Tuesday, May 19, 2015
Dabney Hall, Garden of the Associates – The Garden of the Associates

Science in a Small World - Poster Session #2

Tuesday, May 19, 2015
Dabney Hall, Garden of the Associates – The Garden of the Associates

Science in a Small World - Poster Session #1

Five from Caltech Elected to American Academy of Arts and Sciences

The American Academy of Arts and Sciences has elected five Caltech community members as academy fellows. They are faculty members Michael B. Elowitz, professor of biology and bioengineering and an investigator with the Howard Hughes Medical Institute; Mory Gharib (PhD '83), Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering, director of the Ronald and Maxine Linde Institute of Economic and Management Sciences, and vice provost; and Linda C. Hsieh-Wilson, professor of chemistry; and Caltech trustees James Rothenberg and Maria Hummer-Tuttle. The American Academy is one of the nation's oldest honorary societies. Members are accomplished scholars and leaders representing diverse fields including academia, business, public affairs, the humanities, and the arts.

 

Michael B. Elowitz was noted for his work that "helped to initiate synthetic biology." Elowitz studies genetic circuits—interacting genes and proteins that enable cells to sense environmental conditions and to communicate. He and his group build simplified synthetic genetic circuits and study their effects in bacteria, yeast, and mammalian cells. He has received numerous honors in recognition of his work, including a MacArthur Fellowship in 2007.
 

Mory Gharib and his group use nature's own design principles—apparent in fins, wings, blood vessels, and more—as inspiration for a myriad of inventions. They have studied fluid flows inside the zebrafish heart to develop efficient micropumps and more efficient artificial heart valves, and cactus spine to develop arrays of nanoneedles, based on carbon nanotubes, for painless drug delivery. Gharib holds nearly 100 patents, and was elected to the National Academy of Engineering in 2015.

Linda C. Hsieh-Wilson was noted for her pioneering work in the new fields of chemical glycobiology and chemical neurobiology. Her work combines organic chemistry and neurobiology in order to understand how carbohydrates contribute to fundamental brain processes such as cell growth and neuronal communication, neural development, and memory at the molecular level. She and her group discovered a means for suppressing tumor-cell growth by blocking the attachment of certain sugars to proteins, restricting delivery of certain carbohydrates to proteins within the tumor.

Maria Hummer-Tuttle, a lawyer, was a partner and chair of the management committee and co–managing partner of Manatt, Phelps and Phillips in Los Angeles. She currently serves on the boards of Caltech, the J. Paul Getty Trust, the W. M. Keck Foundation, the Suu Foundation, and the Foundation for Art and Preservation in Embassies. Hummer-Tuttle is president of the Hummer Tuttle Foundation, serves on the advisory board of the USC Center on Public Diplomacy at the Annenberg School as well as on the program advisory committee of the Annenberg Retreat at Sunnylands, and is a member of the Pacific Council on International Policy, the Council on Foreign Relations, and the Getty Conservation Institute Council.

Jim Rothenberg is chairman of the Capital Group Companies, Inc. In addition to his service on the Caltech board, he serves on the boards of Capital Research and Management Company, the Capital Group Companies, Inc., and American Funds Distributors, Inc. In addition, he is a portfolio counselor for the Growth Fund of America, as well as vice chairman of the Growth Fund of America and Fundamental Investors. A chartered financial analyst, he was named to the Harvard Corporation as the treasurer of Harvard University in 2004. He also serves as a director of Huntington Memorial Hospital in Pasadena.

Elowitz, Gharib, and Hsieh-Wilson join 83 current Caltech faculty as members of the American Academy. Also included in this year's list are five alumni: Robert Cohen (MS '70, PhD '72), St. Laurent Professor of Chemical Engineering at MIT and codirector of the DuPont-MIT Alliance; Alexei Filippenko (PhD '84), professor of astronomy at UC Berkeley; Katherine Hayles (MS '69), professor of literature at Duke University; Michael Snyder (PhD'83), professor and chair of genetics at Stanford University; and Donald Truhlar (PhD '70), professor of chemistry at the University of Minnesota.

