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Engineering Solutions to Biomedical Problems

Jose Contreras-Vidal (Credit: John T. Consoli/University of Maryland)

Biomedical engineering plays a crucial role in translational research, and degree programs in the discipline are now offered at universities around the world. (See, for example, the June Science Careers article "Designing a Career in Biomedical Engineering.") At the same time, many classically trained engineers are working at the interface of engineering and medicine. Science Careers spoke to five such scientists whose work involves engineering solutions to human health problems.

"Engineers are not going to replace biologists, nor should we try to. ... The value of having engineers in medicine is that we're trained in a different way and approach problems in a different way." -- Marc Levenston

Applied fluid dynamics

Some engineers use computer models to test new designs of airplane wings or engines. Alison Marsden applies them to children's hearts.

Normally, the heart's right ventricle pumps blood to the lungs and the left ventricle pumps oxygenated blood throughout the body. In children with single ventricle defects, only one of these pumps is functioning. Marsden's team has developed a variation of the common surgical treatment for this defect, called Fontan reconstruction, that they believe will improve patient outcomes. Their research uses MRIs from patients to create computer models that help surgeons decide between the traditional surgery and their variation. The models also help surgeons determine where to disconnect and reconnect blood vessels and the optimal angles of connection.

Alison Marsden

Marsden, an assistant professor of mechanical and aerospace engineering at the University of California (UC), San Diego, is creating similar models for other heart conditions, including Kawasaki disease and coronary artery bypass grafting. The models would allow cardiologists and surgeons to tailor surgery for each patient based on individual anatomy, blood-flow patterns, and other factors. "We want to be able to customize surgery like you would customize dental implants or an orthopedic device," she says.

The application of fluid dynamics -- or any other engineering discipline -- to medicine wasn't on Marsden's radar until late in her education. Her father, a mathematician, gave her math workbooks that he had devised. Her mother, an avid hiker and photographer, signed her up for science workshops. She gravitated toward mechanical engineering, earning an undergraduate degree at Princeton University and a master's degree and Ph.D. at Stanford University.

"After my Ph.D., I was trying to decide what to do next," she says. "I enjoyed the work I had done but was looking for something more people-related." A conversation with Stanford's Charles A. Taylor led to a postdoctoral stint in his lab, the Cardiovascular Biomechanics Laboratory in the Department of Bioengineering. "We realized I could apply tools I had to some of the projects ongoing in his lab."

Although she had no formal training in biology or medicine, Marsden, now 34, found it easy to pick up medical terminology and concepts. "If I had known earlier on that I was going to get into biomedical engineering, I may have taken some formal courses," she says. "But I found it was easier to pick up the medical terminology than it would have been the other way around -- to suddenly have to understand partial differential equations, for example."

The interdisciplinary nature of her work requires good communication skills and good organizational skills. "You need to communicate with people from many different areas," she says. "You have to explain your work to someone outside your field, such as a cardiologist. Sometimes I have to walk into a room and talk to a patient's family about joining a research study."

Marsden sees biomedical engineering and other interdisciplinary sciences as hot spots for young women. "I think women sometimes get scared away from traditional, focused engineering fields, but they often have skills that are very applicable to fields like bioengineering," she says. "You may end up managing a team of people, all with different backgrounds, and you have to relate to all of them in some way. I think women can really shine at that."

From airplane structure to cell mechanics

Stephanie Pulford, 31, can pinpoint the moment biomedical engineering entered her life. While working as an aircraft structural engineer for US Airways, she began reading about bones and how mechanical stress affects their form and function. "You can see that bones form load-bearing structures that line up with the direction of maximum stress," she says. She became fascinated with the similarities between these structures and structures that humans had engineered for their own use.

That interest led her to the graduate program in mechanical and aerospace engineering at UC Davis, where she is a fourth-year doctoral student. Pulford studies the mechanics of how cells move, in the lab of Alex Mogilner. "I used to take cell movement for granted, but it's very complicated," she says. "A cell grabs and pulls and drags and adjusts itself to its surroundings. It's very much a structural process. There's a lot that engineering has to offer."

Pulford treats the cell as a black box, gathering observations from the outside. What forces does a cell put on its environment? What shape does it take? "Then I take an educated guess about what the cell might be doing internally and I write a computer model to simulate it," she says. "I can test a lot of hypotheses, knock out the ones that don't work, and see if my models can predict movement."

Because she came to UC Davis with an undergraduate degree that was "straight-up engineering," Pulford took classes and attended seminars to strengthen her background in biology. In her second year, Pulford was one of seven scholars in UC Davis' Integrating Medicine into Basic Science program. The Howard Hughes Medical Institute (HHMI) sponsors 23 of these so-called Med into Grad programs nationwide, designed to introduce biomedical engineering graduate students to clinical medicine.

