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    MIT-Takeda Program wraps up with 16 publications, a patent, and nearly two dozen projects completed

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    When the Takeda Pharmaceutical Co. and the MIT School of Engineering launched their collaboration focused on artificial intelligence in health care and drug development in February 2020, society was on the cusp of a globe-altering pandemic and AI was far from the buzzword it is today.As the program concludes, the world looks very different. AI has become a transformative technology across industries including health care and pharmaceuticals, while the pandemic has altered the way many businesses approach health care and changed how they develop and sell medicines.For both MIT and Takeda, the program has been a game-changer.When it launched, the collaborators hoped the program would help solve tangible, real-world problems. By its end, the program has yielded a catalog of new research papers, discoveries, and lessons learned, including a patent for a system that could improve the manufacturing of small-molecule medicines.Ultimately, the program allowed both entities to create a foundation for a world where AI and machine learning play a pivotal role in medicine, leveraging Takeda’s expertise in biopharmaceuticals and the MIT researchers’ deep understanding of AI and machine learning.“The MIT-Takeda Program has been tremendously impactful and is a shining example of what can be accomplished when experts in industry and academia work together to develop solutions,” says Anantha Chandrakasan, MIT’s chief innovation and strategy officer, dean of the School of Engineering, and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “In addition to resulting in research that has advanced how we use AI and machine learning in health care, the program has opened up new opportunities for MIT faculty and students through fellowships, funding, and networking.”What made the program unique was that it was centered around several concrete challenges spanning drug development that Takeda needed help addressing. MIT faculty had the opportunity to select the projects based on their area of expertise and general interest, allowing them to explore new areas within health care and drug development.“It was focused on Takeda’s toughest business problems,” says Anne Heatherington, Takeda’s research and development chief data and technology officer and head of its Data Sciences Institute.“They were problems that colleagues were really struggling with on the ground,” adds Simon Davies, the executive director of the MIT-Takeda Program and Takeda’s global head of statistical and quantitative sciences. Takeda saw an opportunity to collaborate with MIT’s world-class researchers, who were working only a few blocks away. Takeda, a global pharmaceutical company with global headquarters in Japan, has its global business units and R&D center just down the street from the Institute.As part of the program, MIT faculty were able to select what issues they were interested in working on from a group of potential Takeda projects. Then, collaborative teams including MIT researchers and Takeda employees approached research questions in two rounds. Over the course of the program, collaborators worked on 22 projects focused on topics including drug discovery and research, clinical drug development, and pharmaceutical manufacturing. Over 80 MIT students and faculty joined more than 125 Takeda researchers and staff on teams addressing these research questions.The projects centered around not only hard problems, but also the potential for solutions to scale within Takeda or within the biopharmaceutical industry more broadly.Some of the program’s findings have already resulted in wider studies. One group’s results, for instance, showed that using artificial intelligence to analyze speech may allow for earlier detection of frontotemporal dementia, while making that diagnosis more quickly and inexpensively. Similar algorithmic analyses of speech in patients diagnosed with ALS may also help clinicians understand the progression of that disease. Takeda is continuing to test both AI applications.Other discoveries and AI models that resulted from the program’s research have already had an impact. Using a physical model and AI learning algorithms can help detect particle size, mix, and consistency for powdered, small-molecule medicines, for instance, speeding up production timelines. Based on their research under the program, collaborators have filed for a patent for that technology.For injectable medicines like vaccines, AI-enabled inspections can also reduce process time and false rejection rates. Replacing human visual inspections with AI processes has already shown measurable impact for the pharmaceutical company.Heatherington adds, “our lessons learned are really setting the stage for what we’re doing next, really embedding AI and gen-AI [generative AI] into everything that we do moving forward.”Over the course of the program, more than 150 Takeda researchers and staff also participated in educational programming organized by the Abdul Latif Jameel Clinic for Machine Learning in Health. In addition to providing research opportunities, the program funded 10 students through SuperUROP, the Advanced Undergraduate Research Opportunities Program, as well as two cohorts from the DHIVE health-care innovation program, part of the MIT Sandbox Innovation Fund Program.Though the formal program has ended, certain aspects of the collaboration will continue, such as the MIT-Takeda Fellows, which supports graduate students as they pursue groundbreaking research related to health and AI. During its run, the program supported 44 MIT-Takeda Fellows and will continue to support MIT students through an endowment fund. Organic collaboration between MIT and Takeda researchers will also carry forward. And the programs’ collaborators are working to create a model for similar academic and industry partnerships to widen the impact of this first-of-its-kind collaboration.  More

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      2023-24 Takeda Fellows: Advancing research at the intersection of AI and health

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      The School of Engineering has selected 13 new Takeda Fellows for the 2023-24 academic year. With support from Takeda, the graduate students will conduct pathbreaking research ranging from remote health monitoring for virtual clinical trials to ingestible devices for at-home, long-term diagnostics.

      Now in its fourth year, the MIT-Takeda Program, a collaboration between MIT’s School of Engineering and Takeda, fuels the development and application of artificial intelligence capabilities to benefit human health and drug development. Part of the Abdul Latif Jameel Clinic for Machine Learning in Health, the program coalesces disparate disciplines, merges theory and practical implementation, combines algorithm and hardware innovations, and creates multidimensional collaborations between academia and industry.

      The 2023-24 Takeda Fellows are:

      Adam Gierlach

      Adam Gierlach is a PhD candidate in the Department of Electrical Engineering and Computer Science. Gierlach’s work combines innovative biotechnology with machine learning to create ingestible devices for advanced diagnostics and delivery of therapeutics. In his previous work, Gierlach developed a non-invasive, ingestible device for long-term gastric recordings in free-moving patients. With the support of a Takeda Fellowship, he will build on this pathbreaking work by developing smart, energy-efficient, ingestible devices powered by application-specific integrated circuits for at-home, long-term diagnostics. These revolutionary devices — capable of identifying, characterizing, and even correcting gastrointestinal diseases — represent the leading edge of biotechnology. Gierlach’s innovative contributions will help to advance fundamental research on the enteric nervous system and help develop a better understanding of gut-brain axis dysfunctions in Parkinson’s disease, autism spectrum disorder, and other prevalent disorders and conditions.

