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 Thursday, 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 self-proclaimed agnostic, Dr. Collins 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

The MIT Media Lab this week launched a wellness initiative designed to spark innovation in the area of health and wellbeing, and to promote healthier workplace and lifestyle behaviors.  

With support from the Robert Wood Johnson Foundation (RWJF), which is providing a $1 million grant, the new initiative will address the role of technology in shaping our health, and explore new approaches and solutions to wellbeing. The program is built around education and student mentoring; prototyping tools and technologies that support physical, mental, social, and emotional wellbeing; and community initiatives that will originate at the Media Lab, but be designed to scale.

The program begins with the fall course “Tools for Well Being,” followed by “Health Change Lab” in the spring. In addition to concept and technology development, these courses will feature seminars by noted experts who will address a wide range of topics related to wellness. These talks will be open to the public, and made available online. Speakers will include Walter Willett, a physician and noted nutrition researcher; Chuck Czeisler, a physician and sleep expert; Ben Sawyer, a game developer for health applications; Matthew Nock, an expert in suicide prevention; Dinesh John, a researcher on health sciences and workplace activity; Lisa Mosconi, a neuroscientist studying the prevention of Alzheimer’s disease; and Martin Seligman, a founder of the field of positive psychology. More information about the courses, speakers, and presentation topics and dates can be found at: http://wellbeing.media.mit.edu.

The RWJF grant will also support five graduate-level research fellows from the Program in Media Arts and Sciences who will be part of a year-long training program. The funding will enable each fellow to design, build, and deploy novel tools to promote wellbeing and health behavior change at the Media Lab, and then at scale.

One of the significant ways that this program will impact Media Lab culture is in the review of all thesis proposals submitted by students in media arts and sciences. Media Lab faculty recently added a new requirement that all proposals consider the impact of the work on human wellbeing.

Other Media Lab-wide aspects of the initiative include:

  • A monthly health challenge that would engage the entire lab, with review and analysis of each month’s deployment to help inform the next month’s initiative.
  • Pairing students with one another — to build awareness of wellbeing as a social function, not just a perosonal goal, and to draw on people’s inclination to solve the problems of others differently than their own.

“Wellbeing is a very hard problem that has yet to be solved by psychologists, psychiatrists, neuroscientists, biologists or other experts in the scientific community,” says Rosalind Picard, a professor of media arts and sciences and one of the three principal investigators on the initiative. “It’s time to bring MIT ingenuity to the challenge.”

“RWJF is working to build a culture of health in the U.S. where all people have opportunities to make healthy choices and lead healthy lifestyles. Technology has long shaped the patterns of everyday life, and it is these patterns­ — of how we work, eat, sleep, socialize, recreate and get from place to place — that largely determine our health,” says Stephen Downs, chief technology and information officer at RWJF. “We’re excited to see the Media Lab turn its creative talents and its significant influence to the challenge of developing technologies that will make these patterns of everyday life more healthy.”

Along with Picard, the other two principal investigators on the Advancing Wellness initiative are Pattie Maes, the Alex W. Dreyfoos Professor of Media Arts and Sciences, and Kevin Slavin, an assistant professor of media arts and sciences.

PhD student Karthik Dinakar, a Reid Hoffman Fellow at the Media Lab, will co-teach the two courses with the three principal investigators. Susan Silbey, the Leon and Anne Goldberg Professor of Humanities, Sociology and Anthropology, will also create independent assessments through the year on the impact of this project.

By Alexandra Kahn | MIT Media Lab

A new technique for studying the lifecycle of the hepatitis B virus could help researchers develop a cure for the disease.

In a paper published today in the journal Proceedings of the National Academy of Sciences, Sangeeta Bhatia of MIT and Charles Rice of Rockefeller University describe using microfabricated cell cultures to sustain hepatitis B virus in human liver cells, allowing them to study immune responses and drug treatments.

Around 400 million people worldwide are infected with the hepatitis B virus (HBV); of those, one-third will go on to develop life-threatening complications, such as cirrhosis and liver cancer.

Although there is an effective HBV vaccine, only around 50 percent of people in some countries where the disease is endemic are vaccinated. A complete cure for the disease is very rare, once someone has been chronically infected.

