Nobel Prize in Physiology or Medicine

Summary

The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin) is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according to Alfred Nobel's 1895 will, are awarded "to those who, during the preceding year, have conferred the greatest benefit to humankind". Nobel Prizes are awarded in the fields of Physics, Chemistry, Physiology or Medicine, Literature, and Peace. The Nobel Prize is presented annually on the anniversary of Alfred Nobel's death, 10 December. As of 2022, 114 Nobel Prizes in Physiology or Medicine have been awarded to 226 laureates, 214 men and 12 women. The first one was awarded in 1901 to the German physiologist, Emil von Behring, for his work on serum therapy and the development of a vaccine against diphtheria. The first woman to receive the Nobel Prize in Physiology or Medicine, Gerty Cori, received it in 1

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The 2003 Nobel Prize in Medicine or Physiology has been awarded for discoveries concerning Magnetic Resonance Imaging (MRI), a technique that revolutionalized medical diagnostics over the last two decades. Such spectacular development would not have been possible without the use of paramagnetic contrast agents, GdIII complexes in majority. By reducing the relaxation time of the surrounding water protons, these agents enhance the intrinsic contrast of MR images. The efficacy of a contrast agent is expressed by its molar relaxivity, the longitudinal proton relaxation rate enhancement referred to 1 mM GdIII concentration. Theory predicts a 20-fold increase in the relaxivity (compared to the commercially available contrast agents) of a GdIII complex when its rotation and electron spin relaxation are slow, and the rate of water exchange between the inner sphere and the bulk is in an optimal region. Novel applications in MRI call for very high efficacy contrast agents. It implies not solely high molar relaxivity per GdIII, but high relaxivity per molecular volume/mass. In cell imaging e.g., biological constraints limit the amount of contrast agent deliverable into one cell without destroying it. Consequently, agents with many efficiently relaxing paramagnetic centers confined into a small space are advantageous over large macromolecules with few GdIII. The main objective of this work was to prepare new potential contrast agents displaying not only high molar relaxivities but also concentrated relaxivities, i.e. confined into a small molecular space. In this perspective, we have synthesized and characterized three new ligands and their GdIII complexes. The first contrast agent synthesized is a metallostar self-assembly with six GdIII ions tightly packed around a FeII(bpy)3 core. In the second system, a rigid xylene core was used to hold three GdIII ions via DTTA chelating units. The third complex is a surfactant molecule that upon concentration trigger self-assembles into a micellar aggregate which has been found to be the most rigid micelle ever reported in the context of MRI contrast agents. In the aim of describing the efficacy per unit of mass of a contrast agent, we have introduced the concept of "density of relaxivity". Comparison of the "density of relaxivity" of current contrast agents shows that two of our novel systems described in this work display the highest "density of relaxivity" ever reported. Furthermore, we have also performed an in vivo MRI feasibility study with the metallostar as a potential medical MRI contrast agent. Dynamic γ scintigraphic and biodistribution studies were also carried out on the metallostar to complement the MRI results and to give a better idea of its pharmacokinetics.

EPFL2006

Comparative genomics of the mycobacteria

Stewart Cole

The genus mycobacteria includes two important human pathogens Mycobacterium tuberculosis and Mycobacterium lepra. The former is reputed to have the highest annual global mortality of all pathogens. Their slow growth, virulence for humans and particular physiology makes these organisms extremely difficult to work with. However the rapid development of mycobacterial genomics following the completion of the Mycobacterium tuberculosis genome sequence provides the basis for a powerful new approach for the understanding of these organisms. Five further genome sequencing projects of closely related mycobacterial species with differing host range, virulence for humans and physiology are underway. A comparative genomic analysis of these species has the potential to define the genetic basis of these phenotypes which will be invaluable for the development of urgently needed new vaccines and drugs. This minireview summarises the different techniques that have been employed to compare these genomes and gives an overview of the wealth of data that has already been generated by mycobacterial comparative genomics.

2000

EPFL2006