Founded in 1780 by John Adams, James Bowdoin, John Hancock, and other scholar-patriots, the academy aims to serve the nation by cultivating "every art and science which may tend to advance the interest, honor, dignity, and happiness of a free, independent, and virtuous people." The academy has elected as fellows and foreign honorary members "leading thinkers and doers" from each generation, including George Washington and Ben Franklin in the 18th century, Daniel Webster and Ralph Waldo Emerson in the 19th, and Albert Einstein and Woodrow Wilson in the 20th.

A full list of new members is available on the academy website at https://www.amacad.org/content/members/members.aspx.

The new class will be inducted at a ceremony on October 10, 2015, in Cambridge, Massachusetts.

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Chemists Create “Comb” that Detects Terahertz Waves with Extreme Precision

Light can come in many frequencies, only a small fraction of which can be seen by humans. Between the invisible low-frequency radio waves used by cell phones and the high frequencies associated with infrared light lies a fairly wide swath of the electromagnetic spectrum occupied by what are called terahertz, or sometimes submillimeter, waves. Exploitation of these waves could lead to many new applications in fields ranging from medical imaging to astronomy, but terahertz waves have proven tricky to produce and study in the laboratory. Now, Caltech chemists have created a device that generates and detects terahertz waves over a wide spectral range with extreme precision, allowing it to be used as an unparalleled tool for measuring terahertz waves.

The new device is an example of what is known as a frequency comb, which uses ultrafast pulsed lasers, or oscillators, to produce thousands of unique frequencies of radiation distributed evenly across a spectrum like the teeth of a comb. Scientists can then use them like rulers, lining up the teeth like tick marks to very precisely measure light frequencies. The first frequency combs, developed in the 1990s, earned their creators (John Hall of JILA and Theordor Hánsch of the Max Planck Institute of Quantum Optics and Ludwig Maximilians University Munich) the 2005 Nobel Prize in physics. These combs, which originated in the visible part of the spectrum, have revolutionized how scientists measure light, leading, for example, to the development of today's most accurate timekeepers, known as optical atomic clocks.

The team at Caltech combined commercially available lasers and optics with custom-built electronics to extend this technology to the terahertz, creating a terahertz frequency comb with an unprecedented combination of spectral coverage and precision. Its thousands of "teeth" are evenly spaced across the majority of the terahertz region of the spectrum (0.15-2.4 THz), giving scientists a way to simultaneously measure absorption in a sample at all of those frequencies.

The work is described in a paper that appears in the online version of the journal Physical Review Letters and will be published in the April 24 issue. The lead author is graduate student and National Science Foundation fellow Ian Finneran, who works in the lab of Geoffrey A. Blake, professor of cosmochemistry and planetary sciences and professor of chemistry at Caltech.

Blake explains the utility of the new device, contrasting it with a common radio tuner. "With radio waves, most tuners let you zero in on and listen to just one station, or frequency, at a time," he says. "Here, in our terahertz approach, we can separate and process more than 10,000 frequencies all at once. In the near future, we hope to bump that number up to more than 100,000."

That is important because the terahertz region of the spectrum is chock-full of information. Everything in the universe that is warmer than about 10 degrees Kelvin (-263 degrees Celsius) gives off terahertz radiation. Even at these very low temperatures molecules can rotate in space, yielding unique fingerprints in the terahertz. Astronomers using telescopes such as Caltech's Submillimeter Observatory, the Atacama Large Millimeter Array, and the Herschel Space Observatory are searching stellar nurseries and planet-forming disks at terahertz frequencies, looking for such chemical fingerprints to try to determine the kinds of molecules that are present and thus available to planetary systems. But in just a single chunk of the sky, it would not be unusual to find signatures of 25 or more different molecules.

