The precise characteristics of these changes could not be predicted for a given crystal, but trends were noted across crystals of a given compound. At room temperature, dose series acquired on stationary crystals of biotin, Cu(II)-serine, and Zn(II)-methionine displayed high-amplitude nonmonotonic fluctuations in reflection intensities with increasing fluence (Fig. , Supplementary movies 1-3). Equivalent dose series on Zn(II)-histidine displayed generally mild non-monotonic intensity fluctuations (Fig. , Supplementary movie 4), while more beam-hardy Co(II)-porphyrin crystals only exhibited minimal monotonic decay (Fig. , Supplementary movie 5). We noted, however, that when illuminated with as much as 100 e -/Å 2 fluence at 200 kV, the Co(II)-porphyrin crystals would likewise exhibit gradual anomalous intensity fluctuations of this sort (Fig. ). These characteristic behaviors, shown for crystals illuminated at 200 kV in Figure , were mirrored at 300 kV (Fig. ). They were also observed for crystals prepared on a variety of TEM grid support films, including extra thick carbon support films, reducing the likelihood that changes were an artifact of the choice of support film or grid type (Fig. ). To rule out any drifting of the sample stage as a root cause of the observed lattice changes, control experiments were carried out in which multiple single diffraction patterns were collected on a stationary crystal separated by 1-2 minute intervals with the beam blanked, followed by continuous illumination of the crystal and collection of a diffraction series. Non-monotonic intensity fluctuations, and the appearance of previously unmeasured reflections, only proceeded while the electron beam irradiated a crystal (Fig. ). These observations collectively pointed to non-monotonic intensity changes being a beam-induced effect on the particular crystal illuminated.