The NMR community is mourning the passing of Ray Freeman on May 1, 2022. Ray was a pioneering force who introduced many modern NMR pulse sequences and multi-dimensional solution NMR techniques to the field of chemistry.
Growing up in Nottingham in central England, Ray received a prestigious Open Scholarship to study at Lincoln College, Oxford. Delayed by a two-year stint as a radar instructor in the Royal Air Force, he finally entered Oxford University in the fall of 1951. There, he worked with the legendary Rex Richards, gaining his Doctor of Philosophy degree for work on NMR detection of a wide range of nuclei, in particular 59Co. In 1957, he started post-doctoral work in the laboratory of Anatole Abragam, the renowned physicist and sole author of “Principles of Nuclear Magnetism”, a monograph that is often considered the “bible of magnetic resonance.” There, in Saclay, France, he worked under direct supervision of another NMR giant, Robert Pound, developing key innovations in field-frequency control that enabled the recording of high-resolution NMR spectra with greatly relaxed requirements for magnet stability. More importantly, he also met Anne-Marie Périnet-Marquet, and they married in 1958. After returning to the UK in 1959 with his bride, Ray worked as Senior Scientific Officer at the National Physical Laboratory, continuing work in magnetic resonance, most notably a method for measuring the relative signs of 1H-1H J couplings by double irradiation experiments.
Drawn by the technical innovations developed at Varian Associates in Palo Alto, California, Ray took a 1-year leave of absence to join the group of Wes(ton) Anderson. On multiple occasions he described to us, his students, sometimes in nostalgic terms, the passionate and innovative atmosphere of his time working with Wes, his associate Howard Hill, and others at Varian. What was intended to be a 1-year stint, turned into a 12-year stay. He received a USA permanent resident card, which he kept active by visiting the USA at least once a year after returning to Oxford University in 1973. There, he was appointed as Senior Lecturer at Magdalen College. His small research group in the Physical Chemistry Laboratory (the “PCL”) on South Parks Road was equipped with a single Varian CFT-20 spectrometer, an 80-MHz spectrometer but dedicated to 13C detection at 20-MHz. By today's standards the spectrometer was extremely primitive. It had a temperamental electromagnet, and used an early computer equipped with an impressive 32 kilobytes of memory, which was programmed directly in octal machine code (strings of digits from 0 to 7). Incredibly, Freeman's group managed to program many seminal experiments within this extremely cramped digital space, including sophisticated pulse programming and Fourier transformation, as well as a complete two-dimensional NMR system including the associated processing and plotting routines. A current mobile phone has approximately 1 million times more memory.
This work resulted in numerous innovations that greatly expanded the applications of NMR to chemistry. They included the DANTE sequence for selective excitation, methods for generating high resolution spectra in inhomogeneous magnetic fields and – in 1976, the first demonstrations of the power of double Fourier transformation in high-resolution NMR, correlating the frequencies of directly coupled 1H and 13C nuclei. This work built on the concept of 2D NMR, first introduced by Jean Jeener in 1973, and appeared very soon after the 1976 landmark paper by Richard Ernst and colleagues, also in the Journal of Chemical Physics, that discussed much of the mathematical basis of 2D NMR in very rigorous terms. Ray’s descriptions provided the perfect complement to Richard’s published work that – heavy on physics and mathematics – often proved difficult to digest for the chemistry community. Ray went through exceptional efforts to explain the new experiments in the clearest possible terms, generally relying on simple vector pictures of nuclear spins, and choosing applications that would prove of interest to practicing chemists. This highly visible work was acknowledged by his election to Fellow of the Royal Society in 1979.
In 1987, Ray moved to Cambridge University as John Humphrey Plummer Professor in Magnetic Resonance and was elected a Fellow of Jesus College. He was the President of ISMAR (1990-1992) and, next to numerous other honours, he received ISMAR’s most prestigious award, the ISMAR Prize, in 1998. Despite taking statutory retirement in 1999, Ray remained actively engaged in the NMR community for many years thereafter.
