The most plausible option I have ever explored is to have a pretty decent amount of skill with a 3D design program like CAD, load up a factory engine case into the program and work around it to produce the blueprints to cast a completely new case, build a new crankshaft to deal with the extra cylinders, and have a new jug and head cast to fit the stock components. "Grafting two engines together" is a nice way of saying, build your own engine cases and crank shaft from scratch to mate up a bucket load of stock parts to work together. The other big part of it is the cam shafts, two sets driven by two gears central on the crank? Or two long cams made to fit the new head casting...
Depending on how far you can go financially and with overall skill with drafting and design, you could pull off a multi cylinder engine for a bike for an affordable amount, or it could cost $40,000. Until you track down the places that can cast, machine, and fabricate all the uncommon parts for the build it's really up in the air how much it would cost.
As for the two 250's, I think it is the idea of less rotating mass, less weight, and higher rev's that drives the idea behind sticking with smaller engines for such builds. I've seen quite a few bikes with one off engines like the 500/8.
This one was also using the Suzuki 250, but in an inline six configuration.
I've nowhere near the skill, time, dedication, or money to build something like that, but I have explored it to great lengths to see just how far it goes. Seems every few years someone rolls out a new home brew multi cylinder machine that appears to have the fit and finish of a production engine.
I think (not totally sure) that the biggest V8 race bike I've ever seen that measured up in competition was a 500cc Moto Guzzi. There was a bit of on bike footage from a festival at the IOM a few years back too.
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