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I'm tinkering with a "what if" idea - Romulans learn of the doomsday machine encounters (Borrowing from FASA's "A Doomsday Like Any Other") from pilfered Starfleet records in 2320 and the Tal Shiar send a small team of cosmetically enhanced operatives through the Guardian of Forever posing as Constellation officers. They then hijack the machine, destroy the Constellation, and return the device to Romulus where they study it and learn to replicate its technology. The Romulans are unable to make the neutronium hull but are able to make copies of the machine with normal hulls. Conquering ensues. However, the other races manage to salvage bits and pieces of the technology here and there and eventually make their own versions of the devices. Jump forward about ten years; The Alpha and Beta quadrants are now nearly devoid of habitable worlds because of the devistation caused by small fleets of these devices running amok.
It'd probably work best as an adventure maybe not a campaign setting. I dunno, I'm still playing with it. Any feedback would be appreciated.
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For whatever reason, I always imagined the Doomsday Machine as being alive. Maybe they end up being able to grow one of their planet-munching stomachs, but it requires a giant-sized warbird framework.
Accordingly the other galactic powers could amp up other kinds of weapons research in order to compete. The Federation creates the Genesis Torpedo, the Klingons and the Tholians join forces to deploy system-scale Interphasic Wave Generators.
One possible result is that, faced with MAD, everyone starts trying to replicate the Romulans' success at altering the past, and the Temporal Cold War starts 700 years early...