[Q] Now what was the big problem, Dorothy, getting into protein structure solution?

It was to find how to solve the phase problem and actually, the... there was only one method known in the 1930s in which the phase problem could be solved which was by isomorphous replacement. And that in fact is if you're being strictly honest, you date back to a paper by Duane in the American Academy in 1925 or '26 which the first electron density maps are calculated by a formula of course proposed by WH Bragg. But in 1915 when nobody had done it until 1926, curiously enough, and they point out having looked at and seeing what was happening with their figures, that in fact... well assuming they knew the structure in their calculation, they didn't need to know it, that all the signs were determined by the heavy atoms, the heaviest atom present, which was the chloride of sodium chloride. And they also pointed out that alternatively, we would have found it by comparing the signs for sodium chloride and potassium chloride but somehow nobody saw that immediately, so Bragg himself did his first electron density maps with signs calculated from the positions he'd already found from the atoms and dioxide and so on. And Henry Lipson says how they suddenly realised that in fact all these signs were determined by the calcium in the structure.