APPENDIX II: Synchrotrons, Demonstrated Potential of Major Shared Instrumentation Facilities

Synchrotron development was originally driven predominantly by condensed matter physics and materials science applications. In 1971 Rosenbaum, Holmes, and Witz published a paper in Nature discussing the potential of synchrotron radiation as a source for X-ray diffraction. By the mid 70's Holmes published an X-ray fiber diagram of a glycerinated fiber bundle for Lethocerus maximus flight muscle. During the 70's and 80's technology for monochromators and mirrors were developed at the synchrotron facilities throughout the world (DESY, Darsbury, Cornell, Brookhaven, Stanford), and in 1985 Michael Rossman and colleagues published in Nature the crystal structure of the human common cold virus using synchrotron radiation from the CHESS facility at Cornell. During the 1980's MAD phasing methods that depended upon the "tunability" of synchrotron sources were developed so that by 1990 synchrotron radiation had become a major resource for structural molecular biology research. These events have led to a powerful new capability for biomedical and biotechnology research that depends upon the use of large shared facilities with unique characteristics. The unique characteristic of synchrotrons for these applications being the high X-ray intensities and wavelength tunability of the source. During the 1990's the use of synchrotron facilities for protein crystallo- graphy in particular has undergone a rapid, almost exponential, expansion aided by the development of new detector technologies and cryocrystallography techniques that protect samples from radiation damage. In 1996 half of the protein crystal structures published in Nature involved the use of synchrotron radiation and the field continues to expand. There are approximately twenty synchrotron beam lines distributed among the five U.S. synchrotron facilities that serve the structural biology community, in addition to those at six more international centers in France, Britain, and Japan. The heavy demand on these resources has its origins in the work done to make experiments at synchrotron facilities easier and more accessible to the experts who help to drive the technology forward, as well as to the non- expert users who recognize the power of these techniques applied to their problem. The Biosync Report on Structural Biology and Synchrotron Radiation: Evaluation of Resources and Needs (http://www.ornl.gov/hgmis/ biosync) gives a snap shot of where the structural biology community of synchrotron users are today and their projections about the future. They make an important case for the need for regional facilities, easy access, quality instrumentation, user support, including developing enabling technologies. While a synchrotron facility as a whole is a huge investment (hundreds of millions of dollars), individual beam lines for specific user communities at the sources are of comparable scale to the cost of a GHz class NMR sector in the NMRC.