Tiselius, Arne Wilhelm Kaurin

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(b. Stockholm, Sweden, 10 August 1902; d, Stockholm, 29 October 1971)

physical biochemistry.

Most of Tiselius’ ancestors on both sides were scholars and many had shown great interest in science, especially biology. His father, Hans Abraham J:son Tiselius, had taken a degree in mathematics at Uppsala University. His mother, Rosa Kaurin, was the daughter of a Norwegian clergyman. His father died in 1906, and his mother moved with Tiselius and his sister to Göteborg, where her parents-in-law lived and the family had close friends.

Tiselius’ profound interest in science was awakened in the grammar school at Göteborg, where he had an inspiring teacher of chemistry and biology. Gradually it became clear to him that he wanted to study at the University of Uppsala with The Svedberg, the leading physical chemist in Sweden. In September 1921 he entered that university, with which he remained associated for the rest of his life. In May 1924 he received the M.A. in chemistry, physics, and mathematics. In November 1930 he presented a doctoral dissertation on electrophoresis and was appointed docent in chemistry. A special chair in biochemistry was created for Tiselius at the Faculty of Science in 1938; he retired thirty years later.

Tiselius married Ingrid Margareta(Greta)Dalén in 1930. He was healthy for most of his life, although during the last few years he was told to reduce his activities in order not to overstrain his heart. It was difficult for him to follow this advice, and after an important meeting at Stockholm he suffered a severe heart attack and died the following morning.

Modest, quiet, and warm-hearted, Tiselius possessed a sense of humor that was both acutely witty and gentle. He was deeply interested in natural history and had a wide knowledge of botany and ornithology. He often made excursions into the countryside to watch and photograph birds.

Tiselius was awarded the 1948 Nobel Prize in chemistry “for his work on electrophoresis and adsorption analysis and especially for his discovery of the complex nature of the proteins occurring in blood serum.” He received honorary doctorates from twelve universities and was a member or honorary member of more than thirty learned societies, including the National Academy of Sciences in Washington and the Royal Society.

In the summer of 1944 Tiselius became a member of a governmental committee established to recommend measures for improving conditions for scientific research, especially basic research. Most of the proposals were approved by the Swedish Parliament, and a number of improvements were introduced. When the Swedish Natural Science Research Council was established in 1946, Tiselius was appointed chairman for the first four years.

In 1947 Tiselius became member of the Nobel Committee for Chemistry and vice-president of the Nobel Foundation. At the International Congress of Chemistry held at London in 1947, he was elected vice-president in charge of the section for biological chemistry of the International Union of Pure and Applied Chemistry. Four years later, at the conference in New York, he was elected president of the union. In the 1960’s he was active in the creation of the Science Advisory Council to the Swedish government, which, under the chairmanship of the prime minister, deals with Swedish research policy.

In the last decade of his life Tiselius was quite concerned about the problems created by the evolution of science; although eager for society to benefit from the advances, he was aware that scientific developments may present a severe threat to mankind. He gave much thought to the opportunity for the Nobel Foundation to use its unique position and status in a way that would complement its awarding of prizes. He took the initiative by starting Nobel symposia in each of the five prize fields. The participants not only discussed the latest developments but also attempted to assess their social, ethical, and other implications. He firmly believed that the Nobel Foundation could and should play an important role in bringing science to bear on the solution of the most pertinent problems of mankind.

Tiselius entered Svedberg’s laboratory as research assistant in July 1925, at the beginning of an outstandingly fruitful intellectual period there. In September 1923 Svedberg had returned to Uppsala with many new ideas after eight months a the University of Wisconsin. He had constructed his first low-speed ultracentrifuge and was then developing the first high-speed device to be used to study the size and shape of protein particles. Svedberg also was interested in determining the electrophoretic properties of proteins, and Tiselius participated in this work. His first paper, published jointly with Svedberg (1926), described a new method for determining the mobility of proteins.

Svedberg was so heavily engaged in the development of his ultracentrifuges that he gave Tiselius free rein to continue the study of electrophoresis. Tiselius began to read biochemistry, which was not included in the chemistry curriculum at that time, and was fascinated by the enormous variability – and especially by the specificity – of biochemical substances.

