Friday, June 22, 2007

This Week's Citation Classic

Hershey AD & Chase M. 1952. Independent functions of viral protein and nucleic acid in growth of bacteriophage. J. Gen. Physiol. 36: 39-56.

This week's citation classic is cited by practically every undergraduate genetics textbook, with good cause. The experiments they describe, the so-called Blender Experiments, are a marvel of elegance, simplicity and fundamental importance.

Until Alfred Hershey and Martha Chase, there was still debate regarding the nature of the genetic material. Was it DNA or protein? While Avery, MacLeod and McCarty's pneumococcal work ostensibly clinched the case for DNA, but this work was largely ignored and there remained some holdouts (isn't that always the case). Some, including double Nobel laureate Linus Pauling, considered DNA too simple a molecule to play such an important role as the genetic organizing principle for the entire organism. Hershey and Chase provided the final nail for the protein coffin.

Knowing that DNA, but not protein, possesses phosphorus, and protein, but not DNA, possesses sulfur, Hershey and Chase added either radioactive phosphorus or sulfur to cultures of T2 phages and E. coli, and later separated out the phages. Hershey and Chase now had two types of bacteriophages: one with a radioactive external protein coat, the other with highly radioactive DNA. These phages were added to fresh cultures, incubated for a short time, then whirled in a kitchen blender causing the phages to fall off the bacteria. The cultures were then separated using a centrifuge; the heavier bacterial cells fell to the bottom and formed a pellet, the lighter bacteriophages and loose phage parts remained in the liquid (called supernatant).

Hershey and Chase examined the pellet and the supernatant for radioactivity. 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 DNA, but not the protein, entered the bacterial cells, clinching the case for DNA as the genetic material.

As further proof, Hershey and Chase found that offspring of the original viruses had radioactive DNA, but not radioactive protein, showing that the DNA was passed down from parent to offspring. It is fair to say that the scientific community, including Pauling, were now convinced of the fundamental nature of DNA.


  1. Hi John,

    First of all let me just inform you that the previous comment is in Portuguese (Brazilian) and it's comment spam. It has nothing to do with your post. It's a tshirt website of some sort.

    On the other hand, I'd like to let you know that I've just tagged you with the latest "8 random facts about me" blog meme.

    Feel free to ignore this comment (and delete it) if you are not interested.

    My 8 random facts are up at my site, go give them a look.


    PS: I tagged you because I've been reading your blog since day one and it's been very interesting. :)

  2. Glancing through the pdf of Hershey and Chase's research, I was surprised to see that they didn't cite Avery, MacLeod, and McCarty. These two sets of experiments are so closely connected in textbooks (and therefore in my mind) that it seems strange. Any idea on whether this is because Hershey-Chase didn't see a connection, or is it because papers were written differently then (introductions of older papers seem much shorter than they are now, for example)?

  3. Rick: Thanks for the tag. I can't find your site, clicking on your name brings me to a blank page.

    Yukon Slim: My guess is that they simply weren't aware of it. The rapid dissemination of scientific information that we now take for granted wasn't quite as rapid back then. It's not as if they had Pubmed and could simply enter DNA as a search term and find all the titles published using that term. I suspect back then scientists relied on word of mouth, and the general consensus is that the Avery paper was completely ignored after publication.

    Check out this paper as well;