      Vivek Gopalakrishnan

      Vivek Gopalakrishnan is a PhD candidate in the Harvard-MIT Program in Health Sciences and Technology. Gopalakrishnan’s goal is to develop biomedical machine-learning methods to improve the study and treatment of human disease. Specifically, he employs computational modeling to advance new approaches for minimally invasive, image-guided neurosurgery, offering a safe alternative to open brain and spinal procedures. With the support of a Takeda Fellowship, Gopalakrishnan will develop real-time computer vision algorithms that deliver high-quality, 3D intraoperative image guidance by extracting and fusing information from multimodal neuroimaging data. These algorithms could allow surgeons to reconstruct 3D neurovasculature from X-ray angiography, thereby enhancing the precision of device deployment and enabling more accurate localization of healthy versus pathologic anatomy.

      Hao He

      Hao He is a PhD candidate in the Department of Electrical Engineering and Computer Science. His research interests lie at the intersection of generative AI, machine learning, and their applications in medicine and human health, with a particular emphasis on passive, continuous, remote health monitoring to support virtual clinical trials and health-care management. More specifically, He aims to develop trustworthy AI models that promote equitable access and deliver fair performance independent of race, gender, and age. In his past work, He has developed monitoring systems applied in clinical studies of Parkinson’s disease, Alzheimer’s disease, and epilepsy. Supported by a Takeda Fellowship, He will develop a novel technology for the passive monitoring of sleep stages (using radio signaling) that seeks to address existing gaps in performance across different demographic groups. His project will tackle the problem of imbalance in available datasets and account for intrinsic differences across subpopulations, using generative AI and multi-modality/multi-domain learning, with the goal of learning robust features that are invariant to different subpopulations. He’s work holds great promise for delivering advanced, equitable health-care services to all people and could significantly impact health care and AI.

      Chengyi Long

      Chengyi Long is a PhD candidate in the Department of Civil and Environmental Engineering. Long’s interdisciplinary research integrates the methodology of physics, mathematics, and computer science to investigate questions in ecology. Specifically, Long is developing a series of potentially groundbreaking techniques to explain and predict the temporal dynamics of ecological systems, including human microbiota, which are essential subjects in health and medical research. His current work, supported by a Takeda Fellowship, is focused on developing a conceptual, mathematical, and practical framework to understand the interplay between external perturbations and internal community dynamics in microbial systems, which may serve as a key step toward finding bio solutions to health management. A broader perspective of his research is to develop AI-assisted platforms to anticipate the changing behavior of microbial systems, which may help to differentiate between healthy and unhealthy hosts and design probiotics for the prevention and mitigation of pathogen infections. By creating novel methods to address these issues, Long’s research has the potential to offer powerful contributions to medicine and global health.

      Omar Mohd

      Omar Mohd is a PhD candidate in the Department of Electrical Engineering and Computer Science. Mohd’s research is focused on developing new technologies for the spatial profiling of microRNAs, with potentially important applications in cancer research. Through innovative combinations of micro-technologies and AI-enabled image analysis to measure the spatial variations of microRNAs within tissue samples, Mohd hopes to gain new insights into drug resistance in cancer. This work, supported by a Takeda Fellowship, falls within the emerging field of spatial transcriptomics, which seeks to understand cancer and other diseases by examining the relative locations of cells and their contents within tissues. The ultimate goal of Mohd’s current project is to find multidimensional patterns in tissues that may have prognostic value for cancer patients. One valuable component of his work is an open-source AI program developed with collaborators at Beth Israel Deaconess Medical Center and Harvard Medical School to auto-detect cancer epithelial cells from other cell types in a tissue sample and to correlate their abundance with the spatial variations of microRNAs. Through his research, Mohd is making innovative contributions at the interface of microsystem technology, AI-based image analysis, and cancer treatment, which could significantly impact medicine and human health.

      Sanghyun Park

      Sanghyun Park is a PhD candidate in the Department of Mechanical Engineering. Park specializes in the integration of AI and biomedical engineering to address complex challenges in human health. Drawing on his expertise in polymer physics, drug delivery, and rheology, his research focuses on the pioneering field of in-situ forming implants (ISFIs) for drug delivery. Supported by a Takeda Fellowship, Park is currently developing an injectable formulation designed for long-term drug delivery. The primary goal of his research is to unravel the compaction mechanism of drug particles in ISFI formulations through comprehensive modeling and in-vitro characterization studies utilizing advanced AI tools. He aims to gain a thorough understanding of this unique compaction mechanism and apply it to drug microcrystals to achieve properties optimal for long-term drug delivery. Beyond these fundamental studies, Park’s research also focuses on translating this knowledge into practical applications in a clinical setting through animal studies specifically aimed at extending drug release duration and improving mechanical properties. The innovative use of AI in developing advanced drug delivery systems, coupled with Park’s valuable insights into the compaction mechanism, could contribute to improving long-term drug delivery. This work has the potential to pave the way for effective management of chronic diseases, benefiting patients, clinicians, and the pharmaceutical industry.

      Huaiyao Peng

      Huaiyao Peng is a PhD candidate in the Department of Biological Engineering. Peng’s research interests are focused on engineered tissue, microfabrication platforms, cancer metastasis, and the tumor microenvironment. Specifically, she is advancing novel AI techniques for the development of pre-cancer organoid models of high-grade serous ovarian cancer (HGSOC), an especially lethal and difficult-to-treat cancer, with the goal of gaining new insights into progression and effective treatments. Peng’s project, supported by a Takeda Fellowship, will be one of the first to use cells from serous tubal intraepithelial carcinoma lesions found in the fallopian tubes of many HGSOC patients. By examining the cellular and molecular changes that occur in response to treatment with small molecule inhibitors, she hopes to identify potential biomarkers and promising therapeutic targets for HGSOC, including personalized treatment options for HGSOC patients, ultimately improving their clinical outcomes. Peng’s work has the potential to bring about important advances in cancer treatment and spur innovative new applications of AI in health care. 

