

By Dr. Annie Brewster and Jonathan Adler
Guest Contributors

As a patient you’ve no doubt had moments when you feel like your doctor just doesn’t get you, or, that you don’t get your doctor.

If you’ve never felt rushed, ignored, overlooked or vulnerable during the course of your medical care, you’ve probably never been a patient in the U.S. health care system.

And if you’re a doctor, or another type of health care provider, you’ve probably felt hassled, frustrated, and powerless to help your patient, despite your best intentions.

In today’s medical system, the patient-doctor relationship is often challenged, in large part because there’s no room for us to actually engage with each other as people, to hear each other’s stories.

In medicine, there are unspoken but clear rules about what is appropriate behavior within the context of the patient-doctor relationship: doctors should never reveal intimate details about their own lives, and patients should never ask. Patients, meanwhile, should stick to the facts of whatever is ailing them, giving their provider the data for diagnosis and treatment planning, without superfluous anecdotal detail.

Professional boundaries are certainly important. There is validity to the argument that doctors need to keep distance in order to make clear medical decisions, striving to minimize the biasing impact of emotion. And perhaps it is also true that patients benefit from some distance, in thinking of their doctor as an authority figure rather than a friend.  But this obsession with boundaries has conspired with the pressures of efficiency and economy that constrain the health care system to remove some very personal (and important) elements of the patient-provider relationship.

We are far from the small town medicine of the past, when patients and doctors knew the details  of each other’s lives because their worlds intersected outside of the exam room.

Nowadays, in the 15-20 minute appointments that we are alloted, the patient-provider relationship can feel sterile and robotic. At its worst, it can feel antagonistic. Doctors are over-loaded and time constrained, with fear of litigation and the rules of HIPAA pressing in on them, and a payment model that rewards quantity over quality.

Patients often feel hurried and neglected; overwhelmed by the task of presenting the frightening aspects of their health in the right way to get answers and treatment. Physician burnout is ubiquitous, as is patient dissatisfaction.

It is our belief that by highlighting the humanity of both individuals in the relationship, the patient-doctor bond can be strengthened, with increased satisfaction all around.

Taking it one step further, we believe that reviving the humanity in this relationship will ultimately lead to better health outcomes.

So, here at Health Story Collaborative we’ve designed a program in which a patient and a doctor come together to share and listen to one another’s personal narratives. This new patient-provider model is a variation of our already existing Healing Story Sessions program. In short, our goal is to create a space where both patient and provider can be human.

We recently launched this project in collaboration with the Cambridge Health Alliance, with a grant from the Arnold P. Gold Foundation. We met on a Tuesday evening recently with Tracey Pratt, a woman with diabetes and her health care provider of many years, Dr. David Baron. As they shared their stories, an audience, including other diabetes patients, Dr. Baron’s wife and other medical providers, listened on.

We worked with both speakers in advance to craft their narratives, encouraging personal refection as well as their thoughts about the their mutual relationship.

Tracey talked about her passion for teaching, her travel to the Great Wall of China, and about learning Merengue in Havana, Cuba. She also detailed some of the difficulties she had managing her diabetes.

David told stories about growing up in rural Ohio, picking corn in the fields as a teenager, about his time in the Peace Corps in the Dominican Republic, and his journey to becoming a doctor. Continue reading

Research News Flash: Scientists Grow Cells For Possible Diabetes Cure

Human Stem Cell Beta Cells/Photo Courtesy Doug Melton, Harvard University

Human Stem Cell Beta Cells/Photo Courtesy Doug Melton, Harvard University

In what is being called a major advance on the road toward more effective diabetes treatment, Harvard researchers report that they’ve been able to grow large quantities of human, insulin-producing pancreatic “beta cells” from human embryonic stem cells. Why is this important?

As the leader of this massive, years-long effort, Doug Melton, the superstar Harvard stem cell researcher said in a news conference Tuesday: “This finding provides a kind of unprecedented cell source that could be used both for drug discovery and cell transplantation therapy in diabetes.” And as NPR’s Rob Stein put it: “The long-sought advance could eventually lead to new ways to help millions of people with diabetes.”

Reporter Karen Weintraub, writing for National Geographic, describes why the research, conducted in diabetic mice, has taken so long, with so many twists and turns:

The researchers started with cells taken from a days-old human embryo. At that point, the cells are capable of turning into any cell in the body. Others have tried to make beta cells from these human embryonic stem cells, but never fully succeeded. Melton’s team spent a decade testing hundreds of combinations before finally coaxing the stem cells into becoming beta cells.

