The Magazine of Engineering and the Sciences at UC Santa Barbara
Detection and Diagnosis Q&A with Pierre Wiltzius Autism Vaccines Diamond Spin Second-hand Smoke
THIRTEEN, SUMMER 2009
A Note From Dean Tirrell
(I’m pre-empting my colleagues Pierre Wiltzius and David Awschalom here, for reasons that will soon be apparent…) Last issue, we quoted Isaac Asimov saying, “The only constant is change…” This issue brings still more change—it’s the last in which I’ll be involved. After a very rewarding ten years as dean of the College of Engineering, it’s time for me to turn the helm over, and to get back to spending more time on my research and teaching. It’s been a very good ten years: In 1999, our graduate program in engineering was ranked 25th in the nation. We’re now firmly in the top 20 at 18th, with two departments in the top 10, and our program ranks 12th among those at public universities. In growing our faculty from 104 to 145, we made 70 new hires, including several international superstars, such as Shuji Nakamura, and many young stars of the future. Strongly reflecting the quality of our faculty, our research funding tripled over the same period, from $33 million in 1999 to about $90 million this year. We also established five new major interdisciplinary research centers, including the Solid State Lighting and Energy Center, the California NanoSystems Institute, the Institute for Collaborative Biotechnologies (ICB), and the Mitsubishi Center for Advanced Materials, which collectively bring about $25 million of new research funds to campus every year. We most recently established the Institute for Energy Efficiency, which has already garnered $19 million of Department of Energy funds for its Center for Materials for Energy Efficiency. Our bioengineering initiative here, currently centered on ICB and the Center for Stem Cell Biology and Engineering, is ranked number two in the nation among bioengineering programs, and is gaining momentum. The Burnham Institute for Medical Research is increasing its presence here, and we’re making good progress toward a dedicated building for bioengineering. Continued progress in bioengineering and biomedical research is critical for society, and I’m proud of the contributions UCSB has made and clearly will continue to make. Three of the four feature articles in this issue are in that area. It’s also where I’ve focused much of my own research, and now I’m returning to it full time—as of July 1 of this year, I’ll be chair of the Department of Bioengineering at UC Berkeley, our sister UC institution. I look forward to my new responsibilities and opportunities at Berkeley, but I’ll also be watching with interest and pride as UCSB continues to grow and lead in this area. Thank you for your generous and continuing support, which has made much of our progress possible over the last ten years.
Matthew Tirrell Dean, College of Engineering
Pierre Wiltzius Dean of Mathematical, Life and Physical Sciences, College of Letters & Science
David Awschalom Scientific Director, California NanoSystems Institute
THIRTEEN, summer 2009
Tools for Tomorrow Bioengineering research teams at UCSB are developing some of the world’s most advanced and sophisticated techniques and devices for the detection and diagnosis of pathogens and harmful substances.
q &A: Pierre Wiltzius
UCSB’s Dean of Science talks with us about what brought him (back) to Santa Barbara and what he sees in the future for the sciences here.
Rain Man and Einstein 50 years ago, autism was little understood, and its casualties were relegated to institutions. Today, UCSB is leading the way both in understanding the mechanisms of the disease and in developing effective treatments for it.
Taking the Guesswork out of vaccines
Picking the right strain of a pathogen against which to develop a seasonal vaccine has always been an educated guess, and not always successful. Now UCSB researchers have found the key to creating vaccines effective against multiple strains.
Diamonds are a spin’s best friend
What is this?
Understanding and controlling single-electron spins is viewed as the future of information and communication technologies. UCSB’s spintronics center is figuring out how to work with this phenomenon at room temperature, making such devices practical for the real world.
Second-hand smoke has long been known to be harmful, but the mechanism by which it inflicted its damage wasn’t clearly understood. Recent research here has gone a long way toward answering that question.
Shorts... Have you heard?
Tools for Tomorrow
Food safety, medical diagnostics, and chemical defense meet at the microscale and nanoscale at UC Santa Barbara.
Bioengineering research teams at UCSB, drawn from multiple departments in Engineering and the Sciences, are developing some of the world’s most advanced and sophisticated detection and diagnostic techniques. The tools they are working on have extraordinary potential, from sensing and eliminating a single cancer-causing tumor cell in an otherwise healthy body, to detecting traces of drugs, explosives, and other hazardous materials at concentrations of parts-per-trillion. Some similar results may be achievable already in a laboratory. “Given a fully-equipped laboratory and enough time, you can detect almost anything,” says Kevin Plaxco, Professor of Chemistry and Biochemistry. What sets UCSB’s latest research apart is the goal of providing the same or better information much faster and much more conveniently—in many cases using mobile, hand-held devices. “What has been a slow, lab-bound approach, we want to convert to less than 15 minutes—that’s typically how long, for example, someone has with their doctor—and hand held.” Plaxco says.
ICB, a UCSB-led collaboration with the Massachusetts Institute of Technology (MIT) and the California Institute of Technology (Caltech), acts as the base for some 200 faculty members and researchers. Seeking to adapt and replicate some of the processes and biomolecular behaviors found in the natural world, many of these researchers are working at or close to the nanoscale. Using state-of-the-art equipment available at UCSB, they are developing more easily managed and controlled ways of detecting and analyzing a broad range of molecules and microbes found in water, blood, air and food. This process of separating, identifying, and counting the components in such materials invites a number of possible approaches, including many based on biological recognition. Examples of this include the binding of one strand of DNA to its complement (to form a double helix), the binding of an antibody to the virus it neutralizes, both of which are high affinity and specificity. karen Ko
While that’s a clear reference to the medical implications of this biotechnology, potential applications are very much broader: researchers are working on projects that will impact food safety, the environment, industry, security, the military and more.
from UCSB’s Institute for Collaborative Biotechnologies (ICB), Materials Research Laboratory (MRL,) and the California NanoSystems Institute (CNSI).
Other approaches depend on the specific optical (spectroscopic) signatures produced when target molecules bind to specially prepared nano surfaces, and the concentrated light emitted when specific nano particles are brought into close contact via a biorecognition event.
According to Martin Moskovits, former Dean of Science and currently Professor of Chemistry and Biochemistry, the need for detection and diagnostics is not new – he says it was an issue even back in the Middle Moskovits has been part of a team Ages. As modern life becomes ever Professor Kevin Plaxco and his research researching how these electrical and faster and more complex, however, team are focused on studying detection light signals can be used to detect and detection and diagnostics are racing devices more sensitive and still with handanalyze even low concentrations of certain to keep pace. molecules. held convenience and price. Biotechnology has also become a The technology has clear medical rapidly evolving field in part because of the increasing numbers potential—molecules being constantly released by the body in and varieties of hazards out there—infectious diseases, security breath and perspiration, for example, could tell a doctor much and military threats, chemical and biological agents—that we about a patient’s health. Initially, however, Moskovits has his need to be aware of so they can be dealt with or avoided. sights set on detecting explosives.
