1955

Electrophoresis

Arne Wilhelm Kaurin Tiselius (1902–1971), Oliver Smithies (b. 1925)

The electrochemistry work of the early nineteenth century led to one of the most widely used techniques in biochemistry and molecular biology by the middle of the twentieth. That’s because biomolecules carry charged groups as part of their structures (the acidic and basic amino acids and the phosphate groups on DNA and RNA). Such groups carry their molecules through a solution toward an oppositely-charged electrode. Swedish biochemist Arne Wilhelm Kaurin Tiselius pioneered the use of this effect for analytical chemistry in 1937, showing that proteins migrated through a buffer solution according to their size and charge. It wasn’t an easy technique, though, and it couldn’t separate closely related compounds well. Chemists needed a way to standardize the mixtures and slow the process down, leading to experiments with thicker solutions and even jelly-like materials.

British-born American geneticist Oliver Smithies reported in 1955 that starch gels were an excellent system for this purpose, a finding that immediately popularized the technique (although starch has largely been replaced by other materials, such as the polymer acrylamide). These days, premade gel strips and plates are loaded into an electrophoresis machine, the sample is added, and a voltage is applied, causing the various parts of the sample mixture to migrate and resolve into bands along the gel, very much like chromatography. Once the run is finished, the bands are stained with dyes or other reagents to make them visible. The standard blue dye for protein gels, Coomassie stain, would be the color of protein chemistry’s flag if it had one.

Since DNA and RNA molecules are all negatively charged, they migrate through the gel according to their size—a phenomenon that has been extremely useful in identifying them. These gels are often run with a standard mixture of DNA or RNA pieces of known size loaded along one side so that the unknown bands can be compared to the bands on the standard (“ladder”) mixture. Modern molecular biology is all about manipulation of proteins and nucleic acids, and so many gels are run in a typical research lab that the field would probably grind to a halt without them!

Ms. Edna Ardales, a researcher from the International Rice Research Institute, uses UV light to review an electrophoresis gel from a DNA sample in 2007. Such “sequencing gels” have been replaced by faster techniques now, but the technique behind them is still in constant use.