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From the President

Strength Built Through Research

The Covid-19 pandemic is teaching us every day what it means to confront a truly global problem. From the sudden reordering of daily life to the most tragic personal consequences, few of us have been left unaffected. For any institution, a challenge of this magnitude naturally has serious practical implications; the arrival of Covid-19 drastically changed campus life overnight and forced us to reinvent nearly every aspect of our operations.

Yet despite this strain, without breaking stride, the people of MIT also began to make immediate scientific and technical contributions to fighting the pandemic. Two factors made this possible: the signature problem-solving drive of our faculty, staff, and students, and the fact that MIT had been laying the groundwork to fight a pandemic— and other urgent global challenges—through our longstanding commitment to fundamental research.

In science and engineering, MIT researchers were already grappling with deep questions bearing on human health: How do we develop effective treatments to fight pathogens? Could new data science methods help us understand the spread of infectious disease? What can atmospheric chemistry reveal about how hazardous substances in the atmosphere affect human health, and how should this inform decision making on climate policy?

At the same time, social scientists had been probing how work conditions influence employees’ health, while urban planners were investigating how the neighborhoods we live in shape our personal health outcomes. The answers they found often cast a harsh light on longstanding inequities, making it painfully clear, as we have all seen through the Covid-19 crisis, that socioeconomic disparities play a major role in determining the health of individuals and communities.

In effect, in the face of a pandemic, decades of wide-ranging fundamental research provided a springboard for practical action. As stewards and champions of this research, MIT has the opportunity—and the responsibility—to launch bold, innovative responses not only to the current Covid-19 crisis but to an array of global problems in human health, from the persistent threat of malaria to the impacts of climate change. With its focus on global health, this issue of Spectrum offers a glimpse of some of MIT’s extraordinary minds at work. And it makes clear that our common humanity demands that we respond to global health crises with global collaboration.

Sincerely,

reif-signature-2016

L. Rafael Reif

Christopher “Jack” Blazes ’22 used the skills he learned in 6.837 to computer-generate a variety of trees. Image: Courtesy of Blazes

Subjects

Algorithms for Art

Class takes deep dive into the making of computer graphics

Christopher “Jack” Blazes ’22 used the skills he learned in 6.837 to computer-generate a variety of trees. Image: Courtesy of Blazes

Title
6.837 Introduction to Computer Graphics

Instructor
Justin Solomon
Associate Professor, Department of Electrical Engineering and Computer Science
Principal Investigator, Computer Science and Artificial Intelligence Lab (CSAIL)

Solomon: “Computer graphics is all about simulating the real world on a piece of silicon.”

From the Catalog

Introduction to computer graphics algorithms, software, and hardware. Topics include ray tracing, the graphics pipeline, transformations, texture mapping, shadows, sampling, global illumination, splines, animation, and color.

The Class

A vast invisible world of algorithms powers the artful computer-generated images we see on screens from televisions to smartphones. 6.387 Introduction to Computer Graphics walks students through behind-the-scenes aspects of digitally created visual content.

Solomon: “We follow the path of visual content as it moves through your computer, all the way from describing a set of shapes to the actual pixels on your computer screen.”

“Computer graphics is a densely mathematical and technical discipline,” says associate professor Justin Solomon, who heads CSAIL’s Geometric Data Processing Group. “We really don’t cover the artistic graphic design aspects in this course. It’s more on the mechanics of how a computer generates visual content.”

Helen Ho ’19, SM ’20, who took the class as an undergraduate and later served as a teaching assistant: “It was really exciting for me to build on all the concepts that I’d learned in the more fundamental computer science classes and visually see the things that I could create.”

The class follows the computer graphics pipeline, breaking it into focused topics:

TOPIC 1: Whether the end product will be a forest of animated trees or a graphical depiction of complex data, the first step in any computer graphics project is to determine exactly what should be shown on the screen. Students learn how computers represent such things as curves, surfaces, and deformations, as well as how to capture the position and lens of a virtual camera (transformations).

TOPIC 2: The next step is to capture how stationary graphics can change over time—in other words, to animate. Lectures include both computer algorithms and the tried-and-true animation techniques used for the Walt Disney Classics of the early 20th century.

TOPIC 3: Students study two different rendering techniques, the computer processes used to transform data into visual content: ray tracing (high quality but long processing time) and rasterization (real-time rendering used to avoid lag time in interactive graphics such as video games).

Ray tracing algorithmically simulates the path of light rays as they encounter objects; it gives visual realism to computer-animated films.

With rasterization, visual content can be generated and displayed at speeds of at least 29.97 frames per second, the speed at which computer screens update visual content to outpace the human visual system.

TOPIC 4: At the end of the semester, the class addresses the different types of hardware used in each of the rendering techniques. Students discuss how advancements in graphics processing hardware, for example, have enabled the speedy processing necessary for artificial intelligence and machine learning.

“This is a discipline where the technology is changing every day in really fundamental ways,” says Solomon. “Everything has become so much more sophisticated. The visual content is absolutely stunning in modern games, movies, and design software. That’s really a byproduct of research in this discipline, advances in the hardware, and efficient computing.”

The Assignments

The assignments track the lectures, leading students through the graphics pipeline.

TOPIC 1: Students create stationary 3-D drawings of visual elements such as curves, textures, and various surfaces.

