By George B. Kauffman
According to the late Ulf Lagerkvist, a member of the Swedish Academy of Sciences who participated in judging nominations for the Chemistry Prize, “It is in the nature of the Nobel Prize that there will always be a number of candidates who obviously deserve to be rewarded but never get the accolade.” Usually, a losing candidate merely accepts the injustice. But in the case of the 2003 Nobel Prize in Physiology or Medicine of $1.3 million, awarded 10 years ago to University of Illinois Chemist Paul C. Lauterbur (1929-2007) and University of Nottingham (UK) Physicist Sir Peter Mansfield (b. 1933) “for their discoveries concerning magnetic resonance imaging,” the undoubtedly deserving candidate, Raymond Vahan Damadian, M.D. (b. 1936), an American of Armenian descent, did not take this injustice lying down.
A group called “The Friends of Raymond Damadian” protested the denial with full-page advertisements, “The Shameful Wrong That Must Be Righted” in the New York Times, Washington Post, the Los Angeles Times, and Stockholm’s Dagens Nyheter. His exclusion scandalized the scientific community, in general, and the Armenian community, in particular. Damadian correctly claimed that he had invented the MRI and that Lauterbur and Mansfield had merely refined the technology. On Sept. 2, 1971, Lauterbur had acknowledged that he had been inspired by Damadian’s earlier work.
Because Damadian was not included in the award, even though the Nobel statutes permit the award to be made to as many as three living individuals, his omission was clearly deliberate. The possible purported reasons for his rejection have included the fact that he was a physician not an academic scientist; his intensive lobbying for the prize; his supposedly abrasive personality; and his active support of creationism. None of these constitute valid grounds for the denial.
The careful wording of the prize citation reflects the fact that the Nobel laureates did not come up with the idea of applying nuclear magnetic resonance (NMR) (the term was later changed to avoid the public’s fear of the word “nuclear,” even though nuclear energy is not involved in the procedure) to medical imaging. Today magnetic resonance imaging (MRI) is universally used to image every part of the body and is particularly useful in diagnosing cancer, strokes, brain tumors, multiple sclerosis, torn ligaments, and tendonitis, to name just a few conditions. An MRI scan is the best way to see inside the human body without cutting it open.
The original idea of applying NMR to medical imaging (MRI) was first proposed by Damadian, a physician, scientist, and an assistant professor of medicine and biophysics at the Downstate Medical Center State University of New York in Brooklyn. Growing up in Forest Hills, N.Y., he attended the Julliard School and became a proficient violinist. When he was still a boy, he lost his grandmother to a slow death by cancer. He vowed to find a way to detect this dreaded disease in its early, still treatable stages.
MRI scanners make use of the fact that body tissue contains lots of water (H2O), and hence protons (1H nuclei), which will be aligned in a large magnetic field. Each water molecule contains two protons. When a person is inside the scanner’s powerful magnetic field, the average magnetic moment of many protons becomes aligned with the direction of the field. A radio frequency current is briefly turned on, producing a varying electromagnetic field. This electromagnetic field has just the right frequency, known as the resonance frequency, to be absorbed and flip the spin of the protons in the magnetic field. After the electromagnetic field is turned off, the spins of the protons return to thermodynamic equilibrium and the bulk magnetization becomes realigned with the static magnetic field. During this relaxation, a radio frequency signal (electromagnetic radiation in the RF range) is generated, which can be measured with receiver coils.
Information about the origin of the signal in three-dimensional space can be obtained by applying additional magnetic fields during the scan. These additional magnetic fields can be used to generate detectable signals only from specific locations in the body (spatial excitation) and/or to make magnetization at different spatial locations precess at different frequencies, which enables http://en.wikipedia.org/wiki/K-space_(MRI) encoding of spatial information. The 3D images obtained in MRI can be rotated along arbitrary orientations and manipulated by the doctor to be better able to detect tiny changes of structures within the body. These fields, generated by passing electric currents through gradient coils, make the magnetic field strength vary depending on the position within the magnet. Protons in different tissues return to their equilibrium state at different relaxation rates.
Using a primitive NMR machine, Damadian found that there was a lag in T1 and T2 relaxation times between the electrons of normal and malignant tissues, allowing him to distinguish between normal and cancerous tissue in rats implanted with tumors. In 1971, he published the seminal article for NMR use in organ imaging in the journal Science (“Tumor Detection by Nuclear Magnetic Resonance,” March 19, 1971, vol. 171, pp. 1151-1153). Nevertheless, many individuals in the scientific and NMR community considered his ideas far-fetched, and he had few supporters at this time.
However, Damadian received a grant from the National Institutes of Health (NIH) in 1971 to continue his work. He proposed to use whole body scanning by NMR for medical diagnosis in a patent application, “Apparatus and Method for Detecting Cancer in Tissue,” filed on March 17, 1972 (U.S. Patent No. 3789832, issued Feb. 5, 1974). By February 1976, he was able to scan the interior of a live mouse using his FONAR (field focused nuclear magnetic resonance) method.
In 1977, using his machine christened “Indomitable,” now preserved in the Smithsonian Institution in Washington, D.C., Damadian tried to scan himself, but the test failed because of his excessive weight. On July 3, 1977, he obtained the first human NMR image—a cross-section of his slender postgraduate assistant Larry Minkoff’s chest, which revealed heart, lungs, vertebræ, and musculature. Minkoff had to be moved over 60 positions with 20-30 signals taken from each position. Congratulatory telegrams poured in from all over the world, including one from Mansfield.
In early 1978, Damadian established the FONAR Corporation in Melville, N.Y., to produce MRI scanners. Later that year he completed his design of the first practical permanent magnet for an MRI scanner, christened “Jonah.” By 1980 his QED 80, the first commercial MRI scanner, was completed.
The MRI imaging industry expanded rapidly with more than a dozen different manufacturers. On Oct. 6, 1997, the Rehnquist U.S. Supreme Court awarded him $128,705,766 from the General Electric Company for infringement of his patent.
Damadian is universally recognized as the originator of the MRI (by President Ronald Reagan, among others) and has received numerous prestigious awards such as the National Medal of Technology in 1988, the same year he was inducted into the National Inventors Hall of Fame. He was named Knights of Vartan 2003 “Man of the Year,” and on March 18, 2004, he received the Bower Award from the Franklin Institute of Philadelphia for his development of the MRI.
George B. Kauffman is Professor Emeritus of Chemistry at California State University, Fresno, Calif.