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    Search algorithm reveals nearly 200 new kinds of CRISPR systems

    Microbial sequence databases contain a wealth of information about enzymes and other molecules that could be adapted for biotechnology. But these databases have grown so large in recent years that they’ve become difficult to search efficiently for enzymes of interest.

    Now, scientists at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health have developed a new search algorithm that has identified 188 kinds of new rare CRISPR systems in bacterial genomes, encompassing thousands of individual systems. The work appears today in Science.

    The algorithm, which comes from the lab of pioneering CRISPR researcher Professor Feng Zhang, uses big-data clustering approaches to rapidly search massive amounts of genomic data. The team used their algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust) to mine three major public databases that contain data from a wide range of unusual bacteria, including ones found in coal mines, breweries, Antarctic lakes, and dog saliva. The scientists found a surprising number and diversity of CRISPR systems, including ones that could make edits to DNA in human cells, others that can target RNA, and many with a variety of other functions.

    The new systems could potentially be harnessed to edit mammalian cells with fewer off-target effects than current Cas9 systems. They could also one day be used as diagnostics or serve as molecular records of activity inside cells.

    The researchers say their search highlights an unprecedented level of diversity and flexibility of CRISPR and that there are likely many more rare systems yet to be discovered as databases continue to grow.

    “Biodiversity is such a treasure trove, and as we continue to sequence more genomes and metagenomic samples, there is a growing need for better tools, like FLSHclust, to search that sequence space to find the molecular gems,” says Zhang, a co-senior author on the study and the James and Patricia Poitras Professor of Neuroscience at MIT with joint appointments in the departments of Brain and Cognitive Sciences and Biological Engineering. Zhang is also an investigator at the McGovern Institute for Brain Research at MIT, a core institute member at the Broad, and an investigator at the Howard Hughes Medical Institute. Eugene Koonin, a distinguished investigator at the NCBI, is co-senior author on the study as well.

    Searching for CRISPR

    CRISPR, which stands for clustered regularly interspaced short palindromic repeats, is a bacterial defense system that has been engineered into many tools for genome editing and diagnostics.

    To mine databases of protein and nucleic acid sequences for novel CRISPR systems, the researchers developed an algorithm based on an approach borrowed from the big data community. This technique, called locality-sensitive hashing, clusters together objects that are similar but not exactly identical. Using this approach allowed the team to probe billions of protein and DNA sequences — from the NCBI, its Whole Genome Shotgun database, and the Joint Genome Institute — in weeks, whereas previous methods that look for identical objects would have taken months. They designed their algorithm to look for genes associated with CRISPR.

    “This new algorithm allows us to parse through data in a time frame that’s short enough that we can actually recover results and make biological hypotheses,” says Soumya Kannan PhD ’23, who is a co-first author on the study. Kannan was a graduate student in Zhang’s lab when the study began and is currently a postdoc and Junior Fellow at Harvard University. Han Altae-Tran PhD ’23, a graduate student in Zhang’s lab during the study and currently a postdoc at the University of Washington, was the study’s other co-first author.

    “This is a testament to what you can do when you improve on the methods for exploration and use as much data as possible,” says Altae-Tran. “It’s really exciting to be able to improve the scale at which we search.”

    New systems

    In their analysis, Altae-Tran, Kannan, and their colleagues noticed that the thousands of CRISPR systems they found fell into a few existing and many new categories. They studied several of the new systems in greater detail in the lab.

    They found several new variants of known Type I CRISPR systems, which use a guide RNA that is 32 base pairs long rather than the 20-nucleotide guide of Cas9. Because of their longer guide RNAs, these Type I systems could potentially be used to develop more precise gene-editing technology that is less prone to off-target editing. Zhang’s team showed that two of these systems could make short edits in the DNA of human cells. And because these Type I systems are similar in size to CRISPR-Cas9, they could likely be delivered to cells in animals or humans using the same gene-delivery technologies being used today for CRISPR.

    One of the Type I systems also showed “collateral activity” — broad degradation of nucleic acids after the CRISPR protein binds its target. Scientists have used similar systems to make infectious disease diagnostics such as SHERLOCK, a tool capable of rapidly sensing a single molecule of DNA or RNA. Zhang’s team thinks the new systems could be adapted for diagnostic technologies as well.

    The researchers also uncovered new mechanisms of action for some Type IV CRISPR systems, and a Type VII system that precisely targets RNA, which could potentially be used in RNA editing. Other systems could potentially be used as recording tools — a molecular document of when a gene was expressed — or as sensors of specific activity in a living cell.

    Mining data

    The scientists say their algorithm could aid in the search for other biochemical systems. “This search algorithm could be used by anyone who wants to work with these large databases for studying how proteins evolve or discovering new genes,” Altae-Tran says.

    The researchers add that their findings illustrate not only how diverse CRISPR systems are, but also that most are rare and only found in unusual bacteria. “Some of these microbial systems were exclusively found in water from coal mines,” Kannan says. “If someone hadn’t been interested in that, we may never have seen those systems. Broadening our sampling diversity is really important to continue expanding the diversity of what we can discover.”