“If you were going to make a fancy kind of raspberry chocolate cake with vanilla frosting, you’d pretty much know all the components you have to add, but it’s the way you add them and the order and the timing, how long you cook it” that makes the difference, Melton, also a Howard Hughes Medical Institute investigator, said at [the] news conference. “The solution took a long time.”

Here’s (a lot) more detail from the Harvard news release, written by B.D. Colen:

Harvard stem cell researchers today announced that they have made a giant leap forward in the quest to find a truly effective treatment for type 1 diabetes, a condition that affects an estimated three million Americans at a cost of about $15 billion annually.

With human embryonic stem cells as a starting point, the scientists are for the first time able to produce, in the kind of massive quantities needed for cell transplantation and pharmaceutical purposes, human insulin-producing beta cells equivalent in most every way to normally functioning beta cells.

Doug Melton, who led the work and who twenty-three years ago, when his then infant son Sam was diagnosed with type 1 diabetes, dedicated his career to finding a cure for the disease, said he hopes to have human transplantation trials using the cells to be underway within a few years.

“We are now just one pre-clinical step away from the finish line,” said Melton, whose daughter Emma also has type 1 diabetes.

A report on the new work has today been published by the journal Cell. Continue reading

Let’s Explore Diabetes With Honeybees (Seriously — It Could Work In Urban Slums)

Three trained bees in a special harness that holds them in place for the diabetes-detecting experiment. (Photo courtesy of Juliet Phillips, Bee Healthy project.)

Three trained bees in a special harness that holds them in place for the diabetes-detecting experiment. (Photo courtesy of Juliet Phillips, Bee Healthy project.)

By Richard Knox

The latest book by humorist David Sedaris is implausibly titled “Let’s Explore Diabetes with Owls.” But as we all know, life is stranger than literature: Now, an imaginative team of social entrepreneurs has devised a way to explore diabetes with bees — that is, to train honeybees to diagnose hidden cases of diabetes.

It’s no crackpot idea. It’s in the running with five other finalists for a million-dollar prize given each year by the Clinton Foundation.

Here’s the concept: Bees are 10,000 times more sensitive to chemicals in the air than humans. The breath of humans with diabetes contains higher levels of a chemical called acetone. Bees are easily trained to stick out their tongues when they detect a certain concentration of acetone.

Put a bunch of these trained bees into tiny harnesses, have a person breathe into a straw aimed at the constrained bees and voila! A diabetes screening system that doesn’t require laboratories, expensive machines, highly trained technicians, dietary fasting, or more than a modicum of money.

It may be a good way to screen large numbers of people for undiagnosed diabetes in developing countries such as India, where the disease is burgeoning even faster than in overfed America.

Juliet Phillips of the Bee Healthy project studies a bee in harness, ready to be bathed in the breath of a volunteer. The bee is trained to stick out its tongue if it scents a certain level of a chemical in the volunteer’s breath, signaling diabetes. (Photo courtesy of Juliet Phillips, Bee Healthy project)

Juliet Phillips of the Bee Healthy project studies a bee in harness, ready to be bathed in the breath of a volunteer. The bee is trained to stick out its tongue if it scents a certain level of a chemical in the volunteer’s breath, signaling diabetes. (Photo courtesy of Juliet Phillips, Bee Healthy project)

“Millions of people aren’t aware they have this disease,” says Juliet Phillips, a leader of the project, called “Bee Healthy.” “They aren’t even aware there is this disease. So there’s a need to screen people for diabetes that’s free for people in slums but also culturally acceptable.”

Phillips and her colleague Tobias Horstmann were in Boston this month to test the idea on a group of people with known diabetes. The experiment, at the Joslin Diabetes Center, found that bees could identify the diabetic patients 70 percent of the time.

“That’s not as high as we want to go, but we believe we can get there,” Horstmann says. “We can get improvement in the training of bees.”

In addition, the Boston patients in the test all had well-controlled diabetes, so the level of acetone in their breath was much lower than undetected diabetics in a developing country whose diabetes is out of control. Continue reading

SmartPhone ‘Pancreas’ For Type 1 Diabetes: Promising Test Results

The 'bionic pancreas' developed by a Boston University/Massachusetts General Hospital research team consists of a smartphone (above) hardwired to a continuous glucose monitor and two pumps (below) that deliver doses of insulin or glucagon every five minutes. (Photo:  Boston University Department of Biomedical Engineering)

The ‘bionic pancreas’ developed by a Boston University/Massachusetts General Hospital research team consists of a smartphone (above) hardwired to a continuous glucose monitor and two pumps (below) that deliver doses of insulin or glucagon every five minutes. (Photo: Boston University Department of Biomedical Engineering)

It’s not a cure. But researchers have just reported promising results on a “bionic pancreas” for managing Type 1 diabetes, which affects some 2 million Americans.

