How falling off a horse led to discovering the opiate receptor

“Any way you can make love, somebody’s already thought of. Any crazy caper you can get up to, any great meal you can think of, any combination of children or idea of how to raise them – somebody’s already thought of. But nobody’s ever discovered an opiate receptor before.”

– Candace Pert1

Shortly before starting graduate school in pharmacology at Johns Hopkins University in 1970, Candace Pert broke her back in a riding accident2. She took morphine to treat the pain, and subsequently became curious as to how this miraculous drug acted to produce such profound analgesic effects.

Now I’m not saying it’s a great thing she broke her back, but let’s just say if someone had to get injured and take morphine in 1970, Candace Pert was a good pick. At the time, how morphine and its chemical cousin heroin acted to produce feelings of pleasure and reduce feelings of pain was still a mystery. There were two major possibilities:

  1. Morphine was acting to increase or decrease the amount of another known neurotransmitter. (This is how cocaine and MDMA exert their effects.)
  2. Morphine was actually binding a new, undiscovered receptor. If true, then there must also exist a corresponding undiscovered neurotransmitter! (This is how nicotine and THC in marijuana works.)

Scientists should never have a favorite hypothesis, they should only want to figure out the truth. Emotion is, after all, an incredible implementer of bias. But come on. Clearly the more exciting hypothesis is #2: if true, that means there is a whole new class of neurotransmitters and receptors that no one knows about!

Candace Pert thought #2 might be the case, and she started in the Snyder Lab determined to find the ‘opiate receptor’. This is not, however, what Solomon Snyder wanted her to do. According to Pert, he was focused on discovering another elusive receptor at the time: the insulin receptor.

Pert was undeterred. She did what I know many students still do to this day: ignored her adviser. Not completely, mind you. She went about looking for the insulin receptor during the day. But at night, she pursued her own interest in secrecy. Dramatically, during a time-sensitive last step to radioactively label the receptor, her baby-sitter bailed and she did the experiment with her 5 year old son at the lab bench beside her2. The radioactive labeling worked: there was clearly some protein in mammalian nervous tissue binding opiates with such high affinity that it had to be a receptor.

I imagine, after seeing the results, that Solomon Snyder changed his mind and thought the project was a good idea. All said and done, it was the greatest discovery his lab ever made, and resulted in him winning the prestigious Lasker Award in 1978 (which Pert was excluded from).

Now we know there are actually three major classes of opioid receptors: mu, delta, and kappa. Pert discovered the mu-opioid receptor, which is the receptor that mediates the rewarding and analgesic effects of heroin, morphine, codeine, and other synthetic prescription painkillers like oxycontin, oxycodone, etc.

The landmark paper by Pert and Solomon, published in 1973 by Science3, has 2 tables and no figures. How times have changed.

References:

  1.  Candace B. Pert, neuroscientist who discovered opiate receptor, dies at 67. Washington Post https://www.washingtonpost.com/national/health-science/candace-b-pert-neuroscientist-who-discovered-opiate-receptor-dies-at-67/2013/09/18/c84ef128-1eda-11e3-8459-657e0c72fec8_story.html
  2. Scientist discovered opiate receptor LA Times obituaries: Candace Pert http://articles.latimes.com/2013/sep/24/local/la-me-candace-pert-20130924
  3. Pert & Synder Opiate Receptor Demonstration in Nervous Tissue Science 1973 vol 179 No. 4077  https://www.ncbi.nlm.nih.gov/pubmed/4687585

 

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