To be able to definitively identify specific molecules within such a tangle of terahertz signals, scientists first need to determine exact measurements of the chemical fingerprints associated with various molecules. This requires a precise source of terahertz waves, in addition to a sensitive detector, and the terahertz frequency comb is ideal for making such measurements in the lab.

"When we look up into space with terahertz light, we basically see this forest of lines related to the tumbling motions of various molecules," says Finneran. "Unraveling and understanding these lines is difficult, as you must trek across that forest one point and one molecule at a time in the lab. It can take weeks, and you would have to use many different instruments. What we've developed, this terahertz comb, is a way to analyze the entire forest all at once."

After the device generates its tens of thousands of evenly spaced frequencies, the waves travel through a sample—in the paper, the researchers provide the example of water vapor. The instrument then measures what light passes through the sample and what gets absorbed by molecules at each tooth along the comb. If a detected tooth gets shorter, the sample absorbed that particular terahertz wave; if it comes through at the baseline height, the sample did not absorb at that frequency.

"Since we know exactly where each of the tick marks on our ruler is to about nine digits, we can use this as a diagnostic tool to get these frequencies really, really precisely," says Finneran. "When you look up in space, you want to make sure that you have such very exact measurements from the lab."

In addition to the astrochemical application of identifying molecules in space, the terahertz comb will also be useful for studying fundamental interactions between molecules. "The terahertz is unique in that it is really the only direct way to look not only at vibrations within individual large molecules that are important to life, but also at vibrations between different molecules that govern the behavior of liquids such as water," says Blake.

Additional coauthors on the paper, "Decade-Spanning High-Precision Terahertz Frequency Comb," include current Caltech graduate students Jacob Good, P. Brandon Carroll, and Marco Allodi, as well as recent graduate Daniel Holland (PhD '14). The work was supported by funding from the National Science Foundation.

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Understanding the Earth at Caltech

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Credit: Courtesy J. Andrade/Caltech

The ground beneath our feet may seem unexceptional, but it has a profound impact on the mechanics of landslides, earthquakes, and even Mars rovers. That is why civil and mechanical engineer Jose Andrade studies soils as well as other granular materials. Andrade creates computational models that capture the behavior of these materials—simulating a landslide or the interaction of a rover wheel and Martian soil, for instance. Though modeling a few grains of sand may be simple, predicting their action as a bulk material is very complex. "This dichotomy…leads to some really cool work," says Andrade. "The challenge is to capture the essence of the physics without the complexity of applying it to each grain in order to devise models that work at the landslide level."

Credit: Kelly Lance ©2013 MBARI

Geobiologist Victoria Orphan looks deep into the ocean to learn how microbes influence carbon, nitrogen, and sulfur cycling. For more than 20 years, her lab has been studying methane-breathing marine microorganisms that inhabit rocky mounds on the ocean floor. "Methane is a much more powerful greenhouse gas than carbon dioxide, so tracing its flow through the environment is really a priority for climate models and for understanding the carbon cycle," says Orphan. Her team recently discovered a significantly wider habitat for these microbes than was previously known. The microbes, she thinks, could be preventing large volumes of the potent greenhouse gas from entering the oceans and reaching the atmosphere.

Credit: NASA/JPL-Caltech

Researchers know that aerosols—tiny particles in the atmosphere—scatter and absorb incoming sunlight, affecting the formation and properties of clouds. But it is not well understood how these effects might influence climate change. Enter chemical engineer John Seinfeld. His team conducted a global survey of the impact of changing aerosol levels on low-level marine clouds—clouds with the largest impact on the amount of incoming sunlight Earth reflects back into space—and found that varying aerosol levels altered both the quantity of atmospheric clouds and the clouds' internal properties. These results offer climatologists "unique guidance on how warm cloud processes should be incorporated in climate models with changing aerosol levels," Seinfeld says.

