Svedberg Develops the Ultracentrifuge

Date 1924

Theodor Svedberg’s development of the ultracentrifuge enabled scientists to separate colloidal particles, including proteins, carbohydrates, cell organelles, and viruses.

Locale Uppsala, Sweden

Key Figures

• Theodor Svedberg (1884-1971), Swedish physical chemist
• John B. Nichols (fl. early twentieth century), American chemist
• Herman Rinde (fl. early twentieth century), Swedish chemist

Summary of Event

Many essential aspects of modern knowledge in the fields of chemistry, biochemistry, and biology are indebted to Theodor Svedberg’s development of the machine he called the ultracentrifuge. By definition, an ultracentrifuge is a fast centrifuge that produces a convection-free centrifugal field. Such a device is useful for the study of the properties of dissolved solutes, including the measurement of their molecular weights through sedimentation velocity and sedimentation equilibrium techniques, the identification of both their molecular sizes and their shapes, and the characterization of synthetic and natural macromolecules on the basis of the property called buoyant density. A centrifuge is a machine in which a compartment (rotor) is spun around a central axis to develop centrifugal force, which is measured in gravities and can be used to separate colloid particles and materials of different densities.

Svedberg was a Swedish physical chemist with a great interest in biology. Svedberg’s decision to become a physical chemist is said to have been based in part on his belief that numerous unsolved biological problems could be explained as chemical phenomena that could be studied best with the techniques of physical chemistry. He received B.S. and Ph.D. degrees in 1905 and 1907, respectively, from the University of Uppsala. In 1912, the university appointed him to the first Swedish chair of physical chemistry. One of Svedberg’s main lifelong interests was an understanding of the chemistry of colloids. It was this interest that led him to develop the ultracentrifuge.

A colloid is a mixture in which tiny particles of one or several substances are dispersed in another substance (very often water). Colloid particles are much larger than crystalloidal molecules (for example, sugar) or crystalloidal ions (for example, sodium and chloride ions). They are usually too small to settle out under the force of gravity or to be seen with light microscopes. The size of colloid particles ranges from 5 to 200 nanometers. Examples of very important biological colloid particles are proteins, deoxyribonucleic acid (DNA), and the viruses.

In his thesis, Svedberg described an electrical method for producing very pure colloidal suspensions of metals. Through continued efforts, he identified many other important aspects of the physical chemistry of colloids. A particularly frustrating aspect of carrying out these studies was that it was very important to identify the exact sizes of the colloid particles. This was difficult to do because the available methodology involved examining the rate of their settling out (sedimentation), and only the very largest colloid particles sedimented at rates that were useful.

Svedberg believed that sedimentation of colloid particles could be hastened to a point where their study would be practical if they could be subjected to the increased gravitational fields produced in a high-speed centrifuge. He proposed to design such a centrifuge in a fashion that would allow the sedimentation of the particles to be followed photographically. Svedberg began his work on this “optical” centrifuge while he was a visiting professor at the University of Wisconsin, Madison, in 1923. The centrifuge he developed there, in collaboration with John B. Nichols, was not entirely successful because, although the user could follow the sedimentation of colloid particles, convection problems prevented the unequivocal identification of their sizes.

After returning to Sweden, Svedberg continued his efforts and aimed to develop convection-free centrifugal sedimentation. In 1924, he and his colleague Herman Rinde succeeded in doing so. At first, Svedberg and Rinde studied inorganic colloids. They soon discovered, however, that the very important, poorly understood biological macromolecules called proteins would also sediment in their centrifugal fields. The researchers then quickly made important discoveries in fundamental protein chemistry. First, they demonstrated that all the molecules of any particular protein are of one size (monodisperse particles). These data contrasted greatly with those obtained with metal colloids, which are composed of particles of many sizes (polydisperse), and flew in the face of the established belief that proteins were also polydisperse. The Svedberg centrifuge, which he named the ultracentrifuge, allowed scientists to measure the sizes and the shapes of proteins, making it an invaluable research tool for biology, biochemistry, and medicine.

Svedberg received the 1926 Nobel Prize in Chemistry for his work on disperse systems. The Nobel Committee stated that these endeavors “proved the real existence of molecules and atoms.” In his Nobel acceptance lecture, Svedberg described the great potential he foresaw for the use of the ultracentrifuge in chemistry, medicine, physics, and biology. Over the next sixteen years, he improved the device’s design and function, and by 1936 he had produced an ultracentrifuge capable of spinning a centrifuge rotor at 120,000 revolutions per minute and of producing a centrifugal force of 525,000 times the force of gravity.

Using the improved ultracentrifuge, Svedberg and his coworkers examined hundreds of proteins from many different kinds of plants and animals. They found that the molecular weights of different proteins vary greatly, and they learned that proteins are round, monodisperse molecules possessed of high molecular weights. They also discovered that the same proteins from different species have similar or identical molecular weights. Svedberg and his colleagues also studied the properties of carbohydrates (for example, cellulose and starch) in the ultracentrifuge and learned that these biomolecules are very long, thin, polydisperse molecules. This work, much of which is described in Svedberg’s coauthored book The Ultracentrifuge (1940), was essential to the development of modern life science.

