After undergoing surgery to remove diseased sections of the colon, up to 30 percent of patients experience leakage from their sutures, which can cause life-threatening complications.

Many efforts are under way to create new tissue glues that can help seal surgical incisions and prevent such complications; now, a new study from MIT reveals that the effectiveness of such glues hinges on the state of the tissue in which they are being used.

The researchers found that a sealant they had previously developed worked much differently in cancerous colon tissue than in colon tissue inflamed with colitis. The finding suggests that for this sealant or any other kind of biomaterial designed to work inside the human body, scientists must take into account the environment in which the material will be used, instead of using a “one-size fits all” approach, according to the researchers.

“This paper shows why that mentality is risky,” says Natalie Artzi, a research scientist at MIT’s Institute for Medical Science and Engineering (IMES) and senior author of a paper describing the findings in the Jan. 28 online edition of Science Translational Medicine. “We present a new paradigm by which to design and examine materials. Detailed study of tissue and biomaterial interactions can open a new chapter in precision medicine, where biomaterials are chosen and rationally designed to match specific tissue types and disease states.”

After characterizing the adhesive material’s performance in different diseased tissues, the researchers created a model that allows them to predict how it will work in different environments, opening the door to a more personalized approach to treating individual patients.

Elazer Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology and a member of IMES, is also a senior author of the paper. The paper’s lead authors are graduate student Nuria Oliva and former graduate student Maria Carcole.

Exploring material properties

Artzi and Edelman originally developed this tissue glue several years ago by combining two polymers — dextran (a polysaccharide) and a highly branched chain called dendrimer. In a 2009 paper, the researchers demonstrated that such adhesives work better when tailored to specific organs. In their new paper, they explored what happens when an adhesive is used in the same organ but under different disease conditions.

They show that the adhesive actually performed better in cancerous colon tissue than in healthy tissue. However, it performed worse in tissue inflamed with colitis than in healthy tissue.

Further studies of the molecular interactions between the adhesive and tissue explained those differences in behavior. The tissue glue works through a system where molecules in the adhesive serve as “keys” that interact with “locks” — chemical structures called amines found in abundance in structural tissue known as collagen.

When enough of these locks and keys bind each other, the adhesive forms a tight seal. This system is disrupted in colitic tissue because the inflammation breaks down collagen. The more severe the inflammation, the less adhesion occurs. However, cancerous tissue tends to have excess collagen, so the adhesive ends up working better than in healthy tissue.

“Now we show that adhesive-material performance is not organ-dependent, but rather, disease type and state-dependent,” says Artzi, who is also an assistant professor at Harvard Medical School.

Predicting adhesion

Using this data, the researchers created a model to help them alter the composition of the material depending on the circumstances. By changing the materials’ molecular weight, the number of keys attached to each polymer, and the ratio of the two polymers, the researchers can tune it to perform best in different types and states of tissue.

An inherent property of the adhesive is that any unused keys are absorbed back into the polymer, preventing them from causing any undesired side effects. This would allow the researchers to create two or three different versions that could cover a wide range of tissues.

“We can take a biopsy from a patient for a quick readout of disease state that would serve as an input for our model, and the output is the precise material composition that should be used to attain adequate adhesion,” Artzi says. “This exercise can be done in a clinical setting.”

Joseph Bonventre, chief of the renal unit and director of the bioengineering division at Brigham and Women’s Hospital in Boston, agrees that the study represents an important step toward a more personalized approach.

“You want the best adhesive possible, and they really show how changes in the characteristics of the tissue will alter the adhesive character,” says Bonventre, who was not involved in the research. “They’re moving in the direction of doing a quick test in the operating room and selecting the biomaterial most likely to be effective, rather than developing biomaterials that try to work for all conditions.”

Doctors have begun using this kind of personalized approach when choosing drugs that match individual patients’ genetic profiles, but it has not yet spread to the selection of biomaterials such as tissue glue. The MIT team now hopes to move the sealant into clinical trials and has founded a company to help that process along.

“It’s something that we want to do as rapidly as possible,” Edelman says. “We’re excited. It’s not often that you have a technology that is this close to clinical introduction.”

The research was funded by the National Institutes of Health and the MIT Deshpande Center for Technological Innovation. 

By Anne Trafton | MIT News Office

The classroom and workplace are equally necessary components in the development of any student. The former teaches the fundamentals and theories of a specific field. The latter offers the chance to see how those theories play out with actual colleagues, bosses, and clients. Since markets can emerge from anywhere, that practical experience also needs to have a reach that extends beyond time zones and borders.

To address this, the MIT International Science and Technology Initiatives (MISTI) serves as a program to match students with companies, universities, and research organizations around the world in summer internships. It’s not merely a positive component for the students, it’s a necessary one. “This is a shrinking world and you either know how to work in multi-cultural teams or you are just not going to be successful,” says Rosabelli Coelho-Keyssar, program manager of MISTI-Brazil.

Growing for 20 years

MISTI started in 1994 in two countries. Now it’s in 19, established in places like China, Germany, France, India, and Israel, and growing in others like Brazil, Chile, Korea, Russia, and South Africa. The program has placed over 5,400 students — currently about 550 a year — in fully-funded internships with over 450 corporate partners and research laboratories. The industries span automotive, energy, health, electronics, management, and finance sectors, and the companies range from BMW, Canon, Covidien, Ferrari, Google, and Intel to Motorola, Pfizer, Samsung, Shell, and Siemens.

