Confirming That DNA Is the Answer: The Hershey-Chase Experiment
Although the Avery-MacLeod-McCarty experiment (1944) provided pretty solid evidence for DNA being the transforming principle, people were still skeptical. Many scientists were fixated on the idea that protein had to be the medium on which life's instruction manual was recorded. After all, proteins control virtually every cellular process, and accordingly exhibit remarkable functional diversity. It was only logical to assume that proteins also carried out the function of genetic record-keeping.
DNA, on the other hand, was viewed as a boring molecule whose repetitive structure was unlikely to be conducive to recording the genome. This is, to some extent, a valid idea; after all, even with all we know about DNA now, isn’t it still remarkable that your entire body’s functions are carefully recorded in a sequence of As, Gs, Ts, and Cs?
This prevalent skepticism warranted a new experiment. So in 1951, Alfred Hershey and Martha Chase designed an experiment with Streptococcus pneumoniae (again), in order to settle the debate about whether DNA or protein is the genetic material.
Martha Chase and Alfred Hershey.
The procedure for the Hershey-Chase experiment is as follows. First, bacteriophages (viruses that infect bacteria) were treated with one of two radiolabeled solutions: Sulfur-35 or Phosphorus-32. These are simply sulfur and phosphorus, respectively, with some extra neutrons in the nucleus of the atom. This treatment makes them easier to visualize with special imaging equipment.
The S-35 would become incorporated into the phage’s proteins, and the P-32 would become incorporated into the phage’s DNA. This is because each element is unique to the corresponding macromolecule. Sulfur is found in proteins (think: cysteine, methionine, disulfide bonds, etc.), while phosphorus is found in DNA (think: sugar-phosphate backbone). Try to think of an amino acid with phosphorus in it, or a place in DNA where sulfur would be present. Even if you did come up with some insular example, it would likely be in very low abundance, and therefore negligible, in the context of the Hershey-Chase experimental setup.
The next step in the procedure is to allow the phages to infect the Streptococcus, and observe which radioactive element is injected by the viruses. If P-32 is detected in the bacteria, DNA was injected into the bacterium. If S-35 is detected, protein was injected.
To isolate the cells, Hershey and Case used centrifugation to separate particles in solution by density. Cells sank to the bottom and formed a pellet, while empty phage particles remained in the supernatant.
P-32 was detected in the pellet, indicating that DNA was injected from the phages into the bacteria. S-35 was detected in the supernatant, indicating that the protein component of the viruses stayed in the protein coat. It was finally established: DNA is the genetic material. In 1952, Hershey and Chase published a paper detailing their findings.
That’s the end of this series of articles detailing identification of the transforming principle. Now I need inspo, so please dm me (humble hornworth #7404) on Discord if you have any article topic suggestions. <3
More resources:
Beautiful video explaining this experiment: https://youtu.be/GwOu-3kZ5tk
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961593/ - nice article that puts together the pertinent “DNA-appreciation experiments” and provides links to the original papers!
My previous 2 articles in this series:
