Imagine that you are at a shopping mall somewhere in a major city — Los Angeles or New York, let’s say. All of a sudden, people around you start falling to the floor. A police officer who is called to the scene takes out a slim gadget about the size of a tiny Post-it note. He waves it over the collapsed shoppers and then slides it into a wireless handheld device and presses a button. Within minutes, a text message flashes across the instrument’s screen, a reply from police headquarters confirming that a toxic agent has been released and that authorities know exactly what it is as well as the correct antidote to administer.
Such a speedy response to a terrorist attack still sounds like science fiction, but it could well be reality in the not-too-distant future. And when that happens, chances are that the handheld bio-analyzers employed will be based on microelectromechanical technologies developed at UCLA. A device capable of detecting poisonous gases is most likely to use miniature “lab-on-a-chip” technology, a unique version of which Chang-Jin Kim, a professor in the Department of Mechanical and Aerospace Engineering, has spent the past four years developing.
Or consider another scenario that is likely to shape the future. A cardiologist inserts two catheters, each about the thickness of a thin piece of spaghetti, into the heart of a child born with defective valves — a congenital condition that currently requires one or more open-heart surgeries. Introduced through a puncture near the child’s groin, one of the catheters threads through an artery while the other goes up through a vein, giving the cardiologist access to all chambers and valves of the heart. At the tip of either catheter is a piece of thin-film nitinol, an extremely strong, malleable and biocompatible nickel-titanium alloy that is four times thinner than human hair and can be “trained” to assume any shape. When it pops out of the catheter it becomes a prosthetic aortic or pulmonary valve — valve replacement without surgery.
Two UCLA faculty members — Daniel Levi, a pediatric cardiologist at the David Geffen School of Medicine at UCLA, and Gregory Carman, an associate professor in the Department of Mechanical and Aerospace Engineering — are developing just such a valve. They might also use thin-film nitinol technology to develop a ventricular-assist device for patients whose hearts have difficulty pumping. It’s a distinctly futuristic aim that Levi describes as “our ultimate goal.” The idea is to wrap the heart of a patient in thin-film nitinol trained to expand and contract, thereby helping the heart’s pumping action.
Kim, Levi and Carman are part of a broad and diverse group of UCLA professors, researchers and students engaged in an ambitious interdisciplinary effort to help transform the frontiers of science and society. They are working on potentially revolutionary technologies of such enormous diagnostic, therapeutic and predictive value that our civilization appears set to take what the American futurist Alvin Toffler has called “a quantum leap forward.”
In The Third Wave, his best-selling 1980 book, Toffler noted the vital contributions of the agricultural and industrial revolutions. Looking to the future, he proposed that “a third wave will sweep across history and complete itself in a few decades … tearing our families apart, rocking our economy, paralyzing our political systems, shattering our values.” Everything from medicine, defense and space travel to foods, fashion and art will surely be transformed.
Indeed, much of Toffler’s vision appears to be on the brink of coming true. Some of the most remarkable future developments will be in medicine. Based on what has been learned of the human genome, drugs will be tailor-made for individual patients and administered through ultra-precise delivery systems implanted into the body. Rapid diagnostic testing will be possible at home, and invasive procedures like open-heart surgery will be performed on outpatients.
“We are going to see the miniaturization of biomedical diagnostic devices, just the way we have seen the miniaturization of computers,” says Edward R.B. McCabe, co-director of the UCLA Center for Society and Genetics. “Engineering and medicine are going to improve medical care in ways we can’t even fathom.”
This brave new world will largely be powered by molecular biology and the information sciences, whose impact is likely to be as world-shattering as were the Copernican and Darwinian revolutions. Molecular biology, which studies the simplest strata of life, and the information sciences have developed a close partnership since the 1980s, the decade that began with the revolution in microelectronics and went on to spawn the Information Age and the Gene Age. Today, we are in the era of integrative technologies and it’s not hard to understand why molecular biology and computer science have teamed up: The former, the handmaiden of the Human Genome Project and genetic engineering, generates a colossal amount of data that can be processed, understood and used only with the help of powerful computers.
This “silicon-life interface,” as the marriage of biology and computer science is sometimes called, has profound implications. “We have begun to breathe into inert sand — the silicon at our feet — a level of complexity rivaling life itself,” says Gregory Stock, director of the Program on Medicine, Technology, and Society at UCLA’s School of Public Health. “And our world will never be the same.”