And the news has a moving personal story behind it, a father seeking to help his son. As NPR’s Rob Stein reports, Boston University biomedical engineer Ed Damiano shifted the focus of his career after his son, David, was diagnosed with Type 1 diabetes at 11 months.

Damiano has developed a system he calls a “bionic pancreas” designed to help people better manage their blood sugar. He’s racing to get it approved by the Food and Drug Administration before his son leaves for college in three years.

In tests with 52 teenagers and adults, the device did a better job controlling blood sugar than the subjects typically did on their own. The results were reported Sunday at an American Diabetes Association meeting in San Francisco and also published in the New England Journal of Medicine. Continue reading

Exporting The Couch Potato Lifestyle (And Obesity) Via TV, Computers, Cars

(Aaron Escobar/Wikimedia Commons)

(Aaron Escobar/Wikimedia Commons)

A new study finds that the luxuries of modern life come at an extremely high cost: a greater chance of becoming obese or developing diabetes.

Researchers report that in lower-income countries, ownership of a household device — including a car, computer or TV — significantly “increased the likelihood of obesity and diabetes.”  Specifically, owning these items was “associated with decreased physical activity and increased sitting, dietary energy intake, body mass index and waist circumference.” Of the three “devices,” owning a TV had the strongest association with the bad health outcomes.

In poorer countries, such big-ticket items are clearly less prevalent than in rich countries, however they are fast becoming more ubiquitous. And so, apparently, are the ills associated with sitting around watching TV, typing on a computer and driving.

Here’s more from the news release:

The spread of obesity and type-2 diabetes could become epidemic in low-income countries, as more individuals are able to own higher priced items such as TVs, computers and cars. The findings of an international study, led by Simon Fraser University health sciences professor Scott Lear, are published today in the Canadian Medical Association Journal.

Lear headed an international research team that analyzed data on more than 150,000 adults from 17 countries, ranging from high and middle income to low-income nations.

Researchers, who questioned participants about ownership as well as physical activity and diet, found a 400 per cent increase in obesity and a 250 per cent increase in diabetes among owners of these items in low-income countries.

The study also showed that owning all three devices was associated with a 31 per cent decrease in physical activity, 21 per cent increase in sitting and a 9 cm increase in waist size compared with those who owned no devices. Continue reading

Food And Health: A ‘Whole’ Chat With Author T. Colin Campbell

fruits

Most of us know we’re supposed to eat more fruits and vegetables and less processed food, but there’s a growing health movement that goes much farther, arguing that most of our modern diseases – diabetes, heart disease and many cancers – can largely be blamed on the animal fat in our diet. (See this recent story about the link between diabetes and a diet rich in red meat.)

Dr. T. Colin Campbell, an emeritus professor of Nutritional Biochemistry at Cornell University, is a key researcher behind this whole-food, plant-based diet push.

Campbell, firebrand author of The China Study, the well-known tome on nutrition and disease, has just released a new book, Whole, which is already climbing the New York Times bestseller list.

Nutrition expert T. Colin Campbell

Nutrition expert T. Colin Campbell (Courtesy)

As its name suggests, Campbell advocates eliminating processed foods, oils, and animal protein, including dairy, in favor of plant-based protein. New York Times food columnist Mark Bittman has long championed a modified version of this – a “vegan before 6 p.m.” diet of meat-free breakfasts and lunches – as he promotes in his own new book, VB6.

Campbell, who is highly critical of the mainstream nutrition research establishment, makes the case that eating a whole food, plant-based diet can prevent some diseases and reverse the progression of many others, and he has decades of peer-reviewed articles to support his claims.

The message that there are concrete choices we can make to improve our health is an empowering one, and Campbell’s mission has increasing traction. Yet the whole-food, plant-based diet is still considered more extreme than what most mainstream health experts suggest, and cooking virtually all meals from scratch and eliminating many everyday food staples is not always an easy transition.

In putting so much emphasis on nutrition as the basis for illness, other complexities arise. For instance, does viewing the diet as a panacea for preventing or reversing disease create expectations for some patients that are impossible to meet? Where might this leave the millions of patients with genetic diseases or autoimmune diseases – which aren’t associated with lifestyle and diet in the same way?

Curious about these potential consequences, I asked Dr. Campbell directly. Here is an edited version of our conversation: Continue reading