The interdisciplinary research teams working in this area draw from chemical, electrical, and mechanical engineering, computer science, and materials; and chemistry, biochemistry, physics, and molecular biology. The teams include scientists
He and Carl Meinhart, Associate Professor of Mechanical Engineering and Director of UCSB’s Microfluidics Laboratory, are the principals of SpectraFluidics. The Goleta-based company,
“Now we need about one billion cells grouped together before we can see them and detect a tumor,” explains Daugherty. “Our plan is to drop that number down, by a factor of ten or 100 or more.” launched about a year ago, aims to develop inexpensive yet sensitive and highly accurate means of instantly detecting airborne explosives molecules. SpectraFluidics’ hand-held and stationary sensors will feature onboard computers with programs set to recognize only the specific light or electrical patterns caused by the presence of the target molecules. Moskovits sees a security role for such sophisticated technology, at places like airports, and a military role during conflicts, such as the wars in Iraq and Afghanistan, where the accurate sensing of trace molecules in the air could, for instance, alert troops to roadside bombs. SpectraFluidics is just one of a burgeoning number of UCSB-based biotech start-ups, many of them in the Santa Barbara area, looking for ways to transform an idea that works in the laboratory into a piece of technology that people are willing to buy. Another local venture, Nanex, working in conjunction with ICB researchers, is developing what it describes as “a lab-on-a-chip” solution for medical diagnostics at hospitals, clinics and other health facilities. “Our solution is a low cost, low power, lightweight instrument, wellsuited for point-of-care detection of pathogens and genetic markers,” says the company website, describing a sensor equipped for a range of bio-assays and molecular diagnostics. The road to market can be a long, difficult, and expensive journey. Plaxco says research into biotechnology devices has been going on for more than 50 years, but little has so far seen the commercial light of day: the best example that has is the blood glucose monitor for diabetics. Plaxco has been working alongside Professor of Physics and Nobel laureate Alan Heeger, and H. Tom Soh, Associate Professor of Materials and of Mechanical Engineering, on biomolecular sensors designed for real-time detection at the point of care. The three men
also collaborated closely with Nanex on product development. Their point of departure is that current methods for the detection of pathogens are cumbersome, laboratory-bound procedures that typically require days to return an answer. To address this problem, “we are developing a reagentless, electronic technology that can detect these materials in seconds with a convenient, hand-held electronic device,” Plaxco says. Sumita Pennathur, Assistant Professor of Mechanical Engineering, is working in the areas of biometric identification and microfluidics, researching the development of biosensors that could be used to detect and diagnose a range of diseases. Speaking from a conference on molecular bioseparations held recently in Boston, she described a hand-held device she hopes will isolate and identify DNA from a cheek swab in as little as 30 seconds. Such technology could prove valuable in settings as diverse as military checkpoints and medical clinics. Though Pennathur estimates her research is still three to four years away from commercial development, she sees potential in such areas as AIDS and cancer research, detection of toxic chemicals, and monitoring water quality. She’s a big fan of the collaborative environment at UCSB, especially the seamless overlapping within the ICB. “We talk a lot amongst ourselves; we also hold social events every quarter with the students, to get them sharing ideas as well. “It all helps spread knowledge and is so easy to do at UCSB where everyone is very helpful and accessible. It’s an awesome atmosphere.” Plaxco shares that enthusiasm. “The ICB has helped us create a strong community of disparate research groups,” he says. “It’s also been a life-saving source of funding.”
Professor Patrick Daugherty and his collegues at CytomX Therapeutics (an early stage, privately-funded biotechnology company developing proteolytically-activated biotherapeutics based on UCSB research) have crafted a molecule that is activated by protease at cancer tissue binding sites. After clipping the mask molecule on the antibody, binding occurs on the target molecule. This specificity enables direct delivery of therapeutic agents to the desired site.
Those kinds of responses are music to the ears of David Gay, the ICB’s director of technology, who sits at the interface between the institute’s principal funder——the Army Research Office——and academia and industry.
For Plaxco and the others, the real value in all this research is making products that help people: “Our focus is on things that we think will directly improve people’s health and safety,” he stated.
The Army began a five-year funding commitment in August 2003, and has since renewed for a further five years. Gay states that the institute received $44 million during the first five-year period. The Army’s budget for ICB in the second five years, fiscal years 2009 through 2013, totals $84 million, of which $15 million has been received so far for FY 2009.
Professor Kimberly Turner, Chair of the Department of Mechanical Engineering, shares this vision, and believes biotechnology is going to revolutionize the future of healthcare.
In both cases, the amounts have gradually increased as the Army responded positively to the results coming out of the ICB. “The point is, we are delivering,” says Gay.
“The technology has matured to the point where it’s right for diagnostics, especially medical diagnostics,” she says. “I think this is going to be a huge market in the next five to 10 years.”
“Our mission is to accelerate innovation,” he added, pointing to the transition of technology to the marketplace through young companies like CytomX Therapeutics, Cynvenio Biosystems, and Sirigen.
Turner has been working on the ultra-sensitive detection of carbon monoxide and other gases, developing technology that could potentially also alert users to a range of hazards from toxic chemicals and explosives to food-borne pathogens.
Both CytomX, based in Goleta, and Cynvenio, located in Westlake, were founded by Patrick Daugherty, Associate Professor of Chemical Engineering, Soh, and Heeger.
She sees many advantages for this type of detection and diagnostic technology: it’s small, easy to use, works fast, and is sufficiently cheap to manufacture that units could be disposable.
Cynvenio focuses on advanced instrumentation for bioseparation and cell-sorting applications, using microfluidics technology. “Integrating multiple steps of a complex assay, all on a chip, to obtain highly sensitive and error-free results rapidly and inexpensively … that’s the revolution that’s coming,” predicts Soh.
She believes the low cost and high convenience will have a major impact on procedures like lab tests and cancer screening which can become “much simpler and cheaper”.
His work at UCSB and Cynvenio was recently recognized at the annual conference of the Association for Laboratory Automation, in Palm Springs, where he won the 2009 ALA Innovation award for the most creative solutions to some of today’s most important problems in biotechnology.
Turner also foresees the day when the technology will be readily available off the retail shelf, enabling people to buy self-testing kits at the drug store and do many health-related tests themselves.
CytomX is addressing the early detection and treatment of tumors and vulnerable plaque. The company hopes to provide diagnostic tools for people at risk from cancerous tumors, and from heart attacks or strokes caused when plaque from artery walls ruptures and enters the bloodstream.
Links: Institute for Collaborative Biotechnologies (All faculty members mentioned are linked at ICB’s site) icb.ucsb.edu
Their teams are using molecular and cellular engineering to achieve this. They have learned how to manipulate certain molecules, blocking their normal function and instead giving them the ability to sniff out and bind only with molecules indicating tumors or atrisk plaque. These pre-programmed molecules, engineered in vitro, are introduced into the patient’s bloodstream and the results scanned using a magnetic resonance imaging (MRI) machine.
Cytomx Biosystems cytomx.com Cynvenio Therapeutics cynvenio.com Nanex nanex.us Sirigen sirigen.com
“Now we need about one billion cells grouped together before we can see them and detect a tumor,” explains Daugherty. “Our plan is to drop that number down, by a factor of ten or 100 or more.” Finding tumors at such an early stage would enable much earlier treatment and far better patient prognoses.
Having proved the concept, Daugherty says the science is now being tested in mice. Many more animal and human trials lie ahead, but he hopes a commercial product could be ready for approval in less than three years.
q u e s t i o n an d a n s w e r
Pierre Wiltzius Pierre Wiltzius has been UC Santa Barbara’s Dean of Mathematical, Life, and Physical Sciences (MLPS), holding the Susan and Bruce Worster Chair for the Dean of Science, since October of last year. He came to UCSB from the Beckman Institute for Advanced Science and Technology at the University of Illinois, Urbana-Champaign, where he had been the director since 2001; there he also held faculty appointments in the Departments of Physics and of Materials Science and Engineering. From 1984 to 2001, he was at Bell Laboratories, where his last position was director of semiconductor physics research. He holds a Ph.D. in physics from E.T.H. Zurich, and spent two years here at UC Santa Barbara as a postdoctoral research fellow in physics, from 1982 to 1984. In addition to having received widespread praise for his leadership of the Beckman Institute, Dean Wiltzius is a highly regarded researcher and pioneer in the areas of soft-condensed matter, colloidal self-assembly, photonic crystals, and microphotonics. He is a Fellow of the American Physical Society and of the American Association for the Advancement of Science, and a Senior Member of the IEEE. In 2001 he received an R&D 100 Innovation Award from R&D Magazine, for printed plastic display circuits. Convergence recently talked with Dean Wiltzius to find out a bit more about how he got (back) to UCSB, how he views the MLPS division here, and what his vision is for its future. How did you find yourself at UCSB in 1982? When I received my Ph.D. in physics from the E.T.H. (Swiss Federal Institute of Technology) in Zurich in 1981, I knew I wanted to come to the U.S. to do a postdoctoral fellowship—that was where the action was in physics. There were several postdoc positions in soft condensed matter—my area of specialization. Ultimately, however, the chance to work with David Cannell, one of the foremost scientists in the field, combined with the beauty of the UC Santa Barbara campus and the surrounding area, were irresistible. I began the two-year appointment thinking I’d do my postdoc and return to an academic appointment in Europe, to begin the climb up the predictable and somewhat rigid academic ladder there. Twenty-five years later, you’re back. Tell us about the intervening years… I never did go back to Europe to work—I was recruited at the end of my postdoc by Bell Labs, which was quite a compliment. Bell Labs had been where some of the most advanced scientific and technological work in the world was done. I was there for 16 years, eventually becoming first a department head and then a division director. Some of those years were great—the ’96 to ’01 dot com era, for example— and sometimes things were not as much fun, as when the dot com bubble burst in 2001. I’d been thinking about getting back into academia, and the director’s job at the Beckman Institute was a very natural, “soft” re-entry into that world. It’s purely a research institute, with no undergraduate component, which made
the transition from Bell Labs easier… Things were going great at Beckman—and then I got the phone call from the UCSB search committee. I’d been following the campus for twenty five years, since my postdoc here, and watched it grow in both size and stature. The campus made some key hires—Alan Heeger, Fred Wudl, and Jim Langer—while I was here in 1982, which sort of set the track in terms of UCSB’s continuing ascendancy in the sciences. What factors were most influential in your deciding to accept the position as our Dean of Science when it was offered? When the search committee’s call came, I realized I’d been missing involvement with undergraduate education, which is, after all, a pretty big piece of the university environment. UCSB is very strong in science and engineering research and undergraduate education, and there’s a “Santa Barbara spirit” that’s in the campus DNA. “Interdisciplinarity” is a term used as a totem and overhyped at many institutions, but it was the basis for the Beckman Institute, and it pervades research here—I think it’s fostered, in part, by the campus’s simplicity of structure, with no large professional schools complicating relationships and priorities. My own research has always had an interdisciplinary basis, so UCSB is a very good fit, as was Beckman. The physical compactness of the campus also contributes to the interdisciplinarity here. It’s a five-minute walk to get to any collaborator on the campus. Of the other 62 members of the American Association of Universities—the top research universities in the country—only Caltech and Princeton enjoy the same combination of a structure uncomplicated by professional schools and the physical compactness that we have here.
