Well, my first important discovery came aboutthrough a rather unusual
process.
More than almost everything else I have done,it was theory-driven rather than being
data-driven.
It was theory-driven in a sense that a postulatehad arisen out of the course of the
examination of the contemporary scene.
Namely, Avery, et al had shown transfer ofinheritable characteristics in a bacterium.
One was deeply motivated to want to know moreabout whether there were things like genes
in bacteria.
The approach that speculatively aroseand how to respond to is, "could one would
find out if there's a possibility of geneticrecombination, of crossing between bacterial
cells ?" My work with Neurospora had givenme
the methodological tools to facilitate gettingan answer to that question because I had been
studying nutritional mutants in Neurosporaand had been selecting for nutritionally wild
type,where we coined the term "prototrophic" revertants
as part of our study, their behavior.
So, bythat selective process, we knew we had a means
by which a particular genotype could befished out-a needle in the haystack - and
the magnet would be their ability to growon a
minimal medium.
So, on a theoretical basis one was able toput together a thought experiment
that said, "If bacteria can be crossed, andif you start out with two different nutritional
mutants, and if they exchange with one another,they will form prototrophic genotypes; you
will be able to select for them, and definetheir occurrence even if they happened very,
veryrarely," by a rather simple procedure: plating
the mixtures on minimal agar.
So, there was acase where the experimental design was worked
out as a theoretical postulate: "Does geneticrecombination occur?
Does it not occur?" and that was all workedout in advance of ever
doing the experiment.
Well, somewhat to my surprise, it worked very,very promptly.
I wasrather fearful when the first positive results
came in.
I was worried deeply that this was goingto be an artifact: that my hopes would be
dashed; I didn't want to get too excited aboutit.
Iwas scared.
I knew this was a very import finding, butI didn't want to be out on a limb until
I could be absolutely certain.
I didn't even want to commit myself emotionallyto
consequence until then.
So, it was a matter of going back to grindstoneand repeating the
experiment many times, doing it differentways and being sure that it was a totally
reliableand reproducible result.
Put in every control I could think of to besure I had controlled for
possible artifacts.
Happily, with bacteria, one can redo theseexperiments -- you can run one
or two cycles a day on this kind of experimentationso within a few weeks it was possible to
get a total validation of that.
Well, all that happened almost precisely 50years ago.
I arrivedin New Haven in March, 1946 and by early June
had it completely taped down that crossingwas taking place.