Credit: Yan Hu/Aroian Lab/UC San Diego

Tiny parasitic worms infect nearly half a billion people worldwide, causing gastrointestinal issues, cognitive impairment, and other health problems. Biologist Paul Sternberg is on the case. His lab recently analyzed the entire 313-million-nucleotide genome of the hookworm Ancylostoma ceylanicum to determine which genes turn on when the worm infects its host. A new family of proteins unique to parasitic worms and related to the early infection process was identified; the discovery could lead to new treatments targeting those genes. "A parasitic infection is a balance between the parasites trying to suppress the immune system and the host trying to attack the parasite," Sternberg observes, "and by analyzing the genome, we can uncover clues that might help us alter that balance in favor of the host."

Credit: K.Batygin/Caltech

Earth is special, not least because our solar system has a unique (as far as we know) orbital architecture: its rocky planets have relatively low masses compared to those around other sun-like stars. Planetary scientist Konstantin Batygin has an explanation. Using computer simulations to describe the solar system's early evolution, he and his colleagues showed that Jupiter's primordial wandering initiated a collisional cascade that ultimately destroyed the first generation population of more massive planets once residing in Earth's current orbital neighborhood. This process wiped the inner solar system's slate clean and set the stage for the formation of the planets that exist today. "Ultimately, what this means," says Batygin, "is that planets truly like Earth are intrinsically not very common."

Credit: Nicolás Wey-Gόmez/Caltech

Human understanding of the world has evolved over centuries, anchored to scientific and technological advancements and our ability to map uncharted territories. Historian Nicolás Wey-Gόmez traces this evolution and how the age of discovery helped shape culture and politics in the modern era. Using primary sources such as letters and diaries, he examines the assumptions behind Europe's encounter with the Americas, focusing on early portrayals of native peoples by Europeans. "The science and technology that early modern Europeans recovered from antiquity by way of the Arab world enabled them to imagine lands far beyond their own," says Wey-Gómez. "This knowledge provided them with an essential framework to begin to comprehend the peoples they encountered around the globe."

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At Caltech, researchers study the Earth from many angles—from investigating its origins and evolution to exploring its geology and inner workings to examining its biological systems. Taken together, their findings enable a more nuanced understanding of our planet in all its complexity, helping to ensure that it—and we—endure. This slideshow highlights just a few of the Earth-centered projects happening right now at Caltech.

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Inhibitor for Abnormal Protein Points the Way to More Selective Cancer Drugs

Nowhere is the adage "form follows function" more true than in the folded chain of amino acids that makes up a single protein macromolecule. But proteins are very sensitive to errors in their genetic blueprints. One single-letter DNA "misspelling" (called a point mutation) can alter a protein's structure or electric charge distribution enough to render it ineffective or even deleterious.

Unfortunately, cells containing abnormal proteins generally coexist alongside those containing the normal (or "wild") type, and telling them apart requires a high degree of molecular specificity. This is a particular concern in the case of cancer-causing proteins.

"With present technologies, developing a drug that will target only the mutant version of a protein is difficult," notes Blake Farrow, a graduate student in materials science at Caltech and a Howard Hughes Medical Institute Fellow. "Most anticancer agents indiscriminately attack both mutant and healthy proteins and tissues."

Farrow is part of a Caltech-led team that recently created a new type of highly selective molecule that can actively distinguish a mutated protein from the wild type by binding only the mutated protein.

The work was described in a paper that appeared in Nature Chemistry on April 13.

The project was begun by Kaycie Deyle (PhD '14), now a postdoctoral fellow at École Polytechnique Fédérale de Lausanne, and utilized a number of novel technologies, including click chemistry and protein-catalyzed capture (PCC). Click chemistry is a technique for rapidly and reliably constructing molecular assemblies from modular components. PCC screening, which was developed by the Caltech researchers, uses click chemistry to reveal which of several candidate molecules will bind (and "click") most strongly to a given region of a specific protein.