Christopher “Jack” Blazes ’22: “We went through each of the major steps of creating an image on the screen. I liked that structure a lot.”

TOPIC 2: Students control an articulated 3-D character and generate a posable human figure using algorithms that determine the angles of joints. They output the character for display on screen.

TOPIC 3: Students create a simple cloth simulator, where a sphere is draped in a material that can respond to user interactions.

TOPIC 4: Two separate assignments tackle rendering. First, students use ray tracing to generate high-resolution visual content. Second, they use rasterization to create an interactive 3-D scene with shadows that shift and scenery that changes as characters move around.

The final assignment is an open-ended project that lets the students explore their creativity while implementing the technical skills they’ve learned throughout the semester. Formatted as a competition, the project gives the winner a chance to attend the annual SIGGRAPH conference on computer graphics and interactive techniques held by the Association for Computing Machinery.

Blazes: “Mine was about procedurally generating trees and making them look realistic with some amount of randomness.”

Ho: “Our project extended on techniques we learned in class. We wanted to make a more flexible outer skin that still moved with the underlying skeleton but was less rigid than what we’d created for our assignment. We animated a running man, for example, and could see his stomach jiggle and things like that.”

What Computer Graphics Is (And Isn’t)

Solomon is careful at the beginning of the class to clarify that while computer graphics is an inherently creative discipline, 6.387 is not an animation or graphic design class. Rather, it dives into the heavy mathematical and technical techniques that lie behind the art.

“We see all this content in movies, all these great computer graphics effects,” says Ho. “But I think prior to coming into this class, a lot of students, including me, don’t know what goes into creating these effects. There is actually a significant amount of math, algorithms, and data structures that contribute to the final visual artistry.” The skills learned in class can be used outside of animated movies, of course.

Career opportunities include video game design, computer-aided design, and additive manufacturing. Students can also apply what they’ve learned to write fast, heavily processor-dependent software, such as that used for genomics research and climate modeling.

“We’re surrounded by computer screens all the time,” says Solomon. “And sure, those screens are interfaces to really complicated computational machinery, but they’re also pieces of technology for generating visual content. This area has exploded in terms of its importance and the impressively cool things that people are doing.”

Image: Amber Shen ’22

Wide Angle

Drawing Together for Justice

Image: Amber Shen ’22

At MIT, making a better world means more than work done in the lab or lecture hall; it means striving to create lasting impact. This spring, roommates Sarah Acolatse ’22 and Emily Han ’22 decided they wanted to address racial injustice. “Seeing the news about the deaths of George Floyd and Breonna Taylor, I wanted to do something,” Acolatse says, referring to two Black people whose names became rallying cries of the Black Lives Matter movement after they died in the hands of police this year. “I felt pretty helpless.”

Sharing an interest in digital art, Acolatse and Han decided to found MIT Drawn Together, a collective of artists that creates commissioned works of art in exchange for donations of at least $25. Drawn Together collects these donations and contributes them to the Black Lives Matter Foundation and other organizations focused on racial justice.

“We realized that a bunch of MIT students are very talented artists, and we decided to start a project that would let them use that talent for good,” Han says. Education on justice issues, she points out, is also a significant part of the mission. “It’s a great way to circulate information and show how donations are used.”

The roommates received an enthusiastic response when they announced the project to their fellow undergraduates via email, and their Instagram feed brought the project’s popularity to the next level. “We thought it would be a super small project, but a lot of people wanted to help,” Acolatse says. By the end of July, the pair had a “club” of more than 20 artists—mostly MIT undergraduates— that regularly meets online to discuss their artwork and give each other feedback and support. Some alumni have also gotten involved by promising matching grants from their employers. “I feel a real sense of community, even though we’re not together on campus,” Acolatse says.

In just two months, Drawn Together artists created more than 100 original pieces, raising more than $3,500. The founders plan to continue the project indefinitely. “After starting this project, I feel like I have been able to express whatever passion I have to support the people I love and care about,” Acolatse says. “It has made me realize that a lot of people really do care about these important issues, and it’s been heartwarming to see.”

As the pandemic unfolded, the MIT community quickly rolled up its collective sleeves and went to work. Image: Getty Images

Global Health

Rapid Response

How the MIT community addressed the pandemic during the first few months of 2020

As the pandemic unfolded, the MIT community quickly rolled up its collective sleeves and went to work. Image: Getty Images

The first cluster of Covid-19 cases was reported to the World Health Organization on December 31, 2019. As the pandemic unfolded, the MIT community quickly rolled up its collective sleeves and went to work—contributing research, donating personal protective equipment, assessing economic impacts, teaching remote classes, and much more. This timeline provides a snapshot of MIT’s extensive efforts to address the crisis during the first few months.

January

A team of researchers at the McGovern Institute for Brain Research at MIT, the Broad Institute of MIT and Harvard, and other departments and centers begin developing tests for Covid-19 using SHERLOCK, a diagnostic tool based on the genome editor CRISPR.

February

The Cambridge-based biotech company Moderna announces it has an experimental vaccine ready to test. Moderna was founded in 2010 by Institute Professor Robert S. Langer ScD ’74, investor Noubar Afeyan PhD ’87, and researchers from Harvard Medical School.

Chemical engineers at MIT’s Koch Institute for Integrative Cancer Research dive into work on a Covid-19 vaccine and on ways to ramp up future vaccine manufacturing.

