Interaction

Winter 2007

Quantifying the body

Courtesy Chand John, Frank C. Anderson and Scott Delp

Biomechanics researchers are using simulations of gait to quantify how individual muscles contribute to an observed movement.

“Bringing it together” is a phrase often used by the people in charge of Simbios (Simulation of Biological Structures), one of Stanford’s two centers for biomedical computation funded by the National Institutes of Health (NIH). Their goal is to bring quantitative and life sciences together; specifically, to use physical and mathematical modeling to create computerized simulations of biological structures and functions.

Those are two pretty different worlds. One of Simbios’ two principal investigators, Russ Altman, says readily that “being at the Clark Center was critical to making this happen.” The fact that computer scientists and geneticists and engineers and biologists were all in the same space—the James H. Clark Center, home to Bio-X and the Department of Bioengineering—made grant-writing and, later, research possible, he said.

Scott Delp, Simbios’ co-PI agreed, adding, “The strength we have in biology, mechanics and computer science makes interdisciplinary science work.”

Jeanette Schmidt

“Simbios is truly interdisciplinary,” said executive director Jeanette Schmidt. “It doesn’t always come easy, defining which components of a biological problem can be tackled by computation. We really try to bring it all together though. The art is to find the place where computation is most useful and needed and might not be obvious.”

Schmidt said she, Altman and Delp inhabit that middle area on the spectrum between mathematics and biology.

“Scientists already are different creatures than they were 10 years ago,” she said. “They have to be trained in other disciplines. But it will always be critical to have biologists in their wet labs, people in the middle and people who are purely computational. You need all three for good interdisciplinary research.

“Not every biologist needs to be trained in computation,” she added. “But computation will infiltrate their labs one way or another. You can’t imagine a biology lab anymore without a computer.”

It was that necessary juxtaposition that inspired the National Institutes of Health in 2004 to begin funding the biomedical computation centers under its Roadmap Initiative. Simbios was among the first batch of four; a second group of three came later, including Stanford’s National Center for Biomedical Ontology.

Simbios’ specific mission falls under the NIH’s “New Pathways to Discovery” theme, aimed at building a better toolbox. It includes bioinformatics, computational biology, imaging, structural biology and nanomedicine. At Simbios, the computational focus is on simulation of structural motions; at other NIH centers computation might mean simulating the immune system or a pandemic or making sense of vast amounts of data derived from complex experiments.

Russ Altman

Chand John, a doctoral student in computer science, started off in computer graphics, but two years ago he joined Delp’s lab to work on neuromuscular biomechanics. John’s objective is to create algorithms to enable simulations of human movement so that doctors can better assess problems and medical solutions.

“The ultimate achievement,” he said, “would be if a surgeon could record the motion of a patient with a movement disorder, use our software to determine what muscles are misbehaving in that patient, simulate how different surgeries would alter the patient’s movement and successfully decide which surgery would best improve that patient’s movement.”

Simbios’ principal contribution is an easy-to-use, open-source simulation toolkit, SimTK, which allows biomedical computation to be integrated across laboratories and disciplines. Until now, such software was being developed in a multitude of what amounted to cottage industries, and one was often incompatible with another.

Courtesy Simbios

All the NIH centers have a computational core, but “to keep the computation honest,” Schmidt said, they also must focus on specific biological problems that can be addressed by computation. In the case of Simbios, the four problems are neuromuscular dynamics, cardiovascular dynamics, myosin dynamics and RNA folding.

One of the bioengineering graduate students working on RNA structure prediction in Altman’s lab is Magda Jonikas, and she got there precisely because she saw it as a way of bringing it all together. She started off in protein and tissue engineering but missed the math. In Altman’s lab, using physics-based methods and informatics, she gets not only the math but the Simbios community as well.

“Working in Simbios has been a great experience so far, not just because I find the goals of the program interesting, but also because of the community of people,” she said.

Simbios’ home is the Department of Bioengineering, a pioneer in its own right, belonging to both the School of Engineering and the School of Medicine. Simbios depends on the department mostly for lodging and administrative support (its funding comes entirely from the NIH), but the proximity has certainly created good synergy, Altman said.

Scott Delp

Thinking back to the birth of the Bioengineering Department, Engineering Dean Jim Plummer shook his head.

“Three years ago, if you had asked, how can we make this work, we’d have put together a list of problems so long you couldn’t imagine it,” Plummer said. “It would have seemed unsolvable. But [Medical School Dean] Phil Pizzo and I said, we don’t know the answers, but we’ll solve them one by one. And we’ve worked on these problems, one by one, and there are solutions. It’s not rocket science.”

Rocket science appears to be one of the few things Altman, Delp and Schmidt do not have training in. Altman’s degrees are in biochemistry, medicine and medical information sciences, though he teaches in the departments of Genetics and Bioengineering. Schmidt has a PhD in computer science, is self-taught in biology and spent years at a major biotech company. While Delp’s degrees are in mechanical engineering, he was the first chair of Bioengineering. Today they all—along with colleagues in biology, computer science, mathematics, chemistry and a multitude of medical specialties, most obviously surgery—are essentially creating a new research arena.

One of the NIH mandates is that the centers disseminate their research. Simbios does so in stunning fashion with Biomedical Computation Review, a quarterly with the motto “Diverse disciplines, one community.”

A recent article in the journal reported that there are now some 60 undergraduate, graduate and certificate programs in the United States offering some version of biomedical computing, with training in both computation and life sciences.

As the field matures, central questions will be how to train and teach a field that is a composite, and how to deal with the spectrum of disciplines.

Courtesy Simbios

Images of slices of the abdominal aorta under varying degrees of stress due to exercise.

Referring to the familiar Stanford d.school metaphor of the T-shaped scholar (with horizontal breadth and vertical depth), Delp said the Bioengineering Department thus far has concentrated on breadth. As new courses are developed (a process that entails a good deal of hard work and modesty, Delp said, as not every field can be deemed essential core material), the vertical will gain in importance.

“We can bring math and theory to biology precisely because we have such disciplinary strengths at Stanford,” Altman said. “The departments are the underpinning of Simbios. And Clark was the most important thing.”

As for the disciplinary spectrum at places such as Simbios, John provides a geometric correction.

“It’s much more than a spectrum,” he said. “I think of it as a tetrahedron, a pyramid with a triangle as its base. The three vertices of the base triangle represent life sciences, mathematics and computation. The fourth vertex, which lies above the triangle, represents generality.”