As a test case, the researchers investigated a point mutation called E17K, which occurs in a specific region of Akt1, a protein hundreds of amino acids long. Akt1 plays a key role in cell growth and proliferation, and its E17K mutation is closely linked to an increase in the development of tumors and the survival of cancer cells.

Using a synthesized fragment of the cancer-causing form of Akt1, the researchers replaced an amino acid close to the E17K mutation with a structure that could act as a "click handle." The goal was to create a short molecule that could wedge itself into the folds of the protein, binding to the E17K mutation at one end and "clicking" to the handle at the other.

Candidate molecules were constructed by splicing amino acids together into short chains five amino acids long, which is just enough to reach from the click handle to the mutation site. With almost two dozen amino acids to choose from for each of the five slots, the researchers were faced with over a million possible configurations.

A multistep PCC screening process narrowed this large number of candidates down to one combination that bound to the mutant version of the protein 10 times more strongly than to the wild type. The code letters representing the five amino acids making up the molecule gave it its informal name: "yleaf."

Next, a second PCC screening process was used to find amino acid chains that could be used to extend the yleaf molecule, giving it the ability to grip multiple naturally occurring features of the Akt1 molecule, rather than requiring a click handle to be artificially inserted. Testing of this wider-wingspan yleaf showed that not only did it bind almost exclusively to its intended target (and nowhere else, including the unmutated form of Akt1), but also that in doing so it inhibited the protein's activity and hence could be expected to impair its ability to support tumor growth. In fact, the extended yleaf molecule inhibited the mutated protein a thousand times better than it did the wild-type form.

James Heath, the Elizabeth W. Gilloon Professor and Professor of Chemistry at Caltech and corresponding author of the paper, says this selective inhibitor strategy "is certainly a very important first step" toward new cancer drug modalities. With additional design considerations to facilitate passage through the cell membrane, compounds of this sort could become the basis of new drugs for targeting and inhibiting abnormal protein molecules in living cells, he says.

In addition to Farrow, Deyle, and Heath, other authors on the Nature Chemistry paper, "A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1," are Michelle Wong, Aiko Umeda, Arundhati Nag, and Samir Das from Caltech; Ying Qiao Hee and Jeremy Work, who contributed to the work at Caltech as a Summer Undergraduate Research Fellow and an Amgen Scholar, respectively; Bert Lai from Indi Molecular; and Steven W. Millward from the University of Texas MD Anderson Cancer Center. The work was supported by the Institute for Collaborative Biotechnologies, the National Cancer Institute, the Defense Advanced Research Projects Agency and the Jean Perkins Foundation. Research was performed in collaboration with Indi Molecular (founded by Heath), which seeks to commercialize PCC technology.

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Abedi Receives Fellowship for New Americans

Mohamad Abedi, a PhD candidate in bioengineering, has received a Paul & Daisy Soros Fellowship for New Americans. Thirty fellows were selected from nearly 1,200 applicants "for their potential to make significant contributions to US society, culture, or their academic field," according to the fellowship program description. Each Soros Fellow will receive up to $90,000 to help cover two years of tuition, and other educational and living expenses, while studying any subject at any university in the United States. The fellowship was established to assist young new Americans—permanent residents, naturalized citizens, or children of naturalized citizen parents—at critical points in their educations.

"I'm honored and excited to receive this fellowship. Coming to the United States provided me with a plethora of opportunities and support that allowed me to pursue my dream and be here at Caltech today," Abedi says.

Abedi was born to Palestinian refugees in the United Arab Emirates. As a child he frequently visited family in the Beddawi refugee camp in Lebanon. The lack of adequate health care resources he saw there motivated him to pursue a degree in bioengineering.

"As a bioengineer, I hope to develop low-cost medical technologies that could provide people with health care regardless of their geographical location and financial capabilities," Abedi says.