What are the biggest differences in your responsibilities here and at the Beckman Institute?
Are you challenging departments which may not be as strong as those that enjoy national prominence to move up to that level?
At Beckman, I had about 170 faculty members, of which 120 had a physical presence at the institute and 50 were “affiliated.” Each of them also had a primary home department. I had some influence in the hiring process for the Beckman faculty at UIUC, but no decision authority. Here, I have about 290 faculty members in our ten departments and 4 interdepartmental programs, and as dean, one of my primary responsibilities is to direct and manage the hiring and retention of the very best people. Much of that responsibility at UIUC was in the hands of the department heads. How do you attract and then retain a top-notch faculty? You have to start with a great intellectual environment, which we clearly have here at UCSB. Our world-class faculty in engineering and the sciences, and the free flow of ideas here between disciplines, result in a very fertile and stimulating climate—one that promotes the scholarship and research which earns us a place in the upper ranks of major universities. You also have to have a sound and firstclass infrastructure, so that the faculty can concentrate on their work without being distracted by logistics or facilities matters or by administrative details… In hard infrastructure—laboratories, offices, and other facilities—I think we’re reasonably competitive. We need to keep building if we’re going to stay that way. We are a bit on the lean side when it comes to support staff … but that’s an opportunity for our campus to grow and become “right-sized.”
I’m challenging all of our departments—even the strongest—to improve, to get stronger… We can always improve, and we will. The biggest impact I can have is to provide the resources to opportunity facilitate that growth.
Our biggest for the sciences and engineering together is, I think, to take advantage of the interdisciplinarity that’s in UCSB’s DNA—its value, and the uniqueness of its strength here, can’t be overemphasized. Today’s societal problems are extremely large and complex, and they require integrated, systems solutions rather than point solutions. We’re ideally set up to take on those problems, with our strong departments as a foundation and our interdisciplinary research centers and institutes engendering the integration of our strengths.
Are there some specific problems that you feel need to be addressed in order for us to keep moving up? Well, for one thing, we’re not currently getting a geographically diverse student body… That’s true across the campus, not just in the sciences, and it has significant budgetary as well as cultural repercussions. Geographic diversity in our student body will help improve our strengths… To be a truly top-tier research university, we have to keep reaching beyond provincialism. In the same vein, we have to reduce the expense of having foreign graduate students—it’s very expensive now, which makes recruitment more difficult and creates an economic incentive for our faculty members to accept their graduate students from California first and then from the rest of the US. That limits our access to the huge pool of excellent students from abroad, and results in a less culturally and intellectually diverse graduate corpus. Also the
Fundraising, of course, is always a challenge—probably more so for public universities than private. The current economic climate is certainly not helpful, but, as the economy recovers, we have a huge opportunity as the ‘60s graduates and the baby boomers are coming of age for philanthropy. That’s a very large cohort that’s had a lot of economic success, and they’re starting to become concerned with giving back, with helping others and leaving a significant legacy.
The third factor is student quality, both undergraduate and graduate. Ours is generally very good, and we need to continue on the upslope we’ve been on, perhaps steepening the curve. Some of our departments and programs—physics, geography, and earth and marine sciences, for example—compete very effectively with any school out there, including Berkeley and Stanford. The rest can, and will, get to that point. One of the big issues that needs attention in attracting out-of-state and international graduate students is the large tuition differential.
I think we can also do more to help move our discoveries out of the academy and into commerce. We’re doing a lot of brilliant science here which results in some great discoveries, but those discoveries only benefit society when they’re applied to solving problems and then those solutions are commercialized, making
them broadly available. Alan Heeger, Galen Stucky and Kevin Plaxco, to name a few, come to mind as being very effective in this respect—more of our scientists could perhaps follow their examples. Commercialization of our intellectual property both makes our work better known and generates some helpful revenue, both for the university and for the researchers.
the Environment or an Institute of the Science and the Mind are additional examples of potential future focuses. Is that going to be a sea change in higher education, or at least in research universities? It’s not “going to be…” It’s already happening. Some of the long established, large, well-known schools can get bogged down in 150 or 300+ years of academic tradition, complicated by the interests and influence of their professional schools, making this sort of change more challenging for them—we’re both relatively young and of a manageable size and structure, so we can be nimble and agile and choose the most effective ways to organize ourselves, with relative freedom…
Are you saying that all our science should have “real world” applications? Not at all… That’s more the perspective of the engineers, who by definition solve real-world problems. We can’t get to the applied science and engineering without having the theory and the fundamental science first. In this day and age, however, the traditional definitions and boundaries are largely obsolete— we have scientists engineering solutions to problems, and we have engineers doing fundamental research, and we have a tremendous amount of collaboration between the two. What do you see as the biggest opportunities for the sciences at UCSB? Our biggest opportunity for the sciences and engineering together is, I think, to take advantage of the interdisciplinarity that’s in UCSB’s DNA—its value, and the uniqueness of its strength here, can’t be overemphasized. Today’s societal problems are extremely large and complex, and they require integrated, systems solutions rather than point solutions. We’re ideally set up to take on those problems, with our strong departments as a foundation and our interdisciplinary research centers and institutes engendering the integration of our strengths. Our Institutes for Collaborative Biotechnologies and for Energy Efficiency are great examples of what I’m talking about, and I think we’ll see some of our bioengineering, stem cell research, and nanotechnology expertise coming together in something like a “nanomedicine” center, creating, among other things, nanofabricated biomarkers for both diagnostics and therapeutics. We also have a number of different areas of expertise in imaging, and I can see those possibly converging… We can make some real breakthroughs, in part because we’re able to drive our own research rather than having its direction dictated by clinicians. A good example is some of the neuroscience Mike Gazzaniga and Ken Kosik are doing—their breakthrough work is proof that their field doesn’t have to be driven by pathology, as it is so often when there’s a medical school involved. Going beyond what’s become almost a traditional collaboration between the sciences and engineering here, I see a huge opportunity in incorporating the social and political sciences into some of our interdisciplinary centers. We’re beginning to see that already, with the Institute for Energy Efficiency’s policy and economics solutions group working alongside the solid-state lighting and computing and communications groups. The Media Arts and Technology program is another example—they’re bridging the arts, the sciences, and engineering. We’ll be seeing more and more of this synergistic interdisciplinarity here, and that’s going to be a big factor in our moving farther up in the rarified world of top-tier research universities. An Institute for
Higher education in general, and our campus in particular, are also going to be seeing a big wave of retirements in the next ten years—some departments here may have as much as 50% of their tenured faculty turning over. That’s both a challenge and an opportunity. It will be tough to fill all those positions with the people we want, but it’s a real chance to renew our vision and to incorporate some new competencies… The “no silos” interdisciplinary centers and institutes need a different sort of leadership than the traditional single-discipline academic departments, and those centers and institutes represent our future. Is there anything you’d like to say in closing? This is an exciting time to be at UCSB, as the sciences and engineering here are clearly moving up—from an already very high level—in research, innovation, teaching, and reputation. I’m delighted to be part of that growth, and to be in a position to foster it.
