A musical life: Carlos Prieto ’59 in conversation and concert

World-renowned cellist Carlos Prieto ’59 returned to campus for an event to perform and to discuss his new memoir, “Mi Vida Musical.”

At the April 9 event in the Samberg Conference Center, Prieto spoke about his formative years at MIT and his subsequent career as a professional cellist. The talk was followed by performances of J.S. Bach’s “Cello Suite No. 3” and Eugenio “Toussaint’s Bachriation.” Valerie Chen, a 2022 Sudler Prize winner and Emerson/Harris Fellow, also performed Phillip Glass’s “Orbit.”

Prieto was born in Mexico City and began studying the cello when he was 4. He graduated from MIT with BS degrees in 1959 in Course 3, then called the Metallurgical Engineering and today Materials Science and Engineering, and in Course 14 (Economics). He was the first cello and soloist of the MIT Symphony Orchestra. While at MIT, he took all available courses in Russian, which allowed him, years later, to study at Lomonosov University in Moscow.

After graduation from MIT, Prieto returned to Mexico, where he rose to become the head of an integrated iron and steel company.

“When I returned to Mexico, I was very active in my business life, but I was also very active in my music life,” he told the audience. “And at one moment, the music overcame all the other activities and I left my business activities to devote all my time to the cello and I’ve been doing this for the past 50 years.”

During his musical career, Prieto played all over the world and has played and recorded the world premieres of 115 compositions, most of which were written for him. He is the author of 14 books, some of which have been translated into English, Russian, and Portuguese.

Prieto’s honors include the Order of the Arts and Letters from France, the Order of Civil Merit from the King of Spain, and the National Prize for Arts and Sciences from the president of Mexico. In 1993 he was appointed member of the MIT Music and Theater Advisory Committee. In 2014, the School of Humanities, Arts, and Social Sciences awarded Prieto the Robert A. Muh Alumni Award.

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The MIT Edgerton Center’s third annual showcase dazzles onlookers

On April 9, a trailer with the words “Born by Fire” emblazoned on the back pulled down MIT's North Corridor (a.k.a. the Outfinite). Students, clad in orange construction vests, maneuvered their futuristic creation out of the trailer, eliciting a surge of curious bystanders. The aerodynamic shell is covered by 5 square meters of solar panels. This multi-occupancy solar car, Gemini, designed and built by the Solar Electric Vehicle Team (SEVT), is slated to race in the 2024 American Solar Challenge. Positioned just outside Building 13, Gemini made its inaugural public appearance at this year’s Edgerton Center Student Teams Showcase. The team’s first-place trophy from an earlier competition sat atop, glistening in the sunlight.

Next, MIT Motorsports arrived with their shiny red electric race car, MY24. SEVT, embodying MIT's spirit of collaboration, paused their own installation to assist the Motorsports team in transporting MY24 into Lobby 13. Such camaraderie is commonplace among Edgerton teams. MY24 is slated to compete in two upcoming events: the FSAE Hybrid event in Loudon, New Hampshire on May 1, followed by the FSAE Motorsports event in Michigan, later in June.

At the Third Annual Edgerton Center Showcase, Lobby 13 was abuzz with students, faculty, and visitors drawn in by the passion and excitement of members of 14 Edgerton Center student teams. Team members excitedly unveiled a wide range of technologies, including autonomous waterborne craft, rockets, wind turbines, assistive devices, and hydrogen-powered turbine engines. “Seeing the culmination of what MIT students can build in so many different forms was inspiring. It was great to see everyone's passion and creativity thriving in each of the team's projects,” says junior Anhad Sawhney, president of the MIT Electronics Research Society (MITERS) and captain of the Combat Robotics Club.

In one corner, children congregated around the Combat Robotics table, captivated by clips of the team competing on the Discovery channel’s Battlebots series. Nearby, towering rockets almost brushing the ceiling captured the gaze of onlookers. Suddenly, a symphony of electrical crackles filled the air. Visitors quickly discovered the source was not an AV malfunction, but a Tesla coil created by MITERS, where lightning danced to the pitch input using a computer keyboard. Established in 1973, MITERS — a member-run project space and machine shop — continues to give students the chance to tinker and create quirky inventions such as the motorized shopping cart, DOOMsled.

Adjacent to MITERS, students on the Spokes team dished ice cream into a bike-powered blender. A quick ride down the street created milkshakes for many to enjoy. Spokes is an Edgerton team of students who will bike across the country this summer, teaching STEM outreach classes along the way. Their curriculum is inspired by MIT's hands-on approach to education.

One of the newest Edgerton Center teams, The Assistive Technology Club, showed an array of innovations poised to revolutionize lives. Their blind assistance team is designing an app that uses machine learning to describe the most relevant features of the environment to visually impaired users. Their adaptive game controller team is designing a one-handed game controller for a user who is paralyzed on one side of her body due to a stroke. Junior Ben Lou, from the robotic self-feeding device team, has a rare disease called spinal muscular atrophy. He shares, “Eating is a basic necessity, but current devices that help people like me eat are not versatile with different foods, unaccommodating to users with different positional needs, generally difficult to set up, and extremely expensive. The self-feeding team is completely re-imagining the way a self-feeding device can work. Instead of operating with a spoon, which cannot handle a wide range of foods and is prone to spillage (among other issues), our device operates with an entirely new utensil.”

