The man is bound by the limits of nature itself. To know the universe from outside, man will have to be outside the universe. But nothing natural or physical can exist outside the universe. Hence the knowledge of the universe from without is not possible. Also to know the internal workings of the universe or its part, man's frame of reference should be less than or within the system of his observation. But to observe the internal workings of the smallest indivisible substance, man's frame of reference will have to be smaller than the smallest substance possible, which in itself is a contradiction. Hence man can neither know the true world from within and neither the true world from without. This means that man can only know all the possibilities within the two ultimate ways of perceiving the truth but not the truth itself. Yet we deceive ourselves in believing that we are only a little away from the transcendental reality which appears to be distant no matter how close we get to it.
But there may be a different way of thinking about this demarcation. Man can know the whole Universe from within and the smallest particle from without. So by changing the approach we find that by being equal to or greater than the smallest particle possible we can observe its outer workings. Also by being equal to or lesser than the universe, that is, the biggest natural existence, we can understand it from within.
But to know a substance completely we need to know that substance from within as well as without, which seems not to be possible when we reach the lower infinity and the upper infinity. Hence man will always be trapped between these infinities. He may know everything, from within and without, between these infinities but will always be left one step behind in understanding of the true reality.
It is like integration and differentiation. In calculus, we always tend to reach 0 or 1 but we never do reach them. The real answers are always like 0.00000000000000000001 or 0.999999999999999. This leads me into believing that the fundamentality of my understanding to the limits of knowledge has put limits to mathematics itself. Mathematics then cannot justify itself to be an absolute and independent source of knowledge. It then becomes only a highly advanced way of almost reaching the fundamental truths without ever reaching them. How scary and insane is that? It is these times that lead me into believing, it is only human belief and conviction in something higher than his understanding of the universe that can truly save him from pure skepticism.