Link: UCSB Division of Mathematical, Life, and Physical Sciences science.ucsb.edu
Rain Man and Einstein... It’s not yet known what causes autism. One of the more prevalent theories of recent years—the idea of a link between childhood vaccines and autism—has failed to hold up in scientific studies. “Every case of autism is a little different,” says Ken Kosik, co-director of the Neuroscience Research Institute at UCSB.
Decades ago, children with severe social problems—many who didn’t talk and didn’t behave—were dispatched to psychiatric hospitals. Called “autistic,” they languished in a life of hopelessness, separated from family, friends, and normal life. Now UC Santa Barbara is leading the way, on two major fronts, in understanding and treating what has come to be recognized as a complex of disorders manifested in varying degrees of severity.
There’s no cure for the disorder, but skilled intervention can minimize problems and improve the lives of patients and their families. “Our end goal,” Koegel says, “is for people with autism to be fully productive members of society with good jobs, loving families and friends, and a satisfying life...” The Koegels believe this someday will be possible, for even the most severe cases.
It was at the infamous Camarillo State Hospital that Lynn Koegel first encountered people with what’s now known as autism spectrum disorder. Now, years later, she is one of the most renowned clinicians in the field; she runs UCSB’s Koegel Autism Center together with her equally renowned husband, Robert Koegel, whom she first met at Camarillo.
While clinicians like the Koegels have made great progress in figuring out how best to help people with autism, little is known about what happens in the brain to give rise to its symptoms. “Something’s not working right” in the brains of people with autism, Lynn Koegel says, “but we don’t understand what…” Because autism encompasses such a range of symptoms that vary widely in their severity, it’s exceedingly tough to figure out the mechanisms that give rise to the disorder. “It’s very complex…” Kosik says. “There are certainly many different ways to acquire it. Different genes can go wrong in different people.”
“Things have really changed a lot,” Lynn Koegel says. Severely autistic people are no longer consigned to an invisible, institutionalized life, and the number of people diagnosed with autism spectrum disorder has increased considerably in the last few years, now affecting 1 in 150, although it’s not clear why.
Some cases of autism are known to be caused by abnormalities in certain genes, but those are the minority of instances. In most cases, Kosik says, there are almost certain to be small contributions from many genes—as is the case for other complex disorders, such as diabetes and heart disease, that are very challenging to understand and address.Kosik, who has spent most of his career researching the mechanisms in the brain that produce the devastating symptoms of Alzheimer ’s disease, recently turned his attention to autism.
“This is an epidemic that won’t go away,” Koegel says. “It’s not just people being more aware— although they are—it really is an increase in numbers.” Awareness has increased in recent years due both to the efforts of autism-focused nonprofits, and to the 1988 Oscar-winning movie Rain Man, which featured Dustin Hoffman as Raymond Babbitt, the autistic older brother of Charlie Babbitt, played by Tom Cruise. Autism is a developmental disability that causes problems with social interaction and communication. Autism is a “spectrum disorder” which affects individuals with a considerable range and severity of symptoms. People with Asperger’s syndrome, the mildest form of autism spectrum disorder, may have good verbal, quantitative, or artistic skills, but they typically have trouble understanding body language and other non-verbal cues, and often have an obsessive interest in a single object or topic. Famous scientists and artists, including Einstein, Newton, Darwin, Orwell, van Gogh, and Mozart, are often said to have had Asperger’s. People whose autism is severe typically have far more limited engagement with the world around them—they may not speak and may engage in repetitive behaviors, such as rocking back and forth or waving their hands repeatedly.
While he and the Koegels haven’t yet worked together, Kosik says he’s “looking forward to having some discussions with them” and “building some bridges here” between their clinical work and his focus on the genetic and biochemical mechanisms that underlie brain disorders. To try to figure out what sets apart the autistic brain, Kosik chose to focus on snippets of genetic material called microRNAs, to see how they might be involved in the disorder. MicroRNAs were discovered about 15 years ago; since then, these tiny fragments have had a big impact. The study of microRNAs is “one of the most explosive fields in all of biology,” Kosik says. They play a key role in regulating genes, and scientists have linked them to some cancers and other diseases.
MicroRNAs are found in all animals—humans probably have close to a thousand of them, according to Kosik—and they serve a kind of fine tuning role. “They take a biological system and tweak it so it’s working properly,” he says.
“It seems so logical,” Koegel adds, “but back in the early days not many people knew what to do. We’re also learning that if you vary the task, children with autism learn a lot more.” Rather than trying to deal with problem behaviors one at a time, the Koegels’ method—termed “Pivotal Response Treatment”—focuses on key aspects of a child’s development, such as motivation or social initiations. They have researched and developed “Pivotal Behaviors” that, once taught, have a widespread positive effect on lots of other untreated behaviors. They are, in a sense, “pivotal” to learning.
MicroRNAs play a particularly important role in the brain, Kosik says, especially in the early years of life, when it develops most rapidly. Because that’s also the time when symptoms of autism start to show up, Kosik decided to look at whether microRNAs are somehow involved in the disorder. “It was a very logical connection,” he says.
Kosik studied microRNAs in the brains of people with autism, using samples donated to tissue banks after their deaths. He found that a number of the several hundred microRNAs he analyzed were expressed differently in those samples, compared to tissue from people without autism. “We are by no means trying to say that the microRNA regulation that we observed is cause and effect,” Kosik says. “There’s almost certainly something more fundamental going on,” he says.“We’re in very early days in terms of understanding of this disorder.”.
than repeatedly looping words on a page.
“It’s really important,” Koegel says, “to figure these kids out and learn some of the tools.” Those tools can also help children without autism. For example, she says, kids will take more easily to handwriting if they pen postcards to friends, rather
While much of the research and training done at the Koegel Autism Center focuses on children, Lynn Koegel and others at UCSB have also begun working with UCSB students who have been diagnosed with Asperger’s syndrome.
A better understanding of the mechanisms in the brain that underlie autism could help scientists develop drug treatments for the disorder, or perhaps ways of preventing it. In the meantime, however, interventions like those pioneered by Lynn and Robert Koegel are the gold standard for autism treatment.
The disorder has been paid little attention until now, Koegel says, because the problems associated with it are relatively mild. People with Asperger’s typically do fine academically, but “their social communication with peers is a real problem,” she says. “A lot of them end up spending their lunch in the library”
“We’ve come a long way since the days when children with autism weren’t getting an education,” says Lynn. Rather than keeping children with autism out of normal classes, the Koegels advocate mainstreaming. That way, children with autism benefit from being exposed to the typical behaviors of their peers and to the expectations educators and parents put on children without autism. The Koegels’ approach to managing autism has changed the way clinicians, teachers and families around the country, and the world, deal with individuals with autism.
People with Asperger’s syndrome generally want the same things as most of their peers, she says—a good job, friends, a family of their own—but find it hard to establish and maintain relationships. Those difficulties can lead to a multitude of problems, from legal tangles triggered by misunderstandings to depression. The UCSB program aims to help the students succeed beyond the realm of books and exams. Participants get help upgrading their social skills—learning to look people in the eye when they’re talking, for example—and even run through practice dates.
In the past, Koegel says, “we just punished kids (with autism) when they had bad behaviors. Now we figure out why they are behaving badly. A lot of the time it’s because the kids are bored or the work is too hard.” The Koegels’ treatment strategy focuses on positive reinforcement that takes advantage of a child’s interests. “We let them choose the activity—” Koegel says. “Toys, books, activities they enjoy. Let’s say they like balls. If they say they want to bounce the ball, we’ll let them bounce the ball.”
The program, made possible by a large donation from Eli and Edythe L. Broad, only began last year, but Koegel says the students are definitely socializing more and are happier.
As encouraging as those results are, one of the keys to success in treating autism—whether the relatively mild difficulties associated with Asperger’s syndrome or the devastating problems that accompany more severe forms of autism—is early intervention.
