Episode 99.5: Candidate genes

Here’s another one for the annals of “entire scientific field becomes totally misguided for decades”. How could it have been possible that so many scientists fell for the idea of candidate genes—that there were individual gene variants that explained huge chunks of variation in depression, aggression, intelligence, and many more psychological traits? How could they have written literally hundreds of peer-reviewed papers based on completely false “results”?

Well, they did. Here’s the story.

(Why 99.5? We’re putting off doing Episode 100, just so we can mark the occasion with an even better topic).

The Science Fictions podcast is brought to you by Works in Progress magazine, the journal of underrated ideas for making the world a better place. Today we talked about the new article on why Japan’s railways are so good and what other countries can learn from them. Read all their articles, for absolutely zero cost, at worksinprogress.co.

Show notes

* The first study on 5HTTLPR and depression, from 1996

* Caspi et al.’s seminal 2003 Science paper on gene-environment interaction with 5HTTLPR and depression

* “Orchid genes” in The Atlantic; Wired; The New York Times

* Caspi et al’s 2002 paper on MAOA, the “warrior gene”

* Article on the Maori people and MAOA

* 2009 story on an Italian court reducing a sentence due to MAOA

* Though no such luck in New Mexico in 2021

* Scott Alexander’s classic 2019 article on candidate genes

* Failure to replicate the 5HTTLPR GxE as early as 2005

* 2009 meta-analysis with flat-as-a-pancake results for 5HTTLPR

* Letter about the lopsided nature of its citations

* 2011 “critical review” of candidate gene studies

* 2019 Border et al. study attempting to replicate depression candidate genes

* 2025 GWAS of depression

* A Google Scholar search for “5HTTLPR depression”, restricted to articles published in 2026

Credits

The Science Fictions podcast is produced by Julian Mayers at Yada Yada Productions.