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Pioneers

The frontiers of science provide ample space to explore innovation. Meet nine of the pioneers.

  • Age:
    32

    Jonathan Viventi

    A high-resolution interface reveals the brain storms of people suffering seizures.

    On his cell phone, Jonathan Viventi, a biomedical engineer at New York University’s Polytechnic School of Engineering, displays what looks like a meteorologist’s map of a fast-moving storm: red, orange, yellow, green, and blue patches swirl in ominous, complex patterns. In fact, the video represents the highest-resolution electrical data yet recorded over a large surface of an animal’s brain during an epileptic seizure. 

    Previously, researchers using lower-resolution technology had observed repetitive spiking patterns during seizures. But those recordings were “vastly undersampling the electrical activity of the brain,” says Viventi. His innovation was to develop a better interface that could capture more detail, revealing patterns of waves rotating, changing direction, and moving across the brain’s surface.

    The improved imaging is possible because of an implant that is roughly one centimeter square and can be positioned, in theory, anywhere on the surface of the brain. The implant incorporates flexible electronics into an array of sensors; indeed, Viventi was the first to move electronics, which are usually rigid and located far from such sensors, directly to the brain’s surface. “This allows us to amplify and combine signals directly at the source, so that we don’t need to have one wire for each sensor,” he says. That, he adds, “lets us build much higher-resolution interfaces with the brain.” 

    Viventi’s brain ­interface has both an array of sensors and flexible electronics.

    Viventi imagines that doctors will use his implants as a temporary way to monitor seizures and plan treatment, including further surgery, in people with epilepsy. In the longer term, he hopes that permanent implants for patients with severe epilepsy can sense brain activity and stimulate the appropriate regions. He hopes to win approval for clinical trials of his devices, though to date the team has only done experiments on animals. 

    Viventi first became interested in epilepsy when he was a graduate student in bioengineering at the University of Pennsylvania. It was because he was struck by the crude technology used to evaluate the patients that he decided to develop a system for recording sensitive signals from thousands of sensors placed directly on the surface of the brain—a mission that at the time seemed “kind of crazy,” he says.

    Ultimately, one of the biggest challenges will be adapting the electronic interface so that it doesn’t degrade over time. “Our bodies are full of salt water, and salt does not work well with electronics,” he says.

    Amanda Schaffer

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  • Age:
    34

    Emily Balskus

    More precise knowledge of the bacteria in our guts could lead to better-targeted treatments for chronic conditions.

    Problem:
    Some 100 trillion bacteria live in our intestines, and their activities are strongly linked to illnesses like heart disease and colon cancer—and are critical in maintaining our general health. Although we know these microbes play an essential role in metabolizing drugs and digesting food, we know relatively little about the chemical transformations they use to get the job done. Learning more about them will be essential to creating new drugs and therapies and shaping dietary guidelines for individual patients.

    Solution:
    Emily Balskus, an assistant professor of chemistry and chemical biology at Harvard, uses a variety of approaches, including advanced DNA sequencing, to discover new metabolic pathways and to study how gut bacteria use chemical reactions to survive. In one example of her success, Balskus’s Harvard lab has been credited with uncovering the bacterial enzymes in the human gut that convert the essential nutrient choline to trimethylamine, a metabolite linked to heart disease. Because a majority of choline comes from food, learning more about its relationship to intestinal bacteria could illuminate the link between diet and the risk of heart disease. 

    —Kristin Majcher

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  • Age:
    31

    Duygu Kuzum

    Brain-inspired chips could mean better computer processing and neural implants.

    Inspired by the architecture of the brain, Duygu Kuzum has designed electronic devices that mimic the behavior of synapses, the connections between neurons. When she was a graduate student at Stanford, Kuzum initially focused on high-­performance electronics for computer processors. But during a summer internship at Intel, she had a kind of neuro-epiphany. “I was always thinking, ‘Okay, now I’m designing and trying to increase the performance of these electronic components and trying to build a computer to be used by another computer, which is the human brain,’” she says. “And I realized that these two computers are built on and operate on fundamentally different principles.”

    So Kuzum set out to design a computer chip based on the way the brain’s synapses process information. Unlike computer circuits, which are based on the binary choices of on or off, 0 or 1, synapses can operate more like a dimmer switch, with variations in strength. Using that insight, Kuzum and her Stanford colleagues created “nanoelectric synaptic grids”—miniaturized computer circuits that can understand and recall rather sophisticated patterns. The prototype opens the way to the development of small, portable, energy-­efficient computers that can process complex sources of data, such as visual and auditory information. That same architecture, Kuzum believes, can also be used to design neural implants and prosthetic devices that act as ­supple, realistic interfaces between computer controls and living brain tissue.

    Kuzum, who grew up and went to university in Ankara, Turkey, moved to a postdoc position at the University of Pennsylvania in 2011 and is now trying to create a new type of brain electrode using graphene, a form of carbon that is both flexible and transparent. Implanted in neural tissue, the electrodes could let researchers record the activity of nerve cells while simultaneously imaging their behavior.

