Fred Sanger on Large-Scale Sequencing Strategies: The Human Genome Project
  Fred Sanger     Biography    
Recorded: 16 Jun 2005

Well, I haven’t really been involved in it because I retired, you see, about ‘82. I think it was, wasn’t it. So I had developed these methods and had applied it—the largest DNA that we’ve been able to apply it to was the Lambda phage.

One of the problems was this initial degradation. You see, we had to get smaller fragment to use with the dideoxy method. Really, it wouldn’t have been possible to do anything larger than the Lambda by that because the mixture would be too complicated to get pure fragments to start with.

Yes, well, it was a question, you see, of getting small fragments and what they did is to use restriction enzyme digest and you get a lot of smaller fragments. But if you take a human genome and just cut it down into restriction enzymes you get say a million fragments and you’ve got to fractionate them. The way they did this is by taking a bacteriophage, the vector.You can take a circular phage and you take fragments and you can put these fragments into the phage and then you can grow the phage and plate it out on a plate and get of lots of little plaques, lots of plaques and you can pick them out one at a time and so you fractionate and then you grow them up, you see, and you can make a lot of fragments, a lot of phages which just have this one component in. So in this way you fractionate by picking out a lot of spots on the plates. That has made a big difference between working on lambda and working on the human genome, really. I think that was the most important development.

Frederick Sanger, OM, CH, CBE, FRS (born 13 August 1918) is an English biochemist and twice a Nobel laureate in chemistry. In 1958 he was awarded a Nobel prize in chemistry "for his work on the structure of proteins, especially that of insulin". In 1980, Walter Gilbert and Sanger shared half of the chemistry prize "for their contributions concerning the determination of base sequences in nucleic acids". The other half was awarded to Paul Berg "for his fundamental studies of the biochemistry of nucleic acids, with particular regard to recombinant-DNA".

He is the fourth (and only living) person to have been awarded two Nobel Prizes, either wholly or in part.