Frank Stahl, a professor emeritus of molecular biology, doesn’t teach classes at the University anymore, but every intro-level biology student knows him, at least through his work.
Stahl was one half of the groundbreaking 1957 Meselson-Stahl experiment, which demonstrated how DNA replicates. The study has been called “the most beautiful experiment in biology” by John Cairns, a noted biochemist.
In 1953, James Watson and Francis Crick published their famous paper describing the double-helix structure of DNA. The Watson and Crick model theorized that DNA was semiconservative — that is, when it replicates it splits into two strands and uses one of the halves for the new strand — but it had not been proven.
“At the time, there wasn’t a widespread faith that Watson and Crick’s model was correct, or even that DNA was genetic material,” Stahl said. “If an experiment confirmed it, it would add a lot of gravitas to the theory.”
Enter Stahl, who around 1956 was finishing up his graduate studies in biology at the University of Rochester.
The chair of the department told Stahl he needed to take a physiology class to complete his degree, to which Stahl responded, “Well, that’s a problem because the physiology professor is stupid, and I’ll be damned if I take a class of his.”
The compromise, which both parties were happy with, was to send Stahl to nearby Woods Hole to study, where it just so happened that Watson was a professor. Stahl signed up for Watson’s lab, where he met Meselson — Watson’s teaching assistant at the time. Stahl and Meselson started talking about an experiment to confirm Watson and Crick’s model, but were both too busy to pursue it.
Coincidentally, both soon ended up at the California Institute of Technology as research fellows. Stahl had received a research grant to study bacterial genetics, but his experiments were going badly. However, serendipity struck again … on Stahl’s door.
“On the day I realized I had completely messed up, Meselson knocked on my door and asked if I’d like to do the DNA experiment,” Stahl said. With his own research fizzling, it wasn’t a hard choice to make.
The two worked on the experiment for roughly a year and half, most of which Stahl says they were “bumbling around” trying to figure out how to set it up.
What they finally arrived at was as clever as it was elegant.
“If you jump into a salt solution, such as the Dead Sea or the Great Salt Lake, you’ll stop sinking at a certain point and float according to your density,” Stahl said. “Molecules will do the same thing if you put them in a centrifuge.”
Meselson and Stahl reasoned they could use this property to figure out how DNA replicates.
They cultivated two strains of bacteria — one in a dish containing a denser than normal isotope of nitrogen, N15, and the other in normal nitrogen, N14. Since nitrogen is a building block of DNA, the two predicted the DNA molecules using N15 would sink lower than the N14 DNA when placed in a centrifuge.
The experiment went as predicted, with N15 DNA lower than N14. But what happened next is where the scientists earned their bread.
Meselson and Stahl took the bacteria from the N15 solution and placed it in the N14 dish, allowing the bacteria to divide only once.
When placed in the centrifuge, the new DNA ended up almost exactly between the two, meaning that when the bacteria divided, it used half of the old N15 DNA and created the other half using N14.
Allowing the bacteria to further divide created two distinct populations — one with a mix of N14 and N15, and one with only N14.
Theory confirmed.
“Watson and Crick nailed it,” Stahl said.
For his own part, Stahl is modest about the experiment.
“I look at that mostly as Meselson’s work,” he said. “I was just in the right place at the right time.”
Stahl took a position at the University in 1959 and has remained ever since, studying genetic recombination.
The Meselson-Stahl experiment isn’t even his favorite moment as a scientist. He said that honor goes to some of his work at the University with his late wife, Mary Stahl, who was also his laboratory assistant.
During a particularly troublesome experiment, Stahl considered giving up, but Mary would not hear of it.
“She refused to quit,” Stahl said, “and she ended up finding the condition to make it work, and work beautifully.”
The lesson Stahl took away from it: “If you have a good hypothesis, prove it right or wrong; don’t quit.”
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