Author: MIT News

Translating MIT research into real-world results

by Carolyn Blais | Abdul Latif Jameel Water and Food Systems Lab |

Inventive solutions to some of the world’s most critical problems are being discovered in labs, classrooms, and centers across MIT every day. Many of these solutions move from the lab to the commercial world with the help of over 85 Institute resources that comprise MIT’s robust innovation and entrepreneurship (I&E) ecosystem. The Abdul Latif Jameel Water and Food Systems Lab (J-WAFS) draws on MIT’s wealth of I&E knowledge and experience to help researchers commercialize their breakthrough technologies through the J-WAFS Solutions grant program. By collaborating with I&E programs on campus, J-WAFS prepares MIT researchers for the commercial world, where their novel innovations aim to improve productivity, accessibility, and sustainability of water and food systems, creating economic, environmental, and societal benefits along the way.

The J-WAFS Solutions program launched in 2015 with support from Community Jameel, an international organization that advances science and learning for communities to thrive. Since 2015, J-WAFS Solutions has supported 19 projects with one-year grants of up to $150,000, with some projects receiving renewal grants for a second year of support. Solutions projects all address challenges related to water or food. Modeled after the esteemed grant program of MIT’s Deshpande Center for Technological Innovation, and initially administered by Deshpande Center staff, the J-WAFS Solutions program follows a similar approach by supporting projects that have already completed the basic research and proof-of-concept phases. With technologies that are one to three years away from commercialization, grantees work on identifying their potential markets and learn to focus on how their technology can meet the needs of future customers.

“Ingenuity thrives at MIT, driving inventions that can be translated into real-world applications for widespread adoption, implantation, and use,” says J-WAFS Director Professor John H. Lienhard V. “But successful commercialization of MIT technology requires engineers to focus on many challenges beyond making the technology work. MIT’s I&E network offers a variety of programs that help researchers develop technology readiness, investigate markets, conduct customer discovery, and initiate product design and development,” Lienhard adds. “With this strong I&E framework, many J-WAFS Solutions teams have established startup companies by the completion of the grant. J-WAFS-supported technologies have had powerful, positive effects on human welfare. Together, the J-WAFS Solutions program and MIT’s I&E ecosystem demonstrate how academic research can evolve into business innovations that make a better world,” Lienhard says.

Creating I&E collaborations

In addition to support for furthering research, J-WAFS Solutions grants allow faculty, students, postdocs, and research staff to learn the fundamentals of how to transform their work into commercial products and companies. As part of the grant requirements, researchers must interact with mentors through MIT Venture Mentoring Service (VMS). VMS connects MIT entrepreneurs with teams of carefully selected professionals who provide free and confidential mentorship, guidance, and other services to help advance ideas into for-profit, for-benefit, or nonprofit ventures. Since 2000, VMS has mentored over 4,600 MIT entrepreneurs across all industries, through a dynamic and accomplished group of nearly 200 mentors who volunteer their time so that others may succeed. The mentors provide impartial and unbiased advice to members of the MIT community, including MIT alumni in the Boston area. J-WAFS Solutions teams have been guided by 21 mentors from numerous companies and nonprofits. Mentors often attend project events and progress meetings throughout the grant period.

“Working with VMS has provided me and my organization with a valuable sounding board for a range of topics, big and small,” says Eric Verploegen PhD ’08, former research engineer in MIT’s D-Lab and founder of J-WAFS spinout CoolVeg. Along with professors Leon Glicksman and Daniel Frey, Verploegen received a J-WAFS Solutions grant in 2021 to commercialize cold-storage chambers that use evaporative cooling to help farmers preserve fruits and vegetables in rural off-grid communities. Verploegen started CoolVeg in 2022 to increase access and adoption of open-source, evaporative cooling technologies through collaborations with businesses, research institutions, nongovernmental organizations, and government agencies. “Working as a solo founder at my nonprofit venture, it is always great to have avenues to get feedback on communications approaches, overall strategy, and operational issues that my mentors have experience with,” Verploegen says. Three years after the initial Solutions grant, one of the VMS mentors assigned to the evaporative cooling team still acts as a mentor to Verploegen today.

Another Solutions grant requirement is for teams to participate in the Spark program — a free, three-week course that provides an entry point for researchers to explore the potential value of their innovation. Spark is part of the National Science Foundation’s (NSF) Innovation Corps (I-Corps), which is an “immersive, entrepreneurial training program that facilitates the transformation of invention to impact.” In 2018, MIT received an award from the NSF, establishing the New England Regional Innovation Corps Node (NE I-Corps) to deliver I-Corps training to participants across New England. Trainings are open to researchers, engineers, scientists, and others who want to engage in a customer discovery process for their technology. Offered regularly throughout the year, the Spark course helps participants identify markets and explore customer needs in order to understand how their technologies can be positioned competitively in their target markets. They learn to assess barriers to adoption, as well as potential regulatory issues or other challenges to commercialization. NE-I-Corps reports that since its start, over 1,200 researchers from MIT have completed the program and have gone on to launch 175 ventures, raising over $3.3 billion in funding from grants and investors, and creating over 1,800 jobs.

Constantinos Katsimpouras, a research scientist in the Department of Chemical Engineering, went through the NE I-Corps Spark program to better understand the customer base for a technology he developed with professors Gregory Stephanopoulos and Anthony Sinskey. The group received a J-WAFS Solutions grant in 2021 for their microbial platform that converts food waste from the dairy industry into valuable products. “As a scientist with no prior experience in entrepreneurship, the program introduced me to important concepts and tools for conducting customer interviews and adopting a new mindset,” notes Katsimpouras. “Most importantly, it encouraged me to get out of the building and engage in interviews with potential customers and stakeholders, providing me with invaluable insights and a deeper understanding of my industry,” he adds. These interviews also helped connect the team with companies willing to provide resources to test and improve their technology — a critical step to the scale-up of any lab invention.

In the case of Professor Cem Tasan’s research group in the Department of Materials Science and Engineering, the I-Corps program led them to the J-WAFS Solutions grant, instead of the other way around. Tasan is currently working with postdoc Onur Guvenc on a J-WAFS Solutions project to manufacture formable sheet metal by consolidating steel scrap without melting, thereby reducing water use compared to traditional steel processing. Before applying for the Solutions grant, Guvenc took part in NE I-Corps. Like Katsimpouras, Guvenc benefited from the interaction with industry. “This program required me to step out of the lab and engage with potential customers, allowing me to learn about their immediate challenges and test my initial assumptions about the market,” Guvenc recalls. “My interviews with industry professionals also made me aware of the connection between water consumption and steelmaking processes, which ultimately led to the J-WAFS 2023 Solutions Grant,” says Guvenc.

After completing the Spark program, participants may be eligible to apply for the Fusion program, which provides microgrants of up to $1,500 to conduct further customer discovery. The Fusion program is self-paced, requiring teams to conduct 12 additional customer interviews and craft a final presentation summarizing their key learnings. Professor Patrick Doyle’s J-WAFS Solutions team completed the Spark and Fusion programs at MIT. Most recently, their team was accepted to join the NSF I-Corps National program with a $50,000 award. The intensive program requires teams to complete an additional 100 customer discovery interviews over seven weeks. Located in the Department of Chemical Engineering, the Doyle lab is working on a sustainable microparticle hydrogel system to rapidly remove micropollutants from water. The team’s focus has expanded to higher value purifications in amino acid and biopharmaceutical manufacturing applications. Devashish Gokhale PhD ’24 worked with Doyle on much of the underlying science.

