In bioscience and biotechnology there exist, depending on perspective, different schools of thought concerned with biological processes at different length scales — molecular biology, genetics, and cell biology. Given that biological machines operate in the non-equilibrium state, irrespective of perspective we have to understand how the pieces are made, how their physical forces exert control, and how feedback and feedforward of elements allow for robustness and function. New frontiers of research are now directed toward the observation of phenomena as they occur in space and time; in the language of biology, visualization. With the power of molecular and genetic tools we should be able to visualize molecular motions, understand physical phenomena, and develop new concepts for specific control and global function, or so-called emergence. Studies at this level of the physics and chemistry of biology define the physical forces involved in biological complexity and constitute the foundation of physical biology. I believe that physical biology as a new discipline should aim at understanding mechanistically how physical forces and interactions govern biological function, from the molecular to the cellular scale. In physical biology, this focus on structure and dynamics is distinct from the aim of mapping the engineering of information and its flow, the wiring in cells, and without visualization, structure and dynamics remain dark and elusive.

At Caltech, the main mission of the newly-established Physical Biology Center for Ultrafast Science and Technology (UST) is to develop the science and technology for observing complex molecular structures in motion using diffraction, spectroscopy, and microscopy. Such combined atomic-scale resolutions in space and time constitute the basis for a new field of study in what we refer to as four-dimensional (4D) structural dynamics. For imaging in real time the method of choice at Caltech is 4D ultrafast electron microscopy and diffraction developed recently to provide the ability to image complex structures with the spatial resolution of electron microscopy, but with timed (femtosecond) single-electron packets. The vision is a new integrated science of structure and dynamics with the aim of deciphering the fundamental physics of chemical and biological behavior, from atoms to cells. Faculty from the fields of physics, chemistry, and biology form the core for the collaborative research at UST, the founding center of physical biology at Caltech.

Ahmed Zewail