As students in his group in the late 70s, we had a first-row seat in witnessing and participating in the explosion of novel technology that has characterized the NMR field for now over 70 years. Ray played a pivotal role in laying the foundations of today’s NMR. Not only did he generate the excitement that greatly expanded the interest in NMR spectroscopy, he also mentored and trained the largest cohort of future academic leaders in NMR. Next to his scientific excellence, his unique mentoring style set him apart from many of his colleagues. He guided his group primarily by asking questions, requiring us to explain, prove, demonstrate ideas and concepts, thus steering us into directions he deemed important. This approach generated a sense of accomplishment and satisfaction for his students, of being excited when we could convince Ray of the relevance of whatever we had come up with. Although Ray had a very much hands-off approach to mentoring, he occasionally would wander into the spectrometer room and try to fine tune the shims on his newly acquired Varian XL-200 spectrometer, sometimes with disastrous consequences. Gareth Morris, who had returned as a post-doc to his group in 1979, solved this problem for us by installing a very large dial on the XL-200 front panel, not connected to anything on the inside, and marked in large lettering “Supervisor Fine Control”.
Next to his scientific genius, Ray’s work was amplified by being an outstanding communicator. Although to those who attended his presentations, this may have seemed effortless, he spent many weeks preparing and optimizing each of these. His exceptional sense of, often self-deprecating humor, his hand-drawn illustrations, and his uncanny ability to explain complex subjects in simple terms invariably made his presentation the center of NMR conferences, in particular the annual ENC, for several decades‡.
Of the numerous memories in Ray’s group, the lengthy daily discussions we had in the Tea Room of the PCL stand out. The entire PCL staff would gather there for tea or coffee, twice daily for ca 15 minutes. Invariably, Ray’s group overstayed our welcome by at least an hour before being chased out by Gladys, the cafeteria manager. Much of Ray’s mentoring took place during these meetings by simply asking questions and awakening our interest in what he considered to be the key limitations of what was possible by NMR. Solutions to practical problems, such as radiofrequency field inhomogeneity and composite pulse decoupling are prime examples. The latter was of particular interest to Ray. After Richard Ernst had introduced the benefits of “noise decoupling”, the requirements for high RF power with increasing magnetic field strengths became acute. The prevailing wisdom at that time was that decoupling could only be made more broadband by extending its frequency spectrum. Steered by his intuition, Ray wanted to get a more pictorial understanding of heteronuclear decoupling in the time domain, and proposed a technique involving a series of 180° pulses. Although this simple method was not effective, the idea of analyzing decoupling in the time domain instead of the frequency domain turned out to be the key insight, from which all else followed. Spurred by Ray's insight, the Freeman group developed composite pulse decoupling by deploying Average Hamiltonian Theory, a technique developed by John Waugh in the context of solid-state NMR. The cherry on the cake was that John Waugh had previously declared the problem of broadband decoupling to be insoluble. The intense rivalry and the rapid progress by the Freeman group stimulated John Waugh to develop his own approach. In back-to-back presentations at the ENC, John and Ray presented their solutions to the standing-room-only crowd at the overfilled Asilomar lecture hall. If there were any tensions between Ray and John prior to that meeting, these were fully resolved when each gained a full appreciation of the alternate solution described by their counterpart.
Two more notable innovations around this time were the development of the INEPT and INADEQUATE pulse sequences. The INADEQUATE experiment was the most popular and visible application of the new science of multiple-quantum NMR. The INEPT pulse sequence is now an essential building block of an enormous number of high-resolution NMR techniques, so much so that the original meaning of the English word INEPT (incapable, clumsy) has been effectively superseded by its technical meaning, at least among the NMR community. This illustrates another lasting legacy of Ray Freeman: the use of acronyms. The ideal acronym should describe the experiment without too many linguistic contortions, while also being amusing or self-deprecating. Much time was spent thinking of excellent acronyms, in some cases for experiments that did not exist yet!
One of us (M.H.L.) can testify to the mixture of frustration and admiration that Ray's work engendered in Richard Ernst. Richard knew that he had a deeper theoretical mastery than Ray, but he also knew that he could never match Ray's humour and powers of communication.
The innovations introduced by Ray are far too numerous to recount, but many of them are pictorially presented in his three books, “A Handbook of Magnetic Resonance” (1987), “Spin Choreography” (1998), and “NMR in Chemistry and Medicine" (2003). Although we have lost a pioneering giant of modern NMR spectroscopy with Ray’s passing, we also know that the path down which he led us will continue to define the future of solution NMR – and that it will be a path lined with excellent and amusing acronyms.
Ad Bax and Malcolm Levitt
‡A beautiful example of Ray's humour and art of hand-drawn illustrations can be seen in this historical power point file [73 slides, 54 MB], which was provided to us by Ted Becker. This presentation was made by Ray for the 50th ENC in 2009 and run as a continuous display.