MIT undergraduate and graduate students start applying in the middle of the fall and can continue into the spring if positions are available, all while meeting certain requirements. They need to carry a minimum 4.0 out of 5.0 GPA. They’ll already have had work experience from previous internships. Because it’s international, students in most programs need to have the equivalent of two to four semesters in the local language, but since the program is known, students will start taking the necessary classes before they apply, says April Julich Perez, MISTI’s associate director. Adding to that, MISTI prepares the students on their destination’s current events, politics, and culture, and helps them handle various paperwork needs and the logistics of moving. The intent is for the student to relocate smoothly and be able to be productive from the first day on the job, Coelho-Keyssar says.

For companies, the advantage of working with MISTI is that they get access to MIT students and their networks — the people who will start future companies and be the next generation of faculty, says Chappell Lawson, associate professor of political science and MISTI faculty director. But while the program is a boost for a student’s prospects, MISTI is a partnership, not just a résumé builder. “The hosts have to believe in it, want to continue in it, and continue to cover the costs of an internship,” he says. “We expect the students will contribute, and we expect them to demonstrate their MIT work ethic, adding real value to their hosts.”

Creating a match with Covidien

MISTI is not a static program. Students can select from existing internships, but if one doesn’t exist, “We will just go out and try to find something that will fit that student’s interest,” Coelho-Keyssar says. One example was the teaming of healthcare company Covidien and Ricardo De Armas, a fourth-year mechanical engineering student who applied in late 2013 for a placement in the summer of 2014.

De Armas had an interest in medical devices. The Venezuelan native wanted to gain work experience in the field, and, while he was fluent in Spanish, he wanted to improve his Portuguese. An internship with those qualities didn’t exist, but MISTI staff connected with the MIT-Brazil program reached out to Covidien and created an opportunity, Coelho-Keyssar says. The Dublin-based global healthcare company was looking to expand its research and development presence in Brazil, says Cliff Emmons, vice president of research and development, tailored products, and emerging markets at Covidien.

The decision to partner with MIT wasn’t difficult. Emmons says the Institute is central to the medical device ecosystem; has established the “standard of an engineer”; and maintains an academic approach that isn’t purely academic. “It has an emphasis on creating businesses versus creating research papers. It’s critical to have that startup mentality,” he says.

But Covidien wasn’t just merely looking for competence or entrepreneurship. Any candidate also had to be able to quickly adapt to the local environment, both socially and in the workplace. The preparation that students receive was another part of what attracted Covidien to MISTI, Emmons says.

The company was setting up one of its Covidien Centers of Innovation, with a research and development lab in São Paulo, and De Armas was hired to assist the director as a project manager, helping to procure equipment, learning how it operates, and training others. The project came with challenges, Emmons says. The deadline was tight — the research and development lab had to be ready to open and enable health-care professionals to directly collaborate with research and development staff by the end of De Armas’ internship. Equipment from around the world had to be shipped, coordinated, and secured. And all of this was happening as Brazil hosted the World Cup.

Emmons says that entering into the program, the company was looking to invest in the development of global leaders. On that front, the partnership was successful. “There was a beautiful synergy between the goal of MISTI-Brazil and Covidien,” he says.

Covidien was also pleased with De Armas. The company knew from the outset that an MIT student would be technically smart, but the distinguishing factor that made De Armas exceed expectations was his overall fluency and his ability to immerse himself into the workplace. “I always knew that our Brazil commercial team viewed themselves as a family,” Emmons says, “and it’s fantastic to see this family grow.”

By Steve Calechman | MIT Industrial Liaison Program

Sophisticated medicine

January 31, 2015

“I’m mostly driven by how to fix things,” states Sangeeta Bhatia. “I’m always thinking about how to solve problems by repurposing tools.” Although not a mechanic, Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology (HST), Electrical Engineering and Computer Science (EECS), and Institute for Medical Engineering and Science (IMES), does run a repair shop of sorts. As director of the Laboratory for Multiscale Regenerative Technologies, she tackles some of medicine’s most intractable problems, developing sophisticated devices and methods for diagnosing and treating human disease.

Bhatia’s research defies traditional academic categories, drawing simultaneously on biological and medical sciences, and multiple engineering disciplines. She has generated dozens of patents, several business spinouts, and earned a host of major scientific honors, including the 2014 Lemelson-MIT Prize, a $500,000 award recognizing an outstanding American midcareer inventor, and the David and Lucile Packard Fellowship, given to the nation’s most promising young professors in science and engineering.

A member of the Koch Institute for Integrative Cancer Research, her unorthodox career got an early start, thanks in part to Bhatia’s self-described passion for “tinkering.” As a child, she could fix the family’s broken answering machine, and was handy with hot glue guns “in a Martha Stewart way.” Her father, recognizing her potential as an engineer, brought her to the lab of an MIT acquaintance who was using focused ultrasound to heat up tumors. Her encounter with technology used against deadly disease proved formative.