“Our platform technology could potentially be used for selective separations in very diverse market segments, ranging from individual consumers to large industries and government bodies with varied use-cases,” Gokhale explains. He goes on to say, “The I-Corps Spark program added significant value by providing me with an effective framework to approach this problem … I was assigned a mentor who provided critical feedback, teaching me how to formulate effective questions and identify promising opportunities.” Gokhale says that by the end of Spark, the team was able to identify the best target markets for their products. He also says that the program provided valuable seminars on topics like intellectual property, which was helpful in subsequent discussions the team had with MIT’s Technology Licensing Office.

Another member of Doyle’s team, Arjav Shah, a recent PhD from MIT’s Department of Chemical Engineering and a current MBA candidate at the MIT Sloan School of Management, is spearheading the team’s commercialization plans. Shah attended Fusion last fall and hopes to lead efforts to incorporate a startup company called hydroGel.  “I admire the hypothesis-driven approach of the I-Corps program,” says Shah. “It has enabled us to identify our customers’ biggest pain points, which will hopefully lead us to finding a product-market fit.” He adds “based on our learnings from the program, we have been able to pivot to impact-driven, higher-value applications in the food processing and biopharmaceutical industries.” Postdoc Luca Mazzaferro will lead the technical team at hydroGel alongside Shah.

In a different project, Qinmin Zheng, a postdoc in the Department of Civil and Environmental Engineering, is working with Professor Andrew Whittle and Lecturer Fábio Duarte. Zheng plans to take the Fusion course this fall to advance their J-WAFS Solutions project that aims to commercialize a novel sensor to quantify the relative abundance of major algal species and provide early detection of harmful algal blooms. After completing Spark, Zheng says he’s “excited to participate in the Fusion program, and potentially the National I-Corps program, to further explore market opportunities and minimize risks in our future product development.”

Economic and societal benefits

Commercializing technologies developed at MIT is one of the ways J-WAFS helps ensure that MIT research advances will have real-world impacts in water and food systems. Since its inception, the J-WAFS Solutions program has awarded 28 grants (including renewals), which have supported 19 projects that address a wide range of global water and food challenges. The program has distributed over $4 million to 24 professors, 11 research staff, 15 postdocs, and 30 students across MIT. Nearly half of all J-WAFS Solutions projects have resulted in spinout companies or commercialized products, including eight companies to date plus two open-source technologies.

Nona Technologies is an example of a J-WAFS spinout that is helping the world by developing new approaches to produce freshwater for drinking. Desalination — the process of removing salts from seawater — typically requires a large-scale technology called reverse osmosis. But Nona created a desalination device that can work in remote off-grid locations. By separating salt and bacteria from water using electric current through a process called ion concentration polarization (ICP), their technology also reduces overall energy consumption. The novel method was developed by Jongyoon Han, professor of electrical engineering and biological engineering, and research scientist Junghyo Yoon. Along with Bruce Crawford, a Sloan MBA alum, Han and Yoon created Nona Technologies to bring their lightweight, energy-efficient desalination technology to the market.

“My feeling early on was that once you have technology, commercialization will take care of itself,” admits Crawford. The team completed both the Spark and Fusion programs and quickly realized that much more work would be required. “Even in our first 24 interviews, we learned that the two first markets we envisioned would not be viable in the near term, and we also got our first hints at the beachhead we ultimately selected,” says Crawford. Nona Technologies has since won MIT’s $100K Entrepreneurship Competition, received media attention from outlets like Newsweek and Fortune, and hired a team that continues to further the technology for deployment in resource-limited areas where clean drinking water may be scarce.

Food-borne diseases sicken millions of people worldwide each year, but J-WAFS researchers are addressing this issue by integrating molecular engineering, nanotechnology, and artificial intelligence to revolutionize food pathogen testing. Professors Tim Swager and Alexander Klibanov, of the Department of Chemistry, were awarded one of the first J-WAFS Solutions grants for their sensor that targets food safety pathogens. The sensor uses specialized droplets that behave like a dynamic lens, changing in the presence of target bacteria in order to detect dangerous bacterial contamination in food. In 2018, Swager launched Xibus Systems Inc. to bring the sensor to market and advance food safety for greater public health, sustainability, and economic security.

“Our involvement with the J-WAFS Solutions Program has been vital,” says Swager. “It has provided us with a bridge between the academic world and the business world and allowed us to perform more detailed work to create a usable application,” he adds. In 2022, Xibus developed a product called XiSafe, which enables the detection of contaminants like salmonella and listeria faster and with higher sensitivity than other food testing products. The innovation could save food processors billions of dollars worldwide and prevent thousands of food-borne fatalities annually.

J-WAFS Solutions companies have raised nearly $66 million in venture capital and other funding. Just this past June, J-WAFS spinout SiTration announced that it raised an $11.8 million seed round. Jeffrey Grossman, a professor in MIT’s Department of Materials Science and Engineering, was another early J-WAFS Solutions grantee for his work on low-cost energy-efficient filters for desalination. The project enabled the development of nanoporous membranes and resulted in two spinout companies, Via Separations and SiTration. SiTration was co-founded by Brendan Smith PhD ’18, who was a part of the original J-WAFS team. Smith is CEO of the company and has overseen the advancement of the membrane technology, which has gone on to reduce cost and resource consumption in industrial wastewater treatment, advanced manufacturing, and resource extraction of materials such as lithium, cobalt, and nickel from recycled electric vehicle batteries. The company also recently announced that it is working with the mining company Rio Tinto to handle harmful wastewater generated at mines.

But it’s not just J-WAFS spinout companies that are producing real-world results. Products like the ECC Vial — a portable, low-cost method for E. coli detection in water — have been brought to the market and helped thousands of people. The test kit was developed by MIT D-Lab Lecturer Susan Murcott and Professor Jeffrey Ravel of the MIT History Section. The duo received a J-WAFS Solutions grant in 2018 to promote safely managed drinking water and improved public health in Nepal, where it is difficult to identify which wells are contaminated by E. coli. By the end of their grant period, the team had manufactured approximately 3,200 units, of which 2,350 were distributed — enough to help 12,000 people in Nepal. The researchers also trained local Nepalese on best manufacturing practices.

“It’s very important, in my life experience, to follow your dream and to serve others,” says Murcott. Economic success is important to the health of any venture, whether it’s a company or a product, but equally important is the social impact — a philosophy that J-WAFS research strives to uphold. “Do something because it’s worth doing and because it changes people’s lives and saves lives,” Murcott adds.

As J-WAFS prepares to celebrate its 10th anniversary this year, we look forward to continued collaboration with MIT’s many I&E programs to advance knowledge and develop solutions that will have tangible effects on the world’s water and food systems.

Learn more about the J-WAFS Solutions program and about innovation and entrepreneurship at MIT.

AI model can reveal the structures of crystalline materials

by Anne Trafton | MIT News |

For more than 100 years, scientists have been using X-ray crystallography to determine the structure of crystalline materials such as metals, rocks, and ceramics.

This technique works best when the crystal is intact, but in many cases, scientists have only a powdered version of the material, which contains random fragments of the crystal. This makes it more challenging to piece together the overall structure.

MIT chemists have now come up with a new generative AI model that can make it much easier to determine the structures of these powdered crystals. The prediction model could help researchers characterize materials for use in batteries, magnets, and many other applications.

“Structure is the first thing that you need to know for any material. It’s important for superconductivity, it’s important for magnets, it’s important for knowing what photovoltaic you created. It’s important for any application that you can think of which is materials-centric,” says Danna Freedman, the Frederick George Keyes Professor of Chemistry at MIT.

