Science Classics: The Beadle and Tatum Experiment

This blog post is my entry for Skull’s in the stars’s challenge.

- Beadle and Tatum, 1941

About 15 years before Watson and Crick proposed a model for DNA and back when scientists were in disagreement about how genetic information was actually stored, there was the Beadle and Tatum experiment. 

In 1941, American geneticists  George Beadle and Edward Tatum, at Stanford University, rediscovered the ideas of the British physician, Archibald Garrod; who, in 1909, proposed that a single gene was responsible for the production of a single protein.  Garrod was studying an inherited disease known as alkaptonuria, the production of red colored urine due to an enzyme deficiency.

Based on this work, which had gone largely ignored until then, Beadle and Tatum proposed that, if the “one gene, one enzyme” hypothesis is true, they should be able to produce mutant organisms (in this case the bread mold, Neurospora crassa) with a single gene mutation, corresponding to a single defunct enzyme.

Keep in mind, this is before DNA and cloning experiments and long scientists knew how to produce specific genetic knockouts. Beadle and Tatum, therefore, had to induce non-specific mutations with x-ray and UV radiation.  But, by controlling the growth media of the Neurospora, they were able to identify single mutations in biochemical pathways of amino acid synthesis.

Mutated Neurospora was grown in a medium containing all 20 biological amino acids, and the mutated spores were subsequently crossed with wild type spores.  Next, the next generation of spores were grown in a medium containing one one of the essential amino acids.  If, for example, there was a mutation in a protein that synthesized proline, then the spore would only grow if proline was in the medium (For more background information on amino acid biosynthesis pathways, this is a good resource).  Using this method, they were able to link the mutation of a specific gene (which was demonstrated in 1926 by Hermann Joseph Muller) the disfunction of an enzyme related to the synthesis of a specific amino acid.

As in interesting side note to the overall purpose of the experiment, was that they discovered a way by which they could determine the complexity of a specific pathway, by describing pivotal genes, and their enzymes:

in addition to minimal media controlling just the amino acid content, other vitamins and nutrients where also controlled, vitamin B6, for example they realized they could use their technique in a different way.  This was a method which they could use to discover entire new pathways, discovering what vitamins and nutrients are essential to growth, and what pathways they are involved in:

The Beadle and Tatum experiment was later revised to include all classes of polypeptides, and not just enzymes, into the “one gene” idea.  But, it was their work that was seminal in providing a to link the fields of biochemistry and genetics, providing a way to look at biochemical pathways and protein enzymes through the lens of genetic information, paving the way for later scientists like Watson and Crick, and many others.

Beadle and Tatum shared a Noble Prize in Medicine or Physiology (1958) for their work.  A copy of their original paper can be viewed here, I believe for free.

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