The program showed her the importance of collaboration and partnership in biology, medicine, and engineering, she says. "I was constantly exposed to new modes of thought, and new problems for engineering to solve. I'd certainly been interested in interdisciplinary work before the HHMI program, but the program gave me a great opportunity to see just how well that kind of scientific cross-pollination works."

Making it work, Pulford says, requires communication skills. "Within engineering there's a lexicon, a way of talking about things, and within medical fields you speak a language, too. You need to be able not only to get information but also describe your research in a useful way to people in other fields. You have to be a translator as well as a researcher."

Putting the "bio" in biomechanics

As an undergraduate student in mechanical engineering at the University of Florida, Marc Levenston was intrigued by biomedical engineering but had only a basic biology background. His Ph.D. research at Stanford focused on computer simulations of how mechanical stresses affect bone growth and adaptive changes around implants. He was doing biomechanics but "with a little 'b' and a big 'M'," he says. Wanting to pursue more experimental research, he headed to the Massachusetts Institute of Technology for a postdoc to join a lab of engineers who focused on cell and tissue culture experiments.

Marc Levenston

At Stanford University's Mechanical Engineering Department, where he is now an associate professor, Levenston, 44, emphasizes the bio side of biomechanics. One of his project areas involves cartilage in the human knee, elucidating the series of events that lead to osteoarthritis. Using tissue culture models of cartilage and the meniscus, Levenston's team stresses the cells and tissues and studies what happens to them structurally and biochemically -- for example, whether different genes are expressed, whether metabolism changes, or whether different types of cartilage cells respond differently to the same stress.

One aim of this work is to find ways to detect the disease at its earliest stages, even before symptoms start. "People study osteoarthritis as a disease of cartilage," Levenston says. "But does it start in the cartilage or elsewhere in the joint?"

Another of Levenston's projects examines how cells' physical and mechanical environment drives the fate of certain types of adult stem cells. "We put them in a 3D environment where we can compress or stretch them, simulating the regional mechanics of what happens in the body," Levenston explains. "Then we see how that interacts with biochemical cues. ... Can the mechanical environment influence what the cell becomes?"

If mechanical stresses can influence cell fate -- and Levenston's research is showing that it can -- then one day it may be possible to use these biomechanical manipulations to engineer cartilage, ligament, or muscle. This type of research could also help tissues heal themselves. "Sometimes healing doesn't happen the way we want it to," he says. "This research has applications for how to encourage normal healing."

Despite his firm presence in the world of biology, Levenston still defines himself as an engineer. "I'm not a biologist, but I'm using tools of biologists to probe a mechanical system," he says. "Engineers are not going to replace biologists, nor should we try to."

For classically trained engineers, Levenston's advice is to be open to possibilities outside your field. "You should be willing to consider areas of research you've never thought of, which would require skills you'd never thought of," he says. "The value of having engineers in medicine is that we're trained in a different way and approach problems in a different way."

The immune system: "A very complex chemical plant"

Yale University associate professor Tarek Fahmy gave up a Sunday afternoon last month to talk about his research to a room full of reporters. Fahmy, who worked as a chemical engineer at DuPont for 5 years before doing a Ph.D. in immunopathology, had just explained the complex relationship between the lymphatic system and the circulatory system when a reporter interrupted him.

"How much is chemical engineering a part of what you do?" the reporter asked. "It's all we do," Fahmy replied. The immune system "is all plumbing. It's all pumps and pipes and check valves. It's a very complex chemical plant."

Tarek Fahmy

Fahmy, 38, designs nanosystems that can interact with that chemical plant -- the immune system -- in different ways. For example, he's designing nanoparticles that bait specific immune system cells by displaying certain features on their surface; inside, the nanoparticles contain an antigen of a particular microbe. The nanoparticles provide a novel way to vaccinate people against a particular pathogen, such as, say, West Nile virus, without using the pathogen itself. For another project, his lab is creating nanosensors designed to detect whether the immune system is responding to a particular therapy.

Long before moving to Yale, Fahmy earned a bachelor's degree in chemical engineering at the University of Delaware. He landed a job at DuPont's Experimental Station doing research on polymers such as polytetrafluoroethylene (better known as Teflon). After a few years, DuPont transferred Fahmy to a manufacturing plant in Parkersburg, West Virginia. He was less interested in the work there and felt geographically isolated.