Save This Date
These days, fortunately, educators and doctors place tremendous emphasis on detecting problems in young children and beginning treatment as soon as possible. That constitutes a major break with previous attitudes, Koegel says, when “pediatricians used to say, ‘Just wait…’” Signs of the disorder usually appear in the first years of life. Children with autism tend to be slow to develop language skills, don’t wave or gesture like other children, and don’t respond to their name being called. “If a child over the age of 18 months isn’t talking,” Koegel says, “a specialist should evaluate them.” “We’re happy to get them at two (years of age), but our goal would be to get them in infancy some day,” Koegel says. With early intervention, she says autistic children can show marked improvement. She cites the example of a child she worked with as part of an episode of the television series “Supernanny,” in which a childcare specialist—sometimes helped by professionals like Koegel—comes to the rescue of a family in crisis. The boy with autism, aged three, wasn’t speaking before he met Koegel, but began talking during the week she worked on the show. Early intervention makes sense to Kosik. “In terms of the biology,” he says, “it’s very reasonable.” At that age, “the brain is very plastic,” Kosik adds, and with early intervention, “we may be able to direct the formation of pathways in directions that might make a person healthier.” “Every year that goes by,” Koegel says, “there are more and more kids that do better and better.” Links: Autism information from the National Institutes of Health: www.nichd.nih.gov/health/topics/asd.cfm UCSB Koegel Autism Center:
Monday, October 26,
education.ucsb.edu/autism Ken Kosik: lifesci.ucsb.edu/mcdb/faculty/kosik
UC Santa Barbara BioEngineering Insights Conference 13
Taking the guesswork out of vaccines
Vaccines are one of the great successes of modern medicine—they’ve saved millions of lives by preventing infections by a wide variety of pathogens. Unfortunately, the organisms they’re supposed to protect against come in many different varieties, while most vaccines only offer a defense against, at most, a handful of closely-related germs.
That’s why new flu vaccines are produced every year, carefully tailored to fight the specific strains predicted to be the most widespread around the world in the coming flu season. It’s also why vaccines don’t work against pathogens that are constantly mutating, resulting in a broad spectrum of strain variants against which conventional vaccines are ineffective. “That’s the Achilles’ heel of vaccines,” says Michael Mahan, a bacterial geneticist in UCSB’s Department of Molecular, Cellular, and Developmental Biology. Together with Douglas Heithoff — Mahan’s former student, now a research scientist in the department — and colleagues at the University of Utah, he’s working to develop a new generation of vaccines, termed cross-protective, that protect against many strains of a given pathogen.
cause sickness in some hosts but not in others. In humans, different strains of Salmonella can cause food poisoning, blood poisoning (sepsis), and typhoid fever. For most people, gastroenteritis caused by Salmonella is unpleasant, but short-lived. In the elderly, the very young, and people whose immune systems are compromised by HIV or cancer treatments, however, an infection can be fatal. In these severe cases, bacteria may spread from the intestines to the blood and then to other organs.
In the past, vaccines have been developed using a somewhat empirical approach. “They work, but you usually don’t know why,” Heithoff says. “We’re trying to use a mechanistic approach toward vaccine design.” To do that, they first took a careful look at how microbes operate during infection. “We’re working to understand the mechanisms of disease at the molecular level,” Mahan says, “in order to make better medicines.”
Scientists Douglas Heithoff, left, and Michael Mahan with their new vaccine.
They’ve been studying Salmonella, a bacterium that is found in the digestive tracts of mammals, reptiles, birds, and insects, and is spread in feces. Salmonella infects up to 1.5 billion people annually worldwide, with more than a million cases in the U.S. alone. There are around 2,500 known strains of the bacterium, and any given strain can
Humans usually pick up Salmonella from contaminated beef or chicken. Vegetarians aren’t immune though, since Salmonella carried in animal waste can contaminate fields where vegetables are grown and facilities where food is processed or prepared. A Salmonella outbreak that hit headlines early this year was traced to contaminated peanut butter and other products containing peanuts. It infected hundreds of people in dozens of states and has been linked to at least nine deaths. One strain of Salmonella causes typhoid fever, a sometimes-fatal illness that is very
rare in the U.S., but affects more than 20 million people in the developing world each year, according to the Centers for Disease Control. That strain is only known to infect humans, and spreads as a result of poor water sanitation and hygiene practices. There is a vaccine against typhoid, developed decades ago, but it’s not particularly effective, Mahan says. It offers protection only against a few related strains of typhoid-causing Salmonella, so it’s no help in fighting the other strains that can sicken or kill. In their earlier work on Salmonella, Mahan and Heithoff studied how the bacterium is able to lurk benignly in some hosts, and then rapidly wreak havoc once it finds its way into others. They discovered an enzyme that acts as a master switch. This switch controls “many, many virulence functions,” Mahan says, allowing the bacterium to quickly transform from harmless hitchhiker to deadly invader. While this switch is a great asset for the microbe, it’s also its greatest vulnerability —and a terrific target for a new vaccine. Mahan and Heithoff created one by inactivating the switch, thereby disarming the bacterium. They used this crippled Salmonella — which can’t cause illness, but still provokes an immune response — as a vaccine.
In the meantime, Mahan, Heithoff, and their colleagues are continuing to test their Salmonella vaccine in animals, with good results. Used in humans, a vaccine effective against many strains of the bacterium could save thousands of lives, and could spare millions of other people from very unpleasant illnesses.
They’ve tested their new Salmonella vaccine in mice, chickens, and cows, and found that it gave the animals immunity to more than 20 strains of Salmonella isolated from various infected animals from around the world. Mahan and Heithoff ’s vaccine has another advantage over those that are currently in use: It doesn’t cause an increase in a specific type of inhibitory immune cells—cells that are associated with immune declines in cancer patients. The researchers have also shown that these inhibitory cells become more abundant with the normal aging process, which Mahan says, “may explain why the aged are more susceptible to disease and why they are difficult to effectively vaccinate,” He continued, “We’re currently working on interventions that negate these inhibitory cells—those interventions have the potential to reduce disease susceptibility and increase vaccination efficiency in the elderly.” Although the researchers have focused on developing a new vaccine for Salmonella, the same kind of master switch is found in other dangerous bacteria, including those that cause cholera, dysentery and the plague. Mahan believes that one day crossprotective vaccines will be developed against those and other infectious microbes. Viruses, like those that cause the flu, are a trickier target, Mahan says, “because they rapidly mutate and have very little genetic material.” He’s optimistic, however, that a new generation of human vaccines can be developed against both bacteria and viruses, offering a broader, more effective defense against multiple strains of microbes, rather than against just one or two variants. His biggest reservation is that currently unknown pathogens could turn up in humans, surprising us and leaving us illprepared for their attack. “Cross-protective vaccines may work against a wide range of strains of germs, but what about the ‘bugs’ we don’t know about?” he asks.
Mahan and Heithoff predict that cross-protective Salmonella vaccines will one day be approved for human use, but “The first of them is at least 10 years away…” Heithoff says. Human benefits from their research, however, are closer than that: when their new vaccine is cleared for use in livestock— which “isn’t too far in the future,” according to Mahan— it will reduce human food-borne illnesses by reducing levels of Salmonella in farm animals. That, in turn, will ensure that less of the pathogen finds its way into kitchens and restaurants, and ultimately into people’s digestive tracts. “We have to make the food supply safer,” Mahan says. “It’s unacceptable to me that a child could eat a cheeseburger and die, or spend the rest of his or her life on dialysis. We can do better, and we’re making good progress…” Links: Michael Mahan’s homepage: llifesci.ucsb.edu/mcdb/faculty/mahan UCSB’s Department of Molecular, Cellular and Developmental Biology: lifesci.ucsb.edu/mcdb NIH’s Medline Plus page on Salmonella: nlm.nih.gov/medlineplus/salmonellainfections.html CDC Salmonella home page: cdc.gov/salmonella
Diamonds are a
spin’s best friend… Spintronics, the exploitation of spin as well as charge in electrons, became a commercial reality in 1998. That year, hard disc drive heads based on giant magnetoresistance (GMR), a phenomenon resulting from spin, made possible a dramatic increase in data density in storage devices. Even your notebook computer now has data storage measured in hundreds of gigabytes rather than hundreds of megabytes—a thousand-fold increase. David Awschalom, a UC Santa Barbara professor of physics and of electrical and computer engineering, believes that huge performance increase is modest compared to what’s coming, and he should know—Awschalom and his research group have been paving the way for more than fifteen years, continuously advancing spintronics both in theory and in the tools and methods to verify and implement that theory.