Beyond showcasing projects, the event served as a forum for idea exchange and collaboration. The MIT Wind team brought their first working prototype of their model wind turbine, which they will use as a baseline for competing in the Collegiate Wind Competition next year. “We hope to continue working on rotor optimization and blade fabrication, power conversion, and offshore foundation design to be competitive with the other CWC teams next year,” says team captain Kirby Heck. “As a new Edgerton Center team, the showcase was an amazing opportunity for our team members to engage with industry partners, interact with the MIT community, and explore how we fit within the broader constellation of teams within Edgerton at MIT. We also received helpful feedback on our current design and have plenty of new ideas on how we can innovate for our next design iteration.” 

The event included a short program, where SEVT captain Adrienne Wing Suen Lai and first-year Rachel Mohommed of the Electric Vehicle Team gave a shout-out to all the teams. A special tribute was also paid to Peggy Eysenbach, the event's organizer and the development officer at the Edgerton Center, with a bouquet of flowers. Edgerton Center Director and Professor Kim Vandiver welcomed the MIT community to the event and gave a brief review of the 30-year history of engineering teams sponsored by the Edgerton Center.

Vandiver believes that through all the fun and creativity, strong careers emerge. “Participation in an engineering team is great professional preparation. Upon graduation, these leaders are unafraid of hard problems, and rapidly rise in project management roles,” Vandiver says.

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3 Questions: A shared vocabulary for how infectious diseases spread

On April 18, the World Health Organization (WHO) released new guidance on airborne disease transmission that seeks to create a consensus around the terminology used to describe the transmission of infectious pathogens through the air.

Lydia Bourouiba, the director of the MIT Fluid Dynamics of Disease Transmission Laboratory and the Fluids and Health Network, an associate professor in the MIT departments of Civil and Environmental Engineering and Mechanical Engineering, and a core member of the Institute for Medical Engineering and Science, served on the WHO expert team that developed the guidance. For more than a decade, Bourouiba’s laboratory has been researching fundamental physical processes underlying how infectious diseases spread from person to person.

The new WHO guidance puts forth new definitions of key terminology pertaining to respiratory infectious disease transmission. This reflects a new, shared understanding of how respiratory infectious pathogens move from one person to the next: through the exhalations of turbulent “puff clouds” that carry infectious contaminants in a continuum of droplet sizes and can lead to exposure at a range of distances.

Bourouiba’s lab has pioneered this physical picture and worked closely with a range of stakeholders over the years to ensure that public health guidance incorporates the latest science, improving preparedness for emerging respiratory pathogens. Bourouiba spoke with MIT News about the new WHO guidance.

Q: How did you become involved in creating these new guidelines?

A: I have been researching exhalation emissions for more than a decade. After the first SARS outbreak in 2003, I realized that the mechanisms by which respiratory pathogens are transmitted from one host to the next were essentially considered too random and too brief to be amenable to systematic investigation. Hence, the physical act of pathogen transmission was relegated to a black box. However, I also realized the fundamental importance of understanding these events mechanistically, to ultimately be able to mitigate such transmission events in a rational and principled manner. For this, we needed to understand the fluid physics and biophysics of respiratory emissions.

In the Fluid Dynamics of Disease Transmission Laboratory at MIT, we have been investigating these respiratory emissions. Our work showed that prior guidelines — specifically, the dichotomy of “large” versus “small” drops and isolated droplet emissions (essentially from spray bottles) — were not at all what we actually see and quantify when investigating respiratory emissions. We focused on establishing the full physics of such processes, from emission physiology to the fluid dynamics and biophysics of the exhalation flows and the interaction of the exhaled turbulent multiphase flow with the conditions of the ambient environment (air currents, temperature, and humidity).

Since 2015, I have also been working with the MIT Policy Lab at the Center for International Studies to disseminate our findings to public health officials and various agencies. We organized multiple conferences where we brought in scientists, clinicians, virologists, epidemiologists, microbiologists, and representatives from the U.S. Centers for Disease Control and Prevention and other groups, both before and during the pandemic.

In 2022, I was asked to serve on the World Health Organization’s technical consultation expert team, which was tasked with reaching a consensus on a new framework on respiratory infectious disease transmission. That process lasted about two years and culminated so far in the publication of the new guidelines. The process was obviously accelerated by the Covid-19 pandemic and the issues it brought to the fore regarding the inadequate old definitions. The goal of convening the consultation group was to bring together leading experts from around the globe and from very diverse fields — ranging from fluid physics to clinical medicine and epidemiology — to think through how best to redefine terms related to respiratory infectious disease transmission in light of the latest science. These new guidelines are very much a first step in a series of important consultations and efforts.

