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In 1992, psychiatrist Judith L. Herman shared her groundbreaking analysis of psychological trauma, Trauma and Recovery. For years this has been among the “must read” books  on the topic, and Dr. Herman has remained a leading authority in the field. In a 2022 edition, she would add an epilogue that examines new understandings and developments in trauma research and treatment during the ensuing decades.

Throughout this time, I sensed that a lot of folks who are deeply interested in trauma wondered if Dr. Herman might have another major work in her, one that might advance our understanding of this important topic even further. This welcomed volume has arrived in the form of Truth and Repair: How Trauma Survivors Envision Justice (2023).

In this three-part series of posts, I’m taking a good look at Truth and Repair and applying its precepts to two topics that recur often on this blog, workplace bullying and therapeutic jurisprudence.

The path to Truth and Repair

In her new book, Dr. Herman summarizes that Trauma and Recovery identified three general stages of recovery from trauma, all closely focused on the individual survivor: The first stage is “the complex and demanding task of establishing safety in the present, with the goal of protection from further violence.” The second stage involves “revisit[ing] the past in order to grieve and make meaning of the trauma.” And the third stage involves a “refocus on the present and future, expanding and deepening…relationships with a wider community and…sense of possibility in life.”

It was the contemplation of a “fourth and final stage of recovery,” that of justice, which prompted Herman to work towards a new book. After all, she reasoned, “(i)f trauma is truly a social problem, and indeed it is, then recovery cannot be simply a private, individual matter.” 

With this new focus, Herman interviewed “twenty-six women and four men who are survivors of childhood sexual abuse, sexual assault, sex trafficking, sexual harassment, and/or domestic violence.” The results of these conversations helped her to conceptualize elements of justice and healing from a trauma survivor’s perspective.

Elements of justice and truth

Through her interviews, Dr. Herman identified three precepts of justice and truth, as defined by trauma survivors:

Acknowledgment — “The first precept of survivors’ justice is the desire for community acknowledgment that a wrong has been done,” for public recognition of a “survivor’s claim to justice must be the moral community’s first act of solidarity” with the survivor.

Apology — Perpetrators should provide a genuine apology for their traumatizing offenses, taking responsibility for their actions and offering to make amends. In some instances, an apology may “create the possibility of repairing a relationship.”

Accountability — While trauma survivors interviewed by Herman were ambivalent about punishment for perpetrators and complicit bystanders, many were drawn to the broader precept of accountability for individuals and institutions. Ideas behind restorative justice — a movement that embraces values of “nondomination, empowerment, and respectful listening” — resonated strongly in this context.

Elements of healing and repair

Dr. Herman’s interviews also identified three precepts of healing and repair, again as defined by trauma survivors:

Restitution — Restitution can take the form of money to cover a survivor’s losses and recovery, but it also can be defined in more systemic ways, such as creating more humane justice systems and safer institutional spaces (including workplaces). This broader take on restitution expands on the traditional legal notion of “made whole,” typically defined largely as financial compensation.

Rehabilitation — Because our justice systems, especially those governing criminal behavior, are vested mainly in the objective of punishment, “we know little about what it would actually take to bring perpetrators to relinquish violence and feel genuine remorse for their crimes.” Nevertheless, if we can find ways to “instill empathy or a feeling of common humanity in those who lack it,” we may create moral awakenings that truly safeguard our communities.

Prevention — Prevention, of course, means reducing potential exposure to traumatizing acts and events and help trauma victims in their healing. Educational programs, bystander training, and counseling and support for victims are among the preventive measures that can be implemented.

***

Truth and Repair is much richer and more fulsomely detailed on a deeply human level than I can provide in a relatively digestible summary. Indeed, this important book merits a close reading by anyone who is interested in how we, as a society, respond to psychological trauma. 

Brevity aside, I hope this gives you a good sense of Dr. Herman’s essential theme. In the next two blog posts, I will apply these findings to (1) the experience of targets of severe workplace bullying and potential responses by the legal system; and (2) the interdisciplinary field of therapeutic jurisprudence, which examines the therapeutic and anti-therapeutic properties of our laws, legal systems, and legal institutions.

Source: Judith Herman’s “Truth and Repair,” Part I: Trauma survivors’ perspectives on justice and healing

“Raise the Bar: Lead the World” is the U.S. Department of Education’s call to action to transform P-12 education and unite around what truly works. Raising the bar means recognizing that our nation already has what it takes to continue leading the world. Through initiatives such as the Parent Empowerment Pop-Ups, which are interactive sessions

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Source: Parent Empowerment Pop-Ups: Partnering with Parents for Perspective

Arnoldo Hax, the Alfred P. Sloan Professor of Management Emeritus at the MIT Sloan School of Management and an operations management expert who introduced a customer-centered approach to competitive strategy with his Delta Model, died April 20. He was 87.

Hax joined MIT Sloan in 1973 as a member of the Operations Management group. An industrial engineer who believed that management could be improved through rationalization, Hax was an early member of the strategy group at MIT Sloan, and strengthened ties with the School of Engineering.

