Chalupa's First Law
No matter how good or bad things are at any given point in time (in science as in life), remember that "this too shall pass."
This is key for attaining longevity in this business... people who "violate" or are unaware of this rule are doomed to failure. In other words, it is vitally important how one deals with success and failure in doing cutting edge science. Failure is the rule even among the most successful working scientists (since 90% of grant application are typically rejected and the top journals reject even a higher percentage); and with respect to success, in all but a few exceptional cases, institutional memory is exceedingly fleeting (i.e., yesterday's superstars are unrecognized by today's grad students, postdocs, junior faculty). So you've got to keep pitching if you want to stay in the science game.
Chalupa's Second Law
Don't underestimate the importance of fashion in doing science.
Another key for success in science...if you're too far ahead of the herd (with very few exception) you're not going to get funded by NIH/NSF or published in the premier journals. This is in spite of the fact that they claim that they fund innovative research. Anyone who has spend as much time on grant review committees as I have will recognize the power of this rule. In other words, there is a price to pay for originality and every working scientist knows this is the case.