In his daily work with electrophoresis, Tiselius was often worried by impure or badly defined materials. Even substances that were found to be homogeneous in the ultracentrifuge would often prove inhomogeneous in the electrophoresis experiments. This was particularly true with the serum proteins. He gradually concluded that definition and purification were all-important for the whole of biochemistry. Thus separation became the key problem, and Tiselius was convinced that a solution would require a number of methods besides electrophoresis and ultracentrifugation. He gave some thought to the further development of chromatographic and adsorption methods, and made some preliminary experiments with them. Finally he decided to continue the exploration of electrophoresis and presented his dissertation in November 1930. In the year of his retirement (1968) he described his feelings after the dissertation as follows:

I remember very vividly that I felt disappointed. The method was an improvement, no doubt, but it led me just to the point where I could see indications of very interesting results without being able to prove anything definite. I can still remember this as an almost physical suffering when looking at some of the electrophoresis photographs, especially of serum proteins. I decided to take up an entirely different problem, but a scar was left in my mind which some years later would prove to be significant.

After finishing his dissertation, Tiselius worked on new problems that gave him experience in other fields. He considered this important because he hoped to qualify for a chair in chemistry.

Through his reading Tiselius had learned about the unique capacity of certain zeolite minerals to exchange their water of crystallization for other substances, the crystal structure remaining intact even after the water of crystallization had been removed in vacuo. It was known that the optical properties changed when the dried crystals were rehydrated, but until then no quantitative study of the phenomenon had been made. Tiselius saw the possibilities of this accidental observations, found the governing factors, and developed a very elegant and accurate optical method for the quantitative measurement of the diffusion of water vapor and other gases into zeolite crystals. The later portion of the work was carried out at the Frick Chemical Laboratory at Princeton University in 1934–1935, while Tiselius held a Rockefeller Foundation fellowship for study under Hugh S. Taylor.

Even if Tiselius could not concentrate on biochemistry during his stay in the United States, it proved to be a very stimulating year that decisively influenced his career. The atmosphere in the Frick Laboratory was inspiring, but of even greater importance for Tiselius’ later work was his frequent contact with research carried on by the Rockefeller Institute in its laboratories in Princeton and New York. This contact led to friendships with J. H. Northrop, W. M. Stanley, and M. L. Anson, as well as the opportunity to meet K. Landsteiner, M. Heidelberger, and L. Michaelis. From discussion with them it became clear to Tiselius that to solve some of their problems they needed some new method that had been in his mind for years but that he had been unable to realize. Encouraged by the discussions with these friends, he was again convinced that the development of new and more efficient separation processes was a key problem in biochemistry and decided to concentrate on this problem. While still in the United States, he began a total reconstruction of the electrophoresis apparatus.

After his return to Uppsala, Tiselius radically redesigned the experimental technique. The apparatus he developed could be used safely with potential gradients in the U-tube at least ten times those in any earlier electrophoresis apparatus, and made it possible to obtain a much higher resolving power for protein mixtures. The movement of the boundaries could be followed optically by August Toepler’s Schlieren method. The U-tube could be divided into well-defined sections after the conclusion of the experiments, thus allowing samples to be taken from different parts of the tube for chemical and biological analyses.

The first experiments, carried out with horse serum, immediately demonstrated the advantage of the new instrument. The Schlieren pattern showed four protein bands with different mobilities. The fastest-moving band corresponded to the serum albumin boundary; and the next three bands disclosed, for the first time, the presence of at least three electrophoretically different components in serum globulin. Tiselius tentatively named them α, β, and γ globulin. Serum from other animals yielded similar patterns, but with quantitative differences. It also was shown that the antibodies (immunoglobulins) usually were found in the γ globulin or between the β and γ globulin bands.

The method was subsequently tested by Tiselius and his co-workers in all possible ways, new and better refractometric methods were introduced, and various minor changes were made. The new technique also allowed the electrophoretic isolation of the three globulin fractions, and it was thus found that their chemical properties were different. Tiselius soon suspected that each of these three main globulin components consisted of several individual proteins that by chance had similar mobilities. Later methods have verified this suspicion, and many individual proteins have been isolated from the three main globulin fractions.

