I agree, and I agree with @anon50609448 that we probably can’t directly perceive the base reality (or noumena as philosophers would say). But because we can’t directly perceive reality, I think we even have to question what that means. We construct this distinction between phenomena and noumena because we assume there’s a sort of binary difference. Why? Because we’re used to the idea of cause-and-effect, so we assume this extends beyond the limits of our perception. But causality is an empirical observation. Moreover, it’s one that, while it does hold sway in the more fundamental realm of quantum mechanics, it does so in a probabilistic way that’s alien to the deterministic way our minds and senses have evolved to interpret the universe. This to me suggests we should not be especially confident in the actual existence of this base reality. Sure it’s a helpful tool in using our maps, but we should be willing to doubt it.
Now I’m not a mathematician (though theoretical physics has a related problem), but I get the impression that what Wolfram was getting at in the interview is not that we should assume we can understand base reality, but that we have to realize that precisely because we can’t, we must realize our mathematics might not be the only one we can use to do things like study systems and even make useful models of the physical world. Our system of mathematics has been useful, but it’s self-consistency has also caused us to search for mathematical tools that are consistent with that particular system we’ve built on axioms that ultimately derived from how we perceive the world (AKA geometry and arithmetic, and then later on algebra and set theory).
As a physicist, I’m sometimes troubled by the confidence theorists have in the elegance of mathematics. I think it might be giving them a case of confirmation bias…not that they’re approach is wrong (that’s why we have experimental physics, to point the telescope so to speak), but that they could be limiting themselves to a tiny fraction of the possible approaches by their desire for tools and solutions that appeal to their aesthetic senses.