March

MIT Emergency Management establishes the Covid-19 planning team and working groups on March 5. MIT Solve, which uses social impact challenges to tackle the world’s biggest problems, launches a $10,000 global challenge seeking innovations focused on prevention, detection, and response to Covid-19.

Open-source, low-cost ventilator.
A group of researchers worked on an open-source, low-cost ventilator.

On March 10, MIT announces all classes will move online on March 30. Undergraduates are asked to depart campus residences by March 17. The MIT E-Vent team—including mechanical engineering professor Alex Slocum Sr. ’82, SM ’83, the Walter M. May and A. Hazel May Professor, his son surgical resident Alexander Slocum Jr. SB ’08, SM ’10, PhD ’13, and MIT research scientist Nevan Hanumara MS ’06, PhD ’12— forms to work on rapid deployment of an open-source, low-cost ventilator first introduced in 2010 by a student team in Course 2.75 Medical Device Design.

Faculty and staff begin working from home on March 13. The MIT Abdul Latif Jameel Clinic for Machine Learning in Health forms AI Cures to apply machine-learning methods to finding promising antiviral molecules.

The Stanford-MIT Healthy Elections project launches, bringing academics and election administration experts together to address the unprecedented and ongoing threat that the pandemic poses to the 2020 elections.

Drawing on technology developed at MIT’s Institute for Medical Engineering and Science (IMES), startup E25Bio works to develop a quick paper-strip test for Covid-19. Students from MIT and Harvard University launch CovEducation, a mentoring platform that provides support for children while schools are closed.

MIT students collectively construct a 1:1 scale replica of MIT online in Minecraft. The MIT Innovation Initiative begins work on the Covid-19 Rapid Innovation Dashboard, which will become a hub of MIT’s Covid-19-related activities. A team of MIT chemists reports designing a drug candidate that may block coronaviruses’ ability to enter human cells.

MIT students collectively constructed a 1:1 scale replica of Minecraft.
MIT students collectively constructed a 1:1 scale replica of Minecraft.

Economists, including MIT’s Iván Werning, argue that the supply shock of Covid-19 has led to an even larger demand shock, as affected workers lose income and all consumers cut back on spending, and that policy responses are needed to address both types of shocks.

MIT researchers and colleagues propose repurposing a blood clot drug—a protein called tissue plasminogen activator—to aid Covid-19 patients in acute respiratory distress. The Covid-19 Policy Alliance, a team of MIT faculty and experts, maps the most risk-prone counties in the United States.

More than 50 departments, labs, and centers—as well as individual community members, including alumni and friends around the world—donate personal protective equipment to health care workers. Mail Services and Custodial Services team up to get thousands of items to area hospitals.

Roughly 1,200 MIT subjects move to a remote teaching and learning model. A website developed by the Teaching and Learning Lab, Open Learning, and Information Systems and Technology provides soup-to-nuts instructions on preparing classes for remote delivery.

Face shield.
MIT initiates the mass manufacture of disposable face shields, spearheaded by Project Manus.

MIT initiates mass manufacture of disposable face shields  for Covid-19 response. MIT’s Project Manus, led by mechanical engineering professor Martin Culpepper SM ’97, PhD ’00, spearheads the project in collaboration with a number of MIT and community partners, including physician Elazer R. Edelman ’78, SM ’79, PhD ’84, director of IMES and the MIT Medical Outreach Team, and the Edward J. Poitras Professor at IMES.

This high-magnification image shows mucin polymers, the key component of mucus. Image: Courtesy of Katharina Ribbeck

Fall 2020

A Slippery Viral Defense

Katharina Ribbeck works to boost protection offered by mucus

This high-magnification image shows mucin polymers, the key component of mucus. Image: Courtesy of Katharina Ribbeck

Our cells pump out more than a liter of mucus a day: a slimy line of defense against pathogens, toxins, and viruses. Unfortunately, SARS-CoV-2 seems to sneak past mucus with perplexing ease.

Katharina Ribbeck, the Mark Hyman Jr. Career Development Associate Professor of Biological Engineering, wants to pinpoint exactly how SARSCoV- 2, the virus that causes Covid-19, binds to and travels through mucus. “We want to get to the bottom of mucus’s role as an immune barrier,” she says.

Anyone with a cold or allergies is hyperaware of how continuously the body secretes mucus. But mucus, generally scorned as snot, is not just a product of the nose. Part viscous liquid and part elastic solid, mucus hydrates, lubricates, and transports fluids throughout the body. Dedicated cells adjust the amount and type of mucus secreted depending on the threat detected.

Understudied biopolymers

Mucus first captured Ribbeck’s attention when she was studying a different polymer system at the University of Heidelberg. Mucus and its main structural component, biopolymers called mucins, struck her as significantly understudied given their importance in health and disease. Her research to date has drawn attention to the value of mucins, which are now being eyed by the food, agriculture, and biomedical industries for potential use in consumer products.

Bolstering mucus’s role as a security force is its community of microorganisms, or microbiome, which act on toxins and pathogens. Ribbeck and colleagues have identified components within mucus that don’t necessarily kill pathogens but disarm them. Some of these are members of a diverse family of sugars called glycans that protrude from mucin’s bottlebrush-shaped filaments. The exact function of these sugars is still a mystery; Ribbeck calls them “therapeutic libraries” with broad-spectrum effects on microbes, both good and bad.