Yet for all the promise of science, skeptics and critics rightly point out, the fact remains that much human misery has yet to be alleviated. Poverty is endemic worldwide — more than 800 million people live with chronic hunger and nearly 9 million die every year from hunger-related causes. Disease is still rampant and the world continues to wait for a host of breakthroughs that have long seemed imminent, such as a general cure for cancer. “The big questions — how to control a cell’s function, how to interfere with a cell becoming a cancer, how to stop heart disease — are still out there to be answered,” says Mike Teitell ’85, M.S. ’85, Ph.D. ’91, M.D. ’93, chief of UCLA’s Division of Pediatric and Developmental Pathology. “The key is bringing fresh ideas along with new tools and technologies to the same old problems.”
Teitell has made some progress along that path. In 2002, his lab created the first genetic animal model, by modifying specific genes in a specific way, for two of the major forms of white-blood-cell cancers. Lately, his work has revolved around the most high-tech tools for the detection, treatment and prediction of cancers. One of these is the atomic-force microscope (AFM), a kind of celebrity scientific instrument whose development in the 1980s coincided with the widespread adoption of the personal computer worldwide. The AFM is credited with boosting nanotechnology, an umbrella term for a variety of rapidly developing engineering techniques used to manipulate materials one-millionth the size of a pinhead.
The AFM is based on the scanning tunneling microscope, which was designed at IBM and recognized with a Nobel Prize in 1986, around the time when Jim Gimzewski, a professor in the UCLA Department of Chemistry and Biochemistry, was beginning his career at the IBM Zurich Research Laboratory in Switzerland. Gimzewski is one of the pioneers of AFM technology. Since coming to UCLA in 2001, he has teamed up with Teitell to advance cancer research, mainly by using the AFM to analyze the mechanical properties of cells on a nanoscale (one nanometer is a billionth of a meter). “It’s a brand-new method we’re developing for the diagnosis of cancer cells,” says Gimzewski.
The AFM works by detecting a projected laser beam that is reflected off a highly sensitive cantilever that ever-so-lightly probes whatever is being studied — suspected cancer cells in Gimzewski’s and Teitell’s case. When the cells move — or more precisely, vibrate — the laser beam also moves, and this movement is recorded and analyzed to determine whether the cells are healthy, diseased or responding to treatment. Teitell and Gimzewski are trying to link this motion of cells to the prediction, diagnosis and treatment of cancer. They can, for example, assess a cell’s responses to various drugs by dousing them with a chemical and watching their movement. That’s a big advance over a typical pathologist’s light microscope that only provides a static picture of dead, dehydrated cells, says Teitell. “With the AFM, you get an integrated picture of how cells look and respond to treatment.”
Another way of studying cellular behavior is to listen to them sing — literally. Any mechanical vibration is accompanied by sound, but it was Gimzewski and graduate student Andrew Pelling who first discovered that healthy yeast cells naturally vibrate at a high frequency and emit high-pitched sounds, while dying cells are muffled. (Their discovery was reported in the prestigious journal Science in August.) Gimzewski has named the fledgling science “sonocytology,” cytology being the branch of biology that studies cells.
While UCLA isn’t the only institution engaged in this kind of work, the novelty of the effort here “is that we’re building a database of signatures of different types of cancer cells and then comparing different cancers to that database,” says Teitell, who looks forward to the day when his research will allow him to directly interrogate cells in patients. “It’s a futuristic aim that’s years away,” he says. But in the near future, adds Teitell, aided by advances in genetic analysis, it could be possible to tell patients not just what kind of cancer they have but “how it will respond to a certain battery of drugs and what course the disease will likely take.”
Cells dance and sing to communicate with one another, and understanding how they do this is the key to genetic engineering and the prevention, diagnosis and treatment of disease. But humans aren’t the classical model for research in cell-to-cell communication. That distinction goes to bacteria, which have been around for much longer than we have. Over the past five years, the genomes of hundreds of strains of bacterial cells have been sequenced. Using mathematical techniques, scientists have been able to interpret the complex, hidden signals that enable bacteria to express genes, making different genes distinct from each other.
“The goal is to teach bacteria a new language,” says James Liao, a professor of chemical engineering at the Henry Samueli School of Engineering and Applied Science. Earlier this year, Liao discovered a way to alter cell metabolism, thereby allowing cells to artificially communicate with each other. Scientists like Liao can now synchronize cell behavior in bacteria to create “designer biosystems” capable of manufacturing a range of naturally derived commercial products such as antibiotics, plastics, even renewable energy. “Most of our chemicals today come from petroleum,” says Liao. “In the next few decades, we will replace petroleum-based chemicals with biologically based chemicals.”
