A number of groups, two groups in fact: a group at Utah began using zinc finger nuclease and I'll explain those in a minute, to... to introduce mutants in drosophila. A man called Dana Carroll. Now he used the zinc finger nuclease developed by a man called [Srinivasan] Chandrasegaran who worked with Jeremy Berg. Now what he did, he made a zinc finger nuclease which was, had no specificity other than the DNA, other than the zinc finger part of recognising the DNA. This he took from the catalytic domain of restriction enzyme called FOCII which he had been studying. And he showed that this... that his targeting depended purely on the zinc finger which he used. Now the early work was done making three zinc fingers and it was used by a man called Matthew Porteus in David Baltimore's lab, to show stimulation of gene editing or gene correction in a model system using GFP protein. And they got factors of sort of modest ten, a factor of ten or something like that, 20 depending on what they did. Now, these were fairly home-made zinc fingers which he made himself. As I've said before you could write down the sequence of a zinc finger from all the published work which would bind the two sequences enough, what's the word? Redundancy that almost anything will bind. So it wasn't... it wasn't optimised in any way, not very efficient but it showed that you could stimulate... multory combination this way, or gene replacement. Gene replacement is what it is but it's not the whole gene, so gene editing is the best word or gene correction. I think editing is the best word of all but they tend to call it correction.

Another group was the group of Dana Carroll who I mentioned were they made their own zinc fingers and using Chandrasegaran catalytic domain, they made mutants of drosophila and they made fingers of various kinds... nothing was under control. Many of the mutants they did died, but those that survived they were able to select on the phenotype. So they had some success with that, making mutants in drosophila. So these are model experiments but now if you want to target into a patient you have to make sure there's nothing hanging over you... you can't start having selection, you have to do it in one go. And it must be absolutely targeted uniquely. So... what Sangamo... there's a group led by Michael Holmes, under Philip Gregory, these are the people... Holmes, Fernhoff and Gregory and they published a paper, it appeared in Nature on June the 5th this year. It was on-line in April and the paper was sent in last November. I had a hand in writing that paper, I don't appear as an author but I'm thanked for reading the manuscript. I was thanked for a critical reading of the manuscript, but critical this would be... in fact I wrote quite bits of it, but never mind. I think Nature editing. So it had quite a long history and the reason was I discovered that Nature were very... careful, there were very worried about publishing a paper that was zinc correction, so soon after the death of the French children, the editor clearly didn't understand that this was something different as well in gene addition and because they want to make the paper short they wanted to cut the preamble where this was explained and so on. But anyway, it appeared in Nature and they consulted quite a lot of other people, I know this because people have told me about this. So that's a great step forward and the paper's entitled Highly Efficient Correction of Endogenous Gene using Zinc Fingers [sic] or something rather like that, that's what it is. It's zinc finger nucleases. So it's a great triumph and what was done was this.