Q: How did your research change the WHO’s description of how diseases are transmitted through the air?

A: Our research established that these isolated droplets are not just exhaled as isolated droplets moving semiballistically [that will settle out of the air relatively near to the person who released them]. Instead, they are part of a multiphase turbulent puff gas cloud that contains a continuum of droplet sizes, where the cloud provides a comparatively warm and moist — and hence protective — environment for these droplets and the pathogens they contain, with respect to ambient air. One of our first papers establishing this concept was published in 2014. And we have showed since that models that do not include the proper physics of these turbulent puff clouds can dramatically underestimate the ranges of propagation and also completely shift estimates of risk and pathogen persistence in an indoor space.

These turbulent puff clouds are inhomogeneous, with potential for highly concentrated pathogen-bearing droplet load regions that can persist for a comparatively long time while moving very quickly across an indoor space in some of the most violent exhalations. Their dynamics enable potential effective inhalation exposure at a range of distances, long and short. This continuum and physical picture of concentrated packets of droplets and their impact on persistence of pathogen infectivity and exposure are in complete contrast with the notion of homogeneous mixing indoors, and the prior false dichotomy of “large” droplets that fall ballistically and “small” droplets that essentially evaporate immediately to form aerosols assumed to be deactivated. The prior picture led to the belief that only very few infectious diseases are airborne or requiring air management. This dichotomy, with other misconceptions, rooted in science from the 1930s, has surprisingly persisted in guidelines for decades.

The new guideline is a major milestone, not only because these guidelines do not change very often — every 10 or 15 years at best — but also because in addition to the WHO, five national or transnational health agencies have already endorsed the findings, including the U.S. Centers for Disease Control and Prevention, which also acknowledged the importance of the shift. 

Q: What are the biggest implications of these changes?

A: An agreed-upon common terminology is critical in infectious disease research and mitigation. The new guidelines set the foundation for such a common understanding and process. One might think it is just semantics or a small, incremental change in our understanding. However, risk calculations actually vary tremendously based on the framework one uses. We used mathematical models and physical experiments and found that the physical picture change has dramatic implications on risk estimations.

Another major implication was discussed in one of our publications from the very early stages of the pandemic, which stressed the urgent need for health care workers to have N95 masks because of these cloud dynamics and the associated importance of paying attention to indoor air management. Here again, risk calculations without the puff cloud dynamics would suggest that a typical hospital room or emergency department would dilute sufficiently the pathogen load so as to not pose a high risk. But with the puff cloud and dynamic of the droplets of a continuum of sizes within it, and coupled with it, it becomes clear that health care workers could still be exposed via inhalation to significant viral loads. Thus, they should have been provided N95 masks, in most conditions, when entering the space hosting a Covid-19 patient, even if they were not in their immediate vicinity. That article was the first to call attention to the importance of masking of health care workers due to the actual exhalation puff cloud and continuum of droplet sizes, shaping airborne transmission.

It took public health agencies more than six months to start considering shifting their masking guidelines during Covid-19. But this WHO document is broader than Covid-19. It redefines the basic definitions surrounding all respiratory infectious diseases — those that we know and those yet to come. That means there will be a different risk assessment and thereby different decision trees and policies, trickling down to different choices of protective equipment and mitigation protocols, and different parts of health agencies or facilities that might be activated or deployed.

The new guidelines are also a major acknowledgement that infectious disease transmission is truly an interdisciplinary area where scientists, clinicians, and public health officials of different backgrounds need to communicate with each other efficiently and clearly and share their insights, be it fundamental physics or clinical infectious diseases.  So, it is not just the content of these guidelines, but also the way this update unfolded. Hopefully it changes the mindset for responding to such public health threats.

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Two MIT teams selected for NSF sustainable materials grants

Two teams led by MIT researchers were selected in December 2023 by the U.S. National Science Foundation (NSF) Convergence Accelerator, a part of the TIP Directorate, to receive awards of $5 million each over three years, to pursue research aimed at helping to bring cutting-edge new sustainable materials and processes from the lab into practical, full-scale industrial production. The selection was made after 16 teams from around the country were chosen last year for one-year grants to develop detailed plans for further research aimed at solving problems of sustainability and scalability for advanced electronic products.

Of the two MIT-led teams chosen for this current round of funding, one team, Topological Electric, is led by Mingda Li, an associate professor in the Department of Nuclear Science and Engineering. This team will be finding pathways to scale up sustainable topological materials, which have the potential to revolutionize next-generation microelectronics by showing superior electronic performance, such as dissipationless states or high-frequency response. The other team, led by Anuradha Agarwal, a principal research scientist at MIT’s Materials Research Laboratory, will be focusing on developing new materials, devices, and manufacturing processes for microchips that minimize energy consumption using electronic-photonic integration, and that detect and avoid the toxic or scarce materials used in today’s production methods.