Tiselius had hoped that his new electrophoresis technique might also be useful in elucidating a problem of great interest to him, the isolation and identification of the large fragments and polypeptides obtained by a mild breakdown of protein molecules. In this respect the method was a disappointment; he felt that electrophoresis was hardly specific enough for separating the multitude of substances occurring in materials of biological origin. He then became interested in adsorption methods, which had been used to some extent in organic and biochemical preparations. The separation had hitherto been studied mainly on the column. Tiselius saw the possibility of developing a new quantitative analytical method in which the separation in the eluate emerging from the column could be observed by refractometric methods similar to those used in electrophoresis. He also gave a theoretical treatment that related the retardation volume of an adsorbed substance to its adsorption coefficient and the mass of adsorbent in the column. He considered the modification of adsorption behavior arising from the presence of a second, more strongly adsorbed solute. Specific retardation volumes were determined for a number of amino acids and peptides; and it was found that the length of the carbon chain had a decisive influence, each additional CH2 group producing a marked increase. The retardation volumes of neutral amino acids remained unaffected over a wide range of pH, while those of the acidic and basic amino acids showed a strong pH dependence.

A very important technical improvement was made by Tiselius and S. Claesson in 1942 with their introduction of interferometric methods to measure the concentration of the eluate. The object of this development was to overcome the instability arising from the very slight density differences between neighboring layers of eluate by restricting convective mixing to very small volumes. The volume of the interferometric channel was only 0.13 ml. The experimental arrangement was exceptionally well suited for the detailed study of the different types of chromatographic processes and led to important theoretical advances and to their experimental verification.

All the early experiments were carried out by frontal analysis that allowed determination of the concentration of the components in a mixture but did not result in their separation. The latter could be done by using an elution method. The eluted components, however, showed a very marked “tailing.” Tiselius showed in 1943 that this could be prevented by adding to the eluting solution a substance with higher adsorption affinity than any of the components in the mixture. The method has since been called displacement analysis.

In the following decade Tiselius and his coworkers made several modifications and improvements in this technique. In most of the work activated charcoal had been used as an adsorbent, and many attempts were made to modify its adsorptive properties by various pretreatments. Tiselius (1954) also tried to use calcium phosphate in the hydroxyl-apatite form as an adsorbent for proteins in conjuntion with phosphate buffers as eluting agents, with some degree of success, but the definitive solution to the problem for protein chromatography came with the development of the celluloseion exchangers by E. A. Peterson and H. A. Sober (1956). Tiselius’ decisive contribution to chromatography lay in the elucidation of the fundamental processes involved.

Until the mid-1940’s Tiselius did a large part of the experimental work by himself, sometimes with the assistance of a technician. After that time great demands were made on him, and he could spend little time in his laboratory. Studies on paper electrophoresis and zone electrophoresis were continued by his co-workers and students under his direction, and much work on other separation problems was delegated to his collaborators. Two important new separation methods originated in Tiselius’ laboratory. The dramatic separation of particles and of macromolecules, obtained by P. Å. Albertsson, used partition in aqueous polymer two-phase systems of, for instance, dextran and polyethylene glycol. In the gel-filtration method, devised by J. Porath and Per Flodin, fractionation is obtained according to size and shape of the dissolved molecules.

It was characteristic of Tiselius that he took up well-recognized qualitative experimental phenomena, analyzed them critically, and established their fundamental theoretical basis. As a consequence he was able to introduce essential improvements in experimental technique. His contributions to the development of new methods for analysis and separation of biological systems mark an era in the study of macromolecules and have contributed to the enormous development in biochemistry since the end of the 1930’s.


I. Original Works. Only a few of Tiselius’ 161 published papers can be mentioned here. A complete bibliography is in the biography by Kekwick and Pedersen (see below). They include “A New Method for Determination of the Mobility of Proteins,” in Journal of the American Chemical Society, 48 (1926), 2272–2278, written with T. Svedberg; “Über die Berechnung thermodynamischer Eigenschaften von kolloiden Lösungen aus Messungen mit der Ultrazentrifuge,” in Zeitschrift für physikalische Chemie, 124 (1926), 449–463; the revision and enlargement of Svedberg’s Colloid Chemistry (New York, 1928); “The Moving Boundary Method of Studying the Electrophoresis of Proteins,” in Nova acta Regiae Societatis scientiarum upsaliensis, 4th ser., 7, no. 4 (1930), 1–107; “Adsorption and Diffusion in Zeolite Crystals,” in Journal of Physical Chemistry, 40 (1936) 223–232; “A New Apparatus for Electrophoretic Analysis of Colloidal Mixtures,” in Transactions of the Faraday Society,33 (1937), 524–531, originally sent for publication to a biochemical journal but refused as being “too physical” “Electrophoresis of Serumglobulin II. Electrophoretic Analysis of Normal and Immune Sera,” in Biochemical Journal, 31 (1937), 1464–1477; “A New Method of Adsorption Analysis and Some of Its Applications,” in Advances in Colloid Science, 1 (1942), 81–98; “Adsorption Analysis by Interferometric Observation,” in Akriv För kemi, mineralogi och geologi, 15B , no. 18 (1942), 1–6, written with S. Claesson; “Displacement Development in Adsorption Analysis,” ibid., 16A no. 18 (1943), 1–11; “Electrophoresis and Adsorption Analysis as Aids in Investigations of Large Molecular Weight Substances and Their Breakdown Products,” in Les Prix Nobel en 1948, 102–121, in Nobel Lectures in Chemistry 1942–1962 (Amsterdam, 1964), 195–215; “Chromatography of Proteins on Calcium-Phosphate Columns,” in Arkiv för kemi, 7 (1954), 443–449: “Separation and Fractionation of Macromolecules and Particles,” in Science, 141 (1963), 13–20, written with J. Porath and P.Å. Albertsson; and the autobiographical essay “Reflections From Both Sides of the Counter,” in Annual Review of Biochemistry, 37 (1968), 1–24.

