In bias we trust?

When the stakes are high, machine-learning models are sometimes used to aid human decision-makers. For instance, a model could predict which law school applicants are most likely to pass the bar exam to help an admissions officer determine which students should be accepted.

These models often have millions of parameters, so how they make predictions is nearly impossible for researchers to fully understand, let alone an admissions officer with no machine-learning experience. Researchers sometimes employ explanation methods that mimic a larger model by creating simple approximations of its predictions. These approximations, which are far easier to understand, help users determine whether to trust the model’s predictions.

But are these explanation methods fair? If an explanation method provides better approximations for men than for women, or for white people than for Black people, it may encourage users to trust the model’s predictions for some people but not for others.

MIT researchers took a hard look at the fairness of some widely used explanation methods. They found that the approximation quality of these explanations can vary dramatically between subgroups and that the quality is often significantly lower for minoritized subgroups.

In practice, this means that if the approximation quality is lower for female applicants, there is a mismatch between the explanations and the model’s predictions that could lead the admissions officer to wrongly reject more women than men.

Once the MIT researchers saw how pervasive these fairness gaps are, they tried several techniques to level the playing field. They were able to shrink some gaps, but couldn’t eradicate them.

“What this means in the real-world is that people might incorrectly trust predictions more for some subgroups than for others. So, improving explanation models is important, but communicating the details of these models to end users is equally important. These gaps exist, so users may want to adjust their expectations as to what they are getting when they use these explanations,” says lead author Aparna Balagopalan, a graduate student in the Healthy ML group of the MIT Computer Science and Artificial Intelligence Laboratory (CSAIL).

Balagopalan wrote the paper with CSAIL graduate students Haoran Zhang and Kimia Hamidieh; CSAIL postdoc Thomas Hartvigsen; Frank Rudzicz, associate professor of computer science at the University of Toronto; and senior author Marzyeh Ghassemi, an assistant professor and head of the Healthy ML Group. The research will be presented at the ACM Conference on Fairness, Accountability, and Transparency.

High fidelity

Simplified explanation models can approximate predictions of a more complex machine-learning model in a way that humans can grasp. An effective explanation model maximizes a property known as fidelity, which measures how well it matches the larger model’s predictions.

Rather than focusing on average fidelity for the overall explanation model, the MIT researchers studied fidelity for subgroups of people in the model’s dataset. In a dataset with men and women, the fidelity should be very similar for each group, and both groups should have fidelity close to that of the overall explanation model.

“When you are just looking at the average fidelity across all instances, you might be missing out on artifacts that could exist in the explanation model,” Balagopalan says.

They developed two metrics to measure fidelity gaps, or disparities in fidelity between subgroups. One is the difference between the average fidelity across the entire explanation model and the fidelity for the worst-performing subgroup. The second calculates the absolute difference in fidelity between all possible pairs of subgroups and then computes the average.

With these metrics, they searched for fidelity gaps using two types of explanation models that were trained on four real-world datasets for high-stakes situations, such as predicting whether a patient dies in the ICU, whether a defendant reoffends, or whether a law school applicant will pass the bar exam. Each dataset contained protected attributes, like the sex and race of individual people. Protected attributes are features that may not be used for decisions, often due to laws or organizational policies. The definition for these can vary based on the task specific to each decision setting.

The researchers found clear fidelity gaps for all datasets and explanation models. The fidelity for disadvantaged groups was often much lower, up to 21 percent in some instances. The law school dataset had a fidelity gap of 7 percent between race subgroups, meaning the approximations for some subgroups were wrong 7 percent more often on average. If there are 10,000 applicants from these subgroups in the dataset, for example, a significant portion could be wrongly rejected, Balagopalan explains.

“I was surprised by how pervasive these fidelity gaps are in all the datasets we evaluated. It is hard to overemphasize how commonly explanations are used as a ‘fix’ for black-box machine-learning models. In this paper, we are showing that the explanation methods themselves are imperfect approximations that may be worse for some subgroups,” says Ghassemi.

Narrowing the gaps

After identifying fidelity gaps, the researchers tried some machine-learning approaches to fix them. They trained the explanation models to identify regions of a dataset that could be prone to low fidelity and then focus more on those samples. They also tried using balanced datasets with an equal number of samples from all subgroups.

These robust training strategies did reduce some fidelity gaps, but they didn’t eliminate them.

The researchers then modified the explanation models to explore why fidelity gaps occur in the first place. Their analysis revealed that an explanation model might indirectly use protected group information, like sex or race, that it could learn from the dataset, even if group labels are hidden.

They want to explore this conundrum more in future work. They also plan to further study the implications of fidelity gaps in the context of real-world decision making.

Balagopalan is excited to see that concurrent work on explanation fairness from an independent lab has arrived at similar conclusions, highlighting the importance of understanding this problem well.

As she looks to the next phase in this research, she has some words of warning for machine-learning users.

“Choose the explanation model carefully. But even more importantly, think carefully about the goals of using an explanation model and who it eventually affects,” she says.

This work was funded, in part, by the MIT-IBM Watson AI Lab, the Quanta Research Institute, a Canadian Institute for Advanced Research AI Chair, and Microsoft Research.

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SMART researchers enable early-stage detection of microbial contamination in cell therapy

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART), MIT’s research enterprise in Singapore, have identified a critical quality attribute (CQA) that potentially allows the development of a rapid and sensitive process analytical technology for sterility. Specifically, this technology enables the detection of early-stage microbial contamination in human cell therapy products (CTPs).

Cell therapy represents one of the most advanced biotechnology revolutions in medicine, with strong potential to repair damaged tissues and treat a range of conditions such as degenerative diseases and cancer. It works by delivering living cells to replace or repair damaged tissue and cells. Notably, the manufacturing processes of many CTPs are complex, and the products themselves have short shelf lives. During the manufacturing process, cells in culture are vulnerable to microbial contamination due to the use of nutrient media, which supports human cell growth but can also support the growth of harmful microorganisms. Therefore, CTPs present a risk of possible transmission of infectious agents from cells to patients, which may cause serious bacterial infections.

To control microbial risks and ensure the product safety of CTPs, sterility testing and monitoring are required in the manufacturing process and before patient infusion. This can be achieved by identifying CQAs, which are key properties or characteristics of CTPs that should fall within appropriate limits or ranges to achieve the products’ desired quality. The identification of a secreted metabolite biomarker thus paves the way toward developing a rapid and accurate sterility test method that could determine microbial safety as early as possible, without also affecting the human cells that serve as the patient’s medicine.

A breakthrough developed by researchers in SMART's Critical Analytics for Manufacturing Personalized-Medicine (CAMP) interdisciplinary research group, is critical in overcoming the challenges of widespread adoption and manufacturing of CTPs.

The method developed by CAMP utilizes the ratio of two metabolites, nicotinic acid to nicotinamide, as a biomarker to detect a broad spectrum of microbial contaminants in cell cultures. The team’s research is explained in a paper titled “The ratio of nicotinic acid to nicotinamide as a microbial biomarker for assessing cell therapy product sterility,” published recently in the journal Molecular Therapy: Methods & Clinical Development.

“This team-based, interdisciplinary approach to technology development that addresses critical bottlenecks in cell therapy manufacturing — including safety assessment that is as fast as therapy production — is a hallmark of SMART CAMP’s research goals,” says Krystyn Van Vliet, MIT professor of materials science and engineering, associate provost, and associate vice president for research who is also co-lead of SMART CAMP with Hanry Yu, professor at the National University of Singapore.

As part of the research, the media (or fluid) of cell therapy products that were intentionally contaminated or uncontaminated with microbes were collected and analyzed through liquid chromatography-mass spectrometry-based metabolomics. The researchers identified secreted metabolites that were uniquely found in microbe-contaminated human cell cultures but not in uncontaminated ones, based on the analysis.

Among these metabolites found in human cell culture media, nicotinic acid was found to be widely conserved in cell cultures contaminated with multiple types of microorganisms. Upon further analysis, CAMP’s studies revealed that nicotinic acid production was associated with nicotinamidase, an enzyme that converted the nicotinamide in the culture medium into nicotinic acid. The research findings showed that nicotinamidase was not found in mammals, including humans, and the majority was found in bacteria species. Therefore, the ratio of nicotinic acid to nicotinamide indicated the presence of microbial contaminations in human CTPs.

This method surpasses existing and conventional techniques in terms of both sensitivity and speed. It can detect microbial contaminations in half-a-day, depending on the type of microorganism tested. In contrast, conventional methods require up to 14 days for detection. Alternative microbiological methods also face several limitations, such as the invasive process of cell extraction from and during the manufacturing process, requiring an incubation period for microbial enrichment that lengthens detection time to multiple days, or detecting only a limited range of bacterial species.

Overcoming existing limitations, the method developed by CAMP is able to detect cell therapy contamination rapidly, using a small volume of spent cell culture medium in a non-cell destructive manner while maintaining the human CTP. Furthermore, this approach can differentiate between live and dead bacteria. Dead bacteria are non-infectious, and the ability to identify and measure only live bacteria, which pose a health threat, could lead to lower false-positive rates.

“Our novel analytical test method is the first reported method that identified a secreted metabolite biomarker as a potential sterility CQA to detect microbial contaminations caused by a broad range of microbial species. The method addresses one of the key challenges of developing a rapid sterility process analytical technology in the manufacturing process of CTPs to ensure the timely and accurate assessment of microbial safety, which will accelerate the adoption and production of high-quality CTPs,” says Jiayi Huang, senior postdoc at SMART CAMP and lead author of the paper.

“This sterility biomarker has the possibility to become a rapid method for early detection of microbes for manufacturers. As we can sample the supernatant of the cell therapy product directly without the need for subculturing precious cells, this could be an important advantage for monitoring along the cell therapy production process. We are pursuing a number of translational paths forward, including small-scale mass spectrometry and optical methods,” adds Stacy L. Springs, principal investigator at SMART CAMP, executive director at the MIT Center for Biomedical Innovation, and co-corresponding author.

