I'd encourage everyone reading the AMA to take a lot of what Musk is saying with a grain of salt. The Interplanetary Transport System (ITS) is a wildly ambitious project that is attempting to accomplish more things in a shorter period of time than the Apollo program (and on a substantially smaller budget to boot). Check out Robert Zubrin's article, which presents a much more salient critique of SpaceX's current plans…
He then claims that ISRU is impractical due to hypothetical resource constraints.
Zubrin then claims that the Spaceship is a "habitat" that should only go one way. SpaceX has decided that the habitat should be built on Mars from indigenous materials. A one-way Spaceship is vastly more expensive than a reusable one.
Zubrin dismisses fast transit to Mars entirely on the basis of not being a free-return trajectory with a symmetric time span (6 months out, 6 months back). The free return is only if use if the spacecraft is not going to land. The number of failure modes where the Spaceship can't land on Mars but can still manoeuvre into Earth orbit are very small. The Spaceship is designed for aerobraking and landing, not orbital capture.
He then goes on to criticise the four-month express crew transfer as having no payload capacity, when the intent was only to show that rapid crew transfer is possible. The benefit of the shorter trip is less exposure to harmful radiation. The assumption is that sufficient resources already exist on Mars to house and feed the new arrivals.
A multi-component system as proposed by Zubrin with an Earth-Mars transport with separate craft for leaving Earth and landing on Mars adds far more complexity, more moving parts, more ways for things to fail.
The SpaceX monolithic approach us safer simply because there are fewer things that can go wrong.
Zubrin's supposed improvements are to split the Spaceship into propulsion and habitation modules, with the habitation module having its own vacuum engines for Mars intercept and landing, and then some way of splitting those motors away from the habitat upon landing so they can be cannibalised or returned to Earth.
Which is to say, Zubrin has spent so much time evangelising Mars Direct that he no longer considers any other option as valid.
SpaceX are pursuing the engineering goal of sending large payloads to Mars and back to Earth with best use of resources. They want the incremental cost of moving people and things around the solar system to be as low as possible. Zubrin wants a single transit to be as low cost as possible, meaning use of disposable spacecraft, meaning higher costs overall.