Molecular Biology is the offspring of biochemistry and genetics

This, to this day, is not a very happy marriage.

Both sides tolerate one another, but the biochemists lean on function and the geneticists lean on math and statistics.

The progeny, or molecular biologists, fall in the middle, trying to muffle the yelling and screaming of the other two, but this diversity of ideas is actually what makes science great - even if mom and dad fight sometimes!

But, before we dig into the birth of this dysfunctional family, it is important to highlight that in the 1900's, the idea of a 'gene' was an abstract one.

We all know Mendel and his peapods, that traits are inherited and it was thought that this was all controlled by genes, but 'how' any of that worked biologically was essentially a mystery.

George Beadle was fascinated with the 'how' and spent many years in a Drosophila (fruit fly) lab trying to connect pigments to whatever a gene was.

And he rightly hypothesized it involved biochemical pathways.

He realized that approaching the problem from the perspective of the end product, the pigment, was wrong.

And this meant he had to figure out how to break the 'gene' and link it directly to biochemistry.

But doing that in a complex multicellular organism like a fruit fly was going to be impossible so he switched to a much simpler one: Neurospora!

Now, Neurospora, being a fungus, has certain features that made it ideal for this project.

Fungi are haploid (1 copy of the genome per cell, not 2) for a good portion of their life and heritable genetic changes are easy to track in their offspring because you don’t have to worry about any compensatory interference from an alternate working copy!

Beadle realized he could create mutations in fungi and then link those to biochemical processes.

But how do you make mutations in genes in 1941?

With X-rays!

So, he irradiated a bunch of haploid Neurospora and then grew them on different types of food:

One that had everything they needed to live (complete), and one that did not (minimal).

Once he found mutants that could grow on complete but not minimal, he added back individual components to the minimal food to figure out what the fungi couldn't make anymore.

What he found is shown in the figure above, which displays the growth rate of normal Neurospora (black dots) and a mutant (open dots) that couldn’t make vitamin B6 anymore.

This mutant could be saved though, and its growth rate controlled based on how much B6 (numbers) was added back to the food.

Given enough B6, the mutant could grow just as well as the normal one!

This might seem super basic, but it was the first clear evidence that linked a biochemical process directly to a heritable gene - the rest is molecular biology!