Scaling the use of topological materials

Li explains that some materials based on quantum effects have achieved successful transitions from lab curiosities to successful mass production, such as blue-light LEDs, and giant magnetorestance (GMR) devices used for magnetic data storage. But he says there are a variety of equally promising materials that have shown promise but have yet to make it into real-world applications.

“What we really wanted to achieve is to bring newer-generation quantum materials into technology and mass production, for the benefit of broader society,” he says. In particular, he says, “topological materials are really promising to do many different things.”

Topological materials are ones whose electronic properties are fundamentally protected against disturbance. For example, Li points to the fact that just in the last two years, it has been shown that some topological materials are even better electrical conductors than copper, which are typically used for the wires interconnecting electronic components. But unlike the blue-light LEDs or the GMR devices, which have been widely produced and deployed, when it comes to topological materials, “there’s no company, no startup, there’s really no business out there,” adds Tomas Palacios, the Clarence J. Lebel Professor in Electrical Engineering at MIT and co-principal investigator on Li’s team. Part of the reason is that many versions of such materials are studied “with a focus on fundamental exotic physical properties with little or no consideration on the sustainability aspects,” says Liang Fu, an MIT professor of physics and also a co-PI. Their team will be looking for alternative formulations that are more amenable to mass production.

One possible application of these topological materials is for detecting terahertz radiation, explains Keith Nelson, an MIT professor of chemistry and co-PI. This extremely high-frequency electronics can carry far more information than conventional radio or microwaves, but at present there are no mature electronic devices available that are scalable at this frequency range. “There’s a whole range of possibilities for topological materials” that could work at these frequencies, he says. In addition, he says, “we hope to demonstrate an entire prototype system like this in a single, very compact solid-state platform.”

Li says that among the many possible applications of topological devices for microelectronics devices of various kinds, “we don’t know which, exactly, will end up as a product, or will reach real industrial scaleup. That’s why this opportunity from NSF is like a bridge, which is precious, to allow us to dig deeper to unleash the true potential.”

In addition to Li, Palacios, Fu, and Nelson, the Topological Electric team includes Qiong Ma, assistant professor of physics in Boston College; Farnaz Niroui, assistant professor of electrical engineering and computer science at MIT; Susanne Stemmer, professor of materials at the University of California at Santa Barbara; Judy Cha, professor of materials science and engineering at Cornell University; industrial partners including IBM, Analog Devices, and Raytheon; and professional consultants. “We are taking this opportunity seriously,” Li says. “We really want to see if the topological materials are as good as we show in the lab when being scaled up, and how far we can push to broadly industrialize them.”

Toward sustainable microchip production and use

The microchips behind everything from smartphones to medical imaging are associated with a significant percentage of greenhouse gas emissions today, and every year the world produces more than 50 million metric tons of electronic waste, the equivalent of about 5,000 Eiffel Towers. Further, the data centers necessary for complex computations and huge amount of data transfer — think AI and on-demand video — are growing and will require 10 percent of the world’s electricity by 2030.

“The current microchip manufacturing supply chain, which includes production, distribution, and use, is neither scalable nor sustainable, and cannot continue. We must innovate our way out of this crisis,” says Agarwal.

The name of Agarwal’s team, FUTUR-IC, is a reference to the future of the integrated circuits, or chips, through a global alliance for sustainable microchip manufacturing. Says Agarwal, “We bring together stakeholders from industry, academia, and government to co-optimize across three dimensions: technology, ecology, and workforce. These were identified as key interrelated areas by some 140 stakeholders. With FUTUR-IC we aim to cut waste and CO2-equivalent emissions associated with electronics by 50 percent every 10 years.”

The market for microelectronics in the next decade is predicted to be on the order of a trillion dollars, but most of the manufacturing for the industry occurs only in limited geographical pockets around the world. FUTUR-IC aims to diversify and strengthen the supply chain for manufacturing and packaging of electronics. The alliance has 26 collaborators and is growing. Current external collaborators include the International Electronics Manufacturing Initiative (iNEMI), Tyndall National Institute, SEMI, Hewlett Packard Enterprise, Intel, and the Rochester Institute of Technology.

Agarwal leads FUTUR-IC in close collaboration with others, including, from MIT, Lionel Kimerling, the Thomas Lord Professor of Materials Science and Engineering; Elsa Olivetti, the Jerry McAfee Professor in Engineering; Randolph Kirchain, principal research scientist in the Materials Research Laboratory; and Greg Norris, director of MIT’s Sustainability and Health Initiative for NetPositive Enterprise (SHINE). All are affiliated with the Materials Research Laboratory. They are joined by Samuel Serna, an MIT visiting professor and assistant professor of physics at Bridgewater State University. Other key personnel include Sajan Saini, education director for the Initiative for Knowledge and Innovation in Manufacturing in MIT’s Department of Materials Science and Engineering; Peter O’Brien, a professor from Tyndall National Institute; and Shekhar Chandrashekhar, CEO of iNEMI.

“We expect the integration of electronics and photonics to revolutionize microchip manufacturing, enhancing efficiency, reducing energy consumption, and paving the way for unprecedented advancements in computing speed and data-processing capabilities,” says Serna, who is the co-lead on the project’s technology “vector.”

