Difference between revisions of "Nobel Prize Controversy"

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The controversy surrounding the 2003 Nobel Prize in medicine for MRI: the case of Damadian, Lauterbur, and Mansfield

—by Christoph Champ; Biophysics, Molecular Spectroscopy Project, Winter 2004; Submitted 3. March 2000

Introduction

Progress in science is a methodical and cumulative process. Each step forward is made by considering the contributions of all those that have come before. Science is also a communal process in which collaboration is the norm. However, every once in a while, a leap forward is made by a few individuals. This "leap" may be a new theory, application of previous theories, or a discovery. It may very well be the natural progression of science for these periodic leaps; indeed, they may even be expected (as was the structure of DNA). These leaps might also be completely unexpected and made by individuals thinking outside-the-box. A discovery or a new theory may gain all the attention; however, sometimes it is the application of these discoveries and theories that have the most profound influence. Such applications may every once-in-awhile leave the confines of academia and enter the world of practical medicine.

One such application was the transition of nuclear magnetic resonance (NMR) into magnetic resonance imaging (MRI). The transition was gradual and influenced by many great scientists and researchers. In fact, these fields continue to be actively researched. Of the multitude of individuals involved in this field—from the early days of theoretical postulations to current practical medical diagnoses—a simple consideration of those individuals who have received a Nobel Prize should reveal leading figures. These were those scientists that the Nobel Assembly felt made those "leaps" required for the Prize in Physiology or Medicine. Of course, any assembly (or committee) is by no means infallible and oversights can and do happen.

The decisions of whom to award the Nobel Prize made by the Nobel Assembly each year are governed primarily by Alfred Nobel's will. They also can only award a maximum of three each year for a particular category (eg, Physics). No award may be given posthumously. Finally, the reasoning and debates behind the Nobel Assembly's decisions are closed for 50 years after the Prize has been awarded [14]. The Assembly never reverses its decisions and there have been controversies over these decisions in the years since it began, in 1901. One such controversy has arisen over the 2003 decision for Physiology or Medicine. The winners were Paul Lauterbur and Sir Peter Mansfield. Few would protest the significance of their contributions to the fields of NMR and MRI. However, one individual, Dr Raymond Damadian, argues that he should be included among the winners of this Prize. This paper will consider the controversy surrounding Dr Damadian's claims, whether or not he should have received the Nobel Prize, and how his contributions differed from Lauterbur's and Mansfield's.

Body

In order to understand the Nobel Assembly's decisions in who to award the Nobel Prize each year, it is convenient to consider the history of such awards: who to and what for. The Nobel Assembly is made up of human beings and as such they are certainly able to make mistakes. These mistakes are commonly controversial but have yet to be remedied. Of course, there can be controversy where there is no error. These arise from false assumptions and assertions.

History of Mistakes

There is a tendency for the public to incorrectly assume that the Nobel Assembly has failed to award important figures of their contributions to science. These assumptions are most likely due to the public’s unfamiliarity with the foundation's rules. A classic example of this is the case of Rosalind Franklin (1920-1958), an important figure in the structural discovery of DNA. The fact that her X-ray image of crystallized DNA was used by Watson and Crick to deduce the structure is an important enough contribution to warrant Rosalind Franklin sharing the Nobel Prize with Watson and Crick. However, since the Prize cannot be awarded posthumously and by the time the award was given (in 1962), Rosalind Franklin had passed away [13,14].

Of course, there have also been cases where an overlooked contributor was still living when the Prize was given to a colleague who had done equal (or even lesser) work on the contribution made. An example of this was the 1923 award to John J.R. Macleod and Frederick G. Banting for their discovery of insulin (in 1922). It was Macleod’s departmental colleague's, of which he was the chair, who did the actual work (and he wasn’t even present during the period when the discovery was made). Fortunately, in this case there was no animosity among those involved and the Prize money was even shared with Charles Best and James Collip; the main collaborators in the project [16]. However, even in this well-defined case, the Nobel Assembly did not change their decision.

It is possible for the Nobel Assembly to be correct in who they award the Nobel Prize but not for what that individual actually discovered. Such was the case with Johannes A.G. Fibiger. A competent biologist who mistakenly proposed that Spiroptera neoplastica (a parasite) was the source of stomach cancer in rats. He was awarded the Nobel Prize in 1926 for this explanation, even though it was later understood to be only vitamin deficiency in the rats he used in his study [16].

We have yet another controversy; this one arising from the 2003 award in Physiology or Medicine. This controversy may have been fabricated by a sore loser—Raymond Damadian—or there might actually have been an oversight, or even a purposeful denial by the Nobel Assembly. In order to resolve this controversy, it is necessary to consider the correct questions whose terms have been properly defined.

The first question to consider is: For what were the awards in question granted? From the Nobel Press Literature, we learn that Paul Lauterbur and Sir Peter Mansfield won because of "their discoveries concerning magnetic resonance imaging"[14]. Both of these awards were for imaging the signals generated from NMR. These were by no means the first for NMR related research. In fact, there have been seven Nobel Prizes for NMR related discoveries. Let us now consider the science behind the controversy.

The Science Behind The Controversy

There are two basic steps, which were essential to the development of MRI: The development of nuclear magnetic resonance spectroscopy and the invention of a practical method of imaging of NMR signals. The controversy considered in this paper is over MRI.