Bhatia was determined to become a biomedical engineer, earning an undergraduate degree in the field. She came to view the human body “as a fascinating machine” whose failures she might address by designing interventions. But it was while she was simultaneously pursuing her doctorate in medical engineering at MIT and her MD at Harvard Medical School that Bhatia’s core research concerns began to crystallize.

Investigating a potential artificial organ to process the blood of patients suffering liver failure, Bhatia improvised a novel approach. Borrowing microfabrication technology from the semiconductor industry, she arrayed liver cells on a synthetic surface, and to her delight, this hybrid tissue remained alive in the lab for weeks. Scientists had long sought a way to sustain liver cells ex vivo, and Bhatia had delivered a biomedical first.

With her innovative adaptation of engineering tools for medically useful applications, Bhatia conjured a unique research methodology. And she also found her primary research subject: “I had an ‘aha’ moment, and realized I loved studying the liver.”

Diseases of the liver, unlike those of other organs, don’t have ready treatments. Severe alcohol abuse, hepatitis, and a host of other liver diseases sicken and kill millions each year. In addition, many aspects of the liver remain a mystery, including its unique tissue architecture and ability to regenerate. “It seemed like an incredible opportunity; anything you provided might have an impact,” says Bhatia.

Motivated by this opportunity, Bhatia began generating a steady stream of liver-focused bioengineering tools. For instance, she transformed her hybrid microfabricated liver tissue into a platform for screening drugs outside the body. In a current study, Bhatia is using an artificial liver as a testing ground for a drug with the potential to destroy the malaria parasite at different stages of its life cycle.

She is also closing in on the “naively audacious” goal of building a replaceable liver for patients in need of a liver transplant. Her team has identified chemical compounds that send regeneration signals to liver cells, and she is now successfully growing human livers in mice.

Bhatia has more recently aimed her biotech arsenal at targets beyond the liver. Exploiting nanoparticles, she is devising an inexpensive urine test for cancer that could prove immensely useful in the developing world. She has also begun attacking two of the deadliest cancers, ovarian and pancreatic, designing nanomaterials that can penetrate tumors with a cargo of RNA to silence spreading cancer genes.

“As an engineer, I have a hammer, and look for the next nail,” Bhatia says. “But as a physician, I also want to pick problems with the most clinical impact.”

By Leda Zimmerman | MIT Spectrum

Once a patient infected with the Ebola hemorrhagic virus starts showing symptoms, it can take several hours under the best conditions, and up to several days in remote areas, to get diagnostic results using conventional tests, such as identification of viral RNA. Further complicating the process, Ebola symptoms are very similar to those of other fevers, such as typhoid and malaria. Because time is of the essence in tracking Ebola and preventing its spread, researchers at MIT’s Institute for Medical Engineering and Science (IMES) are working on a new device that uses nanoparticles to capture the virus in patient blood samples and would offer much faster results. Lee Gehrke, the Hermann von Helmholtz Professor in IMES and a professor of microbiology and immunology at Harvard Medical School, described the project to MIT News.

Q. How does your experimental device detect Ebola and other diseases in patient blood samples?

A. One can detect Ebola, like any other hemorrhagic virus, in two ways: with lots of instruments or without lots of instruments. The media contains reports of a new Ebola test every week these days, and most of those are “black boxes” that have of lots moving parts and specialized chemical kits. Lots of these devices end up breaking down in the developing world. 

We prefer a simple device, so we made paper with inkjet-printed molecules and specially tuned nanoparticles that bind to the virus. Then we use lasers to create fluidic pathways that control specific binding reactions of our Ebola-specific molecules. Our lab has traditionally been an RNA virus lab, so we are very interested in translating molecular-scale information into a macro-scale diagnostic that would improve health care.  

Q. How could such a device help to monitor and contain disease outbreaks such as the current Ebola outbreak?

A. Surveillance and acute triage. Once health care professionals use our paper fluidic device to detect the virus, they can isolate that patient and initiate a treatment plan in minutes. Waiting an hour for lab results could mean infecting the rest of the waiting room. A fast diagnostic is more than convenient; it really affects the system of care. 

Given large-scale usage, we can aggregate the diagnostic results into a crowd-sourced, real-time surveillance platform. The goal is to anticipate the spread of the epidemic in a distributed manner. We’re not going to stop Ebola by counting what happened yesterday; rather, we have to be able to detect what’s happening now so we can make predictions about the future. Our goal is for every first aid kit, every clinic, and every home in a village to have a cheap, rapid test where they can self-report results within 30 minutes. It’s giving all these great platforms for mobile health a verifiable ground-truth mechanism, just like a meteorologist relies on small weather stations across Massachusetts to make forecasts about tomorrow’s chance of snow.

Sierra Leone, Liberia, and Guinea are not going to develop their own Centers for Disease Control and Prevention overnight. This is one way to advance their epidemiological preparedness. The data can be analyzed in real time to provide early warning of virus infections, and to monitor the locations of virus infections. 

Q. What stage of development is the device in now? What future steps are needed before it can be deployed?

A. The device detects Ebola and other viruses in the laboratory. We are in the middle of exciting engineering field studies and animal studies to evaluate device efficacy for deployment. We have a great team of collaborations around the world and around the country and everyone is moving as fast as possible to implement the technology with our clinical partners in West Africa. The next major step after validating the detection is selecting the right diffusion strategy — do we mass-manufacture a specific detection device? Or do we create local production protocols that would be adaptable in producing a variety of different types of devices dependent on need? Do we stamp out molds for the housing, or 3-D print locally? We have to be able to simulate field temperatures and humidity in the lab to make sure the devices are field-rugged. These are the types of questions we are discussing in the lab and in the field every week so that the technology helps people as soon as possible.