“Once a liver cell is infected, the viral genome persists inside the nucleus, and that can reactivate later,” says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. “So although we have a vaccine, it’s important to find a way to study this persistent form of the virus to try to identify treatments that could efficiently clear it.”

“Finicky” hepatocytes

To develop a treatment for HBV, researchers need to be able to study infected liver cells, known as hepatocytes, so they can understand how the virus interacts with them.

But while researchers have previously been able to infect cultures of human hepatocytes with HBV, the cells’ limited lifespan has made it difficult to study the virus, says Bhatia, who is also a Howard Hughes Medical Institute investigator and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

“That’s because the hepatocyte — the main cell in the liver — is unstable,” she says. “It’s a very finicky cell, and when you isolate it from the liver and try to culture it under conventional conditions, it rapidly loses its repertoire of liver functions.”

So the team set out to develop a technique to keep the liver cells stable and functioning long enough to monitor their response to the virus and antiviral drugs.

They based their approach on a system they had previously developed for studying the hepatitis C virus, in which they were able to successfully infect human hepatocytes with the virus and use it to compare antiviral regimens.

The hepatocytes are first patterned onto surfaces dotted with tiny spots of collagen, and then surrounded by supportive tissue made up of stromal cells, which act as connective tissue and support the hepatocytes in carrying out their liver functions.

Two complementary systems

To apply the technique to infection with HBV, the researchers developed two complementary systems. One uses primary hepatocytes obtained from livers donated for transplant; the second uses stem cells derived from human skin samples and guided into hepatocyte-like cells, Bhatia says.

When they compared the relative merits of the two systems, they found that the primary liver cells had a stronger immune response when infected with the virus than the stem cell progeny. However, unlike the primary hepatocytes, the hepatocyte-like cells offer an unlimited supply of test cells, since the researchers can simply grow more as required, Bhatia says.

“But that being said, both systems were able to grow this persistent nuclear form [of HBV], so we think they offer complementary tools,” she says.

The paper’s lead authors are Amir Shlomai of Rockefeller University, and graduate student Vyas Ramanan and former postdoc Robert E. Schwartz, both of MIT.

To investigate whether the cell cultures could be used to test new treatments for the disease, the researchers monitored their response to two existing drugs. They found that the infected cultures responded to the drugs in the same way that liver cells inside the body are known to do. This means the systems could be used to help predict how effective new treatments will be in eradicating the virus from liver cells, Bhatia says.

Having developed the technique, the researchers now plan to begin using it to investigate new treatments for HBV. They also plan to use the model to study liver cells’ natural antiviral response in more detail, and in particular to try to understand why cells from different donors have different immune responses to the disease.

Raymond Chung, vice chief of the gastrointestinal unit at Massachusetts General Hospital, who was not involved in the research, says that despite the availability of effective vaccines, researchers have made few inroads into eliminating HBV. “While we have excellent suppressive therapies, there are no truly curative treatments, in large measure because we have been handicapped by the lack of robust cell-culture models that support HBV infection,” he says.

“The new approach described here provides one avenue by which we may more effectively study the HBV lifecycle, and in so doing identify new agents that block additional steps in that lifecycle,” he adds. “Using such an approach could bring us one step closer to a cure for HBV.”

By Helen Knight | MIT News correspondent

Seven MIT faculty members are among 204 leaders from academia, business, public affairs, the humanities and the arts elected to the American Academy of Arts and Sciences, the academy announced today.

One of the nation’s most prestigious honorary societies, the academy is also a leading center for independent policy research. Members contribute to academy publications, as well as studies of science and technology policy, energy and global security, social policy and American institutions, the humanities and culture, and education.