Freedman and Jure Leskovec, a professor of computer science at Stanford University, are the senior authors of the new study, which appears today in the Journal of the American Chemical Society. MIT graduate student Eric Riesel and Yale University undergraduate Tsach Mackey are the lead authors of the paper.

Distinctive patterns

Crystalline materials, which include metals and most other inorganic solid materials, are made of lattices that consist of many identical, repeating units. These units can be thought of as “boxes” with a distinctive shape and size, with atoms arranged precisely within them.

When X-rays are beamed at these lattices, they diffract off atoms with different angles and intensities, revealing information about the positions of the atoms and the bonds between them. Since the early 1900s, this technique has been used to analyze materials, including biological molecules that have a crystalline structure, such as DNA and some proteins.

For materials that exist only as a powdered crystal, solving these structures becomes much more difficult because the fragments don’t carry the full 3D structure of the original crystal.

“The precise lattice still exists, because what we call a powder is really a collection of microcrystals. So, you have the same lattice as a large crystal, but they’re in a fully randomized orientation,” Freedman says.

For thousands of these materials, X-ray diffraction patterns exist but remain unsolved. To try to crack the structures of these materials, Freedman and her colleagues trained a machine-learning model on data from a database called the Materials Project, which contains more than 150,000 materials. First, they fed tens of thousands of these materials into an existing model that can simulate what the X-ray diffraction patterns would look like. Then, they used those patterns to train their AI model, which they call Crystalyze, to predict structures based on the X-ray patterns.

The model breaks the process of predicting structures into several subtasks. First, it determines the size and shape of the lattice “box” and which atoms will go into it. Then, it predicts the arrangement of atoms within the box. For each diffraction pattern, the model generates several possible structures, which can be tested by feeding the structures into a model that determines diffraction patterns for a given structure.

“Our model is generative AI, meaning that it generates something that it hasn’t seen before, and that allows us to generate several different guesses,” Riesel says. “We can make a hundred guesses, and then we can predict what the powder pattern should look like for our guesses. And then if the input looks exactly like the output, then we know we got it right.”

Solving unknown structures

The researchers tested the model on several thousand simulated diffraction patterns from the Materials Project. They also tested it on more than 100 experimental diffraction patterns from the RRUFF database, which contains powdered X-ray diffraction data for nearly 14,000 natural crystalline minerals, that they had held out of the training data. On these data, the model was accurate about 67 percent of the time. Then, they began testing the model on diffraction patterns that hadn’t been solved before. These data came from the Powder Diffraction File, which contains diffraction data for more than 400,000 solved and unsolved materials.

Using their model, the researchers came up with structures for more than 100 of these previously unsolved patterns. They also used their model to discover structures for three materials that Freedman’s lab created by forcing elements that do not react at atmospheric pressure to form compounds under high pressure. This approach can be used to generate new materials that have radically different crystal structures and physical properties, even though their chemical composition is the same.

Graphite and diamond — both made of pure carbon — are examples of such materials. The materials that Freedman has developed, which each contain bismuth and one other element, could be useful in the design of new materials for permanent magnets.

“We found a lot of new materials from existing data, and most importantly, solved three unknown structures from our lab that comprise the first new binary phases of those combinations of elements,” Freedman says.

Being able to determine the structures of powdered crystalline materials could help researchers working in nearly any materials-related field, according to the MIT team, which has posted a web interface for the model at crystalyze.org.

The research was funded by the U.S. Department of Energy and the National Science Foundation.

A new way to reprogram immune cells and direct them toward anti-tumor immunity

by Danielle Doughty | Department of Chemistry |

A collaboration between four MIT groups, led by principal investigators Laura L. Kiessling, Jeremiah A. Johnson, Alex K. Shalek, and Darrell J. Irvine, in conjunction with a group at Georgia Tech led by M.G. Finn, has revealed a new strategy for enabling immune system mobilization against cancer cells. The work, which appears today in ACS Nano, produces exactly the type of anti-tumor immunity needed to function as a tumor vaccine — both prophylactically and therapeutically.

Cancer cells can look very similar to the human cells from which they are derived. In contrast, viruses, bacteria, and fungi carry carbohydrates on their surfaces that are markedly different from those of human carbohydrates. Dendritic cells — the immune system’s best antigen-presenting cells — carry proteins on their surfaces that help them recognize these atypical carbohydrates and bring those antigens inside of them. The antigens are then processed into smaller peptides and presented to the immune system for a response. Intriguingly, some of these carbohydrate proteins can also collaborate to direct immune responses. This work presents a strategy for targeting those antigens to the dendritic cells that results in a more activated, stronger immune response.

Tackling tumors’ tenacity

The researchers’ new strategy shrouds the tumor antigens with foreign carbohydrates and co-delivers them with single-stranded RNA so that the dendritic cells can be programmed to recognize the tumor antigens as a potential threat. The researchers targeted the lectin (carbohydrate-binding protein) DC-SIGN because of its ability to serve as an activator of dendritic cell immunity. They decorated a virus-like particle (a particle composed of virus proteins assembled onto a piece of RNA that is noninfectious because its internal RNA is not from the virus) with DC-binding carbohydrate derivatives. The resulting glycan-costumed virus-like particles display unique sugars; therefore, the dendritic cells recognize them as something they need to attack.

“On the surface of the dendritic cells are carbohydrate binding proteins called lectins that combine to the sugars on the surface of bacteria or viruses, and when they do that they penetrate the membrane,” explains Kiessling, the paper’s senior author. “On the cell, the DC-SIGN gets clustered upon binding the virus or bacteria and that promotes internalization. When a virus-like particle gets internalized, it starts to fall apart and releases its RNA.” The toll-like receptor (bound to RNA) and DC-SIGN (bound to the sugar decoration) can both signal to activate the immune response.

Once the dendritic cells have sounded the alarm of a foreign invasion, a robust immune response is triggered that is significantly stronger than the immune response that would be expected with a typical untargeted vaccine. When an antigen is encountered by the dendritic cells, they send signals to T cells, the next cell in the immune system, to give different responses depending on what pathways have been activated in the dendritic cells.

Advancing cancer vaccine development

The activity of a potential vaccine developed in line with this new research is twofold. First, the vaccine glycan coat binds to lectins, providing a primary signal. Then, binding to toll-like receptors elicits potent immune activation.

The Kiessling, Finn, and Johnson groups had previously identified a synthetic DC-SIGN binding group that directed cellular immune responses when used to decorate virus-like particles. But it was unclear whether this method could be utilized as an anticancer vaccine. Collaboration between researchers in the labs at MIT and Georgia Tech demonstrated that in fact, it could.

Valerie Lensch, a chemistry PhD student from MIT’s Program in Polymers and Soft Matter and a joint member of the Kiessling and Johnson labs, took the preexisting strategy and tested it as an anticancer vaccine, learning a great deal about immunology in order to do so.

“We have developed a modular vaccine platform designed to drive antigen-specific cellular immune responses,” says Lensch. “This platform is not only pivotal in the fight against cancer, but also offers significant potential for combating challenging intracellular pathogens, including malaria parasites, HIV, and Mycobacterium tuberculosis. This technology holds promise for tackling a range of diseases where vaccine development has been particularly challenging.”

Lensch and her fellow researchers conducted in vitro experiments with extensive iterations of these glycan-costumed virus-like particles before identifying a design that demonstrated potential for success. Once that was achieved, the researchers were able to move on to an in vivo model, an exciting milestone for their research.

