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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

Toward A Less Invasive Mode Of Deep Brain Stimulation

Imagine this futuristic tableau: A severely depressed person walks into her doctor’s office, sits in a specially designed chair with a coil around her head, and with little more than an IV injection, undergoes deep brain stimulation to treat her deep, dark psychological illness.

Well, that’s not going to happen any time soon, but engineers at MIT are working on the building blocks that could make that fictional scenario a reality.

They’ve developed a method — a proof-of-concept, really — to stimulate brain tissue using external magnetic fields and injected magnetic nanoparticles that resemble small bits of rust. This technique allows for direct stimulation of neurons, which could someday be an effective treatment for a variety of neurological diseases, like Parkinson’s, and even further in the future, for severe, treatment-resistant psychiatric disorders like depression, without the need for highly invasive brain implants or external connections. The research is published in the journal Science.

(Allan Ajifo/Flickr)

(Allan Ajifo/Flickr)

Current treatments have been effective in reducing or eliminating tremors associated with Parkinson’s but involve major brain surgery to implant wires that are connected to an outside power source.

Polina Anikeeva, an assistant professor of materials science and engineering at MIT, says the new research suggests a much less invasive possibility. I asked her to describe the research in an accessible way and here’s what she said:

First, I want to clearly say that we are still very far away from any clinical or even pre-clinical application, this is a first proof-of-concept study, looking at the possibility of using these materials to stimulate neurons deep in the brain.

What we’ve done is to give a simple injection of nanomaterials (iron oxide) that look like small bits of rust [but aren’t actually rust], deep into the brain. This allows us to deliver stimulus using a magnetic field, which is converted into heat by the little rust particules. Now we have a system where a magnetic field is applied from the outside and with a simple injection of the materials we can deliver the stimulas deep in the brain without the connectors and without the implants. We don’t have to be invasive in order to do the stimulation.

Continue reading

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Sugar On The Brain Circuit: Mice Seeking Sweets May Hold Key To Compulsive Overeating

You know the feeling: you’re tired, cranky, low or just have a serious, relentless desire for something sweet. Part of your brain cries out, “No, don’t do it, this will end badly.” But another (louder) part wants what it wants and won’t let up until that pint of Cherry Garcia, or red velvet cupcake or Caramel Macchiato is in plain sight. It’s an itch that must be scratched.

Now, brain scientists at MIT say they’ve identified a specific neural circuit in mice that can increase that compulsive overeating of sweets, but doesn’t interfere with normal eating patterns necessary for survival. More specifically, turning on this set of neurons drove mice to seek the reward of a sugary drink even in the face of punishment (a shock to the foot); and compelled them to eat voraciously even when full.  When the researchers shut down this pathway, however, the compulsive sucrose-seeking decreased.

Why does this matter? The new research, published in the journal Cell, may ultimately provide a target for the treatment of compulsive overeating and sugar addiction in humans, without undermining the clearly critical drive of eating to live, the scientists say.

“Imagine if I told you that in the future, we could change the way our neural circuits communicate in a way that I did not want to binge on sweets, but still allowed me to eat healthy foods when I’m hungry?” says Kay Tye, the study’s senior author and an assistant professor in the Department of Brain & Cognitive Sciences at MIT. “Obviously there is a ton of work that needs to be done to make this vision a reality, but our study suggests that it is possible.”

A Binge-Free Future?

As obesity rates have spiked in recent decades, experts say that overeating in general and consuming too much sugar in particular are major threats to human health.

But Tye says “the real underlying problems are the cravings that lead to compulsive eating, and the behavior of compulsive overeating itself.”

To tease out what might be driving that compulsion, Tye looked to a particular set of neurons in the mouse brain.

She and her colleagues showed that when mice perform reward-seeking actions enough that they become habits, that activates neurons connecting two key areas: a brain region called the lateral hypothalamus (an area important for hunger, feeding and homeostasis) and the ventral tegmental area (a brain region important for motivation and reward).

