Saturday, October 13, 2007

The Most Beautiful Experiment in Biology

 

John Dennehy at Evilutionary Biologust has done it again. This week's citation classic is, indeed, a classic. It's the Meselson-Stahl paper from 1958 demonstrating that DNA is replicated semi-conservatively [The Most Beautiful Experiment in Biology].

The description of the experiment as the "most beautiful experiment in biology" comes from John Cairns as quoted in Horace Judson's book The Eight Day of Creation [see The Story of DNA (Part 1)]. It's a description that few of us could dispute. I grew up on the stories of famous experiments like this one and everyone around me at the time wanted to be like Matt Meselson or Franklin Stahl. If they couldn't be Meselson or Stahl then maybe Jacob, Monod, Hershey, Pardee or a host of other members of the phage group. Personally, I was envious of those who worked on bacteriophage lambda.

Over the years we kept reminding each new generation of the Meselson-Stahl experiment by describing it in the textbooks. The figure on the left is from my 1994 book. I'm sure that any student who took biochemistry or molecular biology in the 70's, 80's, and even part of the 90's, was taught this experiment.

Alas, it's no longer in the textbooks and the current generation of students probably has no idea who Meselson and Stahl are. They're probably befuddled by the reference to the most beautiful experiment in biology.

I vividly remember the debate when we decided to take it out of the textbook. Now that we can describe the molecular machinery of DNA replication it follows naturally that replication has to be semi-conservative. It no longer seems necessary to describe a separate experiment that demonstrates this obvious fact. In fact, it is often counter-productive to do so since it requires setting up the context—a time when this strong prediction of Watson and Crick had not been tested. That's not easy when even high school students know the facts.

So out it went, but not without some sadness for the passing of an era. I suppose it won't be long before some other experiment takes its place as the most beautiful. It will probably be something to do with microarrays or florescent dyes.



Many of the classic experiments are no longer taught to undergraduates. It's the nature of the beast, I suppose. Those experiments became classics because they showed us something we didn't know previously. That "something" was so important that it now seems obvious. We don't need to teach it.

14 comments :

  1. I'm an undergrad and was taught about the beauty in my cell and molecular biology class!

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  2. I learned about this experiment in high school and again in my undergraduate courses. I don't see why teaching the historical context of the experiment -- which, I agree was very beautiful and elegant -- is counterproductive. I think it is productive to teach us the innovative methods of researchers -- the methodologies -- so that we can go on and innovate ourselves (or, as you said, be inspired by such innovation). Don't you think?

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  3. Why not ask students to explain the result that was not obtained? How would biology be different if the results had indicated conservative instead of semi-conservative replication?

    Put a different way - what of M&S had done their experiment in a plant system, using a typical double-stranded plant DNA virus (which would be a pararetorvirus)?

    This most beautiful of experiments can still be relevant and surprising.

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  4. Actually, this experiment is described in the current introductory genetics textbook Genetics: A Conceptual Approach by Benjamin Pierce.

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  5. Perhaps it would be fun to have a poll? Ask your readers to nominate beautiful experiments, do a digest of the papers, and then hold a vote?

    There are some gorgeous ones out there in my own field (sex chromosomes and gametogenesis).

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  6. I'd consider myself part of the current generation of students (I finished my undergrad 2 years ago and am in grad school now). I learned about this in pretty much every undergrad class that talked about DNA replication. It got to the point we weren't really learning it anymore, though one of my friends described the lecture like watching a favorite movie again. We already knew what happened but still enjoy seeing it again.

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  7. It is sad to think that the M-S experiment would no longer be taught. Of course we can't insist that everyone learn the evidence for every aspect of what we currently know -- that's not practical. We have to accept some things as givens, i.e., "facts", and go on from there. Back when I was teaching I used to ask my students how they knew that the WC structure of DNA was correct, especially the anti-parallel nature of the two strands. No one knew, but all believed. Sometimes I assigned the paper from the Kornberg lab that showed that the two strands had to have different polarity, but it was pretty difficult for most undergraduates to understand and took a lot of class time to explain, so I eventually abandoned that approach. But I think that it is important that students be exposed to the evidence for what we believe to be true -- otherwise science becomes faith-based, just like religion.

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  8. Just because I have to flaunt my connection, I must mention that Frank Stahl was on my Ph.D. thesis committee ... and he's also a very nice guy.

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  9. Hi Larry--first time I've commented on your blog. Shame on me!

    Anyway, maybe one of the reasons it's not covered in at the undergrad level is because it's covered in some detail in the Grade 12 Molecular Genetics unit in Biology. That one, and Hershey and Chase.

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  10. One of the "unfortunate" results of the ever-increasing knowledge base in science is that it is becoming impossible to cover everything one might like in a mere semester at the introductory level. More often than not, what gets squeezed out first is the historical context of the factual material--the "how do we know?" stuff. It's increasingly difficulat to justify the time spent in recounting the Darwin-on-the-Beagle story, or the classical (and, yes, beautiful) experiments at the dawn of molecular biology.
    Still, you'll find most of these experiments at least mentioned in all of the popular introductory Bio texts. They can be assigned as reading if lecture time is too precious (that's what I do).

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  11. In 1983 our mutual friends Mike and Kim Ellison moved to MIT for the next stage of their training and in February, 1984 Tony Percival-Smith and I flew down to Boston to visit. It was sort of like a pilgrimage for two budding molecular geneticists (recall from an earlier post that this was the same trip when Barb Ruskin showed us her gel with the RNA splicing lariat and we speculated about its structure). Walking down the hallway in Harvard we passed an office labelled, "Matthew Meselson." Suffice it to say that we experienced something close to an epiphany (I don't really know what an epiphany is, so I am using it to mean a moment of splendiferous awe).

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  12. I learned this in high school in the mid-90s. Our teacher got us to predict what would have been observed with both semi-conservative and conservative replication, and then compared our predictions to the actual results. A great way to teach this experiment and science in general!

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  13. Oh, it's also in the current edition of Introduction to Genetic Analysis by Griffiths, etc.

    Must just be the Canadian textbooks that no longer mention it.

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  14. Proc Natl Acad Sci U S A. 1980 Jul;77(7):3870-4

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