    This work was supported by the Howard Hughes Medical Institute; the K. Lisa Yang and Hock E. Tan Molecular Therapeutics Center at MIT; Broad Institute Programmable Therapeutics Gift Donors; The Pershing Square Foundation, William Ackman and Neri Oxman; James and Patricia Poitras; BT Charitable Foundation; Asness Family Foundation; Kenneth C. Griffin; the Phillips family; David Cheng; and Robert Metcalfe. More

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    Rewarding excellence in open data

    The second annual MIT Prize for Open Data, which included a $2,500 cash prize, was recently awarded to 10 individual and group research projects. Presented jointly by the School of Science and the MIT Libraries, the prize highlights the value of open data — research data that is openly accessible and reusable — at the Institute. The prize winners and 12 honorable mention recipients were honored at the Open Data @ MIT event held Oct. 24 at Hayden Library. 

    Conceived by Chris Bourg, director of MIT Libraries, and Rebecca Saxe, associate dean of the School of Science and the John W. Jarve (1978) Professor of Brain and Cognitive Sciences, the prize program was launched in 2022. It recognizes MIT-affiliated researchers who use or share open data, create infrastructure for open data sharing, or theorize about open data. Nominations were solicited from across the Institute, with a focus on trainees: undergraduate and graduate students, postdocs, and research staff. 

    “The prize is explicitly aimed at early-career researchers,” says Bourg. “Supporting and encouraging the next generation of researchers will help ensure that the future of scholarship is characterized by a norm of open sharing.”

    The 2023 awards were presented at a celebratory event held during International Open Access Week. Winners gave five-minute presentations on their projects and the role that open data plays in their research. The program also included remarks from Bourg and Anne White, School of Engineering Distinguished Professor of Engineering, vice provost, and associate vice president for research administration. White reflected on the ways in which MIT has demonstrated its values with the open sharing of research and scholarship and acknowledged the efforts of the honorees and advocates gathered at the event: “Thank you for the active role you’re all playing in building a culture of openness in research,” she said. “It benefits us all.” 

    Winners were chosen from more than 80 nominees, representing all five MIT schools, the MIT Schwarzman College of Computing, and several research centers across the Institute. A committee composed of faculty, staff, and graduate students made the selections:

    Hammaad Adam, graduate student in the Institute for Data, Systems, and Society, accepted on behalf of the team behind Organ Retrieval and Collection of Health Information for Donation (ORCHID), the first ever multi-center dataset dedicated to the organ procurement process. ORCHID provides the first opportunity to quantitatively analyze organ procurement organization decisions and identify operational inefficiencies.
    Adam Atanas, postdoc in the Department of Brain and Cognitive Sciences (BCS), and Jungsoo Kim, graduate student in BCS, created WormWideWeb.org. The site, allowing researchers to easily browse and download C. elegans whole-brain datasets, will be useful to C. elegans neuroscientists and theoretical/computational neuroscientists. 
    Paul Berube, research scientist in the Department of Civil and Environmental Engineering, and Steven Biller, assistant professor of biological sciences at Wellesley College, won for “Unlocking Marine Microbiomes with Open Data.” Open data of genomes and metagenomes for marine ecosystems, with a focus on cyanobacteria, leverage the power of contemporaneous data from GEOTRACES and other long-standing ocean time-series programs to provide underlying information to answer questions about marine ecosystem function. 
    Jack Cavanagh, Sarah Kopper, and Diana Horvath of the Abdul Latif Jameel Poverty Action Lab (J-PAL) were recognized for J-PAL’s Data Publication Infrastructure, which includes a trusted repository of open-access datasets, a dedicated team of data curators, and coding tools and training materials to help other teams publish data in an efficient and ethical manner. 
    Jerome Patrick Cruz, graduate student in the Department of Political Science, won for OpenAudit, leveraging advances in natural language processing and machine learning to make data in public audit reports more usable for academics and policy researchers, as well as governance practitioners, watchdogs, and reformers. This work was done in collaboration with colleagues at Ateneo de Manila University in the Philippines. 
    Undergraduate student Daniel Kurlander created a tool for planetary scientists to rapidly access and filter images of the comet 67P/Churyumov-Gerasimenko. The web-based tool enables searches by location and other properties, does not require a time-intensive download of a massive dataset, allows analysis of the data independent of the speed of one’s computer, and does not require installation of a complex set of programs. 
    Halie Olson, postdoc in BCS, was recognized for sharing data from a functional magnetic resonance imaging (fMRI) study on language processing. The study used video clips from “Sesame Street” in which researchers manipulated the comprehensibility of the speech stream, allowing them to isolate a “language response” in the brain.
    Thomas González Roberts, graduate student in the Department of Aeronautics and Astronautics, won for the International Telecommunication Union Compliance Assessment Monitor. This tool combats the heritage of secrecy in outer space operations by creating human- and machine-readable datasets that succinctly describe the international agreements that govern satellite operations. 
    Melissa Kline Struhl, research scientist in BCS, was recognized for Children Helping Science, a free, open-source platform for remote studies with babies and children that makes it possible for researchers at more than 100 institutions to conduct reproducible studies. 
    JS Tan, graduate student in the Department of Urban Studies and Planning, developed the Collective Action in Tech Archive in collaboration with Nataliya Nedzhvetskaya of the University of California at Berkeley. It is an open database of all publicly recorded collective actions taken by workers in the global tech industry. 
    A complete list of winning projects and honorable mentions, including links to the research data, is available on the MIT Libraries website. More

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    Summer research offers a springboard to advanced studies

    Doctoral studies at MIT aren’t a calling for everyone, but they can be for anyone who has had opportunities to discover that science and technology research is their passion and to build the experience and skills to succeed. For Taylor Baum, Josefina Correa Menéndez, and Karla Alejandra Montejo, three graduate students in just one lab of The Picower Institute for Learning and Memory, a pivotal opportunity came via the MIT Summer Research Program in Biology and Neuroscience (MSRP-Bio). When a student finds MSRP-Bio, it helps them find their future in research. 

