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Living State Physics History

Research into the physics of living systems can be said to have begun at Vanderbilt with Max Delbrück, who was a member of the Physics Department faculty from 1940 to 1947. It was then that he and his group conducted fundamental studies that provided the foundation for modern molecular biology. 

By the early 1960s, the Physics Department had established a few faculty positions in the area of biological physics, which were held by Otto Blüh, Robert Lagemann, and Galen Lenhert, and Lagemann administered a training grant in biophysics at this time. Joint appointments with members of the School of Medicine provided expertise in radiology and radiological sciences, medical physics, and nuclear medicine, a practice that continues today.>> 

In 1977, John Wikswo joined the department, fresh from graduate and postdoctoral work studying the cardiac magnetic field at Stanford University in the Division of Cardiology and the physics laboratory of William Fairbank. His goal was to build a program in the measurement of biological magnetic fields and make the first measurement of the magnetic field of an isolated nerve, which, along with John Barach and John Freeman, was accomplished by 1980. More than a dozen years of support by the Office of Naval Research, the NIH, and the Veterans Administration led to the first measurements of the magnetic field of a single nerve axon and other studies that provided, for the first time, a firm biophysical foundation for the production and detection of the magnetoencephalogram and other biomagnetic signals. 

By the late 1980s, Wikswo had recognized that the holy grail of biomagnetic measurements, biological activity that was detectable magnetically but was electrically silent, would be hard to find in one-dimensional systems. He was the first to recognize that usually ignored differences in the electrical anisotropy between the intracellular and extracellular spaces of a sheet of cardiac tissue would lead to just such a situation. It was necessary to devise a new class of Superconducting Quantum Interference Device (SQUID) magnetometers that had the spatial resolution and sensitivity required to detect these fields and raise the $300,000 to get the instrument built; by 1991 the Wikswo group had found the desired field pattern and devised magnetic imaging algorithms that have become the gold standard in the field. Recognizing that the same instrumentation, scanning stages, and analysis algorithms could detect flaws in metals and plastics, they mounted a 10-year program that was funded by the Air Force Office of Scientific Research (AFOSR), private industry, and the German government. This work evolved into an AFOSR-sponsored initiative and produced the only technique yet known that can measure the instantaneous rate of corrosion occurring inside an aging aircraft lap joint. This work in turn attracted long-term support from the Air Force. In the course of these investigations, it was found that the mathematical models of electrically and magnetically silent fields applied not only to cardiac muscle but also riveted aluminum. 

Meanwhile, with colleagues in the Medical Center, Wikswo had begun to measure cardiac conduction velocity during ischemia and infarct and in the presence of antiarrhythmic drugs. During one of these experiments, he recognized the existence of virtual cathodes in cardiac tissue, which happened to be related to the same anisotropy differences that produced the magic magnetic fields. The cardiac community paid little notice until Wikswo and his collaborators showed that these anisotropy differences and associated virtual cathodes and anodes could explain an old puzzle in cardiac electrophysiology, produce a previously unrecognized form of cardiac reentrant activation, and provide key mechanisms for understanding the success or failure of cardiac defibrillation. This work also led the investigations into the nonlinear dynamics of cardiac stimulation. 

The continuing exploration of biomagnetic measurements picked up another first, the magnetic field of intestinal smooth muscle, which has spawned a large, well-funded and productive collaboration with Bill Richards and Alan Bradshaw that is developing SQUID measurements into the first noninvasive clinical tool for the diagnosis of acute mesenteric ischemia and other gastrointestinal disorders. 

In the quest for the higher spatial resolution SQUIDs, Franz Baudenbacher was recruited to lead an NSF- and NIH-funded project that has produced the world's best SQUID microscope and used it in an experiment, in collaboration with a geobiology group at Caltech, to characterize the thermal history of a Martian meteorite from its magnetic signature and show that material could be transported from Mars to earth without sterilization. This NanoSQUID has the potential to revolutionize the magnetic measurement of geophysical samples, and it successfully recorded beautiful data of the electrically silent magnetic fields of currents propagating through cardiac tissue, made possible by productive excursions into geophysics and NDE! 

In 2000, Wikswo and his colleagues designed and launched a major initiative to "Instrument and Control a Single Cell." A $5 million grant from Vanderbilt created the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) as the springboard. VIIBRE’s mission – to invent the tools and develop the skills that are required to understand biological systems across spatiotemporal scales – is being carried out in a wide range of systems biology projects that aim to determine how cells react to chemical and biological weapons, how best to specify dynamic metabolic and signaling pathways, why cancer cells crawl in response to chemical gradients and endothelial cells form capillaries, how T cells are activated and their signaling pathways can be studied, and how to accelerate wound healing and contemplate why mammalian limbs don't regenerate. Wikswo has assembled a cadre of high school, undergraduate and graduate students, postdocs, faculty, and staff to explore the interface of physics, chemistry, engineering, biology and medicine. VIIBRE researchers have established microfabrication and microfluidics facilities and training unique at Vanderbilt, and created new devices for the study of cellular metabolic dynamics and signaling, chemotaxis and haptotaxis, development, angiogenesis, and cancer growth and metastasis. 

In 2003, Shane Hutson joined the Physics faculty. He holds a secondary appointment in the Department of Biological Sciences and is a Faculty Fellow of VIIBRE. His research in biophotonics is currently investigating the physical mechanisms underlying laser tissue ablation, both with mid-IR free electron lasers (FELs) and table-top UV lasers; using laser-microsurgery to probe the inter- and intra-cellular forces that drive morphogenesis (i.e., the development of an organism's form); and using genetics, laser-microsurgery and quantitative modeling to integrate the genetic and mechanical aspects of embryonic wound healing.

The VIIBRE web site picks up from here.