Liao’s research is part of a field known as metabolic engineering. He’s done some remarkable things with bacteria. By changing the regulation of a gene in the ubiquitous bacteria Escherichia coli, he obtained lycopene, a nutrient-rich substance in tomatoes that is known to fight prostate cancer. In another experiment, Liao changed the genetic-control loop of a gene in a bacterial cell. The cell glowed whenever the gene was expressed. What’s more, it glowed in a rhythmic fashion and even amplified its luminescence when “ordered” to do so.
“The glowing is totally artificial,” explains Liao. “The idea was to ask ourselves whether we can design something that makes the cell behave in a complicated fashion. To carry the idea further, electronics engineers can design anything — no one is surprised by the developments in the silicon world anymore. The challenge is to approach that direction in biological systems. Eventually we want to be able to manipulate DNA just as we manipulate electronics. Designing bacteria is the early beginning, and as we do more and more complex things we can go on to humans.”
And perhaps even create synthetic forms of life that have never existed before. Bizarre as this might sound, attempts to do just that have been under way. Last year, Craig Venter, an American geneticist who headed a controversial private effort to sequence the human genome, launched a project to build a synthetic bacterium — by writing its genome. It was biotechnology’s most audacious attempt to rewrite the language of life by, in effect, playing God.
Can such efforts create life artificially? “Life requires information, and information is very important, but it’s not the only thing,” says Liao. “We still need energy and materials — information can’t do everything.” The key to the science of the 21st century and beyond, in Liao’s view, is integrating information with biological functionality. “We’re entering a systems world where there are no hierarchies and it’s very difficult to say what controls what,” says Liao. “In this holistic world, everything interacts and everything is limiting.”
Whatever the future might look like, it’s worth noting that integrative technology already has the ability to create lifelike materials and systems. Perhaps the best example of this is what occurred in the laboratory of Carlo Montemagno, professor and chair of the Department of Bioengineering, in the fall of 2000. Montemagno, a microengineer with a background in biology, created the world’s first robot propelled by muscle power.
He did this by attaching a cord of living cardiac tissue taken from a rat to the underside of an arched strip of silicon as wide as a human hair and no bigger than the zero in the numerals “2000” etched on a penny. Montemagno placed this delicate contraption in a carbon-dioxide incubator for about a week. The cardiac fibers were fuelled by a simple glucose solution, and their contraction and relaxation made the silicon arch bend and stretch, producing a crawling motion in the “microbot,” or more appropriately, “musclebot.”
Montemagno struggled for three years to create his musclebot, an appealing alternative to micromotors, which need electricity to function. NASA’s Institute for Advanced Concepts funded his project as part of a larger mission to develop futuristic technologies. Montemagno’s job was to create musclebots that interacted with one another, like ants, in the event of an emergency in space. The idea was that astronauts could create musclebots on the spot if, say, their spacecraft got damaged by micrometeorites.
“[The astronauts] would have a whole mass of skeletons — 100,000 of these microbots sitting in a small box, and a single vial of cells,” explains Montemagno, who will never forget the day when he and one of his student collaborators peered into an AFM microscope in their lab and found their musclebot crawling. “The microbots would be put in the cell culture, and they would live for three to seven days” — entirely on biological energy.
Not everybody is happy with the march of science into the 21st century. In a 325-page report, “Beyond Therapy: Biotechnology and the Pursuit of Happiness,” published last year by the President’s Council on Bioethics, Leon Kass, the Hertog Fellow in Social Thought at the American Enterprise Institute and chair of the council, decried the looming biotech-enabled world as one that “cheapens rather than enriches America’s most cherished ideals.” A year earlier, in his book Our Posthuman Future: Consequences of the Biotechnology Revolution, the noted author and political scientist Francis Fukuyama expressed a fear that “biotechnology will cause us in some way to lose our humanity — that is, some essential quality that has always underpinned our sense of who we are and where we are going, despite all of the evident changes that have taken place in the human condition through the course of history.”
Such criticism is hardly new to scientists, and many of them feel it’s unfair. “It’s asking too much of science to provide answers to everything, as was once the case with religion,” says Roberto Peccei, a theoretical physicist and UCLA’s vice chancellor of research. Yet the debate between scientists and ethicists is a serious one. “The sum of the crises that have to do with genetic manipulation,” Peccei predicts, “will raise issues for individuals that are on the scale of what nuclear weapons once had to do with the globe.”
Biotechnology is already under scrutiny and nanotechnology is increasingly being seen as a cause for concern. Last year, the Prince of Wales, who has led a successful campaign against genetically modified crops and foods in Britain, created banner headlines with his reported pronouncement that self-replicating nanorobots would transform the planet into “grey goo.” And in an article that he wrote for a British daily in July, the heir to the British throne warned that although nanotechnology is “a triumph of human ingenuity,” it could unleash a disaster similar to the one that was caused decades ago by the “wonder drug” thalidomide, which led to the births of thousands of deformed babies.