“If we want to understand how the brain gives rise to these feelings, thoughts and actions, we need to know more than what they are saying, we need to know who they are talking to,” Tye said. The team used so-called “optogenetic projection-defined phototagging” [essentially using laser light to activate or silence neurons] to see “which neurons…were saying what…and who they were talking to…”

These neural communications are quite distinct, Tye said; for instance, it’s important to distinguish between two types of reward-seeking behavior: binge-eating and drug addiction: “You don’t need cocaine to survive, you need food to survive,” she said.

The “Wanting” Neurons

Tye says that one of the biggest challenges with treating the obesity that comes from compulsive overeating disorders is that “most treatments are just a band-aid — treating the symptoms instead of the core problems.  Gastric bypass for example, is something that just makes it harder to eat, it doesn’t always change a person’s habits and eventually many people relapse and regain the weight.” Again, she theorizes that it’s the craving embedded in the brain that drives the compulsive behavior. She says there may be a distinctive set of  “wanting neurons” as opposed to “liking neurons.” Continue reading

Winning Ideas In Contest On ‘How To Make The Breast Pump Not Suck’

A team at the MIT Media Lab's "hackathon" on "How To Make The Breast Pump Not Suck" presents its ideas. (Carey Goldberg/WBUR)

A team at the MIT “hackathon” on “How To Make The Breast Pump Not Suck” presents its ideas. (Carey Goldberg/WBUR)

Anyone who’s ever had a close encounter with a breast pump knows that it sucks in multiple ways: It sucks out breast milk, and it sucks because it makes mothers feel like milk cows at the mercy of a loud, dumb, unwieldy, uncomfortable machine.

“Pumping is the worst, it really is,” said Erin Freeburger, a mother and a user-experience designer who was attending her first-ever “hackathon” this weekend: the MIT Media Lab’s “Make The Breast Pump Not Suck!” contest. “That’s why we’re all here. No one here is like, ‘What? It’s fine, how it is!’ It’s awful. But we love our babies more than we hate our pumps, so that’s why we’re motivated to be here today.”

We love our babies more than we hate our pumps.

– Erin Freeburger

Freeburger’s team was among ten squads of brainstormers who took on the intense weekend challenge of improving upon current breast pump designs — and her team won the first prize of $3,000 and a trip to Silicon Valley to court investors. Their concept: The “Mighty Mom” utility belt, is “a fashionable, discreet, hands-free wearable pump that automatically logs and analyzes your personal data.” Milk data, that is.

The concept, she explained, involves both hardware — the utility belt to hold pumping parts needed on the go — and software: It imagines a “smart” breast pump that would collect and track data and upload it to the cloud: milk volume, even fat and protein content as analyzed by infrared sensors. (My reaction: So it’s, like, the iPump?)

The team that would ultimately win the "Make the Breast Pump Not Suck"  hackathon with its "Mighty Mom" utility belt. (Photo: Mason Marino)

The team that would ultimately win the “Make the Breast Pump Not Suck” hackathon with its “Mighty Mom” utility belt. (Photo: Mason Marino)

Other winners, according to the contest site: Second prize of $2,000 to “a sturdy, easy-to-clean, minimal-parts, hands-free compression bra designed by nursing moms. The bra helps women manually express breastmilk (a technique proven to be as effective as electric pumps) without their hands.”

It’s not an iPhone, it’s a mortar and pestle.

– Victoria Solan

And third prize of $1,000 to “an open software and hardware platform to make the breast pumping experience smarter, more data-rich and less isolating. PumpIO puts pumping women in touch with lactation consultants and communities as they are pumping, when they have questions and to help reinforce their commitment to their baby.”

And special recognition goes to “a breast pump that mimics the way that a baby suckles with massage and compression. This team also designed soft, low-profile flanges to be worn discreetly.” And more special recognition to this winner of the popular vote:

Compress Express: A breast pump that mimics the natural and age-old art of hand expression, instead of archaic vacuum technology that dominates the market. Inspired by the simplicity of blood pressure cuffs, this project’s gentle compression technology enables efficient milk expression and creates a discreetly wearable, virtually silent and hands-free breast pumping experience.

Debra Abbaszadeh, a founder of Simple Wishes, a hands-free bra company based in San Francisco, said she thought “the whole idea of compression versus expression was really interesting. I think it requires a lot of work. I think the concepts, exactly as they are, are not quite there, but it’s a very interesting idea.”

