 In the 1990s, Richards and collaborators used a combination of theory and experiment to investigate how the well-packed interior of proteins can nevertheless accommodate mutations.In the 1970s, with a succession of students and postdocs, the lab developed a series of chemical, photochemical, and cross-link labels for determining the position and relationships of proteins in biological membranes (), including glutaraldehyde and what was one of the two first general uses of the exceptionally tight interaction of biotin with avidin, anchored to ferritin for use in electron microscopy.The biotin–avidin system quickly became a central method in cell biology, immunology, and protein engineering, as well as electron microscopy.