II. Secondary Literature. Tiselius’ collaborator S. Hjertén published a biography of his former teacher, “Arne Tiselius 1902–1971,” in Journal of Chromatography, 65 (1972), 345–348; a bibliography of Tiselius’ papers is in R. A. Kekwick and K. O. Pedersen, “Arne Tiselius 1902–1971,” in Biographical Memoirs of Fellows of the Royal Society, 20 (1974), 401–428. An earlier publication dealing with Tiselius’ scientific life is K. O. Pedersen, “Arne Tiselius,” in Acta chemica scandinavica, 2 (1948), 620–624. The important new approach to the chromatography of proteins is given in E. A. Peterson and H. A. Sober, “Chromatography of Proteins. I. Cellulose Ion-Exchange Adsorbents,” in Journal of the American Chemical Society, 78 (1956), 751–755. In honor of Tiselius’ sixtieth birthday a number of his friends published “Perspectives in the Biochemistry of Large Molecules,” which is Archives of Biochemistry and Biophysics, supp. 1 (1962).

Kai O. Pedersen

Arne Wilhelm Kaurin Tiselius

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Arne Wilhelm Kaurin Tiselius


Swedish Biochemist

Arne Tiselius was a Nobel Prize-winning biochemist who helped to develop techniques for separating mixtures of proteins into their individual components. These methods allowed researchers to obtain specific proteins for further study.

Arne Tiselius was born in Stockholm, Sweden, in 1902, and he became interested in chemistry during childhood. He went on to study this subject at Uppsala University. A major factor in his decision to attend this school was the presence of Theodor Svedberg (1884-1971), a well-known chemist. By 1924, Tiselius had earned his master's degree in chemistry, physics, and mathematics. He remained at the university in order to work as a research assistant to Svedberg.

Svedberg was interested in isolating individual proteins from organisms. One of the techniques he considered using was electrophoresis. In this technique, a mixture of electrically charged molecules (such as proteins) is placed in an electric field. Molecules with a negative charge move toward the positive end of the field, and vice versa. Molecules with more charge move faster than do those with less charge. In addition, smaller molecules move faster than larger molecules. As a result, electrophoresis can separate a mixture of proteins into individual bands based on the proteins' charge and size.

Tiselius began working with Svedberg on the use of electrophoresis to separate proteins called albumins. Albumins are a group of similar proteins that help to transport substances in the bloodstream. By 1930, Tiselius had earned his doctorate degree and had become an assistant professor in chemistry. At the time, the field of biochemistry—which includes the study of proteins—was not officially recognized at Uppsala University. Therefore, Tiselius decided to turn to more traditional fields of chemistry in order to become a full professor.

For several years, he studied zeolite minerals. The crystals of these minerals adsorb water; that is, they attract water to their surfaces. These crystals can also adsorb other chemicals such as ethyl alcohol, bromine, and mercury. While working with these minerals at Princeton University in the United States, Tiselius met biologists and chemists who knew of his work with Svedberg. They encouraged him to continue with his investigation into electrophoresis because they felt it would be of use to their own projects in protein research.