You might think, given the huge market for breast pumps in a country where most women work and most mothers breastfeed, that pump makers would already have been racing to improve on designs.

So why should a hackathon — an intense team brainstorming session that originated in computer engineering — even be needed?

Despite the commercial efforts, clearly, “Most women are still dissatisfied,” said Victoria Solan, a historian of architecture and design who attended the hackathon. “There’s a lot of talk about how they’re painful, they’re uncomfortable, they don’t work well. So I think the organizers’ original claim — that there’s no reason that the breast pump shouldn’t be as well designed as the iPhone — is true. It’s not. It’s not an iPhone, it’s a mortar and pestle.”

But as some hackathon participants discovered, improving upon it is not necessarily easy. Continue reading

Case Of The Dead Rabbit: Rights Group Wants MIT Fined For Animal Accident

(pdpics.com/wikimedia commons)

(pdpics.com/wikimedia commons)

Animal rights activists want MIT fined over the death of a lab rabbit that was accidentally thrown in a machine that washes cages, The Boston Herald reports:

Ohio-based Stop Animal Exploitation NOW, which monitors animal research, wants the U.S. Department of Agriculture to hit MIT with a $10,000 penalty — the maximum under the federal Animal Welfare Act.

“Obviously, killing any animal is serious,” SAEN executive director Michael Budkie said. “But being so negligent as to leave an animal in a cage that’s sent through a cage-washer — which means the animal is really boiled alive — that is deserving of a very serious penalty. … The animal must have suffered horribly.”

On Jan. 16, an 11-year animal husbandry technician at MIT’s Division of Comparative Medicine failed to remove a rabbit from a cage before placing the cage in a washer, according to a 
Feb. 13 MIT letter to the Nat­ional Institutes of Health’s Office of Laboratory Animal Welfare. The animal later was discovered dead in the bottom of the cage.

After DCM management determined the incident involved “gross negligence and was inexcusable,” the technician resigned Jan. 31.

The February letter, written by MIT’s vice president for research and sent to the NIH Office of Laboratory Animal Welfare, said following the rabbit incident, new protocols were put in place:

Screen shot 2014-06-05 at 4.41.19 PM Continue reading

Boston Study: What Higher Standardized Test Scores Don’t Mean

Students at Roxbury Prep Charter School, which is known for its high achievement test scores,  in 2011. (Jesse Costa/WBUR)

Students at Roxbury Prep Charter School, which is known for its high achievement test scores, in 2011. (Jesse Costa/WBUR)

The MIT researchers avoid loaded terms like intelligence, so let me be the blunt one and sum up a provocative new Boston-based study coming out soon in the leading psychology journal Psychological Science:

If you’re a kid who’s lucky enough to go to a school that boosts your performance on standardized tests like the MCAS, you’re scoring higher because you know more, but probably not because you’ve gotten smarter. And by smarter, I mean better at certain measurable cognitive skills that psychologists call “fluid intelligence” or “fluid reasoning” — like working memory and problem-solving in a novel situation.

MIT sums up the findings:

In a study of nearly 1,400 eighth-graders in the Boston public school system, the researchers found that some schools have successfully raised their students’ scores on the Massachusetts Comprehensive Assessment System (MCAS). However, those schools had almost no effect on students’ performance on tests of fluid intelligence skills, such as working memory capacity, speed of information processing, and ability to solve abstract problems.

The researchers calculated how much of the variation in MCAS scores was due to the school that students attended. For MCAS scores in English, schools accounted for 24 percent of the variation, and they accounted for 34 percent of the math MCAS variation. However, the schools accounted for very little of the variation in fluid cognitive skills — less than 3 percent for all three skills combined.

Even stronger evidence came from a comparison of about 200 students who had entered a lottery for admittance to a handful of Boston’s oversubscribed charter schools, many of which achieve strong improvement in MCAS scores. The researchers found that students who were randomly selected to attend high-performing charter schools did significantly better on the math MCAS than those who were not chosen, but there was no corresponding increase in fluid intelligence scores.

