Lederberg on his failures and regrets

Well, I don't know if it could have been avoided. I carried the study of conjugation in bacteria to a very considerable point, precisely because I was the main exponent, I felt I had to take a very conservative view, not to invoke hypotheses or processes for which there was not firm evidence, and I think partly for that reason, and partly because there's just so much any one person can do, the later steps of understanding this process fell to Francois Jacob and Elie Wollman, and I would have enjoyed being able to do that too, and they were the ones who did it. And, there was a certain rigidity, I was building a system, I had to defend many aspects of it against a lot of critics who didn't understand it at all, and in the process of doing that after a few years, you became locked into one specific view, and I've learned to be a little more flexible, I hope I have, dealing with problems a little later on. So, I think that's the place where I might have added one more brick to the edifice, but why should one person do it all?

Well...but they were very brilliant experiments on Jacobe's part, but I had had the idea that conjugation literally meant that two cells -- I was visualizing something like paramecia -- you had two intact cells, they exchange nuclei, they might be symmetrically equivalent, but at least it would be like fertilization, where a gamete delivers and entire genome into the cell, and I was running into some difficulty in interpretation of the genetic data, but I was finding all kinds of complicated ways -- it got to be a little bit like Ptolemy's epicycles -- of embracing the data within the framework of that model, and what Jacob and Wollman discovered was that -- originally it was a hypothesis, and I didn't put much stock in it at first, because at first there wasn't that strong data for it -- but they thought that the chromosome is transferred progressively from the male cell to the female cell, and that it takes about 100 minutes for the process to be completed, and that many of these transfers are interrupted before it's completed, so the act of fertilization in E.coli involves sometimes only tiny bits of DNA, sometimes larger bits, sometimes larger ones, and then very very rarely you have pretty much the whole chromosome coming in. So that was their alternative model. I should have been both more ingenious, and thinking of it first, and pertinent to the knowledge that they in fact built a pretty good case for it. So, all that happened 30 years ago, in the mid-50s when all of that was ironed out. Beyond that, well, one thinks of all the experiments one might have done and didn't get around to. I don't know if you call that failures or not. I can't complain. There was one thing I can recall. I was part of the planning for the Viking landing mission on Mars, and we were so imbued with the idea that there would either be no signal, or there would be a tiny signal. Suppose life there is very sparse, and they only had a few equivalents of bacteria. We struggled very hard to make our instruments sensitive enough, so that we could pick up the faintest signs of chemical activity. It ended up there was a lot of chemical activity, and we have not adequately modeled what happens when you take a soil and expose it incessantly to ultraviolet light for a long period of time, and then study the chemical reactivity of that product, and it turned out under those conditions, the UV generates ozone, the ozone oxidizes surface materials, you get superoxides of some of the metals, and bango, they will react chemically with some of the substrates that we were feeding it, and we didn't pay enough attention to that side of it. We were so struggling to, so focused on trying to detect the tiniest signal, that we didn't think of all the possible artifacts that might have come along. You know, we were given an impossible task, and that was to design in advance the one and only experiment, and we had no chance of a sequential process, in which you look at the preliminary results and say oh, that's interesting, let's try this, let's try that and so on. It all had to be put into a capsule and sent, it was a one shot kind of deal. So, to that extent in some ways the experiments were less conclusive than they ought to have been, although I think that we made a pretty firm case in the end with the built-in chemical observation capability that would almost preclude there being any living organisms at that latitude, and I haven't given up all of Mars yet, but at least in those latitudes...And, fortunately, there was other instrumentation, there was a mass spectrometer that was also sent along, it found no evidence of any organic material in the Mars surface, and if the oxidated activity that our experiments were demonstrating were the result of bugs, it would've been a very strong signal on the mass spectrometer, so I think we were able to come to a reasonable conclusion, but, you know, you asked me for something that in retrospect we could have done better, so I gave you an example.