After moving with his family to California during his final year of high school, Abedi began a degree in biomedical engineering at UC Irvine, where he worked on building affordable diagnostic devices that could run on air instead of electricity. At UC Irvine, he also ventured into synthetic biology to study bacterial genetic circuits—interacting genes and proteins that enable cells to sense and communicate with one another.

Now a first-year graduate student in the lab of Mikhail Shapiro, assistant professor of chemical engineering, Abedi aims to develop tools for the noninvasive modulation of brain circuitry. These would eventually allow scientists to understand and treat neurological and psychiatric diseases involving the dysfunction of local neural circuits, such as depression or obsessive-compulsive disorder.

"Understanding the human brain, where trillions of cells work in harmony to form a magnificent structure, is arguably the most ambitious target of scientific inquiry," Abedi says. "I am interested in utilizing tools from cellular and molecular engineering to study the brain, with the overarching goal of improving human health and welfare worldwide."

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Two Caltech Seniors Win Hertz Fellowships

Adam Jermyn and Charles Tschirhart join the 51st class of Hertz fellows

Caltech seniors Adam Jermyn and Charles Tschirhart have been named 2015 Hertz Fellowship winners. Selected from a pool of approximately 800 applicants, the awardees will receive up to five years of support for their graduate studies. According to the Hertz Foundation, fellows are chosen for their intellect, their ingenuity, and their potential to bring meaningful improvement to society. Jermyn and Tschirhart bring the number of Caltech undergraduate Hertz fellows to 60.

Adam Jermyn, a physics major from Longmeadow, Massachusetts, works with so-called "emergent phenomena," which "is a broad term referring to situations where we know all of the laws on a fundamental level but where there are so many pieces working together that the consequences aren't known," he says. For example, the basic laws governing fluid mechanics are simple equations that relate such easily measured quantities as density, velocity, and temperature to one another, but simulating the behavior of two gases as they mix in a turbulent flow can tax the capacity of a supercomputer.

Jermyn's senior thesis models how a pulsar—a type of celestial radio source that flashes as fast as a thousand times per second—disrupts the atmosphere of a companion star. Pulsars are neutron stars—supernova cinders that pack the mass of a couple of suns into a sphere roughly the size of Manhattan. The spin imparted by the supernova's explosion and equally violent collapse creates a beam of tightly focused radio waves. If a neutron star were "aimed" at Earth, the beam's fleeting illumination would register as a flash in our radio telescopes every time it swept across us. Meanwhile, the pulsar's intense gravity distorts the companion star, creating a bulge on its surface. Like Earth's moon, the star's rotation is tidally locked, always presenting the same side to its dominant neighbor. The companion star's atmosphere gets siphoned away, layer by layer, forming a turbulent tendril of gas that winds in an ever-tightening spiral around the pulsar as the stolen material accretes onto its surface.

Charles Tschirhart of Naperville, Illinois, is a double major in applied physics and chemistry. His interests lie at the opposite end of the scale—in the world of nanotechnology, where lengths are measured in nanometers, or billionths of a meter. In the summer of 2012, he was part of a team that built nanoelectrodes—tiny silicon needles that penetrate a cell wall without damaging the cell to monitor the electrical activity within.

Tschirhart and Jermyn share an interest in fluid mechanics. "I think the biggest difference between what Adam and I do is that he is a theorist, and I am an experimentalist," Tschirhart says. "Physicists pretend that a fluid is a continuum of infinitely divisible matter and thus doesn't have any 'graininess' to it." But because atoms and molecules do have finite sizes, "once you get down to small enough scales," he says, "even water becomes 'grainy.'" The fluid becomes more viscous, as it takes effort to force the grains past one another. For his senior thesis, Tschirhart determined the nanoviscosity of silicone oil by measuring the thickness of a thin film of oil, smearing it even thinner with a stream of air and measuring its thickness again. The thickness should decrease in a linear manner, but this doesn't happen when the layer gets thin enough. "These films aren't much thicker than the size of a molecule," he says. "This is where noncontinuum effects show up." These effects could affect how engineers approach tasks as diverse as lubricating hard drives and extracting crude oil from porous rocks.

