Chasing Men on Fire: The Story of the Search for a Pain Gene

by Stephen G Waxman, James E. Rothman

A thirty-year quest, from genes to pain-signaling neurons to people with a rare genetic disorder that makes them feel they are on fire. Two soldiers, both with wounds injuring the same nerve, show very different one is disabled by neuropathic pain, unable to touch the injured limb because even the lightest contact triggers excruciating discomfort; the other notices numbness but no pain at all. Could the difference lie in their genes? In this book, described in the foreword by Nobel Laureate James Rothman as “so well written that it reads like a detective novel,” Stephen Waxman recounts the search for a gene that controls pain—a search spanning more than thirty years and three continents. 
 
The story moves from genes to pain-signaling neurons that scream when they should be silent to people with a rare genetic disorder who feel they are on fire. Waxman explains that if pain-signaling neurons are injured by trauma or disease, they can become hyperactive and send pain signals to the brain even without external stimulus. Studying the hyperactive mutant pain gene in man on fire syndrome has pointed the way to molecules that produce pain more broadly within the general population, in the rest of us. Waxman's account of the many steps that led to discovery of the pain gene tells the story behind the science, of how science happens.

Genres: Science, Genetics, Medicine

593 pages, Kindle Edition

Published March 2, 2018

Reviews

[Steve · Rating 4 out of 5]

This is a detailed explication of the search for a “pain” gene associated with erythromelalgia and the means to treat it. A gene was found associated with the Nav1.7 sodium channel. The last 2/3 of the book detail the search for the gene and mutations in detail and include a good number of the scientific papers.

While it is meant to be for both the interested scientist and the lay person, it will be difficult for many to get past the details of voltage clamps and more. But the lesson at the end is that we can find personalized treatment for a good number of genetically linked disorders. There is much to discover and it does take a long time.

In erythromelalgia a genetic mutation that occurs in the SCN9A alters the function of one particular type of sodium channels. The alteration makes the threshold for firing significantly lower (and it may alter their location and number). The years it took to locate the gene and then to approve and finish useful research needs to somehow be honed to make the process faster.

Basic research and applied research leads to increased knowledge that informs future avenues of research.

[Chan No · Rating 4 out of 5]

I think this was recommended on a blog i was skimming as a good overview of the drug target validation process.

It opens like it’s going to be a popular science book for laypeople, defining various types of pain and some basic neuroscience. The writing style is very nice.

Subsequent chapters have an outline of how some bit of knowledge came to be, like descriptions of how collaborations were initiated, and then the bulk of it is the actual relevant journal article that resulted, which took me by surprise. Thankfully, unlike a lot of papers I’ve been forced to read, these are relatively elegant and concise. The figures are also aesthetically pleasing.

It’s not a bad format now that I think about it, and maybe more PIs should make a compilation like this. It would make a good set reading for a neuroscience course. In an ideal world, all journal articles would come with a “natural language” synopsis.

[Mills College Library]

616.0472 W356 2018