The process of making tomacco was first revealed in a 1959 Scientific American article, which stated that nicotine could be found in the tomato plant after grafting. Due to the academic and industrial importance of this breakthrough process, this article was reprinted in a 1968 Scientific American compilation, Bio-Organic Chemistry, on page 170. (ISBN 0-7167-0974-0)

A Simpsons fan, Rob Baur of Lake Oswego, Oregon, inspired by the episode and remembering reading the article in a textbook, cultivated real Tomacco in 2003. Tests on the plant revealed nicotine in the leaves. He was featured on the “E-I-E-I-(Annoyed Grunt)” audio commentary in the Season 11 DVD box set discussing the plant and resulting fame and mentioned selling one plant on eBay for $16 and going on to make a potato/tomato hybrid, which the media gave no attention to.

The 2004 convention of the American Dialect Society named tomacco as the new word “least likely to succeed.”