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    Professor Emeritus Richard Wurtman, influential figure in translational research, dies at 86

    Richard Wurtman, the Cecil H. Green Distinguished Professor Emeritus and a member of the MIT faculty for 44 years, died on Dec. 13. He was 86.

    Wurtman received an MD from Harvard Medical School in 1960 and trained at Massachusetts General Hospital before joining the laboratory of Nobel laureate Julius Axelrod at the National Institutes of Health in 1962. In 1967, MIT invited him to start a neurochemistry and neuropharmacology program in the Department of Nutrition and Food Science. In the early 1980s he joined the newly formed Department of Brain and Cognitive Sciences. Wurtman was also deeply involved in the National Institutes of Health-established Clinical Research Center at MIT, which he also directed for 25 years.

    His initial placement in Nutrition and Food Science was fortuitous, recalled Wurtman in a 2011 profile, because it “sensitized me to the fact that nutrients are chemicals the way drugs are chemicals. A compound like folic acid is a vitamin in foods, but when given alone in higher doses it becomes a drug that safeguards the developing nervous system.”

    Wurtman’s search for new biological properties and therapeutic uses of known molecules — hormones, nutrients, or existing pharmaceuticals — was highly fruitful. His research on the pineal gland, which started when he was a medical student, led to the discovery that melatonin, the hormone made by the gland, regulates sleep. 

    “Dick Wurtman was a pioneer in studying the role of neurotransmitters in the brain, and neuroendocrine regulation of normal and abnormal brain function,” says Newton Professor of Neuroscience Mriganka Sur, who served as head of the Department of Brain and Cognitive Sciences from 1997 to 2012. “His work on the impact of nutrition on neurotransmitters such as acetylcholine and on neuronal membrane synthesis laid the groundwork for later translational work on brain diseases such as Alzheimer’s disease.”

    Wurtman’s lab discovered that consuming carbohydrates increases tryptophan levels in the brain and consequently the production of the neurotransmitter serotonin. This led to a long collaboration with his wife Judith Wurtman, an MIT research affiliate, in which they found that carbohydrates were often consumed by individuals as a form of self-medication when they experienced changes in mood, such as late in the afternoon or when suffering from premenstrual syndrome (PMS). The Wurtmans’ research led to the development of Sarafem, the first drug for severe PMS, and a drink, PMS Escape, used for milder forms of this syndrome.

    To commercialize some of his findings, Wurtman founded Interneuron Pharmaceuticals in 1988; the company was renamed Indevus in 2002 and acquired by Endo Pharmaceuticals in 2009.

    Wurtman’s research advanced the idea that substrate availability, and not simply enzyme activity, can control metabolic processes in the brain. He discovered that the dietary availability of neurotransmitter precursors (e.g., acetylcholine, dopamine, and GABA) can increase their levels in the brain and modulate their metabolism. Moreover, he applied this concept to synaptic structural components such as brain phosphatides and found that dietary intake of three rate-limiting precursors — uridine, choline, and the omega-3 fatty acid DHA — led to increased brain phosphatide levels, increased dendritic spine density, and improved memory performance. These findings led to the development of Souvenaid, a specifically formulated multi-nutrient drink based on the three essential phosphatide precursors of Wurtman’s later research. It has been the subject of numerous clinical trials for Alzheimer’s disease, and, most recently, for age-related cognitive decline.

    “Dick Wurtman was a pioneer on studying how nutrients influence brain function,” says Li-Huei Tsai, Picower Professor of Neuroscience and director of The Picower Institute for Learning and Memory. “His nutrient clinical trial work and establishment of the MIT Clinical Research Center have been tremendously helpful for my own work on understanding how high doses of supplement choline could potentially help reduce certain Alzheimer’s risk, and our team’s development of clinical studies at MIT to test Alzheimer’s therapies.”