      Priyanka Raghavan

      Priyanka Raghavan is a PhD candidate in the Department of Chemical Engineering. Raghavan’s research interests lie at the frontier of predictive chemistry, integrating computational and experimental approaches to build powerful new predictive tools for societally important applications, including drug discovery. Specifically, Raghavan is developing novel models to predict small-molecule substrate reactivity and compatibility in regimes where little data is available (the most realistic regimes). A Takeda Fellowship will enable Raghavan to push the boundaries of her research, making innovative use of low-data and multi-task machine learning approaches, synthetic chemistry, and robotic laboratory automation, with the goal of creating an autonomous, closed-loop system for the discovery of high-yielding organic small molecules in the context of underexplored reactions. Raghavan’s work aims to identify new, versatile reactions to broaden a chemist’s synthetic toolbox with novel scaffolds and substrates that could form the basis of essential drugs. Her work has the potential for far-reaching impacts in early-stage, small-molecule discovery and could help make the lengthy drug-discovery process significantly faster and cheaper.

      Zhiye Song

      Zhiye “Zoey” Song is a PhD candidate in the Department of Electrical Engineering and Computer Science. Song’s research integrates cutting-edge approaches in machine learning (ML) and hardware optimization to create next-generation, wearable medical devices. Specifically, Song is developing novel approaches for the energy-efficient implementation of ML computation in low-power medical devices, including a wearable ultrasound “patch” that captures and processes images for real-time decision-making capabilities. Her recent work, conducted in collaboration with clinicians, has centered on bladder volume monitoring; other potential applications include blood pressure monitoring, muscle diagnosis, and neuromodulation. With the support of a Takeda Fellowship, Song will build on that promising work and pursue key improvements to existing wearable device technologies, including developing low-compute and low-memory ML algorithms and low-power chips to enable ML on smart wearable devices. The technologies emerging from Song’s research could offer exciting new capabilities in health care, enabling powerful and cost-effective point-of-care diagnostics and expanding individual access to autonomous and continuous medical monitoring.

      Peiqi Wang

      Peiqi Wang is a PhD candidate in the Department of Electrical Engineering and Computer Science. Wang’s research aims to develop machine learning methods for learning and interpretation from medical images and associated clinical data to support clinical decision-making. He is developing a multimodal representation learning approach that aligns knowledge captured in large amounts of medical image and text data to transfer this knowledge to new tasks and applications. Supported by a Takeda Fellowship, Wang will advance this promising line of work to build robust tools that interpret images, learn from sparse human feedback, and reason like doctors, with potentially major benefits to important stakeholders in health care.

      Oscar Wu

      Haoyang “Oscar” Wu is a PhD candidate in the Department of Chemical Engineering. Wu’s research integrates quantum chemistry and deep learning methods to accelerate the process of small-molecule screening in the development of new drugs. By identifying and automating reliable methods for finding transition state geometries and calculating barrier heights for new reactions, Wu’s work could make it possible to conduct the high-throughput ab initio calculations of reaction rates needed to screen the reactivity of large numbers of active pharmaceutical ingredients (APIs). A Takeda Fellowship will support his current project to: (1) develop open-source software for high-throughput quantum chemistry calculations, focusing on the reactivity of drug-like molecules, and (2) develop deep learning models that can quantitatively predict the oxidative stability of APIs. The tools and insights resulting from Wu’s research could help to transform and accelerate the drug-discovery process, offering significant benefits to the pharmaceutical and medical fields and to patients.

      Soojung Yang

      Soojung Yang is a PhD candidate in the Department of Materials Science and Engineering. Yang’s research applies cutting-edge methods in geometric deep learning and generative modeling, along with atomistic simulations, to better understand and model protein dynamics. Specifically, Yang is developing novel tools in generative AI to explore protein conformational landscapes that offer greater speed and detail than physics-based simulations at a substantially lower cost. With the support of a Takeda Fellowship, she will build upon her successful work on the reverse transformation of coarse-grained proteins to the all-atom resolution, aiming to build machine-learning models that bridge multiple size scales of protein conformation diversity (all-atom, residue-level, and domain-level). Yang’s research holds the potential to provide a powerful and widely applicable new tool for researchers who seek to understand the complex protein functions at work in human diseases and to design drugs to treat and cure those diseases.

      Yuzhe Yang

      Yuzhe Yang is a PhD candidate in the Department of Electrical Engineering and Computer Science. Yang’s research interests lie at the intersection of machine learning and health care. In his past and current work, Yang has developed and applied innovative machine-learning models that address key challenges in disease diagnosis and tracking. His many notable achievements include the creation of one of the first machine learning-based solutions using nocturnal breathing signals to detect Parkinson’s disease (PD), estimate disease severity, and track PD progression. With the support of a Takeda Fellowship, Yang will expand this promising work to develop an AI-based diagnosis model for Alzheimer’s disease (AD) using sleep-breathing data that is significantly more reliable, flexible, and economical than current diagnostic tools. This passive, in-home, contactless monitoring system — resembling a simple home Wi-Fi router — will also enable remote disease assessment and continuous progression tracking. Yang’s groundbreaking work has the potential to advance the diagnosis and treatment of prevalent diseases like PD and AD, and it offers exciting possibilities for addressing many health challenges with reliable, affordable machine-learning tools.  More

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      A more effective experimental design for engineering a cell into a new state

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      A strategy for cellular reprogramming involves using targeted genetic interventions to engineer a cell into a new state. The technique holds great promise in immunotherapy, for instance, where researchers could reprogram a patient’s T-cells so they are more potent cancer killers. Someday, the approach could also help identify life-saving cancer treatments or regenerative therapies that repair disease-ravaged organs.

      But the human body has about 20,000 genes, and a genetic perturbation could be on a combination of genes or on any of the over 1,000 transcription factors that regulate the genes. Because the search space is vast and genetic experiments are costly, scientists often struggle to find the ideal perturbation for their particular application.   

      Researchers from MIT and Harvard University developed a new, computational approach that can efficiently identify optimal genetic perturbations based on a much smaller number of experiments than traditional methods.

      Their algorithmic technique leverages the cause-and-effect relationship between factors in a complex system, such as genome regulation, to prioritize the best intervention in each round of sequential experiments.

      The researchers conducted a rigorous theoretical analysis to determine that their technique did, indeed, identify optimal interventions. With that theoretical framework in place, they applied the algorithms to real biological data designed to mimic a cellular reprogramming experiment. Their algorithms were the most efficient and effective.

      “Too often, large-scale experiments are designed empirically. A careful causal framework for sequential experimentation may allow identifying optimal interventions with fewer trials, thereby reducing experimental costs,” says co-senior author Caroline Uhler, a professor in the Department of Electrical Engineering and Computer Science (EECS) who is also co-director of the Eric and Wendy Schmidt Center at the Broad Institute of MIT and Harvard, and a researcher at MIT’s Laboratory for Information and Decision Systems (LIDS) and Institute for Data, Systems and Society (IDSS).

