detail for the way that structural information is extracted from single molecule diffraction data, the issue of damage limits for single molecule imaging remains inconclusive.

One of the most actively pursued routes to single molecule imaging involves measuring thousands of copies of a molecule one by one. The resulting data is extremely noisy and the molecular orientations are not known. The issue of molecular orientation must be resolved to assemble a 3D dataset, which can be performed by several algorithms [@LohEMC2009; @Fung2009; @Giannakis2012; @Kassemeyer2013]. The hallmark of these methods is that they are able to cope with signals as low as 0.01 photons per Shannon-Nyquist pixel [@Tegze2012]. After the 3D dataset has been assembled, the atomic structure is recovered via coherent diffractive imaging methods[@Marchesini2007].

The crucial information needed to resolve the unknown orientations, and finally the structure, is contained in the modulations of diffraction signal arising from interference between different atoms, often called “speckles" (see Fig. \[fig:diffraction\_and\_explosion\]). Radiation damage changes the structure of the sample dynamically such that the final diffraction pattern is the sum of the diffraction from many modified structures, each with a different distribution of ions and ion displacements. It has been shown that averaging the diffraction 