You could see that with the… with the mutants that affected the assembly of a phage, and amber mutants were studied extensively by Edgar and others of bacteriophage T4… were studied extensively by them, in which they found that all the pieces of phage that we have identified, when we smashed phage up with enzymes and had classified things as cores and sheaths and heads and used electron microscopy, the negative staining… now all extracts of these bacteria infected with phages missing in one particular gene could just be looked at. And of course a most remarkable menagerie was discovered. There were mutants with free heads and free tails – they hadn't glued them together. There were mutants in which the heads hadn't formed but formed polyheads. These are long, long tubes. There were polysheaths. And using all of this one could now get on to studying the most interesting questions of... of virus assembly. And the whole idea that this is made by a kit, that you make the parts first and then the parts stick together; really I think opened up the whole of the concept of how you make elaborate cell structures, and by this hierarchical self-assembly mode. And so they... by using all of these techniques, that could be studied; there were similar things in… in lambda, studying the assembly of lambda, identifying all the genes. But the interesting thing is… is that one needed some kind of in vitro technique. That is, although the genes gave you… although the temperature… although the conditional lethal experiments gave you a means of saturating the genetics, that is we'll find all the ways we can of breaking this thing. You can break it this way; you can break it that way. To find out what is being broken needs some other approach. In the... the morphological mutants of phages, people found that they could just mix two extracts, so if they had one that only made heads and one that only made tails, they could just mix the two extracts and the heads and tails would glue together. I mean, that's self-assembly with a vengeance. And you could go and order all these extracts by just mixing them in the right order and seeing whether you got good phage coming out. So you could work what was an early… early step... what was a late step in assembly; did assembly branch into two parts which then united as indicated by being able to make heads and tails separately? And so you had an in vitro method of replicating the function. And that means you could study the effect of mutation on it and it would make sense. The meaning of the gene could be determined by this way. In DNA replication you could do the same thing. You could actually take an extract, see if it made DNA. If something was missing from it, you could then purify a wild-type extract, the normal extract, and see what you had to add to this to replace the missing function. In this way you could get hold of the… the protein product of the gene and characterise its biochemistry. And of course this kind of analysis really opened up the whole definition of the internal machinery of the cell.