Nanotechnology does have potentially adverse health, safety and environmental effects, as a major new report by Britain’s Royal Society and the Royal Academy of Engineering recently concluded. The report warns that while nanoparticles contained in computer chips are not known to be harmful, free-floating nanoparticles and nanotubes used to produce such things as pharmaceuticals and cosmetics could have negative side effects. The report also expressed concern about the possible military use of nanotechnologies leading to “entirely new threats that might be hard to detect or counter.”
Raising public awareness about nanotechnology is another challenge. A lot of people haven’t heard of nanotechnology, let alone how it is shaping our world, and this is a matter of great concern to many scientists. “Nanotechnology is in our watches, cars, hospitals and it shuffles information around,” says Gimzewski, who led a team at IBM that created one of the icons of nanotechnology — the world’s smallest abacus made of soccer ball-shaped molecules of carbon. On the other hand, explains Gimzewski, nanotechnology is about “therapies and new ideas — the next big thing that’s going to change the world in 20 years.”
Including, surely, the academic world, for nanotechnology is one of those disciplines that truly works on the interstices. “It is breaking down boundaries and providing an umbrella under which people from mathematics to engineering to the life sciences are coming together,” says J. Fraser Stoddart, director of the California NanoSystems Institute (CNSI) at UCLA and holder of the Fred Kavli Chair in NanoSystems Sciences. “The very best of young people are responding to nanotechnology with gusto because they’re not hemmed in by the feeling that they’ve got to be a chemist or an engineer or a biologist.”
Sitting in the CNSI conference room one recent afternoon, Stoddart, an internationally renowned chemist, mused over his lifelong obsession with molecules — a time often spent, by his own admission, attracting criticisms for his “exotic but crazy” pursuits in the lab. This past May, he was part of a team of scientists that developed a molecular model of a symbol from Renaissance Italy, the Borromean rings, by bringing 18 components together in a spontaneous feat of nanoengineering. The rings, just three in number and 2.5 nanometers from tip to tip, are interlocked in such a manner that if any of them is broken, the whole assembly collapses.
The Borromean rings could be a form of a drug-delivery system or used in molecular electronics as a switching device capable of performing simple logic functions and displaying random access memory. Although the fundamental science behind a molecular computer has already been done, Stoddart says he and his colleagues “got a huge kick” out of making the Borromean rings, which are, for them, a source of fascination as old as science itself. And for very good reason. “In science you expect one thing to happen, and something else happens,” says Stoddart. “That’s the point. Almost all major discoveries have been stumbled upon.”
Ever since he was a boy growing up on a farm in his native Scotland, says Stoddart, “I was fired up by the wish to do things that no one had ever done before — to feel that I had the ability to change the way things happen. That’s what drove me to science. And the one thing you cannot do is resist it. You can’t stop the march of new technologies. It’s relentless. It’s exciting.”
Pervasively Connected by Technology
Computer buffs are on their way to becoming “computer buses,” thanks to Microsoft. On June 22, the information technology giant was awarded U.S. Patent 6,754,472 for its proposal to develop a “method and apparatus for transmitting power and data using the human body.” The idea: Instead of radio signals or infrared, use the conductivity of human skin to seamlessly link such electronic devices as mobile phones, PDAs and pagers.
Baffled? Welcome to the fast-approaching era of pervasive computing, or “PerC,” the next critical frontier of information technology characterized by computers that are ever more miniaturized, embedded, omnipresent, always on and capable of sensing, processing and actuating endless cyclones of information anytime, anyplace. Also known as ubiquitous computing, ambient intelligence or simply post-PC computing, this emerging world, fertilized by the mobile Internet era, seeks to regulate interaction among users and computing devices that are both mobile and embedded in the public sphere.
“Computation is normally seen as occurring outside the human body, but that distinction may be eroding,” says Dana Cuff, director of the Institute for Pervasive Computing and Society, a transdisciplinary group at UCLA.“ When information is embedded in everything, all of a sudden the environment’s role in our lives is not only much greater, but qualitatively different.”
PerC stems from a consensus in the scientific community about the continuing validity of Moore’s Law, which refers to Intel cofounder Gordon Moore’s 1965 observation that the computer power available on a chip approximately doubles every 18 to 24 months. The law is expected to hold true for at least another decade, helping create microprocessors of such small size and cost that they can be embedded in just about anything from electrical devices and automobiles to toys and tools — all rendered “smart” because of their digital connection through wireless networks.