By Anne Trafton | MIT News Office

Koch Institute faculty member Sangeeta Bhatia has been selected as one of Foreign Policy magazine’s 100 Leading Global Thinkers of 2014 for her work in developing inexpensive and noninvasive diagnostics for the early detection of colon cancer.

The annual list identifies top minds with translational ideas in politics, business, technology, the arts, and the sciences that have the potential to impact millions around the world. This year’s list, published today, has a particular focus on disruptive ideas and technologies. The honorees were recognized today at an event in Washington, D.C., where U.S. Secretary of State John Kerry was the keynote speaker.

Bhatia, the John J. and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, was specifically recognized for her work in developing accessible diagnostics for colon cancer that would enable earlier detection.

If colon cancer is detected early, while cancer cells are confined to the colon or rectum, the five-year survival rate for patients is 90 percent. However, such early detection represents only 40 percent of diagnoses, hindered in large part by expensive and invasive tests, such as colonoscopies.

Bhatia and her lab recognized this critical gap and developed nanoparticles and a simple, inexpensive, paper-strip urine test that can reveal the presence of cancer within minutes. With this diagnostic, the researchers envision that patients would be injected with nanoparticles that amplify signals from tumor proteins, naturally occurring biomarkers that are not otherwise detectable due to their location and small numbers. When tumor proteins interact with the nanoparticles, hundreds of synthetic biomarkers are released and then excreted in the urine. Similar to a home pregnancy test, Bhatia’s paper-strip system can, in mouse models, reveal the presence of cancer in minutes.

This sort of point-of-care test could represent a significant advance in bringing cancer detection to developing nations and remote locations that lack extensive medical infrastructure. In countries where more advanced diagnostics are available, synthetic biomarkers could be beneficial as an inexpensive and noninvasive alternative to traditional diagnostics.

While Bhatia’s paper-strip diagnostic has thus far only been tested in mice, she is working to commercialize this technology to accelerate its delivery to patients. She and her team are also adapting the diagnostic for other medical applications, such as fibrosis, thrombosis, and prostate cancer.

Bhatia received the 2014 Lemelson-MIT Prize in recognition for her work in cancer detection and in liver-tissue engineering. She is also a Howard Hughes Medical Institute Investigator, a member of MIT’s Institute for Medical Engineering and Science, and a member of the Broad Institute of MIT and Harvard.

By Kevin Leonardi | Koch Institute

Bose grants reward risk

January 31, 2015

Solar cells made from coal, smart nanoparticles that work with bacteria to fight cancer, and an effort to enhance human cognition by stimulating brain waves are just a few examples of the high-risk, high-impact projects funded by the first round of Prof. Amar G. Bose Research Grants.

As a scientist, Bose — a longtime member of the MIT faculty, and the founder of Bose Corporation — was driven to explore new and controversial research areas, and strongly believed in pursuing projects that many others felt were impossible. The grant program named for him embraces that philosophy, investing in the development of visionary researchers and giving them the opportunity to explore areas outside their field of expertise.

“Any truly groundbreaking research will likely be found to be risky, inappropriate, or unrealistic by many of the established practitioners in the field,” says Vanu Bose ’88, SM ’94, PhD ’99, son of Amar Bose, who died last year. “Historically, many of the innovative and groundbreaking advances in a field have come from people outside of, or on the periphery of, the particular field, since they are often able to bring a fresh perspective to the problems and ideas.”

Such projects are often less likely to be funded by traditional funding sources. The Bose grant program seeks out this type of visionary research, offering up to $500,000 over three years. The first five grant recipients were selected from more than 100 MIT faculty members who applied last year, and were evaluated according to the likelihood that the research could not be funded through traditional means; the intellectual adventurousness of the research; and the prospect of the research having a significant influence on the researcher’s career.

Targeted cancer therapy

In a project she describes as “synthetic biology meets nanotechnology,” Sangeeta Bhatia is working to create bacterial-derived “minicells” as programmable therapeutic vehicles that can be remotely triggered by “smart” nanoparticles.

Under this plan, researchers would use targeted nanomaterials that home to tumors to trigger bacterial circuits that would locally deliver toxic cancer drugs, sparing healthy tissues. In one example, Bhatia is using heat generated by gold nanorods to trigger a programmed genetic circuit that produces peptides that cause cell death.

This high-risk project, which combines two disparate fields, has the potential to transform cancer therapy, but funding such a project through traditional means would have been extremely challenging, says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, and a member of the Koch Institute for Integrative Cancer Research.

“The Bose grant has allowed us to explore how nanotechnology may synergize with the field of synthetic biology in an unusually open-ended way,” Bhatia says. “Of course, we are ultimately interested in human health applications in cancer and liver disease, but it is too early to pick a ‘killer application’ and raise federal funding around it. We feel very fortunate for these catalytic funds at such a pivotal time, to allow us to sort out what is its disruptive potential.”