“He was a big proselytizer for the idea that management can be made more effective,” says Professor Emeritus Michael Scott Morton of MIT Sloan. “The Delta Model was the synthesis of the factors that he saw as most important in setting a strategy.”

Inside the Delta Model

Customer bonding is at the heart of strategy; it is “fundamental” for a company to get to know the customer and provide a unique value proposition from its competitors, Hax said in a 2010 interview with Emerald Publishing.

His customer-centric view challenged the notion of putting the competition at the center of a strategy and prioritizing domination over competitors.

“The danger here is that you tend to view strategy as rivalry and the way to win is to beat someone,” he said. “That anchors us in the past, and most dangerously, it creates an obsession about the competitor’s behavior.”

To illustrate this idea, Hax and MIT Sloan’s Dean Wilde created the Delta Model. In a 1999 MIT Sloan Management Review article, they wrote that under the Delta Model, strategy and execution are connected through adaptative processes. This is achieved by:

• defining the three strategic positionings (best product, total customer solution, and system lock-in);
• aligning a firm’s competencies with the desired strategic position;
• seeking a coherent integration across business processes to produce unifying action; and
• incorporating supplier and complementor companies to ensure fulfillment of the customer value proposition.

The Delta Model was an alternative to Michael Porter’s Five Forces, the strategy field’s dominant framework.

“Porter's view was quite simple: You were either a low-cost producer or you were differentiated in some shape or form. But Arnoldo's point was that there are different ways to compete,” says MIT Sloan Deputy Dean Michael Cusumano.

“The Delta Model was more from a customer perspective. You can either compete with the best product — and ‘best’ could be related to lower cost or differentiated through quality — or you can compete as a total solutions provider, or you could have what Arnoldo called a system lock-in. Today, we would call that platform competition.”

Nicolás Majluf PhD ’79, a systems and industrial engineering professor at the Catholic University of Chile, completed his PhD in management at MIT Sloan. He and Hax co-authored several books and papers on the content and process of corporate strategy.

“He told me many times when we were writing, ‘I want to be helpful, I want to tell people how to do strategic management,’” Majluf says. “He was trying to help companies, and he was refining the Delta Model at every step of his consulting work.”

Hax’s mathematical background led him to create 10 “Haxioms” for his Delta Model and “a distillation of his knowledge in strategy.”

The 10 Haxioms are:

1. The center of strategy is the customer.
2. You don’t win by beating the competition, you win by achieving customer bonding.
3. Strategy is not war, it is love.
4. A product-centric mentality is constraining. Open your mindset to include the customers, the suppliers, and the complementors as your key constituencies.
5. Try to understand your customer deeply. Strategy is done one customer at a time.
6. Commodities only exist in the minds of the inept.
7. The two foundations of strategy are: Customer segmentation and customer value proposition, and the firm as a bundle of competencies.
8. Reject these two clichés: “The customer is always right,” and “I know the customer needs and how to satisfy them.”
9. The strategic planning process is a dialogue among the key executives of the firm.
10. Metrics are essential; experimentation is crucial.

The Delta Model isn’t the only work Hax produced at MIT Sloan with real-world applications.

In 1973 he authored a paper on hierarchical production planning, which outlined four levels of decision-making, each with its own characteristics such as the type of manager in charge of execution, the scope of the planning activity, the level of collected information, and timeline. 

“The lower one gets in the hierarchy, the narrower is the scope of the plan, the lower is the management level involved, the more detailed is the information needed, and the shorter the planning time horizon,” Hax wrote. “Each level of planning has its own objectives and constraints in which decisions have to be made.”

Connecting with the business community

Born in Santiago, Chile, Hax helped launch what is now the Leadership in Global Operations program, a dual-degree engineering and MBA track, and he led the MIT-Chile program — in 2013 he received the Medal of the Order of Commander from the president of Chile.

Hax’s integrative approach to strategy spurred him to explore new partnerships within MIT and made him notably successful with his consulting clients.

“Even though he came from operations research, having consulted with lots of companies and worked with them on planning and execution, he realized that you need people trained in organizations and strategy and management processes,” Cusumano says.

Gerhard Schulmeyer SM ’74 tapped Hax for help while Schulmeyer was navigating leadership positions including president and CEO of Siemens in the United States and as a senior vice president at Motorola.

“He helped me sort out where the strategy stood and what the changes were for the companies I took over,” says Schulmeyer, who eventually became a professor of the practice at MIT Sloan.

Executives loved him because “he could speak their language and he was teaching strategy,” says Thomas Magnanti, professor of operations research at MIT Sloan. “He was teaching how corporations can improve themselves, and these senior people who were coming to industry loved that.”

A version of this article was first published by MIT Sloan.

