Like the fact we can't even explain an everyday phenomena all humans experience like consciousness. If you don't understand a common phenomena that (supposedly) occurs in the brain, you have a fundamental lack of knowledge on how the brain itself works, and thus simulating it would not be a thing possible to do.

Another hint is the fact that we can't currently even simulate a single cell because of how much complex they are, and the most advanced neuron models (like hodgkin-huxley) are still gross simplifications of how we think a real neuron works. We don't have any proof that this is a possible thing, it is something people believe it is the case, but pretty much could be a dead-end.

Other is that we don't have a way to reliably know the state of the alive brains without modifying them, so reproducing one with fidelity appears to be very hard or maybe even impossible.

And so on.