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.