In agreement with SCHLENK (I78) "nucleotide" is here taken to mean a phosphoric ester of an N-glycoside of a heterocyclic base. Although they fall outside the scope of this definition, phosphorylated derivatives of riboflavin are added in recognition of their close relation to the main body of nucleotides. A complete review of even the organic chemistry of nucleotides and their derivatives would now form a substantial monograph. The smaller and less characteristic fragments of the nucleotides, namely the hetero- cyclic bases, the component sugars and the derived sugar phosphates, are therefore excluded from this article. * Their chemistry is of longer standing and is covered in standard works. On the other hand knowledge of the "nucleosides", the N-glycosides of heterocyclic bases, has expanded very considerably in recent years and an account of the relevant work is therefore included. With regard to the nucleotides themselves attention is focussed on work published in the last few years leading to improved characterisation, more exact structural knowledge and increased availa- biIity. Only such enzymatic experiments as bear direct1y on structural problems are discussed and therefore much fascinating work by KALCKAR, FRIEDKIN et al. and by KORN BERG has been omitted. I t would be unthinkable to present a review on nucleotides without mentioning that the foundations of the subject were laid by P. A. LEVENE. His monograph with BASS (I36) was published in 1931 and two reviews by LYTHGOE (I50, I5I) cover the intervening period until 1944.

In 1939, when the electron optics laboratory of Siemens & Halske Inc. began to manufacture the first electron microscopes, the biological and medical profes sions had an unexpected instrument at their disposal which exceeded the reso lution of the light microscope by more than a hundredfold. The immediate and broad application of this new tool was complicated by the overwhelming prob lems inherent in specimen preparation for the investigation of cellular struc tures. The microtechniques applied in light microscopy were no longer appli cable, since even the thinnest paraffin layers could not be penetrated by electrons. Many competent biological and medical research workers expressed their anxiety that objects in high vacuum would be modified due to complete dehydration and the absorbed electron energy would eventually cause degrada tion to rudimentary carbon backbones. It also seemed questionable as to whether it would be possible to prepare thin sections of approximately 0. 5 11m from heterogeneous biological specimens. Thus one was suddenly in posses sion of a completely unique instrument which, when compared with the light microscope, allowed a 10-100-fold higher resolution, yet a suitable preparation methodology was lacking. This sceptical attitude towards the application of electron microscopy in bi ology and medicine was supported simultaneously by the general opinion of colloid chemists, who postulated that in the submicroscopic region of living structures no stable building blocks existed which could be revealed with this apparatus."

Als im Jahre 1939 in Berlin im Laboratorium fur Elektronenoptik der Siemens & Halske AG die ersten Elektronenmikroskope serienmassig fabriziert wurden, stan- den den Biologen und Medizinern unerwartet Gerate zur Verfugung, welche das Aufloesungsvermoegen der Lichtmikroskope um das 100fache ubertrafen. Der sofor- tigen und breiten Anwendung dieses neuen Verfahrens in der Erforschung der zel- lularen Strukturen standen aber fast unuberwindliche praparative Schwierigkeiten im Wege. Die bisher in der Lichtmikroskopie verwendete Mikrotechnik konnte nicht ubernommen werden, weil selbst die feinsten Paraffinschnitte von den Elek- tronen nicht durchstrahlt werden konnten. Viele damals kompetente Biologen und Mediziner ausserten auch die Befurchtung, dass die im Hochvakuum befindlichen Objekte durch die vollstandige Entwasserung verandert und schliesslich durch die absorbierte Elektronenenergie bis zu einem rudimentaren Kohlenstoffskelett abge- baut werden wurden. Es schien auch zweifelhaft, ob es gelingen wurde, Dunn- schnitte in der Groessenordnung von 0,5 j. Lm aus den heterogen zusammengesetzten biologischen Praparaten herzustellen. Man besass ploetzlich ein voellig neuartiges In- strument, das gegenuber dem Lichtmikroskop eine um zwei Zehnerpotenzen hoehe- re Aufloesung ermoeglichte, aber keine dafur geeignete Praparationstechnik I Diese skeptische Einstellung zur Anwendung des Elektronenmikroskopes in der Biologie und Medizin wurde gleichzeitig auch durch die Lehrmeinung der damals aktuellen Kolloidchemie unterstutzt, in der postuliert wurde, dass es im amikrosko- pischen Bereich der lebenden Strukturen keine stabilen Bauelemente gebe, die man mit diesem Gerat abbilden koennte. Man stellte sich damals das Cytoplasma, die Kernmatrix, den Inhalt der Mitochondrien und Plastiden als ein amorphes, homo- genes Gelgerust ohne definierte Strukturhierarchie vor.