    In the program, undergraduate STEM majors from outside MIT spend the summer doing full-time research in the departments of Biology, Brain and Cognitive Sciences (BCS), or the Center for Brains, Minds and Machines (CBMM). They gain lab skills, mentoring, preparation for graduate school, and connections that might last a lifetime. Over the last two decades, a total of 215 students from underrepresented minority groups, who are from economically disadvantaged backgrounds, first-generation or nontraditional college students, or students with disabilities have participated in research in BCS or CBMM labs.  

    Like Baum, Correa Menéndez, and Montejo, the vast majority go on to pursue graduate studies, says Diversity and Outreach Coordinator Mandana Sassanfar, who runs the program. For instance, among 91 students who have worked in Picower Institute labs, 81 have completed their undergraduate studies. Of those, 46 enrolled in PhD programs at MIT or other schools such as Cornell, Yale, Stanford, and Princeton universities, and the University of California System. Another 12 have gone to medical school, another seven are in MD/PhD programs, and three have earned master’s degrees. The rest are studying as post-baccalaureates or went straight into the workforce after earning their bachelor’s degree. 

    After participating in the program, Baum, Correa Menéndez, and Montejo each became graduate students in the research group of Emery N. Brown, the Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering in The Picower Institute and the Institute for Medical Engineering and Science. The lab combines statistical, computational, and experimental neuroscience methods to study how general anesthesia affects the central nervous system to ultimately improve patient care and advance understanding of the brain. Brown says the students have each been doing “off-the-scale” work, in keeping with the excellence he’s seen from MSRP BIO students over the years. For example, on Aug. 10 Baum and Correa Menéndez were honored with MathWorks Fellowships.

    “I think MSRP is fantastic. Mandana does this amazing job of getting students who are quite talented to come to MIT to realize that they can move their game to the next level. They have the capacity to do it. They just need the opportunities,” Brown says. “These students live up to the expectations that you have of them. And now as graduate students, they’re taking on hard problems and they’re solving them.” 

    Paths to PhD studies 

    Pursuing a PhD is hardly a given. Many young students have never considered graduate school or specific fields of study like neuroscience or electrical engineering. But Sassanfar engages students across the country to introduce them to the opportunity MSRP-Bio provides to gain exposure, experience, and mentoring in advanced fields. Every fall, after the program’s students have returned to their undergraduate institutions, she visits schools in places as far flung as Florida, Maryland, Puerto Rico, and Texas and goes to conferences for diverse science communities such as ABRCMS and SACNAS to spread the word. 

    Taylor Baum

    Photo courtesy of Taylor Baum.

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    When Baum first connected with the program in 2017, she was finding her way at Penn State University. She had been majoring in biology and music composition but had just switched the latter to engineering following a conversation over coffee exposing her to brain-computer interfacing technology, in which detecting brain signals of people with full-body paralysis could improve their quality of life by enabling control of computers or wheelchairs. Baum became enthusiastic about the potential to build similar systems, but as a new engineering student, she struggled to find summer internships and research opportunities. 

    “I got rejected from every single progam except the MIT Center for Brains, Minds and Machines MSRP,” she recalls with a chuckle. 

    Baum thrived in MSRP-Bio, working in Brown’s lab for three successive summers. At each stage, she said, she gained more research skills, experience, and independence. When she graduated, she was sure she wanted to go to graduate school and applied to four of her dream schools. She accepted MIT’s offer to join the Department of Electrical Engineering and Computer Science, where she is co-advised by faculty members there and by Brown. She is now working to develop a system grounded in cardiovascular physiology that can improve blood pressure management. A tool for practicing anesthesiologists, the system automates the dosing of drugs to maintain a patient’s blood pressure at safe levels in the operating room or intensive care unit. 

    More than that, Baum not only is leading an organization advancing STEM education in Puerto Rico, but also is helping to mentor a current MSRP-Bio student in the Brown lab. 

    “MSRP definitely bonds everyone who has participated in it,” Baum says. “If I see anyone who I know participated in MSRP, we could have an immediate conversation. I know that most of us, if we needed help, we’d feel comfortable asking for help from someone from MSRP. With that shared experience, we have a sense of camaraderie, and community.” 

    In fact, a few years ago when a former MSRP-Bio student named Karla Montejo was applying to MIT, Baum provided essential advice and feedback about the application process, Montejo says. Now, as a graduate student, Montejo has become a mentor for the program in her own right, Sassanfar notes. For instance, Montejo serves on program alumni panels that advise new MSRP-Bio students. 

    Karla Alejandra Montejo

    Photo courtesy of Karla Alejandra Montejo.

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    Montejo’s family immigrated to Miami from Cuba when she was a child. The magnet high school she attended was so new that students were encouraged to help establish the school’s programs. She forged a path into research. 