    “Dick’s legacy resides within the careers of hundreds of trainees and collaborators he launched or enhanced, the 1,000-plus published research articles, his numerous patent awards, and people who benefited from his therapeutic approaches,” says former postdoc Bertha Madras, now a professor of psychobiology at McLean Hospital and Harvard Medical School. “Yet, these quantitative metrics, legacies of research and mentoring, do not illustrate the charitable qualities of this remarkable man. I witnessed his deep intellect, boundless energy, enthusiasm, optimism, and generosity toward trainees, qualities that helped to sustain me during crests and troughs encountered in the adventures of a scientific career. Dr. Richard Wurtman was a creative, brilliant scientist, a mentor, a devoted husband to his beloved wife.”

    “Dick was an inspiration, a motivation, and a guide to all his students and colleagues in shaping thoughts to be precise and purposeful,” says Tony Nader PhD ’89, who did his doctoral research with Wurtman. “His rigorous scientific approach and the application of his findings have contributed to make life better. His legacy is huge.”

    Richard and Judith Wurtman have also made a lasting philanthropic impact at MIT. They endowed a professorship in the Department of Brain and Cognitive Sciences in honor of the late Institute Professor and provost Walter Rosenblith; the chair was held first by Ann Graybiel, who is now an Institute Professor; Nancy Kanwisher is the current Walter A. Rosenblith Professor of Cognitive Neuroscience. The Wurtmans have also been longtime supporters of MIT Hillel.

    Elazer R. Edelman, the Edward J. Poitras Professor in Medical Engineering and Science at MIT, professor of medicine at Harvard Medical School, and director of the MIT Institute for Medical Engineering and Science, recalls that Wurtman was also supportive of the Harvard-MIT Program in Health Sciences and Technology: “He changed our school and our world — he and Judith coupled immense charity with exceptional intellect and they made us all better for it.”

    Richard Wurtman is survived by his wife, Judith; daughter Rachael; son David and daughter-in-law Jean Chang; and grandchildren Dvora Toren, Yael Toren and Jacob Vider.  More

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    These neurons have food on the brain

    A gooey slice of pizza. A pile of crispy French fries. Ice cream dripping down a cone on a hot summer day. When you look at any of these foods, a specialized part of your visual cortex lights up, according to a new study from MIT neuroscientists.

    This newly discovered population of food-responsive neurons is located in the ventral visual stream, alongside populations that respond specifically to faces, bodies, places, and words. The unexpected finding may reflect the special significance of food in human culture, the researchers say. 

    “Food is central to human social interactions and cultural practices. It’s not just sustenance,” says Nancy Kanwisher, the Walter A. Rosenblith Professor of Cognitive Neuroscience and a member of MIT’s McGovern Institute for Brain Research and Center for Brains, Minds, and Machines. “Food is core to so many elements of our cultural identity, religious practice, and social interactions, and many other things that humans do.”

    The findings, based on an analysis of a large public database of human brain responses to a set of 10,000 images, raise many additional questions about how and why this neural population develops. In future studies, the researchers hope to explore how people’s responses to certain foods might differ depending on their likes and dislikes, or their familiarity with certain types of food.

    MIT postdoc Meenakshi Khosla is the lead author of the paper, along with MIT research scientist N. Apurva Ratan Murty. The study appears today in the journal Current Biology.

    Visual categories

    More than 20 years ago, while studying the ventral visual stream, the part of the brain that recognizes objects, Kanwisher discovered cortical regions that respond selectively to faces. Later, she and other scientists discovered other regions that respond selectively to places, bodies, or words. Most of those areas were discovered when researchers specifically set out to look for them. However, that hypothesis-driven approach can limit what you end up finding, Kanwisher says.

    “There could be other things that we might not think to look for,” she says. “And even when we find something, how do we know that that’s actually part of the basic dominant structure of that pathway, and not something we found just because we were looking for it?”

    To try to uncover the fundamental structure of the ventral visual stream, Kanwisher and Khosla decided to analyze a large, publicly available dataset of full-brain functional magnetic resonance imaging (fMRI) responses from eight human subjects as they viewed thousands of images.

    “We wanted to see when we apply a data-driven, hypothesis-free strategy, what kinds of selectivities pop up, and whether those are consistent with what had been discovered before. A second goal was to see if we could discover novel selectivities that either haven’t been hypothesized before, or that have remained hidden due to the lower spatial resolution of fMRI data,” Khosla says.