Common metrics for these efforts are needed, says Norris, co-lead for the ecology vector, adding, “The microchip industry must have transparent and open Life Cycle Assessment (LCA) models and data, which are being developed by FUTUR-IC.” This is especially important given that microelectronics production transcends industries. “Given the scale and scope of microelectronics, it is critical for the industry to lead in the transition to sustainable manufacture and use,” says Kirchain, another co-lead and the co-director of the Concrete Sustainability Hub at MIT. To bring about this cross-fertilization, co-lead Olivetti, also co-director of the MIT Climate and Sustainability Consortium (MCSC), will collaborate with FUTUR-IC to enhance the benefits from microchip recycling, leveraging the learning across industries.

Saini, the co-lead for the workforce vector, stresses the need for agility. “With a workforce that adapts to a practice of continuous upskilling, we can help increase the robustness of the chip-manufacturing supply chain, and validate a new design for a sustainability curriculum,” he says.

“We have become accustomed to the benefits forged by the exponential growth of microelectronic technology performance and market size,” says Kimerling, who is also director of MIT’s Materials Research Laboratory and co-director of the MIT Microphotonics Center. “The ecological impact of this growth in terms of materials use, energy consumption and end-of-life disposal has begun to push back against this progress. We believe that concurrently engineered solutions for these three dimensions will build a common learning curve to power the next 40 years of progress in the semiconductor industry.”

The MIT teams are two of six that received awards addressing sustainable materials for global challenges through phase two of the NSF Convergence Accelerator program. Launched in 2019, the program targets solutions to especially compelling challenges at an accelerated pace by incorporating a multidisciplinary research approach.

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Ian Waitz named vice president for research

In a letter to the MIT community today, President Sally Kornbluth announced the appointment of Ian A. Waitz to the position of vice president for research. In the role, Waitz will report to the president and oversee MIT’s vast research enterprise. The appointment is effective May 1.

Waitz, who is also the Jerome C. Hunsaker Professor of Aeronautics and Astronautics, brings deep knowledge of MIT to the position. Over more than 30 years, he has served in a wide range of roles across the Institute, where he has made his mark through energy, optimism, persistence, and a commitment to MIT’s mission of using education and innovation to create a better world.

“Ian brings a rare range and depth of understanding of MIT’s research and educational enterprise, our daily operations, our institutional challenges and opportunities, our history and our values — and an unmatched record of solving hard problems and getting big, high-stakes things done well,” Kornbluth wrote. 

“MIT’s research enterprise is a critical part of our mission, not just for the impact that innovation and discovery have on the world, but also for the way it enables us to educate people by giving them problems that no one else has ever solved before,” Waitz says. “That builds a sort of intellectual capacity and resilience to work on really hard problems, and the nation and the world need us to work on hard problems.”

Waitz will step down from his current role as vice chancellor overseeing undergraduate and graduate education, where he was instrumental in advancing the priorities of the Chancellor’s Office, currently led by Melissa Nobles.

In that role, which he has held since 2017, Waitz worked with students, faculty, and staff from across the Institute to revamp the first-year undergraduate academic experience, helped steer the Institute through the Covid-19 pandemic, and led efforts to respond to graduate student unionization. Waitz also led a strategic restructuring to integrate the former offices of the Dean for Undergraduate Education and the Dean for Graduate Education, creating the Office of the Vice Chancellor and leading to a more aligned and efficient organization. And, he spearheaded projects to expand professional development opportunities for graduate students, created the MIT Undergraduate Advising Center, worked to significantly expand undergraduate financial aid, and broadly expanded support for graduate students.

“I think my experience gives me a unique perspective on research and education at MIT,” Waitz says. “Education is obviously an amazing part of MIT, and working with students bridges education and the research. That’s one of the things that’s special about a research university. I’m excited for this new role and to continue to work to further strengthen MIT’s exceptional research enterprise.”

Waitz will be filling a role previously held by Maria Zuber, the E. A. Griswold Professor of Geophysics, who now serves as MIT’s presidential advisor for science and technology policy. Waitz says he’s eager to dive in and work to identify ways to help MIT’s prolific research engine run more smoothly. The move is just the latest example of Waitz leaning into new opportunities in service to MIT.

Prior to assuming his current role as vice chancellor, Waitz served as the dean of the School of Engineering between 2011 and 2017, supporting the school’s ability to attract and support exceptional students and faculty. He oversaw the launch of programs including the Institute for Data, Systems, and Society (IDSS), the Institute for Medical Engineering and Science (IMES), the Sandbox Innovation Fund, and the MIT Beaver Works program with Lincoln Laboratory. He also strengthened co-curricular and enrichment programs for undergraduate and graduate students, and worked with department heads to offer more flexible degrees.

