The discovery of factor X: a personal reminiscence.

Abstract

Thromb Haemost 2007; 98: 16–19 When I chose to become a physician at age 15, I had in mind to practice internal medicine in a medium-sized city not too far from Zurich, Switzerland. However, fate decided otherwise. After my graduation from medical school I was searching hard to find a place as an intern and resident but realized that this was hardly possible in the city of Zurich. At that time about three quarters of all interns and residents were unpaid, and even these volunteer positions were extremely hard to get. I went to a smaller hospital in the vicinity of Zurich where Dr. Fritz Koller (Fig. 1) was head of the internal medicine department. Asking him for an internship, I was told that there was a long waiting list to obtain an unpaid internship, but – “Do you have the scientific fire for research” he asked me unexpectedly. I was baffled at this question but Dr. Koller explained to me that there was a position available at his haemostasis research laboratory at the Department of Medicine of the University Hospital in Zurich. The Emil Barrel Foundation sponsored this position with $125/month. I started a few days later and was told to find out more about the presumptive factor X that had been postulated by François Duckert, Paul Flückiger, Martin Matter and Fritz Koller (1). The fifties were an exciting time in the field of blood coagulation. In the forties factor V/labile factor/accelerin had just been discovered. In 1949 Alexander et al. postulated, on the basis of quite inconclusive data, the existence of a further coagulation factor, termed serum prothrombin conversion accelerator (SPCA) (2). A first case of a congenital deficiency of this factor was described in 1951 (3). In the same year further publications confirmed the existence of a stable factor, present in plasma (Owen and Bollman), called proconvertin by Owren and factor VII by Koller et al. (4, 5).The latter article became a citation classic and has now been cited 477 times (6). Paul Owren was possibly aware of the forthcoming article by Koller et al., when in spring 1951, he published a one-page description of proconvertin in the Scandinavian Journal of Clinical and Laboratory Investigation (4), followed a few months later by more complete descriptions (7, 8). In 1952 plasma thromboplastin component (PTC)/ Christmas factor (later on called factor IX) was independently discovered by Aggeler et al. in San Francisco and by Biggs et al. in Oxford. The thromboplastin generation test developed by Biggs, Douglas and MacFarlane in 1950 was to become a very important tool in the differentiation of factor VII from factor X, of factor VIII (antihaemophilic globulin) from factor IX, and in the discovery of plasma thromboplastin antecedent (PTA, factor XI) in 1953 and Hageman factor (factor XII) in 1955 (9). The field of coagulation seemed to explode in these years, and very often discoveries of new factors were made independently by researchers in Europe and the United States, resulting in a profusion of different names. Under the leadership of Irving S. Wright, an international Committee for the Standardization of the Nomenclature of Blood Clotting Factors was created at a meeting in Basel, Switzerland in 1954. In 1958 the committee met in Montreux where the Roman numeral designation of clotting factors was proposed by Koller. Many reservations to this proposal were voiced (10–12), but finally it was adopted and the Stuart-Prower factor became officially factor X. Gradually the tasks of this committee expanded and included standardization issues. The name was changed to International Committee on Thrombosis and Haemostasis (ICTH). Fritz Koller was its first secretary general from 1960 to 1962. Back to my task. Under the guidance of François Duckert (Fig. 2), a biochemist, I had to prepare protein fractions devoid of factor X and to test them using the thromboplastin generation test of Biggs and collaborators. I must have performed thousands of these tests, but the presumptive factor X remained an unsolved enigma. I remember how I was labouring to produce fractions Prof. Fedor Bachmann 50 th A n n iv er sa ry (1 95 7– 20 07 )

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Cite this paper

@article{Bachmann2007TheDO, title={The discovery of factor X: a personal reminiscence.}, author={Fedor Bachmann}, journal={Thrombosis and haemostasis}, year={2007}, volume={98 1}, pages={16-9} }