2. Knowledge comes from using reason to understand our sense experiences. The iterative nature of the scientific method is what hones this process towards truth. In a large and changing universe, eternal absolutes are extremely difficult to prove. We must act based on the best available knowledge. This leaves us almost entirely with probabilistic knowledge, which means we must act with confidence and caution appropriate to the probability, being especially careful in realms where knowledge is uncertain and consequences of error are large.
Let's break that down because there are many historical arguments wrapped up in these sentences. First, there is the part about using reason to understand our sense experiences. Many philosophers in history have argued that we are born as blank slates and only learn through the information conveyed to us through our senses - where else would the information come from?* However(!), other philosophers say, looking at things such as illusions, the relativity of observations, or memory error show that our senses can be deceived or are faulty. They have used this dependence on weak senses to declare that all knowledge is therefore suspect and relative. This unfortunate viewpoint is still expressed by many people today: college freshmen who have had their first philosophy class, wallowing stoners who justify their idleness by declaring everything to be an illusion anyway, and post-modernists and mystics who exhibit the same level of thinking as these first two. The rebuttal to these arguments is that while our knowledge does rely on sense observation, which can be faulty, we are not reliant on single observations. We are able to use more than one observation, from more than one person, and compare the differences using our reason, our memory, and our tools. We can determine where we have been tricked or misinformed. Long before we formally defined this iterative technique as the scientific method, we used repeated actions to learn things as simple as how a stone will travel through the air, or as complex as how the sun travels along the horizon throughout the year (even though we now know through further observations that the sun isn't the object that's actually traveling).
So, we can know the world, and we know the process we should use to gain that knowledge. How far can it take us? Well, quite far so far. Far enough, for example, to see that the universe is immensely large - far too big a place for us to see and know all at once. This alone is enough to tell us that there are real limits to the extent of our knowledge. We cannot know things with 100% certainty because we cannot know the entirety of the universe. As an extreme example to illustrate the point, we do not know what lies beyond our visible universe. Perhaps there are many universes in a multiverse and one is expanding toward us with the energy and rapidity to destroy everything we see in the blink of an eye. Now, we can observe over 13 billion years of history within our universe and see no evidence of an event like this happening, but that does not rule out its possibility. Therefore, as stated in the tenet, we are left with probabilistic knowledge.**
Does being only 99.99...% sure that the sun will rise tomorrow mean that all knowledge is fatally flawed and we should abandon all efforts of planning and learning? Of course not! It is merely a reminder that we are not perfected creations and should not be surprised to see our knowledge grow and change as our observations and logical reasoning grow and change. It is a reminder that we will always have work to do in this endeavor to understand the universe and our survival within it. And it is a caution that we must be careful about going too far down an uncertain path (with, for example, climate change, genetic modifications, geoengineering, or agriculture monocultures) without hedging our bets against our uncertainties. We must find the balance between our ignorance and our hubris. We must find confidence - not meek under-confidence, not rash over-confidence. We must have a proud humility about what we have learned and what we still need to know. These are not new recommendations, but are merely confirmed by a full understanding of the sources and limits of our knowledge. They should not be forgotten.
* While the blank slate theory has been rebuffed by the observation of innate instinctual responses passed on through the genetic makeup of our bodies, this covers only a tiny percentage of our adult knowledge and actions. The rest results from the ongoing interaction of our environmental experiences (experienced through our senses) with our genetic makeup - the "nature x nurture" answer to that old debate.
** This applies for all things outside of our own definitions. We know with 100% certainty that 2 + 2 = 4 because we have defined it so. But mathematics are not a concrete aspect of the universe.