Source: Professor Emeritus Arnoldo Hax, who reprioritized corporate strategy, dies at 87

The Biden-Harris Administration is committed to ensuring all students are guaranteed an educational environment free from discrimination on the basis of sex. To that end, amending the Department of Education’s (Department’s) regulations that implement Title IX of the Education Amendments of 1972 (Title IX) is a top priority to ensure full protection against sex discrimination for all

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Source: A Timing Update on Title IX Rulemaking

The “interdisciplinary approach” is something that has been lauded for decades for its ability to break down silos and create new integrated approaches to research.

For Munther Dahleh, founding director of the MIT Institute for Data, Systems, and Society (IDSS), showing the community that data science and statistics can transcend individual disciplines and form a new holistic approach to addressing complex societal challenges has been crucial to the institute's success.

“From the very beginning, it was critical that we recognized the areas of data science, statistics, AI, and, in a way, computing, as transdisciplinary,” says Dahleh, who is the William A. Coolidge Professor in Electrical Engineering and Computer Science. “We made that point over and over — these are areas that embed in your field. It is not ours; this organization is here for everyone.”

On April 14-15, researchers from across and beyond MIT joined together to celebrate the accomplishments and impact IDSS has had on research and education since its inception in 2015. Taking the place of IDSS’s annual statistics and data science conference SDSCon, the celebration also doubled as a way to recognize Dahleh for his work creating and executing the vision of IDSS as he prepares to step down from his director position this summer.

In addition to talks and panels on statistics and computation, smart systems, automation and artificial intelligence, conference participants discussed issues ranging from climate change, health care, and misinformation. Nobel Prize winner and IDSS affiliate Professor Esther Duflo spoke on large scale immunization efforts, former MLK Visiting Professor Craig Watkins joined a panel on equity and justice in AI, and IDSS Associate Director Alberto Abadie discussed synthetic controls for policy evaluation. Other policy questions were explored through lightning talks, including those by students from the Technology and Policy Program (TPP) within IDSS.

A place to call home

The list of IDSS accomplishments over the last eight years is long and growing. From creating a home for 21^st century statistics at MIT after other unsuccessful attempts, to creating a new PhD preparing the trilingual student who is an expert in data science and social science in the context of a domain, to playing a key role in determining an effective process for Covid testing in the early days of the pandemic, IDSS has left its mark on MIT. More recently, IDSS launched an initiative using big data to help effect structural and normative change toward racial equity, and will continue to explore societal challenges through the lenses of statistics, social science, and science and engineering.

“I'm very proud of what we've done and of all the people who have contributed to this. The leadership team has been phenomenal in their commitment and their creativity,” Dahleh says. “I always say it doesn't take one person, it takes the village to do what we have done, and I am very proud of that.”

Prior to the institute’s formation, Dahleh and others at MIT were brought together to answer one key question: How would MIT prepare for the future of systems and data?

“Data science is a complex area because in some ways it's everywhere and it belongs to everyone, similar to statistics and AI,” Dahleh says “The most important part of creating an organization to support it was making it clear that it was an organization for everyone.” The response the team came back with was to build an Institute: a department that could cross all other departments and schools.

While Dahleh and others on the committee were creating this blueprint for the future, the events that would lead early IDSS hires like Caroline Uhler to join the team were also beginning to take shape. Uhler, now an MIT professor of computer science and co-director of the Eric and Wendy Schmidt Center at the Broad Institute, was a panelist at the celebration discussing statistics and human health.

In 2015, Uhler was a faculty member at the Institute of Science and Technology in Austria looking to move back to the U.S. “I was looking for positions in all different types of departments related to statistics, including electrical engineering and computer science, which were areas not related to my degree,” Uhler says. “What really got me to MIT was Munther’s vision for building a modern type of statistics, and the unique opportunity to be part of building what statistics should be moving forward.”

The breadth of the Statistics and Data Science Center has given it a unique and a robust character that makes for an attractive collaborative environment at MIT. “A lot of IDSS’s impact has been in giving people like me a home,” Uhler adds. “By building an institute for statistics that is across all schools instead of housed within a single department, it has created a home for everyone who is interested in the field.”

Filling the gap

For Ali Jadbabaie, former IDSS associate director and another early IDSS hire, being in the right place at the right time landed him in the center of it all. A control theory expert and network scientist by training, Jadbabaie first came to MIT during a sabbatical from his position as a professor at the University of Pennsylvania.

“My time at MIT coincided with the early discussions around forming IDSS and given my experience they asked me to stay and help with its creation,” Jadbabaie says. He is now head of the Department of Civil and Environmental Engineering at MIT, and he spoke at the celebration about a new MIT major in climate system science and engineering.

A critical early accomplishment of IDSS was the creation of a doctoral program in social and engineering systems (SES), which has the goal of educating and fostering the success of a new type of PhD student, says Jadbabaie.

“We realized we had this opportunity to educate a new type of PhD student who was conversant in the math of information sciences and statistics in addition to an understanding of a domain — infrastructures, climate, political polarization — in which problems arise,” he says. “This program would provide training in statistics and data science, the math of information sciences and a branch of social science that is relevant to their domain.”