Both students took Physics 11, a course taught by the late Professor Thomas Tombrello. Tombrello launched this class in 1989 to teach encourage freshman to think creatively, and taught it annually until his death in September 2014. This year, Jermyn and Tschirhart are helping teach it. "Physics 11 really shaped the way I ask questions, and I have Tom Tombrello to thank for that," says Jermyn. "He pushed us to think about things obliquely," Tschirhart concurs. "After I got over my initial nerves, I found myself enjoying [the two rounds of Hertz interviews], which made it much easier to answer the questions creatively."

Both plan to defer their Hertz doctoral fellowships while they take advanced degrees in England. Tschirhart will be attending the University of Nottingham as a Fulbright Scholar for one year, where he plans to develop new applications for atomic force microscopy, a powerful technique for "photographing" nanoscale objects. Jermyn will be at the University of Cambridge for two years as a Marshall Scholar investigating the processes by which planets form around binary star systems.

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A Spotlight on Inventing

On Thursday, March 19, Caltech is hosting the fourth annual conference of the National Academy of Inventors. The NAI is a nonprofit organization that was founded in 2010 by the U.S. Patent and Trademark Office to encourage inventors and also enhance the visibility and understanding of the value of academic technology and innovation.

Its annual conference will bring hundreds of NAI members—inventors, researchers, scientists, engineers, and scholars from more than 200 institutions around the country—to Caltech. While here, they will share big ideas, discuss opportunities for future innovations, and also celebrate the newest class of NAI fellows. According to the NAI, election to fellow status is a "high professional distinction accorded to academic inventors who have demonstrated a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development, and the welfare of society." The newest class of 170 fellows includes four Caltech professors.

The conference is "a very exciting opportunity for Caltech," says Caltech vice provost Morteza Gharib (PhD '83), the Hans W. Liepmann Professor of Aeronautics and Bioinspired Engineering, and an NAI charter fellow. "Having an organization that brings some of our greatest minds together to look at the problems we are facing and support them in finding solutions is a noble cause, and we at Caltech are proud to be supporters of that."

Advancing innovation and the transfer of new technologies and ideas to society and industry is both a personal and professional passion for Gharib. The holder of nearly 100 patents, he leads a research group at Caltech that studies examples from the natural world—fins, wings, blood vessels, embryonic structures, and entire organisms—to gain inspiration for inventions that have practical uses in power generation, drug delivery, dentistry, and more. As vice provost, he also oversees Caltech's Office of Technology Transfer and Corporate Partnerships. OTT plays an instrumental role in helping Caltech's researchers commercially realize their ideas, making sure that their work is protected, patented, and licensed along the way. As of the close of fiscal year 2014, Caltech managed more than 1,700 active U.S. patents. Since the office was established in 1995, its staff has helped launch more than 150 start-up companies.

To learn more about what it means to be an inventor, we recently chatted with Gharib and two of Caltech's newest NAI fellows—Frances Arnold and Carver Mead (BS '56, MS '57, PhD '60).

Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and director of the Donna and Benjamin M. Rosen Bioengineering Center, pioneered methods of "directed evolution" to engineer new proteins in the lab. The method is now widely used to create catalysts for industrial processes, including the production of fuels and chemicals from renewable resources.

Mead, the Gordon and Betty Moore Professor of Engineering and Applied Science, Emeritus, has significantly advanced the technology of integrated circuits by developing a method called very-large-scale integration (VSLI) that allows engineers to combine thousands of transistors onto a single microchip, thus exponentially expanding computer processing power.

 

What does it mean to be an inventor?

Arnold: It means I get to play—with ideas—and create new things that solve problems.