This discovery also benefited from the perspectives of co-authors Scott Rice, principal investigator at SMART CAMP, faculty at National Technical University, and deputy research director at Singapore Center for Environmental Life Sciences Engineering with expertise in microbial communities; and Yie Hou Lee, scientific director of SMART CAMP with expertise in metabolomic analysis.

The study provides a new way to detect adventitious microbial contamination based on the microbes’ secreted metabolite into the human cell culture’s surrounding fluid or supernatant. The team at SMART CAMP is currently working on translating the research to an innovative sterility process analytical technology to improve CTP quality. The impact of the research findings also applies beyond the field of medicine, offering new possibilities for the development of relevant products and technologies to detect microbial contamination in other industries, including health care, food, cosmetics, and the environment.

The research is carried out by SMART and supported by the National Research Foundation (NRF) Singapore under its Campus for Research Excellence And Technological Enterprise (CREATE) program.

CAMP is a SMART interdisciplinary research group launched in June 2019. It focuses on better ways to produce living cells as medicine, or cellular therapies, to provide more patients access to promising and approved therapies. The investigators at CAMP address two key bottlenecks facing the production of a range of potential cell therapies: CQA and PAT. Leveraging deep collaborations within Singapore and MIT in the United States, CAMP invents and demonstrates CQA/PAT capabilities from stem to immune cells. Its work addresses ailments ranging from cancer to tissue degeneration, targeting adherent and suspended cells, with and without genetic engineering.

CAMP is the R&D core of a comprehensive national effort on cell therapy manufacturing in Singapore.

SMART was established by MIT and the NRF in 2007. SMART is the first entity in CREATE. SMART serves as an intellectual and innovation hub for research interactions between MIT and Singapore, undertaking cutting-edge research projects in areas of interest to both. SMART currently comprises an Innovation Center and five IRGs: Antimicrobial Resistance, CAMP, Disruptive and Sustainable Technologies for Agricultural Precision, Future Urban Mobility, and Low Energy Electronic Systems.

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Convenience-sized RNA editing

Last year, researchers at MIT’s McGovern Institute for Brain Research discovered and characterized Cas7-11, the first CRISPR enzyme capable of making precise, guided cuts to strands of RNA without harming cells in the process. Now, working with collaborators at the University of Tokyo, the same team has revealed that Cas7-11 can be shrunk to a more compact version, making it an even more viable option for editing the RNA inside living cells. The new, compact Cas7-11 was described May 27 in the journal Cell along with a detailed structural analysis of the original enzyme.

“When we looked at the structure, it was clear there were some pieces that weren’t needed, which we could actually remove,” says Research Scientist and McGovern Fellow Omar Abudayyeh, who led the new work with Research Scientist and McGovern Fellow Jonathan Gootenberg and collaborator Hiroshi Nishimasu from the University of Tokyo. “This makes the enzyme small enough that it fits into a single viral vector for therapeutic applications.”

The authors, who also include former McGovern Institute postdoc Nathan Zhou and Kazuki Kato from the University Tokyo, see the new three-dimensional structure of Cas7-11 as a rich resource to answer questions about the basic biology of the enzymes and reveal other ways to tweak its function in the future.

Targeting RNA

Over the past decade, the CRISPR-Cas9 genome editing technology has given researchers the ability to modify the genes inside human cells — a boon for both basic research and the development of therapeutics to reverse disease-causing genetic mutations. But CRISPR-Cas9 only works to alter DNA, and for some research and clinical purposes, editing RNA is more effective or useful.

A cell retains its DNA for life, and passes an identical copy to daughter cells as it duplicates, so any changes to DNA are relatively permanent. However, RNA is a more transient molecule, transcribed from DNA and degraded not long after.

“There are lots of positives about being able to permanently change DNA, especially when it comes to treating an inherited genetic disease,” Gootenberg says. “But for an infection, an injury, or some other temporary disease, being able to temporarily modify a gene through RNA targeting makes more sense.”

Until Abudayyeh, Gootenberg, and their colleagues discovered and characterized Cas7-11, the only enzyme that could target RNA had a messy side effect; when it recognized a particular gene, the enzyme — Cas13 — began cutting up all the RNA around it. This property makes Cas13 effective for diagnostic tests, where it is used to detect the presence of a piece of RNA, but not very useful for therapeutics, where targeted cuts are required.

The discovery of Cas7-11 opened the doors to a more precise form of RNA editing, analogous to the Cas9 enzyme for DNA. However, the massive Cas7-11 protein was too big to fit inside a single viral vector — the empty shell of a virus that researchers typically use to deliver gene editing machinery into patient’s cells.

Structural insight

To determine the overall structure of Cas7-11, Abudayyeh, Gootenberg, and Nishimasu used cryo-electron microscopy, which shines beams of electrons on frozen protein samples and measures how the beams are transmitted. The researchers knew that Cas7-11 was like an amalgamation of five separate Cas enzymes, fused into one single gene, but were not sure exactly how those parts folded and fit together.

“The really fascinating thing about Cas7-11, from a fundamental biology perspective, is that it should be all these separate pieces that come together, but instead you have a fusion into one gene,” Gootenberg says. “We really didn’t know what that would look like.”

The structure of Cas7-11, caught in the act of binding both its target tRNA strand and the guide RNA, which directs that binding, revealed how the pieces assembled and which parts of the protein were critical to recognizing and cutting RNA. This kind of structural insight is critical to figuring out how to make Cas7-11 carry out targeted jobs inside human cells.

The structure also illuminated a section of the protein that wasn’t serving any apparent functional role. This finding suggested the researchers could remove it, re-engineering Cas7-11 to make it smaller without taking away its ability to target RNA. Abudayyeh and Gootenberg tested the impact of removing different bits of this section, resulting in a new compact version of the protein, dubbed Cas7-11S. With Cas7-11S in hand, they packaged the system inside a single viral vector, delivered it into mammalian cells, and efficiently targeted RNA.

The team is now planning future studies on other proteins that interact with Cas7-11 in the bacteria that it originates from, and also hopes to continue working towards the use of Cas7-11 for therapeutic applications.

“Imagine you could have an RNA gene therapy, and when you take it, it modifies your RNA, but when you stop taking it, that modification stops,” Abudayyeh says. “This is really just the beginning of enabling that tool set.”

This research was funded, in part, by the McGovern Institute Neurotechnology Program, K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience, G. Harold and Leila Y. Mathers Charitable Foundation, MIT John W. Jarve (1978) Seed Fund for Science Innovation, FastGrants, Basis for Supporting Innovative Drug Discovery and Life Science Research Program, JSPS KAKENHI, Takeda Medical Research Foundation, and Inamori Research Institute for Science.

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Joel Moses, Institute Professor Emeritus and computer science trailblazer, dies at 80

Institute Professor Emeritus Joel Moses PhD ’67, an innovative computer scientist and dedicated teacher who held multiple leadership positions at MIT, died on May 29 after a long battle with Alzheimer’s and Parkinson’s diseases. He was 80 years old.

Moses, a professor in the Department of Computer Science and Electrical Engineering and the former Engineering Systems Division, served as associate department head, department head, dean of engineering, and provost during his distinguished career.

“Our community will forever be grateful to Joel for his vision, dedication, and citizenship, and I will forever be grateful for his brilliant mind and his wonderful heart,” MIT President L. Rafael Reif wrote in a letter to the MIT community today.

As a researcher, Moses is well-known for his work to develop Macsyma in the late 1960s, which was one of the first computer systems that could manipulate complex mathematical expressions, like those in algebra or calculus.

The Macsyma program enables a computer to solve mathematical problems such as differentiating and integrating expressions, manipulating matrices, and deriving symbolic solutions of equations. Macsyma was faster and more accurate than other methods — problems in engineering or physics that would have taken six or seven months to calculate could now be solved in under an hour. The program influenced many powerful computational tools that are an outgrowth of Moses’ research. He was honored by the National Academy of Engineering in 1986 for this pioneering work in symbolic algebraic manipulation by a computer.

“One of the lessons that I have learned from Joel is that we gain flexibility at the cost of increased complexity as we proceed from tree structures, through layered systems, to arbitrary networks,” says Gerald Jay Sussman ’68, PhD ’73, the Panasonic Professor of Electrical Engineering, who first met Moses when he took a computer programming class that Moses, then an undergraduate at Columbia University, was teaching for high school students. “The most astonishing point is that Joel’s philosophy of the connection between the structure of a system and the ability to adapt it to new conditions is not just about computer systems, but rather about such diverse systems as corporate and military structure and social order. His extensive administrative work at MIT powerfully illustrates this philosophy. He continually constructed new avenues of communication among previously disconnected entities, building layered systems that could rapidly adjust to novel and unanticipated conditions.”

Moses’ skills as an administrator were felt across MIT. As dean of engineering, he launched a long-range plan called “Engineering with a Big E” to incorporate concepts from the social sciences and management into the engineering curriculum. He also oversaw the creation of MIT’s first five-year combined bachelor’s and master’s programs in engineering.

Later, as provost, Moses saw the need for a building that would bring electrical engineering and computer science closer together to foster faculty collaboration and provide opportunities for students. His vision culminated in the opening of the Ray and Maria Stata Center in 2001. At the groundbreaking ceremony, Moses was honored for his efforts to make the building a reality.

He was also instrumental in the creation of the Systems Design and Management graduate program, a unique multidisciplinary program that prepares graduates for leadership roles at the intersection of engineering and business. An advocate for student success, Moses worked to increase payments for research and teaching assistants and tripled the funding for undergraduate and graduate student associations’ activities.

Moses was born in Mandatory Palestine in 1941. His parents, Bernhard and Golda, who were Jewish, had fled Nazi Germany two years before his birth through a harrowing journey that saw them arrested in Palestine and nearly sent back to Berlin for fear they were German spies.

