JOVANA
Library Glossary Getting Started Three Levels Fields How it works Mission
Join the mission
Back to the library
Biology 1952

Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage

Alfred Hershey & Martha Chase

Tag the virus's protein and its DNA, blend them apart — only the DNA goes in. So genes are DNA.

Choose your version
In depth · the introduction

A virus is just a protein shell wrapped around a strand of DNA. So which of the two carries the instructions for making more virus? Two scientists settled it with a kitchen blender.

The big idea

In 1952 nobody was sure what genes were made of. A virus that attacks bacteria — a bacteriophage — is almost embarrassingly simple: a coat of protein around a core of DNA, and nothing else. To reproduce, it lands on a bacterium and injects something that hijacks the cell into building hundreds of new viruses. The question was: does it inject its protein, or its DNA?

Hershey and Chase found a way to tell the two apart. They tagged the protein with one radioactive marker and the DNA with another, let the tagged viruses infect bacteria, then knocked the empty shells loose in a blender and checked which marker had gone inside. The protein tag stayed outside, on the discarded shells. The DNA tag went in. Whatever a virus passes on to make copies of itself, it is the DNA.

How it came about

Alfred Hershey was a quiet, exacting biologist at Cold Spring Harbor; Martha Chase was his research assistant, and she ran the experiments at the bench. They worked with phage T2, a virus shaped like a tiny lunar lander that grabs onto E. coli by its tail. The trick was chemical: protein contains sulfur but no phosphorus, and DNA contains phosphorus but no sulfur. So they grew one batch of phage with radioactive sulfur (which lit up only the protein) and another with radioactive phosphorus (which lit up only the DNA).

After the tagged phages latched onto bacteria and injected, the spent coats were still clinging to the outside of the cells. Hershey and Chase dropped the soup into an ordinary Waring blendor — the kind used for milkshakes — and spun it. The shearing force snapped the empty shells off without killing the bacteria. A spin in a centrifuge then separated the heavy cells from the light debris, and a Geiger counter read off where the radioactivity had landed. The sulfur was in the debris; the phosphorus was in the cells. This was not actually the first hint that DNA was the genetic material — Avery had shown it with chemistry in 1944 — but the blender made it impossible to ignore.

Why it mattered

For decades, most biologists had bet on protein as the stuff of genes. Protein is built from twenty different amino acids — a rich alphabet — while DNA has just four bases and seemed too monotonous to spell out a living thing. The blender experiment, simple and visual, flipped the consensus. It told the world to stop studying protein and start studying DNA. The very next year, Watson and Crick worked out the double helix — and once you knew the gene was DNA, the race to read it was on.

A way to picture it

Imagine a letter delivered in an envelope. The envelope is addressed, stamped, sealed — it does the job of getting the message to your door, and then you throw it away. The letter inside is what actually says something. Hershey and Chase showed that a virus's protein coat is the envelope — it docks onto the cell and delivers — while the DNA is the letter, the part with the instructions. The blender was simply the act of tearing off the envelope to see that the message had already slipped inside.

An interactive Waring blendor jar holding bacteria infected by phage: each cell has an orange DNA core (P-32) already inside and an indigo protein coat (S-35) stuck to its outside. Drag the blending-time slider and the spinning blades shear the indigo coats off into the supernatant — about 75–80% of the sulfur floats free — while the orange DNA stays with the cells; only about 15–25% of the phosphorus comes loose.

Where it sits

This experiment is the second beat of a three-beat story. First, in 1944, Avery, MacLeod and McCarty showed that pure DNA could transform one kind of bacterium into another — strong chemistry, quietly received. Then, in 1952, Hershey and Chase made the point unforgettable with the blender. And in 1953, Watson and Crick revealed the double helix that explained how DNA could store and copy a message. Read together in this Library, the three mark the moment biology learned that life is written in a four-letter chemical code.

The original document
Original source text

The claim

A. D. Hershey & Martha Chase · J. Gen. Physiol. 36 (1952): 39–56 · received April 9, 1952
The experiments reported in this paper show that one of the first steps in the growth of T2 is the release from its protein coat of the nucleic acid of the virus particle, after which the bulk of the sulfur-containing protein has no further function.

Removing the coats with the blendor

Removal of Phage Coats from Infected Bacteria
If this precarious attachment is preserved during the progress of the infection … it ought to be a simple matter to break the empty phage membranes off the infected bacteria, leaving the phage DNA inside the cells.
The following experiments show that this is readily accomplished by strong shearing forces applied to suspensions of infected cells, and further that infected cells from which 80 per cent of the sulfur of the parent virus has been removed remain capable of yielding phage progeny.
This suspension was spun in a Waring blendor (semimicro size) at 10,000 r.p.m. The suspension was cooled briefly in ice water at the end of each 60 second running period.

Sulfur out, phosphorus in

75 to 80 per cent of the phage sulfur can be stripped from infected cells by violent agitation of the suspension. … The release of sulfur is accompanied by the release of only 21 to 35 per cent of the phage phosphorus, half of which is given up without any mechanical agitation.
These facts show that the bulk of the phage sulfur remains at the cell surface during infection, and takes no part in the multiplication of intracellular phage. The bulk of the phage DNA, on the other hand, enters the cell soon after adsorption of phage to bacteria.

The cautious summary

Summary, points 4 and 8
Suspensions of infected cells agitated in a Waring blendor release 75 per cent of the phage sulfur and only 15 per cent of the phage phosphorus to the solution as a result of the applied shearing force. The cells remain capable of yielding phage progeny.
This protein probably has no function in the growth of intracellular phage. The DNA has some function. Further chemical inferences should not be drawn from the experiments presented.
Department of Genetics, Carnegie Institution of Washington · Cold Spring Harbor · published September 20, 1952