Within the lungs, these sugars may act as receptors for the signature spike proteins that enable coronaviruses to slip inside a cell and replicate. But sugars in the protective mucosal layer could potentially prevent the virus from entering the cell by mimicking receptors on the cell surface, offering decoy binding sites.

It’s been suggested that influenza A sneaks through mucus by slicing off these decoys. It’s not clear whether SARS-CoV-2 uses this tactic or another means to avoid being trapped in mucus like an insect in tree sap.

An inhaled virus such as SARS-CoV-2 must navigate a relatively thick layer of mucus. Ribbeck says it’s unlikely that viral particles can diffuse through mucus faster than mucus can sweep them out of the body, so SARS-CoV-2 must have evolved a strategy to co-opt or overcome mucus’s defenses. “Something in our understanding of Covid-19 pathogenesis is missing,” she says. Does the virus move through mucus differently than do other particles its size to escape retention? Does it use spike proteins to bind to substances and to propel itself forward, or hitchhike a ride with other microbes?

Exactly how SARS-CoV-2 enters the body is what Ribbeck’s lab has been investigating this year with the help of a National Science Foundation grant. Analyzing samples from healthy and infected patients, both symptomatic and asymptomatic, should help the team understand in more detail how pathogenesis occurs, she says.

Boosting function

Although researchers don’t yet have the tools to precisely tune mucus production within the body, Ribbeck says she and her colleagues are considering ways to engineer, reconstitute, or replenish mucus molecules on body surfaces that have run low or where mucus is not as functional as it should be. There might even be a way to boost the mucus microbiome by supplementing it, the same way that probiotics supplement the gut microbiome.

Repairing or enhancing mucus holds out the hope of a novel approach to foiling viruses such as SARS-CoV-2. “Perhaps it binds to something within mucus in a way that we could potentially disrupt,” Ribbeck says. “Or we could equip the mucus barrier with molecules that trap and clear the virus.” Mucus is already an effective security force; Ribbeck hopes to identify and deliver the extra firepower it needs to overcome a formidable enemy.

Professor Kate Brown studies how human behaviors lead to disasters such as the 1986 nuclear explosion in Chernobyl, left, and the 2020 Covid-19 pandemic, right. Photos (left): Francois Lochon / Gamma-Rapho via Getty Images; (right): Dan Kitwood/Getty Images

Global Health

Unnatural Disasters

Historian links health consequences to human actions

Professor Kate Brown studies how human behaviors lead to disasters such as the 1986 nuclear explosion in Chernobyl, left, and the 2020 Covid-19 pandemic, right. Photos (left): Francois Lochon / Gamma-Rapho via Getty Images; (right): Dan Kitwood/Getty Images

The coronavirus pandemic is not a purely natural disaster. According to Kate Brown, a professor in the MIT Program in Science, Technology, and Society, zoonotic diseases— those initially transmitted from animals to humans, including Covid-19—can occur more frequently and strike more powerfully as a direct consequence of the stresses humans place on the environment.

Contributing to the current pandemic and to other infectious disease flare-ups in recent decades is the fact that animals and humans now live in increasingly close quarters, with human populations encroaching ever further into wildlife zones, Brown maintains. Modern industrial-scale agriculture is another culprit: tens of thousands of chickens, for example, can be raised within a single barn in just six weeks, an accelerated time frame that encourages pathogens to transform from sublethal residents into deadly invaders.

Although self-isolation is a key preventative strategy, the human body is not hermetically sealed, Brown points out. “We’re wading through an atmosphere filled with viruses and bacteria, antibiotic-resistant microbes and radioactive contaminants, and our bodies act like nets in the ocean, catching and filtering almost everything passing through.” Protecting ourselves when we are so porous is a huge challenge, compounded by the fact that we face a vast array of environmental toxins predominantly of anthropogenic origin, in addition to the threats posed by virulent biological agents.

Brown has catalogued many cases where human behavior has compromised the environment, thereby jeopardizing human health and welfare, in a series of award-winning books.

The first, A Biography of No Place: From Ethnic Borderland to Soviet Heartland (Harvard University Press, 2004), describes a region along the Ukraine-Poland border chronically besieged by war, famine, and ethnic cleansing. She chose the first-person voice for this and her other books, which is unusual for historical works, in order to “bring readers along and help them visualize these places.”

In Plutopia: Nuclear Families in Atomic Cities and the Great Soviet and American Plutonium Disasters (Oxford University Press, 2013), Brown profiled two cities that were built around the world’s first nuclear plants to produce weapons-grade plutonium, one in Hanford, Washington, and the other in Ozersk, Russia. Over a period of decades, each plant unleashed some 350 million curies of radioactivity with devastating repercussions. Similar tales unfold in Dispatches from Dystopia: Histories of Places Not Yet Forgotten (University of Chicago Press, 2015), in which Brown explores “modernist wastelands” such as America’s biggest Superfund site, a former copper mine near Butte, Montana, despoiled by arsenic, heavy metals, and contaminated soil, and its counterpart, a ravaged mining town in Kazakhstan. Manual for Survival (W. W. Norton & Company, 2019), meanwhile, takes a close look at the medical and environmental consequences of fallout from the 1986 Chernobyl nuclear disaster. Long-lived radionuclides released in that accident are still circulating, with high levels of radiation emitted just this year during forest fires near the reactor complex.