Prior to that, Waitz served as the head of MIT’s Department of Aeronautics and Astronautics, where he has been a faculty member since 1991. His research focuses on developing technological, operational, and policy options to mitigate the environmental impacts of aviation. He is a member of the National Academy of Engineering, a fellow of the American Institute of Aeronautics and Astronautics, and has worked closely with industry and government throughout his career.

“One lesson I’ve learned is that the greatest strength of MIT is our students, faculty, and staff,” Waitz says. “We identify people who are real intellectual entrepreneurs. Those are the people that really thrive here, and what you want to do is create a low-friction, high-resource environment for them. Amazing things bubble up from that.”

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A closed-loop drug-delivery system could improve chemotherapy

When cancer patients undergo chemotherapy, the dose of most drugs is calculated based on the patient’s body surface area. This is estimated by plugging the patient’s height and weight into an equation, dating to 1916, that was formulated from data on just nine patients.

This simplistic dosing doesn’t take into account other factors and can lead to patients receiving either too much or too little of a drug. As a result, some patients likely experience avoidable toxicity or insufficient benefit from the chemotherapy they receive.

To make chemotherapy dosing more accurate, MIT engineers have come up with an alternative approach that can enable the dose to be personalized to the patient. Their system measures how much drug is in the patient’s system, and these measurements are fed into a controller that can adjust the infusion rate accordingly.

This approach could help to compensate for differences in drug pharmacokinetics caused by body composition, genetic makeup, chemotherapy-induced toxicity of the organs that metabolize the drugs, interactions with other medications being taken and foods consumed, and circadian fluctuations in the enzymes responsible for breaking down chemotherapy drugs, the researchers say.

“Recognizing the advances in our understanding of how drugs are metabolized, and applying engineering tools to facilitate personalized dosing, we believe, can help transform the safety and efficacy of many drugs,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.

Louis DeRidder, an MIT graduate student, is the lead author of the paper, which appears today in the journal Med.

Continuous monitoring

In this study, the researchers focused on a drug called 5-fluorouracil, which is used to treat colorectal cancers, among others. The drug is typically infused over a 46-hour period, and the dosage is determined using a formula based on the patient’s height and weight, which gives the estimated body surface area.

However, that approach doesn’t account for differences in body composition that can affect how the drug spreads through the body, or genetic variations that influence how it is metabolized. Those differences can lead to harmful side effects, if too much drug is present. If not enough drug is circulating, it may not kill the tumor as expected.

“People with the same body surface area could have very different heights and weights, could have very different muscle masses or genetics, but as long as the height and the weight plugged into this equation give the same body surface area, their dose is identical,” says DeRidder, a PhD candidate in the Medical Engineering and Medical Physics program within the Harvard-MIT Program in Health Sciences and Technology.

Another factor that can alter the amount of drug in the bloodstream at any given time is circadian fluctuations of an enzyme called dihydropyrimidine dehydrogenase (DPD), which breaks down 5-fluorouracil. DPD’s expression, like many other enzymes in the body, is regulated on a circadian rhythm. Thus, the degradation of 5-FU by DPD is not constant but changes according to the time of the day. These circadian rhythms can lead to tenfold fluctuations in the amount of 5-fluorouracil in a patient’s bloodstream over the course of an infusion.

“Using body surface area to calculate a chemotherapy dose, we know that two people can have profoundly different toxicity from 5-fluorouracil chemotherapy. Looking at one patient, they can have cycles of treatment with minimal toxicity and then have a cycle with miserable toxicity. Something changed in how that patient metabolized chemo from one cycle to the next. Our antiquated dosing fails to capture that change, and patients suffer as a result,” says Douglas Rubinson, a clinical oncologist at Dana-Farber Cancer Institute and an author of the paper.

One way to try to counteract the variability in chemotherapy pharmacokinetics is a strategy called therapeutic drug monitoring, in which the patient gives a blood sample at the end of one treatment cycle. After this sample is analyzed for the drug concentration, the dosage can be adjusted, if needed, at the beginning of the next cycle (usually two weeks later for 5-fluorouracil). This approach has been shown to result in better outcomes for patients, but it is not widely used for chemotherapies such as 5-fluorouracil.

The MIT researchers wanted to develop a similar type of monitoring, but in a manner that is automated and enables real-time drug personalization, which could result in better outcomes for patients. In their “closed-loop” system, drug concentrations can be continually monitored, and that information is used to automatically adjust the infusion rate of the chemotherapy drug and keep the dose within the target range. Such a closed-loop system enables personalization of the drug dose in a manner that considers circadian rhythm changes in the levels of drug-metabolizing enzymes, as well as any changes in the patient’s pharmacokinetics since their last treatment, such as chemotherapy-induced toxicity of the organs that metabolize the drugs.

The new system they designed, known as CLAUDIA (Closed-Loop AUtomated Drug Infusion regulAtor), makes use of commercially available equipment for each step. Blood samples are taken every five minutes and rapidly prepared for analysis. The concentration of 5-fluorouracil in the blood is measured and compared to the target range. The difference between the target and measured concentration is input to a control algorithm, which then adjusts the infusion rate if necessary, to keep the dose within the range of concentrations between which the drug is effective and nontoxic.