From an early age, Moses showed an interest in math — he was asked to grade papers for his fourth-grade math class when the teacher was out of town. When Moses was 13, his family emigrated from the new state of Israel to Brooklyn, New York.

He attended Columbia University, and while his parents tried to convince him to become a doctor, Moses chose mathematics instead. As a master’s student at Columbia, Moses first realized he could use computers to do math. This laid the groundwork for Macsyma and his later research. He earned a PhD at MIT in 1967, working under the supervision of artificial intelligence pioneer Marvin Minsky, and wrote his thesis about the design and development of a computer program for performing symbolic integration.

After graduation, Moses joined the faculty as an assistant professor in computer science and began work on Macsyma in earnest two years later. An original member of the Artificial Intelligence Laboratory (which would later merge with the Laboratory for Computer Science to form CSAIL), his research efforts were centered on key algorithms that could simplify and integrate mathematical expressions.

“Joel was a beloved member of the CSAIL community. His impact on CSAIL, MIT, and beyond has been extraordinary. His Macsyma project developed in the 1970s was the first attempt to use a machine to do symbolic mathematics — the system is still in use today. He will be greatly missed,” says Daniela Rus, the Andrew and Erna Viterbi Professor of Electrical Engineering and Computer Science and director of CSAIL.

Moses was also an avid music lover. In 1968, he attended an MIT party held after a concert at the New England Conservatory, where he met Peggy Garvey, who had been singing jazz at the concert. They were married for 52 years. Music remained important to him, and 30 years later, while on sabbatical at Columbia, Moses auditioned for and won a spot in a singing class at the prestigious Juilliard School.

Moses began his career as an administrator in 1974, when he was named associate director of the Laboratory for Computer Science and then associate head of the Department of Electrical Engineering and Computer Science (EECS) in 1978. Moses once said that, unlike many of his fellow faculty members, he found administration, and especially committee work, to be particularly interesting.

“You really get to the essence of issues, surprisingly, and ideas come forth that you wouldn’t have expected,” he said in a 2009 interview.

For Moses, administration often involved supporting others, especially junior faculty members, and finding ways to encourage collaboration. As EECS department head in 1981, he launched a popular seminar series, affectionately called “the Moses Seminar,” where faculty from every school gathered to talk about technical issues. Moses also spearheaded a series of faculty dinners and created a symposium that sought to build bridges between faculty in the humanities and their colleagues in engineering and science.  

“Joel’s ‘Moses Seminar’ Friday lunches were a real highlight for me, exemplifying Joel and MIT at their finest. Topics discussed were from all over the ’Tute, and collegiality and bantering were the norm,” reflects Institute Professor Ron Rivest. “Joel’s calm and amused manner inspired us all; he was the visionary who made them happen.”

During his time as provost, Moses led key budgeting initiatives and launched a retirement incentive plan that improved the financial footing of MIT while creating more openings for new faculty. Moses, who enjoyed helping those around him succeed, said his favorite part of being provost was presenting faculty awards.

Fiercely dedicated to improving his alma mater at every turn, Moses was also warm, friendly, and always ready to share a laugh with friends and colleagues. For instance, as provost, he began each meeting with department heads by asking someone to tell a joke.

After stepping down as provost in 1998, Moses rejoined the faculty and was named an Institute Professor one year later. He continued to be active in research and administration, most recently as acting director of MIT’s Engineering Systems Division.

Moses is survived by his wife, Peggy, sons Jesse and David, and brother, Abraham. Gifts in memory of Joel Moses may be made to MIT to support the Student Life, Wellness, and Support Fund, and to the Hebrew Rehabilitation Center at NewBridge on the Charles.

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MIT engineers boost signals from fluorescent sensors

Fluorescent sensors, which can be used to label and image a wide variety of molecules, offer a unique glimpse inside living cells. However, they typically can only be used in cells grown in a lab dish or in tissues close to the surface of the body, because their signal is lost when they are implanted too deeply.

MIT engineers have now come up with a way to overcome that limitation. Using a novel photonic technique they developed for exciting any fluorescent sensor, they were able to dramatically improve the fluorescent signal. With this approach, the researchers showed they could implant sensors as deep as 5.5 centimeters in tissue and still get a strong signal.

This kind of technology could enable fluorescent sensors to be used to track specific molecules inside the brain or other tissues deep within the body, for medical diagnosis or monitoring drug effects, the researchers say.

“If you have a fluorescent sensor that can probe biochemical information in cell culture, or in thin tissue layers, this technology allows you to translate all of those fluorescent dyes and probes into thick tissue,” says Volodymyr Koman, an MIT research scientist and one of the lead authors of the new study.

Naveed Bakh SM ’15, PhD ’20 is also a lead author of the paper, which appears today in Nature Nanotechnology. Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT, is the senior author of the study.

Enhanced fluorescence

Scientists use many different kinds of fluorescent sensors, including quantum dots, carbon nanotubes, and fluorescent proteins, to label molecules inside cells. These sensors’ fluorescence can be seen by shining laser light on them. However, this doesn’t work in thick, dense tissue, or deep within tissue, because tissue itself also emits some fluorescent light. This light, called autofluorescence, drowns out the signal coming from the sensor.

“All tissues autofluoresce, and this becomes a limiting factor,” Koman says. “As the signal from the sensor becomes weaker and weaker, it becomes overtaken by the tissue autofluorescence.”

To overcome this limitation, the MIT team came up with a way to modulate the frequency of the fluorescent light emitted by the sensor so that it can be more easily distinguished from the tissue autofluorescence. Their technique, which they call wavelength-induced frequency filtering (WIFF), uses three lasers to create a laser beam with an oscillating wavelength.

When this oscillating beam is shined on the sensor, it causes the fluorescence emitted by the sensor to double its frequency. This allows the fluorescent signal to be easily picked out from the background autofluorescence. Using this system, the researchers were able to enhance the sensors’ signal-to-noise ratio more than 50-fold.

One possible application for this kind of sensing is to monitor the effectiveness of chemotherapy drugs. To demonstrate this potential, the researchers focused on glioblastoma, an aggressive type of brain cancer. Patients with this type of cancer usually undergo surgery to remove as much of the tumor as possible, then receive the chemotherapy drug temozolomide (TMZ) to try to eliminate any remaining cancer cells.

This drug can have serious side effects, and it doesn’t work for all patients, so it would be helpful to have a way to easily monitor whether it’s working or not, Strano says.

“We are working on technology to make small sensors that could be implanted near the tumor itself, which can give an indication of how much drug is arriving at the tumor and whether it’s being metabolized. You could place a sensor near the tumor and verify from outside the body the efficacy of the drug in the actual tumor environment,” he says.

When temozolomide enters the body, it gets broken down into smaller compounds, including one known as AIC. The MIT team designed a sensor that could detect AIC, and showed that they could implant it as deep as 5.5 centimeters within an animal brain. They were able to read the signal from the sensor even through the animal’s skull.

Such sensors could also be designed to detect molecular signatures of tumor cell death, such as reaction oxygen species.

“Any wavelength”

In addition to detecting TMZ activity, the researchers demonstrated that they could use WIFF to enhance the signal from a variety of other sensors, including carbon-nanotube-based sensors that Strano’s lab has previously developed to detect hydrogen peroxide, riboflavin, and ascorbic acid.

“The technique works at any wavelength, and it can be used for any fluorescent sensor,” Strano says. “Because you have so much more signal now, you can implant a sensor at depths into tissue that were not possible before.”

For this study, the researchers used three lasers together to create the oscillating laser beam, but in future work, they hope to use a tunable laser to create the signal and improve the technique even further. This should become more feasible as the price of tunable lasers decreases and they become faster, the researchers say.

To help make fluorescent sensors easier to use in human patients, the researchers are working on sensors that are biologically resorbable, so they would not need to be surgically removed.

The research was funded by the Koch Institute for Integrative Cancer Research and Dana-Farber/Harvard Cancer Center Bridge Project. Additional funding was provided by the Swiss National Science Foundation, the Japan Society for the Promotion of Science, the King Abdullah University of Science and Technology, the Zuckerman STEM Leadership Program, the Israeli Science Foundation, and the Arnold and Mabel Beckman Foundation.

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“The world needs your smarts, your skills,” Ngozi Okonjo-Iweala tells MIT’s Class of 2022

On a clear warm day, the MIT graduating class of 2022 gathered in Killian Court for the first in-person commencement exercises in three years, after two years of online ceremonies due to the Covid-19 pandemic.

Ngozi Okonjo-Iweala MCP ’78, PhD ’81, director-general of the World Trade Organization, delivered the Commencement address, stressing the global need for science-informed policy to address problems of climate change, pandemics, international security, and wealth disparities. She told the graduates: “In these uncertain times, in this complex world in which you are entering, you need not be so daunted, if you can search for the opportunities hidden in challenges.” She urged them to go “into the world to embrace the opportunities to serve.”

An expert in global finance, economics, and international development, Okonjo-Iweala is the first woman and first African to lead the WTO. She earned a master’s degree in city planning from MIT in 1978, and a PhD in regional economics and development in 1981.

Okonjo-Iweala began her address by paying tribute to MIT President L. Rafael Reif, who earlier this semester announced plans to end his decade-long tenure in that role. Calling this a “bittersweet day” because of his departure, she honored “his academic, institutional, and thought leadership of these past 10 years.”

She spoke warmly of the way MIT had helped her while she was a graduate student struggling to pay the bills. She was assured that the Institute would do whatever was needed to make sure she could complete her studies, she recalled, saying, “They had my back.” Noting that this year’s graduating class had their own educational journeys challenged by the global pandemic, she described how her own early education was interrupted for three years by civil war in her home country of Nigeria. She also noted the recent tragic shootings in Uvalde, Texas, saying that “I feel grief as a mother and a grandmother.”

“MIT has helped make me who I am today,” she said. “My parents made it clear to me that education was a privilege, and that with that privilege comes responsibility — the responsibility to use it for others, not just for yourself.”

