The best scientists and other professional problem solvers embrace the phrase:
“When life gives you lemons, make lemonade”
Wikipedia: Elbert Hubbard in a 1915 obituary he penned and published for dwarf actor Marshall Pinckney Wilder
I once interviewed a smart candidate for a faculty position, and one of the selling points that he raised was the large number of studies that he had started but that didn’t pan out. He was saying this to suggest that he had already done the hard work of sifting through the many dead ends that we all have regularly hit and that what was left was a smaller set that are more likely to work. In other words, he thought this was a strength in his application.
I interpreted his comment as evidence that he didn’t know how to make lemonade out of lemons. Others had similar sentiments, and he didn’t get the job. Maybe “Lemonade Seller” should be listed in professional resume as our first job experience.

One of the hardest things to do in science (perhaps in life) is to know when to give up on something. Sometimes we find ourselves like Sisyphus pushing a rock up a hill, and we can waste an awful lot of time and energy on something that just isn’t going to ever work. It is critical to know when to quit.
But in my experience, many scientists are like our smart faculty candidate and they give up too soon. I don’t know how to teach students when to stop and when to push, but most of the time I find myself encouraging trying other approaches to solve the problem rather than quit altogether.
It is hard to work on something for a long time and have it fail repeatedly. But this sometimes is the life of a scientist, who often doesn’t know the solution to a problem before figuring it out. However, like Sisyphus, many of us just try to push harder and harder, and this can be exhausting or impossible.
When we are pushing rocks up hills, we tend to not see alternate paths off to the side that may not seem direct but ultimately may be a lot easier. My mental image is Sewall Wright’s adaptive landscape that provides an abstract way to think about how mutations in populations of interbreeding species can lead to adaptation and evolution.

A similar abstract concept can describe how a protein can fold. Without something like a funnel, proteins would require longer than the age of the universe to fold into their active structures.

I think that often when problems seem intractable, we are pushing up a steep slope that may seem direct, but we are blind to easier paths that take us more quickly to the goal. When I reach this point in my own work, I try to take a break and mentally step back. Oftentimes the alternative path comes to me in a walk or run or working in my leathershop. Or sometimes I just conclude that it was a stupid idea that will never work and I move on.
As I was thinking about this blog post on my run today, I passed a young girl in a yard with a lemonade stand. I didn’t have money and was too gross and sweaty to stop. I wanted to shout that she should become a scientist when she grows up, but I thought that might just confuse her and her mother. Instead I just smiled and waved.