    “I didn’t even know what research was,” she says. “I wanted to be a doctor, and I thought maybe it would help me on my resume. I thought it would be kind of like shadowing, but no, it was really different. So I got really captured by research when I was in high school.” 

    Despite continuing to pursue research in college at Florida International University, Montejo didn’t get into graduate school on her first attempt because she hadn’t yet learned how to focus her application. But Sassanfar had visited FIU to recruit students and through that relationship Montejo had already gone through MIT’s related Quantitative Methods Workshop (QMW). So Montejo enrolled in MSRP-Bio, working in the CBMM-affiliated lab of Gabriel Kreiman at Boston Children’s Hospital. 

    “I feel like Mandana really helped me out, gave me a break, and the MSRP experience pretty much solidified that I really wanted to come to MIT,” Montejo says. 

    In the QMW, Montejo learned she really liked computational neuroscience, and in Kreiman’s lab she got to try her hand at computational modeling of the cognition involved in making perceptual sense of complex scenes. Montejo realized she wanted to work on more biologically based neuroscience problems. When the summer ended, because she was off the normal graduate school cycle for now, she found a two-year post-baccalaurate program at Mayo Clinic studying the role a brain cell type called astrocytes might have in the Parkinson’s disease treatment deep brain stimulation. 

    When it came time to reapply to graduate schools (with the help of Baum and others in the BCS Application Assistance Program) Montejo applied to MIT and got in, joining the Brown lab. Now she’s working on modeling the role of  metabolic processes in the changing of brain rhythms under anesthesia, taking advantage of how general anesthesia predictably changes brain states. The effects anesthetic drugs have on cell metabolism and the way that ultimately affects levels of consciousness reveals important aspects of how metabolism affects brain circuits and systems. Earlier this month, for instance, Montejo co-led a paper the lab published in The Proceedings of the National Academy of Sciences detailing the neuroscience of a patient’s transition into an especially deep state of unconsciousness called “burst suppression.” 

    Josefina Correa Menendez

    Photo: David Orenstein

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    A signature of the Brown lab’s work is rigorous statistical analysis and methods, for instance to discern brain arousal states from EEG measures of brain rhythms. A PhD candidate in MIT’s Interdisciplinary Doctoral Program in Statistics, Correa Menéndez is advancing the use of Bayesian hierarchical models for neural data analysis. These statistical models offer a principled way of pooling information across datasets. One of her models can help scientists better understand the way neurons can “spike” with electrical activity when the brain is presented with a stimulus. The other’s power is in discerning critical features such as arousal states of the brain under general anesthesia from electrophysiological recordings. 

    Though she now works with complex equations and computations as a PhD candidate in neuroscience and statistics, Correa Menéndez was mostly interested in music art as a high school student at Academia María Reina in San Juan and then architecture in college at the University of Puerto Rico at Río Piedras. It was discussions at the intersection of epistemology and art during an art theory class that inspired Correa Menéndez to switch her major to biology and to take computer science classes, too. 

    When Sassanfar visited Puerto Rico in 2017, a computer science professor (Patricia Ordóñez) suggested that Correa Menéndez apply for a chance to attend the QMW. She did, and that led her to also participate in MSRP-Bio in the lab of Sherman Fairchild Professor Matt Wilson (a faculty member in BCS, CBMM, and the Picower Institute). She joined in the lab’s studies of how spatial memories are represented in the hippocampus and how the brain makes use of those memories to help understand the world around it. With mentoring from then-postdoc Carmen Varela (now a faculty member at Florida State University), the experience not only exposed her to neuroscience, but also helped her gain skills and experience with lab experiments, building research tools, and conducting statistical analyses. She ended up working in the Wilson lab as a research scholar for a year and began her graduate studies in September 2018.  

    Classes she took with Brown as a research scholar inspired her to join his lab as a graduate student. 

    “Taking the classes with Emery and also doing experiments made me aware of the role of statistics in the scientific process: from the interpretation of results to the analysis and the design of experiments,” she says. “More often than not, in science, statistics becomes this sort of afterthought — this ‘annoying’ thing that people need to do to get their paper published. But statistics as a field is actually a lot more than that. It’s a way of thinking about data. Particularly, Bayesian modeling provides a principled inference framework for combining prior knowledge into a hypothesis that you can test with data.” 

    To be sure, no one starts out with such inspiration about scientific scholarship, but MSRP-Bio helps students find that passion for research and the paths that opens up.   More

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    Bringing the social and ethical responsibilities of computing to the forefront

    There has been a remarkable surge in the use of algorithms and artificial intelligence to address a wide range of problems and challenges. While their adoption, particularly with the rise of AI, is reshaping nearly every industry sector, discipline, and area of research, such innovations often expose unexpected consequences that involve new norms, new expectations, and new rules and laws.

    To facilitate deeper understanding, the Social and Ethical Responsibilities of Computing (SERC), a cross-cutting initiative in the MIT Schwarzman College of Computing, recently brought together social scientists and humanists with computer scientists, engineers, and other computing faculty for an exploration of the ways in which the broad applicability of algorithms and AI has presented both opportunities and challenges in many aspects of society.

    “The very nature of our reality is changing. AI has the ability to do things that until recently were solely the realm of human intelligence — things that can challenge our understanding of what it means to be human,” remarked Daniel Huttenlocher, dean of the MIT Schwarzman College of Computing, in his opening address at the inaugural SERC Symposium. “This poses philosophical, conceptual, and practical questions on a scale not experienced since the start of the Enlightenment. In the face of such profound change, we need new conceptual maps for navigating the change.”