One lesson emerging from Brown’s work is that natural and human-made disasters are now so closely entwined it can be hard to disentangle the two. Yet she sees some grounds for hope, albeit from an unlikely source. “The [coronavirus] pandemic is teaching us a great deal,” she says. “We’ve learned how to slow down, to communicate over the phone and internet rather than getting on a plane every other day. And people have shown they’re willing to make economic sacrifices to save lives.” Thanks to these changes, CO2 output has dropped, which means fewer people will die from air pollution and respiratory illnesses, Brown says.

“Economic projections suggest it won’t be easy to get back to where we were,” she adds. “Part of the reset, which I hope is now underway, should involve thinking about more sustainable, just, and equitable ways of resuming our economic activity.”

Brown’s current research, which explores a shift toward more energy-efficient and environmentally forgiving modes of farming, is aligned with that theme. While people today focus on the growth of financial indicators, she says, “we ignore the phenomenal growth around us—the ability of plants to create biomass, turn carbon dioxide into oxygen, and fill our soils with nutrients. That’s the kind of growth that’s really radical, and that’s the kind of growth we should be promoting.”

Steve Nadis is a 1997–98 MIT Knight Science Journalism Fellow.

Image: Betsy Skrip, CBI

Global Health

Building Safer Food Systems

New initiative addresses hazards throughout the supply chain

Image: Betsy Skrip, CBI

The Covid-19 pandemic has drawn new attention to the safety of the global food supply. Early reports suggested that SARS-CoV-2, the novel coronavirus that causes this disease, may have begun its deadly spread from the Huanan Seafood Wholesale Market in Wuhan, China. While we may never know the true origin of the disease, scientists agree that markets that sell fresh meat and fish create the ideal conditions for viruses to jump from animals to humans, and to spread from humans to other humans. The 2002 SARS outbreak began at a similar market in China. Viruses are just one of many potential threats along the food chain that leads from farm to market to table. Those threats have proven deadly. In 2008, milk and infant formula tainted with the chemical melamine sent more than 50,000 Chinese babies to the hospital, killing six. An outbreak of the food-borne bacterium Listeria caused nearly 200 deaths in South Africa between 2017 and 2018. A strain of E. coli bacteria traced back to romaine lettuce from Yuma, Arizona, sickened hundreds of people across 36 US states in 2018.

In summer 2020, the MIT Sloan School of Management launched a new initiative to help keep our food safe: the Food Supply Chain Analytics and Sensing Initiative (FSAS). “This is a global challenge with relevance to every country on the planet,” says Retsef Levi, the J. Spencer Standish Professor of Operations Management and faculty director of FSAS. “Food and agriculture supply chains have major and multifaceted impact on human health and pose major challenges to governments and industry across the globe. We hope that our multidisciplinary work can help inform policies and industry practices and build better global food systems.” FSAS will develop and disseminate new analytical tools that can assess and promote food safety around the world. “The ultimate goal is to revolutionize how risk is managed in food supply chains,” says Stacy Springs, executive director of FSAS. “To do that, we need to extract data, map supply chains, and create the automated tools that will help us identify the areas where the greatest risk resides.”

The multidisciplinary initiative involves faculty and graduate students from MIT’s School of Science and School of Engineering as well as MIT Sloan, and it will work in partnership with additional academic institutions, industry, government agencies, and nongovernmental organizations. There are three areas of work: management of food safety and adulteration risks; design and optimization of agricultural supply chains and markets; and issues of food access and food waste.

The agricultural supply chain study is of particular importance to developing countries, where agriculture is often the largest source of employment and where struggling farmers or merchants may be tempted to cheat on hygiene or even poison their produce. “If you don’t look after the welfare of food producers, you put them in a situation where bad practices and food fraud can occur,” Levi explains.

Solid research foundation

In 2013, Levi and Springs began work with the US Food and Drug Administration to develop predictive models for managing risks from the global food supply chain. The initial focus of this contract was on imports from China. FSAS members also received seed funding from the MIT Abdul Latif Jameel Water and Food Systems Lab to work on research ranging from supply chain mapping to the development of bioassays for identifying unknown adulterants. Three years later, Levi, Springs, and Yasheng Huang, all principal investigators at FSAS, received a $7.5 million grant based on these earlier works to support a broad food-safety study in China. They then took a team of MIT faculty and students on a research trip to China in 2018. “The team’s first focus was on freshwater aquatic supply chains,” Springs says. “We met with many future collaborators, identified public data sources that could support the research, and visited several wholesale markets in Zhejiang province.” From there, Levi’s team set a course to mine much of the available food safety data, create structured databases, and build tools to automate that process.

MIT’s food safety work has since expanded with faculty and research in India, Indonesia, and Thailand. While the scope of FSAS is global, the initiative will tailor its approach to each region. “Food supply chains in China, for example, are even longer and more complex than they are in the United States,” explains Huang, who is also the Epoch Foundation Professor of International Management at MIT Sloan. “And unlike in the US, Chinese farms are extremely decentralized, with tens of millions of individual farmers. It is challenging to identify the best point along the chain to intervene.”

Although some data on food safety and adulteration in China is available to the public, the information is scattered across hundreds of different sites and publications. Analyzing these multiple sources and consolidating data on aquatic food chains led Huang and his colleagues to an important insight: Chinese wholesale markets were a key source of risk in that country’s food supply chain.

