Nucleic acids are replicated with conspicuous fidelity. Infrequently, however, they undergo changes in sequence, and this process of change (mutation) generates the variability that allows evolution. As the result of studies of bacterial variation, it is now widely believed that mutations arise continuously and without any consideration for their utility. In this paper, we briefly review the source of this idea and then describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.

We recently reported that fellow eyes of patients with unilateral neovascular AMD have on average foveal cone ERG amplitudes that are normal, but implicit (peak) times that are slower than normal.'0 Since a defect in choroidal filling is apparently common in patients with AMD'-3 and is associated with visual dysfunction,46 we investigated whether this angiographic finding was also related to the slowed foveal ERG seen in the fellow eyes of patients with the unilateral neovascular form. MethodsWe evaluated the fellow eyes of 67 patients (ages 61 to 89) with unilateral neovascular AMD. These patients were part of a larger group with unilateral neovascular AMD who are being followed prospectively with foveal cone ERGs and other tests of cone function to predict who will develop a choroidal neovascular membrane in the fellow eye; demographic characteristics and ocular findings of this larger group have been described previously." Eligibility criteria for the present report included a corrected Snellen visual acuity of 20/60 or better, sufficiently clear media to allow detailed evaluation of the fundus, macular drusen, and no sign of other retinal disease in the study eye.These study eyes had a foveal cone ERG recorded and had angiograms of clear, readable quality throughout the transit. The angiograms were read by two of the authors JCR and ARG), masked with respect to results of foveal cone electroretinography, to identify those angiograms with a prolonged choroidal filling phase; the latter was characterised by a non-uniform fluorescence extending over at least 5 disc diameters of the posterior pole persisting through the onset of the venous phase of the retinal circulation. 1Foveal cone ERGs were elicited with a 40 white stimulus flickering at 42 Hz presented by a hand held, dual beam stimulator ophthalmoscope (Maculoscope, Doran Instruments, Littleton, MA, USA) as previously described.'0 12 Responses were monitored with a contact lens electrode, amplified, filtered, digitised, summed, and quantified by Fourier analysis with respect to amplitude and phase; phase was then converted to implicit time (that is, time interval from stimulus onset to the corresponding cornea positive response peak). AbstractAimsBackgroundBerman-Gund

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