      Joining Uhler on the paper, which appears today in Nature Machine Intelligence, are lead author Jiaqi Zhang, a graduate student and Eric and Wendy Schmidt Center Fellow; co-senior author Themistoklis P. Sapsis, professor of mechanical and ocean engineering at MIT and a member of IDSS; and others at Harvard and MIT.

      Active learning

      When scientists try to design an effective intervention for a complex system, like in cellular reprogramming, they often perform experiments sequentially. Such settings are ideally suited for the use of a machine-learning approach called active learning. Data samples are collected and used to learn a model of the system that incorporates the knowledge gathered so far. From this model, an acquisition function is designed — an equation that evaluates all potential interventions and picks the best one to test in the next trial.

      This process is repeated until an optimal intervention is identified (or resources to fund subsequent experiments run out).

      “While there are several generic acquisition functions to sequentially design experiments, these are not effective for problems of such complexity, leading to very slow convergence,” Sapsis explains.

      Acquisition functions typically consider correlation between factors, such as which genes are co-expressed. But focusing only on correlation ignores the regulatory relationships or causal structure of the system. For instance, a genetic intervention can only affect the expression of downstream genes, but a correlation-based approach would not be able to distinguish between genes that are upstream or downstream.

      “You can learn some of this causal knowledge from the data and use that to design an intervention more efficiently,” Zhang explains.

      The MIT and Harvard researchers leveraged this underlying causal structure for their technique. First, they carefully constructed an algorithm so it can only learn models of the system that account for causal relationships.

      Then the researchers designed the acquisition function so it automatically evaluates interventions using information on these causal relationships. They crafted this function so it prioritizes the most informative interventions, meaning those most likely to lead to the optimal intervention in subsequent experiments.

      “By considering causal models instead of correlation-based models, we can already rule out certain interventions. Then, whenever you get new data, you can learn a more accurate causal model and thereby further shrink the space of interventions,” Uhler explains.

      This smaller search space, coupled with the acquisition function’s special focus on the most informative interventions, is what makes their approach so efficient.

      The researchers further improved their acquisition function using a technique known as output weighting, inspired by the study of extreme events in complex systems. This method carefully emphasizes interventions that are likely to be closer to the optimal intervention.

      “Essentially, we view an optimal intervention as an ‘extreme event’ within the space of all possible, suboptimal interventions and use some of the ideas we have developed for these problems,” Sapsis says.    

      Enhanced efficiency

      They tested their algorithms using real biological data in a simulated cellular reprogramming experiment. For this test, they sought a genetic perturbation that would result in a desired shift in average gene expression. Their acquisition functions consistently identified better interventions than baseline methods through every step in the multi-stage experiment.

      “If you cut the experiment off at any stage, ours would still be more efficient than the baselines. This means you could run fewer experiments and get the same or better results,” Zhang says.

      The researchers are currently working with experimentalists to apply their technique toward cellular reprogramming in the lab.

      Their approach could also be applied to problems outside genomics, such as identifying optimal prices for consumer products or enabling optimal feedback control in fluid mechanics applications.

      In the future, they plan to enhance their technique for optimizations beyond those that seek to match a desired mean. In addition, their method assumes that scientists already understand the causal relationships in their system, but future work could explore how to use AI to learn that information, as well.

      This work was funded, in part, by the Office of Naval Research, the MIT-IBM Watson AI Lab, the MIT J-Clinic for Machine Learning and Health, the Eric and Wendy Schmidt Center at the Broad Institute, a Simons Investigator Award, the Air Force Office of Scientific Research, and a National Science Foundation Graduate Fellowship. More

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      How an archeological approach can help leverage biased data in AI to improve medicine

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      The classic computer science adage “garbage in, garbage out” lacks nuance when it comes to understanding biased medical data, argue computer science and bioethics professors from MIT, Johns Hopkins University, and the Alan Turing Institute in a new opinion piece published in a recent edition of the New England Journal of Medicine (NEJM). The rising popularity of artificial intelligence has brought increased scrutiny to the matter of biased AI models resulting in algorithmic discrimination, which the White House Office of Science and Technology identified as a key issue in their recent Blueprint for an AI Bill of Rights. 

      When encountering biased data, particularly for AI models used in medical settings, the typical response is to either collect more data from underrepresented groups or generate synthetic data making up for missing parts to ensure that the model performs equally well across an array of patient populations. But the authors argue that this technical approach should be augmented with a sociotechnical perspective that takes both historical and current social factors into account. By doing so, researchers can be more effective in addressing bias in public health. 

      “The three of us had been discussing the ways in which we often treat issues with data from a machine learning perspective as irritations that need to be managed with a technical solution,” recalls co-author Marzyeh Ghassemi, an assistant professor in electrical engineering and computer science and an affiliate of the Abdul Latif Jameel Clinic for Machine Learning in Health (Jameel Clinic), the Computer Science and Artificial Intelligence Laboratory (CSAIL), and Institute of Medical Engineering and Science (IMES). “We had used analogies of data as an artifact that gives a partial view of past practices, or a cracked mirror holding up a reflection. In both cases the information is perhaps not entirely accurate or favorable: Maybe we think that we behave in certain ways as a society — but when you actually look at the data, it tells a different story. We might not like what that story is, but once you unearth an understanding of the past you can move forward and take steps to address poor practices.” 

      Data as artifact 

      In the paper, titled “Considering Biased Data as Informative Artifacts in AI-Assisted Health Care,” Ghassemi, Kadija Ferryman, and Maxine Mackintosh make the case for viewing biased clinical data as “artifacts” in the same way anthropologists or archeologists would view physical objects: pieces of civilization-revealing practices, belief systems, and cultural values — in the case of the paper, specifically those that have led to existing inequities in the health care system. 

      For example, a 2019 study showed that an algorithm widely considered to be an industry standard used health-care expenditures as an indicator of need, leading to the erroneous conclusion that sicker Black patients require the same level of care as healthier white patients. What researchers found was algorithmic discrimination failing to account for unequal access to care.  

