In multiple wavelength anomalous diffraction changes are induced in the atomic scattering factor of a heavy atom bound to the protein by measuring diffraction data at a number of different X-ray energies where the anomalous scattering factors of the heavy atom are significantly different from one another. The largest changes in the anomalous scattering factors of atoms occur around characteristic absorption edges since their values are directly related to the atoms atomic absorption coefficient. This is convenient since the majority of heavy atoms which bind to proteins have absorption edges which lie in the energy range typically used for protein diffraction work, .
The earliest reported multiple wavelength experiment was performed in the early 70's by Hoppe and Jakubowski  where a sealed tube X-ray generator was used with Ni and Co characteristic radiation to determine phases of the protein erythrocruorin containing Fe as its anomalous scatterer. The experiment showed that the small changes in the Fe scattering power induced by a change of wavelength could indeed be used to calculate the unknown phases. The use of characteristic X-ray energies restricted the method somewhat but not long afterwards in the late 70's synchrotron radiation became available to the biological community. A continuously tunable source of X-rays meant that X-ray energies could be selected which matched the scattering properties of the heavy atoms present in the sample protein crystal. In 1978 Phillips  demonstrated that large anomalous scattering effects at the edges of heavy atoms could be taken advantage of in MAD experiment by optimally selecting the X-ray energies to maximise the differences in the heavy atom anomalous scattering around the absorption edge. It was also shown that phasing could be performed in essentially the same way as in the MIR method.
In 1980 Karle  suggested an algebraic approach to the solution of the phase problem which was specifically directed at the MAD method. This approach was thereafter adopted by Hendrickson  in the MADSYS data analysis package and has been used in the ab initio determination of a number of protein structures     . The classical MIR approach to MAD phasing has also been successfully used .