Unfortunately, that insight alone will not lead to greater food safety.

“We need to come up with measures for things we don’t typically measure,” says Huang, whose research centers on government regulations. “A measure for how transparent each local administration is about food safety issues. Or a measure that tells us how actively that local government enforces food safety. No one is measuring this sort of information. It’s up to academics to come up with new ways to harvest and analyze this data.”

Focus on farms

Along with creating and analyzing metrics on wholesale markets, FSAS will also create platforms to collect data from smallholders and family farms—the so-called “first mile” of the food supply chain, which provides more than 50% of the world’s calories. It’s a tough job. “We have very little information about this informal first mile,” says Joann de Zegher, the Maurice F. Strong Career Development Professor and assistant professor of operations management. “But most of the smallholders have mobile phones, allowing us to develop and leverage mobile-based platforms to help them make better decisions.”

De Zegher believes creating a digital platform for smallholders could augment food safety as well as promote sustainability. “Right now, if you’re sourcing from smallholder farms, it’s difficult to know where a specific product or lot comes from,” says de Zegher, who studies palm oil production in Indonesia. “With digital tools, we could trace the origins of a shipment.” Such work could provide food safety information and other benefits, such as determining whether the palm oil came from an area that was deforested illegally.

While enhancing food safety across the globe, FSAS also endeavors to help smallholder farmers thrive. “We and our partners are working to develop platforms that help inform farmers of best practices. The platforms will also create access to new markets for farmers,” says Yanchong Karen Zheng, the Sloan School Career Development Professor, associate professor of operations management, and an FSAS collaborator. “Right now, these farmers have very limited choices of where they can sell their produce.”

Marie-Laurie Charpignon. Photo: Sarah Bastille Photography

Global Health

A Model Approach to Public Health

IDSS researcher applies data science to tracking Covid-19

Marie-Laurie Charpignon. Photo: Sarah Bastille Photography

When Marie-Laure Charpignon started her PhD at the MIT Institute for Data, Systems, and Society (IDSS) in 2018, she never imagined that a year and a half later, the very same data-science skills she was developing would be needed to tackle one of the biggest public-health problems of this century: Covid-19. Yet Charpignon suddenly found herself consumed by Covid-19 research, often working late into the night to model the pandemic’s deadly spread.

Charpignon’s research took this unexpected turn in early 2020 as Covid-19 hit the United States. Her mentor, Maimuna Majumder SM ’15, PhD ’18, invited her to join the newly formed Covid-19 Dispersed Volunteer Research Network, a broad-based effort to put scientists to work fighting the pandemic. Since then, Charpignon has been working with others to model the spread of Covid-19 within different states.

To estimate how quickly the virus is likely to propagate, the model incorporates information on current public health restrictions, the distribution of families, demographics on age and preexisting conditions, and patterns of contact. Researchers can then adjust model inputs to predict how different public-health policies may affect the spread. For example, the model showed that in Georgia, Florida, and Mississippi, implementing initial quarantine lockdowns a week and a half earlier would have saved hundreds of lives—and continuing those lockdowns for several weeks longer could have saved thousands.

Charpignon says the goal is not only to understand spreading dynamics but also to forecast undocumented Covid-19 cases, which can inform vaccine purchase and distribution. “It’s really like resource planning,” she says. “Once you have an estimate, you can start your resource budgeting.”

Until a two-year stint at Microsoft Education, where she saw firsthand how schools struggle to address health issues such as nutrition and disease prevention, Charpignon never considered the intersection between data science and public health. It was clear to her then that public health was a field that needed more research. The experience solidified her next step: pursuing a PhD at IDSS, which focuses on applying advanced analytical tools to complex societal challenges. “IDSS is very interdisciplinary,” she says. “I think this is the future.”

Alzheimer’s research

At IDSS, Charpignon uses computational tools to explore large-scale questions in public health with a focus on nontraditional data sources. Her main project centers on drug repurposing for Alzheimer’s disease. “There is no cure for Alzheimer’s, but as we get older, we all start taking multiple medications,” says Charpignon, who is advised on the project by Roy Welsch, the Eastman Kodak Leaders for Global Operations Professor of Management, and Stan Finkelstein ’71, a senior research scientist with IDSS who has been working on repurposing drugs for many years. The research team began to ask whether some of the drugs that we already take, specifically those for diabetes, might reduce the risk of Alzheimer’s.

To address this question, the team is analyzing tens of thousands of electronic-health records in the United States and the United Kingdom and pairing findings with data on how neural cells respond to different drugs. Early results suggest the diabetes drug metformin may be linked to less severe dementia, a connection that the team is investigating further. Charpignon is also working on other Covid-19 projects. In one, she and her teammates are focusing on social media, examining how sentiment about the Centers for Disease Control and Prevention (CDC) and mask wearing is evolving on Twitter. The researchers extract a representative sample of tweets mentioning the CDC and masks and classify each by sentiments such as fear, anger, and trust or mistrust. They then track how sentiment changes over time and evaluate what happens when influential people express their opinions.

“What we want to understand is how to frame health messaging on social media to drive or influence people,” Charpignon explains. “I think it’s important to do surveillance of reactions on social media and adapt health messaging to this.”

If there is a silver lining to Covid-19, Charpignon says it is bringing newfound attention to public health as a vital area of study. “I think there is a lot of low-hanging fruit” in public health research, she says, and the field will benefit greatly from additional recognition and resources. “Public health should be the responsibility of everyone,” she adds. “There is really a lot of optimization that could be done.”

