Herman Kalckar - First American Work

First American Work

Upon completing his graduate studies, Kalckar received a Rockefeller research fellowship to spend a year at the California Institute of Technology (Caltech). After arriving in the United States in early 1939, Kalckar briefly visited the Cori lab in St. Louis en route to the west coast. The Coris had unsuccessfully attempted to reproduce Kalckar's oxidative phosphorylation work, and Kalckar was able to point out a key element missing in their experiment. During his St. Louis visit Kalckar and Sidney Colowick (1916–1985) became good friends.

Kalckar and his wife arrived in Pasadena in the Spring of 1939 and rapidly became a part of the Caltech social and intellectual community, including Max Delbrück, Linus Pauling, and James and David Bonner. At Delbrück's suggestion he attended C. B. van Niel’s popular Pacific Grove microbiology course, an event that had a life time influence on his research career.

While at Caltech, Kalckar wrote and published what was, arguably, one of his most important papers. Under Pauling's influence he reviewed the literature dealing with biological energetic mechanisms. In 108 pages, including 310 references, the paper was a virtual synopsis of the state of biochemistry at the time. As Kalckar noted:

The aim of this review has been not only to collect and coordinate knowledge from very different fields, like animal physiology, microbiology, enzyme chemistry, organic and physical chemistry, but also to interpret all the fundamental biological phenomena from a dynamic point of view. (p. 167)

Although not highly cited, the paper was important because Kalckar provided strong evidence for the role of "high energy" compounds in metabolic processes. In the paper Kalckar developed an argument for the central role of Adenosine-5'-triphosphate (ATP) as a common metabolic "energy carrier." The paper is not highly cited, most likely, because Kalckar's mentor and friend, Fritz Lipmann, published a similar review in which he introduced the notion of "~P" as a means of representing a "high energy" bond.

The onset of World War II stranded the Kalckars in the United States; Kalckar was offered an appointment as a research fellow at Washington University, and he and his wife moved to St. Louis. Kalckar resumed his friendship with Colowick, and they collaborated to work on the enzyme adenylate kinase in 1942, which they purified from muscle extracts. Further work on nucleotide metabolism allowed him to identify nucleoside phosphorylase, a key enzyme in nucleotide salvage pathways. The work was very important in expanding Kalckar's research interests because previously he had worked with complex physiological systems. In his Washington University work, he focused on individual enzymes and their purification.

At an invitation from Oliver Lowry (1910–1996), Kalckar moved to the New York Public Health Institute as a research associate. The move was an important part of developing Kalckar's research biochemical abilities as an enzymologist, because as Paul Berg commented, he “developed a whole new approach to being able to use enzymes in a novel way.” The lab was equipped with a relatively rare Beckman DU ultraviolet spectrophotometer; Kalckar rapidly used the instrument to develop several novel enzyme assays. In 1947 he published three papers on purine metabolism enzymes, all of which were highly cited (3,200 citations in 2006).