    The symposium offered a glimpse into the vision and activities of SERC in both research and education. “We believe our responsibility with SERC is to educate and equip our students and enable our faculty to contribute to responsible technology development and deployment,” said Georgia Perakis, the William F. Pounds Professor of Management in the MIT Sloan School of Management, co-associate dean of SERC, and the lead organizer of the symposium. “We’re drawing from the many strengths and diversity of disciplines across MIT and beyond and bringing them together to gain multiple viewpoints.”

    Through a succession of panels and sessions, the symposium delved into a variety of topics related to the societal and ethical dimensions of computing. In addition, 37 undergraduate and graduate students from a range of majors, including urban studies and planning, political science, mathematics, biology, electrical engineering and computer science, and brain and cognitive sciences, participated in a poster session to exhibit their research in this space, covering such topics as quantum ethics, AI collusion in storage markets, computing waste, and empowering users on social platforms for better content credibility.

    Showcasing a diversity of work

    In three sessions devoted to themes of beneficent and fair computing, equitable and personalized health, and algorithms and humans, the SERC Symposium showcased work by 12 faculty members across these domains.

    One such project from a multidisciplinary team of archaeologists, architects, digital artists, and computational social scientists aimed to preserve endangered heritage sites in Afghanistan with digital twins. The project team produced highly detailed interrogable 3D models of the heritage sites, in addition to extended reality and virtual reality experiences, as learning resources for audiences that cannot access these sites.

    In a project for the United Network for Organ Sharing, researchers showed how they used applied analytics to optimize various facets of an organ allocation system in the United States that is currently undergoing a major overhaul in order to make it more efficient, equitable, and inclusive for different racial, age, and gender groups, among others.

    Another talk discussed an area that has not yet received adequate public attention: the broader implications for equity that biased sensor data holds for the next generation of models in computing and health care.

    A talk on bias in algorithms considered both human bias and algorithmic bias, and the potential for improving results by taking into account differences in the nature of the two kinds of bias.

    Other highlighted research included the interaction between online platforms and human psychology; a study on whether decision-makers make systemic prediction mistakes on the available information; and an illustration of how advanced analytics and computation can be leveraged to inform supply chain management, operations, and regulatory work in the food and pharmaceutical industries.

    Improving the algorithms of tomorrow

    “Algorithms are, without question, impacting every aspect of our lives,” said Asu Ozdaglar, deputy dean of academics for the MIT Schwarzman College of Computing and head of the Department of Electrical Engineering and Computer Science, in kicking off a panel she moderated on the implications of data and algorithms.

    “Whether it’s in the context of social media, online commerce, automated tasks, and now a much wider range of creative interactions with the advent of generative AI tools and large language models, there’s little doubt that much more is to come,” Ozdaglar said. “While the promise is evident to all of us, there’s a lot to be concerned as well. This is very much time for imaginative thinking and careful deliberation to improve the algorithms of tomorrow.”

    Turning to the panel, Ozdaglar asked experts from computing, social science, and data science for insights on how to understand what is to come and shape it to enrich outcomes for the majority of humanity.

    Sarah Williams, associate professor of technology and urban planning at MIT, emphasized the critical importance of comprehending the process of how datasets are assembled, as data are the foundation for all models. She also stressed the need for research to address the potential implication of biases in algorithms that often find their way in through their creators and the data used in their development. “It’s up to us to think about our own ethical solutions to these problems,” she said. “Just as it’s important to progress with the technology, we need to start the field of looking at these questions of what biases are in the algorithms? What biases are in the data, or in that data’s journey?”

    Shifting focus to generative models and whether the development and use of these technologies should be regulated, the panelists — which also included MIT’s Srini Devadas, professor of electrical engineering and computer science, John Horton, professor of information technology, and Simon Johnson, professor of entrepreneurship — all concurred that regulating open-source algorithms, which are publicly accessible, would be difficult given that regulators are still catching up and struggling to even set guardrails for technology that is now 20 years old.

    Returning to the question of how to effectively regulate the use of these technologies, Johnson proposed a progressive corporate tax system as a potential solution. He recommends basing companies’ tax payments on their profits, especially for large corporations whose massive earnings go largely untaxed due to offshore banking. By doing so, Johnson said that this approach can serve as a regulatory mechanism that discourages companies from trying to “own the entire world” by imposing disincentives.

    The role of ethics in computing education

    As computing continues to advance with no signs of slowing down, it is critical to educate students to be intentional in the social impact of the technologies they will be developing and deploying into the world. But can one actually be taught such things? If so, how?

    Caspar Hare, professor of philosophy at MIT and co-associate dean of SERC, posed this looming question to faculty on a panel he moderated on the role of ethics in computing education. All experienced in teaching ethics and thinking about the social implications of computing, each panelist shared their perspective and approach.

    A strong advocate for the importance of learning from history, Eden Medina, associate professor of science, technology, and society at MIT, said that “often the way we frame computing is that everything is new. One of the things that I do in my teaching is look at how people have confronted these issues in the past and try to draw from them as a way to think about possible ways forward.” Medina regularly uses case studies in her classes and referred to a paper written by Yale University science historian Joanna Radin on the Pima Indian Diabetes Dataset that raised ethical issues on the history of that particular collection of data that many don’t consider as an example of how decisions around technology and data can grow out of very specific contexts.