Jacquin Niles ’94, PhD ’01. Photo: Bryce Vickmark

Global Health

Lessons from an Old Enemy

Jacquin Niles employs biological engineering to fight malaria

Jacquin Niles ’94, PhD ’01. Photo: Bryce Vickmark

Nearly half a million people die each year from malaria, a disease that has been part of the human experience since the dawn of time. With characteristic symptoms of high fever, chills, and weakness, malaria is caused by any of several Plasmodium parasite species, with P. falciparum being responsible for the highest mortality. While the mosquito-borne pathogen has been eradicated in some parts of the world, including the United States and Europe, the developing world continues to suffer.

“An effective vaccine is still highly sought, even after decades of effort; one has recently been approved for clinical use, but it provides only about 30% protection that rapidly wanes,” says Jacquin Niles ’94, PhD ’01, professor of biological engineering and a physician scientist by training. “We have to continue moving forward and doing better.”

To that end, Niles has dedicated his career to fighting malaria.

Disease impacts

About 90% of malaria deaths occur in Africa, with children under five years being most commonly afflicted. Raised in the Caribbean, Niles says he is very familiar with the human cost of disease. “I grew up in a context where exposure to different infectious diseases was always a concern; you could see their impact on people and their livelihoods,” says Niles, who is also the director of the MIT Center for Environmental Health Sciences and an associate member of the Broad Institute of MIT and Harvard. “Seeing this impact has been an important motivation for me to pursue research in this field.”

Niles’s career provides a window into the long, uphill journey scientists face in fighting a disease such as Covid-19. “The process of bringing a new drug to market typically has a lead time of about a decade from initial discovery to ensuring that the drug can be safely and efficaciously used in humans,” he points out. He and his team have been working for more than a decade to establish new ways to disrupt the malaria parasite’s life cycle. “The lab spent a lot of time developing the basic technologies we needed to genetically manipulate the parasite so we could more precisely define its vulnerabilities to help propel drug discovery.”

Battling malaria today centers on treatment with antimalarial drugs, but this has drawbacks. “These parasites are resilient,” Niles says. “Resistance to mainstay antimalarial drugs occurs fairly commonly and then spreads around the globe. Some drugs work very well but for a limited time.” Understanding the strategies the parasite uses to survive can provide new insights into possible therapeutics.

Most recently, Niles and his team have focused on how the parasite metabolizes heme, the molecule that makes blood look red. Malaria parasites spend much of their lives in human red blood cells, consuming hemoglobin and releasing heme, which can be toxic but may also be used to support growth. “Our work is revealing aspects of a complex metabolic network the parasite uses to walk a razor’s edge in regulating the balance between beneficial and harmful effects of heme,” he says. “Actually, it’s amazing that a pathogen adopting such a potentially dangerous lifestyle could be among the most successful.”

Disrupting this balance in heme metabolism provides an opportunity for new therapeutics. “We’ve been focused on understanding if there are additional players involved in heme metabolism that would give us new ways to interfere with this process for therapeutic purposes. Targeting this pathway has provided some of the most successful antimalarial drugs used clinically—namely chloroquine and related drugs,” says Niles. Combining drugs with different modes of attacking the pathogen will be critical to fighting drug resistance, Niles adds. This approach has proven successful in fighting other infectious diseases, such as HIV.

While malaria and other killer infectious diseases of the developing world rarely get attention commensurate with their impact on human lives, Niles has a hopeful attitude toward fighting pathogens, and that includes the Covid-19 virus. “The urgency with which resources have been mobilized to combat the Covid-19 pandemic has been wonderful,” he says. “It will likely require a similarly intentional marshaling of resources to eliminate malaria and reduce the human health burden due to neglected diseases. With continued effort and a diversity of ideas focused on these problems, I am optimistic these goals are attainable.”

Wearing masks to adhere to protocols put in place during the Covid-19 pandemic. PhD students Elvin Yang and Neil Dalvie, conduct research in the lab of Professor J. Christopher Love. Photo: M. Scott Brauer

Global Health

Toward Faster Drug Development

Lab of J. Christopher Love forms consortium to speed manufacture of therapeutics

Wearing masks to adhere to protocols put in place during the Covid-19 pandemic, PhD students Elvin Yang and Neil Dalvie conduct research in the lab of Professor J. Christopher Love. Photo: M. Scott Brauer

Learn more about the MIT Better World (Health) event on February 18, featuring Neil Dalvie, PhD candidate in the Love Lab in the Department of Chemical Engineering, and J. Christopher Love, Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering.

“Our lab aims to transform biopharmaceutical development from discovery to manufacturing to make new drugs as accessible as possible globally,” says J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering. “Pursuing a Covid-19 vaccine has been the perfect chance to advance these ideas—a real live-fire test for us.”

Under pressure from the pandemic, Love and his team worked not only to design and build potentially life-saving vaccine candidates but also to further his larger vision: changing the drug-development pipeline to get treatments to patients faster. On June 22, in the midst of Covid-19 research, he announced the AltHost Consortium, an MIT-led group for open-access sharing of research and information with pharmaceutical giants Amgen, Biogen, Pfizer, Roche, and Sanofi. By leveraging contributions from this consortium, and harnessing his lab’s novel methods for evaluating and rapidly manufacturing biologically based medicines, Love was able to fashion coronavirus vaccine possibilities in record time.

