Now What? by Jo Ann Shroyer

From Kitty Hawk to the Internet, engineering innovations have profoundly changed the way we live.

Take a look at the National Academy of Engineering’s (NAE) list of the top 20 technical achievements of the 20th Century and imagine life without such staples as air travel, cars, laser and fiber optics, radio, television, telephones, digital technology, computers and the Internet.

Engineers may rightly claim a central role in the most dynamic 100 years of technical change in human history.

But Now What?

The NAE tried to answer that question with its list of grand engineering challenges for the 21st Century. Not surprisingly, nearly every item is part of our daily conversation: the cost of energy, the health of the environment, preventing and curing disease, managing and securing information, optimizing transportation, preventing terrorism, and feeding the world.

Innovations in any of these categories could be game changers in the same way that the technical achievements of the 20th Century have transformed modern life.

We could see revolutionary changes in transportation and energy; a transformation in medicine, with highly personalized diagnosis, treatment and prevention; and the visualization of huge data sets as explorable virtual worlds that allow engineers and scientists to walk inside crystals, examine the structure of atoms and molecules, or fly through the otherwise unreachable stretches of the cosmos.

The road to this remarkable technical future will be paved, in part, by research going on at UC Davis, where we have particular strengths in relevant fields. Here are some of the researchers who are engineering that future.

Inspired by Nature

Atul Parikh, a professor in the Department of Applied Science, describes himself and his research team as molecular engineers. Inspired by nature, they work to optimize specific functions of living cells by using molecules responsible for those functions. The goal is to create synthetic cells that can efficiently perform single tasks like sensing and binding to toxins or creating fuel. “Cells in biological systems have evolved to multitask,” Parikh said. “Because they are designed to do a lot of different things, they are not particularly efficient at any single thing.”

Parikh and his team focus on understanding the physical chemical phenomena that control the surface of a cell, with the goal of engineering synthetic pseudo-cells that can do one of those surface tasks very well. “Every biological cell is packaged in a lipid bilayer containing signaling molecules that regulate how that cell behaves,” Parikh said. “We take that little piece of the system and try to figure out how it functions so that we can either make an artificial version of it or incorporate it into artificial settings.”

Artificial therapeutic protocells could provide back-up for human cells that do not always recognize toxins in time to stop them, Parikh explained. “But engineered cells with only one job to do—bind to a specific toxin—could act faster and keep you healthy.”

Another goal is to design therapeutic cells that can reprogram diseased cells and change their behavior. “A classic example is macular degeneration, which is of interest to us,” Parikh said. “We want to be able to first understand how the retina pigment epithelial cells undergo premature death following certain assaults, like oxidative stress. We can then design therapeutic cells that can block the death.” Prohibiting this process could limit the vascular changes in the central retina that lead to degeneration and blindness.

“Artificial cells could provide back-up for human cells that do not always recognize toxins in time to stop them.”

In addition to health applications, engineered protocells could play an important role in finding solutions to our energy problems. They could potentially be used to exploit photosynthesis to generate fuel and electricity. Parikh’s group is currently investigating whether light-absorbing proteins can be incorporated into living cells to stimulate the production of fuel.

A promising focus of attention is cyanobacteria—the plentiful single-cell bacteria that have been part of Earth’s biosphere for more than 3.5 billion years, living and colonizing in water and manufacturing their own food. Cyanobacteria played a central role in the development of the earth’s atmosphere, steering the course of evolution and sourcing the origin of chlorophyll in plants. Colonies of these bacteria play numerous important roles in nature; agriculture relies upon them for nitrogen to grow crops like rice. However, nature has not designed them to produce fuel for our cars. This idea is now the focus of research.

Most interesting to Parikh’s team and other researchers is a waste product of these abundant, multitasking organisms. “Basically, they release hydrogen under certain environmental conditions,” Parikh said. “We aren’t interested in the other products they make; we just want them to maximize hydrogen.” The US Department of Energy (DOE) is interested in the potential of hydrogen as an energy source and has encouraged a wide range of research, including the development of biological sources of this colorless, odorless, non-toxic gas. So, Parikh’s group is collaborating with their National Laboratory partners to understand the hydrogen production machinery in cyanobacteria and possibly engineer the organism to efficiently generate hydrogen in quantities that are meaningful. As a fuel source, cyanobacteria would take up much less space than other botanical sources under consideration.