Those elected from MIT this year are:

  • Elazer Reuven Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology
  • Michael Greenstone, the 3M Professor of Environmental Economics
  • Keith Adam Nelson, a professor of chemistry
  • Paul A. Seidel, a professor of mathematics
  • Gigliola Staffilani, the Abby Rockefeller Mauzé Professor of Mathematics
  • Sherry Roxanne Turkle, the Abby Rockefeller Mauzé Professor of the Social Studies of Science and Technology
  • Robert Dirk van der Hilst, the Schlumberger Professor of Earth Sciences and head of the Department of Earth, Atmospheric and Planetary Sciences

“It is a privilege to honor these men and women for their extraordinary individual accomplishments,” Don Randel, chair of the academy’s Board of Directors, said in a statement. “The knowledge and expertise of our members give the Academy a unique capacity — and responsibility — to provide practical policy solutions to the pressing challenges of the day. We look forward to engaging our new members in this work.”

The new class will be inducted at a ceremony held on Oct. 11 at the academy’s headquarters in Cambridge.

Since its founding in 1780, the academy has elected leading “thinkers and doers” from each generation, including George Washington and Benjamin Franklin in the 18th century, Daniel Webster and Ralph Waldo Emerson in the 19th century, and Albert Einstein and Winston Churchill in the 20th century. The current membership includes more than 250 Nobel laureates and more than 60 Pulitzer Prize winners.

By News Office

The following notice was sent Thursday afternoon to individuals at MIT and Harvard Medical School by representatives of the joint Harvard-MIT Health Sciences and Technology (HST) program. Eliana Hechter was a student in HST who had been working toward an M.D. degree from Harvard.

To the Harvard Medical School, MIT, and HST Communities:

It is with great sadness that we report the untimely death of Dr. Eliana Hechter, a first-year MD student in HST. Her family notified the medical school this morning, and have not yet made definitive plans regarding services or a memorial. As information becomes available, we will share it with you. We encourage students, administration, and faculty to come together as a community to remember Eliana as a student with tremendous promise, and one who has been lost far too soon.

Losing a member of our community is always difficult and we want to remind you that there are resources here to help you with grief or stress (please see below).

David Cohen, Emery Brown, Matthew Frosch, Patty Cunningham, and Rick Mitchell

— on behalf of HST

MIT Medical’s Mental Health and Counseling Service

E23 — 3rd Floor

On weekdays: call 617-253-2916 to schedule an appointment

For more urgent issues, visit them during walk-in hours on weekday afternoons from 2–4 p.m.

For very urgent issues, call one of the numbers below; a mental health clinician is on call and available 24 hours a day, seven days a week:

Weekdays (M-Th 8 a.m.–7 p.m., F 8 a.m.–5 p.m.): 617-253-2916

Nights/weekends: 617-253-4481

Chaplains at MIT

Contact information for individual Chaplains is available online here:

http://studentlife.mit.edu/rl/mit-chaplains

MIT’s Office of the Dean for Graduate Education (ODGE)

3-132

The office provides two pamphlets, “How to help someone in distress” and the MIT Medical brochure “Caring for our community.”

See also: http://web.mit.edu/student/personal_support.html

By News Office

MIT spinoff WiCare, founded by mechanical engineering alumna Danielle Zurovcik SM ’07, PhD ’12, has been named one of six finalists in this year’s Hult Prize competition.

The Hult Prize Foundation is a nonprofit organization focused on supporting social entrepreneurs. This year’s challenge is to solve non-communicable disease in urban slums, and winners receive $1M in seed funding.

Zurovcik, who developed a revolutionary negative pressure wound therapy pump (NPWT) as a PhD student in MechE, started WiCare (Worldwide Innovative Healthcare Inc.) with the goal of bringing high-quality medical devices to low-income countries. She is currently a fellow in the D-Lab Scale-Ups fellowship program.

Her Wound-Pump differs from other NPWT pumps on the market because of its unique materials, application method, and size. Standard pumps cost approximately $100 per day to overcome their inefficient energy usage, preventing low- and middle-income patients from utilizing the therapy. But because the Wound-Pump eliminates such energy waste, it costs less than $2 to manufacture and doesn’t require electricity at all.

Hult Prize finalists will give their presentations this summer, and the winner will be announced in September.

By Alissa Mallinson | Department of Mechanical Engineering

A paper diagnostic for cancer

October 20, 2014

Cancer rates in developing nations have climbed sharply in recent years, and now account for 70 percent of cancer mortality worldwide. Early detection has been proven to improve outcomes, but screening approaches such as mammograms and colonoscopy, used in the developed world, are too costly to be implemented in settings with little medical infrastructure.  

