Sir

In his Correspondence “Excitement over X-ray lasers is excessive” (ref. 1), responding to your News Feature2 about the applications of X-ray free-electron lasers (FELs), Richard Henderson raises two points. First, that the development of X-ray FELs for biological applications threatens the field of structural biology because it will use up money needed for existing techniques; and second, that the development of existing techniques will be more fruitful than investing in an expensive, unproven technology such as X-ray FELs. I believe that both of these arguments are incorrect.

Synchrotron machines were developed by physicists and materials scientists, and have evolved to benefit biology. When the first dedicated synchrotron light sources came to life more than 20 years ago, they produced X-rays with intensities 50–100 times greater than a rotating anode generator. Yet synchrotron radiation triggered a revolution in the life sciences, and today almost 15,000 X-ray structures feature in the protein data bank as a result.

Did the construction of synchrotrons harm biology? Certainly not. Should one be afraid of a much bigger step ahead when the first X-ray FEL comes to life? I don't think so.

If one takes the speed of walking and multiplies it by 1010, the result is a speed 100 times faster than the speed of light. The expected improvement in peak brilliance offered by X-ray FELs over existing synchrotrons is of this magnitude. These machines will bring us into a world for which only predictions exist.

A lack of hands-on experimental data on the behaviour of matter under these conditions makes very detailed forecasts difficult. But one thing is certain: X-ray FELs will generate fresh thinking, new science and a new scientific community. To imply that there is nothing that X-ray FELs can discover in biology is misguided.

The money for building and running the Linac Coherent Light Source at Stanford (first of the planned X-ray FELs) will come from the US Department of Energy. These funds have no direct 'crossover' to biomedical research or biology. Every one of the five synchrotron X-ray sources in the United States was built and is operated by agencies that do not deal with biology.

One can make arguments for the advantages of using electrons, as outlined by Henderson, or others for using X-ray pulses. One can estimate that the conventional handicap of X-rays over electrons could be reversed3 and made into a net gain on very small samples, when extremely intense and very short X-ray pulses will be produced. This is the domain of the X-ray FELs.

There is surely room for more than one avenue to be explored — different techniques will be appropriate for different biological structures and processes. This flexibility is intrinsic to the nature of research and essential for scientific progress. There are no threats here, only challenges.