    Milo Phillips-Brown, associate professor of philosophy at Oxford University, talked about the Ethical Computing Protocol that he co-created while he was a SERC postdoc at MIT. The protocol, a four-step approach to building technology responsibly, is designed to train computer science students to think in a better and more accurate way about the social implications of technology by breaking the process down into more manageable steps. “The basic approach that we take very much draws on the fields of value-sensitive design, responsible research and innovation, participatory design as guiding insights, and then is also fundamentally interdisciplinary,” he said.

    Fields such as biomedicine and law have an ethics ecosystem that distributes the function of ethical reasoning in these areas. Oversight and regulation are provided to guide front-line stakeholders and decision-makers when issues arise, as are training programs and access to interdisciplinary expertise that they can draw from. “In this space, we have none of that,” said John Basl, associate professor of philosophy at Northeastern University. “For current generations of computer scientists and other decision-makers, we’re actually making them do the ethical reasoning on their own.” Basl commented further that teaching core ethical reasoning skills across the curriculum, not just in philosophy classes, is essential, and that the goal shouldn’t be for every computer scientist be a professional ethicist, but for them to know enough of the landscape to be able to ask the right questions and seek out the relevant expertise and resources that exists.

    After the final session, interdisciplinary groups of faculty, students, and researchers engaged in animated discussions related to the issues covered throughout the day during a reception that marked the conclusion of the symposium. More

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    Celebrating open data

    The inaugural MIT Prize for Open Data, which included a $2,500 cash prize, was recently awarded to 10 individual and group research projects. Presented jointly by the School of Science and the MIT Libraries, the prize recognizes MIT-affiliated researchers who make their data openly accessible and reusable by others. The prize winners and 16 honorable mention recipients were honored at the Open Data @ MIT event held Oct. 28 at Hayden Library. 

    “By making data open, researchers create opportunities for novel uses of their data and for new insights to be gleaned,” says Chris Bourg, director of MIT Libraries. “Open data accelerates scholarly progress and discovery, advances equity in scholarly participation, and increases transparency, replicability, and trust in science.” 

    Recognizing shared values

    Spearheaded by Bourg and Rebecca Saxe, associate dean of the School of Science and John W. Jarve (1978) Professor of Brain and Cognitive Sciences, the MIT Prize for Open Data was launched to highlight the value of open data at MIT and to encourage the next generation of researchers. Nominations were solicited from across the Institute, with a focus on trainees: research technicians, undergraduate or graduate students, or postdocs.

    “By launching an MIT-wide prize and event, we aimed to create visibility for the scholars who create, use, and advocate for open data,” says Saxe. “Highlighting this research and creating opportunities for networking would also help open-data advocates across campus find each other.” 

    Recognizing researchers who share data was also one of the recommendations of the Ad Hoc Task Force on Open Access to MIT’s Research, which Bourg co-chaired with Hal Abelson, Class of 1922 Professor, Department of Electrical Engineering and Computer Science. An annual award was one of the strategies put forth by the task force to further the Institute’s mission to disseminate the fruits of its research and scholarship as widely as possible.

    Strong competition

    Winners and honorable mentions were chosen from more than 70 nominees, representing all five schools, the MIT Schwarzman College of Computing, and several research centers across MIT. A committee composed of faculty, staff, and a graduate student made the selections:

    Yunsie Chung, graduate student in the Department of Chemical Engineering, won for SolProp, the largest open-source dataset with temperature-dependent solubility values of organic compounds. 
    Matthew Groh, graduate student, MIT Media Lab, accepted on behalf of the team behind the Fitzpatrick 17k dataset, an open dataset consisting of nearly 17,000 images of skin disease alongside skin disease and skin tone annotations. 
    Tom Pollard, research scientist at the Institute for Medical Engineering and Science, accepted on behalf of the PhysioNet team. This data-sharing platform enables thousands of clinical and machine-learning research studies each year and allows researchers to share sensitive resources that would not be possible through typical data sharing platforms. 
    Joseph Replogle, graduate student with the Whitehead Institute for Biomedical Research, was recognized for the Genome-wide Perturb-seq dataset, the largest publicly available, single-cell transcriptional dataset collected to date. 
    Pedro Reynolds-Cuéllar, graduate student with the MIT Media Lab/Art, Culture, and Technology, and Diana Duarte, co-founder at Diversa, won for Retos, an open-data platform for detailed documentation and sharing of local innovations from under-resourced settings. 
    Maanas Sharma, an undergraduate student, led States of Emergency, a nationwide project analyzing and grading the responses of prison systems to Covid-19 using data scraped from public databases and manually collected data. 
    Djuna von Maydell, graduate student in the Department of Brain and Cognitive Sciences, created the first publicly available dataset of single-cell gene expression from postmortem human brain tissue of patients who are carriers of APOE4, the major Alzheimer’s disease risk gene. 
    Raechel Walker, graduate researcher in the MIT Media Lab, and her collaborators created a Data Activism Curriculum for high school students through the Mayor’s Summer Youth Employment Program in Cambridge, Massachusetts. Students learned how to use data science to recognize, mitigate, and advocate for people who are disproportionately impacted by systemic inequality. 
    Suyeol Yun, graduate student in the Department of Political Science, was recognized for DeepWTO, a project creating open data for use in legal natural language processing research using cases from the World Trade Organization. 
    Jonathan Zheng, graduate student in the Department of Chemical Engineering, won for an open IUPAC dataset for acid dissociation constants, or “pKas,” physicochemical properties that govern how acidic a chemical is in a solution.
    A full list of winners and honorable mentions is available on the Open Data @ MIT website.