It will be interesting to see how this study resonates in the eternally contentious discussion about standardized tests and the fraught practice of “teaching to the test.” To get a clearer sense of what the study says about testing — and what it doesn’t — I spoke with the paper’s senior author, MIT neuroscience professor John Gabrieli, of the McGovern Institute for Brain Research. Our conversation, lightly edited:

Let’s begin with the ending: How would you sum up what this study found?

Our core findings were that which school a student attended did influence his or her test scores on statewide tests, but it did not appear to influence their fluid cognitive abilities; abilities such as how quickly you process novel information, how much information you can juggle in your mind, what people call ‘working memory,’ and how much you can apply novel, fluid reasoning to novel problems.

And what were the skills that it did affect?

They affected what psychologists call ‘crystallized knowledge,’ knowledge of vocabulary and language, knowledge of arithmetic and calculation, the kinds of things that we teach in schools and we want students to know.

So in lay language, what school you attend could affect how much you know, but not how smart you are? Continue reading

Blind Opera Superstar Andrea Bocelli Seeks High-Tech Vision At MIT

Blind opera star Andrea Bocelli speaks during a MIT workshop to introduce new technologies to empower blind people to become more independent. (Stephan Savoia/AP)

Blind opera star Andrea Bocelli speaks during a MIT workshop to introduce new technologies to empower blind people to become more independent. (Stephan Savoia/AP)

What’s a young blind Italian student to do when his beautiful blond crush, Mary, approaches?

Well, if a slew of new assistive technologies now being developed at MIT and Northeastern come to fruition, the intimate interaction might unfold like this: the blind student, wearing a cutting-edge device — a smart jacket, for instance — equipped to communicate a complex array of information privately to a blind user, will be able to sense Mary’s presence, facial expressions and body language, chat intelligently with her about literature and move in to squeeze her hand when a rival suitor approaches.

The characters here are fictional, of course. But the overarching ambitions of this research, funded by the blind Italian opera superstar Andrea Bocelli’s foundation, are both intimate and far-reaching. “The idea was a huge bet,” Bocelli said today. He was speaking through a translator at a workshop at MIT to introduce the array of new technologies to empower blind people to live, study and work more independently. “To create a tool, a device, that would basically substitute itself for the eyes.” He characterized the research as going from the “impossible to the possible.”

The genesis of the Bocelli-MIT venture was a post-concert meeting in Boston several years ago, Bocelli said. He brainstormed with several MIT professors to find out what kind of technology for the blind would “be possible.” Since then, a collaborative team of cross-disciplinary researchers have developed prototypes that may someday be able to deliver critical data to the blind: everything from dynamic information about safe walking terrain and hazards, to enhancing social interactions in real-time through wearable devices or a vibrating watch with a high-resolution tactile display that can deliver important information through the skin.

“I have to be honest, the idea of this project was not born of my own needs — I am in a privileged situation,” with an entourage of helpers all around, said Bocelli, who grew up with low vision and then became completely blind in childhood following a sports-related accident. But “there are many people, some of them my friends, that are living alone in a city, and they have the issue of going to work on their own, going grocery shopping, locating the items on the shelves…The issue is really living on one’s own.” Speaking at a news conference, Bocelli conceded that one day, he might use the technology himself: “Of course, when it will come to fruition, it will be helpful to me as well — because the main problem is that humanity has people who are never happy with what they have. This technology will be helpful first for people who are on their own, but then it will come in handy for people like me, who want to be on their own some times.”

Specifically, The Andrea Bocelli Foundation says it’s given about $500,000 to fund researchers at MIT, and Northeastern to develop these technologies.

A central endeavor is called The Fifth Sense Project (seeking to replace the missing sense of sight) Continue reading

MIT Report Graphically Details Lives Of Students Under Pressure

From The Tech‘s special report on student stress at MIT

This student newspaper report, “Under Pressure” provides possibly the best data visualization ever of college stress — and leave it to MIT to do it. The ambitious and beautifully realized analysis of the MIT pressure cooker draws on the detailed responses of more than 3,100 students who opened up about their academic workload, social life, sleep habits and extracurricular activities.

