There's one fact that seems unavoidably, uncomfortably true about being human (or, presumably, any other sentient being). It's so obvious as to be almost a tautology; a fact so banal that it almost doesn't merit mentioning. Ready? Here it is:
We prefer feeling good to feeling bad.
Now, if you're looking for counterexamples to this statement (you pedantic bastard), they're not hard to find. Masochists enjoy pain. We often take on short-term punishment for long-term gains. Some of us love to wallow in self-pity.
But if you analyze those examples carefully, you'll find that we haven't really countered anything: in every case, our motivation is the same. We want to do something to make things feel better, somehow -- even if the means are counterintuitive. This is what is referred to as suffering (and the urge to escape it) in Buddhism. It includes not just overt suffering, but that constant buzzing sense of discontent and incompleteness that most of us recognize (and yearn to consummate).
Okay, so let's say we buy this for now. So what?
Well, by early adulthood (at the latest), most of us have developed a rather refined and increasingly static set of mental heuristics that help us achieve that basic goal. We've got a list of preferences a mile long (and that should keep us relatively pacified over the course of our slow, unceremonious march toward death), or in lieu of that, at least a sense of personality that allows us to sidestep that particular cliché: you see, we're adventurous!
But how adventurous can we really be, when most of our assumptions about the very nature of reality are so static?
Consider: when you were a baby, you had no idea what the hell was going on. There were sights, sounds, fear, joy, wonderment... sometimes all at once. A marvelous, confusing dance of experience. Maybe like being on a months-long LSD trip.
Over time, you started developing a model of this experience that would stay with you for a long time to come. If you were particularly curious and bratty, someone was forced to explain to you that this whole lively dance was somehow equivalent to, or caused by, some mushy stuff inside your skull. Just what it meant for the liveness of experience to be the same as, or a byproduct of, matter, they couldn't tell you.
But it didn't matter; such concerns are easily hand-waved away. All of the contents or details of your experience -- the sights, sounds, smells, emotions, thoughts, etc. -- are easy enough to correlate with the firing of neurons, after all. And if you weren't watching very carefully, you forgot that this didn't settle the basic mystery: the sheer fact of experience, quite orthogonal to any of its details.
If you were intellectually honest but only tepidly adventurous, perhaps at this point you bought the premise of promissory materialism, sort of the scientific materialist's version of the god of the gaps. We don't exactly know yet, but since reality is made exclusively out of stuff, eventually we will explain everything in terms of stuff.
Spot o' materialism, Mr. Dawkins?
But maybe something still tickles the back of your skull-meat: it is incontrovertible that conscious experience seems to be happening. Even if I dispute it, that dispute takes the form of a thought occurring inside this seeming-ness of experience. Everything else -- including this seeming physical reality, and even my certainty of it -- I only know of via this experience. And as a result, all of that stuff is, and always will be, ontologically suspect. What would it even mean to catch a glimpse of reality that bypassed experience? Try to imagine it -- and then notice that your imagined solution took place inside of experience.
And if consciousness is physical, then where is it located? In my brain? Then why is it that my brain can be moved (say, out of the back of my skull) without conscious experience moving?
So no, it can never be entirely satisfying to accept that the most basic, unassailable fact of existence will be explained in terms of some of its contents (e.g., matter). Otherwise, it's easy to see that given a sufficiently convincing dream, you could be tricked into absolutely certainty that consciousness is caused by, well... the sky is not even the limit.
So we'll have to settle for tentative certainty: in this dream I find myself in, it sure seems that the brain is somehow involved in consciousness. And though we may never be able to close that gap entirely, it doesn't seem particularly worthwhile to leave the question open.
Or does it?
Okay, he didn't really exactly say this, but... close enough.
What if the first truth about humanity -- that we seek to escape sucky-ness, but fail the vast majority of the time -- is somehow intimately connected to the assumptions we've boxed ourselves into regarding the second (the sheer fact of experience)? This is more or less the claim of Mahayana Buddhism. How would we test such a hypothesis?
Well, we can use science -- but not the kind that clutches onto metaphysical assumptions like the assured primacy of physical reality. A much more radical kind. One that strips us of everything that we can be stripped of. That is, everything but direct experience itself.
Now, if you were to try this by yourself, you'd (probably) very quickly run into an immense difficulty: your mind just won't shut up. And it sure as hell won't buy into this suspicious plan to investigate experience directly. It's always been the intermediary and arbiter of experience, and damned if it will go down without a fight.
At this point you could settle for the booby prize: fail to recognize that this yammering mind is not the same thing as direct experience, and simply declare something like "I think, therefore I am." And who could blame you? Thought is bloody persistent.
But if you're persistent and passionate enough, you may eventually catch a glimpse of the machinery that runs the whole show. You will not have shed the mind -- for what good would you be without being able to think anything? But you will have transcended it: witnessed its mechanism and functional value without mistaking any of its coarse or subtle proclamations as Truth.
And if it the result just so happens to live up to the Buddha's original promise of unconditional freedom -- that by transcending the tyranny of mind, one also transcends suffering itself, well that's a fine cherry on top, wouldn't it?