“SES has been filling a gap,” adds Jadbabaie. “We wanted to bring quantitative reasoning to areas in social sciences, particularly as they interact with complex engineering systems.”

“My first year at MIT really broadened my horizon in terms of what was available and exciting,” says Manxi Wu, a member of the first cohort of students in the SES program after starting out in the Master of Science in Transportation (MST) program. “My advisor introduced me to a number of interesting topics at the intersection of game theory, economics, and engineering systems, and in my second year I realized my interest was really about the societal scale systems, with transportation as my go-to application area when I think about how to make an impact in the real world.”

Wu, now an assistant professor in the School of Operations Research and Information Engineering at Cornell, was a panelist at the Celebration’s session on smart infrastructure systems. She says that the beauty of the SES program lies in its ability to create a common ground between groups of students and researchers who all have different applications interests but share an eagerness to sharpen their technical skills.

“While we may be working on very different application areas, the core methodologies, such as mathematical tools for data science and probability optimization, create a common language,” Wu says. “We are all capable of speaking the technical language, and our diversified interests give us even more to talk about.”

In addition to the PhD program, IDSS has helped bring quality MIT programming to people around the globe with its MicroMasters Program in Statistics and Data Science (SDS), which recently celebrated the certification of over 1,000 learners. The MicroMasters is just one offering in the newly-minted IDSSx, a collection of online learning opportunities for learners at different skill levels and interests.

“The impact of branding what MIT-IDSS does across the globe has been great,” Dahleh says. “In addition, we’ve created smaller online programs for continued education in data science and machine learning, which I think is also critical in educating the community at large.”

Hopes for the future

Through all of its accomplishments, the core mission of IDSS has never changed.

“The belief was always to create an institute focused on how data science can be used to solve pressing societal problems,” Dahleh says. “The organizational structure of IDSS as an MIT Institute has enabled it to promote data and systems as a transdiciplinary area that embeds in every domain to support its mission. This reverse ownership structure will continue to strengthen the presence of IDSS in MIT and will make it an essential unit within the Schwarzman College of Computing.”

As Dahleh prepares to step down from his role, and Professor Martin Wainwright gets ready to fill his (very big) shoes as director, Dahleh’s colleagues say the real key to the success of IDSS all started with his passion and vision.

“Creating a new academic unit within MIT is actually next to impossible,” Jadbabaie says. “It requires structural changes, as well as someone who has a strong understanding of multiple areas, who knows how to get people to work together collectively, and who has a mission."

“The most important thing is that he was inclusive,” he adds. “He didn't try to create a gate around it and say these people are in and these people are not. I don't think this would have ever happened without Munther at the helm.”

Source: Celebrating the impact of IDSS

Troubles at the restaurant chain Burgerim highlight concerns about whether franchisees need more protection in their contracts with franchisers.

Source: Restaurant Chain Franchises Face Scrutiny From the FTC

If we could rewind the tape of species evolution around the world and play it forward over hundreds of millions of years to the present day, we would see biodiversity clustering around regions of tectonic turmoil. Tectonically active regions such as the Himalayan and Andean mountains are especially rich in flora and fauna due to their shifting landscapes, which act to divide and diversify species over time.

But biodiversity can also flourish in some geologically quieter regions, where tectonics hasn’t shaken up the land for millennia. The Appalachian Mountains are a prime example: The range has not seen much tectonic activity in hundreds of millions of years, and yet the region is a notable hotspot of freshwater biodiversity.

Now, an MIT study identifies a geological process that may shape the diversity of species in tectonically inactive regions. In a paper appearing today in Science, the researchers report that river erosion can be a driver of biodiversity in these older, quieter environments.

They make their case in the southern Appalachians, and specifically the Tennessee River Basin, a region known for its huge diversity of freshwater fishes. The team found that as rivers eroded through different rock types in the region, the changing landscape pushed a species of fish known as the greenfin darter into different tributaries of the river network. Over time, these separated populations developed into their own distinct lineages.

The team speculates that erosion likely drove the greenfin darter to diversify. Although the separated populations appear outwardly similar, with the greenfin darter’s characteristic green-tinged fins, they differ substantially in their genetic makeup. For now, the separated populations are classified as one single species. 

“Give this process of erosion more time, and I think these separate lineages will become different species,” says Maya Stokes PhD ’21, who carried out part of the work as a graduate student in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS).

The greenfin darter may not be the only species to diversify as a consequence of river erosion. The researchers suspect that erosion may have driven many other species to diversify throughout the basin, and possibly other tectonically inactive regions around the world.

“If we can understand the geologic factors that contribute to biodiversity, we can do a better job of conserving it,” says Taylor Perron, the Cecil and Ida Green Professor of Earth, Atmospheric, and Planetary Sciences at MIT.

The study’s co-authors include collaborators at Yale University, Colorado State University, the University of Tennessee, the University of Massachusetts at Amherst, and the Tennessee Valley Authority (TVA). Stokes is currently an assistant professor at Florida State University.