    To do that, the researchers applied a mathematical method that allows them to discover neural populations that can’t be identified from traditional fMRI data. An fMRI image is made up of many voxels — three-dimensional units that represent a cube of brain tissue. Each voxel contains hundreds of thousands of neurons, and if some of those neurons belong to smaller populations that respond to one type of visual input, their responses may be drowned out by other populations within the same voxel.

    The new analytical method, which Kanwisher’s lab has previously used on fMRI data from the auditory cortex, can tease out responses of neural populations within each voxel of fMRI data.

    Using this approach, the researchers found four populations that corresponded to previously identified clusters that respond to faces, places, bodies, and words. “That tells us that this method works, and it tells us that the things that we found before are not just obscure properties of that pathway, but major, dominant properties,” Kanwisher says.

    Intriguingly, a fifth population also emerged, and this one appeared to be selective for images of food.

    “We were first quite puzzled by this because food is not a visually homogenous category,” Khosla says. “Things like apples and corn and pasta all look so unlike each other, yet we found a single population that responds similarly to all these diverse food items.”

    The food-specific population, which the researchers call the ventral food component (VFC), appears to be spread across two clusters of neurons, located on either side of the FFA. The fact that the food-specific populations are spread out between other category-specific populations may help explain why they have not been seen before, the researchers say.

    “We think that food selectivity had been harder to characterize before because the populations that are selective for food are intermingled with other nearby populations that have distinct responses to other stimulus attributes. The low spatial resolution of fMRI prevents us from seeing this selectivity because the responses of different neural population get mixed in a voxel,” Khosla says.

    “The technique which the researchers used to identify category-sensitive cells or areas is impressive, and it recovered known category-sensitive systems, making the food category findings most impressive,” says Paul Rozin, a professor of psychology at the University of Pennsylvania, who was not involved in the study. “I can’t imagine a way for the brain to reliably identify the diversity of foods based on sensory features. That makes this all the more fascinating, and likely to clue us in about something really new.”

    Food vs non-food

    The researchers also used the data to train a computational model of the VFC, based on previous models Murty had developed for the brain’s face and place recognition areas. This allowed the researchers to run additional experiments and predict the responses of the VFC. In one experiment, they fed the model matched images of food and non-food items that looked very similar — for example, a banana and a yellow crescent moon.

    “Those matched stimuli have very similar visual properties, but the main attribute in which they differ is edible versus inedible,” Khosla says. “We could feed those arbitrary stimuli through the predictive model and see whether it would still respond more to food than non-food, without having to collect the fMRI data.”

    They could also use the computational model to analyze much larger datasets, consisting of millions of images. Those simulations helped to confirm that the VFC is highly selective for images of food.

    From their analysis of the human fMRI data, the researchers found that in some subjects, the VFC responded slightly more to processed foods such as pizza than unprocessed foods like apples. In the future they hope to explore how factors such as familiarity and like or dislike of a particular food might affect individuals’ responses to that food.

    They also hope to study when and how this region becomes specialized during early childhood, and what other parts of the brain it communicates with. Another question is whether this food-selective population will be seen in other animals such as monkeys, who do not attach the cultural significance to food that humans do.

    The research was funded by the National Institutes of Health, the National Eye Institute, and the National Science Foundation through the MIT Center for Brains, Minds, and Machines. More

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    Setting carbon management in stone

    Keeping global temperatures within limits deemed safe by the Intergovernmental Panel on Climate Change means doing more than slashing carbon emissions. It means reversing them.

    “If we want to be anywhere near those limits [of 1.5 or 2 C], then we have to be carbon neutral by 2050, and then carbon negative after that,” says Matěj Peč, a geoscientist and the Victor P. Starr Career Development Assistant Professor in the Department of Earth, Atmospheric, and Planetary Sciences (EAPS).

    Going negative will require finding ways to radically increase the world’s capacity to capture carbon from the atmosphere and put it somewhere where it will not leak back out. Carbon capture and storage projects already suck in tens of million metric tons of carbon each year. But putting a dent in emissions will mean capturing many billions of metric tons more. Today, people emit around 40 billion tons of carbon each year globally, mainly by burning fossil fuels.