To address this gap, MIT engineers have developed a simple, cheap, paper test that could improve diagnosis rates and help people get treated earlier. The diagnostic, which works much like a pregnancy test, could reveal within minutes, based on a urine sample, whether a person has cancer. This approach has helped detect infectious diseases, and the new technology allows noncommunicable diseases to be detected using the same strategy.

The technology, developed by MIT professor and Howard Hughes Medical Institute investigator Sangeeta Bhatia, relies on nanoparticles that interact with tumor proteins called proteases, each of which can trigger release of hundreds of biomarkers that are then easily detectable in a patient’s urine.

“When we invented this new class of synthetic biomarker, we used a highly specialized instrument to do the analysis,” says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science. “For the developing world, we thought it would be exciting to adapt it instead to a paper test that could be performed on unprocessed samples in a rural setting, without the need for any specialized equipment. The simple readout could even be transmitted to a remote caregiver by a picture on a mobile phone.”

Bhatia, who is also a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, is the senior author of a paper describing the particles in the Proceedings of the National Academy of Sciences the week of Feb. 24. The paper’s lead authors are graduate student Andrew Warren, postdoc Gabriel Kwong, and former postdoc David Wood.

Amplifying cancer signals

In 2012, Bhatia and colleagues introduced the concept of a synthetic biomarker technology to amplify signals from tumor proteins that would be hard to detect on their own. These proteins, known as matrix metalloproteinases (MMPs), help cancer cells escape their original locations by cutting through proteins of the extracellular matrix, which normally holds cells in place.

The MIT nanoparticles are coated with peptides (short protein fragments) targeted by different MMPs. These particles congregate at tumor sites, where MMPs cleave hundreds of peptides, which accumulate in the kidneys and are excreted in the urine.

In the original version of the technology, these peptides were detected using an instrument called a mass spectrometer, which analyzes the molecular makeup of a sample. However, these instruments are not readily available in the developing world, so the researchers adapted the particles so they could be analyzed on paper, using an approach known as a lateral flow assay — the same technology used in pregnancy tests.

To create the test strips, the researchers first coated nitrocellulose paper with antibodies that can capture the peptides. Once the peptides are captured, they flow along the strip and are exposed to several invisible test lines made of other antibodies specific to different tags attached to the peptides. If one of these lines becomes visible, it means the target peptide is present in the sample. The technology can also easily be modified to detect multiple types of peptides released by different types or stages of disease.

“This is a clever and inspired technology to develop new exogenous compounds that can detect clinical conditions with aberrantly high protease concentrations,” says Samuel Sia, an associate professor of biological engineering at Columbia University who was not involved in the research. “Extending this technology to detection by strip tests is a big leap forward in bringing its use to outpatient clinics and decentralized health settings.”

In tests in mice, the researchers were able to accurately identify colon tumors, as well as blood clots. Bhatia says these tests represent the first step toward a diagnostic device that could someday be useful in human patients.

“This is a new idea — to create an excreted biomarker instead of relying on what the body gives you,” she says. “To prove this approach is really going to be a useful diagnostic, the next step is to test it in patient populations.”

Developing diagnostics

To help make that happen, the research team recently won a grant from MIT’s Deshpande Center for Technological Innovation to develop a business plan for a startup that could work on commercializing the technology and performing clinical trials.

Bhatia says the technology would likely first be applied to high-risk populations, such as people who have had cancer previously, or had a family member with the disease. Eventually, she would like to see it used for early detection throughout developing nations.

Such technology might also prove useful in the United States, and other countries where more advanced diagnostics are available, as a simple and inexpensive alternative to imaging. “I think it would be great to bring it back to this setting, where point-of-care, image-free cancer detection, whether it’s in your home or in a pharmacy clinic, could really be transformative,” Bhatia says.

With the current version of the technology, patients would first receive an injection of the nanoparticles, then urinate onto the paper test strip. To make the process more convenient, the researchers are now working on a nanoparticle formulation that could be implanted under the skin for longer-term monitoring.

The team is also working to identify signatures of MMPs that could be exploited as biomarkers for other types of cancer, as well as for tumors that have metastasized.