Adele Gabba, a postdoc in the Kiessling Lab, conducted the in vivo experiments with Lensch, and Robert Hincapie, who conducted his PhD studies with Professor M.G. Finn at Georgia Tech, built and decorated the virus-like particles with a series of glycans that were sent to him from the researchers at MIT.

“We are discovering that carbohydrates act like a language that cells use to communicate and direct the immune system,” says Gabba. “It’s thrilling that we have begun to decode this language and can now harness it to reshape immune responses.”

“The design principles behind this vaccine are rooted in extensive fundamental research conducted by previous graduate student and postdoctoral researchers over many years, focusing on optimizing lectin engagement and understanding the roles of lectins in immunity,” says Lensch. “It has been exciting to witness the translation of these concepts into therapeutic platforms across various applications.”

MIT chemists explain why dinosaur collagen may have survived for millions of years

by Anne Trafton | MIT News |

Collagen, a protein found in bones and connective tissue, has been found in dinosaur fossils as old as 195 million years. That far exceeds the normal half-life of the peptide bonds that hold proteins together, which is about 500 years.

A new study from MIT offers an explanation for how collagen can survive for so much longer than expected. The research team found that a special atomic-level interaction defends collagen from attack by water molecules. This barricade prevents water from breaking the peptide bonds through a process called hydrolysis.

“We provide evidence that that interaction prevents water from attacking the peptide bonds and cleaving them. That just flies in the face of what happens with a normal peptide bond, which has a half-life of only 500 years,” says Ron Raines, the Firmenich Professor of Chemistry at MIT.

Raines is the senior author of the new study, which appears today in ACS Central Science. MIT postdoc Jinyi Yang PhD ’24 is the lead author of the paper. MIT postdoc Volga Kojasoy and graduate student Gerard Porter are also authors of the study.

Water-resistant

Collagen is the most abundant protein in animals, and it is found in not only bones but also skin, muscles, and ligaments. It’s made from long strands of protein that intertwine to form a tough triple helix.

“Collagen is the scaffold that holds us together,” Raines says. “What makes the collagen protein so stable, and such a good choice for this scaffold, is that unlike most proteins, it’s fibrous.”

In the past decade, paleobiologists have found evidence of collagen preserved in dinosaur fossils, including an 80-million-year-old Tyrannosaurus rex fossil, and a sauropodomorph fossil that is nearly 200 million years old.

Over the past 25 years, Raines’ lab has been studying collagen and how its structure enables its function. In the new study, they revealed why the peptide bonds that hold collagen together are so resistant to being broken down by water.

Peptide bonds are formed between a carbon atom from one amino acid and a nitrogen atom of the adjacent amino acid. The carbon atom also forms a double bond with an oxygen atom, forming a molecular structure called a carbonyl group. This carbonyl oxygen has a pair of electrons that don’t form bonds with any other atoms. Those electrons, the researchers found, can be shared with the carbonyl group of a neighboring peptide bond.

Because this pair of electrons is being inserted into those peptide bonds, water molecules can’t also get into the structure to disrupt the bond.

To demonstrate this, Raines and his colleagues created two interconverting mimics of collagen — the one that usually forms a triple helix, which is known as trans, and another in which the angles of the peptide bonds are rotated into a different form, known as cis. They found that the trans form of collagen did not allow water to attack and hydrolyze the bond. In the cis form, water got in and the bonds were broken.

“A peptide bond is either cis or trans, and we can change the cis to trans ratio. By doing that, we can mimic the natural state of collagen or create an unprotected peptide bond. And we saw that when it was unprotected, it was not long for the world,” Raines says.

“This work builds on a long-term effort in the Raines Group to classify the role of a long-overlooked fundamental interaction in protein structure,” says Paramjit Arora, a professor of chemistry at New York University, who was not involved in the research. “The paper directly addresses the remarkable finding of intact collagen in the ribs of a 195-million-old dinosaur fossil, and shows that overlap of filled and empty orbitals controls the conformational and hydrolytic stability of collagen.”

“No weak link”

This sharing of electrons has also been seen in protein structures known as alpha helices, which are found in many proteins. These helices may also be protected from water, but the helices are always connected by protein sequences that are more exposed, which are still susceptible to hydrolysis.

“Collagen is all triple helices, from one end to the other,” Raines says. “There’s no weak link, and that’s why I think it has survived.”

Previously, some scientists have suggested other explanations for why collagen might be preserved for millions of years, including the possibility that the bones were so dehydrated that no water could reach the peptide bonds.

“I can’t discount the contributions from other factors, but 200 million years is a long time, and I think you need something at the molecular level, at the atomic level in order to explain it,” Raines says.

The research was funded by the National Institutes of Health and the National Science Foundation.

Engineering proteins to treat cancer

by Austin Chen | MIT News correspondent |

Like many children of first-generation immigrants, Oscar Molina grew up feeling like he had two career choices: doctor or lawyer. He seemed destined for the former as he excelled in high school and planned to major in biochemistry at the University of California at Los Angeles, but as an undergraduate, he fell in love with research.

“I was fascinated by discovery. As I did it more in college, I realized I didn’t want to be a doctor,” he says. “Once I saw that I could make an impact and be at the forefront of therapy with biotech, I knew I wanted to do that.”

If the next couple of years go as planned, his parents will indeed see their son become a doctor — just not exactly the way they might have guessed. He’s entering the fifth year of his PhD program in biology at MIT and is currently working in the lab of Professor Ronald Raines, researching the potential of proteins to kill cancer cells.

Molina, who is the first in his family to attend college, also works to support his fellow students through outreach and community-building efforts. In various roles, including as a Graduate Community Fellow in MIT’s Office of Graduate Education, he sought to connect and encourage students from underrepresented backgrounds as they pursued their own graduate studies.

“I had a lot of opportunities presented to me that made me ask, ‘Why me?’” he says. “I recognize that they were super valuable, and that’s why I should deliver that back to other people.”

Unlocking protein construction chemically

The spirit of giving back isn’t just limited to Molina’s work outside of the lab. He chose chemical biology and the pursuit of new cancer therapies as his research focus partly because his grandfather has been dealing with the disease for the last 10 years. The ultimate goal guiding his research is to make all protein-based cancer therapies more effective.

He and other collaborators in the Raines Lab published a paper in June that takes an important step in that direction, suggesting a way to make fusion proteins with greater customization and improved performance. They discovered that a chemical called 3-bromo-5-methylene pyrrolone can be used to combine three proteins efficiently and with high levels of control and modularity, a significant advance given most of the techniques for protein conjugation are only able to combine two at a time in a single spot.

“Now, we can have chemical control of where we include different things, where we can kind of plug-and-play,” he says.

Researchers can now adjust multiple characteristics at the same time — for example, increasing the protein’s half-life or improving its ability to target cancer cells — while still achieving a homogenous end product. They’re also relevant to immune cell redirection therapies, which require multimeric protein chimeras to activate immune clearance of cancer cells.

“That’s the most interesting thing to me,” he says. “How do we give a biologic therapy the best opportunity to be active and efficacious?”

His upcoming thesis will center around that question as it relates to chemotherapies based on ribonuclease 1, an enzyme that is best-known for cleaving RNA.

Paying it back and paying it forward

While that thesis will likely demand more of Molina than any other project he’s worked on in the past, he’s no stranger to hard work. After his mother and father left their respective homes of Guatemala and El Salvador in the 1990s, they dedicated their lives to giving their children futures that they themselves didn’t have access to.