    Because of the need for new ideas when it comes to carbon storage, Peč has created a proposal for the MIT Climate Grand Challenges competition — a bold and sweeping effort by the Institute to support paradigm-shifting research and innovation to address the climate crisis. Called the Advanced Carbon Mineralization Initiative, his team’s proposal aims to bring geologists, chemists, and biologists together to make permanently storing carbon underground workable under different geological conditions. That means finding ways to speed-up the process by which carbon pumped underground is turned into rock, or mineralized.

    “That’s what the geology has to offer,” says Peč, who is a lead on the project, along with Ed Boyden, professor of biological engineering, brain and cognitive sciences, and media arts and sciences, and Yogesh Surendranath, professor of chemistry. “You look for the places where you can safely and permanently store these huge volumes of CO2.”

    Peč‘s proposal is one of 27 finalists selected from a pool of almost 100 Climate Grand Challenge proposals submitted by collaborators from across the Institute. Each finalist team received $100,000 to further develop their research proposals. A subset of finalists will be announced in April, making up a portfolio of multiyear “flagship” projects receiving additional funding and support.

    Building industries capable of going carbon negative presents huge technological, economic, environmental, and political challenges. For one, it’s expensive and energy-intensive to capture carbon from the air with existing technologies, which are “hellishly complicated,” says Peč. Much of the carbon capture underway today focuses on more concentrated sources like coal- or gas-burning power plants.

    It’s also difficult to find geologically suitable sites for storage. To keep it in the ground after it has been captured, carbon must either be trapped in airtight reservoirs or turned to stone.

    One of the best places for carbon capture and storage (CCS) is Iceland, where a number of CCS projects are up and running. The island’s volcanic geology helps speed up the mineralization process, as carbon pumped underground interacts with basalt rock at high temperatures. In that ideal setting, says Peč, 95 percent of carbon injected underground is mineralized after just two years — a geological flash.

    But Iceland’s geology is unusual. Elsewhere requires deeper drilling to reach suitable rocks at suitable temperature, which adds costs to already expensive projects. Further, says Peč, there’s not a complete understanding of how different factors influence the speed of mineralization.

    Peč‘s Climate Grand Challenge proposal would study how carbon mineralizes under different conditions, as well as explore ways to make mineralization happen more rapidly by mixing the carbon dioxide with different fluids before injecting it underground. Another idea — and the reason why there are biologists on the team — is to learn from various organisms adept at turning carbon into calcite shells, the same stuff that makes up limestone.

    Two other carbon management proposals, led by EAPS Cecil and Ida Green Professor Bradford Hager, were also selected as Climate Grand Challenge finalists. They focus on both the technologies necessary for capturing and storing gigatons of carbon as well as the logistical challenges involved in such an enormous undertaking.

    That involves everything from choosing suitable sites for storage, to regulatory and environmental issues, as well as how to bring disparate technologies together to improve the whole pipeline. The proposals emphasize CCS systems that can be powered by renewable sources, and can respond dynamically to the needs of different hard-to-decarbonize industries, like concrete and steel production.

    “We need to have an industry that is on the scale of the current oil industry that will not be doing anything but pumping CO2 into storage reservoirs,” says Peč.

    For a problem that involves capturing enormous amounts of gases from the atmosphere and storing it underground, it’s no surprise EAPS researchers are so involved. The Earth sciences have “everything” to offer, says Peč, including the good news that the Earth has more than enough places where carbon might be stored.

    “Basically, the Earth is really, really large,” says Peč. “The reasonably accessible places, which are close to the continents, store somewhere on the order of tens of thousands to hundreds thousands of gigatons of carbon. That’s orders of magnitude more than we need to put back in.” More

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    Q&A: Climate Grand Challenges finalists on accelerating reductions in global greenhouse gas emissions

    This is the second article in a four-part interview series highlighting the work of the 27 MIT Climate Grand Challenges finalists, which received a total of $2.7 million in startup funding to advance their projects. In April, the Institute will name a subset of the finalists as multiyear flagship projects.

    Last month, the Intergovernmental Panel on Climate Change (IPCC), an expert body of the United Nations representing 195 governments, released its latest scientific report on the growing threats posed by climate change, and called for drastic reductions in greenhouse gas emissions to avert the most catastrophic outcomes for humanity and natural ecosystems.