She said that what the world needs in this time of multiple global challenges, including Covid-19, climate change, public health, and international security, is an approach “combining science, social science, and public policy, to meet the challenges of our future.”

Okonjo-Iweala, who was formerly head of the World Bank, said that “a common thread running through many of these challenges is the central role for science,” and she stressed the need for technological innovation to address the global problems facing humanity. “New inventions and new ways of doing things will have an impact, mainly to the extent they are scaled up across the dividing lines of income and geography,” she said.

“We don't just need vaccines,” she continued. “We need shots in arms across the world, to be safe. We need new renewable technologies diffused not just in rich countries to fight climate change, but also in poor ones. We need new agricultural technologies built to local conditions and culture, if we're to fight hunger. In other words, we need innovation. But we also need access, equity, diffusion.”

In the case of the global response to the pandemic, she noted that only 17 percent of people in Africa and 13 percent of people in low-income countries have been fully vaccinated, compared to 75 percent of people in high income countries. “Since we all know that no one is safe until everyone is safe, the risk of more dangerous variants and pathogens remains real because of this public policy lapse and the lack of timely international cooperation,” she said.

As for climate change, she pointed out that the world somehow managed to come up with $14 trillion to address the Covid-19 pandemic but has not managed to fulfill the pledges nations made to provide $100 billion to help less-developed nations build renewable energy solutions.

To address these global challenges, she told the new graduates, “the world needs your smarts, your skills, your adaptability, and the great training you have received here at MIT. The world needs you for innovation, for policymaking, for connecting the dots so that implementation can actually happen.”

President Reif, in his charge to the graduates, urged the assembled crowd to shout out a loud “thank you!” to all family, professors, friends, and other who helped them reach today’s milestone. He pointed out that research, including from MIT’s Department of Brain and Cognitive Sciences, shows that “simply expressing gratitude does wonderful things to your brain. It gets different parts of your brain to act in a synchronized way. It lights up reward pathways!”

“All of us could use a reliable device for feeling better. So now, thanks to brain science, Course 9, you have one! The Gratitude Amplifier is unbreakable. Its battery never dies, it will never try to sell you anything, you can use it every day, forever — and it’s free!”

He recalled the example of the way students banded together to create a new space for relaxation on campus, now known as the Banana Lounge, a central location where students could relax with free coffee and bananas. “The students have done this all essentially themselves, applying their skills and the most delightful MIT values.” The project has already distributed a half-million bananas, he said, and produced a “wonderful, tropical, perfectly improbable new MIT institution.”

He urged the graduating students to work to “make the world a little more like MIT. More daring and more passionate. More rigorous, inventive and ambitious. More humble, more respectful, more generous, more kind.” And, he added, “try always to share your bananas!”

Adam Joseph “AJ” Miller, president of the Graduate Student Council, said, “Today marks the end of a chapter, the culmination of so many late nights, to forge lifelong friendships, to hold onto new experiences, to shape our dreams.” He added that “Something I heard a lot about when I first got here was all the doubt so many of us had in ourselves. I can say unequivocally today though, there are no impostors before me. Nobody sits where you sit by accident. You're all now graduates of MIT, carrying on an incredibly impressive history.”

Miller urged his fellow students to “stay confident in yourselves because of the challenges you’ve overcome. Be courageous in trying, because failure is learning and investing in each other.”

Temiloluwa Omitoogun, president of the Class of 2022, told his classmates, “MIT is hard. MIT during an unprecedented pandemic is even harder, but we did it. Even if you don’t realize it, this is a huge accomplishment.” He added that “it’s sad that we’re all parting ways at the moment, but I’m even more excited than sad. I’m excited to see what more you all will accomplish. I look out and I don’t just see friends and classmates. I see future leaders, people who will change the world. I’m going to try my best to keep up and change the world too.”

Later in the day, in a separate ceremony on Briggs Field, each of the members of the undergraduate Class of 2022 had a chance to hear their names read aloud as they walked across the stage to receive their diplomas. Right before this presentation, senior and physics and mathematics major Quinn Brodsky performed a heartful rendition of “Hypotheticals” by Lake Street Dive.

Addressing the graduating seniors, Chancellor Melissa Nobles urged them to “absorb and relish this celebration of what you’ve achieved during your transformative time at MIT. How much you have grown, academically, professionally and personally!” She added that “the lifelong friends and mentors you found here are the people who I know will continue to be sources of encouragement, support, and inspiration as you make your way in the world.”

Recalling the way the pandemic altered their academic careers, she said “you should know now that you can handle whatever life throws your way. Never forget that you are stronger and more resilient than you think you are.” She added, “hold on to the way this pandemic has put certain things into perspective. Time with people we care about is precious. So are our health and wellbeing, and the health and wellbeing of the ones we love. Looking out for others and feeling a sense of shared responsibility for the common good are paramount.”

Nobles concluded that “your journey into the future holds countless possibilities, risks, joys, rewards, sometimes failures, and always surprises. … We wish you well on the road ahead.”

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Chancellor Melissa Nobles' Commencement remarks

Below is the text of Chancellor Melissa Nobles' Commencement remarks, as prepared for delivery today.

Thank you, President Reif. And good afternoon everyone! It is wonderful to have the chance to say few words of admiration, gratitude, and, above all, congratulations to our Class of 2022 graduates, and to the family, loved ones, and friends who’ve traveled from near and far to be here for this momentous occasion.

You all know that saying, “be in the moment.” Well, if there was ever a moment to really be in the moment, believe me Class of 2022: This. Is. It.

Take a second and look around you. Breathe in and then exhale. Let all of this soak in so you can recall with clarity the feelings of pure joy and tremendous accomplishment. Absorb and relish this celebration of what you’ve achieved during your transformative time at MIT. How much you have grown – academically, professionally, and personally.

The knowledge you gained and advanced. The challenges you conquered. The strength and resiliency you found. And the deep connections and tightly knit communities you built over the course of your journey. The lifelong friends and mentors you found here are the people who I know will continue to be sources of encouragement, support, and inspiration as you make your way in the world.

Now, what about the people who’ve been by your side, rooting for you and lifting you up from the very start? I’d like to say a word directly to the parents, siblings, grandparents, extended family members, and dear friends who are gathered in the audience or watching the webcast this afternoon.

You have been steadfast in your belief in the Class of 2022 from day one. You’ve demonstrated your belief and support in so many ways – both big and small – over these past two-plus decades. You helped make this moment possible. And for that, I extend my heartfelt thanks to all of you.

I know that we’re all eager to get on to the main event – the awarding of your hard-earned diplomas – so I promise to keep this short and sweet.

When I thought about what I wanted to say to the Class of 2022, I remembered this fact: You are the only class of current students that had finished a full academic year before Covid turned our worlds upside down in March 2020.

Because of this, your MIT experiences and memories are likely grouped into two categories: our “old normal”, pre-Zoom days and our “new normal” – one that, unfortunately, continues to call on us to contend with loss and disruption; frustration and fear; and, if we’re being honest, just plain exhaustion that go hand-in-hand with living during a pandemic.

In the midst of all of this upheaval and uncertainty, the Class of 2022 has persevered and, I imagine, learned a thing or two about yourselves along the way.

For starters, you should now know that you can handle whatever life throws your way. Never forget that you are often stronger and more resilient than you think you are.

And when you’ve needed help, as we all do from time to time, you’ve known to ask for it from others – sometimes from Deans, faculty, staff, coaches, and always, from your fellow students. Because that’s what the MIT student community does for each other. You’ve shown both your individual and collective resiliency time and time again over the past two-plus years.

Hold on to the way that this pandemic has put certain things into perspective. Time with the people we care about is precious. So are our health and wellbeing, and the health and wellbeing of the ones we love. Looking out for others and feeling a sense of shared responsibility for the common good are paramount.

Remember the simple pleasures of casual, spontaneous interactions in the Infinite, The Stud 5, Hayden and Barker Libraries, the Z Center, and, as President Reif spoke about this morning, the Banana Lounge. Recall how badly you all wanted to be back together again on this campus. And always keep this knowledge top of mind: how truly fortunate every single one of us is to have found a home at MIT.

With these lessons in hand (and also in your minds and hearts), we send you out to the world. As you know, there are really big problems out there that we need you all to help solve. We need you to apply your vast scientific, technological, and humanistic knowledge along with your empathy, compassion, and work ethic to the challenges of climate change, human health, social justice, and preserving our democracy, to name just a few. 

The challenges are large and complex, no doubt. But the skills and knowledge that you all have learned here at MIT combined with your intelligence and determination are bigger. And that means that all of you are capable of meeting these challenges.

As your Chancellor – the person who is responsible for helping to educate “The Whole Student” – I am certain that you can and that you will bring your whole selves to discovering, to advancing knowledge, and to creating new technologies – while also creating personal and professional lives that are rich in meaning and humanity. How can I be so sure? Because that’s exactly what you’ve been doing throughout your time here.

Your journey into the future holds countless possibilities, risks, joys, rewards, and surprises. It’s okay to be nervous but please don’t ever doubt your promise, your purpose, or your strength. I know you’ve got this.

For all that you have achieved and contributed, and all that you aspire to be going forward, MIT honors and congratulates you. And we wish you well on the road ahead.

Thank you, and congratulations Class of 2022!

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President L. Rafael Reif’s charge to the Class of 2022

Below is the text of President L. Rafael Reif's Commencement remarks, as prepared for delivery today.

To the graduates of 2022:  Congratulations!  My job today is to deliver a “charge” to you… and I will get to that in a minute. But first, I want to recognize the people who helped you charge this far!

• To everyone who came here this morning, to celebrate our graduates – welcome to MIT! 
   
• To everyone joining us online, from around the world ­– we are so happy you could be with us!
   
• And to the parents and families of today’s graduates, here and everywhere: A huge “Congratulations” to you as well!  This day is the joyful result of your loving support and sacrifice. And for that, you have our deepest respect and admiration.
  
