> Radiation is less of an issue than what it's made out to be.

That statement is counter to everything I've ever read about persistent low-level radiation exposure over long periods. Curious if you have a source?

> Indeed, only solar flares present dangers, but they travel slowly and there will be at least a day's notice for the crew to seek shelter. The entire spacecraft can't be shielded from a solar flare, but a smaller part can be. That could be a room (pantry) in the centre which houses the food and water supplies, lining the outside.

Sure. In fact, I believe that's the plan for Orion. This limits both the total crew capacity, their operational capability and puts further constraints on scientific and computing equipment (which can't be easily moved).

> Microgravity can also be avoided at small costs by keeping the last upper stage tied to the main spacecraft with a long tether. Rotate that as a counter-weight against the main spacecraft (and the spacecraft itself) to give the crew a ground to stand on.

Maybe... except we've never built anything like that and new construction in vacuum has a way of causing interesting surprises. In the future, sure, there will be at least some microgravity generation and there are a lot of proposals but none are near-term engineering projects. What is the tether made out of? What's your backup when it malfunctions in some fashion? Where do you get the energy to spin the weight and it's counterweight up and down at need? Where do you get the long-duration, vacuum rated gear housing for the tether control mechanism?

> Manufacturing-wise, the main ingredient is a heavy-lift vehicle on the scale of Saturn 5, capable of lifting at least 100 tons to LEO, preferably 150 tons.

Lift vehicles are now well-known enough that corporations can build them in for-profit enterprises. That's simple enough. With an eye to manufacturing, for long-distance space voyages, you've got to look at field-reparable spacecraft. This is a complete unknown for human habitable craft (though Hubble, the space stations and some of the later Gemini missions have given some sense of how that will go) out of range of resupply. There are plans but no operational experience which'll lead to fun surprises.

> Life support is not insurmountable either, although we've seen in the past that NASA needs a better focus at estimating danger (Challenger, Columbia).

That... is a weird statement. There's been no crew loss due to life support systems. Re-entry and launch vehicle mishaps yes, but not life-support.

The primary engineering challenge around life support is, again, we have no experience with closed ecosystems out of range of resupply. We can store food--so agriculture can be dumped, potentially--but carrying enough disposables to manufacture and recycle an atmosphere is a no-go in terms of weight. You've also got the challenge of illness--an inevitability over several years--which we don't have any experience with save "tough it out; it's a short mission".

> You can find this and more in Zubrin's book: "A case for Mars", if you're interested.

I've read Zubrin's book. It's well done but overly optimistic with regard to basic engineering challenges in a like matter to mid-50s proposals for a lunar landing. The discrepancy between those is fascinating and, when it's all said and in the history books, will be in a like fashion to Zubrin's book. Given present levels of technology, we're more likely to send--in the near future and without substantial, multi-generational investment in basic R&D--something like a current-tech space station with a rocket on the ass-end of it.

Anything else is speculative and more akin to near-future scifi than not.