Witnessing their efforts impressed two beliefs into Molina’s worldview: the value of education and the importance of support. Among his family, he is the first to graduate from a U.S. high school, the first to attend a four-year college, and the first to attend graduate school. These “firsts” can weigh heavily, and as he began his studies at MIT, he knew how difficult it can be to carry that burden alone.

“I saw the need and wanted to help other people be the first in their family to do things like go to college,” he says. “I also wanted to help people with similar backgrounds to mine, like being an underrepresented minority or a first-generation college student.”

That desire led Molina to join MIT’s Office of Graduate Education as a Graduate Community Fellow in January 2022, where he worked on supporting various affinity groups across the Institute. This included helping groups out with logistics, funding applications, community outreach and cross-group collaborations. He also spent part of last summer as a pod leader for the MIT Summer Research Program, which works to prepare underrepresented students for graduate education and research.

He’s also leveraged his personal interests to volunteer with various community organizations in Cambridge and Boston. Despite his numerous commitments, he’s an avid marathon runner, and ran the 2022 Boston Marathon while raising nearly $8000 for Boston Scores, a program that provides educational and athletic opportunities for students in the Boston Public Schools system.

After graduation, Molina plans on joining a startup in Boston’s biotech scene while learning more about the venture capital firms that fund their research. Wherever he ends up, he plans on continuing to apply the core truths that brought him where he is now.

“I want to be at the forefront of creating therapies. I really like science. I really like helping others. I really like the ability to create things that are impactful,” he says. “Now it’s time to take that and find my way to what’s next.”

MIT chemists synthesize plant-derived molecules that hold potential as pharmaceuticals

by Anne Trafton | MIT News |

MIT chemists have developed a new way to synthesize complex molecules that were originally isolated from plants and could hold potential as antibiotics, analgesics, or cancer drugs.

These compounds, known as oligocyclotryptamines, consist of multiple tricyclic substructures called cyclotryptamine, fused together by carbon–carbon bonds. Only small quantities of these compounds are naturally available, and synthesizing them in the lab has proven difficult. The MIT team came up with a way to add tryptamine-derived components to a molecule one at a time, in a way that allows the researchers to precisely assemble the rings and control the 3D orientation of each component as well as the final product.

“For many of these compounds, there hasn’t been enough material to do a thorough review of their potential. I’m hopeful that having access to these compounds in a reliable way will enable us to do further studies,” says Mohammad Movassaghi, an MIT professor of chemistry and the senior author of the new study.

In addition to allowing scientists to synthesize oligocyclotryptamines found in plants, this approach could also be used to generate new variants that may have even better medicinal properties, or molecular probes that can help to reveal their mechanism of action.

Tony Scott PhD ’23 is the lead author of the paper, which appears today in the Journal of the American Chemical Society.

Fusing rings

Oligocyclotryptamines belong to a class of molecules called alkaloids — nitrogen-containing organic compounds produced mainly by plants. At least eight different oligocyclotryptamines have been isolated from a genus of flowering plants known as Psychotria, most of which are found in tropical forests.

Since the 1950s, scientists have studied the structure and synthesis of dimeric cyclotryptamines, which have two cyclotryptamine subunits. Over the past 20 years, significant progress has been made characterizing and synthesizing dimers and other smaller members of the family. However, no one has been able to synthesize the largest oligocyclotryptamines, which have six or seven rings fused together.

One of the hurdles in synthesizing these molecules is a step that requires formation of a bond between a carbon atom of one tryptamine-derived subunit to a carbon atom of the next subunit. The oligocyclotryptamines have two types of these linkages, both containing at least one carbon atom that has bonds with four other carbons. That extra bulk makes those carbon atoms less accessible to undergo reactions, and controlling the stereochemistry — the orientation of the atoms around the carbon — at all these junctures poses a significant challenge.

For many years, Movassaghi’s lab has been developing ways to form carbon-carbon bonds between carbon atoms that are already crowded with other atoms. In 2011, they devised a method that involves transforming the two carbon atoms into carbon radicals (carbon atoms with one unpaired electron) and directing their union. To create these radicals, and guide the paired union to be completely selective, the researchers first attach each of the targeted carbon atoms to a nitrogen atom; these two nitrogen atoms bind to each other.

When the researchers shine certain wavelengths of light on the substrate containing the two fragments linked via the two nitrogen atoms, it causes the two atoms of nitrogen to break away as nitrogen gas, leaving behind two very reactive carbon radicals in close proximity that join together almost immediately. This type of bond formation has also allowed the researchers to control the molecules’ stereochemistry.

Movassaghi demonstrated this approach, which he calls diazene-directed assembly, by synthesizing other types of alkaloids, including the communesins. These compounds are found in fungi and consist of two ring-containing molecules, or monomers, joined together. Later, Movassaghi began using this approach to fuse larger numbers of monomers, and he and Scott eventually turned their attention to the largest oligocyclotryptamine alkaloids.

The synthesis that they developed begins with one molecule of cyclotryptamine derivative, to which additional cyclotryptamine fragments with correct relative stereochemistry and position selectivity are added, one at a time. Each of these additions is made possible by the diazene-directed process that Movassaghi’s lab previously developed.

“The reason why we’re excited about this is that this single solution allowed us to go after multiple targets,” Movassaghi says. “That same route provides us a solution to multiple members of the natural product family because by extending the iteration one more cycle, your solution is now applied to a new natural product.”

“A tour de force”

Using this approach, the researchers were able to create molecules with six or seven cyclotryptamine rings, which has never been done before.

“Researchers worldwide have been trying to find a way to make these molecules, and Movassaghi and Scott are the first to pull it off,” says Seth Herzon, a professor of chemistry at Yale University, who was not involved in the research. Herzon described the work as “a tour de force in organic synthesis.”

Now that the researchers have synthesized these naturally occurring oligocyclotryptamines, they should be able to generate enough of the compounds that their potential therapeutic activity can be more thoroughly investigated.

They should also be able to create novel compounds by switching in slightly different cyclotryptamine subunits, Movassaghi says.

“We will continue to use this very precise way of adding these cyclotryptamine units to assemble them together into complex systems that have not been addressed yet, including derivatives that could potentially have improved properties,” he says.

The research was funded by the U.S. National Institute of General Medical Sciences.

The art of the enzyme

by Austin Chen | MIT News correspondent |

As the mountains and trees of California’s Napa Valley drift past the car window, 6-year-old David Kastner is deep in conversation with his father. The conversation is a familiar one, shifting naturally from gravity to electromagnetism. For as long as he can remember, scientific curiosity has been a key part of his conversations on these drives.

“I remember being fascinated by how complex the universe is and how little people know about it,” recalls Kastner, now a fourth-year PhD student in bioengineering. “I always wanted to uncover new truths about the universe.”

Nearly two decades later, Kastner is now at MIT studying a challenging subset of proteins known as metalloenzymes, in the lab of Heather Kulik, a professor of chemical engineering, and Forest White, a professor of biological engineering. With the same curiosity that sparked those on-the-road discussions with his father, Kastner is motivated by a desire to harness the chemical and medical potential of enzymes through computational and mechanistic approaches.

Kastner’s research aims to uncover the fundamental blueprints of reactivity for enzymes using state-of-the-art computational methods. However, his approach to research involves not just physics, chemistry, and biology, but also art, which has been an integral part of his life since childhood. Kastner produces beautiful 3D illustrations of molecular systems that help make his research more accessible to a wider audience.