Detecting tiny particles

Janet Conrad, a professor of physics, is working on new ways to detect neutrinos — tiny elementary particles that are incredibly abundant. More than 40 billion pass through your thumbnail every second, but they almost never interact with matter.

Until now physicists have been trying to detect neutrinos by building underground detectors that are more than 20 stories tall. However, these detectors must rely on the very rare chance of detecting a neutrino produced by the sun or in the atmosphere, or from accelerators located very far away from the detector. These detectors are so big that they cannot be built near large particle accelerators that could generate many more neutrinos.

To overcome that obstacle, Conrad is working on a cyclotron — a smaller-scale particle accelerator that could be installed underground next to an existing neutrino detector. This cyclotron, which would be about 4 meters in diameter, would provide a more abundant nearby source of neutrinos, making it easier to detect them.

“Existing detectors and neutrino sources have already pushed technology to its limits,” Conrad says. “Since neutrino physicists need even higher-intensity, purer, and more versatile sources for precision measurements, we have to look outside of the box. That is what this cyclotron project is about.”

Alternative use for coal

Jeffrey Grossman, a professor in the Department of Materials Science and Engineering (DMSE), and Nicola Ferralis, a research scientist in DMSE, are exploring alternative uses for coal. Instead of burning it, they hope to use it to create a new, cheaper solar cell.

Other researchers have shown that artificial forms of carbon, such as nanotubes and graphene, can be used to build efficient solar cells. Using such cells, you could power a 100-watt light bulb for one year using only 2 grams of carbon, compared with the 350 kilograms that would be needed to power the light bulb by burning coal.

However, these types of carbon materials suffer from the high cost of manufacturing and processing, which makes them more expensive than traditional silicon-based solar cells. The researchers hope to address that drawback by creating solar cells that use natural materials such as coal, tar, bitumen, or kerogen as the photoactive material.

Using these materials could enable the manufacture of solar cells that are even cheaper than silicon cells. In this project, Grossman and Ferralis plan to develop a prototype coal photovoltaic, an effort they describe as “far too risky” for traditional funding sources to consider.

“Even the current state-of-the-art materials research and the traditional funding venues have overlooked the incredible potential of using natural carbonaceous materials (i.e., coal, oil, kerogen) for renewable energy applications, focusing instead solely on artificial carbon materials,” the researchers wrote in their grant proposal.

Brain stimulation

Earl Miller, the Picower Professor of Neuroscience, is investigating how the harmonization of the brain’s rhythms, or brain waves, contributes to consciousness. Brain waves were first recorded using EEG more than 100 years ago, but their role in brain function has been largely ignored, Miller says. Different brain states correlate with certain frequencies of brain waves, but no one knows why.

Miller’s lab has pioneered multiple-electrode recording techniques that allow simultaneous study of hundreds of neurons. Using this approach, his lab has linked brain-wave oscillations with different types of mental activity. Now, he plans to take the next step: manipulating brain communication by artificially enhancing brain rhythms using transcranial electrical stimulation (TES), a noninvasive form of electrical stimulation to the scalp.

“The brain seems to hum to itself, using rhythms and harmony for communication. This humming helps different brain networks talk to one another,” Miller says. “We hope to use TES to boost the humming in a way that will improve brain communication.” 

This could help boost normal cognition by improving focus and memory and may also offer new ways to treat diseases such as autism, ADHD, and schizophrenia, which some neuroscientists suspect may result from problems in communication between different parts of the brain.

Better cell sorting

Joel Voldman, a professor of electrical engineering and computer science, is working on new ways to separate different types of cells based on their inherent physical properties. Most cell-sorting methods, such as flow cytometry, require labeling cells with fluorescent tags pegged to certain molecules found inside the cells.

Sorting cells by properties such as size, shape, or mechanical, electrical, or optical properties offers a way to avoid labeling cells. Voldman has previously developed ways to measure intrinsic properties such as electrical polarizability of cells as they flow through a microfluidic device. In his Bose-funded research project, he plans to design chips that can perform multiple measurements on cells as they flow through a single channel, using computational microscopy — a technique that can track thousands of individual cells across a 1-centimeter area.

“I want to learn which combinations of physical properties are best able to distinguish different sets of cells, so that I can think about implementing systems that use only physical properties as the basis for separation,” Voldman says. “Such systems could analyze cells very quickly, as they would need only minimal sample preparation.”

He plans to begin by measuring a set of cell lines to help determine which combinations of features are most useful for distinguishing different cell types. Eventually, he envisions this project could lead to small tabletop devices that could be used to monitor the progression of disease by analyzing patients’ blood samples.

At a reception honoring the grant recipients tonight, the awardees will present their research projects to MIT President L. Rafael Reif and other invited guests. Faculty and senior research scientists interested in applying for future grants are invited to submit proposals in response to a call for proposals that is issued each year. 

By Anne Trafton | MIT News Office

National Institutes of Health Director Francis Collins yesterday urged an MIT audience to “reflect on what our role is as scientists and citizens of the world.”

“What we’re engaged in is a noble enterprise,” Collins told attendees at the Karl Taylor Compton Lecture, who filled Room 10-250. “It is an opportunity to alleviate suffering and reach out to those who need help.”