    Bringing the global economy to net-zero carbon dioxide emissions by midcentury is complex and demands new ideas and novel approaches. The first-ever MIT Climate Grand Challenges competition focuses on four problem areas including removing greenhouse gases from the atmosphere and identifying effective, economic solutions for managing and storing these gases. The other Climate Grand Challenges research themes address using data and science to forecast climate-related risk, decarbonizing complex industries and processes, and building equity and fairness into climate solutions.

    In the following conversations prepared for MIT News, faculty from three of the teams working to solve “Removing, managing, and storing greenhouse gases” explain how they are drawing upon geological, biological, chemical, and oceanic processes to develop game-changing techniques for carbon removal, management, and storage. Their responses have been edited for length and clarity.

    Directed evolution of biological carbon fixation

    Agricultural demand is estimated to increase by 50 percent in the coming decades, while climate change is simultaneously projected to drastically reduce crop yield and predictability, requiring a dramatic acceleration of land clearing. Without immediate intervention, this will have dire impacts on wild habitat, rob the livelihoods of hundreds of millions of subsistence farmers, and create hundreds of gigatons of new emissions. Matthew Shoulders, associate professor in the Department of Chemistry, talks about the working group he is leading in partnership with Ed Boyden, the Y. Eva Tan professor of neurotechnology and Howard Hughes Medical Institute investigator at the McGovern Institute for Brain Research, that aims to massively reduce carbon emissions from agriculture by relieving core biochemical bottlenecks in the photosynthetic process using the most sophisticated synthetic biology available to science.

    Q: Describe the two pathways you have identified for improving agricultural productivity and climate resiliency.

    A: First, cyanobacteria grow millions of times faster than plants and dozens of times faster than microalgae. Engineering these cyanobacteria as a source of key food products using synthetic biology will enable food production using less land, in a fundamentally more climate-resilient manner. Second, carbon fixation, or the process by which carbon dioxide is incorporated into organic compounds, is the rate-limiting step of photosynthesis and becomes even less efficient under rising temperatures. Enhancements to Rubisco, the enzyme mediating this central process, will both improve crop yields and provide climate resilience to crops needed by 2050. Our team, led by Robbie Wilson and Max Schubert, has created new directed evolution methods tailored for both strategies, and we have already uncovered promising early results. Applying directed evolution to photosynthesis, carbon fixation, and food production has the potential to usher in a second green revolution.

    Q: What partners will you need to accelerate the development of your solutions?

    A: We have already partnered with leading agriculture institutes with deep experience in plant transformation and field trial capacity, enabling the integration of our improved carbon-dioxide-fixing enzymes into a wide range of crop plants. At the deployment stage, we will be positioned to partner with multiple industry groups to achieve improved agriculture at scale. Partnerships with major seed companies around the world will be key to leverage distribution channels in manufacturing supply chains and networks of farmers, agronomists, and licensed retailers. Support from local governments will also be critical where subsidies for seeds are necessary for farmers to earn a living, such as smallholder and subsistence farming communities. Additionally, our research provides an accessible platform that is capable of enabling and enhancing carbon dioxide sequestration in diverse organisms, extending our sphere of partnership to a wide range of companies interested in industrial microbial applications, including algal and cyanobacterial, and in carbon capture and storage.

    Strategies to reduce atmospheric methane

    One of the most potent greenhouse gases, methane is emitted by a range of human activities and natural processes that include agriculture and waste management, fossil fuel production, and changing land use practices — with no single dominant source. Together with a diverse group of faculty and researchers from the schools of Humanities, Arts, and Social Sciences; Architecture and Planning; Engineering; and Science; plus the MIT Schwarzman College of Computing, Desiree Plata, associate professor in the Department of Civil and Environmental Engineering, is spearheading the MIT Methane Network, an integrated approach to formulating scalable new technologies, business models, and policy solutions for driving down levels of atmospheric methane.

    Q: What is the problem you are trying to solve and why is it a “grand challenge”?