      In this instance, rather than viewing biased datasets or lack of data as problems that only require disposal or fixing, Ghassemi and her colleagues recommend the “artifacts” approach as a way to raise awareness around social and historical elements influencing how data are collected and alternative approaches to clinical AI development. 

      “If the goal of your model is deployment in a clinical setting, you should engage a bioethicist or a clinician with appropriate training reasonably early on in problem formulation,” says Ghassemi. “As computer scientists, we often don’t have a complete picture of the different social and historical factors that have gone into creating data that we’ll be using. We need expertise in discerning when models generalized from existing data may not work well for specific subgroups.” 

      When more data can actually harm performance 

      The authors acknowledge that one of the more challenging aspects of implementing an artifact-based approach is being able to assess whether data have been racially corrected: i.e., using white, male bodies as the conventional standard that other bodies are measured against. The opinion piece cites an example from the Chronic Kidney Disease Collaboration in 2021, which developed a new equation to measure kidney function because the old equation had previously been “corrected” under the blanket assumption that Black people have higher muscle mass. Ghassemi says that researchers should be prepared to investigate race-based correction as part of the research process. 

      In another recent paper accepted to this year’s International Conference on Machine Learning co-authored by Ghassemi’s PhD student Vinith Suriyakumar and University of California at San Diego Assistant Professor Berk Ustun, the researchers found that assuming the inclusion of personalized attributes like self-reported race improve the performance of ML models can actually lead to worse risk scores, models, and metrics for minority and minoritized populations.  

      “There’s no single right solution for whether or not to include self-reported race in a clinical risk score. Self-reported race is a social construct that is both a proxy for other information, and deeply proxied itself in other medical data. The solution needs to fit the evidence,” explains Ghassemi. 

      How to move forward 

      This is not to say that biased datasets should be enshrined, or biased algorithms don’t require fixing — quality training data is still key to developing safe, high-performance clinical AI models, and the NEJM piece highlights the role of the National Institutes of Health (NIH) in driving ethical practices.  

      “Generating high-quality, ethically sourced datasets is crucial for enabling the use of next-generation AI technologies that transform how we do research,” NIH acting director Lawrence Tabak stated in a press release when the NIH announced its $130 million Bridge2AI Program last year. Ghassemi agrees, pointing out that the NIH has “prioritized data collection in ethical ways that cover information we have not previously emphasized the value of in human health — such as environmental factors and social determinants. I’m very excited about their prioritization of, and strong investments towards, achieving meaningful health outcomes.” 

      Elaine Nsoesie, an associate professor at the Boston University of Public Health, believes there are many potential benefits to treating biased datasets as artifacts rather than garbage, starting with the focus on context. “Biases present in a dataset collected for lung cancer patients in a hospital in Uganda might be different from a dataset collected in the U.S. for the same patient population,” she explains. “In considering local context, we can train algorithms to better serve specific populations.” Nsoesie says that understanding the historical and contemporary factors shaping a dataset can make it easier to identify discriminatory practices that might be coded in algorithms or systems in ways that are not immediately obvious. She also notes that an artifact-based approach could lead to the development of new policies and structures ensuring that the root causes of bias in a particular dataset are eliminated. 

      “People often tell me that they are very afraid of AI, especially in health. They’ll say, ‘I’m really scared of an AI misdiagnosing me,’ or ‘I’m concerned it will treat me poorly,’” Ghassemi says. “I tell them, you shouldn’t be scared of some hypothetical AI in health tomorrow, you should be scared of what health is right now. If we take a narrow technical view of the data we extract from systems, we could naively replicate poor practices. That’s not the only option — realizing there is a problem is our first step towards a larger opportunity.”  More

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      MIT community members elected to the National Academy of Engineering for 2023

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      Seven MIT researchers are among the 106 new members and 18 international members elected to the National Academy of Engineering (NAE) this week. Fourteen additional MIT alumni, including one member of the MIT Corporation, were also elected as new members.

      One of the highest professional distinctions for engineers, membership to the NAE is given to individuals who have made outstanding contributions to “engineering research, practice, or education, including, where appropriate, significant contributions to the engineering literature” and to “the pioneering of new and developing fields of technology, making major advancements in traditional fields of engineering, or developing/implementing innovative approaches to engineering education.”

      The seven MIT researchers elected this year include:

      Regina Barzilay, the School of Engineering Distinguished Professor for AI and Health in the Department of Electrical Engineering and Computer Science, principal investigator at the Computer Science and Artificial Intelligence Laboratory, and faculty lead for the MIT Abdul Latif Jameel Clinic for Machine Learning in Health, for machine learning models that understand structures in text, molecules, and medical images.

      Markus J. Buehler, the Jerry McAfee (1940) Professor in Engineering from the Department of Civil and Environmental Engineering, for implementing the use of nanomechanics to model and design fracture-resistant bioinspired materials.

      Elfatih A.B. Eltahir SM ’93, ScD ’93, the H.M. King Bhumibol Professor in the Department of Civil and Environmental Engineering, for advancing understanding of how climate and land use impact water availability, environmental and human health, and vector-borne diseases.

      Neil Gershenfeld, director of the Center for Bits and Atoms, for eliminating boundaries between digital and physical worlds, from quantum computing to digital materials to the internet of things.

      Roger D. Kamm SM ’73, PhD ’77, the Cecil and Ida Green Distinguished Professor of Biological and Mechanical Engineering, for contributions to the understanding of mechanics in biology and medicine, and leadership in biomechanics.

      David W. Miller ’82, SM ’85, ScD ’88, the Jerome C. Hunsaker Professor in the Department of Aeronautics and Astronautics, for contributions in control technology for space-based telescope design, and leadership in cross-agency guidance of space technology.

      David Simchi-Levi, professor of civil and environmental engineering, core faculty member in the Institute for Data, Systems, and Society, and principal investigator at the Laboratory for Information and Decision Systems, for contributions using optimization and stochastic modeling to enhance supply chain management and operations.

      Fariborz Maseeh ScD ’90, life member of the MIT Corporation and member of the School of Engineering Dean’s Advisory Council, was also elected as a member for leadership and advances in efficient design, development, and manufacturing of microelectromechanical systems, and for empowering engineering talent through public service.