This is all the more important in the face of the current Ebola outbreak in West Africa, which has claimed nearly 5,000 lives and is expected to take many more, Collins said. He noted that the NIH has been supporting the search for Ebola vaccines since the mid-1990s, and now has two candidates poised to enter Phase II clinical trials in December. “I wish we were one or two years ahead of where we are now,” he added.

In what was undoubtedly the first Compton Lecture with a musical conclusion, Collins then summoned Pardis Sabeti, a Broad Institute researcher, guitarist Bob Katsiaficas, and the MIT Logarhythms a cappella group to help him lead the audience in performing a song, “One Truth,” which Sabeti and Katsiaficas wrote after the deaths of three of Sabeti’s colleagues in Sierra Leone who contracted Ebola last summer.

Striking a balance

During his lecture, Collins also acknowledged the budget limitations that have forced his agency to cut back on its funding of medical research. That only makes it more difficult for the NIH to achieve the right balance between its two missions: supporting basic scientific research and applying new knowledge to enhance human health, Collins said.

“We talk about that every day at NIH,” he said. “I wish we had more resources so we could do more of both.”

Collins noted that MIT received $103 million in NIH funding in fiscal year 2014 and highlighted some of the projects supported by that money. Linda Griffith, a professor in MIT’s biological engineering and mechanical engineering departments, is working on a “liver on a chip” — a small device designed to mimic the three-dimensional architecture of the human liver, allowing researchers to test potential drugs before they go into clinical trials. One version of the chip also includes breast cancer cells, enabling an investigation of what happens when cancer metastasizes to the liver.

Projects like this could help translate the vast amount of information scientists have learned about the molecular basis of disease into treatments for patients. Scientists now understand the causes of nearly 5,500 diseases, but effective therapies exist for only about 500 of those, Collins noted. “There’s a huge gap between what we know and what we’re able to do,” he said.

Devices such as the liver on a chip could help close that gap by reducing the time it takes to get a potential drug from the discovery process to approval by the U.S. Food and Drug Administration — a process that currently takes an average of 14 years.

“This kind of technology is enormously promising for understanding biology, and also to speed up the process of identifying what is a safe and effective drug,” Collins says.

Several MIT researchers were also among the recipients of the recently announced NIH Brain Initiative grants. Six of the 58 grants went to MIT, more than any other institution. At this early stage, most of the projects are dedicated to developing new technologies that will eventually help researchers understand how the brain’s 86 billion neurons communicate with each other to perform functions such as forming memories, processing sensory information, and initiating movement.

“It’s an audacious idea that we might be able to understand how circuits in the human brain do the amazing things they do,” Collins said.

A louder voice

Asked how scientists can help to persuade government officials and the public that scientific research deserves more resources, Collins said that all scientists should be ready to explain their work to anyone who asks about it.

“The job we all have is to be prepared at any moment to explain what we do and why it matters,” he said. “I don’t think the science community has a voice that has been heard as loudly as it should in terms of the importance of what we do.”

He also pointed out some achievements of health research over the past several decades. Over the past 60 years, U.S. deaths from cardiovascular disease have dropped 70 percent, while deaths from cancer are now falling by about 1 percent a year, a modest but hard-fought advance. Furthermore, patients diagnosed with HIV can now expect to live a full lifespan; 30 years ago, the diagnosis was considered a death sentence.

“We need to be tireless in making people aware of why this is a very important investment in our nation,” Collins said.

By Anne Trafton | MIT News Office

Francis S. Collins, director of the National Institutes of Health (NIH), will deliver the fall 2014 Compton Lecture, “Exceptional Opportunities in Biomedical Research,” at 3:30 p.m. on Tuesday, Oct. 28, in Room 10-250. All are welcome; no tickets are required.

Collins is a physician-geneticist who became the 16th director of the NIH, the leading international supporter of biomedical research, in 2009. From 1993–2008, he served as director of the National Human Genome Research Institute (NHGRI) at the NIH. His leadership at the NHGRI guided the efforts that led to the completion of the Human Genome Project (HGP), a collaborative, international research program that mapped and sequenced all the genes that make up human DNA. The work was completed April 2003, two years ahead of its original schedule.

In his own research laboratory, Collins achieved additional success by uncovering the genes associated with type 2 diabetes, neurofibromatosis, Huntington’s disease, cystic fibrosis, and Hutchinson-Gilford progeria syndrome.

A former atheist and agnostic, Collins turned to Christianity in his twenties. He explored the interface of science and faith in the New York Times best-selling book, “The Language of God: A Scientist Presents Evidence for Belief” (Free Press, 2006). He is also the author of “The Language of Life: DNA and the Revolution in Personalized Medicine” (HarperCollins, 2010). He holds a PhD in physical chemistry from Yale University and an MD from the University of North Carolina. In 2007, Collins was honored for his contributions to genetic research with the Presidential Medal of Freedom and in 2009, he received the National Medal of Science. 

The Karl Taylor Compton Lecture Series was established in 1957 to honor the late Karl Taylor Compton, who served as president of MIT from 1930 to 1948 and as chairman of the Corporation from 1948 to 1954. The purpose of the lectureship is to give the MIT community direct contact with the important ideas of our times and with people who have contributed much to modern thought.

The series is sponsored by the Office of the President. 

