Microcosm_ E. Coli and the New Science of Life - Carl Zimmer [91]
CUT AND PASTE
Before 1970, E. coli had no role in biotechnology. It does not naturally produce penicillin or any other precious molecule. It does not turn barley into beer. Most scientists who studied E. coli before 1970 did so to understand how life works, not to learn how to make a profit. They learned a great deal about how E. coli uses genes to build proteins, how those genes are switched on and off, how its proteins help make its life possible. But in order to learn how E. coli lives, they had to build tools to manipulate it. And those tools would eventually be used to manipulate E. coli not simply to learn about life but to make fortunes.
The potential for genetic engineering took E. coli’s biologists almost by surprise. In the late 1960s, a Harvard biologist named Jonathan Beckwith was studying the lac operon, the set of genes that E. coli switches on to feed on lactose. To understand the nature of its switch, Beckwith decided to snip the operon out of E. coli’s chromosome. He took advantage of the fact that some viruses that infect the bacteria can accidentally copy the lac operon along with their own genes. Beckwith and his colleagues separated the twin strands of the DNA from two different viruses. The strands containing the lac operon had matching sequences, so they were able to rejoin themselves. Beckwith and his colleagues added chemicals to the viruses that destroyed single-strand DNA, leaving behind only the double-strand operon. For the first time in history someone had isolated genes.
On November 22, 1969, Beckwith met the press to announce the discovery. He let the world know he was deeply disturbed by what he had just done. If he could isolate genes from E. coli, how long would it take for someone else to figure out a sinister twist on his methods—a way to create a new plague or to engineer new kinds of human beings? “The steps do not exist now,” he said, “but it is not inconceivable that within not too long it could be used, and it becomes more and more frightening—especially when we see work in biology used by our Government in Vietnam and in devising chemical and biological weapons.”
Beckwith flashed across the front page of The New York Times and other newspapers, and then he was gone. The debate over the dangers of genetic engineering disappeared. Other scientists went on searching for new ways to manipulate genes without giving much thought to the danger. Scientists who studied human biology looked jealously at the tools Beckwith and others could use on E. coli. To study a single mouse gene, a scientist might need the DNA from hundreds of thousands of mice. As a result, they knew very little about how animal cells translated genes into proteins. They knew even less about the genes themselves—how many genes humans carry, for example, or the function of each one.
Paul Berg, a scientist at Stanford University, spent many years studying how E. coli builds molecules, and in the late 1960s he wondered if he could study animal cells in the same way. At the time, scientists were learning about a new kind of virus that permanently inserts itself into the chromosomes of animals. The virus was medically important because it could cause its host cells to replicate uncontrollably and form tumors. Berg recognized a similarity between these animal viruses and some of the viruses that infect E. coli. In the 1950s, scientists had learned how to turn E. coli’s viruses into ferries to carry genes from one host to another. Berg wanted to know whether animal viruses could be ferries as well.
Berg began to experiment with a cancer-causing monkey virus called SV40. He pondered how he might insert another gene into it. Eventually he decided he would need to cut open the circular chromosome of SV40 at a specific point. But he had no molecular knife that could make that particular cut.
As it happened, other scientists had just