The Philadelphia Chromosome

I started medical school only a few years after imatinib was successfully approved by the FDA. One of the most memorable lessons from those first few years was about CML and imatinib's use for it. I was dazzled by the very logical chain from translocation to fusion protein to proto-oncogene to inhibitor to cure. There are only a handful of moments that direct someone's life, and this was one of mine: I decided to do cancer genetics (it wasn't until years later that I would drop the “cancer” half of the career plan.) I spent two years in a cancer genetics lab, got involved in one of the first off-label uses of dasatinib and spent time speculating about all of the tyrosine kinase inhibitors of the future. And I've lived in the future, where even having walked away from cancer, I got myself intertwined with lung cancer and EGFR inhibitors and the disappointing resistance that occurs.

So, the Philadelphia chromosome story is a story that is near and dear to my heart. Nonetheless, I found Wapner's rendition of it particularly fascinating. First of all, she doesn't miss a beat: she starts from the very beginning about how dubious scientists were that the Philadelphia chromosome was a spontaneously occurring, somatic, balanced translocation and goes straight through to the ways in which the TK inhibitors that followed were kind of disappointing with the rapid-onset of resistance and the difficulty of detangling primary causative mutations from carrier mutations. Secondly, she really places each step along the research in the context of where science was at the time, keeping track of each of the details ultimately necessary for drug development (several of which I didn't know). And finally, she tells the story in a way that speaks to the broader picture of drug development – the difficulty of investing in orphan diseases, the tension between industry and academia, the fear of testing a drug that might have unforeseen consequences.

It's rare that a popular science book is equally readable by lay and expert audiences, but I think Wapner's done a great job of making this work accessible but detailed.