By MIT Institute Events

The millions of people worldwide who suffer from the painful bladder disease known as interstitial cystitis (IC) may soon have a better, long-term treatment option, thanks to a controlled-release, implantable device invented by MIT professor Michael Cima and other researchers.

In the mid-2000s, a urologist at Boston Children’s Hospital contacted Cima — at the behest of Institute Professor Robert Langer — with a plea: Could he develop an alternative treatment for IC? Treating the debilitating disease — which causes painful and frequent urination that can interrupt daily life — currently requires infusing the drug lidocaine into a patient’s bladder through a catheter. This provides temporary relief and must be repeated frequently.

“You hear that and you say, ‘There has to be a better way,’” says Cima, the David H. Koch Professor of Engineering.

Rising to the challenge, Cima and engineering student Heejin Lee SM ’04, PhD ’09 invented a solution: a pretzel-shaped silicone tube that could be inserted into the bladder, slowly releasing lidocaine over two weeks. Equipped with shape-memory wire, the tube could be straightened to fit into a catheter and spring back into its pretzel shape in the bladder, preventing it from being expelled during urination.

Since 2009, the platform — which was detailed in a 2010 issue of the Journal of Controlled Release — has been developed to carry lidocaine and tested in clinical trials by Taris Biomedical, co-founded by Cima and Langer, a longtime collaborator and entrepreneur.

Last month, pharmaceutical giant Allergan bought the worldwide rights to that specific device, called LiRIS (for lidocaine-releasing intravesical system), for $69 million up front and what could total more than $600 million in milestone payments. Allergan is prepping for phase-three clinical trials for LiRIS, which can deliver 400 milligrams of lidocaine to patients. (Because the device stays in the bladder so long, it also allows for smaller doses, reducing adverse reactions.)

Although future progress now depends on Allergan, Cima hopes to see LiRIS used commercially in a couple of years. But Taris now plans to tailor the platform device to carry other drugs into the bladder to treat various diseases, including bladder cancer. “Urology hasn’t really gotten the benefit of improvement in the biotech revolution. This type of technology can revolutionize how we do drug therapy in urology,” says Cima, who serves on Taris’ board of directors.

Taris taking shape

LiRIS started as Lee’s PhD thesis under the tutelage of Cima and with a grant from the MIT Deshpande Center for Technological Innovation, which allowed the two researchers, along with several MIT graduate students, to test much smaller versions of the device in animals.

“The Deshpande funding was an absolutely critical element in getting the data necessary to raise capital for Taris,” Cima says.

Indeed, collecting clinical data is a major challenge in spinning biotechnology out of the lab, notes Cima, who has founded four other companies in his time at MIT — MicroChips Inc., Springleaf Therapeutics, Entra Pharmaceuticals, and T2 Biosystems. “So if it hadn’t been for the Deshpande-funded study, no one would have believed us,” Cima adds.

In the MIT study, the researchers developed a prototype device by using a laser to cut a hole in a silicone tube to add drugs. “Right when we put it in, it just came right out,” Cima says, laughing. “I remember Heejin came into my office thinking his thesis was about to go out the window. But I said, ‘If we can solve this problem, that’s an invention, because the obvious solution doesn’t work.’” 

Heejin then redesigned the device as a pretzel-shaped structure by incorporating a superelastic wire made from a special nitinol alloy. This structure is threaded into a catheter, and inserted into the bladder. When expelled from the catheter, the device returns to a pretzel shape and floats freely.

The researchers found that the pretzel shape — still used in today’s devices — was critical for retention in the bladder, as it prevents the device from simple expulsion through the urethra when the bladder contracts. With this shape, as the detrusor muscles contract, the two loops overlap and the device stiffens, rendering it unable to unfold or enter the urethra.

The team was able to slowly release drugs over a two-week period — typically long enough to treat an IC flare-up — and the device could then be removed by common cystoscopy procedures. Moreover, the researchers proved that drugs injected slowly into the bladder for so long could actually be absorbed.  

Thanks to the data gathered from the study, Cima and Langer were able to launch Taris, with Lee as chief scientist, with $15 million in funding to enter phase-one clinical trials. (Taris would go on to earn $30 million in subsequent funding rounds.)

“It was a big unmet need,” Langer says of his decision to co-found Taris; he now serves on the company’s board of directors. “Once Michael and some of the students had done the work, collected the data to determine it was feasible, I thought it was something that could make a big impact.”

Surprise findings

Taris’ first trial involved implanting an empty device (with no drugs) inside volunteers to test comfort levels. Half of the volunteers were involved in a mock procedure, where no device was implanted; the other half had the device implanted. “Each night for a couple weeks, a nurse called and asked about every ache and pain,” Cima says. After two weeks, there were none.

But the company’s clinical trials, from 2011 to 2012, delivered surprising findings that, Cima says, drew Allergan to invest in and eventually buy the technology.

Taris tested the device on IC patients, many of whom also had lesions called Hunner’s lesions, which affect about 10 to 15 percent of IC sufferers. Usually, doctors cauterize these lesions (which don’t disappear on their own) while patients are under anesthesia in an operating room. But the resulting scarring sometimes leads to patients losing some bladder function.

“Much to our surprise, in our trials, the lesions in those using LiRIS disappeared after two weeks” in five out of six patients, Cima says.

