Sir

The first building block of the International Space Station was launched on 20 November 1998, but the potential uses of the space station are still under debate. A recommendation to scrap NASA's research on protein crystals was reported recently1. The reason given was that no serious contributions to our knowledge of protein structure have yet been made in space. We wish to point out, on the basis of recent experimental and theoretical evidence, that in many cases the potential benefits of the microgravity environment have not been fully exploited. This explains the low rate of success of protein crystallization in microgravity and opens up the scope for enhancing the efficiency of experimentation in space.

Microgravity eliminates sedimentation and convective mixing, so offering a more homogeneous growth medium compared with growth on Earth. Since this is likely to improve the degree of perfection of the crystals, why has microgravity crystallization not been more successful?

There are four common methods for crystallizing proteins: batch, vapour diffusion, dialysis and free interface diffusion (FID). Vapour diffusion is the most successful technique for crystallization on Earth. Naturally it became the method of choice for crystallization in microgravity. Thanks to the European Space Agency providing new means of conducting experiments in a far more systematic way, a comparison of microgravity crystallization using different methods was facilitated. The results demonstrated that vapour diffusion is not the best technique for crystallization in microgravity2.

Images from CCD cameras recorded during flights showed that some crystals grown by vapour diffusion displayed a cyclic motion within the aqueous drop in which they grow3. This motion is attributed to Marangoni convection, an effect which serves to reduce concentration gradients along the interface between the solution and the vapour4. In the case of FID and dialysis there is no interface between solution and vapour and this cyclic motion does not occur5.

Cyclic movement of the crystals in microgravity destroys the very benefit that is sought from the unique environment of outer space and thus may be a limiting factor in the ultimate perfection (indicated by X-ray diffraction) of the crystals that can be obtained6,7,8.

Several researchers have mentioned that crystals grown in microgravity by dialysis and FID methods appeared to be superior to those grown by vapour diffusion9,10, but those results were not taken seriously enough and most experiments were still done by vapour diffusion. Recent video recordings2,3,5 show beyond any doubt that crystal movement (akin to sedimentation referred to above) takes place in the case of vapour diffusion but not with the other methods.

It is apparent that we may have only now grasped how best to use the microgravity environment. Hence it would be a great shame if the experiments were scrapped now, just at the stage when a better understanding of crystallization in space and its fluid physics and biophysical chemistry is being gained. We are now in a position to explore more efficient ways of increasing the success rate of these experiments. The translation of the results to improve protein structure determination will come later. The stage of basic research is not yet completed to allow targeted exploitation to take place.