Friedrich Cramer (1923–2003): Nucleic Acid Chemist and Philosopher

Abstract

Friedrich Cramer died on June 24, 2003 shortly before his 80th birthday. In him we have lost a colleague of great merit, particularly in the area of nucleic acid chemistry. Friedrich Cramer, or Fritz to his colleagues and friends, was born in Breslau on September 20, 1923. Having been badly wounded in Russia in October 1942, he started studying chemistry a year later in Breslau and continued his studies in Heidelberg from 1944. He received his PhD in 1949 with work on cyclodextrins under the supervision of Karl Freudenberg. He continued to work on this class of compounds for his habilitation, which he completed in 1953. This work formed the basis for the development of cyclodextrins as enzyme models. Cramer could show that compounds enclosed in a cyclodextrin cavity, as so-called inclusion compounds, become available for catalytic reactions through a key–lock interaction similar to that of an enzyme–substrate complex.1 These results were of fundamental interest at the time, and Professor Alexander Todd invited Cramer for a one-year visit to his laboratory in Cambridge. This laboratory was prominent in the budding field of nucleic acid chemistry, and investigations into the type of linkage of the nucleotide monomers in DNA and RNA formed an active research program there.1 Cramer returned to Heidelberg in 1954 and accepted the position of Professor of Organic Chemistry at the Technische Hochschule Darmstadt in 1959. There he built upon his experience gained in Cambridge and began work on the chemical synthesis of oligonucleotides. In 1962 he became a member of the Max-Planck-Gesellschaft and Director of the Department of Chemistry at the newly created Institute for Experimental Medicine in Göttingen. With the new opportunities available to him at this institute he focused on the study of nucleic acids. He was not only interested in the chemical synthesis of oligonucleotides, but he extended his research to tRNA and in particular to the enzymes that play a role in the aminoacylation of tRNA. These studies led to the first attempts to crystallize tRNA. Through probably the first use of nucleotide analogues it was also discovered that aminoacyl synthases occur in two classes, depending on whether they catalyze the binding of the amino acid residue to the 2′ or the 3′ hydroxy group.2 This classification was later fully confirmed by X-ray structural analysis in another laboratory. Work on the specificity of aminoacylation formed the basis for a better understanding of this reaction, which is so important for cell function.3 The work in Cramer's department in many respects formed a foundation for the bioorganic research of nucleic acids, particularly in such modern areas as RNA research. Friedrich Cramer created a very stimulating and lively atmosphere in his department, to which his dislike of hierarchical structures certainly contributed, and he permitted the members of his department to work quite independently. The department was also enriched by the presence of many postdoctoral researchers from abroad at a time when this was not the rule in Germany. His contact with Professor Jan Michalski from Poland, who Cramer had met in Cambridge, laid the foundation for a lively exchange with Poland, which has continued to this day. These international relations also included close contacts with Israel. This stimulating and open environment served to encourage many members of the department to stay in research and to continue to work in the field of nucleic acids. Friedrich Cramer had many varied interests and talents. For example, his sketchbook was a constant companion, and he produced portraits of colleagues and paintings. As the years went on his interest in the philosophical component of the sciences grew, and themes such as complexity, chaos, and the ethics of gene technology attracted his particular attention. These thoughts were the subject of many lectures, articles, and books. His concerns about the significance of science for society as a whole, not frequently encountered among scientists, led to his election as a Fellow of the Wissenschaftskolleg in Berlin for 1989/90 and as a member of the Göttinger Colloquium for Ethical Questions in Science and Technology. Friedrich Cramer's death coincides with the end of an era following the Second World War during which the rebuilding of respect and recognition for Germany was of prime concern. Cramer contributed greatly to this endeavor, alongside his considerable contributions to nucleic acid research.4