  I also know that a few years ago, many of you may have thought that you had succeeded in sending your offspring away for college or graduate school. But things did not
  turn out exactly that way. So please know how much we appreciate you!

Now, to our new graduates. It has always puzzled me when events like this are referred to as “Commencement Exercises,” because they involve so much sitting down!  So I am going to start with a little something to get our hearts moving.

At MIT, one thing we understand is the importance of distinguishing the signal from the noise.  But sometimes, if the noise is noisy enough, it actually becomes the signal!

We all know that getting through MIT is not a “solo performance.” In fact, it usually takes an orchestra of loving assistance! So I would like each of you to hold in your mind now all the people who helped you along the way: your family, your role models, your professors and teaching assistants, your friends.  In a moment, I hope that, together, we can send them a signal ­– in a very noisy way.

To do that, you will need to say two words, as loud as you can: “Thank you!”  You got it? Just those two words, “Thank you!” OK, now, ready? On the count of three: One, two, three – THANK YOU!

Hmm. You are lucky I had already agreed to grade this Pass/No Record. That first attempt was pretty good, but you can do better. I believe in you!  so I am going to give you another chance.

And this time, let’s try it with your hands up in the air! All the way up!  Now, nice and loud, so it’s even noisy for the people online. OK – one, two, three: THANK YOU!

And thank you right back!

So, why did I ask you to do that? I knew it would create a brief pleasant sensation for the people you love.  But I was also after something deeper. Just ask anyone from Brain and Cognitive Sciences (Course….? That’s right, Course 9!). As anyone from Course 9 can tell you, research indicates that simply expressing gratitude does wonderful things to your brain.

It gets different parts of your brain to act in a synchronized way! It lights up reward pathways!  It even gives you a little shot of dopamine! In other words, expressing gratitude and appreciation for other people is good for our brains – and it is very good for our hearts.

We are living in a difficult and complicated moment in history. All of us could use a reliable device for feeling better.  So now – thanks to brain science! – you have one! The Gratitude Amplifier is unbreakable. Its battery never dies, and it will never try to sell you anything. You can use it every day, forever – and it’s free! It is a graduation present you can take with you anywhere, even if all your moving boxes are already taped shut.

I am so extremely grateful to have all of you here on Killian Court, on this wonderful day, for this tremendously important occasion.

I expect that those of you graduating may come to this day with mixed feelings: with excitement for your next steps, but with the sense that you did not get enough time on campus – time with your professors, and especially with each other.

For that reason, I am particularly grateful that you are here in person. And, looking back, I am also grateful for how much I have learned from members of this class.

I want to focus on one effort that several of today’s graduates helped to lead – an effort to create an antidote to intensity.

We all know that MIT is intense. That is part of why we love it: MIT attracts intense people (like all of you!) – and then we push each other, and we inspire each other, intensely.

But everyone needs a break from the intensity sometimes. Different students find different ways to relieve it – Music! Sports! Ballroom dancing! And some students even find relief by inventing ways to relieve stress for other people.

A few years ago, before the pandemic, a group of students on the Undergraduate Association looked around and concluded that what MIT really needed was a casual place, in the middle of campus, where students could stop, relax, hang out, study if need be and get free food, 24 hours a day.

When a space freed up in Room 26-110, the Banana Lounge was born!

Yes, the Banana Lounge. For those who have not been there yet: The Banana Lounge is a long, sunny room, near the main campus crossroads. It is full of colorful paintings, great big leafy plants, Lego sets, bean-bag chairs – and boxes and boxes of bananas.

Now, as a native of Venezuela, I take certain things very seriously, and one of them is tropical fruit. If they had asked me, it would have been all about mangoes! But of course, with a mango, there is that huge, slippery, ridiculous seed; as the students determined very quickly, the mango simply cannot compete with the elegant engineering of the seedless, self-packaged banana.

In its charming quirkiness, the Banana Lounge is “very MIT.” And it turns out to be “very MIT” in every other way, too.

• The students began with a prototype lounge, tested it in real-world conditions and optimized it for efficiency and comfort.
• They evaluated competing fruit for comparative nutritional content, analyzed alternative supply chains, determined the ideal green/yellow ratio in purchasing and worked to minimize the per-banana unit cost.
• They tracked and calibrated the temperature and humidity of their banana inventory in real time, online, and they established protocols to freeze excess supply and to capture the value
  as banana bread.
• They secured funding from a very generous member of the Class of 1987, Brad Feld (who paid for all of this year’s bananas! Thank you, Brad!)  
• And they developed the cutting-edge concept of “free coffee,” which, in their words, was “critical to stimulating the lounge atmosphere and promoting conversation.”

Already, the lounge has served more than five-hundred-thousand bananas! (Two of which were mine…) And it has generated a very significant number of banana-induced naps as well.

The students have done all this essentially themselves… applying their MIT skills and the most delightful MIT values. They identified an unarticulated problem, dared to try a “crazy” idea, worked incredibly hard – and in the process, they built a wonderful, tropical, perfectly improbable new MIT institution.  

And we could not be more grateful.

So it is in that spirit that I deliver my charge to you. I’m going to use a word that feels very comfortable at MIT – although it has taken on a troubling new meaning elsewhere. But I know that our graduates will know what I mean.

After you depart for your new destinations, I want to ask you to hack the world – until you make the world a little more like MIT: More daring and more passionate. More rigorous, inventive and ambitious. More humble, more respectful, more generous, more kind.

And because the people of MIT also like to fix things that are broken, as you strive to hack the world, please try to heal the world, too.

Our society is like a big, complicated family, in the midst of a terrible argument. I believe that one way to make it better is to find ways to listen to each other with compassion, to focus on achieving our shared objectives and to try constantly to remind each other of our common humanity. I know you will find your own ways to help with this healing, too.

This morning, we share with the world almost thirty-seven-hundred new graduates who are ready for this urgent and timeless problem set. 

You came to MIT with exceptional qualities of your own. And now, after years of focused and intense dedication, you leave us, equipped with a distinctive set of skills and steeped in this community’s deepest values: A commitment to excellence. Integrity. Rising on your own merits. Boldness. Humility. An open spirit of collaboration. A strong desire to make a positive impact. And a sense of responsibility to make the world a better place.

So now, go out there. Join the world. Find your calling. Solve the unsolvable. Invent the future. Take the high road. Try always to share your bananas! And you will continue to make your family, including your MIT family, proud.

On this wonderful day, I am proud of all of you. To every one of the members of the graduating Class of 2022: Congratulations!!!! 

Please accept my best wishes for a happy and successful life and career.

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New gels could help the medicine go down

For most children and even some adults, swallowing pills or tablets is difficult. To make it easier to give those medicines, researchers at MIT and Brigham and Women’s Hospital have created a drug-delivering gel that is much easier to swallow and could be used to administer a variety of different kinds of drugs.

The gels, made from plant-based oils such as sesame oil, can be prepared with a variety of textures, from a thickened beverage to a yogurt-like substance. The gels are stable without refrigeration, which could make them easier to get to children in developing nations, but they could also be beneficial for children anywhere, the researchers say. They could also help adults who have difficulty swallowing pills, such as older people or people who have suffered a stroke.

“This platform will change our capacity for what we can do for kids, and also for adults who have difficulty receiving medication. Given the simplicity of the system and its low cost, it could have a tremendous impact on making it easier for patients to take medications,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.

Traverso and his colleagues showed that they could use the gels to deliver several types of medications for the treatment of infectious disease, in the same doses that can be delivered by pills or tablets, in animal studies. The research team is now planning a clinical trial that is expected to begin within a few months.

Former MIT postdoc Ameya Kirtane, now an instructor at Brigham and Women’s Hospital; MIT postdoc Christina Karavasili; and former technical associate Aniket Wahane are the lead authors of the study, which appears today in Science Advances.

Easy to swallow

Nearly 10 years ago, while working on other kinds of ingestible drug-delivery systems, the research team started to think about new ways to make it easier for children to take medications that are normally given as pills. There are existing strategies that can help with this, but none is a perfect solution. Some antibiotics and other drugs can be suspended in water, but that requires clean water to be available, and the drugs need to be refrigerated after being mixed. Also, this strategy doesn’t work for drugs that are not soluble in water.

With drugs that are only available as pills, health care providers may try to dissolve them in water for children to drink, but that also requires a clean water supply, and the dosages may be difficult to get right if the pills are meant for adults.

To try to address those issues, the researchers set out to develop a new drug-delivery system that would be inexpensive, palatable, stable at extreme temperatures, and compatible with many different drugs. They also wanted to make sure that drugs would not need to be mixed with water before dosing, and that the system could be delivered either orally or as a suppository.

Because they wanted their formulation to work with drugs that can’t be dissolved in water, the researchers decided to focus on oil-based gels. Such gels, also known as oleogels, are commonly used in the food industry to change the texture of oily foods, and also to raise the melting point of chocolate and ice cream.

“That approach gave us the capacity to deliver very hydrophobic drugs that cannot be delivered through water-based systems,” Kirtane says. “It also allowed us to make these formulations with a really wide range of textures.”

The researchers explored several types of plant-derived oils, including sesame oil, cottonseed oil, and flaxseed oil. They combined the oils with edible gelling agents such as beeswax and rice bran wax, and found that they could achieve different textures depending on the concentration and type of oil and gelling agent. Some gels end up with a texture similar to that of a thick beverage, like a protein shake, while others are more like yogurt or pudding.

To identify the gels that were the most palatable, the researchers worked with Sensory Spectrum, a consulting firm that specializes in consumer sensory experiences. Working with the company’s panels of professionally trained tasters, the researchers found that the most appealing gels included those made from oils that had a neutral flavor (such as cottonseed oil) or a slightly nutty flavor (like sesame oil).

Delivering many drugs

The researchers chose to test their gels with three water-insoluble drugs drawn from the World Health Organization’s list of essential medicines for children: praziquantel, used to treat parasitic infections; lumefantrine, used to treat malaria; and azithromycin, used to treat bacterial infections.

