Dr. Mueller, Biochemistry and Biophysics

Dr. Paul H. Mueller, former research professor of biochemistry and biophysics in the Perelman School of Medicine, passed away December 16, 2012, at the age of 89.

Dr. Mueller was born in Heinsberg, Germany and earned his medical degree from the University of Bonn, in Germany in 1951. He came to the United States in 1953 on a Fulbright Fellowship to work with Lorente De No at The Rockefeller Institute (now The Rockefeller University), in New York.

Following the fellowship, Dr. Mueller served as a lecturer at the University of Cologne, in Germany. In 1957, he joined a group of researchers at the Eastern Pennsylvania Psychiatric Institute in Philadelphia. In 1974, he joined the department of biochemistry and biophysics at the University of Pennsylvania as an adjunct professor and became a research professor in 1981. He left Penn in 1992.

Dr. Mueller was one of the pioneers of the field of lipid bilayers, as well as neuromorphic engineering, bioinspired smart electronics and biomimetic systems.

Although Alan Lloyd Hodgkin and Andrew Huxley had developed mathematical equations to model a nerve action potential in their Nobel-awarded work, the biological meaning of the capacitance term was not understood. Dr. Mueller and his colleague Dr. Donald Rudin successfully made synthetic phospholipid bilayer membranes (BLMs or black lipid membranes), in 1963 with a capacitance that was similar to that of nerve membranes. Follow up work doping one side of the bilayer (BLM) with proteins resulted in a cation conductance similar to that of the ion selective channels of nerve membranes. Further, the conductance was voltage dependent and, in combination with protamine, could give rise to full-blown action potentials. The consecutive search for molecules that would open the bilayer to ion permeation led to many discoveries including the cation carriers valinomycin, nonactin, the entiatins A and B, and the channel-forming gramicidins (A, B and C). Planar lipid bilayers have become a major research tool for studying ion-conducting channels, vesicle membrane fusion and reconstitution of biological channels and transporters. It was the early seminal results of Dr. Mueller that laid the foundation for many subsequent biological discoveries.

Dr. Mueller's BLM work first demonstrated the construction of elements of biological neurons that could replicate the function of electronic devices, such as tunneling diodes and circuits. These were the first neuromorphic devices developed in the laboratory and may have been the spark that led Dr. Mead to study the relationship between ion dynamics in neurons and electron dynamics in integrated complementary metal-oxide-semiconductor (CMOS) transistors.

Since the late 1980s, a new field of research called neuromorphic engineering, i.e. the physical emulation of neuro-biological principles with modern computational tools, has been growing around the world. It was the early work of Dr. Mueller in the late 1950s and 1960s that planted the seeds for this field and inspired significant discoveries from others. Dr. Mueller exchanged ideas with Dr. Carver Mead of Caltech at The Rockefeller University, and they discussed the potential of using the then-nascent integrated electronics devices to mimic computational functions of the nervous system. Dr. Mead became one of the key players in integrated electronics design and manufacture, even coining the term "Moore's Law," and made integrated electronics ubiquitously accessible by the late 1980s. At the same time, he also invented the term "neuromorphic engineering." These advances would not have been possible without the inspiration and early work of Dr. Mueller.

In the 1970s, he developed one of the first electronic models of a neuron, realized using state-of-the-art integrated electronics components. In the 1980s, the convergence of his interest with the aforementioned development of integrated circuits technology, called Very Large Scale Integration (VLSI), led to a collaboration with Dr. Jan van der Spiegel, professor of electrical and systems engineering in the School of Engineering & Applied Science, which resulted in the creation of the first fully reconfigurable large-scale neural computer in VLSI. This neural computer consisted of hundreds of chips, similar to microprocessor chips but mimicking the analog computational properties of their biological counterparts that modeled neurons, synapses and axons. This work, funded by the Office of Naval Research, led to the formation of Corticon, Inc., which developed other neuromorphic systems for vision, audition and neural information processing in the 1990s and into the 2000s. Importantly, Dr. Mueller's collaborations with engineering faculty at numerous institutions inspired a new generation of leaders.