Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [92]
Berg and his colleagues used EcoR1 to cut open SV40’s chromosome. At one end of SV40’s DNA they added DNA from a virus of E. coli called lambda. In order to fuse the two pieces of DNA together, Berg and his colleagues added to their ends some extra bases that would form bonds. When they were done, they had created a viral hybrid.
Since the hybrid carried the lambda virus’s genes for invading E. coli, Berg wondered whether it could invade the microbe. He asked one of his graduate students, Janet Mertz, to design an experiment. For Berg and Mertz, the experiment started out as yet another interesting question. But some who learned about their plans were filled with dread.
One of the first people to confront Berg with these worries was a bioethicist named Leon Kass. Like Berg, Kass had worked on E. coli, but he had become disillusioned by how fast scientific discoveries were being made and the lack of thought being given to their ethics. Kass warned Berg that manipulating genes could lead to moral quandaries. If scientists could insert genes in embryos, parents might pick out the traits they wanted in their children. They wouldn’t just upgrade genes that would cause sickle-cell anemia or other genetic disorders. They would look for ways to enhance even perfectly healthy children.
“Are we wise enough to be tampering with the balance of the gene pool?” Kass asked Berg.
Berg brushed off Kass’s warning, but when other virus experts began to question his plans, he stopped short. Mertz described to another researcher how she and Berg were going to create a sort of Russian doll with SV40 in lambda and lambda in E. coli. The researcher replied, “Well, it’s coli in people.”
If an SV40-carrying E. coli escaped from Berg’s laboratory, some scientists feared it might make its way into a human host. Once inside a person, it might multiply, spreading its cancer-causing viruses. No one could say whether it would do no harm or trigger a cancer epidemic. In the face of these uncertainties, Berg and Mertz decided to abandon the experiment.
“I didn’t want to be the person who went ahead and created a monster that killed a million people,” Mertz said later.
At the time, Berg’s lab was the only one in the world actively trying to do genetic engineering. The researchers’ methods were elaborate, tedious, and time-consuming. When they scrapped their SV40 experiment, they could be confident that no one would be able to immediately take up where they left off. But it would not be long before genetic engineering would become far easier—and thus far more controversial.
Berg and Boyer continued to study how EcoR1 cuts DNA. They discovered that the enzyme does not make a clean slice. Instead, it leaves ragged fragments, with one strand of DNA extending farther than the other at each end. That dangling strand can spontaneously join another dangling strand also cut by EcoR1. The strands are, in essence, sticky. Berg and Boyer realized no tedious tacking on of extra DNA was necessary to join two pieces of DNA from different species. The molecules would do the hard work on their own.
Boyer soon took advantage of these sticky ends. Instead of viruses, he chose plasmids, those ringlets of DNA that bacteria trade. Working with the plasmid expert Stanley Cohen, Boyer cut apart two plasmids with EcoR1. Their sticky ends joined together, combining the plasmids into a single loop. Each plasmid carried genes that provided resistance to a different antibiotic, and when Boyer and Cohen inserted their new hybrid plasmid in E. coli, the bacteria could resist both drugs. And when one of these engineered microbes divided, the two new E. coli also carried the same engineered plasmids. For the first time a living