      Thirteen additional alumni were elected to the National Academy of Engineering this year. They are: Mark George Allen SM ’86, PhD ’89; Shorya Awtar ScD ’04; Inderjit Chopra ScD ’77; David Huang ’85, SM ’89, PhD ’93; Eva Lerner-Lam SM ’78; David F. Merrion SM ’59; Virginia Norwood ’47; Martin Gerard Plys ’80, SM ’81, ScD ’84; Mark Prausnitz PhD ’94; Anil Kumar Sachdev ScD ’77; Christopher Scholz PhD ’67; Melody Ann Swartz PhD ’98; and Elias Towe ’80, SM ’81, PhD ’87.

      “I am delighted that seven members of MIT’s faculty and many members of the wider MIT community were elected to the National Academy of Engineering this year,” says Anantha Chandrakasan, the dean of the MIT School of Engineering and the Vannevar Bush Professor of Electrical Engineering and Computer Science. “My warmest congratulations on this recognition of their many contributions to engineering research and education.”

      Including this year’s inductees, 156 members of the National Academy of Engineering are current or retired members of the MIT faculty and staff, or members of the MIT Corporation. More

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      Subtle biases in AI can influence emergency decisions

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      It’s no secret that people harbor biases — some unconscious, perhaps, and others painfully overt. The average person might suppose that computers — machines typically made of plastic, steel, glass, silicon, and various metals — are free of prejudice. While that assumption may hold for computer hardware, the same is not always true for computer software, which is programmed by fallible humans and can be fed data that is, itself, compromised in certain respects.

      Artificial intelligence (AI) systems — those based on machine learning, in particular — are seeing increased use in medicine for diagnosing specific diseases, for example, or evaluating X-rays. These systems are also being relied on to support decision-making in other areas of health care. Recent research has shown, however, that machine learning models can encode biases against minority subgroups, and the recommendations they make may consequently reflect those same biases.

      A new study by researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and the MIT Jameel Clinic, which was published last month in Communications Medicine, assesses the impact that discriminatory AI models can have, especially for systems that are intended to provide advice in urgent situations. “We found that the manner in which the advice is framed can have significant repercussions,” explains the paper’s lead author, Hammaad Adam, a PhD student at MIT’s Institute for Data Systems and Society. “Fortunately, the harm caused by biased models can be limited (though not necessarily eliminated) when the advice is presented in a different way.” The other co-authors of the paper are Aparna Balagopalan and Emily Alsentzer, both PhD students, and the professors Fotini Christia and Marzyeh Ghassemi.

      AI models used in medicine can suffer from inaccuracies and inconsistencies, in part because the data used to train the models are often not representative of real-world settings. Different kinds of X-ray machines, for instance, can record things differently and hence yield different results. Models trained predominately on white people, moreover, may not be as accurate when applied to other groups. The Communications Medicine paper is not focused on issues of that sort but instead addresses problems that stem from biases and on ways to mitigate the adverse consequences.

      A group of 954 people (438 clinicians and 516 nonexperts) took part in an experiment to see how AI biases can affect decision-making. The participants were presented with call summaries from a fictitious crisis hotline, each involving a male individual undergoing a mental health emergency. The summaries contained information as to whether the individual was Caucasian or African American and would also mention his religion if he happened to be Muslim. A typical call summary might describe a circumstance in which an African American man was found at home in a delirious state, indicating that “he has not consumed any drugs or alcohol, as he is a practicing Muslim.” Study participants were instructed to call the police if they thought the patient was likely to turn violent; otherwise, they were encouraged to seek medical help.

      The participants were randomly divided into a control or “baseline” group plus four other groups designed to test responses under slightly different conditions. “We want to understand how biased models can influence decisions, but we first need to understand how human biases can affect the decision-making process,” Adam notes. What they found in their analysis of the baseline group was rather surprising: “In the setting we considered, human participants did not exhibit any biases. That doesn’t mean that humans are not biased, but the way we conveyed information about a person’s race and religion, evidently, was not strong enough to elicit their biases.”

      The other four groups in the experiment were given advice that either came from a biased or unbiased model, and that advice was presented in either a “prescriptive” or a “descriptive” form. A biased model would be more likely to recommend police help in a situation involving an African American or Muslim person than would an unbiased model. Participants in the study, however, did not know which kind of model their advice came from, or even that models delivering the advice could be biased at all. Prescriptive advice spells out what a participant should do in unambiguous terms, telling them they should call the police in one instance or seek medical help in another. Descriptive advice is less direct: A flag is displayed to show that the AI system perceives a risk of violence associated with a particular call; no flag is shown if the threat of violence is deemed small.  

      A key takeaway of the experiment is that participants “were highly influenced by prescriptive recommendations from a biased AI system,” the authors wrote. But they also found that “using descriptive rather than prescriptive recommendations allowed participants to retain their original, unbiased decision-making.” In other words, the bias incorporated within an AI model can be diminished by appropriately framing the advice that’s rendered. Why the different outcomes, depending on how advice is posed? When someone is told to do something, like call the police, that leaves little room for doubt, Adam explains. However, when the situation is merely described — classified with or without the presence of a flag — “that leaves room for a participant’s own interpretation; it allows them to be more flexible and consider the situation for themselves.”

      Second, the researchers found that the language models that are typically used to offer advice are easy to bias. Language models represent a class of machine learning systems that are trained on text, such as the entire contents of Wikipedia and other web material. When these models are “fine-tuned” by relying on a much smaller subset of data for training purposes — just 2,000 sentences, as opposed to 8 million web pages — the resultant models can be readily biased.  

      Third, the MIT team discovered that decision-makers who are themselves unbiased can still be misled by the recommendations provided by biased models. Medical training (or the lack thereof) did not change responses in a discernible way. “Clinicians were influenced by biased models as much as non-experts were,” the authors stated.

      “These findings could be applicable to other settings,” Adam says, and are not necessarily restricted to health care situations. When it comes to deciding which people should receive a job interview, a biased model could be more likely to turn down Black applicants. The results could be different, however, if instead of explicitly (and prescriptively) telling an employer to “reject this applicant,” a descriptive flag is attached to the file to indicate the applicant’s “possible lack of experience.”

      The implications of this work are broader than just figuring out how to deal with individuals in the midst of mental health crises, Adam maintains.  “Our ultimate goal is to make sure that machine learning models are used in a fair, safe, and robust way.” More

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      Large language models help decipher clinical notes

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      Electronic health records (EHRs) need a new public relations manager. Ten years ago, the U.S. government passed a law that required hospitals to digitize their health records with the intent of improving and streamlining care. The enormous amount of information in these now-digital records could be used to answer very specific questions beyond the scope of clinical trials: What’s the right dose of this medication for patients with this height and weight? What about patients with a specific genomic profile?

