Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [7]
It would take another decade of research on E. coli and its viruses to start to redeem DNA’s reputation. While Avery was sifting Pneumococcus for genes, Delbrück’s Phage Church was learning how to see E. coli’s viruses. The viruses were no longer mathematical abstractions but hard little creatures. Using the newly invented electron microscope, Delbrück and his colleagues discovered that bacteriophages are elegantly geometrical shells. After a phage lands on E. coli, it sticks a needle into the microbe and injects something into its new host. The shell remains sitting on E. coli’s surface, an empty husk, while the virus’s genes enter the microbe.
The life cycle of E. coli’s viruses opened up the chance to run an elegantly simple experiment. Alfred Hershey and Martha Chase, two scientists at the Cold Spring Harbor Laboratory on Long Island, created viruses with radioactive tracers in their DNA. They allowed the viruses to infect E. coli and then pulled off their empty husks in a fast-spinning centrifuge. Hershey and Avery searched for radioactivity and found it only within the bacteria, not the virus shells.
Hershey and Chase then reversed the experiment, spiking the protein in the viruses with radioactive tracers. Once the viruses had infected E. coli, only the empty shells were radioactive. A decade after Avery’s experiment, Hershey and Chase confirmed his conclusion: genes are made of DNA.
A virus inserts its DNA into E. coli.
No one was more excited by the new results than a young American biologist named James Watson. Watson was only twenty when he was initiated into the Phage Church, blasting E. coli’s viruses with X-rays for his dissertation work. He was taught the conventional view that genes are made of proteins, but his own research was drawing his attention to DNA. He saw Hershey and Chase’s experiment as “a powerful new proof that DNA is the primary genetic material.”
In order to understand how DNA acts as genetic material, however, it was necessary to figure out its structure. Watson was working at the time at the University of Cambridge, where he quickly teamed up with Francis Crick, a British physicist who also wanted to understand the secret of life. Together they pored over clues about DNA and tinkered with arrangements of phosphates, sugars, and bases. In February 1953, they suddenly figured out its shape. They assembled a towering model of steel plates and rods. It was a twisted ladder of sugar and phosphates, with bases for rungs.
The structure was beautiful, simple, and eloquent. It seemed to practically speak for itself about how genes work. Each phosphate strand is studded with billions of bases, arrayed in a line like a string of text. The text can have an infinite number of meanings, depending on how the bases are arranged. By this means, DNA stores the information necessary for building any protein in any species.
The structure of DNA also suggested to Watson and Crick how it could be reproduced. They envisioned the strands being pulled apart, and a new strand being added to each. Building a new DNA strand would be simplified by the fact that each kind of base can bond to only one other kind. As a result, the new strands would be perfect counterparts.
It was a beautiful idea, but it didn’t have much hard evidence going for it. Max Delbrück worried about what he called “the untwiddling problem.” Could a double helix be teased apart and transformed into two new DNA molecules without creating a tangled mess? Delbrück tried to answer the question but failed. Success finally came in 1957, to a graduate student and a postdoc at Caltech, Matthew Meselson and Frank Stahl. With the help of E. coli, they conducted what came to be known as the most beautiful experiment in biology.
Meselson and Stahl realized that they could trace the replication of DNA by raising E. coli on a special diet. E. coli needs nitrogen to grow, because the element is part of every base of DNA. Normal