“Seeing the science in a way that looks so real that you feel like you can touch it can be more impactful than a bar plot or a histogram,” he says. “If scientists were more invested in showing their work in engaging and interesting ways, then we would have more people involved in science.”

Form and function in equal measure

Kastner’s research has spanned quantum chemistry calculations, protein engineering, bioinformatics, synthetic organic chemistry, and mammalian tissue models. He earned his bachelor’s degree in biophysics at Brigham Young University, and once he began his PhD program at MIT, he decided to zero in on metalloenzymes.

Among metalloenzymes, Kastner has chosen to focus on high-valent metalloenzymes, which contain a highly reactive metal atom that has lost many of its electrons and eagerly reacts to regain them. His personal favorites are non-heme iron enzymes, due to their vast repertoire of chemical reactions, direct applicability to human health, and the tunability of their active sites for engineering novel reactivities.

Giving old enzymes new reactivities isn’t easy, however. His first published paper, authored alongside former members of the Kulik Research Group, showed why.

Kastner’s research explores the mechanistic differences between non-heme iron halogenases and hydroxylases, two classes of high-valent enzymes that activate normally unreactive C–H bonds. By investigating trends across structural databases and molecular dynamics simulations, he identified key interactions that result in subtle differences in the substrate positioning angle, influencing reactivity. Kastner’s computational findings suggest new ways of converting between halogenases and hydroxylases.

While an intuition of an enzyme’s structure can go a long way, sometimes you need to move beyond structure. “As soon as you add a metal into the core of an enzyme, it becomes much more challenging to model,” he says. “It requires unique and cutting-edge tools in order to understand reactivity. That’s why we need quantum chemistry calculations so much in our research.”

Trying to unlock the secrets of nature’s most efficient catalysts requires observations at the sharpest level possible. A given enzyme’s structure and reactivity is determined by the interactions between the electrons it contains, hence the reliance on quantum computing methods.

The importance of viewing the entire enzyme from a quantum mechanical lens came to the forefront of Kastner’s research in his most recent publication. Kastner and his collaborators discovered that the reactivity of a class of miniature artificial metalloenzymes was controlled by changes in dynamic charge distributions, which can be thought of as a way of seeing how electrons and charges fluctuate throughout an enzyme’s structure.

“If you’re interested in how life functions, then it only makes sense to look at enzymes and proteins,” he says. “Enzymes are the machinery that evolution came up with to harness physics and chemistry.”

“I’ve always been interested in that question,” he continues. “How do you get from these purely mathematical underlying physical laws to living, breathing organisms with feelings?”

The art of science

In addition to research, Kastner can be found using 3D graphics programs like Blender and VMD to visualize macromolecular systems and their interactions. His work can be seen on the covers of scientific journals published by Nature and the American Chemical Society, but his initial forays into art were far simpler.

“I would draw everything,” he says. “It was the game I would play. I would draw; I would ask my parents to draw for me; I would ask people I would meet, ‘Can you draw this for me?’”

His mother made hyperrealistic art inspired by nature and was the biggest artistic influence on him early on. Kastner described a photorealistic lynx his mother drew with a scratch board hanging at his grandparents’ home that he found particularly inspiring as a child.

He took traditional art quite seriously in high school. He worked with charcoal and oils, winning multiple competitions, but he wasn’t sure how he might apply these skills to his academic interests.

“At that time, I hadn’t realized how to reconcile art and my love of science,” he says. “They still felt so different and no one I talked to tried to combine them at all.”

If he had come of age in late-15th-century Italy, however, that might not have been the case. The Renaissance was defined by figures who didn’t see boundaries between various disciplines, and perhaps none are more enduring than Kastner’s favorite scientist of all time: Leonardo da Vinci.

“It’s pretty incredible that the man who is universally credited as being the grandfather of modern anatomy and physiology is also the same man who painted the ‘Mona Lisa,’” he says. “I feel like the world would be a better place if we had more people like da Vinci who could reconcile the sciences and art.”

In fact, he thinks the erosion of trust in scientists could be eased if that were the case. Peer-reviewed papers are dense and technical because they need to describe complex experiments in a way that makes their results reproducible, but that means the average person probably won’t understand it. That’s where art can help bridge the gap.

“If we communicate our science in ways that connect to ordinary people, I think it will automatically get rid of some of that distrust,” he says. “We need to keep writing papers the way we do; there’s no way around that. However, scientific art can help make this information more accessible. By converting esoteric data into familiar and relatable visuals, researchers can extend an invitation to people of all ages and backgrounds to interact with their science through the universally shared language of art.”

License plates of MIT

by Maia Weinstock | MIT News |

What does your license plate say about you?

In the United States, more than 9 million vehicles carry personalized “vanity” license plates, in which preferred words, digits, or phrases replace an otherwise random assignment of letters and numbers to identify a vehicle. While each state and the District of Columbia maintains its own rules about appropriate selections, creativity reigns when choosing a unique vanity plate. What’s more, the stories behind them can be just as fascinating as the people who use them.

It might not come as a surprise to learn that quite a few MIT community members have participated in such vehicular whimsy. Read on to meet some of them and learn about the nerdy, artsy, techy, and MIT-related plates that color their rides.

A little piece of tech heaven

One of the most recognized vehicles around campus is Samuel Klein’s 1998 Honda Civic. More than just the holder of a vanity plate, it’s an art car — a vehicle that’s been custom-designed as a way to express an artistic idea or theme. Klein’s Civic is covered with hundreds of 5.5-inch floppy disks in various colors, and it sports disks, computer keys, and other techy paraphernalia on the interior. With its double-entendre vanity plate, “DSKDRV” (“disk drive”), the art car initially came into being on the West Coast.

Klein, a longtime affiliate of the MIT Media Lab, MIT Press, and MIT Libraries, first heard about the car from fellow Wikimedian and current MIT librarian Phoebe Ayers. An artistic friend of Ayers’, Lara Wiegand, had designed and decorated the car in Seattle but wanted to find a new owner. Klein was intrigued and decided to fly west to check the Civic out.

“I went out there, spent a whole afternoon seeing how she maintained the car and talking about engineering and mechanisms and the logistics of what’s good and bad,” Klein says. “It had already gone through many iterations.”

Klein quickly decided he was up to the task of becoming the new owner. As he drove the car home across the country, it “got a wide range of really cool responses across different parts of the U.S.”

Back in Massachusetts, Klein made a few adjustments: “We painted the hubcaps, we added racing stripes, we added a new generation of laser-etched glass circuits and, you know, I had my own collection of antiquated technology disks that seemed to fit.”

The vanity plate also required a makeover. In Washington state it was “DISKDRV,” but, Klein says, “we had to shave the license plate a bit because there are fewer letters in Massachusetts.”

Today, the car has about 250,000 miles and an Instagram account. “The biggest challenge is just the disks have to be resurfaced, like a lizard, every few years,” says Klein, whose partner, an MIT research scientist, often parks it around campus. “There’s a small collection of love letters for the car. People leave the car notes. It’s very sweet.”

Marking his place in STEM history

Omar Abudayyeh ’12, PhD ’18, a recent McGovern Fellow at the McGovern Institute for Brain Research at MIT who is now an assistant professor at Harvard Medical School, shares an equally riveting story about his vanity plate, “CRISPR,” which adorns his sport utility vehicle.

