Perspectives in Biology and Medicine

ALPHA-, BETA-, GAMMA-GLOBULIN—ARNE TISELIUS AND THE ADVENT OF ELECTROPHORESIS FRANK W. PUTNAM* For the life of allflesh is the blood thereof.—Leviticus 17 :4 Great innovations in biology and medicine are often rejected at first, and this was the case with the classic paper on protein electrophoresis by Arne Tiselius. Yet, together with Theodor Svedberg's earlier development of the ultracentrifuge, this paper led to a revolution in biochemistry and clinical chemistry and to the virtual demise of colloid chemistry . Today, electrophoresis of one type or another is performed almost daily in nearly every biochemical, clinical, and molecular biology laboratory . Probably every reader of this article has had a serum electrophoretic analysis done, but Tiselius's manuscript reporting his new method was rejected by the BiochemicalJournal as being "too physical" [I]. The paper was finally published in 1937 in Transactions of the Faraday Society [2], ajournai no longer extant. The reaction was immediate and positive. Tiselius was flooded with letters and requests for reprints, including one from Harvey Cushing, who requested a reprint for his library of the classics of medicine [I]. Only 11 years later, Tiselius received the Nobel Prize for this and other achievements in the field of protein electrophoresis that had begun with his doctoral thesis in 1930 [3]. Tiselius loved to tell this story and did so in his biographical article in Annual Review of Biochemistry, which he entitled "Reflections from Both Sides of the Counter" [I]. In this article, he portrayed himself as having had two careers: one as the struggling young scientist dedicated to solving the burning problem of separation of impure natural materials , the other as the administrator and purveyor of research funds and as president of the Nobel Foundation. In the retrospective, he gave *Department of Biology, Indiana University, Bloomington, Indiana 47405.© 1993 by The University of Chicago. All rights reserved. 0031-5982/93/3603-0807$01.00 Perspectives in Biology and Medicine, 36, 3 ¦ Spring 1993 | 323 equal weight to and seemed to recall the same satisfaction from both careers, but his scientific achievements are the main focus of my perspective . Arne Tiselius, the Student Arne Wilhelm Kaurin Tiselius was born August 10, 1902, in Stockholm , the son of the Swedish mathematician Dr. Hans Tiselius and his Norwegian wife Rosa Kaurin. After the untimely death of his father, the family moved to Gothenburg, where Tiselius attended the local realgymnasium . He early exhibited an aptitude for science and a special interest in chemistry. This was encouraged by his teacher, who gave him the key to the laboratory so that the young student could work there after hours [4]. Tiselius loved chemistry and wanted to study under The Svedberg at the University of Uppsala. In 1921 he matriculated at Uppsala and took his first degree (fil. mag.) in chemistry, physics, and mathematics . It is interesting to note that although Tiselius was best known for his research on electrophoresis and its applications to biochemistry, he never took any formal course work in biochemistry. In fact, there was no professor of biochemistry at Uppsala at that time, and very few in all of Europe. When Tiselius began his research career as an assistant to Svedberg in 1925, Uppsala was already becoming known as a world center for macromolecular chemistry. Indeed, the next year Svedberg received the Nobel Prize in Chemistry for development of the ultracentrifuge. Since his doctoral thesis at Uppsala in 1907, Svedberg's main research interest had been in colloid chemistry, but the size heterogeneity of the colloid state had been a baffling problem. He had earlier proposed the use of centrifugal methods to study the sedimentation and size distribution of colloidal particles, but it wasn't until 1923, when he went to the University of Wisconsin at Madison, that he began practical development of the ultracentrifuge together with J. W. Williams and others. Warren Weaver, a physicist who will be mentioned later, contributed calculations on the theory of sedimentation. Svedberg got some of his ideas from the milk separator centrifuge and developed optical techniques to photograph the sedimenting boundary, but convection interfered with the sedimentation even though the centrifugal field was only 5,000 times gravity (5,00Og-). However, after...