“What we’ve developed is a system where you can constantly measure the concentration of drug and adjust the infusion rate accordingly, to keep the drug concentration within the therapeutic window,” DeRidder says.

Rapid adjustment

In tests in animals, the researchers found that using CLAUDIA, they could keep the amount of drug circulating in the body within the target range around 45 percent of the time. Drug levels in animals that received chemotherapy without CLAUDIA remained in the target range only 13 percent of the time, on average. In this study, the researchers did not do any tests of the effectiveness of the drug levels, but keeping the concentration within the target window is believed to lead to better outcomes and less toxicity.

CLAUDIA was also able to keep the dose of 5-fluorouracil within the target range even when the researchers administered a drug that inhibits the DPD enzyme. In animals that received this inhibitor without continuous monitoring and adjustment, levels of 5-fluorouracil increased by up to eightfold.

For this demonstration, the researchers manually performed each step of the process, using off-the-shelf equipment, but they now plan to work on automating each step so that the monitoring and dose adjustment can be done without any human intervention.

To measure drug concentrations, the researchers used high-performance liquid chromatography mass spectroscopy (HPLC-MS), a technique that could be adapted to detect nearly any type of drug.

“We foresee a future where we’re able to use CLAUDIA for any drug that has the right pharmacokinetic properties and is detectable with HPLC-MS, thereby enabling the personalization of dosing for many different drugs,” DeRidder says.

The research was funded by the National Science Foundation Graduate Research Fellowship Program, a MathWorks Fellowship, MIT’s Karl van Tassel Career Development Professorship, the MIT Department of Mechanical Engineering, and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.

Other authors of the paper include Kyle A. Hare, Aaron Lopes, Josh Jenkins, Nina Fitzgerald, Emmeline MacPherson, Niora Fabian, Josh Morimoto, Jacqueline N. Chu, Ameya R. Kirtane, Wiam Madani, Keiko Ishida, Johannes L. P. Kuosmanen, Naomi Zecharias, Christopher M. Colangelo, Hen-Wei Huang, Makaya Chilekwa, Nikhil B. Lal, Shriya S. Srinivasan, Alison M Hayward, Brian M. Wolpin, David Trumper, Troy Quast, and Robert Langer.

de MIT News https://ift.tt/lFcAvgK

Geologists discover rocks with the oldest evidence yet of Earth’s magnetic field

Geologists at MIT and Oxford University have uncovered ancient rocks in Greenland that bear the oldest remnants of Earth’s early magnetic field.

The rocks appear to be exceptionally pristine, having preserved their properties for billions of years. The researchers determined that the rocks are about 3.7 billion years old and retain signatures of a magnetic field with a strength of at least 15 microtesla. The ancient field is similar in magnitude to the Earth’s magnetic field today.

The open-access findings, appearing today in the Journal of Geophysical Research, represent some of the earliest evidence of a magnetic field surrounding the Earth. The results potentially extend the age of the Earth’s magnetic field by hundreds of millions of years, and may shed light on the planet’s early conditions that helped life take hold.

“The magnetic field is, in theory, one of the reasons we think Earth is really unique as a habitable planet,” says Claire Nichols, a former MIT postdoc who is now an associate professor of the geology of planetary processes at Oxford University. “It’s thought our magnetic field protects us from harmful radiation from space, and also helps us to have oceans and atmospheres that can be stable for long periods of time.”

Previous studies have shown evidence for a magnetic field on Earth that is at least 3.5 billion years old. The new study is extending the magnetic field’s lifetime by another 200 million years.

“That’s important because that’s the time when we think life was emerging,” says Benjamin Weiss, the Robert R. Shrock Professor of Planetary Sciences in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS). “If the Earth’s magnetic field was around a few hundred million years earlier, it could have played a critical role in making the planet habitable.”

Nichols and Weiss are co-authors of the new study, which also includes Craig Martin and Athena Eyster at MIT, Adam Maloof at Princeton University, and additional colleagues from institutions including Tufts University and the University of Colorado at Boulder.

A slow churn

Today, the Earth’s magnetic field is powered by its molten iron core, which slowly churns up electric currents in a self-generating “dynamo.” The resulting magnetic field extends out and around the planet like a protective bubble. Scientists suspect that, early in its evolution, the Earth was able to foster life, in part due to an early magnetic field that was strong enough to retain a life-sustaining atmosphere and simultaneously shield the planet from damaging solar radiation.

Exactly how early and robust this magnetic shield was is up for debate, though there has been evidence dating its existence to about 3.5 billion years ago.

“We wanted to see if we could extend this record back beyond 3.5 billion years and nail down how strong that early field was,” Nichols says.

In 2018, as a postdoc working in Weiss’ lab at the time, Nichols and her team set off on an expedition to the Isua Supracrustal Belt, a 20-mile stretch of exposed rock formations surrounded by towering ice sheets in the southwest of Greenland. There, scientists have discovered the oldest preserved rocks on Earth, which have been extensively studied in hopes of answering a slew of scientific questions about Earth’s ancient conditions.

