[Splitting into two lines: The historical development of the analytical and the gas ultracentrifuge]. / Zwei Entwicklungslinien einer Forschungstechnologie: Zur Geschichte der Analytischen Ultrazentrifugen und Gasultrazentrifugen.

In a historical perspective the ultracentrifuge is often taken as perfect example of a research technology according to Shinn and Joerges (Shinn and Joerges 2000, 2002). Research technologies are defined by a generic device, its own metrology and the interstitiality of the historical actors connected with the device. In our paper we give a detailed analysis of the development of the ultracentrifuge and thereby reveal two different lines of development: analytical ultracentrifuges and gas ultra centrifuges used for isotope separation. Surprisingly, we could not find any interstitial and transversal connections for these two lines. The lines end up with two different devices based on two different technical concepts. Moreover, the great majority of the actors stick to one line. These results are in accordance withother authors, who developed the concept of research technologies further and tried to sharpen their definition.

From oil-turbine to Model E: early days in retrospect.

This account deals approximately with the period 1940-1960, in which time Svedberg's invention of the first reliable ultracentrifuge was making a great contribution to developments in physical biochemistry. In the 1930's, only at Uppsala could an ultracentrifuge experiment be conducted, but by the 1960's electrically driven machines-the "Model E"-were widely available, particularly in the USA. The instrument was used extensively to follow fractionation methods for purifying proteins and other biological macromolecules and to determine their sedimentation coefficients and molecular weights. Here the author calls upon some of his own experiences, having been able to work with some of the now-famous contributors to the subject. As an analytical instrument, a good example was the proof by a velocity run that a particular sample of DNA was free of protein. This was essential in allowing the viscosity and titration characteristics to be ascribed to the hydrogen bonds formed between purines and pyrimidines-an observation subsequently proving critical. The Model E was easier to use than the oil-turbine, but discrepancies at first appeared between values for the sedimentation coefficients found from the two machines. These were subsequently resolved when attention was directed to rotor temperature uncertainties.

Richard Havel, Howard Eder, and the evolution of lipoprotein analysis.

In 1956, the JCI published a paper by Richard Havel, Howard Eder, and Joseph Bragdon on a method using an ultracentrifuge to physically separate plasma lipoproteins and chemical methods to analyze their lipid constituents. This paper has been much cited (7081 times as of this writing) in part because it represents a solid method that, with various modifications, has been applicable for the study of lipoproteins for almost half a century.

Spinning with Dave: David Yphantis's contributions to ultracentrifugation.

For nearly 50 years David Yphantis has helped advance analytical ultracentrifugation, promoted rigor in the thermodynamic analysis of biochemical data and encouraged students and colleagues to look for the deepest possible understanding of science. This article, written by five of Dave's students, presents some of the impressions he has made over the years.

Still looking for the Ivory Tower.

Following graduate training, which was disrupted by my changing schools and serving in the Navy in World War II, I arrived in Berkeley in 1948 as an instructor in the Biochemistry Department. Despite numerous academic reorganizations and a host of struggles over the University-imposed Loyalty Oath, dismissal of a faculty member because of political affiliations, free speech for students, and my resistance to mandatory retirement, I survived with the help of great graduate students, postdoctoral fellows, undergraduates, superb research assistants, and a supportive wife. Studies on structure of tobacco mosaic virus led to our investigating an ultracentrifuge anomaly and the construction of a synthetic boundary cell. In turn, this resulted in about 15 years of research on the ultracentrifuge and its application to the study of biological macromolecules. Among the latter, the discovery of large ribonucleoprotein complexes, now known as ribosomes, and chromatophores in photosynthetic microorganisms attracted the most attention. But it was the development of the photoelectric absorption optical system and the incorporation of the Rayleigh interferometer onto the ultracentrifuge that had the greatest impact on our further research. These tools, when applied to our initial research on E. coli aspartate transcarbamoylase (ATCase), led to the discovery of distinct subunits for catalysis and regulation and the global conformational change in the enzyme associated with its role in regulation. For almost 35 years we have been using the techniques of protein chemistry and molecular biology in studies of structural and conformational changes in the enzyme, the genes encoding the different polypeptides, subunit interactions, and assembly of the enzyme from six catalytic and six regulatory chains. Hybrids constructed from inactive mutants were used to demonstrate shared active sites requiring the joint participation of amino acid residues from adjoining polypeptide chains. ATCase is still being studied as a model for understanding allostery as a regulatory mechanism. Circularly permuted polypeptide chains are being used to study the folding and assembly pathways, and the recently determined crystal structure of the active nonallosteric catalytic subunit has led to new questions regarding the activated form of ATCase.