Taking Bearings

October 15, 2003

American chemist and physicist Paul Lauterbur and British physicist Sir Peter Mansfield will equally share the 2003 Nobel Prize in Physiology or Medicine for their “seminal discoveries concerning the use of magnetic resonance to visualize different structures.” Lauterbur (b. 1929), formerly at Stony Brook University, currently conducts research at the Biomedical Magnetic Resonance Laboratory at University of Illinois. Mansfield (b. 1933) is a professor at the University of Nottingham, School of Physics and Astronomy.

Lauterbur and Mansfield’s work showed that a varying (gradient) magnetic field in tissue, could be used to produce an image of the tissue. The development of MRI was one of several powerful diagnostic imaging techniques that revolutionized medicine by allowing physicians to explore bodily structures and functions with a minimum of invasion to the patient.

During the 1970s, advances in computer technologies, in particular the development of algorithms powerful enough to allow difficult equations to be solved quickly enough to be of real-time use in the clinical diagnostic setting and to eliminate “noise” from sensitive measurements, allowed the development of accurate, accessible and relatively inexpensive (when compared to surgical explorations) non-invasive technologies. Because of increased resolution that allowed physicians to see more clearly and with greater detail, physicians were increasingly able to make diagnosis of serious pathology (e.g. tumors) earlier. Earlier diagnosis often translates to a more favorable outcome for the patient.

Nuclear medicine traces its clinical origins to the 1930s and fundamental studies of the reactions that take place in excited atomic nuclei. Applications of what were originally termed nuclear spectroscopic principles became directly linked to the development of non-invasive diagnostic tools used by physicians. In particular, Nuclear Magnetic Resonance (NMR) was one such form of nuclear spectroscopy that eventually found widespread use in the clinical laboratory and medical imaging. NMR is based on the observation that a proton in a magnetic field has two quantized spin states. Accordingly, NMR allowed the determination of the structure of organic molecules and although there are complications due to interactions between atoms, in simple terms, NMR allowed physicians to see pictures representing the larger structures of molecules and compounds (i.e., bones, tissues and organs) obtained as a result of measuring differences between the expected and actual numbers of photons absorbed by a target tissue.

Groups of nuclei brought into resonance, that is, nuclei absorbing and emitting photons of similar electromagnetic radiation (e.g., radio waves) make subtle yet distinguishable changes when the resonance is forced to change by altering the energy of impacting photons. The speed and extent of the resonance changes permits a non-destructive (because of the use of low energy photons) determination of anatomical structures. This form of NMR became the physical and chemical basis of a powerful diagnostic technique termed Magnetic Resonance Imaging (MRI).

MRI scanners rely on the principles of atomic nuclear-spin resonance. Using strong magnetic fields and radio waves, MRI collects and correlates deflections caused by atoms into images of amazing detail. The resolution of MRI scanner is so high that they can be used to observe the individual plaques in multiple sclerosis. In a clinical setting, a patient is exposed to short bursts of powerful magnetic fields and radio waves from electromagnets. MRI images do not utilize potentially harmful ionizing radiation generated by three-dimensional X-ray CT scans and there are no known harmful side effects. The magnetic and radio wave bursts stimulate signals from hydrogen atoms in the patient’s tissues that, when subjected to computer analysis, create a cross-sectional image of internal structures and organs. Diagnosis id further enhanced by the fact that healthy and diseased tissues emit identifiably different signal patterns. More than 60 million MRI scans are performed worldwide each year.

The 2003 award in Medicine is not without controversy. American physician and inventor Raymond Damadian, who runs an MRI imaging company (FONAR) in New York and who claims to have invented the technique, protested his exclusion with full-page advertisements in The New York Times, The Washington Post, and Los Angeles Times.

Although the rules stipulate that Nobel prizes can shared by up to three individuals. Damadian was excluded despite his 1971 paper in Science (R. Damadian Science 171, 1151-1153; 1971) demonstrating the identification of cancerous tissue by NMR (Nuclear Magnetic Resonance). NMR was a forerunner to MRI. Richard Ernst, at the Swiss Federal Institute of Technology, Zurich, won the 1991 chemistry Nobel for improving the resolution of NMR.

Mansfield developed techniques that allowed signals to be analyzed mathematically, making rapid imaging possible.

