NEWS & VIEWS NATURE|Vol 462|24/31 December 2009

OBITUARY In 1945, Ginzburg was invited to become a visiting professor at the newly established radiophysical department at Gorky Vitaly Ginzburg (1916–2009) University in what is now Yekaterinburg, Nobel-prizewinning success in physics achieved in the Soviet system. and he subsequently became chair of a group studying the propagation and radiation of radio waves. Living mainly in Moscow, Vitaly Lazarevich Ginzburg, who died for seven years Ginzburg made annual on 8 November, played a leading part in applications for his wife to be allowed to many aspects of theoretical physics during return there, but these were refused until the Soviet era and after the dismantling after Stalin’s death in 1953. of the Soviet Union in 1991. His research In 1947, he was personally attacked in an

contributions were vast and of the highest article in the Literaturnaya Gazeta, which A. ZEMLIANICHENKO/AP order, culminating in the award of the blamed him for non-patriotic citations in Nobel Prize in Physics in 2003, jointly with his papers and for ‘idealism’. Despite this Alexei Abrikosov and Anthony Leggett, for attack, Igor Tamm, in need of physicists of pioneering studies in superconductivity and the highest quality, arranged that he join superfluidity. the Soviet nuclear-weapons programme. Ginzburg was born in 1916 into a Jewish The leaders of this project — Yulii Khariton, family in Moscow just before the Russian Igor Kurchatov and Yakov Zeldovich — Revolution. His formal school education assembled a brilliant team of physicists and began only at the age of 11. In 1931, Evgeni mathematicians, including Andrei Sakharov, Bakhmet’ev, a professor at Moscow’s Israil Gel’fand, Alexander Kompaneets, Technical University, helped him to get a job Landau and Ginzburg, to develop nuclear as a laboratory assistant in the university’s weapons in response to the United States’ X-ray laboratory. This experience whetted Landau on the theory of superconductivity, development of the atomic and hydrogen his appetite for physics and he entered published in 1950. This work built on bombs. Ginzburg’s major contribution was Moscow State University in 1933 to study this Landau’s theory of second-order phase to propose the use of lithium-6 as the fuel for discipline. Strongly attracted to theoretical transitions. Ginzburg had already applied the Soviet hydrogen bomb, a quite different physics, he was unsure of his mathematical Landau theory to ferroelectric phenomena. process from that adopted in the United ability and decided to work in optics under The crucial advance in the Ginzburg–Landau States. But he did not remain long in the the supervision of Grigory Landsberg. He theory was the concept that, in the transition nuclear programme. went on to take his PhD in 1940 and, having from the normal to the superconducting state, After Stalin’s death, Ginzburg was elected transferred to the Lebedev Physical Institute the phenomenon of symmetry breaking in a corresponding member of the Soviet of the Soviet Academy of Sciences (FIAN) a metal, a characteristic of Landau theory, Academy of Sciences and his wife returned in Moscow, completed his science doctorate was associated with the wavefunction of the to Moscow. He became a full member of the there in 1942. He was to remain a member of metal’s superconducting electrons, a non- academy in 1966 and, on the death of Tamm the FIAN for the rest of his life. gauge invariant process. This new paradigm in 1971, became head of the theoretical The scope of Ginzburg’s research can was to have profound implications for physics department at the FIAN. During be appreciated from his own attempt at a many aspects of quantum physics beyond this period, Sakharov had become politically scientific autobiography, in which he listed, superconductivity, including the Higgs active and was classed as a dissident, being roughly chronologically, his range of interests phenomenon, which gives particles mass. exiled to Gorky in 1980. The FIAN provided in theoretical physics: classical and quantum His broad interests in theoretical physics a scientific home for him, but, as a member of electrodynamics, Cherenkov and transition were reflected in the famous Ginzburg the theoretical physics department, this placed radiation, the propagation of electromagnetic seminars, which were held each week at the significant constraints on Ginzburg, who waves in plasma, radio astronomy and FIAN. Ginzburg stated that the topics for was not allowed to travel abroad for many synchrotron radiation, cosmic-ray and γ-ray discussion should include all theoretical years. Matters changed significantly with the astrophysics, the scattering of light in crystals, physics, except particle physics. His leadership period of perestroika that started in 1985, with the theory of ferroelectrics, and superfluidity at these seminars was impressive: he regularly Ginzburg being appointed a member of the and superconductivity. interrupted the speaker to summarize what Congress of People’s Deputies from 1989 to In all of these areas, he wrote prolifically had just been said so that all listeners could 1991, when the body was dissolved. and made original contributions. For follow the argument. These were celebrated Ginzburg was a strong personality, example, his work on