When Tiselius returned to Uppsala, he once again began to experiment with electrophoresis. He developed new equipment that allowed him to obtain more accurate data, and he was eventually able to separate proteins from the blood serum of horses. Serum is the liquid portion of the blood from which certain molecules have been removed. Electrophoresis separated the serum proteins into four bands. One band consisted of albumins; the other three were unknown. Tiselius named them alpha, beta, and gamma globulins. It is now known that alpha and beta globulins have several important functions such as transporting other substances and aiding in blood clotting. Gamma globulins are also known as antibodies; they play an important role in the immune system. Tiselius's work revealed the complexity of blood proteins, and as a result of this research, he was made the first professor of biochemistry at Uppsala University.

Tiselius soon realized that some biological chemicals are so similar that electrophoresis cannot separate them. In the 1940s, he began to study how adsorption chromatography could be used to isolate proteins. Adsorption chromatography relies on the fact that some chemicals adsorb, or adhere, more strongly to certain materials than do other chemicals. Tiselius developed a method of adsorption chromatography that involves a column packed with zeolite crystals, which act as an adsorbent. When a mixture of proteins is poured into the column, the proteins least attracted to the zeolite crystals pass through the bottom of the column first, and those most attracted to the crystals pass through the column last. Tiselius and Frederick Sanger (1918-1982) used this technique to separate the hormone insulin into its four components.

In 1948, Tiselius was awarded the Nobel Prize for Chemistry for his work on the separation of proteins using electrophoresis and adsorption chromatography. Between 1960 and 1964, he served as president of the Nobel Foundation. He received 11 honorary degrees from various universities and won numerous other awards.


Arne Wilhelm Kaurin Tiselius

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Arne Wilhelm Kaurin Tiselius

The Swedish biochemist Arne Wilhelm Kaurin Tiselius (1902-1971) was awarded the Nobel Prize for Chemistry for his researches on electrophoresis and adsorption analysis, especially for his discoveries concerning the nature of the serum proteins.

Arne Tiselius, son of Dr. Hans A. Tiselius, was born in Stockholm on Aug. 10, 1902. He studied chemistry at the University of Uppsala. Following his graduation in 1925, he became research assistant to the physical chemist Professor The Svedberg, the inventor of the ultra-centrifuge. In 1925 Tiselius began to use electrophoretic analysis, long employed for proteins and enzymes. This method studies the migration of the components in a solution under the influence of an electric field, their moving boundaries being observed by fluorescent photography. Tiselius found the method unsatisfactory, and he developed the method of observing the components by ultraviolet-light photography, using quartz lenses and a special light filter. He considered his method very specific, but he felt that its resolution capacity was not sufficiently high. He graduated as a doctor of science at Uppsala in 1930 with a thesis on this work, and he then became assistant professor of chemistry in the University of Uppsala.

As there was no chair of biochemistry in Sweden, Tiselius turned to the inorganic field, and he published research on the diffusion and adsorption phenomena in zeolite crystals. While holding a Rockefeller Fellowship at Princeton University in the United States, he was stimulated to continue his protein studies. On his return to Uppsala in 1935, he redesigned his electrophoretic apparatus and published his new model in 1937. Outstanding among the numerous advances made with his new apparatus was his demonstration that blood serum consists of albumins and of alpha, beta, and gamma globulins. These methods and results were widely used in the United States during World War II, especially in relation to the fractionating of blood serum for transfusion purposes. In 1938 a research chair of biochemistry was created for Tiselius at Uppsala, and he worked at first in Svedberg's Institute of Physical Chemistry. In 1946 biochemistry became an independent department, and in 1950-1952 a new Institute of Biochemistry was built.

In 1940 Tiselius began to work on adsorption methods, and he developed especially the methods of frontal and displacement analyses. In this work he used chromatographic methods, and he developed his technique to provide accurate quantitative results. For his work in these two fields he was awarded the Nobel Prize in 1948.

Tiselius received honorary degrees from 13 universities and many other honors. In 1949 he became a Foreign Member of the National Academy of Sciences in Washington, and in 1957 he was elected a Foreign Member of the Royal Society. He became Vice President of the Nobel Foundation in 1947 and President in 1960. His published work appeared entirely in scientific journals. Tiselius died in Uppsala on Oct. 29, 1971.

Further Reading

There is a biography of Tiselius in Nobel Lectures, Chemistry, 1942-1962 (1964), which also includes his Nobel Lecture. For his methods and results see A. White, P. Handler, and E. L. Smith, Principles of Biochemistry (3d ed. 1964), and E. and M. Lederer, Chromatography (2d ed. 1957). □

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