The research was funded by a National Science Foundation Graduate Research Fellowship, a Mazumdar-Shaw International Oncology Fellowship, the Ruth L. Kirschstein National Research Service Award from the National Institutes of Health, the Burroughs Wellcome Fund, the National Cancer Institute, and the Howard Hughes Medical Institute.

By Anne Trafton, MIT News Office

To evaluate school quality, states require students to take standardized tests; in many cases, passing those tests is necessary to receive a high-school diploma. These high-stakes tests have also been shown to predict students’ future educational attainment and adult employment and income.

Such tests are designed to measure the knowledge and skills that students have acquired in school — what psychologists call “crystallized intelligence.” However, schools whose students have the highest gains on test scores do not produce similar gains in “fluid intelligence” — the ability to analyze abstract problems and think logically — according to a new study from MIT neuroscientists working with education researchers at Harvard University and Brown University.

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.

“Our original question was this: If you have a school that’s effectively helping kids from lower socioeconomic environments by moving up their scores and improving their chances to go to college, then are those changes accompanied by gains in additional cognitive skills?” says John Gabrieli, the Grover M. Hermann Professor of Health Sciences and Technology, professor of brain and cognitive sciences, and senior author of a forthcoming Psychological Science paper describing the findings.

Instead, the researchers found that educational practices designed to raise knowledge and boost test scores do not improve fluid intelligence. “It doesn’t seem like you get these skills for free in the way that you might hope, just by doing a lot of studying and being a good student,” says Gabrieli, who is also a member of MIT’s McGovern Institute for Brain Research.

Measuring cognition

This study grew out of a larger effort to find measures beyond standardized tests that can predict long-term success for students. “As we started that study, it struck us that there’s been surprisingly little evaluation of different kinds of cognitive abilities and how they relate to educational outcomes,” Gabrieli says.

The data for the Psychological Science study came from students attending traditional, charter, and exam schools in Boston. Some of those schools have had great success improving their students’ MCAS scores — a boost that studies have found also translates to better performance on the SAT and Advanced Placement tests.

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.

In one example of a test of fluid reasoning, students were asked to choose which of six pictures completed the missing pieces of a puzzle — a task requiring integration of information such as shape, pattern, and orientation.

“It’s not always clear what dimensions you have to pay attention to get the problem correct. That’s why we call it fluid, because it’s the application of reasoning skills in novel contexts,” says Amy Finn, an MIT postdoc and lead author of the paper.

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.

However, the researchers say their study is not about comparing charter schools and district schools. Rather, the study showed that while schools of both types varied in their impact on test scores, they did not vary in their impact on fluid cognitive skills. 

“What’s nice about this study is it seems to narrow down the possibilities of what educational interventions are achieving,” says Daniel Willingham, a professor of psychology at the University of Virginia who was not part of the research team. “We’re usually primarily concerned with outcomes in schools, but the underlying mechanisms are also important.”

The researchers plan to continue tracking these students, who are now in 10th grade, to see how their academic performance and other life outcomes evolve. They have also begun to participate in a new study of high school seniors to track how their standardized test scores and cognitive abilities influence their rates of college attendance and graduation.

Implications for education

Gabrieli notes that the study should not be interpreted as critical of schools that are improving their students’ MCAS scores. “It’s valuable to push up the crystallized abilities, because if you can do more math, if you can read a paragraph and answer comprehension questions, all those things are positive,” he says.

He hopes that the findings will encourage educational policymakers to consider adding practices that enhance cognitive skills. Although many studies have shown that students’ fluid cognitive skills predict their academic performance, such skills are seldom explicitly taught.

“Schools can improve crystallized abilities, and now it might be a priority to see if there are some methods for enhancing the fluid ones as well,” Gabrieli says.

Some studies have found that educational programs that focus on improving memory, attention, executive function, and inductive reasoning can boost fluid intelligence, but there is still much disagreement over what programs are consistently effective.

The research was a collaboration with the Center for Education Policy Research at Harvard University, Transforming Education, and Brown University, and was funded by the Bill and Melinda Gates Foundation and the National Institutes of Health.

By Anne Trafton, MIT News Office