The most beautiful experiment in biology

September 19, 2021 • 9:45 am

John Cairns called “the Meselson-Stahl experiment“, published in 1958, “the most beautiful experiment in biology.” (Click on the first screenshot below to see the original paper, but what I really want you to do is watch the video at the bottom).

The paper was by Matt Meselson, who became a Harvard professor and distinguished researcher, and Frank Stahl, who was equally distinguished and worked at The University of Oregon. Both men are now 91, and both are still with us. The videographers shot both men together, 63 years later, to discuss this most important work, one that, in an unbelievably simple and clever experiment, revealed how DNA replicated. (There were several theories about how the genetic material was duplicated.) I always thought they should have won the Nobel Prize for this experiment, but it was not to be.

A bit of backstory: on p. 166 of Horace Freeland Judson’s wonderful book about molecular biology, The Eighth Day of Creation, you can read this:

Soon after Meselson got back to Pasadena that winter, Max Delbrück and his wife carried [Meselson] and Stahl to the Kerkhoff Marine Station, run by Caltech, on the sea at Corona del Mar, and locked them into an upstairs room with two sleeping bags and a typewriter until they wrote the paper.

You can read the Wikipedia link to the experiment, but first watch the video at the bottom first, which explains this lovely bit of experimental molecular genetics. It’s a really wonderful view of two aging scientists remembering their greatest moment.

This video truly conveys the excitement of the early days of molecular genetics in the 1950s after Watson and Crick had published their proposed structure. W&C had suggested a method of replication of DNA, but it wasn’t really “proven” until the Meselson/Stahl experiment.

.  At the end, the two collaborators and friends visit the llamas that Stahl now farms

h/t: Matthew

15 thoughts on “The most beautiful experiment in biology

  1. Wow. I am just blown away by the beauty of this–the experiment, the history, the film, and the men. I want to share this with everyone. There is a 13 year old girl in Kentucky who is brilliant and NEEDS to see this. How wonderful.

  2. What a great video – interesting, funny and heartwarming. I remember reading in one of Feynman’s books that this experiment was one of the reasons he moved to Cal Tech. There was so much cutting edge science going on. Though I think it was as much about the weather and pretty ladies at the beach.
    Glorious video though, and such nice, funny guys. It’s put a smile on my face for the rest of the weekend. Thanks!

    1. I should have also said that, yes it was a profoundly beautiful experiment, and they absolutely deserved the Nobel prize. Their research answered, with clarity and simplicity, one of the most important questions in the whole of biology. Alongside Watson and Crick, they established the molecular basis of heredity. Incredibly, they did so with an experiment that can be understood by a child with only a basic grasp of chemistry. I find that amazing.

  3. For me, John Gurdon’s demonstration that the nucleus from a gut cell in a tadpole transplanted into an enucleated egg can support development of a complete normal tadpole ranks right up there. This showed, of course, that differentiation involves differential expression of genes, not differential retention.

    1. I somewhat knew John Gurdon from my grad school days. Although his area of developmental biology was fairly different from mine, I would always go to see his talks at scientific meetings and read his papers. They were the most lucid and beautifully worded bits of science that I knew.

      1. Gurdon’s work was central to an undergrad Honors seminar that I presented at Berkeley. Imagine my excitement when, planning a sabbatical in Cambridge, I received an offer for a rental apartment from Gurdon’s wife. We took it. Then it turned out that he was the major force behind the Welcome/CRC institute where I was to be working. It is now the Gurdon Insitute. He fostered the most broadly interactive environment I have experienced. There was a nice cafeteria on the top floor and everyone was basically expected to go there for morning coffee, lunch and afternoon tea. Lots of scientific cross fertilization. And all commonly used reagents were available for the taking from a set of shelves. The woman who ran that service worked with me to develop agar/apple juice plates from which clean Drosophila embryos were easily collected (much better than regular Drosophila food).

  4. Another one which is a beauty was André Jagendorf’s demonstration that a pH gradient across the thylakoid membrane of chloroplasts would cause the generation of ATP and hence providing direct support for Peter Michell’s Chemiosmotic theory.

    1. This was indeed a decisive experiment, combined with the demonstration that illuminated chloroplasts would readily take up protons leading to a pH increase in the medium. It rapidly converted the photosynthesis community – including me as a graduate student – to the Michellian camp while the mitochondria people were still engaged in acrimonious debates.

  5. Jerry, many thanks for posting this wonderful clip. There are similar, longer reminiscences of great flights of experimentation in the Conversations in Genetics series on YouTube. My particular favorites, partly due to the experiments and partly due to the speakers’ personalities, are those by Sydney Brenner and by Paul Berg.

  6. The elegant simplicity of the Meselson-Stahl experiment, and the decisiveness and clarity of its results, put the density transfer technique into the pantheon of molecular genetic methods. Brenner, Jacob, and Meselson later used the technique to test the messenger RNA hypothesis (Nature 190 (1961) 576-80). It could be argued that this paper did for gene expression something like what the Meselson-Stahl paper
    did for DNA replication.

    I think at least one other paper from that epoch is as beautiful as the Meselson-Stahl. This was, of
    course, the paper by Crick, Brenner, Barnett, and Watts-Tobin which established the general nature of
    the genetic code from strictly genetic data. In later work, Brenner and his colleagues used genetic and physiological data to establish the base composition of the three stop codons—a marvel of genetic reasoning, although by that time, more direct biochemical methods were making the issue moot.

  7. Thanks so much for posting this video. I grew up in biology learning of this experiment, and taught it to my students. To see the ones who did it talk about it is thrilling.

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