Parikh sees such reprogramming of cells using nature’s own methodology as a critical part of engineering’s future. “Biological systems use a limited number of components to perform many tasks,” he said. “What if we take that same set of building blocks and organize the constituents to make one organism that carries out one task, then reorganize the blocks into a different shape to carry out the next task? Following these cues from nature, we could think of designing materials that dynamically reconfigure, thus performing many sequential tasks over time,” Parikh said. “We are getting closer to being able to design systems that can repair themselves. Nature knows how to heal itself, memorize and reproduce, all without extreme conditions or fancy engineering equipment. I think this is where engineering is going.”

Making Medicine Personal

Parikh and his team are also interested in using what they discover about biological machinery and engineered cells to develop biology-based sensor technology, with the ultimate goal of personalizing medical diagnosis and therapy. They are among many other UC Davis researchers taking diverse paths towards this same goal.

Cristina Davis, assistant professor in the Department of Mechanical and Aeronautical Engineering, works on the design and implementation of non-invasive chemical and biological sensor systems that can detect minute traces of chemicals in complicated environments or in clinical samples such as blood, urine or even breath. These sensors are designed to catch chemicals that previously were below known limits of detection.

“For example, in addition to exhaling carbon dioxide, we also exhale thousands of other chemicals,” Davis said. “These are little physiological markers that can give us information about what is going on inside our bodies.” Diabetics in a metabolic state called ketoacidosis have so much acetone in their blood that you can actually smell its fruity odor on their breath. However, there are many other conditions in which biomarkers or small molecules are at such low levels that they are undetectable. “We are just beginning to figure out that they are associated with diseases,” she said. “If you have information about an environment or the contents of a clinical sample, then you can decide what to do with that information. But without that information, we are kind of shooting from the hip; we don’t have all the knowledge we need to make the best decisions.”

Similarly, medical therapies are still something of a shot in the dark, said Angelique Louie, a professor in the Department of Biomedical Engineering. “Because disease affects each individual in a unique way, each individual’s response to therapy is unique,” she said. Therapeutics still involve a fair amount of trial and error, while nearly any drug has side effects and can weaken normal systems, as in the collateral damage cancer treatment does to fast growing hair and skin cells. “Wouldn’t it be nice to reduce these effects by targeting more effectively?” she asked.

Louie’s lab focuses on developing imaging agents to show where in the body specific molecular markers are being expressed, helping to guide diagnosis and therapy. For example, she and her team have developed an agent that targets macrophages, scavenger cells that accumulate on the walls of a blood vessel when it is inflamed or has a plaque, one of the early warning signs of heart disease.

“Macrophages do not normally accumulate on the walls of blood vessels,” Louie said. “But it’s thought that they are drawn particularly to vulnerable plaques, the ones that are more likely to break apart and cause a heart attack or stroke.” Currently there is no way to determine the instability of a plaque, hence the work Louie and her team are doing. “If we could use imaging to look at these plaques and determine the number of macrophages present, physicians could use that information to stabilize the plaque.”

Louie’s research, like Davis’s, is a little ahead of the game, though. Cardiologists have not developed a solution to the problem of unstable plaques, although drug-delivering stents might be a possibility; and sensors like Davis’s are revealing chemical markers whose relationships to disease are not well understood. “But knowledge in both directions pushes advances,” Davis said. In this way, engineering will continue to play a critical role in the interdisciplinary model that difficult problems require.

“…why some people get sick and some do not…It’s obviously not completely dictated by the genome. I expect technology to answer that question.”