Fish in trees

The new study grew out of Stokes’ PhD work at MIT, where she and Perron were exploring connections between geomorphology (the study of how landscapes evolve) and biology. They came across work at Yale by Thomas Near, who studies lineages of North American freshwater fishes. Near uses DNA sequence data collected from freshwater fishes across various regions of North America to show how and when certain species evolved and diverged in relation to each other.

Near brought a curious observation to the team: a habitat distribution map of the greenfin darter showing that the fish was found in the Tennessee River Basin — but only in the southern half. What’s more, Near had mitochondrial DNA sequence data showing that the fish’s populations appeared to be different in their genetic makeup depending on the tributary in which they were found.

To investigate the reasons for this pattern, Stokes gathered greenfin darter tissue samples from Near’s extensive collection at Yale, as well as from the field with help from TVA colleagues. She then analyzed DNA sequences from across the entire genome, and compared the genes of each individual fish to every other fish in the dataset. The team then created a phylogenetic tree of the greenfin darter, based on the genetic similarity between fish.

From this tree, they observed that fish within a tributary were more related to each other than to fish in other tributaries. What’s more, fish within neighboring tributaries were more similar to each other than fish from more distant tributaries.

“Our question was, could there have been a geological mechanism that, over time, took this single species, and splintered it into different, genetically distinct groups?” Perron says.

A changing landscape

Stokes and Perron started to observe a “tight correlation” between greenfin darter habitats and the type of rock where they are found. In particular, much of the southern half of the Tennessee River Basin, where the species abounds, is made of metamorphic rock, whereas the northern half consists of sedimentary rock, where the fish are not found.

They also observed that the rivers running through metamorphic rock are steeper and more narrow, which generally creates more turbulence, a characteristic greenfin darters seem to prefer. The team wondered: Could the distribution of greenfin darter habitat have been shaped by a changing landscape of rock type, as rivers eroded into the land over time?

To check this idea, the researchers developed a model to simulate how a landscape evolves as rivers erode through various rock types. They fed the model information about the rock types in the Tennessee River Basin today, then ran the simulation back to see how the same region may have looked millions of years ago, when more metamorphic rock was exposed.

They then ran the model forward and observed how the exposure of metamorphic rock shrank over time. They took special note of where and when connections between tributaries crossed into non-metamorphic rock, blocking fish from passing between those tributaries. They drew up a simple timeline of these blocking events and compared this to the phylogenetic tree of diverging greenfin darters. The two were remarkably similar: The fish seemed to form separate lineages in the same order as when their respective tributaries became separated from the others.

“It means it’s plausible that erosion through different rock layers caused isolation between different populations of the greenfin darter and caused lineages to diversify,” Stokes says.

“This study is highly compelling because it reveals a much more subtle but powerful mechanism for speciation in passive margins,” says Josh Roering, professor of Earth sciences at the University of Oregon, who was not involved in the study. “Stokes and Perron have revealed some of the intimate connections between aquatic species and geology that may be much more common than we realize.”

This research was supported, in part, by the mTerra Catalyst Fund and the U.S. National Science Foundation through the AGeS Geochronology Program and the Graduate Research Fellowship Program. While at MIT, Stokes received support through the Martin Fellowship for Sustainability and the Hugh Hampton Young Fellowship.

Source: River erosion can shape fish evolution, study suggests

Using an artificial intelligence algorithm, researchers at MIT and McMaster University have identified a new antibiotic that can kill a type of bacteria that is responsible for many drug-resistant infections.

If developed for use in patients, the drug could help to combat Acinetobacter baumannii, a species of bacteria that is often found in hospitals and can lead to pneumonia, meningitis, and other serious infections. The microbe is also a leading cause of infections in wounded soldiers in Iraq and Afghanistan.

“Acinetobacter can survive on hospital doorknobs and equipment for long periods of time, and it can take up antibiotic resistance genes from its environment. It’s really common now to find A. baumannii isolates that are resistant to nearly every antibiotic,” says Jonathan Stokes, a former MIT postdoc who is now an assistant professor of biochemistry and biomedical sciences at McMaster University.

The researchers identified the new drug from a library of nearly 7,000 potential drug compounds using a machine-learning model that they trained to evaluate whether a chemical compound will inhibit the growth of A. baumannii.

“This finding further supports the premise that AI can significantly accelerate and expand our search for novel antibiotics,” says James Collins, the Termeer Professor of Medical Engineering and Science in MIT’s Institute for Medical Engineering and Science (IMES) and Department of Biological Engineering. “I’m excited that this work shows that we can use AI to help combat problematic pathogens such as A. baumannii.”

Collins and Stokes are the senior authors of the new study, which appears today in Nature Chemical Biology. The paper’s lead authors are McMaster University graduate students Gary Liu and Denise Catacutan and recent McMaster graduate Khushi Rathod.

Drug discovery

Over the past several decades, many pathogenic bacteria have become increasingly resistant to existing antibiotics, while very few new antibiotics have been developed.