    A campus-wide celebration

    Awards were presented at a celebratory event held in the Nexus in Hayden Library during International Open Access Week. School of Science Dean Nergis Mavalvala kicked off the program by describing the long and proud history of open scholarship at MIT, citing the Institute-wide faculty open access policy and the launch of the open-source digital repository DSpace. “When I was a graduate student, we were trying to figure out how to share our theses during the days of the nascent internet,” she said, “With DSpace, MIT was figuring it out for us.” 

    The centerpiece of the program was a series of five-minute presentations from the prize winners on their research. Presenters detailed the ways they created, used, or advocated for open data, and the value that openness brings to their respective fields. Winner Djuna von Maydell, a graduate student in Professor Li-Huei Tsai’s lab who studies the genetic causes of neurodegeneration, underscored why it is important to share data, particularly data obtained from postmortem human brains. 

    “This is data generated from human brains, so every data point stems from a living, breathing human being, who presumably made this donation in the hope that we would use it to advance knowledge and uncover truth,” von Maydell said. “To maximize the probability of that happening, we have to make it available to the scientific community.” 

    MIT community members who would like to learn more about making their research data open can consult MIT Libraries’ Data Services team.  More

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    Emery Brown wins a share of 2022 Gruber Neuroscience Prize

    The Gruber Foundation announced on May 17 that Emery N. Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience at MIT, has won the 2022 Gruber Neuroscience Prize along with neurophysicists Laurence Abbott of Columbia University, Terrence Sejnowski of the Salk Institute for Biological Studies, and Haim Sompolinsky of the Hebrew University of Jerusalem.

    The foundation says it honored the four recipients for their influential contributions to the fields of computational and theoretical neuroscience. As datasets have grown ever larger and more complex, these fields have increasingly helped scientists unravel the mysteries of how the brain functions in both health and disease. The prize, which includes a total $500,000 award, will be presented in San Diego, California, on Nov. 13 at the annual meeting of the Society for Neuroscience.

    “These four remarkable scientists have applied their expertise in mathematical and statistical analysis, physics, and machine learning to create theories, mathematical models, and tools that have greatly advanced how we study and understand the brain,” says Joshua Sanes, professor of molecular and cellular biology and founding director of the Center for Brain Science at Harvard University and member of the selection advisory board to the prize. “Their insights and research have not only transformed how experimental neuroscientists do their research, but also are leading to promising new ways of providing clinical care.”

    Brown, who is an investigator in The Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science at MIT, an anesthesiologist at Massachusetts General Hospital, and a professor at Harvard Medical School, says: “It is a pleasant surprise and tremendous honor to be named a co-recipient of the 2022 Gruber Prize in Neuroscience. I am especially honored to share this award with three luminaries in computational and theoretical neuroscience.”

    Brown’s early groundbreaking findings in neuroscience included a novel algorithm that decodes the position of an animal by observing the activity of a small group of place cells in the animal’s brain, a discovery he made while working with fellow Picower Institute investigator Matt Wilson in the 1990s. The resulting state-space algorithm for point processes not only offered much better decoding with fewer neurons than previous approaches, but it also established a new framework for specifying dynamically the relationship between the spike trains (the timing sequence of firing neurons) in the brain and factors from the outside world.

    “One of the basic questions at the time was whether an animal holds a representation of where it is in its mind — in the hippocampus,” Brown says. “We were able to show that it did, and we could show that with only 30 neurons.”

    After introducing this state-space paradigm to neuroscience, Brown went on to refine the original idea and apply it to other dynamic situations — to simultaneously track neural activity and learning, for example, and to define with precision anesthesia-induced loss of consciousness, as well as its subsequent recovery. In the early 2000s, Brown put together a team to specifically study anesthesia’s effects on the brain.

    Through experimental research and mathematical modeling, Brown and his team showed that the altered arousal states produced by the main classes of anesthesia medications can be characterized by analyzing the oscillatory patterns observed in the EEG along with the locations of their molecular targets, and the anatomy and physiology of the neural circuits that connect those locations. He has established, including in recent papers with Picower Professor Earl K. Miller, that a principal way in which anesthetics produce unconsciousness is by producing oscillations that impair how different brain regions communicate with each other.

    The result of Brown’s research has been a new paradigm for brain monitoring during general anesthesia for surgery, one that allows an anesthesiologist to dose the patient based on EEG readouts (neural oscillations) of the patient’s anesthetic state rather than purely on vital sign responses. This pioneering approach promises to revolutionize how anesthesia medications are delivered to patients, and also shed light on other altered states of arousal such as sleep and coma.

    To advance that vision, Brown recently discussed how he is working to develop a new research center at MIT and MGH to further integrate anesthesiology with neuroscience research. The Brain Arousal State Control Innovation Center, he said, would not only advance anesthesiology care but also harness insights gained from anesthesiology research to improve other aspects of clinical neuroscience.