In 1988, both Damadian and Lauterbur were honored with the National Medal of Technology.Damadian’s first commercial MRI scanner, “Indomitable,” is now housed in the Smithsonian collections. Dommadian’s early images were crude and were ultimately abandoned in favor of images based on the techniques pioneered by Lauterbur.

Physics

The Nobel Prize in Physics, awarded in 2003 for “pioneering contributions to the theory of superconductors and superfluids” is equally shared by Russian born American physicist Alexei A. Abrikosov, Russian Physicist Vitaly L. Ginzburg, and British born American physicist Anthony J. Leggett.

Abrikosov (b.1928) is currently affiliated with the Argonne National Laboratory, Ginzburg (b. 1916) is affiliated with the Lebedev Physical Institute in Moscow, and Leggett (b.1938) conducts research at the University of Illinois.

A superfluid is a liquid that flows without viscosity or inner friction. For a liquid to become superfluid, the atoms or molecules making up the liquid must be cooled or “condensed” to the point at which they all occupy the same quantum state.

Superconductors exhibit near zero resistance to the flow of electrical current and become diamagnetic (opaque to magnetic fields) at very low temperature.

Superconductivity was first discovered in 1911 by Dutch physicist Heike Kamerlingh Onnes (1853-1926). After succeeding in liquefying helium (He), Onnes observed that the electrical resistance of a filament of mercury dropped abruptly to an experimentally undetectable level.

In a perfect ring shaped superconductor, an electrical current would travel indefinitely. Superconducting diamagnets produce powerful magnetic fields.. Because of these unique properties, superconductors have found wide applications in the generation of powerful magnetic fields, magnetometry, magnetic shielding, and other technologies.

A major technological leap resulting from superconductivity research is the development of oscillation SQUIDs (Superconducting QUantum Interference Devices) for use in Magnetoencephalography. SQUIDS can sense very weak magnetic fields and do not require the much stronger magnetic fields associated with MRI studies.

Although superconductor magnets are used at a number of research facilties (e.g., Fermilab), a 1993 U.S. Congress decision to stop funding the Superconducting Super-Collider project planned for construction in Ellis county, Texas has imperiled America’s early edge in applications of superconducting research. Much of the world’s leading research utilizing superconductor magnets is now conducted at CERN, a consortium of several European nations.

Superconductors also enhace the efficiency of power production. Electric generators equipped with superconducting wire are vastly more efficient – and smaller — than generators with conventional copper wiring. Superconducting based technology may also help avoid large blackouts on powergrids because superconducter based storage and superconducting transformers allow rapid intervention (measured in thousandths of a second) whenever there is a current fault or other need to stabilize line voltage.

Military “E” bombs also utilize superconductors to create a strong electro-magnetic pulse (EMP) capable of disabling a target’s electronic resources.

Chemistry

The Nobel Prize in Chemistry for 2003 was awarded “for discoveries concerning channels in cell membranes.” The prize will be equally shared by Pater Agre (b. 1949) at Johns Hopkins University School of Medicine in Baltimore, and by Roderick MacKinnon (b. 1956) at Rockefeller University, Howard Hughes Medical Institute in New York. Agre was specifically cited for his “discovery of water channels.” MacKinnon was specifically cited for his “structural and mechanistic studies of ion channels.”

In 1998 MacKinnon’s work revealed the three-dimensional architecture of a protein that allows a potassium ion channel. The movement of potassium ions through the cell membrane is an essential component in the propagation of nerve signals and the impulses associated with muscle contraction.

Ion channels or pores explain important aspects of changes in cell membrane permeability to the passage of charged atoms such as potassium (K+). And rapid changes in selective permeability (e.g., a change that does not allow the passage of potassium ions but that does allow the passage of smaller sodium ions (Na+)) of membranes. Different channels become portals for specific ions (i.e., there are sodium ion channels, and potassium ion channels that allow passage of those specific ions and no other ions)

Although some channels may allow passage of potassium ions they do not pass smaller sodium ions. Although a channel may consist of proteins with embedded oxygen atoms (polar refers to an uneven distribution of charge within a molecule – in the case of water (H₂O) the oxygen becomes “partially” negative and the hydrogens partially positive), if the pore is too large then there is no dynamic or equilibrium drive for sodium ions to disassociate from the polar water molecules in which they are dissolved. There is no drive or energetic “incentive” for a sodium ion to enter a potassium channel. On the other hand, a potassium ion perhaps finds equal or closer association with oxygen in the properly sized potassium channel.