Several years ago, Collins, Stokes, and MIT Professor Regina Barzilay (who is also an author on the new study), set out to combat this growing problem by using machine learning, a type of artificial intelligence that can learn to recognize patterns in vast amounts of data. Collins and Barzilay, who co-direct MIT’s Abdul Latif Jameel Clinic for Machine Learning in Health, hoped this approach could be used to identify new antibiotics whose chemical structures are different from any existing drugs.

In their initial demonstration, the researchers trained a machine-learning algorithm to identify chemical structures that could inhibit growth of E. coli. In a screen of more than 100 million compounds, that algorithm yielded a molecule that the researchers called halicin, after the fictional artificial intelligence system from “2001: A Space Odyssey.” This molecule, they showed, could kill not only E. coli but several other bacterial species that are resistant to treatment.

“After that paper, when we showed that these machine-learning approaches can work well for complex antibiotic discovery tasks, we turned our attention to what I perceive to be public enemy No. 1 for multidrug-resistant bacterial infections, which is Acinetobacter,” Stokes says.

To obtain training data for their computational model, the researchers first exposed A. baumannii grown in a lab dish to about 7,500 different chemical compounds to see which ones could inhibit growth of the microbe. Then they fed the structure of each molecule into the model. They also told the model whether each structure could inhibit bacterial growth or not. This allowed the algorithm to learn chemical features associated with growth inhibition.

Once the model was trained, the researchers used it to analyze a set of 6,680 compounds it had not seen before, which came from the Drug Repurposing Hub at the Broad Institute. This analysis, which took less than two hours, yielded a few hundred top hits. Of these, the researchers chose 240 to test experimentally in the lab, focusing on compounds with structures that were different from those of existing antibiotics or molecules from the training data.

Those tests yielded nine antibiotics, including one that was very potent. This compound, which was originally explored as a potential diabetes drug, turned out to be extremely effective at killing A. baumannii but had no effect on other species of bacteria including Pseudomonas aeruginosa, Staphylococcus aureus, and carbapenem-resistant Enterobacteriaceae.

This “narrow spectrum” killing ability is a desirable feature for antibiotics because it minimizes the risk of bacteria rapidly spreading resistance against the drug. Another advantage is that the drug would likely spare the beneficial bacteria that live in the human gut and help to suppress opportunistic infections such as Clostridium difficile.

“Antibiotics often have to be administered systemically, and the last thing you want to do is cause significant dysbiosis and open up these already sick patients to secondary infections,” Stokes says.

A novel mechanism

In studies in mice, the researchers showed that the drug, which they named abaucin, could treat wound infections caused by A. baumannii. They also showed, in lab tests, that it works against a variety of drug-resistant A. baumannii strains isolated from human patients.

Further experiments revealed that the drug kills cells by interfering with a process known as lipoprotein trafficking, which cells use to transport proteins from the interior of the cell to the cell envelope. Specifically, the drug appears to inhibit LolE, a protein involved in this process.

All Gram-negative bacteria express this enzyme, so the researchers were surprised to find that abaucin is so selective in targeting A. baumannii. They hypothesize that slight differences in how A. baumannii performs this task might account for the drug’s selectivity.

“We haven’t finalized the experimental data acquisition yet, but we think it’s because A. baumannii does lipoprotein trafficking a little bit differently than other Gram-negative species. We believe that’s why we’re getting this narrow spectrum activity,” Stokes says.

Stokes’ lab is now working with other researchers at McMaster to optimize the medicinal properties of the compound, in hopes of developing it for eventual use in patients.

The researchers also plan to use their modeling approach to identify potential antibiotics for other types of drug-resistant infections, including those caused by Staphylococcus aureus and Pseudomonas aeruginosa.

The research was funded by the David Braley Center for Antibiotic Discovery, the Weston Family Foundation, the Audacious Project, the C3.ai Digital Transformation Institute, the Abdul Latif Jameel Clinic for Machine Learning in Health, the DTRA Discovery of Medical Countermeasures Against New and Emerging Threats program, the DARPA Accelerated Molecular Discovery program, the Canadian Institutes of Health Research, Genome Canada, the Faculty of Health Sciences of McMaster University, the Boris Family, a Marshall Scholarship, and the Department of Energy Biological and Environmental Research program.

Source: Using AI, scientists find a drug that could combat drug-resistant infections

Every three to five days, all of the cells lining the human intestine are replaced. That constant replenishment of cells helps the intestinal lining withstand the damage caused by food passing through the digestive tract.

This rapid turnover of cells relies on intestinal stem cells, which give rise to all of the other types of cells found in the intestine. Recent research has shown that those stem cells are heavily influenced by diet, which can help keep them healthy or stimulate them to become cancerous.

“Low-calorie diets such as fasting and caloric restriction can have antiaging effects and antitumor effects, and we want to understand why that is. On the other hand, diets that lead to obesity can promote diseases of aging, such as cancer,” says Omer Yilmaz, associate professor of biology at MIT.

