The Caltech Experiment That Proved How Life Copies Itself - California Curated substack
In a quiet lab at Caltech in 1958 two young biologists performed what some still call "the most beautiful experiment in biology."
California Curated
Jul 11, 2025
Excerpt
Let's back up: When Watson and Crick proposed their now-famous double helix structure of DNA in 1953 (with significant, poorly recognized help from Rosalind Franklin), they also suggested a theory about how it might replicate. Their idea was that DNA separates into two strands, and each strand acts as a template to build a new one. That would mean each new DNA molecule is made of one old strand and one new. It was called the semi-conservative model. But there were other theories too. One proposed that the entire double helix stayed together and served as a model for building an entirely new molecule, leaving the original untouched. Another suggested that DNA might break apart and reassemble in fragments, mixing old and new in chunks. These were all plausible ideas. But only one could be true.
Picture at the link
Watson and Crick with their model of the DNA molecule (Photo: A Barrington Brown/Gonville & Caius College/Science Photo Library)
To find out, Meselson and Stahl grew E. coli bacteria in a medium containing heavy nitrogen (nitrogen is a key component of DNA), a stable isotope that made the DNA denser than normal. After several generations, all the bacterial DNA was fully "heavy." Then they transferred the bacteria into a medium with normal nitrogen and let them divide. After one generation, they spun the DNA in a centrifuge that separated it by weight. If DNA copied itself conservatively, the centrifuge would show two bands: one heavy, one light. If it was semi-conservative, it would show a single band at an intermediate weight. When they performed the experiment, the result was clear. There was only one band, right between the two expected extremes. One generation later, the DNA split into two bands: one light, one intermediate. The semi-conservative model was correct.
Their results were published in Proceedings of the National Academy of Sciences in 1958 and sent shockwaves through the biological sciences.
https://open.substack.com/pub/californiacurated/p/the-caltech-experiment-that-proved
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