      Unfortunately, most of the data that could answer these questions is trapped in doctor’s notes, full of jargon and abbreviations. These notes are hard for computers to understand using current techniques — extracting information requires training multiple machine learning models. Models trained for one hospital, also, don’t work well at others, and training each model requires domain experts to label lots of data, a time-consuming and expensive process. 

      An ideal system would use a single model that can extract many types of information, work well at multiple hospitals, and learn from a small amount of labeled data. But how? Researchers from MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) believed that to disentangle the data, they needed to call on something bigger: large language models. To pull that important medical information, they used a very big, GPT-3 style model to do tasks like expand overloaded jargon and acronyms and extract medication regimens. 

      For example, the system takes an input, which in this case is a clinical note, “prompts” the model with a question about the note, such as “expand this abbreviation, C-T-A.” The system returns an output such as “clear to auscultation,” as opposed to say, a CT angiography. The objective of extracting this clean data, the team says, is to eventually enable more personalized clinical recommendations. 

      Medical data is, understandably, a pretty tricky resource to navigate freely. There’s plenty of red tape around using public resources for testing the performance of large models because of data use restrictions, so the team decided to scrape together their own. Using a set of short, publicly available clinical snippets, they cobbled together a small dataset to enable evaluation of the extraction performance of large language models. 

      “It’s challenging to develop a single general-purpose clinical natural language processing system that will solve everyone’s needs and be robust to the huge variation seen across health datasets. As a result, until today, most clinical notes are not used in downstream analyses or for live decision support in electronic health records. These large language model approaches could potentially transform clinical natural language processing,” says David Sontag, MIT professor of electrical engineering and computer science, principal investigator in CSAIL and the Institute for Medical Engineering and Science, and supervising author on a paper about the work, which will be presented at the Conference on Empirical Methods in Natural Language Processing. “The research team’s advances in zero-shot clinical information extraction makes scaling possible. Even if you have hundreds of different use cases, no problem — you can build each model with a few minutes of work, versus having to label a ton of data for that particular task.”

      For example, without any labels at all, the researchers found these models could achieve 86 percent accuracy at expanding overloaded acronyms, and the team developed additional methods to boost this further to 90 percent accuracy, with still no labels required.

      Imprisoned in an EHR 

      Experts have been steadily building up large language models (LLMs) for quite some time, but they burst onto the mainstream with GPT-3’s widely covered ability to complete sentences. These LLMs are trained on a huge amount of text from the internet to finish sentences and predict the next most likely word. 

      While previous, smaller models like earlier GPT iterations or BERT have pulled off a good performance for extracting medical data, they still require substantial manual data-labeling effort. 

      For example, a note, “pt will dc vanco due to n/v” means that this patient (pt) was taking the antibiotic vancomycin (vanco) but experienced nausea and vomiting (n/v) severe enough for the care team to discontinue (dc) the medication. The team’s research avoids the status quo of training separate machine learning models for each task (extracting medication, side effects from the record, disambiguating common abbreviations, etc). In addition to expanding abbreviations, they investigated four other tasks, including if the models could parse clinical trials and extract detail-rich medication regimens.  

      “Prior work has shown that these models are sensitive to the prompt’s precise phrasing. Part of our technical contribution is a way to format the prompt so that the model gives you outputs in the correct format,” says Hunter Lang, CSAIL PhD student and author on the paper. “For these extraction problems, there are structured output spaces. The output space is not just a string. It can be a list. It can be a quote from the original input. So there’s more structure than just free text. Part of our research contribution is encouraging the model to give you an output with the correct structure. That significantly cuts down on post-processing time.”

      The approach can’t be applied to out-of-the-box health data at a hospital: that requires sending private patient information across the open internet to an LLM provider like OpenAI. The authors showed that it’s possible to work around this by distilling the model into a smaller one that could be used on-site.

      The model — sometimes just like humans — is not always beholden to the truth. Here’s what a potential problem might look like: Let’s say you’re asking the reason why someone took medication. Without proper guardrails and checks, the model might just output the most common reason for that medication, if nothing is explicitly mentioned in the note. This led to the team’s efforts to force the model to extract more quotes from data and less free text.

      Future work for the team includes extending to languages other than English, creating additional methods for quantifying uncertainty in the model, and pulling off similar results with open-sourced models. 

      “Clinical information buried in unstructured clinical notes has unique challenges compared to general domain text mostly due to large use of acronyms, and inconsistent textual patterns used across different health care facilities,” says Sadid Hasan, AI lead at Microsoft and former executive director of AI at CVS Health, who was not involved in the research. “To this end, this work sets forth an interesting paradigm of leveraging the power of general domain large language models for several important zero-/few-shot clinical NLP tasks. Specifically, the proposed guided prompt design of LLMs to generate more structured outputs could lead to further developing smaller deployable models by iteratively utilizing the model generated pseudo-labels.”

      “AI has accelerated in the last five years to the point at which these large models can predict contextualized recommendations with benefits rippling out across a variety of domains such as suggesting novel drug formulations, understanding unstructured text, code recommendations or create works of art inspired by any number of human artists or styles,” says Parminder Bhatia, who was formerly Head of Machine Learning at AWS Health AI and is currently Head of ML for low-code applications leveraging large language models at AWS AI Labs. “One of the applications of these large models [the team has] recently launched is Amazon CodeWhisperer, which is [an] ML-powered coding companion that helps developers in building applications.”

      As part of the MIT Abdul Latif Jameel Clinic for Machine Learning in Health, Agrawal, Sontag, and Lang wrote the paper alongside Yoon Kim, MIT assistant professor and CSAIL principal investigator, and Stefan Hegselmann, a visiting PhD student from the University of Muenster. First-author Agrawal’s research was supported by a Takeda Fellowship, the MIT Deshpande Center for Technological Innovation, and the MLA@CSAIL Initiatives. More

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      Artificial intelligence predicts patients’ race from their medical images

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      The miseducation of algorithms is a critical problem; when artificial intelligence mirrors unconscious thoughts, racism, and biases of the humans who generated these algorithms, it can lead to serious harm. Computer programs, for example, have wrongly flagged Black defendants as twice as likely to reoffend as someone who’s white. When an AI used cost as a proxy for health needs, it falsely named Black patients as healthier than equally sick white ones, as less money was spent on them. Even AI used to write a play relied on using harmful stereotypes for casting. 