“Our work thinking about how to respond most efficiently in urgent circumstances prepared us for the current crisis,” says Love. “We were able get out of the gate very quickly.”

Tackling Covid-19

Prior to the pandemic, the Love Lab, supported by the Bill and Melinda Gates Foundation (also an AltHost member), had been devising ways to produce and disseminate millions of doses of low-cost vaccines, especially for infectious diseases affecting the world’s most vulnerable populations. Such capabilities for generating vaccine candidates might also, Love and his team recognized, be necessary in case of a pandemic. That need arrived sooner than they imagined. In February 2020, research sponsors presented an urgent challenge to Love: Could you create a Covid-19 vaccine candidate by the end of the month?

Love’s lab, which resides in the Koch Institute for Integrative Cancer Research, brings together graduate research assistants and technical experts in chemical and biological engineering, immunology, and the genomic sciences. This multidisciplinary compass underpins the team’s pathbreaking approach to both drug discovery and manufacturing, an approach intended to skirt the pitfalls of the conventional process for bringing new drug candidates to production.

Currently, vaccines are manufactured in centralized facilities that make large quantities of a single type at a time. If something goes wrong during production, millions of doses can be lost. Manufacturers cannot respond quickly to new disease threats because it can take many months to grow the necessary biological components in such conventional facilities or to reconfigure these facilities to accommodate a different vaccine product.

“To avoid these kinds of bottlenecks, we must invent a simple, efficient method for manufacturing,” says Sergio A. Rodriguez, a third-year PhD student in biological engineering and a member of the Love Lab. “That is precisely what our lab has set out to accomplish.”

The Love Lab’s platform uses genetically engineered yeasts as biofactories for proteins that are the core constituents of many pharmaceuticals. Applying techniques such as CRISPRCas9, a genome editor, the lab can modify yeasts in a matter of days. “We are essentially tuning strains of yeast to produce specific kinds of drugs such as vaccine candidates,” says Neil Dalvie, a fifth-year PhD student in chemical engineering and a graduate research assistant.

Through a series of iterations, researchers test and tweak target proteins, focusing simultaneously on the effectiveness of their products and on whether the manufacturing process yields these products reliably and in sufficient volume to ramp up production.

This kind of innovative drug development, which Love describes as “on-demand biomanufacturing,” could one day enable smaller pharmaceutical companies, stocked with the right ingredients and genetic information, to generate products wherever they are needed.

“It is a streamlined approach where engineering, host biology, immune response, and manufacturability are integrated, giving us an opportunity to design for low-cost medicines that could reach potentially billions of patients,” says Love.

Pandemic work

When MIT shut down research facilities in March, the Love team continued its vital efforts on Covid-19 vaccine discovery and manufacture. Only four staff at a time were allowed in the lab. While Love and the rest of the group contributed from home, Dalvie and three other graduate students were deemed essential workers and stayed on campus. They seized the chance to play leading roles in significant research. “Once the Covid-19 work began, all of us realized the broader impact of our research on the world, and that we must do our best, and quickly,” says Rodriguez. The immediate goal was to produce a vaccine based on the spike protein used by the coronavirus to latch onto receptors in human cells, the first interaction of the virus in its attack. “The idea is that a vaccine that resembles this spike protein would prevent this interaction by generating an immune response where antibodies would neutralize the spike before it binds to the cell,” says Dalvie. The core team set out to transform Pichia pastoris, the host yeast, into an effective biofactory for this target protein.

This work proved a major change of pace for all of them—longer-than-usual days with the added burden of social distancing and constant pressure. The scene on campus sometimes seemed surreal.

“It was weird to see everything so empty and quiet,” says Elvin Yang, a third-year chemical engineering PhD student. “But I was really glad to be in the lab, where it felt like I was working on tangible things and generating results.”

This intense round of research leveraged the Love Lab’s interdisciplinary culture. “Our lab is designed to encourage collaboration, and to ensure that each of us gains a holistic understanding of the host organism and biomanufacturing process,” says Rodriguez. “We didn’t get to say, ‘I’m the one who does yeast purification.’”

“Challenges in production can best be solved when everyone knows the molecular design, host biology, and engineering processes,” says Love. “This is what makes our lab different.”

Vaccine candidate

In just 28 days, the Love Lab managed to produce its first version of a Covid-19 vaccine candidate. But creating a potential vaccine is far from the conclusion of drug R&D. Researchers must also demonstrate that the vaccine can safely engender an effective immune response in animal models and humans. Just as important, the team must prove that its manufacturing approach is agile enough to respond rapidly to potential virus mutations and that its biomanufacturing platform can scale up sufficiently. “To address the pandemic, the world will need billions of doses,” says Love.

To that end, last spring the lab began sending out vaccine components, including its engineered yeast cell lines, to multiple partners around the world for trial manufacturing and evaluation—progress made possible, in part, by the collective research of the AltHost Consortium.

“With our Covid-19 work, we have begun modeling ideas for sharing cell strains and providing access to advanced tools so we can all move forward together on the development of life-saving drugs,” says Love. “I feel fortunate that in these incredibly challenging circumstances, we are able to demonstrate our vision for how we might transform the conventional state of biopharmaceutical manufacturing.”