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Experiments that Inspire

The Hershey-Chase Experiments (1952)

Chris Evers

One of the greatest threats to human health is viral infection. Diseases caused by viruses range from the merely inconvenient (warts, the common cold), to the worrisome (flu, mumps, and measles), to the potentially fatal (hepatitis, polio, and AIDS). Humans are not alone in this suffering - all cellular organisms, even bacteria, can be attacked by viruses.

The first bacterial viruses were discovered in 1917 by scientists working independently in London and Paris. The French scientist, Felix d'Herelle, was studying the feces of patients who had recovered from a bacterial dysentery. This somewhat unpleasant work led him to the discovery of an organism capable of killing bacteria - so small it could pass through a filter. He coined the term "bacteriophage," meaning eater of bacteria, to describe his discovery. d'Herelle was hopeful that this discovery would be useful in fighting disease. It was - in ways he never anticipated: The study of a bacterial virus turned out to be crucial in establishing the identity of DNA as the genetic material of all living things.

In 1952, American biologists Alfred Hershey and Martha Chase set out to determine what composed the genetic material of a bacteriophage. They knew that a bacterial virus was an extremely simple organism, composed only of protein and DNA. The protein makes up the exterior of the virus, and the DNA is contained within it. When a bacterium is infected by a bacteriophage, the bacterium's internal machinery falls under the control of the virus, which uses the bacterium to produce more viruses. What Hershey and Chase wanted to know was: Which substance directed this takeover - DNA or protein?

The experiment that Hershey and Chase devised to differentiate between these possibilities was simple and took advantage of the differences in the composition of protein and DNA. Protein contains sulfur, DNA doesn't. Protein contains a small amount of phosphorus; DNA contains a lot of phosphorus.

Hershey and Chase added bacteriophage to cultures containing either radioactive sulfur or radioactive phosphorus. The bacteriophages grown in the cultures with radioactive sulfur picked it up and incorporated it into their protein. The bacterial viruses grown in the culture with radioactive phosphorus picked that up, incorporating a little of it into the protein, but most of it into their DNA. Hershey and Chase now had two types of bacteriophages: one with a radioactive external protein coat, the other with highly radioactive DNA. They were ready to begin their experiment.

Each of the two types of radioactive bacteriophage was added to a separate culture of bacteria. The bacteriophages were allowed to infect the bacteria, then the cultures were whirled in a kitchen blender, causing any part of the bacteriophages that hadn't got inside the bacteria to fall off. Next the cultures were spun in a centrifuge, which separates materials suspended in liquid according to their weights. The heavier bacterial cells fell to the bottom and formed a pellet, the lighter bacteriophages and loose phage parts remained in the liquid.

Where was the radioactivity now? It depended on which radioactive element you looked for. In the cultures infected by bacteriophages with radioactive sulfur (with labeled protein), most of the radioactivity was in the liquid with the phages. In the cultures infected by bacteriophages with radioactive phosphorus (with most of the label in their DNA), most of the radioactivity was in the pellet of infected bacteria. Thus, the radioactive protein hadn't entered the bacterial cells, but the DNA had.

The final proof that DNA, not protein, was the genetic material was provided by the offspring of the phosphorus-labeled bacteriophages. They had radioactive DNA, passed down from their parents, but no radioactive protein. These experiments convinced the scientific community that DNA alone was the material of heredity, and inspired Watson and Crick to begin their efforts to discover its structure.

Go to Graphics Gallery: The Hershey-Chase Blender Experiment, Examples of Viral Replication Pathways

Go to next story: One Gene/One Enzyme Hypothesis

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