    “By demonstrating that physics and mathematics can make an enormous contribution to neuroscience, doctors Abbott, Brown, Sejnowski, and Sompolinsky have inspired an entire new generation of physicists and other quantitative scientists to follow in their footsteps,” says Frances Jensen, professor and chair of the Department of Neurology and co-director of the Penn Medicine Translational Neuroscience Center within the Perelman School of Medicine at the University of Pennsylvania, and chair of the Selection Advisory Board to the prize. “The ramifications for neuroscience have been broad and profound. It is a great pleasure to be honoring each of them with this prestigious award.”

    This report was adapted from materials provided by the Gruber Foundation. More

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    What words can convey

    From search engines to voice assistants, computers are getting better at understanding what we mean. That’s thanks to language-processing programs that make sense of a staggering number of words, without ever being told explicitly what those words mean. Such programs infer meaning instead through statistics — and a new study reveals that this computational approach can assign many kinds of information to a single word, just like the human brain.

    The study, published April 14 in the journal Nature Human Behavior, was co-led by Gabriel Grand, a graduate student in electrical engineering and computer science who is affiliated with MIT’s Computer Science and Artificial Intelligence Laboratory, and Idan Blank PhD ’16, an assistant professor at the University of California at Los Angeles. The work was supervised by McGovern Institute for Brain Research investigator Ev Fedorenko, a cognitive neuroscientist who studies how the human brain uses and understands language, and Francisco Pereira at the National Institute of Mental Health. Fedorenko says the rich knowledge her team was able to find within computational language models demonstrates just how much can be learned about the world through language alone.

    The research team began its analysis of statistics-based language processing models in 2015, when the approach was new. Such models derive meaning by analyzing how often pairs of words co-occur in texts and using those relationships to assess the similarities of words’ meanings. For example, such a program might conclude that “bread” and “apple” are more similar to one another than they are to “notebook,” because “bread” and “apple” are often found in proximity to words like “eat” or “snack,” whereas “notebook” is not.

    The models were clearly good at measuring words’ overall similarity to one another. But most words carry many kinds of information, and their similarities depend on which qualities are being evaluated. “Humans can come up with all these different mental scales to help organize their understanding of words,” explains Grand, a former undergraduate researcher in the Fedorenko lab. For example, he says, “dolphins and alligators might be similar in size, but one is much more dangerous than the other.”

    Grand and Blank, who was then a graduate student at the McGovern Institute, wanted to know whether the models captured that same nuance. And if they did, how was the information organized?

    To learn how the information in such a model stacked up to humans’ understanding of words, the team first asked human volunteers to score words along many different scales: Were the concepts those words conveyed big or small, safe or dangerous, wet or dry? Then, having mapped where people position different words along these scales, they looked to see whether language processing models did the same.

    Grand explains that distributional semantic models use co-occurrence statistics to organize words into a huge, multidimensional matrix. The more similar words are to one another, the closer they are within that space. The dimensions of the space are vast, and there is no inherent meaning built into its structure. “In these word embeddings, there are hundreds of dimensions, and we have no idea what any dimension means,” he says. “We’re really trying to peer into this black box and say, ‘is there structure in here?’”

    Specifically, they asked whether the semantic scales they had asked their volunteers use were represented in the model. So they looked to see where words in the space lined up along vectors defined by the extremes of those scales. Where did dolphins and tigers fall on line from “big” to “small,” for example? And were they closer together along that line than they were on a line representing danger (“safe” to “dangerous”)?

    Across more than 50 sets of world categories and semantic scales, they found that the model had organized words very much like the human volunteers. Dolphins and tigers were judged to be similar in terms of size, but far apart on scales measuring danger or wetness. The model had organized the words in a way that represented many kinds of meaning — and it had done so based entirely on the words’ co-occurrences.

    That, Fedorenko says, tells us something about the power of language. “The fact that we can recover so much of this rich semantic information from just these simple word co-occurrence statistics suggests that this is one very powerful source of learning about things that you may not even have direct perceptual experience with.” More

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    Seven from MIT elected to American Academy of Arts and Sciences for 2022

    Seven MIT faculty members are among more than 250 leaders from academia, the arts, industry, public policy, and research elected to the American Academy of Arts and Sciences, the academy announced Thursday.

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

    Those elected from MIT this year are:

    Alberto Abadie, professor of economics and associate director of the Institute for Data, Systems, and Society
    Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health
    Roman Bezrukavnikov, professor of mathematics
    Michale S. Fee, the Glen V. and Phyllis F. Dorflinger Professor and head of the Department of Brain and Cognitive Sciences
    Dina Katabi, the Thuan and Nicole Pham Professor
    Ronald T. Raines, the Roger and Georges Firmenich Professor of Natural Products Chemistry
    Rebecca R. Saxe, the John W. Jarve Professor of Brain and Cognitive Sciences

    “We are celebrating a depth of achievements in a breadth of areas,” says David Oxtoby, president of the American Academy. “These individuals excel in ways that excite us and inspire us at a time when recognizing excellence, commending expertise, and working toward the common good is absolutely essential to realizing a better future.”

    Since its founding in 1780, the academy has elected leading thinkers from each generation, including George Washington and Benjamin Franklin in the 18th century, Maria Mitchell and Daniel Webster in the 19th century, and Toni Morrison and Albert Einstein in the 20th century. The current membership includes more than 250 Nobel and Pulitzer Prize winners. More