Paul Christian Lauterbur, cowinner with Peter Mansfield of the 2003 Nobel Prize in Physiology or Medicine for their independently developed nuclear magnetic resonance (NMR) imaging methods, died of kidney disease on 27 March 2007 at his home in Urbana, Illinois. His conception and early development of magnetic resonance imaging led to the MRI techniques now used an estimated 15 million times each year for medical diagnosis and for fundamental research ranging from studies of brain function to elucidation of solid-state structures.
Paul was born in Sidney, Ohio, on 6 May 1929 and received his BS in chemistry at the Case Institute of Technology in 1951. He was responsible for many innovative advances in physics and chemistry; his conception of MRI was only one of his accomplishments. Following an early interest in a possible biology based on silicon, he took a job at the Mellon Institute in Pittsburgh, Pennsylvania, with a group supported by Dow Corning to synthesize and test organosilicon compounds and polymers. His research there led him to learn about NMR, which was just beginning to be used in chemistry—an application that was developed further at the Army Chemical Center, where he was assigned during the Korean War.
After military service he returned to Mellon and persuaded the Dow Corning group to purchase an NMR spectrometer to study silicon-29. Despite the low NMR sensitivity and low natural abundance of the isotope, Paul published 29Si NMR spectra in 1956 and soon recognized that carbon-13 NMR would be even more interesting but also more difficult experimentally. Nevertheless, in 1957 he published the first study of 13C NMR in more than 100 compounds. In 1958 he followed with the first NMR spectra of compounds containing tin-119.
Paul was widely known and respected in the NMR community for these innovative studies long before he took the time to get his PhD in 1962 at the University of Pittsburgh. His thesis covered applications of 13C NMR to studies of the electronic structures of molecules. In 1963 Paul accepted a faculty position at the new State University of New York at Stony Brook. He measured chemical shift anisotropies in single crystals and studied 13C-labeled proteins and hydrogen-3-labeled steroids while developing increasing interest in biological applications of NMR.
Paul’s research changed dramatically as a result of spending part of the summer of 1971 at NMR Specialties, a small company near Pittsburgh that manufactured a pulsed NMR spectrometer and invited potential customers to use its facilities. Paul observed an interesting experiment being done by Leon Saryan, a postdoctoral fellow from Don Hollis’s group at the Johns Hopkins University. Saryan was trying to duplicate and extend work recently published by Raymond Damadian, who had found in tissues excised from rats significant differences in the 1H NMR relaxation times in normal tissue and implanted tumors. Paul reasoned that the information being obtained probably existed in the living animal and might be studied by NMR—if only one could localize the results rather than averaging them over the entire animal. As Paul said in his article in the Encyclopedia of Nuclear Magnetic Resonance (Wiley, 1996), “That same evening I realized that inhomogeneous magnetic fields labeled signals according to their spatial coordinates, and made a leap of faith to the conclusion that the information could be recovered in the form of pictures.” From long experience operating NMR spectrometers, he realized that the gradient controls normally used to optimize the homogeneity of the magnetic field for a small chemical sample could deliberately be mis-set in a controlled manner to generate linear field gradients along each orthogonal axis. The data could then be back-projected to generate an image. He also calculated that the signal-to-noise ratio from a small volume in a large object would be adequate for reasonable measuring times. Paul went on to say, “I had confidence that whatever physics allowed, engineers could achieve.”
After failing to convince various people and institutions that this idea was good enough to patent, Paul did an experiment with a commercial NMR spectrometer at Stony Brook in 1972, using two capillary tubes of water and demonstrating clearly that the idea worked. His seminal paper was published in Nature in 1973 (volume 242, page 190). The incentive for his work was the biological application, but typical of his fundamental approach to problems and his appreciation of the basic physics, he focused initially on the anomaly of resolving 1-mm features with an RF wavelength of 5 m (foreshadowing later developments in near-field microscopy). Paul pointed out that his NMR experiment succeeded because of the coupling of the static magnetic field to the RF field. He described this new technique as “zeugmato-graphic” imaging, from the Greek word zeugma, “joining.”
This first paper went on to forecast boldly a broad range of potential applications, all of which have now been achieved: pictures of distribution of stable isotopes within an object; images dependent on NMR relaxation times; images of organisms that show soft structures and tissues; in vivo study of malignant tumors based on relaxation times; images displaying chemical compositions or diffusion constants; NMR zeugmatography of solids; electron spin resonance zeugmatography; and internal structures, states, and compositions of microscopic objects. In fact, Paul soon demonstrated many of these applications, including the first image of a living animal (a 4-mm-diameter clam), use of paramagnetic contrast agents, and chemical-shift imaging.
Paul made many further advances in NMR imaging at Stony Brook and at the University of Illinois at Urbana-Champaign, where he moved in 1985. During the past few years, Paul returned to his early interest in the origin of life—this time not in a hypothetical silicon-based biology but in the real world of organic carbon compounds. He described the potential role of molecular imprints and the ways that free-energy-driven processes can lead to molecular evolution.
A book could be written about Paul’s curiosity-driven research, his innovative approach to problems, and his many accomplishments only hinted at here. Those of us who knew him as a valued and warm colleague, the next generation of scientists who were inspired by his brilliance and enthusiasm, and the millions who have benefited from the application of his work in medicine are fortunate that Paul Lauterbur passed our way.