“Based on that list, infectious diseases really stood out in terms of what a country needs to protect its children,” Kirtane says. “A lot of the work that we did in this study was focused on infectious disease medications, but from a formulation standpoint, it doesn’t matter what drug we put into these systems.”

For each of those drugs, the researchers found that oleogels were able to deliver doses equal to or higher than the amounts that can be absorbed from tablets, in tests in animals. The researchers also showed that a water-soluble drug, an antibiotic called moxifloxacin hydrochloride, could be successfully delivered by an oleogel.

To make it possible to use these formulations in areas that may not have refrigeration available, the researchers designed them so that they can be stable at 40 degrees Celsius (104 degrees Fahrenheit) for several weeks, and even up to 60 C (140 F) for one week. Such high temperatures are uncommon but could be reached when drugs are being transported by trucks without refrigeration.

The researchers have obtained FDA approval to run a phase I clinical trial of their olegel formulation of azithromycin, which they hope to start running at the Brigham and Women’s Hospital Center for Clinical Investigation within the next few months.

To store and deliver the drugs, the researchers also designed a dispenser similar to a squeezable yogurt package, with compartments that can be used to separate doses. This could make it easier to deliver the right dosage for each child, depending on their weight.

Other authors of the paper include Dylan Freitas, Katelyn Booz, Dao Thi Hong Le, Tiffany Hua, Stephen Scala, Aaron Lopes, Kaitlyn Hess, Joy Collins, Siddharta Tamang, Keiko Ishida, Johannes Kuosmanen, Netra Unni Rajesh, Nhi Phan, Junwei Li, Annlyse Krogmann, Jochen Lennerz, Alison Hayward, and Robert Langer.

The research was funded by the Bill and Melinda Gates Foundation, a PhRMA Foundational postdoctoral fellowship, a Fulbright scholarship, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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New light-powered catalysts could aid in manufacturing

Chemical reactions that are driven by light offer a powerful tool for chemists who are designing new ways to manufacture pharmaceuticals and other useful compounds. Harnessing this light energy requires photoredox catalysts, which can absorb light and transfer the energy to a chemical reaction.

MIT chemists have now designed a new type of photoredox catalyst that could make it easier to incorporate light-driven reactions into manufacturing processes. Unlike most existing photoredox catalysts, the new class of materials is insoluble, so it can be used over and over again. Such catalysts could be used to coat tubing and perform chemical transformations on reactants as they flow through the tube.

“Being able to recycle the catalyst is one of the biggest challenges to overcome in terms of being able to use photoredox catalysis in manufacturing. We hope that by being able to do flow chemistry with an immobilized catalyst, we can provide a new way to do photoredox catalysis on larger scales,” says Richard Liu, an MIT postdoc and the joint lead author of the new study.

The new catalysts, which can be tuned to perform many different types of reactions, could also be incorporated into other materials including textiles or particles.

Timothy Swager, the John D. MacArthur Professor of Chemistry at MIT, is the senior author of the paper, which appears today in Nature Communications. Sheng Guo, an MIT research scientist, and Shao-Xiong Lennon Luo, an MIT graduate student, are also authors of the paper.

Hybrid materials

Photoredox catalysts work by absorbing photons and then using that light energy to power a chemical reaction, analogous to how chlorophyll in plant cells absorbs energy from the sun and uses it to build sugar molecules.

Chemists have developed two main classes of photoredox catalysts, which are known as homogenous and heterogenous catalysts. Homogenous catalysts usually consist of organic dyes or light-absorbing metal complexes. These catalysts are easy to tune to perform a specific reaction, but the downside is that they dissolve in the solution where the reaction takes place. This means they can’t be easily removed and used again.

Heterogenous catalysts, on the other hand, are solid minerals or crystalline materials that form sheets or 3D structures. These materials do not dissolve, so they can be used more than once. However, these catalysts are more difficult to tune to achieve a desired reaction.

To combine the benefits of both of these types of catalysts, the researchers decided to embed the dyes that make up homogenous catalysts into a solid polymer. For this application, the researchers adapted a plastic-like polymer with tiny pores that they had previously developed for performing gas separations. In this study, the researchers demonstrated that they could incorporate about a dozen different homogenous catalysts into their new hybrid material, but they believe it could work more many more.

“These hybrid catalysts have the recyclability and durability of heterogeneous catalysts, but also the precise tunability of homogeneous catalysts,” Liu says. “You can incorporate the dye without losing its chemical activity, so, you can more or less pick from the tens of thousands of photoredox reactions that are already known and get an insoluble equivalent of the catalyst you need.”

The researchers found that incorporating the catalysts into polymers also helped them to become more efficient. One reason is that reactant molecules can be held in the polymer’s pores, ready to react. Additionally, light energy can easily travel along the polymer to find the waiting reactants.

“The new polymers bind molecules from solution and effectively preconcentrate them for reaction,” Swager says. “Also, the excited states can rapidly migrate throughout the polymer. The combined mobility of the excited state and partitioning of the reactants in the polymer make for faster and more efficient reactions than are possible in pure solution processes.”

Higher efficiency

The researchers also showed that they could tune the physical properties of the polymer backbone, including its thickness and porosity, based on what application they want to use the catalyst for.

As one example, they showed that they could make fluorinated polymers that would stick to fluorinated tubing, which is often used for continuous flow manufacturing. During this type of manufacturing, chemical reactants flow through a series of tubes while new ingredients are added, or other steps such as purification or separation are performed.

Currently, it is challenging to incorporate photoredox reactions into continuous flow processes because the catalysts are used up quickly, so they have to be continuously added to the solution. Incorporating the new MIT-designed catalysts into the tubing used for this kind of manufacturing could allow photoredox reactions to be performed during continuous flow. The tubing is clear, allowing light from an LED to reach the catalysts and activate them.

“The idea is to have the catalyst coating a tube, so you can flow your reaction through the tube while the catalyst stays put. In that way, you never get the catalyst ending up in the product, and you can also get a lot higher efficiency,” Liu says.

The catalysts could also be used to coat magnetic beads, making them easier to pull out of a solution once the reaction is finished, or to coat reaction vials or textiles. The researchers are now working on incorporating a wider variety of catalysts into their polymers, and on engineering the polymers to optimize them for different possible applications.

The research was funded by the National Science Foundation and the KAUST Sensor Initiative.

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Chemists reveal how tau proteins form tangles

One of the hallmarks of Alzheimer’s disease is the presence of neurofibrillary tangles in the brain. These tangles, made of tau proteins, impair neurons’ ability to function normally and can cause the cells to die.

A new study from MIT chemists has revealed how two types of tau proteins, known as 3R and 4R tau, mix together to form these tangles. The researchers found that the tangles can recruit any tau protein in the brain, in a nearly random way. This feature may contribute to the prevalence of Alzheimer’s disease, the researchers say.

“Whether the end of an existing filament is a 3R or 4R tau protein, the filament can recruit whichever tau version is in the environment to add onto the growing filament. It is very advantageous for the Alzheimer’s disease tau structure to have that property of randomly incorporating either version of the protein,” says Mei Hong, an MIT professor of chemistry.

Hong is the senior author of the study, which appears today in Nature Communications. MIT graduate student Aurelio Dregni and postdoc Pu Duan are the lead authors of the paper.

Molecular mixing

In the healthy brain, tau functions as a stabilizer of microtubules in neurons. Each tau protein is made up of either three or four “repeats,” each consisting of 31 amino acid residues. Abnormal versions of either 3R or 4R tau proteins can contribute to a variety of diseases.

Chronic traumatic encephalopathy, caused by repetitive head trauma, is linked to abnormal accumulation of both 3R and 4R tau proteins, similar to Alzheimer’s disease. However, most other neurodegenerative diseases that involve tau feature abnormal versions of either 3R or 4R proteins, but not both.

In Alzheimer’s disease, tau proteins begin to form tangles in response to chemical modifications of the proteins that interfere with their normal function. Each tangle consists of long filaments of 3R and 4R tau proteins, but it wasn’t known exactly how the proteins combine at the molecular level to generate these long filaments.

One possibility that Hong and her colleagues considered was that the filaments might be made of alternating blocks of many 3R tau proteins or many 4R tau proteins. Or, they hypothesized, individual molecules of 3R and 4R tau might alternate.

The researchers set out to explore these possibilities using nuclear magnetic resonance (NMR) spectroscopy. By labeling 3R and 4R tau proteins with carbon and nitrogen isotopes that can be detected with NMR, the researchers were able to calculate the probabilities that each 3R tau protein is followed by a 4R tau and that each 4R tau is followed by a 3R tau protein in a filament.

To produce their filaments, the researchers began with abnormal tau proteins taken from postmortem brain samples from Alzheimer’s patients. These “seeds” were added to a solution containing equal concentrations of normal 3R and 4R tau proteins, which were recruited by the seeds to form long filaments.

To the researchers’ surprise, their NMR analysis showed that the assembly of these 3R and 4R tau proteins in these seeded filaments was nearly random. A 4R tau was about 40 percent likely to be followed by a 3R tau, while a 3R tau was a little more than 50 percent likely to be followed by a 4R tau. Overall, 4R proteins made up 60 percent of the Alzheimer’s disease tau filament, even though the pool of available tau proteins was evenly divided between 3R and 4R. Within the human brain, 3R and 4R tau proteins are also found in roughly equal amounts.

This type of assembly, which the researchers call “fluent molecular mixing,” may contribute to the prevalence of Alzheimer’s disease, compared to diseases that involve only 4R or 3R tau proteins, Hong says.

“Our interpretation is that this would favor the spread and the growth of the toxic Alzheimer’s disease tau conformation,” she says.

Toxic effects

Working with collaborators at the University of Pennsylvania School of Medicine, led by Professor Virginia Lee, the researchers showed that the tau filaments they generated in the lab have a structure very similar to those seen in human patients with Alzheimer’s disease, but they do not resemble filaments grown exclusively from normal tau proteins.