Gharib: An inventor is someone who has the ability to summarize what had not been before into something that has a new form and is novel.

Inventing is not a sudden process either; you don't just come up with an invention. It comes from where you have been, all the influences you have received from your education, your community, and the environment that you are in—from whether you have been challenged or excited by problems.

Mead: I have never thought of myself as an inventor! I always thought of myself as a guy who figures things out and then it just turned out that every once in a while something that I "figured out" would be important. Some of those things turned into inventions. I am just a creative person. I'm someone who likes to solve problems.

 

How does the invention process relate to the scientific process?

Arnold: Many scientists pursue the answer to a question: "How does this work?" Inventors often pursue an answer to a problem: "How can I get this to work?"

Gharib: It's not the same path. Remember that engineers basically invented locomotives, and it wasn't until half a century later that we actually understood the laws of thermodynamics and why this works.

The scientific process is systematic. It relies on certain logical steps that you take—from defining the problem, testing what works, eliminating problems—and that pushes you to be able to be in a position to discover. But in inventing, you see the solutions without knowing or needing to understand why and pursue that.

Mead: For me, it's all the same. I have the same approach for all of my work—it's all just about figuring things out.

 

How has Caltech supported you as an inventor?

Arnold: Caltech has provided me with great students and with the financial support to pursue new ideas, and then not placed the traditional academic constraints on what we can pursue.

Gharib: Our inventors see an environment that is conducive to inventing. Caltech supports them to get their idea translated from the lab into something that is useful, something that is protected, and something that will have a societal impact.

The best example I have of that is that I didn't own a single patent before I came to Caltech—even though I was in academia for 10 years before coming here. It wasn't that I didn't have ideas, it was just that I didn't have a motivation for pursuing those ideas. When I came here, I saw that you can really take your ideas and make them into something for industry, for society, for faculty, and so on, to benefit from.

Mead: I think the best thing Caltech did for me is leave me alone, because I could pursue the things that I felt strongly about. It's always taken a very long time for me to move after having the first inkling of some direction or idea that I am drawn to. I might work for five years on something before I can fully explain to people why I am working on it.

I think Caltech is very special in that way; it doesn't interfere with the creative process.

 

What invention of yours are you most proud of? Why? 

Arnold: I am lucky to have been the first to show how evolution can be used to construct a whole slew of new and useful catalysts. This is a fundamental process that can be used to solve so many important problems. It has been picked up and used by hundreds of academic and industrial labs, all over the world, for everything from making better laundry detergents to producing fuels from renewable resources.

Gharib: Seventy-thousand people have a shunt in their eyes that I developed, and that is helping them avoid having to deal with issues of glaucoma. In addition to that, a 3-D imaging device that I originally developed for naval underwater surveillance is now being used for making dental crowns.

It is a good feeling when you see one of your patents have societal impact.

Mead: My work in the area of very-large-scale integration—figuring out how transistors could scale up and how you could build them better—has affected the world in a profound way, and I am pleased to be a part of that. You can think of it as inventing a method, a way through, but not as a tangible invention of the usual sort.

In regards to more traditional "inventions," there are a couple of other things that have gone out into the world and made a difference. The first was the Schottky-gate field-effect transistor, which I created over Thanksgiving in 1965. It is in the transmitters of all cell phones. The second was an advancement that a graduate student of mine led. He came up with a way of making semiconductor charge-coupled devices (CCDs) work more efficiently, which enabled them to be used in the imaging world. CCDs are still the imaging sensor that is used in astronomical instruments.

Of course, you never know when you are doing something whether it will really be accepted and if people will move on it. So when it happens—when people take something that you do seriously—it's kind of surprising.

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Friday, April 10, 2015
Noyes 147 (J. Holmes Sturdivant Lecture Hall) – Arthur Amos Noyes Laboratory of Chemical Physics

Transforming Chemistry Education

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