For the past decade, Yilmaz has been studying how different diets and environmental conditions affect intestinal stem cells, and how those factors can increase the risk of cancer and other diseases. This work could help researchers develop new ways to improve gastrointestinal health, either through dietary interventions or drugs that mimic the beneficial effects of certain diets, he says. 

“Our findings have raised the possibility that fasting interventions, or small molecules that mimic the effects of fasting, might have a role in improving intestinal regeneration,” says Yilmaz, who is also a member of MIT’s Koch Institute for Integrative Cancer Research.

A clinical approach

Yilmaz’s interest in disease and medicine arose at an early age. His father practiced internal medicine, and Yilmaz spent a great deal of time at his father’s office after school, or tagging along at the hospital where his father saw patients.

“I was very interested in medicines and how medicines were used to treat diseases,” Yilmaz recalls. “He’d ask me questions, and many times I wouldn’t know the answer, but he would encourage me to figure out the answers to his questions. That really stimulated my interest in biology and in wanting to become a doctor.”

Knowing that he wanted to go into medicine, Yilmaz applied and was accepted to an eight-year, combined bachelor’s and MD program at the University of Michigan. As an undergraduate, this gave him the freedom to explore areas of interest without worrying about applying to medical school. While majoring in biochemistry and physics, he did undergraduate research in the field of protein folding.

During his first year of medical school, Yilmaz realized that he missed doing research, so he decided to apply to the MD/PhD program at the University of Michigan. For his PhD research, he studied blood-forming stem cells and identified new markers that allowed such cells to be more easily isolated from the bone marrow.

“This was important because there’s a lot of interest in understanding what makes a stem cell a stem cell, and how much of it is an internal program versus signals from the microenvironment,” Yilmaz says.

After finishing his PhD and MD, he thought about going straight into research and skipping a medical residency, but ended up doing a residency in pathology at Massachusetts General Hospital. During that time, he decided to switch his research focus from blood-forming stem cells to stem cells found in the gastrointestinal tract.

“The GI tract seemed very interesting because in contrast to the bone marrow, we knew very little about the identity of GI stem cells,” Yilmaz says. “I knew that once GI stem cells were identified, there’d be a lot of interesting questions about how they respond to diet and how they respond to other environmental stimuli.”

Dietary questions

To delve into those questions, Yilmaz did postdoctoral research at the Whitehead Institute, where he began investigating the connections between stem cells, metabolism, diet, and cancer.

Because intestinal stem cells are so long-lived, they are more likely to accumulate genetic mutations that make them susceptible to becoming cancerous. At the Whitehead Institute, Yilmaz began studying how different diets might influence this vulnerability to cancer, a topic that he carried into his lab at MIT when he joined the faculty in 2014.

One question his lab has been exploring is why low-calorie diets often have protective effects, including a boost in longevity — a phenomenon that has been seen in many studies in animals and humans.

In a 2018 study, his lab found that a 24-hour fast dramatically improves stem cells’ ability to regenerate. This effect was seen in both young and aged mice, suggesting that even in old age, fasting or drugs that mimic the effects of fasting could have a beneficial effect.

On the flip side, Yilmaz is also interested in why a high-fat diet appears to promote the development of cancer, especially colorectal cancer. In a 2016 study, he found that when mice consume a high-fat diet, it triggers a significant increase in the number of intestinal stem cells. Also, some non-stem-cell populations begin to resemble stem cells in their behavior. “The upshot of these changes is that both stem cells and non-stem-cells can give rise to tumors in a high-fat diet state,” Yilmaz says.

To help with these studies, Yilmaz’s lab has developed a way to use mouse or human intestinal stem cells to generate miniature intestines or colons in cell culture. These “organoids” can then be exposed to different nutrients in a very controlled setting, allowing researchers to analyze how different diets affect the system.

Recently, his lab adapted the system to allow them to expand their studies to include the role of immune cells, fibroblasts, and other supportive cells found in the microenvironment of stem cells. “It would be remiss of us to focus on just one cell type,” Yilmaz says. “We’re looking at how these different dietary interventions impact the entire stem cell neighborhood.”

While Yilmaz spends most of his time running his lab at MIT, he also devotes six to eight weeks per year to his work at MGH, where he is an associate pathologist focusing on gastrointestinal pathology.

“I enjoy my clinical work, and it always reminds me about the importance of the research we do,” he says. “Seeing colon cancer and other GI cancers under the microscope, and seeing their complexity, reminds me of the importance of our mission to figure out how we can prevent these cancers from forming.”

Source: Exploring the links between diet and cancer

On April 24, MIT celebrated outstanding students and employees at the annual Change-Maker Awards for their diligent work to eradicate sexual misconduct and support survivors. These architects of positive change exemplify one of MIT’s core values: striving to make our community a more humane and welcoming place where all can thrive.

Hosted by MIT Violence Prevention and Response (VPR) and the Institute Discrimination and Harassment Response Office (IDHR), the awards are held each April to coincide with Sexual Assault Awareness Month. The awardees were recognized at a ceremony among invited senior leaders and the faculty, staff, and students involved in the Institute’s sexual misconduct prevention and response work. The awards were held in person for the first time since 2019, making this year’s celebration with fellow community members a very special event.