The tau filaments that they generated also replicated the toxic effects of Alzheimer’s tangles, forming aggregates in the dendrites and axons of mouse neurons grown in a lab dish.

The current paper focused mainly on the structure of the rigid inner core of the filaments, but the researchers now hope to further study the structure of the floppier protein segments that extend out from this core. “We would like to figure out just how this protein goes from a healthy and intrinsically disordered state to this toxic, misfolded, and beta-sheet rich state in Alzheimer’s disease brains,” Hong says.

The research was funded by the National Institutes of Health and the BrightFocus Foundation.

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Frank Wilczek receives 2022 Templeton Prize

Nobel Prize-winning theoretical physicist and author Frank Wilczek, the Herman Feshbach Professor of Physics at MIT, has been awarded the 2022 Templeton Prize. This prize is awarded to individuals whose life’s work embodies a fusion of science and spirituality.

“He is one of those rare and wonderful individuals who bring together a keen, creative intellect and an appreciation for transcendent beauty,” says Heather Templeton Dill, president of the John Templeton Foundation, in the foundation’s press release. “Like Isaac Newton and Albert Einstein, he is a natural philosopher who unites a curiosity about the behavior of nature with a playful and profound philosophical mind.” 

Wilczek won the 2004 Nobel Prize in Physics, along with David Gross and David Politzer, for their 1973 discovery of asymptotic freedom in the theory of the strong interaction. Other achievements in physics include proposing a leading explanation for dark matter, the invention of axions, and the discovery and exploitation of new forms of quantum statistics (anyons). 

He has written several popular books, including “A Beautiful Question” (2015) and “The Lightness of Being” (2008). With his wife, Betsy Devine, he wrote “Longing for the Harmonies” (1988).

In his most recent book, “Fundamentals” (2021), Wilczek presents a set of 10 insights drawn from physics and harmonized with artistic and philosophical sources to illuminate characteristics of physical reality.

He is also a columnist for the Wall Street Journal, where he discusses scientific subjects for a broad readership. For his contributions to Physics Today and to Nature, where he explains topics at the frontiers of physics to wider scientific audiences, he received the Lilienfeld Prize of the American Physical Society.  

“The intent of the Templeton Prize is noble and timely, and something the world needs, which is to bring attention to the possibility of new approaches to the problems or situations or challenges that people have traditionally accessed through religion, and many people still do,” he says in his video statement for the Templeton Prize. “The central miracle of physics to me is the fact that by playing with equations, drawing diagrams, doing calculations, and working within the world of mental concepts and manipulations, you are actually describing the real world. If you were looking for trying to understand what God is by understanding God's work, that's it.” 

Wilczek joined MIT in 2000 with appointments in the Department of Physics and the Center for Theoretical Physics. “I feel that MIT, through its unique atmosphere of scientific engagement with the world and its willingness to accommodate my sometimes unusual explorations, has helped me to thrive,” Wilczek says. 

Wilczek received a BS at the University of Chicago in 1970, and a PhD in physics at Princeton University in 1974. He taught at Princeton from 1974 to 1981. From 1981 to 1988, he was the Chancellor Robert Huttenback Professor of Physics at the University of California at Santa Barbara, and the first permanent member of the National Science Foundation’s Institute for Theoretical Physics. With the Institute for Advanced Study, he was the J.R. Oppenheimer Professor until 2000. Since 2002, he has been an adjunct professor in the Centro de Estudios Científicos of Valdivia, Chile.

He is also founding director of the T.D. Lee Institute and chief scientist at Wilczek Quantum Center at Shanghai Jiao Tong University; distinguished professor at Arizona State University; and professor at Stockholm University.

Wilczek has been a Sloan Foundation Fellow (1975–77) and a MacArthur Foundation Fellow (1982–87). He has received UNESCO’s Dirac Medal, the American Physical Society’s Sakurai Prize, the Michelson Prize from Case Western University, and the Lorentz Medal of the Netherlands Academy for his contributions to the development of theoretical physics. In 2004 he received the King Faisal Prize. He is a member of the National Academy of Sciences, the Netherlands Academy of Sciences, and the American Academy of Arts and Sciences, and is a trustee of the University of Chicago.

“Throughout Dr. Wilczek’s philosophical reflections, there is a spiritual quality to his ideas,” says Templeton Dill. “By uncovering a remarkable order in the natural world, Dr. Wilczek has come to appreciate different ways of thinking about reality, and through his written work, he has invited all of us to join him in the quest for understanding.”  

As the 2022 Templeton Prize laureate, Wilczek will participate in several virtual and in-person events, including a 2022 Templeton Prize event in the fall, where he will deliver a Templeton Prize lecture.

Wilczek is the sixth Nobel laureate to receive the Templeton Prize since its inception in 1972 and joins a list of 51 prize recipients including St. Teresa of Kolkata, the Dalai Lama, Archbishop Desmond Tutu, and last year’s prize winner, Jane Goodall.    

The Templeton Prize, valued at more than $1.3 million, was established by the late global investor and philanthropist Sir John Templeton to honor those who harness the power of the sciences to explore the deepest questions of the universe and humankind’s place and purpose within it.

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Congressional seminar introduces MIT faculty to 30 Washington staffers

More than 30 congressional and executive branch staffers were hosted by MIT’s Security Studies Program (SSP) for a series of panels and a keynote address focused on contemporary national security issues. 

Organized by the Security Studies Program, the Executive Branch and Congressional Staff Seminar was held from Wednesday, April 20m to Friday, April 22, in Cambridge, Massachusetts. The program, supported by a generous grant from the Raymond Frankel Foundation, is hosted by MIT every other year to encourage interaction and exchange between scholars studying national security and policymakers.

Staff members from the U.S. House of Representatives, the Senate, and the Congressional Research Service were joined by more than 15 MIT SSP faculty members and research affiliates. Each of them is an expert on one of a broad range of topics, from China’s ambitions to great-power competition.

This year’s program included a guided tour of the MIT Lincoln Laboratory in Lexington, Massachusetts, four intensive panels with SSP faculty and affiliates, and a keynote address by Admiral John Richardson, the former chief of naval operations.

Keynote address

In his address, Richardson argued the United States is facing two simultaneous revolutions that have the potential to reshape the world. First, a political revolution of rising powers is returning the world to multipolarity and spreading authoritarianism. Second, a technological revolution of interconnected new technologies, from artificial intelligence to quantum computing, promises not only to increase speed and efficiency, but also to allow for entirely new capabilities. 

Richardson compared the current moment to two points in history: the turn of the 19th century and the beginning of the Cold War. In both periods, he said, the United States faced intertwined political and technological revolutions. 

In each case, he said, the U.S. and its allies prevailed. This success was won in both the political and technological spheres. 

In those areas, there was a sense of existential urgency that enabled a more adaptable and learning-based approach to the rapid changes of the Cold War, he said. In the end, the United States benefited from a coherent strategy to address worldwide changes.

The current challenges, Richardson said, demand a similar sense of urgency, adaptability, and learning if the U.S. is to prevail in preserving its influence in the world, and its quality of life.

The changing international order

During a panel on the “Changing International Order,” staffers heard from Ford International Professor of Political Science Barry Posen, SSP Senior Advisor Carol Saivetz, and Jonathan Kirshner, a professor of political science and international studies at Boston College.

Posen focused his remarks on Russia and China’s growing power relative to the United States, in the context of the 2008 financial crisis, the Covid-19 pandemic, and the war in Ukraine. Kirshner identified the domestic politics of key participants in the international order, especially domestic dysfunction in the United States, as the chief driver of change. Saivetz offered several hypotheses on the cause of Russia’s invasion of Ukraine, which include pushing back against the expansion of NATO and the European Union, the desire for great power status, concerns about a liberal democracy on its borders, and the influence of the Russian Orthodox Church.

New tools of statecraft

A panel on “New Tools of Statecraft” featured remarks by Richard Nielsen, associate professor of political science at MIT, Mariya Grinberg, assistant professor of political science at MIT, and Joel Brenner, senior advisor to MIT SSP. MIT’s R. David Edelman, director of the Project on Technology, Economy and National Security and Computer Science and Artificial Intelligence Laboratory affiliate, chaired the panel.

Nielsen discussed the role of U.S. influence in a world beset by misinformation. He emphasized that the internet is more fragmented than it has ever been, and America’s ability to shape people’s opinions through the internet is extremely limited. Grinberg, an expert on conflict economies, addressed what policy changes are necessary — and what policy changes were unnecessary — in response to the Covid-19 pandemic’s effects on markets. Brenner observed that many existing tools of statecraft are not “new,” but the speed, coordination, and synchronization of tools is new, as demonstrated by both the Russians and the Ukrainians in the ongoing war.

China’s growing ambitions

A panel on “China’s Growing Ambitions” featured remarks by MIT SSP director and Arthur and Ruth Sloan Professor of Political Science M. Taylor Fravel along with two SSP alumni: Joseph Torigian PhD '16, an assistant professor with the School of International Service at American University, and Fiona Cunningham PhD '18, an assistant professor of political science at the University of Pennsylvania.

Torigian suggested that Chinese General Secretary Xi Jinping’s views are likely a balance between pursuing the Communist Party’s ideals and mission with a deep skepticism of radical policies, and the kind of leftism and radicalism associated with events such as the Cultural Revolution. Xi is ideological, he said, but is flexible. Cunningham spoke broadly on China’s ambitions, and concluded with an argument that the U.S. needs to do more work to implement a more competitive Indo-Pacific policy, especially in terms of trade, and that U.S. officials should work to protect and strengthen existing channels of communication so that they can be functional in a crisis. Fravel discussed recent military changes in China. He noted that China adopted a new military strategy in 2019, which identifies the U.S. and Taiwan as principal adversaries, but stated that this was fundamentally not much more than top-level cosmetic changes to the 2014 military strategy in order to help cement Xi’s role as a military leader. 

