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alisonfloresus · 7 years ago

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The Nobel Prize Controversy About the Discoverer of the MRI

On Oct. 6 2003, the Nobel committee awarded the prize in physiology or medicine to Paul Lauterbur, of the University of Illinois, and Sir Peter Mansfield, of the University of Nottingham, for the invention of the MRI. Controversy immediately erupted. Full-page advertisements appeared in The Washington Post and The New York Times headlined ”The Shameful Wrong That Must Be Righted” and charging at angry length that the Nobel committee was trying to rewrite history. In this two-part article, Dr. Patrick Treacy continues his story on why Dr. Raymond Damadian should have been awarded the 2003 Nobel Prize in Medicine.

The Nobel Prize for Medicine 2003 was given to Paul Lauterbur, the director of the Biomedical Imaging Centre at the University of Illinois, and Sir Peter Mansfield, a physicist at the University of Nottingham in Britain for discoveries that “led to the development of modern magnetic-resonance imaging”. The Nobel Prize Committee awarded the laureates the Prize because they felt that the two recipients had made seminal discoveries concerning the use of magnetic resonance to visualise different structures, which eventually led to the development of modern magnetic resonance imaging, MRI, a breakthrough in medical diagnostics and research.

This year’s Nobel Laureates in Physiology or Medicine are awarded for crucial achievements in the development of applications of medical importance. In the beginning of the 1970s, they made seminal discoveries concerning the development of the technique to visualize different structures. These findings provided the basis for the development of magnetic resonance into a useful imaging method. Many in the field felt the award of the Nobel Prize for the invention of MRI has been long overdue. However, the decision to award the Prize to two scientists, Paul Lauterbur and Sir Peter Mansfield re-ignited a controversy regarding Dr. Raymond Damadian–a medical doctor who regards himself as the true inventor of MRI, and when I spoke to him at Fonar recently claims that this year’s winners made technological improvements based on his discovery. In fact, I gave the discovery of the MRI to Dr. Raymond Damadian to him in an article that I wrote in IMT some years ago. Therefore, who is Dr. Damadian and what are his claims to the Nobel Prize.

Raymond Damadian was born in 1936, the same year that Adolf Hitler gave his blessing to the new ‘people’s car’, the Volkswagen. He entered the University of Wisconsin as a 16-year-old freshman, after winning a scholarship from the Ford Foundation. His major area of study was mathematics, but he then chose to go to study medicine and moved to the Albert Einstein College of Medicine in New York. He completed his residency at the Downstate Medical Center and after a couple of postgraduate courses, assumed a professorship in 1967. It was the same year that Christian Barnard carried out the world’s first human heart transplant operation.

In the late 1960s, Dr Damadian, at the time a physician at State University of New York’s medical centre in Brooklyn, was among the first to contemplate using NMR to scan the human body for disease. One of his postgraduate projects involved measuring the balance of positive electrolytes in living cells and in 1969; he began to use nuclear magnetic resonance to determine the ratios. Damadian considered whether the NMR signal would be different for cancerous cells and began researching on mouse tumour tissue. Following an obscure theory devised by Gilbert Ling, a physiologist, Dr Damadian believed he would be able to distinguish cancerous from healthy tissues based on the structure of the water molecules in the cell. We should take a moment to consider how this works. The dominant NMR signal from cells comes from the hydrogen atoms in water they contain. The signal varies with the configuration of the liquid, depending on whether the water molecules are bound tightly to various cell structures or more loosely held. Dr Damadian was undeterred that most scientists considered Dr Ling’s ideas irrational and he experimented by analysing excised tumours of rats using machines at NMR Specialties, a now-defunct company based in New Kensington, Pennsylvania. He found that the hydrogen nuclei of water in cancerous and healthy tissues showed pronounced differences in relaxation times, and in 1971, he published his findings in a paper entitled “Tumour Detection by Nuclear Magnetic Resonance.” In the paper he stated that NMR signals persisted in cancerous cells longer than in healthy ones and he brashly described how doctors could use MRI to scan the human body for cancerous tumours. He had completed his experiments on mice without any research grant, and he now made it be known that he needed funds to build a human-size scanner. Unfortunately, his audacious claims for the potential of the technique alienated many of his conservative peers, and most of his colleagues ridiculed him, considering the very idea of scanning the body in this way for cancer to be science fictional.