It’s an incredible portrait of a “hosed” student body, kids who feel, at times, overwhelmed by the torrent of information coming at them and the competing, and cumulatively crushing, demands on their time. (One example: the survey found that 2:30 a.m. is the most common bedtime and 50 percent of students feel that they don’t get enough sleep.)

The Tech survey was inspired by Lydia K., an MIT junior who blogged about her own stressful “meltdown” and persistent dread that no matter how smart she was, she was never quite smart enough. The piece triggered an unprecedented response from students at MIT and around the country; MIT’s president Rafael Reif wrote an open letter to The Tech urging everyone at MIT to read Lydia’s piece.

In response, The Tech launched its project on stress: 3,191 MIT undergraduate and graduate students responded to the survey — about 29 percent of the total student population and 35 percent of the undergrads. Among its findings: “The average MIT student sleeps only about 6.5 hours a night, and 52 percent of them have, at one point, felt like they don’t belong at the Institute.” Here’s a bit of the editorial introducing the special issue:

The Institute is a tough place. The classes are hard, the homework is hard, and the tests are hard. It’s difficult to step back and get any perspective, and when things are going bad, competition between peers makes things worse. If you dare lament the amount of work you have, chances are that your neighbor will challenge you and say that he has even more.

Does this competition sound familiar? It should. The “I’m so hosed” game has become a cultural phenomenon at MIT, one that perpetuates the “hardcore” attitude Continue reading

Harvard-MIT Study: Your Ear Is A (Very Weak) Battery

(Wikimedia Commons)

I must be really punchy in a post-election way, but this news release just sent over by Nature fills me with ineffable technophilic delight and makes me want to sing “My ear is a battery” to the tune of “My Heart’s Like A Kick Drum“:

Biotechnology: Battery power from the ear

The battery-like electrochemical gradient that naturally exists in the inner ear of a mammal has been harvested for the first time and used to power a small wireless transmitter. As reported in a study published online this week in Nature Biotechnology, with further optimization, this approach may one day serve to power drug-delivery vehicles, molecular sensors or other devices implanted in the vicinity of the human ear, such as hearing aids.
The ‘endocochlear potential’ in the inner ear is the only electrochemical potential in animals that occurs across such a large anatomical structure. A major challenge in capturing the energy of the endocochlear potential is that the voltage and extractable power are very low—at least ten times lower than what can be captured using the most efficient existing circuits.
Anantha Chandrakasan, Konstantina Stankovic and colleagues overcame this challenge using a specially designed electronics chip. With the chip placed on the surface of an anesthetized guinea pig and connected to tiny electrodes embedded in the cochlea, the authors succeeded in extracting ~1 nW of power for as long as 5 hours, which was enough power to run a wireless radio that transmitted measurements of the endocochlear potential.

A New Device For A Chronic Bladder Problem

The LiRIS device delivers (at left 200 mg and at right 650 mg) lidocaine directly to the bladder for pain relief. Image courtesy of Science Translational Medicine/AAAS

By Karen Weintraub
Guest Contributor

The pain of interstitial cystitis can be as unrelenting as the urge to urinate. Some women go 50-60 times a day – and night. They often feel isolated by their symptoms, and misunderstood by their doctors.

The chronic bladder problem, affecting about 300,000 Americans, is known to be tough to treat. It’s unclear what causes flare-ups, with different triggers in different women. (Men can get interstitial cystitis, too, as can children, but it’s much rarer.) It may take years for a woman to get a diagnosis – for a doctor to believe that it’s not just “all in her head” – and years more to find a treatment that works at least some of the time.

“It is a very complicated disease and these patients are in very tough shape,” said Michael Cima, the David H. Koch professor of engineering at MIT. “There’s a real medical need.”

That’s why Cima, along with a company he cofounded, has developed a device to deliver the painkiller lidocaine inside the bladder, for as long as two weeks. Other similar devices are either so large that they cause pain, he says, or so small that they slip out of the bladder when the person goes to the bathroom.

Cima’s device, published in the current issue of Science Translational Medicine, unfurls once placed inside the bladder into a pretzel shape, so it stays put until removed by a doctor.

“This is the first time anybody’s developed a continuous release of anything in the bladder,” he says. “While other people have tried to do this, they weren’t tolerated and ours was.” Continue reading