transition radiation, weekly events, with most of Moscow’s with deeply held humanitarian views a phenomenon that occurs when high- physicists making an effort to attend. that he maintained throughout the years speed charged particles cross two media of Ginzburg lived through a turbulent era. of Soviet rule. He kept an open mind on different electric permittivity, followed on The Soviet Union entered the Second World issues in theoretical physics, but based from his deep interest in electrodynamics, War in 1941, and the Soviet Academy of his opinions on a strongly developed and his comprehensive treatment of the Sciences was evacuated to Kazan, where intuition for the underlying principles. He topic was truly pioneering. His studies of Ginzburg worked for the next two years. In will be remembered with gratitude by all synchrotron radiation were highly influential 1937, he had married his fellow student Olga who experienced his kindness, and as an in establishing that this process is the Zamsha, but they divorced in 1946. In the inspirational figure who carried out world- dominant non-thermal radiation mechanism same year he married Nina Ermakova, who leading research against a background of in high-energy astrophysical phenomena in had been arrested in 1944 on a trumped-up significant political oppression. radio astronomy. These diverse interests were charge of plotting to kill Stalin. She was Malcolm Longair reflected in a series of influential books. given a lenient sentence and released under Malcolm Longair is at the Cavendish Laboratory, The pinnacle of his scientific achievement an amnesty in 1945, but was not allowed to University of Cambridge, Cambridge CB3 0HE, UK. was his groundbreaking research with Lev return to Moscow. e-mail: [email protected]

996 © 2009 Macmillan Publishers Limited. All rights reserved NATURE|Vol 463|21 January 2010 NEWS & VIEWS must self-organize, using some intrinsic, prob- test and refine the model, and what are its bio- ably physical, property of the axoneme to regu- a X = 0 logical implications? Single-molecule meas- late dynein. Computer simulations showed that urements9 could test whether experimental regulation of dynein by local curvature of the force–detachment relationships for axonemal axoneme, or by modifying the sliding distance X dyneins are within the range required by the between doublets, could both work in princi- –++–theory. Piston-like movement of doublets at 7 ple . Jülicher and colleagues have combined bc the base of cilia, required by the model, has theory and experiment to provide decisive been observed in some systems10, but needs X support for the sliding-control model. Their Time to be tested more generally. More ambitiously, work builds on a simple idea, first proposed by it might be possible to nano-fabricate simpli- Brokaw8, for how sliding might regulate motor Without springs: one With springs: fied model systems, such as those shown in stable oscillations activity to generate self-organized oscillations, group of motors wins Figure 2, and test their properties. an idea conceptually involving a system of Further testing will probably require a opposed motors and springs (Fig. 2). Figure 2 | Self-organized oscillations in a system genetic approach. Here, theory meets medi- Jülicher and colleagues’ initial insight1 was to of opposed motors and springs. a, Thought cal genetics in a potentially fruitful way. Pri- conceptualize the axoneme as an ‘active mater- experiment using an artificial geometry to mary ciliary dyskinesias are inherited diseases ial’, making no assumptions about its micro- illustrate how sliding control leads to oscillations, characterized by paralysis or defective wave- a principle now further refined by Jülicher and scopic properties. A rod of ordinary material 1–3 forms in epithelial cilia and sperm flagella colleagues . Two groups of dynein motors 11 resists a bending force by its stiffness and by anchored to a rigid scaffold walk outwards on due to ultrastructural abnormalities . These frictional resistance to its movement. An two static microtubules oriented with their minus are caused most often by mutations in ciliary axoneme, in contrast, can respond by actively ends outwards. The system can omit or include dyneins, but sometimes in other axonemal deforming in the direction of the applied force, springs (blue zig-zags). b, If the springs are absent, proteins12. The theory opens up the prospect owing to activation of its internal dyneins by the system is unstable and one group of motors of formulating causal explanations of the effect the deformation. This type of response can be wins: the winning motors (solid curve) exert force of mutations on beat waveform, and the flagel- quantified using negative values for the stiffness on the losing motors (dotted curve) in a direction lated single-celled organism Chlamydomonas and viscosity parameters. For certain values of opposite to their walking direction, increasing provides an ideal model for theory–structure– the likelihood that the losing motors will become these parameters, an instability will propagate 8 function studies. Key to this approach will be 1 detached from the microtubule . c, If the springs down the rod, and it will beat spontaneously . are present, as in a, the system undergoes stable careful experimental measurement of aber- An initial implementation1 of this concept rant waveforms, which the theory can relate to oscillations. Oscillations are self-organized in 2 predicted waveforms that propagated in the the sense that no external control of the motors internal molecular behaviour . 