    A: Removing methane from the atmosphere, or stopping it from getting there in the first place, could change the rates of global warming in our lifetimes, saving as much as half a degree of warming by 2050. Methane sources are distributed in space and time and tend to be very dilute, making the removal of methane a challenge that pushes the boundaries of contemporary science and engineering capabilities. Because the primary sources of atmospheric methane are linked to our economy and culture — from clearing wetlands for cultivation to natural gas extraction and dairy and meat production — the social and economic implications of a fundamentally changed methane management system are far-reaching. Nevertheless, these problems are tractable and could significantly reduce the effects of climate change in the near term.

    Q: What is known about the rapid rise in atmospheric methane and what questions remain unanswered?

    A: Tracking atmospheric methane is a challenge in and of itself, but it has become clear that emissions are large, accelerated by human activity, and cause damage right away. While some progress has been made in satellite-based measurements of methane emissions, there is a need to translate that data into actionable solutions. Several key questions remain around improving sensor accuracy and sensor network design to optimize placement, improve response time, and stop leaks with autonomous controls on the ground. Additional questions involve deploying low-level methane oxidation systems and novel catalytic materials at coal mines, dairy barns, and other enriched sources; evaluating the policy strategies and the socioeconomic impacts of new technologies with an eye toward decarbonization pathways; and scaling technology with viable business models that stimulate the economy while reducing greenhouse gas emissions.

    Deploying versatile carbon capture technologies and storage at scale

    There is growing consensus that simply capturing current carbon dioxide emissions is no longer sufficient — it is equally important to target distributed sources such as the oceans and air where carbon dioxide has accumulated from past emissions. Betar Gallant, the American Bureau of Shipping Career Development Associate Professor of Mechanical Engineering, discusses her work with Bradford Hager, the Cecil and Ida Green Professor of Earth Sciences in the Department of Earth, Atmospheric and Planetary Sciences, and T. Alan Hatton, the Ralph Landau Professor of Chemical Engineering and director of the School of Chemical Engineering Practice, to dramatically advance the portfolio of technologies available for carbon capture and permanent storage at scale. (A team led by Assistant Professor Matěj Peč of EAPS is also addressing carbon capture and storage.)

    Q: Carbon capture and storage processes have been around for several decades. What advances are you seeking to make through this project?

    A: Today’s capture paradigms are costly, inefficient, and complex. We seek to address this challenge by developing a new generation of capture technologies that operate using renewable energy inputs, are sufficiently versatile to accommodate emerging industrial demands, are adaptive and responsive to varied societal needs, and can be readily deployed to a wider landscape.

    New approaches will require the redesign of the entire capture process, necessitating basic science and engineering efforts that are broadly interdisciplinary in nature. At the same time, incumbent technologies have been optimized largely for integration with coal- or natural gas-burning power plants. Future applications must shift away from legacy emitters in the power sector towards hard-to-mitigate sectors such as cement, iron and steel, chemical, and hydrogen production. It will become equally important to develop and optimize systems targeted for much lower concentrations of carbon dioxide, such as in oceans or air. Our effort will expand basic science studies as well as human impacts of storage, including how public engagement and education can alter attitudes toward greater acceptance of carbon dioxide geologic storage.

    Q: What are the expected impacts of your proposed solution, both positive and negative?

    A: Renewable energy cannot be deployed rapidly enough everywhere, nor can it supplant all emissions sources, nor can it account for past emissions. Carbon capture and storage (CCS) provides a demonstrated method to address emissions that will undoubtedly occur before the transition to low-carbon energy is completed. CCS can succeed even if other strategies fail. It also allows for developing nations, which may need to adopt renewables over longer timescales, to see equitable economic development while avoiding the most harmful climate impacts. And, CCS enables the future viability of many core industries and transportation modes, many of which do not have clear alternatives before 2050, let alone 2040 or 2030.

    The perceived risks of potential leakage and earthquakes associated with geologic storage can be minimized by choosing suitable geologic formations for storage. Despite CCS providing a well-understood pathway for removing enough of the carbon dioxide already emitted into the atmosphere, some environmentalists vigorously oppose it, fearing that CCS rewards oil companies and disincentivizes the transition away from fossil fuels. We believe that it is more important to keep in mind the necessity of meeting key climate targets for the sake of the planet, and welcome those who can help. More