Derek Lowe dreams of the day when chemists and biologists can understand each other

You’d think that everyone on a drug research team would be able to speak with all of their fellow scientists and have a reasonable chance of being understood. After all, we’re all talking about the same things: potency, selectivity, pharmacokinetics, toxicology. You would, however, be gravely mistaken. 

Part of the problem is specialisation. It’s inevitable that each field will have its own jargon, often impenetrable even to experienced outsiders. The organic chemists have only to start dropping named reactions into the conversation to lose every biologist at the table, while the biologists can lapse into what sound like entire paragraphs of three-letter acronyms. Speaking as a chemist, I can tell you that the biological TLAs get old PDQ, although my colleagues across the table probably feel similarly about the names of long-deceased German chemists. It would be a better world - marginally - if all biologists knew what a Diels-Alder reaction was, and all chemists knew what an open reading frame is. That, unfortunately, is not the world in which we live. 

What’s in a name? 

Another problem is compound nomenclature. The chemists, naturally enough, see each compound as a structure with its own features. The biologists generally have no such ready handles to grasp, so they tend to rely on company registration numbers, which they become so familiar with that they shorten to nicknames. This leads to team meetings where the biologists ask if there’s any more ’235’ around, and the chemists ask them if that’s the one with the methylthiazole, and things deteriorate from there. Often the only common ground is that the biologists remember which chemist actually made the compound (’You know, that one that George sent in that had the long half-life’), which at least narrows things down. 

But there’s a more subtle difficulty, one of worldview. Everyone knows enough about their own field to be aware of its difficulties and its troubling gaps. But we tend to assume better things about everyone else’s areas of expertise. The chemists figure that the formulations people will be able to come up with some way to dissolve and dose their latest compound, even though the stuff may have the physical properties of glass-grinder’s grit. The biologists, for their part, assume that the chemists will always be able to come up with some new structure that addresses the problem of the moment. And that’s very sweet of them, although the truth is that we often have no good ideas about how to solve these things. Less endearing is the timeless assumption that the chemists have heavy, open barrels of whatever compounds the biologists might need, with worn metal scoops dangling from each one by their attached chains. 

Blind faith 

One consequence of their faith in chemists is that biologists are often more enthusiastic about any given compound as a drug lead. The chemists see all the potential problems - shaky patent possibilities, ugly synthesis, not-too-stable side chains - while the biologists only know that it’s the first thing to really hit in their assays in two months. There can be some puzzled looks exchanged while the ’Why are you/aren’t you excited?’ questions get sorted out. To be fair, the chemists often take the biological assay data and run with it, giving it far more interpretative weight than it can bear. I’ve seen an inexperienced chemistry colleague start building a hypothesis based on one compound that was 2 micromolar in potency versus another one which was 3. That was very generous of him, I suppose, to think that the assay had such tight error bars, but I’m not sure if our biologists ever found out how highly he thought of them. 

These different perspectives can send a project down the wrong path, though, if people aren’t careful. Trouble ensues when each group starts blaming the other for the project’s problems, and since every project has problems there’s always fuel for that fire. The chemists start wondering why the biologists can’t get their assays to reproduce, and the biologists grumble about when the chemists are ever going to get around to making some active compounds. Nothing good comes from these discussions if they become a habit. An unjustifiably high opinion may not be a good thing, but it’s better than an unjustifiably low one. 

Derek Lowe is a medicinal chemist working on preclinical drug discovery in the US