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Reading the genetic code set the stage for learning to write in it through genetic engineering: a set of powerful new tools to study and manipulate organisms' genes. Genetic engineering allows scientists to alter the DNA of a cell, plant, or animal in deliberate ways for research purposes, so that they can observe how changes in genes affect an organism. This is called reverse genetics because it is the opposite of the classical method of starting with a phenotype and looking for the gene that is responsible (forward genetics). By the end of the 20th century, it had become routine to make targeted changes in plants, animals, and human cell lines. Genetic engineering also led to the development of applications such as new foods and the use of microbes and animals to produce molecules such as insulin, used in medicine.

DNA naturally undergoes mutations; starting in the 1920s, scientists began learning methods to alter the molecule artificially. Hermann Muller (1890-1967), a former assistant in Morgan's lab, showed that radiation could increase the rate at which mutations occurred. This was soon followed by the discovery of other mutagens (such as chemicals) that could accomplish the same thing. As useful as these techniques were, they all had a drawback: The changes they caused in genes were random and unpredictable. Sometimes it was impossible to connect a change to a specific gene. Researchers dreamed of a day when they could pick a gene, knock it out, and then study its effects over the course of an organism's development and lifetime.

A few key discoveries set the stage for genetic engineering, which would give them that opportunity. In the late 1950s, a Swiss scientist named Werner Arber (1929- ) was investigating how bacteria become resistant to attacks by viruses called phages. Salvador Luria (1912-91), working at the Massachusetts Institute of Technology, had discovered that bacteria had proteins called restriction enzymes that helped protect them from the virus. Arber and Hamilton Smith (1931- ), of Johns Hopkins University, showed that the proteins formed part of a bacterial defense system that chops foreign DNA into small pieces.

Genetic engineering requires a pair of molecular scissors (to remove a gene from one place) and a sort of glue (to paste it in somewhere else). Restriction enzymes provided the scissors. Bacteria contained another type of molecule, called a ligase, which could spot broken ends of DNA and mend the cuts. Organisms need such enzymes because DNA sometimes breaks by mistake. Ligases can scout the molecule and make repairs by matching the broken ends to matching sequences in a chromosome and gluing them into place. Sometimes they insert the fragment in the wrong place. If that happens to be in the middle of a gene, the information gets scrambled. So ligases provided a tool to interfere with existing genes. They can also be used to insert a new gene into an organism's DNA. . .

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