Around that time, Fahmy's father was diagnosed with lymphoma. Fahmy's training as an engineer left him ill-prepared to understand his father's disease: "I felt helpless really." Already interested in a job change, Fahmy began to look for graduate programs close to his family that would take on an engineer interested in immunology. He ended up in the molecular biophysics department at Johns Hopkins University in Baltimore, Maryland.

When the time came to start his Ph.D. research, he joined the lab of physician-scientist Jonathan Schneck, professor of pathology, medicine, and oncology at Johns Hopkins School of Medicine. "He was a clinician and knew quite a bit about a lot of things, and he was dealing with this engineer who thought differently and didn't see things the same way," Fahmy says.

They were able to find a common interest in studying the sensitivity of T cells, one of the key enforcers of the immune system. Activated T cells, which have been exposed to a particular antigen, are more sensitive and generate an immune response to that antigen more quickly and aggressively than naive T cells. Using modeling techniques he learned as an engineer, Fahmy worked out why: "It turns out that activated cells actually have clustered receptors and naive cells don't," he explains. "It's not a difference in the number of receptors, it's spatial orientation."

After finishing his Ph.D., Fahmy moved to Yale for a postdoc with W. Mark Saltzman in the then-new Department of Biomedical Engineering. But he didn't leave immunology: "The guys who wrote the textbooks were here. So I [thought], I know a little bit of immunology, I know a little bit of engineering, and I really want to talk about developing systems that can modulate antigen presentation or expand T cell populations in a specific direction. And I looked up and saw these people. It was a perfect fit."

Working in biomedical engineering requires calm and a propensity for planning, Fahmy says. "You've taken your field and multiplied it by two. Any kind of garbage can come out, anything that's good can get diluted," he says. "It's very important that we approach this interdisciplinary area with a lot of excitement, but I think it needs to be a kind of wise excitement and directed enthusiasm."

- Kate Travis

Studying the brain's electrical system

There used to be a widespread assumption that electroencephalography (EEG) could not be used to reliably record complex brain activity, such as that used in movement or thought, from outside the skull. Usually, physicians place electrodes directly on or inside the brain to record these subtle, complex brain waves. José "Pepe" Contreras-Vidal, an associate professor of kinesiology at the University of Maryland, College Park, questioned that assumption.

José Contreras-Vidal (Credit: John T. Consoli/University of Maryland)

As he worked on ways to extract complex neural signals from EEG readings, Contreras-Vidal discovered why it had never been done before. "People couldn't use EEG to reconstruct movement because they were looking for the information in the wrong place. They thought very high frequencies were needed, whereas we now know that changes in the amplitude of the EEG signals in the very low frequencies are the essential components."

His team found that the relationship between what an electrode can pick up inside the brain and what an EEG records outside the brain is fairly straightforward. They use formulas already well known to engineers to decode the external signal and identify what's going on inside.

These advances in external EEG have enabled Contreras-Vidal and his team to develop brain-computer interfaces for people with spinal cord injuries and degenerative nerve diseases. These interfaces pick up signals in the user's brain, bypass the damaged nerves, and allow the user to literally think his or her way through writing a letter on a computer screen or controlling a prosthetic hand.

Trained as an electrical engineer at the Instituto Tecnológico de Monterrey in Mexico, Contreras-Vidal's interest in the brain began at a young age in his native Mexico. "My mom died from a brain aneurysm when I was 21," he says. That left him curious about the human brain, an interest that took hold when he took a course on neural networks as a master's degree student at the University of Colorado, Boulder. "I thought, this" -- studying the complexity and capability of the brain -- "might be a place to use what I knew in engineering to open new avenues."

As a Ph.D. candidate in cognitive and neural systems at Boston University, he began developing large-scale models of the brain that could be used to understand neural mechanisms. A stint as a postdoc at Arizona State University sharpened his focus on movement disorders, particularly Parkinson's disease. "By then I was combining experimental work with engineering," he said. "It was a very productive environment."

Combining tools and concepts from several fields is a priority for Contreras-Vidal, now 46. He was drawn to the University of Maryland partly because its neuroscience program is a collaboration involving 11 departments. "Important things happen at the intersection of knowledge," he says. "I tell my students that if you specialize in an area, pay attention to related areas and see how best to apply them to your specialty."

This approach helped Contreras-Vidal upset the assumptions about EEG's capabilities. Applying engineering principles to biological questions is the essence of biomedical engineering, and Contreras-Vidal believes that classic engineering training is the best preparation. "There are principles in engineering that do not change, but neuroscience changes every day."

Contreras-Vidal says it comes back to asking why. "Question, push boundaries, come at the problem from a different perspective. I think engineering is a good field to encourage that."

Nancy Volkers is a science writer in Vermont.