The Nobel prize for MRI: a wonderful discovery and a sad controversy

In reporting this 2003's Nobel prize for physiology or medicine to Paul Lauterbur and Peter Mansfield for work leading to magnetic resonance imaging (MRI), Stephen Pincock (Oct 11, p 1203)1 alludes to the puzzling absence of Raymond Damadian—an MD scientist at State University of New York Downstate Medical Center—from the prize and notes that the reason for his absence is now clear. But we see through a glass darkly: the real answer is murkier than ever.

The discovery of MRI in medicine comprised two steps. First was Damadian's report in 1971 of differences in tissue proton relaxation among normal tissues and between normal and cancer tissues, and proposal of external nuclear magnetic resonance (NMR) scanning of live human beings.2 Second came the development of imaging methods during 1972—80. The first methods were devised by Lauterbur—who reconstructed two-dimensional images using magnetic field gradients, imaging two capillary tubes in water3—and by Damadian, who registered a patent in 1972. During 1977—78, and using a video-like field-focusing method with a human-sized superconducting magnet built in his laboratory, Damadian and his students obtained the first whole-body MR images, including those of the chest and abdomen in healthy people and in patients with cancers.4 In 1974, Mansfield had devised a faster pulsed-sequence method which did not rely on Lauterbur's reconstruction technique.

Lauterbur, Mansfield, and Damadian's methods were supplanted by spin-warp imaging, a gradient method developed in 1980. Spin-warp combines phase-encoding with the two-dimensional Fourier MR concept of Richard Ernst, who won the Nobel prize for chemistry in 1991.5

Both steps are essential to medical MRI. In key papers, Ernst5 cites Lauterbur,3 Damadian,2 and Mansfield; the spin-warp paper cites Ernst5 and Damadian.2 For all imaging methods, tissue proton relaxation and density differences account for the contrasts and anatomic detail unique to MRI. This fact led the US High Court of Patents and Supreme Court in 1997 to uphold Damadian's 1972 patent.

That Damadian, Lauterbur, and Mansfield made important contributions in launching medical MRI seems unambiguous. Why, then, did the Nobel prize recognise two scientists whose contributions involved imaging techniques alone, but exclude the third scientist who conceived of whole-body NMR scanning, discovered tissue proton relaxation differences crucial to MRI's genesis and use, and achieved the first human whole-body MR images? This question is compounded by Alfred Nobel's will, which mandates that the physiology or medicine prize be awarded for the most important discovery; the physics and chemistry prizes include important methods. 2003's physiology or medicine prize seems to have ignored the fundamental biomedical discoveries on which imaging methods are based.

Unfortunately the canon of scientific recognition might be abandonded in the real world. There is disciplinary loyalty within the NMR community, with aspersions cast about Damadian as a physician whose early contributions were inconsequential. The main controversy involves Lauterbur's claim of exclusive primacy in the discovery of medical MRI. Although Damadian's work directly led to Lauterbur's, this fact was not acknowledged by Lauterbur until years later, and only after acerbic public complaints by Damadian.

Also, use of field gradients for linear spatial localisation, fundamental to gradient imaging methods, was discovered by Robert Gabillard and independently by Herman Carr and Edwin Purcell in 1952, and described in classic NMR textbooks. This previous work was never acknowledged by Lauterbur, despite published reminders by Carr and others.

It is sad that this important scientific discovery with direct human benefit is marred by controversy, and sadder yet that the Nobel award has exacerbated rather than settle an unnecessary controversy.

References

1 Pincock S. US and UK researchers share Nobel prize. Lancet 2003; 362: 1203. Full Text | PDF(83KB) | CrossRef | PubMed

2 Damadian R. Tumor detection by nuclear magnetic resonance. Science 1971; 71: 1151-1153. PubMed

3 Lauterbur P. Image formation by induced local interactions: examples employing nuclear magnetic resonance. Nature 1973;242: 190-191. CrossRef | PubMed

4 Damadian R, Goldsmith M, Minkoff L. NMR in cancer XVI: FONAR image of the live human body. Physiol Chem Physics 1977; 9:97-100. PubMed

5 Kumar A, Welti D, Ernst RR. NMR Fourier zeugmatography. J Magn Res 1975; 18: 69-83. PubMed