Neville Goodman’s metaphor watch: Open things up

neville_goodmanI haven’t yet mentioned one of the most well known metaphors in medicine: that of the lock and key for molecular interactions. Whether it was suggested previously for straightforward chemical reactions I don’t know, but the idea of the lock and key model is credited to Emil Fischer, a German chemist who won the Nobel Prize in chemistry in 1902, as an explanation for the specificity of enzymic reactions: the enzyme as lock; the substrate as key. There are so many chemical reactions and ideas named after Fischer that I suspect I must have heard his name at school, and perhaps again when learning for postgraduate exams in anaesthesia because he demonstrated, with Joseph von Mering, the sedative action of the barbiturates.

I wrote in an early column that metaphors explain and enliven: the lock and key is metaphor as explanation. It is a good metaphor, and even at nearly 120 years old is not a cliché. But, as with most metaphor as explanation, it is simplistic. Binding of a substrate to an enzyme does not open the enzyme; instead, the substrate splits, or forms a new compound with something else. The lock and key model applies also to receptors on cells, when a neurotransmitter may open an ion channel, or a ligand may cause a conformational change that modulates an action within the cell, nothing having passed through the cell membrane.

The model is obviously still useful in basic biology, but is there any point beyond that? The first PubMed article to refer to it is from 1961, which seems late, and is about taste reception: perhaps active scientists have left it to elementary teachers. Among the most recent articles, there are some about chemistry and non-biological nanoparticles and some about the reproductive isolation of species. Of the 770 articles in total, a high proportion just happen to have lock and key in the title or abstract. In one, something termed “the tryptophan lock” is “a key component required to stabilize activated receptors.” Another, about training in rugby football, was retrieved because the abstract contained “lock forwards” and “key skills.” Frequency of occurrence in PubMed can be misleading.

Scientists may no longer need the lock and key, but it is one of the metaphors used by oncologists to explain targeted treatments to patients. Sixty six patients and nine oncologists participated in a study to document what metaphors were used: 17 metaphors (bus driver, boss, switch, battery, circuit, broken light switch, gas pedal, key turning off an engine, key opening a lock, food for growth, satellite and antenna, interstate, alternate circuit, traffic jam, blueprint, room names, Florida citrus—these last two metaphors used to help patients to understand the specificity of their particular cancer) were used to explain eight molecular testing terms (driver mutations, targeted therapy, hormones, receptors, resistance, exon specificity, genes, and cancer signatures). Good for them.

Neville Goodman is a retired consultant anaesthetist and a writer. He is co-author of a book on medical English.

Competing interests: I have read and understood BMJ policy on declaration of interests and declare that my only competing interest is my co-authorship of a book about medical English.