The beginnings of how this personal and spatial computer interface is being reshaped can be seen in the proliferation of wireless ports for PCs at cafes; the extensive public surveillance systems dotting metropolises like New York and London; and the growing use of wireless “Blackberry” devices that can send out beacons in a crowded area, allowing people to find each other. But the most visible examples come from the household domain: smart homes that have refrigerators and washing machines with remote Internet connections for maintenance access; microwave ovens with integrated Web-pads; even instrumented coffee pots and clothes.
PerC will revolutionize our lives in a number of ways. Think of the millions of baby-boomers, many of them ailing or living on their own — PerC devices will make it possible for relatives to monitor whether they’ve taken their medications or, indeed, eaten their breakfast.
Or think of a crisis such as the one following 9/11, when emergency-response systems in Los Angeles were overloaded and campus e-mail badly jammed. With PerC, information about evacuation and safety could be available to anyone with basic wireless access.
But PerC isn’t without serious ethical issues, such as the use of biometric scanning to ascertain people’s identities and then matching the data to relevant financial, marketing or criminal databases. Whether or not PerC eventually comes to be seen in a positive light will be the subject of great intellectual interest over the coming decade, predicts Cuff, who is also a professor in the Department of Architecture and Urban Design. Meanwhile, she and her colleagues have the challenging task of acting as a bridge between what Cuff describes as “privacy activists wary of every new technology and technologists who rarely recognize the ethical issues their work embodies from the very outset.”
Is It All in the Mind?
Two years ago, Susan Smalley was a self-described “left-brain, cynical scientist” who saw the world through the materialistic lens of cold reason. One day, Smalley, a professor at the Neuropsychiatric Institute (NPI), had an epiphany that radically changed the way she viewed her life and her work, which revolves around genetic research on attention deficit hyperactivity disorder (ADHD).
Smalley went on to explore “mindful awareness,” an ancient Eastern meditative practice that she defines as the “moment-by-moment process of actively attending to, observing and drawing inferences from what one experiences.” The phenomenon has both biological and nonbiological roots, and it made Smalley realize two things that are also key concepts in her field of genetics: Humans are deeply connected to other forms of life on the genetic level, and that they are constantly changing on every level of their existence.
It might seem ironic that awareness would have any role to play in this high-tech era of genomics. But as science gets better at the early detection of risks for disease, prevention rather than intervention will become increasingly important, and that’s where self-help tools such as mindful awareness will be greatly needed. “The current treatment model of taking a pill or getting external help is shifting to a self-care, resilience-building model,” says Lidia Zylowska, a psychiatrist at NPI who works with Smalley on mindfulness research.
Being mindful has other advantages. “When you recognize your interdependence and changing nature, you no longer see yourself as separate from another person, and this is the foundation for building stronger communities,” says Smalley. “There are many people within NPI who believe one of the problems in the world today is the lack of connectedness with one another.” In fact, building stronger communities, both on and off campus, as well as disseminating self-help tools to promote emotional well-being, are key elements of a transition currently under way at NPI. As part of the new NPI, Smalley and her colleagues are scheduled in 2005 to launch a center devoted to research in mindful awareness. In addition, they have developed an interdisciplinary mindful-attention project aimed at using the principles of awareness to treat ADHD, initially in teenagers.
The idea is to show ADHD patients how their disorder manifests, and then “let them step back to look at themselves from a third-person perspective,” says Smalley. The goal, she explains, is to enable them “not to get too attached to whatever activity might be happening in their brain, allowing them to gain more insight into their own way of thinking and seeing and learning how to regulate their lives.”
That acts of the mind affect biology is firmly established in research that is still in its early stages, but the research has enormous therapeutic implications. “Most of that work has looked at the immune system and found many positive changes in it,” says Smalley. “We are going to do empirically sound studies that look at how mindfulness causes changes in the brain.”
One of the experts in this field is Jeffrey Schwartz, a research professor at NPI whose work has shown how positive thinking can permanently alter neural pathways. “A change in perspective is a uniquely human capacity, and the regular paying of attention determines not only how the brain works but also how genes express themselves,” he says. This power, adds Schwartz, can be demonstrated by the “Quantum Zeno Effect,” named after the Greek philosopher Zeno and introduced into science by a group of physicists in 1977.
The phenomenon means that a simple act of observation freezes a quantum system — brain activity, for instance — and suppresses certain transitions to other states, including gene expression. “Quantum physics asserts that all causation does not lie in matter,” says Schwartz. “Physics doesn’t integrate this with the brain, but we’re bringing a new form of causation to science. It’s a major paradigm shift of Copernican magnitude.”