Chancellor Melissa Nobles opened the event by noting that, “Tonight’s honorees — individual students and staff members, a student group, and an entire office — are all amazing leaders and advocates. Day-in and day-out, they are making enduring contributions so that MIT is a more safe, supportive, respectful, and welcoming community for all.”

Nominated by peers and colleagues from across MIT, this year’s Change-Makers were selected for their multifaceted contributions, creative approaches, and breadth and depth of impact. Honors went to an undergraduate student; a graduate student; a student group; an employee group; and a PLEASURE Peer Educator of the Year. For the first time in Change-Maker Awards history, Provost Cynthia Barnhart recognized a longtime MIT employee and Change-Maker with a special recognition award.

The following students and employees are MIT’s 2023 Change-Makers:

• Outstanding Undergraduate Student: Ana Velarde, a third-year undergraduate student in biology and women's and gender studies, is an MIT Change-Maker who goes out of her way to volunteer her time, lifts up fellow community members doing this important work, and regularly facilitates workshops that challenge harmful cultural norms around sexual violence and harassment. Velarde serves on PLEASURE's Executive Committee and has led over 30 hours of peer-to-peer trainings. She co-chaired PLEASURE's biggest event of the year — PLEASURE Week, a week-long series of educational events that reach hundreds of students — to support the student group’s mission of ending sexual violence and promoting healthy relationships. Velarde’s collaboration with MIT faculty also led to a Queer Faculty and Staff Panel.
   
• Outstanding Graduate Student: Jules Drean, a fifth-year PhD student in electrical engineering and computer science and Computer Science and Artificial Intelligence Laboratory affiliate, is this year’s graduate student Change-Maker. Drean advocates for survivors of sexual violence by educating peers about reporting options and supportive measures. He is also a member of the MIT student group Student Advocates for Survivors (SAS). Through his work with the Department of Electrical Engineering and Computer Science's Thrive — a student group that supports all forms of diversity — he curated various initiatives, from a discussion group about a TV show that portrays violence to a self-care class. In all these endeavors, Drean’s thoughtful presence and unhurried compassion bring other graduate students along with him in this critical work.
   
• Outstanding Employee Group: The Office of Graduate Education (OGE) Graduate Support Staff were honored for helping graduate students navigate the aftermath of harassment or assault. They represent graduate students’ concerns on numerous committees and are helping create an online training module about navigating power dynamics. They have also taken on the day-to-day work of managing the Guaranteed Transitional Support Program, advancing funding for graduate students seeking a new lab or principal investigator. The team gladly stepped up to take on this new responsibility because they recognize the positive impact the program has on graduate students. 
   
• Outstanding Student Group: The MIT Monologues (MITMo) is an annual show run by students who create and produce an adaptation of the Vagina Monologues tailored to the MIT community. These students embody what it means to be a Change-Maker as they use theater, one of our most powerful modes of societal change, to challenge and reflect on the harmful attitudes that support sexual violence. The show is a series of performances highlighting subjects ranging from sex, gender equity, and sexual assault. The performances also actively work to highlight the experiences of those from marginalized communities. MITMo donates all profits from the show to the Boston Area Rape Crisis Center, a local nonprofit agency dedicated to helping victims of sexual assault. 
   
• Outstanding PLEASURE Peer Educator: Em McDermott, a graduating senior in biology, is this year’s PLEASURE Peer Educator Change-Maker. PLEASURE is a student-led peer education program that promotes healthy relationships and strives to eliminate sexual violence at MIT. As a Change-Maker, McDermott’s impact at MIT has been profound. This past year, they continued to serve on PLEASURE’s executive board as the communications chair. In the spring, they co-led a seminar on body positivity, body neutrality, and self-love, exploring body shaming systems and offering insight into how to reconnect with the self. Ultimately, McDermott leads with compassion and intentionally empowers others to make their voices heard, serving as a role model for peer educators for years to come.
   
• Special Recognition Award: Maryanne Kirkbride was recognized for her many years of creating change at MIT. As MIT’s deputy Institute community and equity officer and co-founder and former executive director of MindHandHeart, Kirkbride has been serving the MIT community for over 20 years. She is lauded for her creative and committed leadership at MindHandHeart, where she created and led a coalition of students, faculty, and staff who strengthened the fabric of the MIT community. At MindHandHeart she added the Department Support Program to enhance the welcoming and inclusive climate of each academic department. While Kirkbride was a nurse at MIT Medical, focused on public health, she helped secure a federal grant to fund the formation of Violence Prevention and Response, an office that provides support and advocacy for students who have experienced sexual violence. As Kirkbride will be retiring, the Change-Makers Committee felt it was important to celebrate the many ways she has worked to create a more welcoming and supportive MIT.

Source: MIT community members who work to eradicate sexual violence recognized at 2023 Change-Maker Awards