MRI is a spatial presentation of NMR signals. If a researcher was able to pinpoint the location of a given NMR signal within a sample, a map of the entire sample could be made. Thus, first it is necessary to detect NMR signals over a spatially restricted region, with some form of labeling, in order to locate the signal in three-dimensional space. This was accomplished by using a magnetic field gradient. The NMR frequencies are dispersed by the magnetic field gradient and these gradients are then projected in different directions. The location of each signal is labeled by phase and frequency encoding. Then, the resonance frequency at any location can be calculated, and the signal can be traced back to its position. The image made from this is a direct map of proton density of the sample. This image has to be manipulated to make it useful as a medical tool. In order to see the image contrast between tissues, various parameters are necessary in order to distinguish different tissues. Since the longitudinal relaxation time (T1) and the transverse relaxation time (T2) depend on tissue type, they are used to contrast the image. By varying the imaging parameters, the image contrast can be controlled and varied [1].

How The Science Was Discovered

The problem arises because Damadian claims he was the first one to conceive of using NMR for medical diagnosis. He also claims that he built the first imaging machine and that this machine accomplished its purpose by measuring the different T1- and T2-relaxation times.

These claims can be tested and provide the next series of questions we need to answer. Was Damadian, Lauterbur, or Mansfield the first to conceive of using NMR signals to produce an image? Before answering that, we need to define "image". An image of NMR signals should be a two-dimensional, spatial representation of the data. Damadian's 1970 method would fail to meet this definition as an image, since it was one-dimensional and only measured the difference in relaxation times between normal and cancerous tissue. Also, the machine he built (and received a patent for in 1974) was not an imaging device and "cannot be adapted for this purpose"[4].

If we dissect Damadian's claims into individual questions and then check these against the historical record found in published journals, we should be able to arrive at a reasonable judgment as to who should have received the Nobel Prize.

Damadian claims that in 1969 he proposes for the "first time by anyone" a magnetic resonance body scanner [5]. However, as early as 1959, Jay Singer had used NMR to study blood flow in living humans by measuring the relaxation times [15]. A patent was even filed for a "whole-body NMR machine" by Alexander Ganssen, in Germany, so that an investigator could measure flow rate at various locations in the body [6]. This was not an MRI machine, as it didn't produce images and this procedure did not make it into ordinary medical practice until the 1980s (with added imaging capabilities).

Damadian claims that in 1970 he makes the "discovery that makes [MRI scanning] possible" [5]. His discovery uses the measurable differences in T1- and T2-relaxation times. However, these differences in relaxations times had already been used by Bratton in 1965 to study living frog skeletal muscle [2]. In fact, all throughout the late 1960s and early 1970s many researchers had studied relaxation times for all sorts of tissues under various conditions (including human brain tissue and in vivo studies on mice) [3,7,8,9,10].

Damadian claims that his 1972 machine (patent granted in 1974) works as a «means to detect cancer» and is a useable MRI scanner [5]. However, it has been pointed out that this patent does not describe a method or a technique to scan a human body. In fact, the machine in its original form is possibly detrimental to the patients and does not image nor can it be adapted to image the NMR signals [4].

Damadian claims that in 1977 he and his colleagues were the first to achieve an "image of the human body" using his 1972 scanning method [5]. However, in 1975 Mansfield and colleagues proposed a technique which leads to the actual first image of in vivo human anatomy. This was their 1977 image of a cross section through a finger [11,12].

Conclusion

In the end, we are left with the question: What did Damadian do, or propose to do, before anyone else? It appears, after careful analysis of the record that his primary contribution was to notice the difference in relaxation times between normal and cancerous tissue (in mice). This was a significant observation and worthy of recognition. However, was this observation on par with the contributions of Lauterbur and Mansfield? Paul Lauterbur's idea, using field gradients to produce a two-dimensional image, revolutionized NMR into a useable, reliable, and imaging technique [1,4,14]. Sir Peter Mansfield made the process work in near-real time by creating the mathematical methods necessary to quickly decipher the signals returned from the scanner. This technique opened to door for the three-dimensional imaging that is routine today [1,4,11,12,14].

Thus, we have concluded that although significant, Dr Raymond Damadian's contribution was not at the level of Paul Lauterbur's and Sir Peter Mansfield's. The Nobel Assembly's 2003 decision was, therefore, justified and correct.

References

1. Atkins P, de Paula J (2002). Spectroscopy 3: magnetic resonance (Chapter 18). Physical Chemistry (7th Edition). W.H. Freeman and Company – New York.
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3. Cooke R, Wien R (1971). The state of water in muscle tissue as determined by proton nuclear magnetic resonance. Biophys J, 11:1002-1017.
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6. Ganssen A. Bundesrepublik Deutschland – Deutsches Patent-amt: Patentschrift 1566 148. Elektromagnetische Hochfrequenz-spule für Diagnostikeinrichtung. Patentiert für Siemens AG, Berlin und München. Erfinder: Alexander Ganseen. Anmeldetag 10.3.1967; Offenlegungstag 2.4.1970; Bekanntmachungstag: 17.10.1974.
7. Hanson JR (1971). Pulsed NMR study of water in muscle and brain tissue. Biochem Biophys Acta, 230:482-486.
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13. Microsoft® Encarta® Reference Library 2003. © 1993-2002 Microsoft Corporation. All rights reserved.
14. Nobel e-Museum (2004).
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16. Weiss, Rick (2003). Simthsonian Magazine.