The new nuclear era

The “New Nuclear Era” panel featured three MIT faculty and affiliates: Senior Research Associate Jim Walsh, Principal Research Scientist Eric Heginbotham, and Caitlin Talmadge PhD '11, an associate professor with the School of Foreign Service at Georgetown University and an SSP alumna.

Heginbotham discussed the increasing number and variety of roles that nuclear weapons play in international affairs, emphasizing how multipolarity and nuclear proliferation create “nested security dilemmas.” Talmadge similarly highlighted the complexity of the deterrence environment with multiple, multi-sided nuclear competitions occurring at once. Walsh framed the war in Ukraine as a reminder of nuclear danger that motivates the public both to “hug nuclear weapons more closely in a more dangerous world” and to “reduce nuclear danger before unimaginably bad things happen.”

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Magma beneath tectonic collision zones is wetter than previously thought

A new study by geologists at the Woods Hole Oceanographic Institution (WHOI), MIT, and elsewhere has found that colliding continental plates may draw down more water than previously thought. The results could help to explain the explosiveness of some volcanic eruptions, as well as the distribution of ore deposits such as copper, silver, and gold.

The findings are based on an analysis of ancient magmatic rocks recovered from the Himalayan mountains — a geologic formation that is the product of a subduction zone, where two massive tectonic plates have crushed against each other, one plate sliding beneath the other over millions of years.

Subduction zones can be found around the world. As one tectonic plate slides beneath another, it can take ocean water with it, drawing it deep into the mantle, where the liquid can merge with rising magma. The more water magma contains, the more explosive an eruption may be. Subduction zones therefore are the sites of some of the strongest and most destructive volcanic eruptions in the world.

Their analysis, published today in Nature Geoscience, finds that magma at subduction zones, or “arc magmas,” can contain up to 20 percent water content by weight — about double the maximum water content that has been widely assumed. The new estimate suggests that subduction zones draw down more water than previously thought, and that arc magmas are “super-hydrous,” and much wetter than scientists had estimated.

The study’s authors include lead author Ben Urann PhD ’21, who was a graduate student in the MIT-WHOI Joint Program at the time of the study (now at the University of Wyoming); Urann’s PhD advisor Véronique Le Roux of WHOI and the MIT-WHOI Joint Program; Oliver Jagoutz, professor of geology in MIT’s Department of Earth, Atmospheric and Planetary Sciences; Othmar Müntener of the University of Lausanne in Switzerland; Mark Behn of Boston College; and Emily Chin of Scripps Institution of Oceanography.

Deep bends

Previously, estimating the amount of water drawn down in subduction zones was done by analyzing volcanic rocks that have erupted to the surface. Scientists measured signatures of water in these rocks and then reconstructed the rocks’ original water content, when they first absorbed the liquid as magma, deep beneath the Earth’s crust. These estimates suggested that magma contains about 4 percent water by weight on average.

But Urann and Le Roux questioned these analyses: What if there are processes the rising magma undergoes that affect the original water content in a way that scientists did not anticipate?

“The question was, are these rocks that rose quickly and erupted representative of what’s really going on down deep, or is there some surface process that skews those numbers?” Urann says.

Taking a different approach, the team looked to ancient magmatic rocks called plutons, that remained deep beneath the surface, never having erupted in the first place. These rocks, they reasoned, would be more pristine recorders of the water they originally absorbed.

Urann and Le Roux developed new analytical methods by secondary ion mass spectrometry at WHOI to analyze water in plutons collected previously by Jagoutz and Müntener in the Kohistan arc — a region of the western Himalayan mountains comprising a large geologic section of rock that crystallized long ago. This material was subsquentally upheaved to the surface, exposing layers of preserved, unerupted plutons, or magmatic rock.

“These are incredibly fresh rocks,” Urann says. “There is no evidence of the rocks’ crystals being disturbed in any way, so that was the driver for using these samples.”

Urann and Le Roux selected the freshest samples and analyzed them for signs of water. They combined water measurements with the composition of minerals in each crystal and plugged these numbers into an equation to back-calculate the amount of water that must have been absorbed originally by magma, just before it crystallized into its rock form.

In the end, their calculations revealed that the arc magmas contained an original water content of more than 8 percent by weight.

The team’s new estimates may help to explain why volcanic eruptions in some parts of the world are stronger and more explove than others.

“This water content is key to understanding why arc magmas are more explosive,” says Cin-Ty Lee, professor of geology at Rice University who was not involved in the research. “The water content of arc magmas is a bit of a mystery because it’s so hard to reconstruct original water content. Most of the community uses [erupted volcanic rock], but they are far removed from their deep sources. So, if you can go straight to the mantle, that is the way to go. The [rocks in the current study] are as close as one can get.”

The results also may point to locations in the world where ore deposits — and high concentrations of copper, silver and gold — might be found.

“These deposits are thought to form from magmatic fluids — fluids which have separated from the initial magma, which carry copper and other metals in solution,” Urann says. “The problem has always been that these deposits require a lot of water to form — more than you get from magmas with 4 percent water content. Our study shows that super-hydrous magmas are prime candidates to form economic ore deposits.”

This research was supported by the the National Science Foundation and the Woods Hole Oceanographic Institution Ocean Venture Fund.

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Congratulations, Class of 2022!

What have this year’s graduates gained from MIT? As Commencement nears, some say: “Courage in tackling the unknown.” “Selective ambition.” “I am better at failing and recovering.” “I no longer strive for perfection.” “I can do so much more.”

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Virtual worlds apart

What is virtual reality? On a technical level, it is a headset-enabled system using images and sounds to make the user feel as if they are in another place altogether. But in terms of the content and essence of virtual reality — well, that may depend on where you are.

In the U.S., for instance, virtual reality (VR) has its deep roots as a form of military training technology. Later it took on a “techno-utopian” air when it started getting more attention in the 1980s and 1990s, as MIT Professor Paul Roquet observes in a new book about the subject. But in Japan, virtual reality has become heavily oriented around “isekai,” or “other world” fantasies, including scenarios where the VR user enters a portal to another world and must find their way back.

“Part of my goal, in pulling out these different senses of virtual reality, is that it can mean different things in different parts of the world, and is changing a lot over time,” says Roquet, an associate professor of media studies and Japan studies in MIT’s Comparative Media Studies/Writing program.

As such, VR constitutes a useful case study in the interactions of society and technology, and the way innovations can evolve in relation to the cultures that adopt them. Roquet details these differences in the new book, “The Immersive Enclosure: Virtual reality in Japan,” published this week by Columbia University Press.

Different lineages

As Roquet notes in the book, virtual reality has a lengthy lineage of precursor innovations, dating at least to early 20th-century military flight simulators. A 1960s stereoscopic arcade machine, the Sensorama, is regarded as the first commercial VR device. Later in the decade, Ivan Sutherland, a computer scientist with an MIT PhD, developed a pioneering computerized head-mounted display.

By the 1980s in the U.S., however, virtual reality, often linked with technologist Jaron Lanier, had veered off in a different direction, being cast as a liberatory tool, “more pure than what came before,” as Roquet puts it. He adds: “It goes back to the Platonic ideal of the world that can be separated from everyday materiality. And in the popular imagination, VR becomes this space where we can fix things like sexism, racism, discrimination, and inequality. There’s a lot of promises being made in the U.S. context.”

In Japan, though, VR has a different trajectory. Partly because Japan’s postwar constitution prohibited most military activities, virtual reality developed more in relation to forms of popular entertainment such as manga, anime, and video games. Roquet believes its Japanese technological lineage also includes the Sony Walkman, which created private space for media consumption.

“It’s going in different directions,” Roquet says. “The technology moves away from the kind of military and industrial uses promised in the U.S.”

As Roquet details in the book, different Japanese phrases for virtual reality reflect this. One term, “bacharu riariti,” reflects the more idealistic notion that a virtual space could functionally substitute for a real one; another, “kaso genjitsu,” situates virtual reality more as entertainment where the “feeling matters as much as technology itself.”

The actual content of VR entertainment can vary, from multiplayer battle games to other kinds of fantasy-world activities. As Roquet examines in the book, Japanese virtual reality also has a distinct gender profile: One survey in Japan showed that 87 percent of social virtual reality users were male, but 88 percent of them were embodying female lead characters, and not necessarily in scenarios that are empowering to women. Men are thus “everywhere in control yet nowhere to be seen,” Roquet writes, while “covertly reinscribing gender norms.”

A rather different potential application for virtual reality is telework. As Roquet also details, considerable research has been applied to the idea of using VR to control robots for use in numerous settings, from health care to industrial tasks. This is something Japanese technologists share with, say, Mark Zuckerberg of Meta, whose company has become the leading U.S. backer of virtual reality.

“It’s not so much that there’s an absolute divide [between the U.S. and Japan], Roquet says; instead, he notes, there is a different emphasis in terms of “what virtual reality is about.”

What escapism cannot escape

Other scholars have praised “The Immersive Enclosure.” Yuriko Furuhata, an associate professor at McGill University, has called the book “a refreshing new take on VR  as a consumer technology.” James J. Hodge, an associate professor at Northwestern University, has called the book “a must-read for scholars in media studies and general readers alike fascinated by the flawed revolutionary potential of VR.”

Ultimately, as Roquet concludes as the end of the book, virtual reality still faces key political, commercial, and social questions. One of them, he writes, is “how to envision a VR future governed by something other than a small set of corporate landlords and the same old geopolitical struggles.” Another, as the book notes, is “what it means for a media interface to assert control over someone’s spatial awareness.”

In both matters, that means understanding virtual reality — and technology broadly — as it gets shaped by society. Virtual reality may often present itself as a form of escapism, but there is no escaping the circumstances in which it has been developed and refined.

“You can create a space that’s outside of the social world, but it ends up being highly shaped by whoever is doing the creation,” Roquet says.

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