> we're pretty confident we can […] keep humans alive in space for years

Are we? In outer space? Radiation, psychology/isolation, months away from any support in case of an emergency? My understanding is that there are a lot of open questions, and that even a mere fly-by mission would constitute a major new step in manned space flight.

Indeed, we should rather attempt sending such a ship in one piece to the moon first. Right now we would have problems actually assembling such a craft. Note how long and cost intensive it was to assemble a bigger space station.

Gateway program is such a baby step, assembling a base in moon orbit.

Ultimately, we would need an orbital facility to assemble bigger ships well without paying the immense costs of ultra heavy launches.

This is also why a moon base makes so much sense:

* short enough that radiation issues can be swerved.

* can build shielded moon bases (or dig them?) to protect people on the moon itself.

* can mine the resources for and build heavy, shielded ships on the moon itself and launch far more cheaply.

* can also build (on the moon) the shuttles needed to ferry people from earth orbit out to the moon, making it so that the only people exposed to any radiation at all are the first crew to arrive on the moon and stand up a moon base.

I'm not a super expect in space, but I'd argue yes. There is more radiation there, but we know how much and how to shield from it. The ISS does have an "escape module" descent craft allowing the crew to evacuate in a few minutes any time needed, but they've never had to use it yet. IMO that's a good argument that it isn't that big of a deal. Yes, it'll be a bit riskier for the crew in that there's no security blanket of a quick easy escape to Earth in the event of a real emergency, but well shit happens. I don't think there's anything going on as far as isolation that's really more severe than tons of other things that have already been done.

We have absolutely no experience shielding people from solar winds and cosmic radiation in any way that would be meaningful for an interplanetary journey. Even the ISS is benefiting from Earth's magnetosphere and atmosphere.

We have a few vague ideas:

* Thick plating. (How? Not like we can launch it, so we'd have to build the space craft in space using materials mined from e.g the moon or asteroids)

* An artificial magnetosphere, which researchers are still doing feasibility studies on. But there'd be a litany of challenges there as well, such as figuring out how to design it so that we don't see deleterious effects on electronics or people.

Moon jaunts were short enough that it didn't matter, but anything interplanetary will need this challenge to be solved lest we want our explorers to suffer excruciatingly painful deaths.

There was, in fact, a plan in the Apollo Applications Program for a crewed Venus flyby, using the SIVB as a wet workshop for habitation. https://en.wikipedia.org/wiki/Manned_Venus_flyby

It would essentially be an ISS mission with a few extra rocket burn stages and a different view.

Is a fully-assembled ISS capable of withholding torsional stress that would come from insertion burns?

Nobody is talking about doing an insertion

With a much different radiation environment.