Semiconductor spintronics also has the potential to lead to quantum devices, which will be based on controlling the precession of single electron spins, either electrically or optically. Electron spins in semiconductors can be created ‘coherently’ in states that point up, point down, or point in a superposition of up and down states –a quantum mechanical state that may serve as the basis for future quantum machines. That’s where diamonds enter the picture. Synthetic diamond has long interested semiconductor engineers as a material for conventional electronics, for multiple reasons:
“The accelerating pace of discovery in this area is extremely exciting,” commented Awschalom, who is director both of UCSB’s California NanoSystems Institute (CNSI) and of the institute’s Center for Spintronics and Quantum Computation. “We’re seeing semiconductor spintronic devices now where transistors were in the ‘50s—within a few years of being able to change radically the size, capacity, and speed of computing and communications devices.”
• It can be “doped” with select impurities to make it a semiconductor rather than an insulator, which it is when pure. • It’s the best thermal conductor on the planet.
Spin, closely related to magnetism, is a property of elementary particles complementing mass and charge. Spin in electrons causes them to behave like tiny bar magnets. Spin has been understood and accepted in physics since the 1920s, but it took more than seventy years for it to be exploited commercially. The GMR drive heads are based on spin-polarized current flow (current flow in which the spins of all the electrons are aligned) in metallic materials; so is the latest commercial form of non-volatile memory, MRAM (Magnetoresistive Random Access Memory), which offers the speed of conventional SRAM (Static Random Access Memory) with the nonvolatility of flash memory. Solid-state spintronic devices, now looking toward commercialization, are still based on spin-polarized current flow, but in semiconductors instead of metals. The first commercial semiconductor spintronic devices may be spin torque non-volatile memory, with multifunctional devices— single devices capable of logic, storage, and communication— farther out. Both MRAM and spin torque memory can make possible “instant-on” computers which would not have to laboriously reload programs and data from hard drives or from flash memory “solid-state drives,” which are faster than hard drives but substantially slower than spintronic memory. “The beauty of semiconductor spintronics,” commented Awschalom, “is that, unlike systems based on metallic materials, these systems have electronic, optical, and magnetic properties—those properties may be used separately or combined in new schemes, making possible highly multifunctional capabilities for future technologies.”
• It’s compatible with the CMOS (complementary metal oxide semiconductor) technology widely used in integrated circuits for everything from computer CPUs to image sensors. • It has a high refractive index, and is transparent to ultraviolet light and to most frequencies of visible light. • It has an extraordinarily wide band gap, an expression of the energy necessary to move an electron from the valence band (the highest orbital band containing electrons) to the conduction band, where electrons flow freely. Until recently, however, high cost and difficulties during growth in controlling the crystalline structure of the diamond films were major obstacles to taking advantage of diamond’s inherent suitability for electronic and photonic devices. (Earlier research in this area sometimes used polished natural diamonds, as they were purer and larger than then-available synthetic diamonds, and contained naturally-occurring impurities and vacancies (missing carbon atoms in the crystal matrix)—that combination made them good, though expensive, semiconductors.) Now diamond manufacturing costs are dropping, and progress in chemical vapor deposition makes possible the consistent creation of single-crystal diamond thin films, typically a few dozen microns thick over areas as large as many square centimeters, with controllable implantation of dopants and creation of vacancies. Nitrogen is typically used for the dopant, because nitrogen and an adjacent vacancy in the lattice constitute what is termed an N-V center, an ideal environment for exploring the spin of single electrons and single photons.
Awschalom’s work in spintronics has been very timely. He and his research team have been making breakthrough discoveries in spintronics, and in the tools and techniques needed to observe, measure, and control spin states, since 1992. Diamond’s band gap is 5.5 electron volts—five times as large as that of silicon and about twice the energy in a visible-light photon. That means that an electron trapped in an N-V center can be excited by optical-wavelength light without bumping it all the way up to the conduction band; when the electron falls back into the N-V center’s ground state it emits a single photon—it fluoresces. This can happen millions of times per second under continuous illumination.
their places, if we’re to continue advancing the size, speed, capacities, and costs of computing and communications systems. Diamond’s advantages in spintronics are compelling, both as a platform for researching single spins and other quantum phenomena and as a medium for eventual production of commercial quantum devices, and the Awschalom group’s work has kept it clearly at the leading edge of the research in that area. That leadership was emphasized recently when a research consortium led by UCSB’s CNSI and with Awschalom as Principal Investigator, received research funding totaling $6.1 million for two projects to explore the use of diamond in quantum information processing and communications.
It appears that spins in diamond may well also have a significant impact in photonics. N-V centers function as single impurities in diamond, and are thus able to emit one photon at a time. That’s a key capability for the nascent fields of quantum cryptography and quantum communication. Each photon carries one qubit (quantum bit), which represents information just as “conventional” electronic bits do. There is a big difference, however—conventional bits can carry only one of two values, either 0 or 1, while qubits can carry either or both spin states (down or up, or a combination of the two, called a superposition), yielding an infinite number of values.
One of the projects is sponsored by DARPA (Defense Advanced Research Projects Agency), and the other by the Air Force Office of Scientific Research (AFOSR). Those two agencies are among those government research sponsors looking far into the future. Both projects will focus on developing new quantum measurement techniques to manipulate and read single electron spins in diamond, the fabrication and demonstration of prototype quantum bits, and on their on-chip integration with photonics for communication.
David Toyli, a graduate student in Awschalom’s research group, notes, “One of the most remarkable characteristics of N-V centers is that we can manipulate their quantum properties at room temperature. That gives us tremendous flexibility in the types of experiments we canperform He continued, “This work with N-V centers is truly exciting—every few months there’s a new series of discoveries that dramatically changes our perception of what’s possible with this system.” Awschalom’s work in spintronics has been very timely. He and his research team have been making breakthrough discoveries in spintronics, and in the tools and techniques needed to observe, measure, and control spin states, since 1992. They’ve moved from looking at multiple spins at cryogenic temperatures, knowledge reflected in spin current devices, to examining and manipulating single spins at room temperature, which is the basis for practical quantum devices. Over the same time span, microelectronics, in the form of CMOS integrated circuits, has been following Moore’s Law, which states that the number of components on a chip will double every two years, carrying with it proportional increases in performance and/or capacity and decreases in component size and cost. Moore’s Law has limits, however, in conventional microelectronics, and we’re approaching them. We can now cram more than two billion transistors on a chip—to do that, the smallest circuit elements are down to 32nm (slightly over one millionth of an inch) in size. That size is getting very close to the point where the behavior of elementary, subatomic particles is governed by quantum mechanics rather than by the laws of classical physics. When that threshold is crossed, conventional microelectronic circuits and devices can no longer function as intended. Spintronic devices, built on quantum functionality, will have to take
The projects will also involve creating at UCSB a worldclass materials growth and device research facility dedicated to synthetic crystal diamond and diamond heterostructures. Diamond fabricated by the team will support not just the team’s spin and quantum research, but will also complement many ongoing research initiatives on the UCSB campus and around the world, including programs in solid state lighting, nanoelectronics, and atomic-level storage. Other participants in the UCSB-led consortium include Hewlett-Packard Research Labs and faculty members from Lawrence Berkeley National Lab, Harvard, MIT, the University of Iowa, and the Delft University of Technology. Links: Center for Spintronics and Quantum Computation www.csqc.ucsb.edu California NanoSystems Institute at UC Santa Barbara cnsi.ucsb.edu Awschalom Group www.physics.ucsb.edu/~awschalom “The Spin Doctors”, Chemistry World, May 2009 http://www.rsc.org/chemistryworld/restricted/2009/ MAy/TheSpinDoctors.asp
What is this?
Find the answer on the inside back cover.