Another surprise was that follow-up meetings suggested reduced pain even several months following removal of the device. Results of both trials were published in 2012 in the journal Science Translational Medicine. (Last year, Taris began an ongoing focus study specifically on patients with Hunner’s lesions.)

“Pain is a subjective outcome,” Cima says, “but the disappearance of the Hunner’s lesions was a purely objective outcome. That objective result, I believe, is one important factor that Allegan decided to acquire the product. Taris itself had also become a leading expert in interstitial cystitis. So that helped too.”

With the Allergan acquisition funds, Taris will further develop the device to deliver drugs for other bladder diseases, including chemotherapy for bladder cancer — whose high recurrence rate is due, in part, to difficulties delivering drugs in a sustained way. Last year, Taris entered a research collaboration with AstraZeneca to develop novel treatments for bladder cancer.

“This device is a platform,” Cima says. “Whether it’s bladder cancer, overactive or underactive bladder — any of these indications where you might want to deliver drugs right to the bladder — it can do that.”

A member of the MIT Koch Institute, Cima is also working on other drug-delivery projects, such as intraperitoneal chemotherapy delivery to treat ovarian cancer, funded in part by the Bridge Project.

By Rob Matheson | MIT News Office

Given a choice, most patients would prefer to take a drug orally instead of getting an injection. Unfortunately, many drugs, especially those made from large proteins, cannot be given as a pill because they get broken down in the stomach before they can be absorbed.

To help overcome that obstacle, researchers at MIT and Massachusetts General Hospital (MGH) have devised a novel drug capsule coated with tiny needles that can inject drugs directly into the lining of the stomach after the capsule is swallowed. In animal studies, the team found that the capsule delivered insulin more efficiently than injection under the skin, and there were no harmful side effects as the capsule passed through the digestive system.

“This could be a way that the patient can circumvent the need to have an infusion or subcutaneous administration of a drug,” says Giovanni Traverso, a research fellow at MIT’s Koch Institute for Integrative Cancer Research, a gastroenterologist at MGH, and one of the lead authors of the paper, which appears in the Journal of Pharmaceutical Sciences.

Although the researchers tested their capsule with insulin, they anticipate that it would be most useful for delivering biopharmaceuticals such as antibodies, which are used to treat cancer and autoimmune disorders like arthritis and Crohn’s disease. This class of drugs, known as “biologics,” also includes vaccines, recombinant DNA, and RNA.

“The large size of these biologic drugs makes them nonabsorbable. And before they even would be absorbed, they’re degraded in your GI tract by acids and enzymes that just eat up the molecules and make them inactive,” says Carl Schoellhammer, a graduate student in chemical engineering and a lead author of the paper.

Safe and effective delivery

Scientists have tried designing microparticles and nanoparticles that can deliver biologics, but such particles are expensive to produce and require a new version to be engineered for each drug.

Schoellhammer, Traverso, and their colleagues set out to design a capsule that would serve as a platform for the delivery of a wide range of therapeutics, prevent degradation of the drugs, and inject the payload directly into the lining of the GI tract. Their prototype acrylic capsule, 2 centimeters long and 1 centimeter in diameter, includes a reservoir for the drug and is coated with hollow, stainless steel needles about 5 millimeters long.

Previous studies of accidental ingestion of sharp objects in human patients have suggested that it could be safe to swallow a capsule coated with short needles. Because there are no pain receptors in the GI tract, patients would not feel any pain from the drug injection.

To test whether this type of capsule could allow safe and effective drug delivery, the researchers tested it in pigs, with insulin as the drug payload. It took more than a week for the capsules to move through the entire digestive tract, and the researchers found no traces of tissue damage, supporting the potential safety of this novel approach.

They also found that the microneedles successfully injected insulin into the lining of the stomach, small intestine, and colon, causing the animals’ blood glucose levels to drop. This reduction in blood glucose was faster and larger than the drop seen when the same amount of insulin was given by subcutaneous injection.

“The kinetics are much better, and much faster-onset, than those seen with traditional under-the-skin administration,” Traverso says. “For molecules that are particularly difficult to absorb, this would be a way of actually administering them at much higher efficiency.”

“This is a very interesting approach,” says Samir Mitragotri, a professor of chemical engineering at the University of California at Santa Barbara who was not involved in the research. “Oral delivery of drugs is a major challenge, especially for protein drugs. There is tremendous motivation on various fronts for finding other ways to deliver drugs without using the standard needle and syringe.”

Further optimization

This approach could also be used to administer vaccines that normally have to be injected, the researchers say.

The team now plans to modify the capsule so that peristalsis, or contractions of the digestive tract, would slowly squeeze the drug out of the capsule as it travels through the tract. They are also working on capsules with needles made of degradable polymers and sugar that would break off and become embedded in the gut lining, where they would slowly disintegrate and release the drug. This would further minimize any safety concern.

Avi Schroeder, a former Koch Institute postdoc, is also a lead author of the paper. The senior authors are Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, the Institute for Medical Engineering and Science (IMES), and the Department of Chemical Engineering; Daniel Blankschtein, the Herman P. Meissner Professor of Chemical Engineering; and Daniel Anderson, the Samuel A. Goldblith Associate Professor of Chemical Engineering and a member of the Koch Institute and IMES.

The research was funded by the National Institutes of Health.

By Anne Trafton | MIT News Office