Genetics 1941

Genetic Control of Biochemical Reactions in Neurospora

George W. Beadle · Edward L. Tatum

One gene builds one enzyme that runs one step of life's chemistry.

Choose your version

In depth · the introduction

Two scientists broke a humble bread mould on purpose — and in its broken pieces, found the link between a gene and the chemistry of life.

The idea

A living thing builds itself through thousands of tiny chemical steps, and each step is run by a special protein machine called an enzyme. Beadle and Tatum showed that each enzyme is made according to the instructions of a single gene.

So break one gene, and you lose one enzyme, and one chemical step stops. That simple chain — gene to enzyme to reaction — is what they proved.

How it came about

In 1941, at Stanford, George Beadle and Edward Tatum picked the bread mould Neurospora because it normally makes all of its own vitamins and building blocks from almost nothing. That made it the perfect test subject: anything it could no longer make would stand out at once.

They blasted it with X-rays to cause random mutations, then hunted for moulds that had lost the ability to make one specific nutrient. Every time they found one, a single damaged gene was to blame. Repeat the trick again and again, and you map the chemistry of life onto the genes that run it.

Why it mattered

Before this, a 'gene' was an abstract unit of heredity — something passed from parent to child, but nobody knew what it actually did. This experiment gave a concrete chemical answer: a gene makes an enzyme. It turned the gene into something you could probe with chemistry, and founded a whole field, biochemical genetics.

An analogy

Picture a factory assembly line where each station adds one part, run by one worker. If a worker (the enzyme) doesn't show up, the line jams at that station and the half-finished product piles up behind it. You can tell exactly which worker is missing by seeing where the line stalls — and you can keep things moving by handing the line a part from a station past the gap. That is precisely how the broken moulds were brought back to life: feed them an ingredient from past the blocked step, and they grow again.

Where it sits

It builds on Mendel's abstract units of heredity (see Mendel, 1866) and gives them a job to do. It points straight into the molecular age: once DNA was shown to be the genetic material (see Avery, 1944) and its structure found (see Watson–Crick, 1953), Crick could finally say how a gene's sequence becomes an enzyme (see Crick, 1958). The bacterial version of 'genes control chemistry' is Monod and Jacob's discovery of how genes switch on and off (see Monod & Jacob, 1961). Beadle and Tatum shared the 1958 Nobel Prize for this work.

The original document

Original source text

G. W. Beadle & E. L. Tatum · Proc. Natl. Acad. Sci. USA 27 (1941), 499–506 · communicated October 8, 1941

The premise

Beadle and Tatum begin from a simple idea of physiological genetics: that the life of an organism is an integrated web of chemical reactions, and that these reactions are controlled, step by step, by genes. If that is true, then damaging a single gene should disable a single chemical step — a prediction that ought to be testable.

The method — mutants that can no longer feed themselves

They chose the bread mould Neurospora, which normally grows on a 'minimal' medium of sugar, salts, and one vitamin (biotin), making everything else it needs by itself. Spores were exposed to X-rays to induce random mutations; survivors were grown on a rich 'complete' medium and then tested on the minimal medium. A strain that thrived on complete medium but failed on minimal had lost some ability to synthesise a nutrient — and adding back single vitamins or amino acids, one at a time, revealed exactly which one.

What they found

Their first confirmed mutants had each lost the power to make a specific compound — among them vitamin B6, vitamin B1, and p-aminobenzoic acid — and in every case the new requirement was inherited as a single Mendelian gene. A gene, they concluded, governs a particular chemical reaction; mutate the gene and that one reaction fails.

[ … ]

The hypothesis it became

This paper does not use the slogan, but the principle drawn from it became famous as 'one gene–one enzyme': each gene specifies one enzyme that catalyses one step of metabolism. Applied to a whole pathway, the same logic even orders its steps — a mutant is rescued only by intermediates lying at or beyond its block, so the pattern of rescues reads out the sequence of the chemistry.

Stanford University, California · 1941