      Removing sensitive features from the data seems like a viable tweak. But what happens when it’s not enough? 

      Examples of bias in natural language processing are boundless — but MIT scientists have investigated another important, largely underexplored modality: medical images. Using both private and public datasets, the team found that AI can accurately predict self-reported race of patients from medical images alone. Using imaging data of chest X-rays, limb X-rays, chest CT scans, and mammograms, the team trained a deep learning model to identify race as white, Black, or Asian — even though the images themselves contained no explicit mention of the patient’s race. This is a feat even the most seasoned physicians cannot do, and it’s not clear how the model was able to do this. 

      In an attempt to tease out and make sense of the enigmatic “how” of it all, the researchers ran a slew of experiments. To investigate possible mechanisms of race detection, they looked at variables like differences in anatomy, bone density, resolution of images — and many more, and the models still prevailed with high ability to detect race from chest X-rays. “These results were initially confusing, because the members of our research team could not come anywhere close to identifying a good proxy for this task,” says paper co-author Marzyeh Ghassemi, an assistant professor in the MIT Department of Electrical Engineering and Computer Science and the Institute for Medical Engineering and Science (IMES), who is an affiliate of the Computer Science and Artificial Intelligence Laboratory (CSAIL) and of the MIT Jameel Clinic. “Even when you filter medical images past where the images are recognizable as medical images at all, deep models maintain a very high performance. That is concerning because superhuman capacities are generally much more difficult to control, regulate, and prevent from harming people.”

      In a clinical setting, algorithms can help tell us whether a patient is a candidate for chemotherapy, dictate the triage of patients, or decide if a movement to the ICU is necessary. “We think that the algorithms are only looking at vital signs or laboratory tests, but it’s possible they’re also looking at your race, ethnicity, sex, whether you’re incarcerated or not — even if all of that information is hidden,” says paper co-author Leo Anthony Celi, principal research scientist in IMES at MIT and associate professor of medicine at Harvard Medical School. “Just because you have representation of different groups in your algorithms, that doesn’t guarantee it won’t perpetuate or magnify existing disparities and inequities. Feeding the algorithms with more data with representation is not a panacea. This paper should make us pause and truly reconsider whether we are ready to bring AI to the bedside.” 

      The study, “AI recognition of patient race in medical imaging: a modeling study,” was published in Lancet Digital Health on May 11. Celi and Ghassemi wrote the paper alongside 20 other authors in four countries.

      To set up the tests, the scientists first showed that the models were able to predict race across multiple imaging modalities, various datasets, and diverse clinical tasks, as well as across a range of academic centers and patient populations in the United States. They used three large chest X-ray datasets, and tested the model on an unseen subset of the dataset used to train the model and a completely different one. Next, they trained the racial identity detection models for non-chest X-ray images from multiple body locations, including digital radiography, mammography, lateral cervical spine radiographs, and chest CTs to see whether the model’s performance was limited to chest X-rays. 

      The team covered many bases in an attempt to explain the model’s behavior: differences in physical characteristics between different racial groups (body habitus, breast density), disease distribution (previous studies have shown that Black patients have a higher incidence for health issues like cardiac disease), location-specific or tissue specific differences, effects of societal bias and environmental stress, the ability of deep learning systems to detect race when multiple demographic and patient factors were combined, and if specific image regions contributed to recognizing race. 

      What emerged was truly staggering: The ability of the models to predict race from diagnostic labels alone was much lower than the chest X-ray image-based models. 

      For example, the bone density test used images where the thicker part of the bone appeared white, and the thinner part appeared more gray or translucent. Scientists assumed that since Black people generally have higher bone mineral density, the color differences helped the AI models to detect race. To cut that off, they clipped the images with a filter, so the model couldn’t color differences. It turned out that cutting off the color supply didn’t faze the model — it still could accurately predict races. (The “Area Under the Curve” value, meaning the measure of the accuracy of a quantitative diagnostic test, was 0.94–0.96). As such, the learned features of the model appeared to rely on all regions of the image, meaning that controlling this type of algorithmic behavior presents a messy, challenging problem. 

      The scientists acknowledge limited availability of racial identity labels, which caused them to focus on Asian, Black, and white populations, and that their ground truth was a self-reported detail. Other forthcoming work will include potentially looking at isolating different signals before image reconstruction, because, as with bone density experiments, they couldn’t account for residual bone tissue that was on the images. 

      Notably, other work by Ghassemi and Celi led by MIT student Hammaad Adam has found that models can also identify patient self-reported race from clinical notes even when those notes are stripped of explicit indicators of race. Just as in this work, human experts are not able to accurately predict patient race from the same redacted clinical notes.

      “We need to bring social scientists into the picture. Domain experts, which are usually the clinicians, public health practitioners, computer scientists, and engineers are not enough. Health care is a social-cultural problem just as much as it’s a medical problem. We need another group of experts to weigh in and to provide input and feedback on how we design, develop, deploy, and evaluate these algorithms,” says Celi. “We need to also ask the data scientists, before any exploration of the data, are there disparities? Which patient groups are marginalized? What are the drivers of those disparities? Is it access to care? Is it from the subjectivity of the care providers? If we don’t understand that, we won’t have a chance of being able to identify the unintended consequences of the algorithms, and there’s no way we’ll be able to safeguard the algorithms from perpetuating biases.”

      “The fact that algorithms ‘see’ race, as the authors convincingly document, can be dangerous. But an important and related fact is that, when used carefully, algorithms can also work to counter bias,” says Ziad Obermeyer, associate professor at the University of California at Berkeley, whose research focuses on AI applied to health. “In our own work, led by computer scientist Emma Pierson at Cornell, we show that algorithms that learn from patients’ pain experiences can find new sources of knee pain in X-rays that disproportionately affect Black patients — and are disproportionately missed by radiologists. So just like any tool, algorithms can be a force for evil or a force for good — which one depends on us, and the choices we make when we build algorithms.”

      The work is supported, in part, by the National Institutes of Health. More