The plate refers to the genome-editing technique that has revolutionized biological and medical research by enabling rapid changes to genetic material. As an MIT graduate student in the lab of Professor Feng Zhang, a pioneering contributor to CRISPR technologies, Abudayyeh was highly involved in early CRISPR development for DNA and RNA editing. In fact, he and Jonathan Gootenberg ’13, another recent McGovern Fellow and assistant professor at Harvard Medical School who works closely with Abudayyeh, discovered many novel CRISPR enzymes, such as Cas12 and Cas13, and applied these technologies for both gene therapy and CRISPR diagnostics.

So how did Abudayyeh score his vanity plate? It was all due to his attendance at a genome-editing conference in 2022, where another early-stage CRISPR researcher, Samuel Sternberg, showed up in a car with New York “CRISPR” plates. “It became quite a source of discussion at the conference, and at one of the breaks, Sam and his labmates egged us on to get the Massachusetts license plate,” Abudayyeh explains. “I insisted that it must be taken, but I applied anyway, paying the 70 dollars and then receiving a message that I would get a letter eight to 12 weeks later about whether the plate was available or not. I then returned to Boston and forgot about it until a couple months later when, to my surprise, the plate arrived in the mail.”

While Abudayyeh continues his affiliation with the McGovern Institute, he and Gootenberg recently set up a lab at Harvard Medical School as new faculty members. “We have continued to discover new enzymes, such as Cas7-11, that enable new frontiers, such as programmable proteases for RNA sensing and novel therapeutics, and we’ve applied CRISPR technologies for new efforts in gene editing and aging research,” Abudayyeh notes.

As for his license plate, he says, “I’ve seen instances of people posting about it on Twitter or asking about it in Slack channels. A number of times, people have stopped me to say they read the Walter Isaacson book on CRISPR, asking how I was related to it. I would then explain my story — and describe how I’m actually in the book, in the chapters on CRISPR diagnostics.”

Displaying MIT roots, nerd pride

For some, a connection to MIT is all the reason they need to register a vanity plate — or three. Jeffrey Chambers SM ’06, PhD ’14, a graduate of the Department of Aeronautics and Astronautics, shares that he drives with a Virginia license plate touting his “PHD MIT.” Professor of biology Anthony Sinskey ScD ’67 owns several vehicles sporting vanity plates that honor Course 20, which is today the Department of Biological Engineering but has previously been known by Food Technology, Nutrition and Food Science, and Applied Biological Sciences. Sinskey says he has both “MIT 20” and “MIT XX” plates in Massachusetts and New Hampshire.

At least two MIT couples have had dual vanity plates. Says Laura Kiessling ’83, professor of chemistry: “My plate is ‘SLEX.’ This is the abbreviation for a carbohydrate called sialyl Lewis X. It has many roles, including a role in fertilization (sperm-egg binding). It tends to elicit many different reactions from people asking me what it means. Unless they are scientists, I say that my husband [Ron Raines ’80, professor of biology] gave it to me as an inside joke. My husband’s license plate is ‘PROTEIN.’”

Professor of the practice emerita Marcia Bartusiak of MIT Comparative Media Studies/Writing and her husband, Stephen Lowe PhD ’88, previously shared a pair of related license plates. When the couple lived in Virginia, Lowe working as a mathematician on the structure of spiral galaxies and Bartusiak a young science writer focused on astronomy, they had “SPIRAL” and “GALAXY” plates. Now retired in Massachusetts, while they no longer have registered vanity plates, they’ve named their current vehicles “Redshift” and “Blueshift.”

Still other community members have plates that make a nod to their hobbies — such as Department of Earth, Atmospheric and Planetary Sciences and AeroAstro Professor Sara Seager’s “ICANOE” — or else playfully connect with fellow drivers. Julianna Mullen, communications director in the Plasma Science and Fusion Center, says of her “OMGWHY” plate: “It’s just an existential reminder of the importance of scientific inquiry, especially in traffic when someone cuts you off so they can get exactly two car lengths ahead. Oh my God, why did they do it?”

Are you an MIT affiliate with a unique vanity plate? We’d love to see it!

Q&A: What past environmental success can teach us about solving the climate crisis

by Paige Colley | EAPS |

Susan Solomon, MIT professor of Earth, atmospheric, and planetary sciences (EAPS) and of chemistry, played a critical role in understanding how a class of chemicals known as chlorofluorocarbons were creating a hole in the ozone layer. Her research was foundational to the creation of the Montreal Protocol, an international agreement established in the 1980s that phased out products releasing chlorofluorocarbons. Since then, scientists have documented signs that the ozone hole is recovering thanks to these measures.

Having witnessed this historical process first-hand, Solomon, the Lee and Geraldine Martin Professor of Environmental Studies, is aware of how people can come together to make successful environmental policy happen. Using her story, as well as other examples of success — including combating smog, getting rid of DDT, and more — Solomon draws parallels from then to now as the climate crisis comes into focus in her new book, “Solvable: How we Healed the Earth and How we can do it Again.”

Solomon took a moment to talk about why she picked the stories in her book, the students who inspired her, and why we need hope and optimism now more than ever.

Q: You have first-hand experience seeing how we’ve altered the Earth, as well as the process of creating international environmental policy. What prompted you to write a book about your experiences?

A: Lots of things, but one of the main ones is the things that I see in teaching. I have taught a class called Science, Politics and Environmental Policy for many years here at MIT. Because my emphasis is always on how we’ve actually fixed problems, students come away from that class feeling hopeful, like they really want to stay engaged with the problem.

It strikes me that students today have grown up in a very contentious and difficult era in which they feel like nothing ever gets done. But stuff does get done, even now. Looking at how we did things so far really helps you to see how we can do things in the future.

Q: In the book, you use five different stories as examples of successful environmental policy, and then end talking about how we can apply these lessons to climate change. Why did you pick these five stories?

A: I picked some of them because I’m closer to those problems in my own professional experience, like ozone depletion and smog. I did other issues partly because I wanted to show that even in the 21st century, we’ve actually got some stuff done — that’s the story of the Kigali Amendment to the Montreal Protocol, which is a binding international agreement on some greenhouse gases.

Another chapter is on DDT. One of the reasons I included that is because it had an enormous effect on the birth of the environmental movement in the United States. Plus, that story allows you to see how important the environmental groups can be.

Lead in gasoline and paint is the other one. I find it a very moving story because the idea that we were poisoning millions of children and not even realizing it is so very, very sad. But it’s so uplifting that we did figure out the problem, and it happened partly because of the civil rights movement, that made us aware that the problem was striking minority communities much more than non-minority communities.

Q: What surprised you the most during your research for the book?

A: One of the things that that I didn’t realize and should have, was the outsized role played by one single senator, Ed Muskie of Maine. He made pollution control his big issue and devoted incredible energy to it. He clearly had the passion and wanted to do it for many years, but until other factors helped him, he couldn’t. That’s where I began to understand the role of public opinion and the way in which policy is only possible when public opinion demands change.

Another thing about Muskie was the way in which his engagement with these issues demanded that science be strong. When I read what he put into congressional testimony I realized how highly he valued the science. Science alone is never enough, but it’s always necessary. Over the years, science got a lot stronger, and we developed ways of evaluating what the scientific wisdom across many different studies and many different views actually is. That’s what scientific assessment is all about, and it’s crucial to environmental progress.

Q: Throughout the book you argue that for environmental action to succeed, three things must be met which you call the three Ps: a threat much be personal, perceptible, and practical. Where did this idea come from?

