Just like great Rock music, great Science needs Dissatisfaction, Dissent, and Rebellion.

..consider these words "Warburg [his mentor] did not think I had sufficient ability for a successful research career ..... I came to the conclusions that my talents were quite mediocre. It was only my keen interest that drove me to keep trying for a position which would give me scope for research."

These are the words of Hans Krebs, the man who discovered how food is converted to energy  (Kreb's Cycle - a mechanism conserved in every living organism on earth, 1953 Nobel prize).

OK here's a quick insight from writing papers. If a concept is clear in your mind, never ever use a complicated word, when you can use a simpler one. But hey if something is not clear to you (or anyone else for that matter), try using a very obscure word that was only common during the 16th century. The results can sometimes be gratifying (as opposed to good of course)...try it!

The short answer is unfortunately yes. I have never seen (or had) a student or postdoc who has done well and NOT worked hard (trust me I have seen a LOT). When I was seriously doing experiments (not that long ago), my experience was that I had to give every fibre of my being to find anything that was really new. So I suppose putting in long hours is kindof important, but I have come to realize that there is a specific time when one needs to really, really work hard. And that is the time time when everything is going really really well. 

When one is just starting out, and simply "fooling round", trying to find something interesting to do, perhaps it is not that critical to work hard. In fact it may be argued that one should not work that hard during this time. This is a time that is typically filled with disappointment and frustration, and perhaps a cavalier attitude is best. Try your best and come what may ("whatever" as teenagers now say). Trying too hard will only lead to greater frustration, so stay focused but loose.
 
But when you get on the right track after a few months and in your mind's eye can see what mother nature is really saying, that's really the time to work really really hard. This is the time when the methods are all working, the constructs are all made, the experiments are all lined out (pretty much), there is only one thing to do. WORK WORK AND WORK. Get it done. There will be lots of lazy afternoons afterwards. Undoubtedly there will still be setbacks and frustrations (that's how this works, OK), but in the end the pleasure is - as Feynman famously said - in findings things out! 

What makes a good PI? Good students and good postdocs. Its simple.

The best thing about a "Brief Communication" is that the abbreviated format allows only a minimal exposure of your ignorance.    

Anytime you think that "numbers don't tell the whole story", take a look at the numbers in a football/baseball game (passes, interceptions, ERAs, YAC's whatever), and see if the LOSING team has better numbers.

If the experiment is clean, the NUMBERS DON'T LIE.

In the wake of all the failed trials with anti amyloid-beta agents, I will say this for the record. I have read the literature, and being a neuropathologist I have seen hundreds of Alzheimer's brains over the years. Nothing else makes sense. If it is really not amyloid-beta, boy we are REALLY screwed.

Who isin't. That stupid experiment is not working, the project you thought was cool is a damp squib after all, the paper is floating in that glossy journal for a year. Stop for a second to think that at the instant you look at these words, a billion neurons are firing, making it possible for you to see, process and understand the words - all in the blink of an eye. And that's just a small fraction of what's working to keep you alive at this instant.

Doing Science was never easy. The truth is that you can only do this if you must, and there is just nothing else you can really do. OK well you can, but at least you need to give this Science thing your best shot.