For Nichols and Weiss, the objective was to find rocks that still held signatures of the Earth’s magnetic field when the rocks first formed. Rocks form through many millions of years, as grains of sediment and minerals accumulate and are progressively packed and buried under subsequent deposition over time. Any magnetic minerals such as iron-oxides that are in the deposits follow the pull of the Earth’s magnetic field as they form. This collective orientation, and the imprint of the magnetic field, are preserved in the rocks.

However, this preserved magnetic field can be scrambled and completely erased if the rocks subsequently undergo extreme thermal or aqueous events such as hydrothermal activity or plate tectonics that can pressurize and crush up these deposits. Determining the age of a magnetic field in ancient rocks has therefore been a highly contested area of study.

To get to rocks that were hopefully preserved and unaltered since their original deposition, the team sampled from rock formations in the Isua Supracrustal Belt, a remote location that was only accessible by helicopter.

“It’s about 150 kilometers away from the capital city, and you get helicoptered in, right up against the ice sheet,” Nichols says. “Here, you have the world’s oldest rocks essentially, surrounded by this dramatic expression of the ice age. It’s a really spectacular place.”

Dynamic history

The team returned to MIT with whole rock samples of banded iron formations — a rock type that appears as stripes of iron-rich and silica-rich rock. The iron-oxide minerals found in these rocks can act as tiny magnets that orient with any external magnetic field. Given their composition, the researchers suspect the rocks were originally formed in primordial oceans prior to the rise in atmospheric oxygen around 2.5 billion years ago.

“Back when there wasn’t oxygen in the atmosphere, iron didn’t oxidize so easily, so it was in solution in the oceans until it reached a critical concentration, when it precipitated out,” Nichols explains. “So, it’s basically a result of iron raining out of the oceans and depositing on the seafloor.”

“They’re very beautiful, weird rocks that don’t look like anything that forms on Earth today,” Weiss adds.

Previous studies had used uranium-lead dating to determine the age of the iron oxides in these rock samples. The ratio of uranium to lead (U-Pb) gives scientists an estimate of a rock’s age. This analysis found that some of the magnetized minerals were likely about 3.7 billion years old. The MIT team, in collaboration with researchers from Rensselaer Polytechnic Institute, showed in a paper published last year that the U-Pb age also dates the age of the magnetic record in these minerals.

The researchers then set out to determine whether the ancient rocks preserved magnetic field from that far back, and how strong that field might have been.

“The samples we think are best and have that very old signature, we then demagnetize in the lab, in steps. We apply a laboratory field that we know the strength of, and we remagnetize the rocks in steps, so you can compare the gradient of the demagnetization to the gradient of the lab magnetization. That gradient tells you how strong the ancient field was,” Nichols explains.

Through this careful process of remagnetization, the team concluded that the rocks likely harbored an ancient, 3.7-billion-year-old magnetic field, with a magnitude of at least 15 microtesla. Today, Earth’s magnetic field measures around 30 microtesla.

“It’s half the strength, but the same order of magnitude,” Nichols says. “The fact that it’s similar in strength as today’s field implies whatever is driving Earth’s magnetic field has not changed massively in power over billions of years.”

The team’s experiments also showed that the rocks retained the ancient field, despite having undergone two subsequent thermal events. Any extreme thermal event, such as a tectonic shake-up of the subsurface or hydrothermal eruptions, could potentially heat up and erase a rock’s magnetic field. But the team found that the iron in their samples likely oriented, then crystallized, 3.7 billion years ago, in some initial, extreme thermal event. Around 2.8 billion years ago, and then again at 1.5 billion years ago, the rocks may have been reheated, but not to the extreme temperatures that would have scrambled their magnetization.

“The rocks that the team has studied have experienced quite a bit during their long geological journey on our planet,” says Annique van der Boon, a planetary science researcher at the University of Oslo who was not involved in the study. “The authors have done a lot of work on constraining which geological events have affected the rocks at different times.” 

“The team have taken their time to deliver a very thorough study of these complex rocks, which do not give up their secrets easily,” says Andy Biggin, professor of geomagnetism at the University of Liverpool, who did not contribute to the study. “These new results tell us that the Earth’s magnetic field was alive and well 3.7 billion years ago. Knowing it was there and strong contributes a significant boundary constraint on the early Earth’s environment.”

The results also raise questions about how the ancient Earth could have powered such a robust magnetic field. While today’s field is powered by crystallization of the solid iron inner core, it’s thought that the inner core had not yet formed so early in the planet’s evolution.

“It seems like evidence for whatever was generating a magnetic field back then was a different power source from what we have today,” Weiss says. “And we care about Earth because there’s life here, but it’s also a touchstone for understanding other terrestrial planets. It suggests planets throughout the galaxy probably have lots of ways of powering a magnetic field, which is important for the question of habitability elsewhere.”

This research was supported, in part, by the Simons Foundation.

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