We do not know what we do not know.
Our brain is ultimately constrained by what it can learn. These limits are enforced by our senses and synapses, which are ill-equipped to study the very questions to which we most desire an answer. And by the nature of the universe, which is much vaster and more complex than our neural system.
Consider this parable of the dog and the stockbroker. The two are out for a walk. The stockbroker is wondering if he should place a collar on his next trade to lock in a gain. He is deep in thought, oblivious to the world around him, but confident in his financial skills and his knowledge of the markets. The dog cannot, and will not ever understand the intricacies of stock trading. So he trots on, only dimly aware of his master’s concerns. He may ask what is wrong, but cannot answer.
On the other hand, from a patch of urine the dog can smell that Sally is in heat, and would like to slip off his collar and give chase. A fragrant signal to which the stockbroker is immune. Two brains, more or less made of the same stuff, often eerily in sync, yet each might as just as well be inhabiting a separate universe.
Imagine the gap between a bacteria and a man.
A hundred years ago we were unaware that bacteria and viruses existed, so did not ask if a mold could cure an infection. Instead, we ascribed disease to fate, bad luck or an imbalance of humours. Our lack of knowledge and limited direct observational tools broke the link between cause and effect. So we bridged the gap with superstition and the hidden-rule game of religious mysticism.
Just because a question can be asked, does not mean it can be answered.
Progress will continue, and our knowledge base as a species and as a culture will grow. We too were once single cells with emergent consciousness. Where once we were limited to answer questions that a hundred billion slow neurons in a single brain could solve, today we address issues that a billion brains, working in tandem with a billion computers, can surmount.
But, like the dog and stockbroker, we do not know what we do not know. We do not intuit what we cannot sense directly, and even the few lucky ones who can probe the universe with devices that extend our senses and enhance our mental skills eventually run into the limits of their tools.
A billion dogs will never trade stocks.
The cosmos is vast and old and complex. Our brains are slow and small-- shaped and distorted by evolution, burdened by the primary directive of survival. To think we can learn indefinitely is hubris. To think we are asking the most important questions, a divine comedy.
We do not know what we do not know.
(or put another way, in my comment on Quora)
Mankind's greatest tragedy is the compulsion to pose certain questions which we will never be smart enough to answer.
Life would be so much easier if the solution to every puzzle was simpler than the puzzle itself- if there was an answer in the back of the "book" for every question. Some people divine simple answers to hard problems in religion, and find solace in this certainty. Others are comfortable with the messy process of discovery and continual change. As Feynman may have stated "I would rather have questions that can't be answered than answers that can't be questioned!"
The universe is an enormously complex and ultimately unknowable place. We observe the world through a lens distorted by the limitations of a small wet brain, whose sluggish neurons are biased by evolution to favor heuristics over deep insight. We are likely blind to the universe's most important secrets.
In the end, we are doomed to gaze at the promised land from afar, yet never cross the desert.
Still, the trip is worth taking.