He was outraged when the National Institutes of Health refused to give him a grant, so he wrote a personal letter to President Richard M. Nixon, boldly asking him to intercede. The year was 1972, and Nixon was ending his historic visit to the People’s Republic of China. The ploy proved to be effective because the President had also recently decided that the U.S. should declare a multibillion-dollar war on cancer, and he furnished him with a small grant. Damadian also received a telephone call from an administrator at the NIH, ostensibly reprimanding him for writing directly to the president.

However, in the same year, President Nixon’s accomplices were caught placing listening devices in the Democratic Party’s National Committee building giving rise to the Watergate scandal.

Around the same time, Dr Lauterbur, then president of NMR Specialties, got a research team to repeat Dr Damadian’s experiments. Dr Lauterbur had the idea that is now at the core of how MRI scanners operate: to superimpose small variations, or gradients, in the uniform magnetic field normally used in NMR spectroscopy. Changing the field strength affects the resonance frequency of nuclei in direct proportion, and can thus be used to collect spatial information.

In 1973, Dr Lauterbur published his idea in Nature, along with the first MR images, of two tiny tubes filled with water. However, his paper did not cite Dr Damadian’s Science paper, even though Dr Lauterbur made a direct reference to it in a notebook entry made the day after his own discovery. When Damadian found out about this, he was livid and tis is one of the main reasons that bitter antagonism still exists between these two people. Lauterbur began to promote the possibilities of MRI or “zeugmatography”. The mid-1970s saw a flurry of activity in the area as teams at a handful of universities in America and Britain raced to publish images of ever increasing complexity.

In 1973, Sir Peter Mansfield published a paper in which he devised a scheme to acquire MR signals and construct images rapidly by using gradients. His method could theoretically speed up the process of producing images from an hour to a fraction of a second. Because of the hardware requirements, it took more than a decade to implement his “echo-planar” imaging technique, but it is now commonly used to watch the brain at work in functional MRI.

In 1974, Nixon resigned to avoid impeachment and Raymond Damadian was unable to procure the funds required for the precious liquid helium he used to cool the cryogenic magnet in his prototype scanner. In December 1976, he hatched another plan and decided that he would go down and visit President elect Jimmy Carter’s cousins in Plains, Georgia. When, they joined the Carter administration, Damadian made an appeal for research funds.

In 1977, Damadian made a new MRI scanner called Indomitable, and in the summer of that year, he stepped into the machine hoping to make the first MR scan of the human chest. The attempt failed, because he could not fit within the largest radio pickup coil he could get to work. Eventually, one of the graduate students, Larry Minkoff, volunteered and thus became the first person in the world to have a MRI scan. On July 3rd 1977, after four hours and 45 minutes of collecting data from 106 points, the first image of a chest cavity of a live man was created. The image not very detailed but some organs could clearly be seen. In characteristic fashion, Dr Damadian sent out a press release claiming he had created “a new technique for the non-surgical detection of cancer anywhere in the human body” had been created. The gargantuan magnetic apparatus appeared in Popular Science magazine and brought Damadian a certain amount of popular notoriety. At that point, however, the machine had not been tested on cancer patients and many scientists thought creating a diagnostic imaging device based on NMR seemed far-fetched, if not ludicrous. When experts questioned Damadian’s assertion, he was forced to back down, the New York Times published an article, casting doubt on Damadian’s claims, and his project went again unfunded.