In addition to his work with the ultracentrifuge, Svedberg made many other important scientific contributions, including a seminal study of radioactivity and important participation in the development of the Swedish synthetic rubber industry. Svedberg’s scientific endeavors were reported in more than two hundred publications. He received many honors and awards for his efforts, including the Nobel Prize, the Berzelius Medal of the Royal Swedish Academy of Sciences, the Franklin Medal of the Franklin Institute, and honorary doctorates from Harvard University, Oxford University, the Sorbonne, and the University of Delaware.

Significance

Svedberg’s development of the ultracentrifuge had significant impacts on many aspects of chemistry and physics, but nowhere has this device been more generally valuable than in life science research. In fact, most life scientists view the advent of the general availability of ultracentrifuges as one of the outstanding technological events in the field. The great credit given to Svedberg is emphasized by the fact that the sizes of many biological particles, determined by ultracentrifugation, are denoted in “svedberg” units (s units). The impact of ultracentrifugation in the field of biology is made evident by scientists’ use of such “s values” to describe many important components of living cells that mediate or participate in life processes. For example, bacterial ribosomes (which mediate the synthesis of proteins) are described as being composed of 30 and 50 s subunits. Other examples of such usage abound throughout the literature of life science.

Furthermore, the ultracentrifuge enabled biologists, biochemists, physicians, and other life scientists to shift the focus of their endeavors from taxonomic and morphologic study of whole organisms to examination of smaller and smaller parts of such organisms. Examples of such research include the isolation of viruses and identification of the basis for their method of attacking cells, the separation of the subcellular organelles (for example, cell nuclei) and the elucidation of their biological functions, the development of understanding of the molecular basis for storage and utilization of hereditary information, the visualization and description of individual protein and nucleic acid molecules, and the discovery of the methodology for carrying out genetic engineering. Truly, the ultracentrifuge hastened the development of life science into molecular biology.

As Howard K. Schachman points out in Ultracentrifugation in Biochemistry (1959), the utilization of the ultracentrifuge as a research tool has evolved continually, leading to changes “almost as dramatic as the era beginning in 1923 when Svedberg and his collaborators first began to exploit centrifugal fields for the study of macromolecules and colloid particles.” In 1947, fewer than twenty ultracentrifuges were in operation worldwide. By 1959, three hundred sophisticated ultracentrifuges were available to the world scientific community. By the early 2000’s, thousands of these instruments were in service, and they had become routine tools—viewed as necessities—for most life science endeavors.

At the beginning of the twenty-first century, scientists can make measurements that were not even conceptualized by the most advanced early researchers in the field of ultracentrifugation. Many new techniques have been added to supplement the classical methodology, and many new aspects of ultracentrifugation have been developed. One outstanding example is the design of zonal rotors that allow large-scale use of ultracentrifugal technique suitable for industrial application.

Bibliography

Bloomfield, Victor A. “Ultracentrifuge.” McGraw-Hill Encyclopedia of Science and Technology. 6th ed. New York: McGraw-Hill, 1987. Brief summary presents a diagram of an ultracentrifuge, an explanation of the instrument’s design, diagrams of common rotors, and an explanation of usage in molecular weight determination by sedimentation equilibrium or sedimentation velocity. Includes suggestions for further reading.

Chervenka, C. H., and L. H. Elrod. A Manual of Methods for Large Scale Zonal Centrifugation. Palo Alto, Calif.: Spinco Division of Beckman Instruments, 1972. Practical text describes operating principles, equipment needed, and procedures used in large-scale zonal centrifugation. Also discusses methods used for industrial-scale isolation of viruses, subcellular organelles, proteins, and nucleic acids. Includes useful diagrams.

Claesson, Stig, and Kai O. Pederson. “The (Theodor) Svedberg.” In Dictionary of Scientific Biography, edited by Charles Coulston Gillispie. New York: Charles Scribner’s Sons, 1970. Brief biographical article provides an excellent picture of Svedberg and his contributions to science. Discusses his early study of colloid chemistry and his development of the ultracentrifuge as well as other contributions. Includes references.

Koehler, Christopher S. W. “Developing the Ultracentrifuge.” Today’s Chemist at Work, February, 2003, 63-66. Brief article describes Svedberg’s work as well as that of other scientists who contributed to the development of modern ultracentrifuges.

Schachman, Howard K. Ultracentrifugation in Biochemistry. New York: Academic Press, 1959. Classical, highly technical treatise on ultracentrifugation describes many aspects of the construction and biochemical use of ultracentrifuges. Thoroughly covers sedimentation velocity, sedimentation equilibrium, and data interpretation. Recommended for readers seeking in-depth coverage of the topic.

Svedberg, Theodor, and Kai O. Pederson. The Ultracentrifuge. Oxford, England: Clarendon Press, 1940. Describes the development of the ultracentrifuge by Svedberg and his colleagues’ group. Covers most of the theory and methodology of ultracentrifuges of the time and describes the ultracentrifugation of natural and synthetic colloids. Provides a vivid picture of Svedberg and his work.

Tiselius, Arne, and Stig Claesson. “The Svedberg and Fifty Years of Physical Chemistry in Sweden.” Annual Review of Physical Chemistry 18 (1967): 1-8. Discusses Svedberg’s impact on physical chemistry in Sweden. Concisely covers many aspects of his contributions to the chemistry of colloids, from the development of the ultracentrifuge to his overall role in academic science and technology.