    “We cannot 100 percent replicate the brain,” Kuzum concedes. But, she suggests, maybe we can “build a system that’s more brain-inspired.”

    Stephen S. Hall

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  • Age:
    31

    Megan McCain

    Heart on a chip paves the way for personalized cardiac medicines.

    What if there were a way to use a patient’s own cells to test his or her response to a cardiac drug before it was administered? Megan McCain, an assistant professor at the University of Southern California, is developing a so-called heart on a chip, roughly the size of a quarter, to do just that.

    When she was a postdoc at Harvard, McCain began collaborating with cardiologists at Boston Children’s Hospital. Her colleagues took skin cells from a patient, reprogrammed them to become stem cells, and turned the stem cells into heart cells. “Those heart cells should work pretty much the way your native heart cells should work,” she says. “They’ll have the same genetic information.” McCain then engineered tissues from these heart cells and used the heart-on-a-chip system to examine how the structure and function of healthy tissues differed from that of diseased tissues. The patient-specific cells living on a chip offer a more accurate way to predict how an individual’s heart will respond to a drug than, say, tests using lab animals.

    McCain and her team have used the technology to test drug treatment for Barth syndrome, a rare cardiac disease caused by a single-gene mutation. She hopes that this chip will someday be used to test treatments for genetically caused cardiac diseases in general.

    Other researchers have also created simulated organs on chips, but the heart presents specific challenges. “It is very mechanical, and it has an electrical side,” says McCain. “I appreciate how delicate, complex, and interesting the heart is.”

    Alexandra Morris

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  • Age:
    33

    Maryam Shanechi

    Using control theory to build better interfaces to the brain.

    “I was born in Iran. My family immigrated to Canada when I was 16. My parents wanted a better education for me, my brother, and sister. I started out working on information theory, coding theory, and wireless communication. But I wanted to more directly impact people in my research. When I was looking for a PhD topic, I came across neuroscience, and I realized that the same principle could be used to treat brain disorders. 

    “So I moved from decoding wireless signals to decoding brain signals. I develop brain-machine interfaces that record the activity of neurons while someone plans a movement. This could one day allow disabled patients to move just by thinking about it. 

    “My work takes a lot of insight from control theory. Say you reach for a glass of wateryour brain wants that to happen in a certain time frame, and it’s getting visual feedback, and you can adjust the speed. The brain acts as a ‘feedback controller,’ and I have built models for how that works. I also work on brain-machine interfaces for anesthesia. We decode the level of brain activity and adjust the anesthetic accordingly.

    “I started as a professor at Cornell University and moved to the University of Southern California in July. As part of the Obama BRAIN initiative, I’m involved in a project to revolutionize treatments for neuropsychiatric disorders, such as PTSD and depression. We will create a brain-machine interface to decode the neuropsychiatric state of the brain, and decide on a set of electrical stimulation patterns to alleviate the symptoms in real time. This would be an automatic controllera closed-loop system. And I will build that. 

    “We know nothing about the signatures of neuropsychiatric disorders in the brain. We need to discover those. I am really excited, because there is so much we don’t know.” 

    —as told to Antonio Regalado

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  • Age:
    33

    Kay Tye

    Identifying how the connections between regions of the brain contribute to anxiety.

    Neuroscience has often focused on dividing the brain into regions, pinpointing which individual neurons are responsible for specific functions. Kay Tye’s vision of the brain is defined less by discrete addresses than by the roads between them—the connections between groups of neurons. “I think neuroscience as a field is at this threshold of a new understanding of the brain in terms of circuits,” says Tye, a principal investigator at the Picower Institute for Learning and Memory at MIT. The connections a cell makes could be at least as important as its location, she believes.

    As a postdoc at Stanford University, Tye took advantage of a relatively new technology called optogenetics, which allows researchers to use light to turn specific, genetically modified neurons on and off in lab animals. 

    Manipulating the connections in mice between a group of neurons in the amygdala with a group in the hippocampus, she precisely altered behaviors related to both anxiety and social interaction to tease apart the specific connections she suspected played a critical role in anxiety. When the circuit is inhibited, a mouse that normally avoids open areas explores them freely, and when it’s activated, the mouse runs for cover. In a subsequent study, Tye showed that inhibiting a circuit made a mouse sniff and nudge a strange mouse in its cage, while activating it made the mouse ignore the stranger—a test of the animal’s tendency toward social interaction. 

    The idea that manipulating connections between small bundles of brain cells could instantly reshape behavior opens up new possibilities for treating brain disorders. Current drugs, she says, “target the entire body and bathe the whole brain in this soup,” creating many unwanted side effects. If scientists can find a way to safely manipulate the human neural connections involved in feelings such as anxiety, therapies might be more precise and cause fewer side effects. 

    First, researchers will have to identify the various connections that can be manipulated this way. It’s an enormous task given the complexity of the brain. But at least Tye’s breakthroughs have helped get them on the right road. 