2 wrong direction. This problem was fixed by is required. The geometry is more complex in Could any of this help patients with primary allowing some relative movement between real axonemes, but the same concept applies: ciliary dyskinesias? In some patients, cilia lack- doublets at the base of the cilium (stiffness of dyneins on opposite sides of the axoneme oppose ing central pairs still beat, albeit abnormally12. the base enters the mathematics as a boundary each other, and crosslinking proteins supply Guided by mechanistic understanding of the condition), leading to the interesting prediction the springs. (Redrawn from a presentation by underlying defect, it might be possible to cor- F. Jülicher to illustrate a concept for self-organized that cells might control beat direction by regu- 8 rect this by using small molecules that weaken lating the stiffness of inter-doublet links at the oscillations proposed by C. J. Brokaw .) or strengthen dynein. ■ cilium base. The improved model2 was com- T. J. Mitchison is in the Department of Systems pared with experimental data from tethered several fixed parameters that Jülicher and col- Biology, Harvard Medical School, Boston, bull sperm using a ‘sperm equation’. This equa- leagues independently measured and fed into Massachusetts 02115, USA. H. M. Mitchison is at tion predicts sideways oscillations as a function the equation. These include the hydrodynamic the Institute of Child Health, University College both of distance from the base of the flagellum drag of the moving flagellum and its ordinary London, London WC1N 1EH, UK. and of several parameters that describe the stiffness, both of which oppose active defor- e-mails: [email protected]; physical properties of the axoneme. mation, and the beat frequency. The authors [email protected] Any oscillation can be described as a sum of obtained an excellent fit to the data, with both sinusoidal oscillations of increasing frequency, internal stiffness and friction taking the nega- 1. Camalet, S., Jülicher, F. & Prost, J. Phys. Rev. Lett. 82, 1590–1593 (1999). called Fourier modes; sideways oscillations can tive values expected for an active material. 2. Riedel-Kruse, I. H., Hilfinger, A., Howard, J. & Jülicher, F. be described by the temporal Fourier modes Importantly, a microscopic model of dynein HFSP J. 1, 192–208 (2007). of tangent angles. Power-spectrum analysis behaviour, incorporating the force-dependent 3. Hilfinger, A., Chattopadhyay, A. K. & Jülicher, F. Phys. Rev. E 79, 051918 (2009). showed that experimentally observed oscil- detachment concept illustrated in Figure 2, 4. Gibbons, I. R. & Rowe, A. J. Science 149, 424–426 (1965). lations in tangent angles were well approxi- predicted negative values for stiffness and 5. Numata, N. et al. Biochem. Soc. Trans. 36, 131–135 (2008). mated using only the first (fundamental) friction similar to those obtained by fitting the 6. Summers, K. E. & Gibbons, I. R. Proc. Natl Acad. Sci. USA 68, 3092–3096 (1971). Fourier mode, so the sperm equation could be sperm equation. 7. Brokaw, C. J. Cell Motil. Cytoskel. 66, 425–436 (2009). analytically solved using values of this mode. Jülicher and colleagues first solved the sperm 8. Brokaw, C. J. Proc. Natl Acad. Sci. USA 72, 3102–3106 (1975). Tangent angles quantify the curvature of the equation analytically using a linear approxima- 9. Schnitzer, M. J., Visscher, K. & Block, S. M. Nature Cell Biol. 2 2, 718–723 (2000). axoneme at a given position, and the curvature tion corresponding to small displacements , 10. Vernon, G. G. & Woolley, D. M. Biophys. J. 87, 3934–3944 is geometrically related to the sliding distance but a full, nonlinear solution was subsequently (2004). between doublets at that position. The sperm shown to predict similar waveforms3. Overall, 11. Fliegauf, M., Benzing, T. & Omran, H. Nature Rev. Mol. Cell equation thus relates time-dependent angular the model fits the experimental data well and Biol. 8, 880–893 (2007). 12. Castleman, V. H. et al. Am. J. Hum. Genet. 84, 197–209 (2009). movement at each position to the extent and provides a conceptually satisfying explana- rate of inter-doublet sliding at that position, tion for how cilia and flagella beat that unites Correction and to the local forces that either oppose or Brokaw’s mechanistic proposal for controlling 8 In the obituary of Vitaly Ginzburg by Malcolm promote further sliding. sliding with the active-material concept. Pre- Longair (Nature 462, 996; 2009), editorial The model contains two adjustable para- dicting beat frequency is a challenging future intervention introduced the statement that Gorky meters — stiffness and friction of the active goal for theorists, but this will probably require a University was “in what is now Yekaterinburg”. material inside the axoneme that deforms and detailed treatment of the microscopic details. That should have read “in what is now Nizhny exerts force during bending. It also contains What further experiments are needed to Novgorod”.

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