THE language of life has 64 words, and three of those words mean “stop”. When you have such a restricted lexicon, this redundant negativity seems gratuitous. So Lei Wang of the Salk Institute in La Jolla, California, has been trying to change the meaning of one of those words to something more constructive.

The words in question—the other 61 of them, anyway—are genetic instructions for amino acids, the building blocks of proteins which, in turn, make bodies and the biochemicals needed to run them. Read off in order from a protein-coding gene, the letters describe how to make a particular protein. In normal circumstances, there are 20 types of amino acid corresponding to those 61 words (it is not only in the matter of stopping that the language of genes is a language of synonyms). Dr Wang is now able to add to that in mammals, taking the total to 21.

He and his colleague Peter Schultz have been able to pull off this trick in bacteria since 2001, and in yeast since 2003. But mammal cells are far more complex. So to get them to use a 21st type of amino acid as well, Dr Wang and his colleagues had to embrace some fancy biochemistry—as they describe in the latest issue of Nature Neuroscience. Then, to show that this is not merely an academic conjuring trick, they did a piece of practical science with their invention.

To create a new genetic instruction, Dr Wang's team needed not only to identify which new word they wished to add but also to find something that would carry it and to glue the two together. They began by finding a molecule that would carry a novel amino acid to a mammal cell's protein factories. To prevent the genetic code getting lost in translation, that molecule (called a transfer RNA, or tRNA) had to be picky enough to carry only the desired sort of amino acid. Such a component is easier to borrow than to make, so Dr Wang pinched an appropriate tRNA he had previously run up for a bacterium and fiddled with the gene which encodes it to ensure that it would work in a mammalian cell.

Next, he and his colleagues searched for an enzyme capable of sticking the bacterial tRNA to their synthetic amino acid. For this task they looked to the other type of cell with which they are familiar, yeast. Although yeast is a simple organism, its molecular biology is a lot more mammal-like than a bacterium's. Dr Wang took the enzyme that normally attaches one of the 20 natural amino acids to his tRNA in bacteria, and mutated it in about a billion ways in yeast cells in the hope that one of the mutants would fit the mammalian bill perfectly—which, indeed, one of them did.

Having assembled and tested the machinery, he then wanted to do something useful with it. The useful thing in question was to adjudicate between two competing models of how nerve cells operate.

Nerve cells transmit their signals using electrically charged atoms (called ions) of sodium and potassium, which work rather like electrons in a metal wire. To transmit signals, the ions move in and out of the cell through pores—and these openings in the cell walls must snap shut at the end of a transmission. There are two ideas about how this may happen. One proposes that the pore closes when a plug shaped like a ball and chain obstructs the hole. The second suggests that a rod-like plug can block the hole by slipping across it sideways and stopping large ions from passing, rather like a drain cover stops leaves from entering the mouth of a pipe.

An established method—that of taking images of the electron densities of the relevant atoms in order to work out the shape of a molecule—does not offer any clues as to which model is right. Neither does standard genetic engineering, in which some amino acids in the plug are swapped for other natural amino acids. Indeed, Dr Wang tried that by switching an amino acid in the plug for a larger one. His idea was that if the ball-and-chain model were correct, a larger “ball” would not alter its effectiveness as a plug. Should it stop the pore closing, however, it would imply that the rod could no longer get into position.

In fact, nothing did happen, but Dr Wang was not convinced that this proved the ball-and-chain hypothesis. He repeated the experiment with an even bigger “ball”, an artificial amino acid called OmeTyr. Its extra girth made the difference and prevented the pore from closing. To corroborate the result he also tried p-benzoylphenylalanine, a second large and unnatural addition to the amino-acid dictionary. That also prevented the pore from closing. So, Dr Wang concludes, it looks as though the ball-and-chain model is wrong and the rod model is right.