    Courtney Humphries

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  • Age:
    34

    Kathryn Whitehead

    A systematic search discovered nanoparticles that could improve drug delivery.

    While still working on her PhD in chemical engineering at the University of California, Santa Barbara, Kathryn Whitehead created small experimental patches that, when swallowed, adhere to the intestine to deliver insulin. It is a promising alternative to the frequent painful insulin shots that people with diabetes typically need. 

    More recently, Whitehead has been focusing on small interfering RNA (siRNA), which can be used to target and shut off gene expression. These molecules have enormous potential for treating cancers and genetic disorders, but it’s difficult to deliver them to the appropriate cells. Though embedding siRNA in a protective nanoparticle seems like a promising approach, researchers have had difficulty finding nanoparticles that can both navigate to the desired tissue and deliver the molecule across the cell wall. 

    Instead of trying to make educated guesses at particles that might work, as others in the field were doing, Whitehead has systematically tested thousands. While working as a postdoc at MIT’s Koch Institute for Integrative Cancer Research, she screened thousands of potential nanoparticles, zeroing in on the handful with the best results. Four biotech companies have since licensed Whitehead’s patents in RNA delivery materials.

    Now, as an assistant professor of chemical and biomedical engineering at Carnegie Mellon University in Pittsburgh, she is busy analyzing the next batch of nanoparticles and siRNA she’d like to test for various treatments, including some that target lymphoma tumors. Despite her remarkable achievements, she has not had any real “eureka moments” in her lab, she says. “Perseverance is the major theme.”

    Patrick Doyle

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  • Age:
    31

    Hui Wu

    Cheaper and more powerful batteries could help reduce China’s deadly air pollution.

    Hui Wu grew up in a small, quiet city in central China. Few families owned televisions in the 1980s (his was one of the lucky ones), and even fewer had cars. His mother biked to the hospital where she was a nurse. His father, a middle-school chemistry teacher, let him tag along to classes when he was eight or nine years old, sparking an interest in science and experimentation. 

    After earning a PhD at the elite Tsinghua University in Beijing, he went to Stanford as a postdoc, joining the lab of Yi Cui, one of the top battery chemists in the world. But later his father fell ill with lung cancer, and “as an only child, I don’t think I had any choice other than to come back to help my family,” he explains. In 2012, he took a job teaching and researching at Tsinghua. (His father came to Beijing to receive treatment but died last year.) 

    Wu uses nanostructured materials to improve the efficiency of batteries. And he feels the urgency of his quest even more back home, given the alarming levels of pollution in China’s large cities. Sitting in his office on the Tsinghua campus, with a blinking battery tester beside his desk, he reflects, “When I was in California, the sky was always bright blue, but I never see skies like that in Beijing.”

    Longer-lasting batteries could extend the range of electric vehicles, which may be part of the solution to Beijing’s smog—vehicle emissions contribute roughly a third of the fine particles that blacken the skies. Better batteries could also increase storage capacity for solar and wind power, which would make those technologies more affordable in China.

    Today’s consumer electronics and electric vehicles most commonly use lithium-ion batteries, in which lithium ions move between the electrodes during charging and discharging; the negative electrode is typically made of graphite. In theory, replacing graphite with silicon could vastly increase power density, giving batteries with the same weight a much longer life. But silicon swells in volume more than 300 percent as it charges, making it unstable. While at Stanford, Wu helped figure out (working in the same lab as Guihua Yu) how to use a porous polymer gel to encapsulate tiny particles of the silicon, allowing them to expand harmlessly in the space of the polymer matrix. 

    Wu prefers low-tech ways for himself: he lives with his lawyer wife and their toddler on the Tsinghua campus, and he rides a bicycle to his office. He appreciates practical solutions. “I don’t want to create a material that’s only feasible in the lab,” he says. “I’m interested in using science to solve practical problems of our daily life.”

     —Christina Larson

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  • Age:
    33

    Guihua Yu

    Electronic gels could lead to sensors and batteries that are more like biological tissue.

    Since starting his lab at the University of Texas at Austin in 2012, materials scientist Guihua Yu has been controlling the three-dimensional nanostructure of materials to make electrically conductive gels that can serve as electronic skin, more efficient battery electrodes, or tunable chemical sensors. 

    Hydrogels, which are flexible, squishy networks of polymers, are great for supporting the growth of cells in research experiments or binding together active ingredients for drug delivery. But they typically are lousy at conducting electricity. In contrast, electrically conductive polymers are valuable in electronics—for example, in new types of plastic solar cells—but typically can only be made into thin films. Yu figured out how to link conductive-polymer building blocks to make nanostructured gels that had the best qualities of both materials.

    One gel can be used to hold glucose-binding enzymes and nanoparticle catalysts, key elements of a rapid, highly sensitive glucose sensor that might be used for diabetes management. Another makes for a more resilient battery electrode with higher energy density. 

    —Katherine Bourzac