Smokin’… even when you don’t! Joe Zasadzinski doesn’t smoke, but the UCSB professor of chemical engineering and of materials does want to know how the smoke and fumes that waft off lit cigarettes and out of smokers’ mouths might affect him. “Second hand smoke has been implicated in a host of health problems: It can cause lung cancer, and it’s been linked to respiratory infections, asthma, and chronic respiratory problems, such as persistent wheezing and coughing, in children. It hasn’t, however, been fully understood how the damage to the lungs is done. Now Zasadzinski is studying one aspect of how second hand smoke affects the lungs, forcing them to work harder and perhaps causing lasting damage. Second hand smoke—the fumes and particulate matter, both drifting directly from burning cigarettes, cigars, and pipes (sidestream smoke) and exhaled by smokers (mainstream smoke)—contains more than 5,000 chemical compounds, including the same multitude of carcinogens and toxins inhaled by smokers, including carbon monoxide, cyanide, benzene, formaldehyde, and arsenic. (It’s a Group A carcinogen, along with asbestos, benzene, arsenic, and radon…) “The chemistries of primary and second-hand smoke are basically the same,” Zasadzinski says, “although “people argue about concentrations a lot—about who gets more.” When they suck on cigarettes, smokers are, of course, intending to inhale a hefty hit of nicotine-laden smoke. However “the smoker has a filter on his or her end of the cigarette,” Zasadzinski points out, “but there’s no filter on the secondhand smoke that comes out the other end. It’s tough to say who gets the worst of it—the active smoker or the passive bystander.” Regular smokers, however, develop some degree of resilience to the persistent assaults on their lungs, notes Kamlesh Asotra of California’s Tobacco-Related Disease Research Program (TRDRP). Non-smokers don’t, so second hand smoke causes more damage to their lungs than direct smoke does to smokers, Asotra says. (TRDRP disperses funds from state cigarette taxes to researchers—including Zasadzinski.) To look at the effects of second-hand smoke, Zasadzinski, working with Patrick Stenger and Coralie Alonso, also of UCSB’s Department of Chemical Engineering, and researchers at UCLA and UC Davis, focused on a crucial component of the respiratory system: the thin film of liquid on the inside of the lungs. This epithelial lining fluid helps the lungs function and protects them from damage. “If you smoke or you’re around smoker, this is the first place the smoke will hit…” Zasadzinski says. Epithelial lining fluid contains lung surfactant “which is there to make breathing easier,” Zasadzinski says. Lung
surfactant lowers the surface tension between the fluid lining the lungs and air, minimizing the work the lungs do as they expand and contract. “The lower the surface tension, the easier it is to breathe,” Zasadzinski says. “Surfactant’s there to minimize the mechanical work the lungs have to do to move oxygen into, and carbon dioxide out of, the body.” Epithelial lining fluid is continuously regenerated, so “every 24 hours or so the lining of your lungs is basically replaced,” Zasadzinski says. An adult’s lungs contain only about a teaspoon of surfactant, “but if you don’t have it, you’re dead,” he added. Surfactant abnormalities occur in a host of diseases, including asthma, pneumonia, emphysema and sepsis, which can leave sufferers gasping for air. Very premature babies also have trouble breathing, because lung surfactant isn’t produced until the final weeks of pregnancy. Babies born too early can be treated with replacement surfactants derived from pigs or cows. These are pumped into the baby’s lungs—which are accustomed to the fluid-filled environment of the womb—as soon as possible after birth, and help the baby breathe until its lungs start producing their own surfactants, within a couple of days. Replacement surfactants, however, aren’t much use for adults with breathing problems. They would trigger an adult’s stronger immune response, Asotra says, and besides, respiratory distress is usually just one of a host of problems, “treating adults is considerably more complicated,” Zasadzinski says. To study how second hand smoke affects lung surfactants, Zasadzinski and his colleagues used biologically-based replacement surfactants in a lab setup that replicates how smoke interacts with the fluid lining of the lungs—“a very, very elegant” method of mimicking what happens in a living lung, Asotra says. The researchers produced second-hand smoke by burning cigarettes in controlled conditions using a “smoking machine” at UC Davis’ Institute of Toxicology and Environmental Health. They exposed purified water to this smoke for six hours, to create a tainted brew that they then used to test the effects of secondhand smoke on replacement lung surfactants. Zasadzinski and his colleagues reported their results recently in the international journal Biochimica et Biophysica Acta. The extent of the smoke damage to surfactants was “very surprising,” Zasadzinski says. The researchers focused on two proteins that are important in the surfactant function, and found they were both “really badly chewed up” by second-hand smoke.
“Now I can say, ‘Hey buddy, you’re destroying my proteins here.’ “
Smoke exposure changed the chemical composition and structure of the surfactants in the study—most likely by damaging crucial proteins. In a real, breathing animal, that kind of damage makes breathing hard work. “If you’re continuously exposed to tobacco smoke,” Zasadzinski says, “you will have breathing difficulties…” In their study, Zasadzinski and his colleagues exposed surfactants to second-hand smoke for 12 to 24 hours. It’s difficult to equate that to a specific level of exposure in humans, he says, but generally speaking, “it’s typical of an environment where there’s smoking going on.” The study “demonstrates how dangerous and injurious second hand smoke is,” Asotra says. “It’s also helpful in understanding the effects of other kinds of smoke, such as that produced by indoor wood-burning stoves, or by devastating forest fires.” Zasadzinski hopes that further research into how tobacco smoke damages the lungs will help answer the question of “how much exposure is too much exposure?” Studies like his also bring us closer to understanding just how smoke harms the lungs, Asotra says — knowledge that may one day help scientists figure out ways to treat or prevent lung damage from smoke. “It’s one thing to ban smoking,” Zasadzinski says. “It’s another thing to ask, as we are, ‘How do we help people who may be affected?’ “ In the meantime, Zasadzinski can better justify feeling aggrieved when he’s forced to share a clouded room with smokers. “Now I can say, ‘Hey buddy, you’re destroying my proteins here.’ “ Links: The paper Environmental tobacco smoke effects on lung surfactant organization dx.doi.org/10.1016/j.bbamem.2008.11.021 Joe Zasadzinski’s homepage: www.chemengr.ucsb.edu/~ceweb/faculty/zasadzinski UCSB Department of Chemical Engineering: www.chemengr.ucsb.edu/ California Tobacco-Related Disease Research Program: www.trdrp.org
have you heard?
News and Events from Engineering and the Sciences at UC Santa Barbara
Engineering II Addition on Schedule A 13,000 square foot addition to Engineering II is on schedule and is expected to be complete in December. Shown below in February of this year, the project was begun last December. The new space will house the Solid State Lighting and Energy Center (SSLEC), the Materials Department, a Chemical Engineering classroom, and offices for the Institute for Collaborative Technologies (ICB). The SSLEC and Materials portion of the building will be faculty, student, and staff offices, conference rooms and dry research areas. The project, officially known as the “Engineering II Life Safety Improvements and Addition Project,” includes a life safety upgrade in the existing Engineering II Building—the addition of fire sprinklers and an upgrade of the fire alarm system. Internationally known design firm Studios Architecture, which also designed the de la Guerra Dining Commons, is the architect of record. Their rendering of the completed project is shown at bottom. Link: Studios Architecture http://www.studiosarchitecture.com
The KAITEKI Institute, Inc., Glenn Fredrickson, Professor of Chemical Engineering and director of the UCSBbased Mitsubishi Chemical Center for Advanced Materials (MC-CAM), has been named executive director of the KAITEKI Institute, Inc., a global research institute focused on meeting 21st century challenges in energy, the environment, and healthcare. The institute was established earlier this year by Mitsubishi Chemical Holdings Corporation (MCHC), and became operational on April 1. Fredrickson will make six trips a year to Tokyo to consult with the institute’s management, but will otherwise direct the institute from Santa Barbara. “The KAITEKI Institute will be a ‘virtual institute’, without any bricks and mortar facilities of its own,” commented the executive director. “That will allow us apply most of our funding to the research we sponsor, without having also to support a physical infrastructure and the attendant staff and overhead.” 快適 ““Kaiteki,” which traditionally means “comfort” or “ease” in Japanese, was chosen for the institute’s name to represent the global quality of life that will be made possible through sustainable technologies such as artificial photosynthesis, which could solve both environmental and energy problems, and through breakthrough scientific advances in human health care. UCSB Moves into Forefront of Genetic Research Large-scale genomic sequencing is being performed at UC Santa Barbara, moving the campus to the forefront of cuttingedge genetic research. A new instrument, valued at over a half million dollars, has made the most current gene sequencing technologies available on campus to UCSB researchers, The “next generation” sequencer is much faster than earlier models and has a wide range of applications, according to Ken Kosik, M.D., Professor of Molecular, Cellular, and Developmental Biology,
and co-director of UCSB’s Neuroscience Research Institute (NRI). NRI purchased the instrument with funds from the Larry L. Hillblom Foundation, philanthropist Gus Gurley, and the university.