Damadian was naturally furious, and in 1978, he decided to form a new company called FONAR in order to bring MRI scanning to the medical world. He named his new company FONAR, which stood for ‘Field fOcused Nuclear mAgnetic Resonance’ and based it in Melville, New York. The small company struggled against its mighty competitors. Other researchers made their mark on the field, such as Richard Ernst, a Swiss scientist suggested positioning gradients to form a rectangular grid, to simplify the process of creating two-dimensional images. In 1980, two British teams–one from Aberdeen University, the other a collaboration between EMI and Hammersmith Hospital–developed ways to optimise the contrast of images using differences in relaxation times. The Aberdeen group also came up with a practical implementation of Dr Ernst’s technique, known as “spin warp” imaging, the method most commonly used for MRI today.

In 1988, Dr. Damadian was awarded the National Medal of Technology by President Ronald Reagan, which he shared jointly with Dr. Lauterbur, for “their independent contributions in conceiving and developing the application of magnetic resonance technology to medical uses, including whole-body scanning and diagnostic imaging.”. General Electric and Siemens eventually manufactured the MRI Scanner and Damadian spent many years in court trying to defend his patent granted in 1974 for an “apparatus and method for detecting cancer in tissue”. In 1997, after a lengthy legal fight that ended up in the Supreme Court of the United States, General Electric was ordered to pay FONAR nearly $ 130m for patent infringement.

Despite Dr. Damadian’s contribution to medicine, widespread peer acceptance, and now the Nobel prize, have eluded him. He has taken a typically defiant stance and to voice his recent disappointment, he took out several full-page advertisements in the Washington Post, the New York Times, and a Swedish newspaper, Dagens Nyheter, after the announcement was made. He has allowed me to provide a smaller version of this for the Irish Medical Times.

At the end of the day, the question of who deserves credit for discovering the MRI comes down to how much you value the crucial steps in invention. There is little doubt that Dr Damadian was indeed a visionary who initially proposed the idea that MRI scanning through the human body could be used to detect cancers in their early form. I feel that the Nobel Prize Committee was short sighted not to include him in this year’s laureates for his outstanding contribution to medicine. The discovery of MRI has indeed a complex history, made possible by contributions from numerous visionary scientists over a period of more than 50 years, including a handful of Nobel prize winners. In 1952, Felix Bloch of Stanford and Edward Purcell of Harvard shared the Nobel prize for developing a way to measure the phenomenon that underpins MRI: nuclear magnetic resonance (NMR). 1991, Richard Ernst, Switzerland, was awarded the Nobel Prize for contributions relating to high resolution NMR spectroscopy and in 2002, his countryman, Kurt Wüthrich, received another for his development of NMR spectroscopy of the three-dimensional structure of biological macromolecules in solution

There is little doubt that the gradient field was the “key invention” that led to the MRI coming into widespread commercial use but not to recognise Dr Damadian’s contribution is akin to giving the Nobel Prize in Physiology or Medicine 1945 to Sir Howard Walter Florey and Ernst Boris Chain alone for their work in the discovery of Penicillin and not recognising Sir Alexander Fleming’s seminal observation, which led to this miracle of medicine. In 1975, Howard Temin and David Baltimore were independently honoured for the discovery of reverse transcriptase, an enzyme that translates RNA back into DNA. Many viruses, notably H.I.V., employ reverse transcriptase when infecting animal cells. Like Fleming, Renato Dulbecco the third laureate took no part in the work itself but was given a Nobel Prize. In 1986, Gerd Binnig and Heinrich Rohrer received the physics prize for the scanning tunnelling electron microscope. However, they shared it with Ernst Ruska, who had invented the device’s remote ancestor, the first electron microscope. This means that predecessors have been included in Nobels several times and it is for this reason that I propose that we as doctors should protest to the Nobel Prize Committee that a great injustice was done to medicine and ultimately to their own organisation by not recognising Dr Damadian’s rightful contribution to this miracle of science.

from JournalsLINE http://journalsline.com/2017/06/18/the-nobel-prize-controversy-about-the-discoverer-of-the-mri/ from Journals LINE https://journalsline.tumblr.com/post/161962060395

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