A: My observations. You have to perceive the threat: In the case of the ozone hole, you could perceive it because those false-color images of the ozone loss were so easy to understand, and it was personal because few things are scarier than cancer, and a reduced ozone layer leads to too much sun, increasing skin cancers. Science plays a role in communicating what can be readily understood by the public, and that’s important to them perceiving it as a serious problem.

Nowadays, we certainly perceive the reality of climate change. We also see that it’s personal. People are dying because of heat waves in much larger numbers than they used to; there are horrible problems in the Boston area, for example, with flooding and sea level rise. People perceive the reality of the problem and they feel personally threatened.

The third P is practical: People have to believe that there are practical solutions. It’s interesting to watch how the battle for hearts and minds has shifted. There was a time when the skeptics would just attack the whole idea that the climate was changing. Eventually, they decided ‘we better accept that because people perceive it, so let’s tell them that it’s not caused by human activity.’ But it’s clear enough now that human activity does play a role. So they’ve moved on to attacking that third P, that somehow it’s not practical to have any kind of solutions. This is progress! So what about that third P?

What I tried to do in the book is to point out some of the ways in which the problem has also become eminently practical to deal with in the last 10 years, and will continue to move in that direction. We’re right on the cusp of success, and we just have to keep going. People should not give in to eco despair; that’s the worst thing you could do, because then nothing will happen. If we continue to move at the rate we have, we will certainly get to where we need to be.

Q: That ties in very nicely with my next question. The book is very optimistic; what gives you hope?

A: I’m optimistic because I’ve seen so many examples of where we have succeeded, and because I see so many signs of movement right now that are going to push us in the same direction.

If we had kept conducting business as usual as we had been in the year 2000, we’d be looking at 4 degrees of future warming. Right now, I think we’re looking at 3 degrees. I think we can get to 2 degrees. We have to really work on it, and we have to get going seriously in the next decade, but globally right now over 30 percent of our energy is from renewables. That’s fantastic! Let’s just keep going.

Q: Throughout the book, you show that environmental problems won’t be solved by individual actions alone, but requires policy and technology driving. What individual actions can people take to help push for those bigger changes?

A: A big one is choose to eat more sustainably; choose alternative transportation methods like public transportation or reducing the amount of trips that you make. Older people usually have retirement investments, you can shift them over to a social choice funds and away from index funds that end up funding companies that you might not be interested in. You can use your money to put pressure: Amazon has been under a huge amount of pressure to cut down on their plastic packaging, mainly coming from consumers. They’ve just announced they’re not going to use those plastic pillows anymore. I think you can see lots of ways in which people really do matter, and we can matter more.

Q: What do you hope people take away from the book?

A: Hope for their future and resolve to do the best they can getting engaged with it.

Scientists use computational modeling to guide a difficult chemical synthesis

by Anne Trafton | MIT News |

Researchers from MIT and the University of Michigan have discovered a new way to drive chemical reactions that could generate a wide variety of compounds with desirable pharmaceutical properties.

These compounds, known as azetidines, are characterized by four-membered rings that include nitrogen. Azetidines have traditionally been much more difficult to synthesize than five-membered nitrogen-containing rings, which are found in many FDA-approved drugs.

The reaction that the researchers used to create azetidines is driven by a photocatalyst that excites the molecules from their ground energy state. Using computational models that they developed, the researchers were able to predict compounds that can react with each other to form azetidines using this kind of catalysis.

“Going forward, rather than using a trial-and-error process, people can prescreen compounds and know beforehand which substrates will work and which ones won’t,” says Heather Kulik, an associate professor of chemistry and chemical engineering at MIT.

Kulik and Corinna Schindler, a professor of chemistry at the University of Michigan, are the senior authors of the study, which appears today in Science. Emily Wearing, recently a graduate student at the University of Michigan, is the lead author of the paper. Other authors include University of Michigan postdoc Yu-Cheng Yeh, MIT graduate student Gianmarco Terrones, University of Michigan graduate student Seren Parikh, and MIT postdoc Ilia Kevlishvili.

Light-driven synthesis

Many naturally occurring molecules, including vitamins, nucleic acids, enzymes and hormones, contain five-membered nitrogen-containing rings, also known as nitrogen heterocycles. These rings are also found in more than half of all FDA-approved small-molecule drugs, including many antibiotics and cancer drugs.

Four-membered nitrogen heterocycles, which are rarely found in nature, also hold potential as drug compounds. However, only a handful of existing drugs, including penicillin, contain four-membered heterocycles, in part because these four-membered rings are much more difficult to synthesize than five-membered heterocycles.

In recent years, Schindler’s lab has been working on synthesizing azetidines using light to drive a reaction that combines two precursors, an alkene and an oxime. These reactions require a photocatalyst, which absorbs light and passes the energy to the reactants, making it possible for them to react with each other.

“The catalyst can transfer that energy to another molecule, which moves the molecules into excited states and makes them more reactive. This is a tool that people are starting to use to make it possible to make certain reactions occur that wouldn’t normally occur,” Kulik says.

Schindler’s lab found that while this reaction sometimes worked well, other times it did not, depending on which reactants were used. They enlisted Kulik, an expert in developing computational approaches to modeling chemical reactions, to help them figure out how to predict when these reactions will occur.

The two labs hypothesized that whether a particular alkene and oxime will react together in a photocatalyzed reaction depends on a property known as the frontier orbital energy match. Electrons that surround the nucleus of an atom exist in orbitals, and quantum mechanics can be used to predict the shape and energies of these orbitals. For chemical reactions, the most important electrons are those in the outermost, highest energy (“frontier”) orbitals, which are available to react with other molecules.

Kulik and her students used density functional theory, which uses the Schrödinger equation to predict where electrons could be and how much energy they have, to calculate the orbital energy of these outermost electrons.

These energy levels are also affected by other groups of atoms attached to the molecule, which can change the properties of the electrons in the outermost orbitals.

Once those energy levels are calculated, the researchers can identify reactants that have similar energy levels when the photocatalyst boosts them into an excited state. When the excited states of an alkene and an oxime are closely matched, less energy is required to boost the reaction to its transition state — the point at which the reaction has enough energy to go forward to form products.

Accurate predictions

After calculating the frontier orbital energies for 16 different alkenes and nine oximes, the researchers used their computational model to predict whether 18 different alkene-oxime pairs would react together to form an azetidine. With the calculations in hand, these predictions can be made in a matter of seconds.

The researchers also modeled a factor that influences the overall yield of the reaction: a measure of how available the carbon atoms in the oxime are to participate in chemical reactions.

The model’s predictions suggested that some of these 18 reactions won’t occur or won’t give a high enough yield. However, the study also showed that a significant number of reactions are correctly predicted to work.

“Based on our model, there’s a much wider range of substrates for this azetidine synthesis than people thought before. People didn’t really think that all of this was accessible,” Kulik says.

Of the 27 combinations that they studied computationally, the researchers tested 18 reactions experimentally, and they found that most of their predictions were accurate. Among the compounds they synthesized were derivatives of two drug compounds that are currently FDA-approved: amoxapine, an antidepressant, and indomethacin, a pain reliever used to treat arthritis.

This computational approach could help pharmaceutical companies predict molecules that will react together to form potentially useful compounds, before spending a lot of money to develop a synthesis that might not work, Kulik says. She and Schindler are continuing to work together on other kinds of novel syntheses, including the formation of compounds with three-membered rings.

“Using photocatalysts to excite substrates is a very active and hot area of development, because people have exhausted what you can do on the ground state or with radical chemistry,” Kulik says. “I think this approach is going to have a lot more applications to make molecules that are normally thought of as really challenging to make.”