After showing that we could recombine the chains, our task of course was to show how the individual amino acid sequence of each individual antibody differed from the next one, and that, we proposed, was the result of somatic recombination – an event that geneticists have obviously understood for many, many years of work outside of the soma in... in evolutionary time and in inheritance. So this recombination was proposed in the way of a theory that, inside each cell, recombination events caused the variable regions to vary. And, as I said before, this was three quarters right, but there was another addition which we hadn't explicitly mentioned – namely that there's also somatic mutation. So that meant there were special enzymes treating the DNA for antibodies.
It was an extraordinary piece of theoretical challenge and it was very pleasing because this was one case where theory mattered. Not only Macfarlane Burnet's theory but a whole bunch of people arguing about how you got the origin of diversity. The pun was that you needed a generator of diversity, G-O-D, and so everybody was looking for G-O-D. In fact, I had the privilege, in the middle of this somatic recombination theory of discussing it with my friend Jacques Monod, the great molecular biologist in... in France, at the Institut Pasteur. He and Jacob had invited me at this stage to give a lecture there and Monod and I particularly became close friends and we used to argue like crazy about the details of this... and I won't go into that now, but I do think it's worth a side bar to show how personalities differ and how people differ in respect to intellectual accomplishments.
We used to talk about different minds and one of the minds I brought up was Sigmund Freud, and he said, 'Gerry, Sigmund Freud is not only silly but he's a charlatan.' And I said, 'Jacques, what are you talking about? He wasn't a scientist even though he thought he was, but he was a great intellectual pioneer; he did more for understanding the notion of unconscious... the unconscious than anybody, even though other people had the idea before him.' And he said, 'Look, this is ridiculous.' And we had quite a heated exchange. At which point in exasperation I said, 'Jacques, all right, let's put it this way.' He said, 'Look, I have no unconscious; I'm responsible for everything I do.' By the way, he was of Huguenot extraction; I don't know if that had something to do with it. He said, 'I am responsible; there is no unconscious. This is Jacques.' And I finally said, 'Jacques, let's put it this way, everything Freud said applies to me and nothing to you.' And he said, 'Exactly, my dear fellow.' So, coming back, we used to argue about this origin of diversity and it remained quite a dilemma as to how to show it, until Susumu Tonegawa used molecular biological techniques to show how you had recombination of so-called V, D and J portions as well as somatic mutation occurring in the antibody genes.
