Professor Spencer Smythe was an expert in the fields of robotic and arachnid. One day he asked J. Jonah Jameson to fund his projects since he had become convinced by Jameson's editorials that Spider-Man was a menace. After a demonstration of how Smythe's robot could sense and track spiders, Jameson hired Smythe to capture Spider-Man after Peter convinced him thinking he could easily beat the robot. Jameson himself controlled the robot, meaning that Spidey found himself chased by a machine with Jameson's face. The robot proved to be a difficult opponent however, Spider-Man escaped by removing a section of the robot's chest plate and disconnecting some wires and by leaving his Spidey suit wrapped in the robot's tentacles while he puppeted his suit with some webbing making Jameson think he captured Spider-man.
Smythe, angered at the fact his robot couldn't capture Spider-Man, became obsessed with the Web-Crawler, turning to crime to pay his research and constantly modifying his robots, which he started to call Spider-Slayers. However, Spider-Man always defeated them by utilizing a key flaw in their designs; the second one, for example, was capable of tracking a unique energy signature produced by spiders, but Spider-Man lured it back to Smythe's laboratory, which caused it to overload from the many of spiders Smythe kept there. Smythe also began to set up cameras all over the city and began to work with gangster by informing them of which directions police would come from so they could bypass them. He also captured Spider-man with a modified version of his Spider-Slayers, but Spidey escaped and defeated Smythe and captured all the criminals.
Eventually, Smythe's career came to an end when radioactive materials used in the creation of the robots poisoned him and was doomed to a slow and agonizing death. He blamed Jameson and Spidey for his impending death so Smythe handcuffed the two of them together with a bomb which would explode in 24 hours so they would suffer the agony of inescapable death. Unfortunately for Smythe, his disease was too advanced for him to survive the 24 hours himself, and he died thinking he had killed Spidey and Jameson. Peter Parker, however,was able to abort the bomb by freezing its controls mere moments before it would have detonated due to his skill with mechanical devices. After his death his son Alistair took over his work and his revenge.
Smythe was also a partner of Mark Raxton, until Raxton double-crossed him, and the both fought. During this fight, Raxton became the Molten Man.