Looking years into the future, Louie said, the goal is to truly personalize medicine. This is the focus of her work, developing agents that could visualize disease markers, bond with the drugs that target diseased cells and reflect whether the drug is working or not. “For example, there are cancers that are difficult to diagnose in the early stages when a cure is more likely,” she said. “I hope that this technology can aid in early diagnosis, finding what treatment works best and determining the dosage appropriate for each unique individual. It sounds a little like something out of Star Trek right now, but we’ll get there someday.”

Davis agrees, anticipating that in the very far future, technology will enable doctors to give patients personalized diagnosis and treatment in the office while they wait. She points to the huge advances in mapping the human genome as inspiration. “In the past 15 years, novel instrumentation allowed us to do really rapid sequencing and to splice together all that information into a giant road map of the genes.” The challenge now is to understand how this information maps to health and disease. “Telling us why some people get sick and some do not,” Davis said. “It’s obviously not completely dictated by the genome. I expect technology to answer that question.”

Davis also believes that engineering will play a critical role in rapid response to emerging infectious diseases. Sensors, information networks, data repositories and intelligent algorithms can make possible rapid identification and response, vaccine development and targeted therapies. “The biosciences will play a huge role in this future, but engineers can provide screening platforms to test different approaches. We have a lot of work to do.”

Navigating Immense Oceans of Data

“We are in the midst of an amazing technical revolution, particularly in the life sciences,” said Bernd Hamann, professor of computer science and associate vice chancellor for research in the UC Davis Office of Research. “Researchers are producing peta-, tera- and exa-scale data sets, big numbers; we cannot even conceive what these numbers mean,” he said. In fact, the world is swamped with digital information. “The problem is what to do with it all.” The situation poses intriguing challenges and opportunities for computer scientists who must develop ways to analyze, visualize and interact with these oceans of information.

“In fact, I think we have passed the break-even point,” Hamann said. “We are producing more data than the human mind can process in any meaningful way.”

“Someday we will be able to model the human cognitive process and design computer systems that can do this just as well.”

However, engineers like Hamann are devising ways to transform information into computer graphics that reveal patterns and relationships. “But we have gone beyond that,” Hamann said. “We have created interactive real-time visualization systems that take the fullest advantage of the human visual system to comprehend complicated structures in three dimensions.” The Division of Mathematics and Physical Sciences, in collaboration with the College of Engineering, has developed the Keck CAVES (Center for Active Visualization in the Earth Sciences), a room-sized virtual environment that allows human beings to immerse themselves in a three-dimensional crystal, for example, zooming in and out, up and down, examining atoms and molecular bonds. Hamann is a lead researcher for the Keck CAVES team that is directed by geology professor Louise Kellogg.

“We certainly already have very good statistical methods and automated data analysis systems,” Hamann said. “But this state-of-the-art technology takes advantage of the fact that the human visual system is still the best way to pick out the most interesting parts of three-dimensional data sets.” The Keck CAVES experience also will expand understanding of how the human brain and eyes process information. “Someday we will be able to model the human cognitive process and design computer systems that can do this just as well. But we are far, far away from that.”

In fact, data visualization itself is still a relatively new discipline, said computer science professor Kwan-Liu Ma. It builds upon knowledge from several areas of study, including computer science, signal processing, statistics, visual perception, art and others. “I see this as the future of engineering research and education. We must cross over the boundaries of disciplines,” Ma said. “Something the College already does very well.”

Data visualization can manifest complex relationships and processes, reduce search time and memory load, and allow perceptual inference, Ma said. “In the context of scientific discovery, these pictures enable scientists to not only validate their hypothesis but also see the previously unseen.”

Ma and his team also strive to optimize the user interface in visualization so that scientists can concentrate on data exploration and interpretation rather than on the interface itself. And they design visual interfaces that support collaborative analysis and reasoning so it is easier to share knowledge and increase productivity.

In the end, Ma sees the visualization work he does as something that also could change daily life. He envisions a future in which we are more mobile, while being connected to information. “Our lives will follow information flow,” he said. “I am very excited about how my visualization research can enhance people’s ability to extract knowledge from vast amounts of information for making critical decisions in their businesses, their social lives and their personal pursuits. A picture really is worth a thousand words,” Ma said.