New portal identifies top-quality chemical probes

Just as bad ingredients can make for an unsatisfying and perhaps downright unpleasant meal, bad chemical probes can lead to incorrect or misleading scientific outcomes. University of Toronto biochemist Aled Edwards is a staunch advocate of this perspective, so much so that he has spearheaded an initiative to help the research community sort out the quality of probes being used. “We calculated that it’s costing hundreds of millions, likely billions of dollars of investment into results that just aren’t right,” Edwards says, referring to a paper that he and an international group of like-minded colleagues published in Nature Chemical Biology this past August. 

Their concern stems from the use of reagents that academic investigators may use to demonstrate and publish a particular finding, when in reality the observation was simply an indirect consequence of a larger suite of chemical interactions. For instance, a protein inhibitor might reveal a response with respect to some condition of interest, such as diabetes, and an ensuing publication will link that particular protein to that particular response. However, Edwards suggests that there might be much more happening. “Sometimes you see a result because you want to see a result,” he says. “You just keep adding compound until you see something. It’s really a slippery slope and easy to do. Perhaps they used a compound that inhibits a hundred different pathways in a cell and saw a change, a completely non-specific phenomenon. But because the chemical was advertised as a specific inhibitor, the connection is made.”

In order to determine the quality of that connection, Edwards adds, it will be necessary to know the qualities of the original probe. That goal is the foundation of, a portal that offers information on which probes have been demonstrated as being most useful for specific biological targets, as well as how they should be employed and what problems or limitations they might pose.  “We want to make this thing independent,” says Edwards, describing the site as a Wikipedia-based approach to enabling people and institutions with a vested interest in chemical probes to assess how these agents work. This initiative has already received support from the Wellcome Trust in the United Kingdom and formal endorsement from research bodies including the Eli and Edythe L. Broad Institute of MIT and Harvard in Massachusetts, the UK’s Institute of Cancer Research and the international Structural Genomics Consortium at the University of Toronto.

According to Edwards, it can take a great deal of time and money to design chemical probes with the kind of highly selective properties that make for clear-cut conclusions. Since most of these probes originate in academia, those two key resources are often in short supply. That makes the role of this portal all the more crucial, according to Edwards. “We needed to figure out some alternative way to inform the scientific community when a tool is a good one and when a tool is a bad one.”