“This sequencer will serve as the cornerstone of genomics research here at UCSB, allowing us to do state-of-the-art work.” said Dr. Kosik. He also noted, “The study of human embryonic stem cells is among the most important ways we will utilize it...” Links: Neuroscience Research Institute www.nri.ucsb.edu Ken Kosik home page http://www.lifesci.ucsb.edu/mcdb/ faculty/kosik
UCSB claims multiple firsts with monolithic optical router. Researchers Steve Nicholes and Milan Mašanovi have produced the world’s first eight-channel monolithic tunable optical router, operating error-free at 40 Gbit/s per port. That yields a total of 640Gb/s on a single InP/InGaAsP chip which incorporates more than 200 functional elements and consumes less than 16 watts. “We are able to use a structure with quantum wells sandwiched in the center of the waveguide to achieve high-gain semiconductor optical amplifiers and high-power sampledgrating distributed Bragg reflectors,” said project leader Daniel Blumenthal. Not resting
have you heard?
News and Events from Engineering and the Sciences at UC Santa Barbara
on his eight-channel laurels, Blumenthal already has his eye on 64-channel optical routers, with the goal of reducing an entire rack’s worth of routing hardware to a single card. Link: engineering.ucsb.edu/news/264 New Energy Research Center Funded with $19 Million from Stimulus Act UC Santa Barbara’s Institute for Energy Efficiency will be home to one of 46 new multi-million-dollar Energy Frontier Research Centers (EFRCs). The UCSB EFRC is one of 16 to be funded by President Obama’s American Recovery and Reinvestment Act. It will receive a total of $19.0 million over the five-year initial award period. The EFRCs, which will pursue advanced scientific research on energy, are being established by the U.S. Department of Energy Office of Science at universities, national laboratories, nonprofit organizations, and private firms across the nation. The objective of the center is to discover and develop materials that control the interactions between light, electricity, and heat at the nanoscale, for significantly improved efficiencies in solar energy conversion, solid-state lighting, and thermoelectrics for conversion of heat into electricity. Links: UCSB Institute for Energy Efficiency www.iee.ucsb.edu Department of Energy’s EnergyFrontier Research Centers www.er.doe.gov/bes/EFRC.html
McKernan Awarded AMS Cole Prize James McKernan, professor of mathematics at UC Santa Barbara, and Christopher Hacon, of the University of Utah, have been named winners of the 2009 American Mathematical Society (AMS) Frank Nelson Cole Prize in Algebra. Presented only once every three years by the AMS, the Cole Prize is one of the highest distinctions in algebra. According to the prize citation, McKernan and Hacon were awarded the Cole Prize “for their groundbreaking joint work on higher dimensional birational algebraic geometry. This work concerns the minimal model program, by which S. Mori and other researchers made great progress in understanding the geometry of threedimensional projective algebraic varieties in recent decades. Link: McKernan home page: www.math.ucsb.edu/~mckernan Umesh Mishra, Professor of Electrical & Computer Engineering, has been elected to the National Academy of Engineering (NAE) in recognition of his “contributions to the development of gallium-nitride electronics and other high-speed, high-power semiconductor electronic devices.” Mishra’s election brings to XX the College of Engineering’s membership in NAE.
has just released its 2010 rankings of America’s Best Graduate Schools, and the news is good for the College of Engineering. The College as a whole moved up from 19th in the country to 18th (tie), and is the 12th-ranked public graduate engineering school. Over the last ten years, UCSB’s College of Engineering has climbed steadily in the US News & World Report rankings, moving up an average of two places every three years. These rankings include over 1,500 graduate school programs nationwide, and are the most comprehensive listing of its kind. Link: usnews.com/sections/rankings/
faculty member at UCSB since 1990, Mishra has broad experience in both industry and academia. His current research focuses on electronics and photonics, in the areas of high-speed transistors, semiconductor device physics, quantum electronics, optical control, design and fabrication of millimeter-wave devices, in situation processing and integration techniques, and on optoelectronics.
Tirrell Named to American Academy of Arts and Sciences. College of Engineering Dean Matthew Tirrell has been elected a fellow of the American Academy of Arts and Sciences. Tirrell is also a member of the National Academy of Engineering and a Fellow of the American Institute of Medical and Biological Engineers, the American Association for the Advancement of Science, and the American Physical Society. This year’s fellows come from 28 states and 11 countries. They represent universities, museums, national laboratories, private research institutes, businesses, and foundations. The newly elected group includes Nobel laureates and recipients of the Pulitzer and Pritzker prizes, MacArthur fellowships, Oscars, Grammy and Tony awards, and the National Medal of Arts. “These remarkable men and women have made singular contributions to their fields, and to the world,” said Academy President Emilio Bizzi. Written and reported by staff writers and editors from the Office of Public Affairs.
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The Magazine of Engineering and the Sciences at UC Santa Barbara
THIRTEEN, SUMMER 2009 Editor: Tony Rairden Creative Director: Peter Allen Writers: Anna Davison Frank Nelson Vic Cox George Foulsham Gail Gallessich Copy Editor: Karen Ko
This image illustrates the process of amyloid fiber formation via parallel stacking of monomeric protein units and oligomeric protein building blocks to elongated protein ‘strings’. Songi Han, her student Anna Pavlova, and coworkers are developing a generally applicable magnetic resonance tool to study the molecular basis of the early stages of protein aggregation occurring in situ. When protein-protein binding occurs, the surface hydration water at the interaction interface will be perturbed or excluded. Water is “squeezed out” at the interface whenever tight binding occurs, as detected by specifically tethered spin labels (shiny yellow dots). A. Pavlova, E. R. McCarney, D. W. Peterson, F. W. Dahlquist, J. Lew, S. Han, Site-specific dynamic nuclear polarization of hydration water as a generally applicable approach to monitor protein aggregation, Phys. Chem. Chem. Phys (2009) in press.
A couple of issues ago, we promised you more on our biomedical research and engineering. Here we bring you several more of the many stories in that area that we have here on campus. Extending our already broad interdisciplinarity, our article on autism ranges beyond our usual “engineering and the sciences” beat, as the clinical side of UCSB’s work on autism is actually taking place in the Givertz Graduate School of Education even as the neurological aspects are explored in our Neuroscience Research Institute. Our other biomedical research pieces, on understanding the deleterious effects of second-hand smoke, creating vaccines that can inoculate against multiple strains of pathogens, and detection and diagnostics, are complemented by an article on quantum spins in diamond. That last article leads us toward a full circle: The quantum information devices that may be made possible by the research described would be orders of magnitude faster and more capable than what we think of as computers today, and such devices would, in turn, significantly accelerate biomedical research, more and more of which has a computational foundation. We hope you enjoy this issue, and that you’ll stay caught up with what’s happening in engineering and the sciences here between issues by occasionally checking in at Convergence Online, convergence.ucsb.edu. TR
Editorial Board: Matthew Tirrell, Dean, College of Engineering Pierre Wiltzius, Dean of Mathematical, Life and Physical Sciences, College of Letters and Science Bruce Luyendyk, Associate Dean of Mathematical, Life & Physical Sciences, College of Letters and Science David Awschalom, Scientific Director, California NanoSystems Institute Kevin Almeroth, Associate Dean for Advancement, College of Engineering Frank Doyle, Associate Dean for Research, College of Engineering Glenn Beltz, Associate Dean for Undergraduate Studies, College of Engineering Kristi Newton, Assistant Dean for Development, Engineering and the Sciences Tony Rairden, Communications Manager, College of Engineering Peter Allen, Marketing Director, College of Engineering Joy Williams, Assistant Dean for Budget and Administration, College of Engineering Andrea Huebner, Publications Director, UCSB Alumni Association Michelle Keuper, Executive Assistant to the Dean, College of Letters and Science Convergence is a publication of Engineering and the Sciences at the University of California, Santa Barbara, CA 93106-5130. If you have comments or questions about this publication, contact please Tony Rairden at email@example.com.
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