Contrary to the legends about brilliant ideas just falling from the trees like apples, great innovators don't sit or wander aimlessly waiting for inspiration to hit them in the head. Serendipity is real, of course, as are eureka moments in the shower, but the most prolific innovators actively work to increase their odds of making momentous discoveries.

Whether by choosing topics heretofore underexplored, selecting important problems, charting new territory, or leveraging existing skills, great innovators have a knack for positioning themselves in the right place at the right time.

In a recent conversation with William G. Kaelin Jr., 2019 Nobel laureate and the Sidney Farber Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute, he shared that: "When I was a young boy, my father liked to fish. And I learned that one of the most important decisions a fisherman makes is where to fish. Likewise, when you are a scientist, one of the most important decisions you make is what to work on."

Embedded within the idea of finding the right place to fish are a series of conscious and unconscious decisions that great minds like Kaelin’s make every day. I'm going to share five critical lessons, but before we get there, we need a (very) brief background.

At the risk of drastically oversimplifying, Kaelin's Nobel Prize-winning work revealed the mechanism that enables cells to sense and adapt to changes in oxygen levels. When he first started his lab, Dr. Kaelin studied von Hippel-Lindau disease, a rare hereditary syndrome caused by defects to the tumor suppressor gene VHL. People with this disease are significantly more likely to develop various tumors, including malignant kidney cancers. These tumors act as though they're profoundly deprived of oxygen 24/7 which, in turn, causes them to produce hormones that stimulate the production of more red blood cells and blood vessels. As you might imagine, those red blood cells and blood vessels help the tumors survive and grow. But Dr. Kaelin's work led to the creation of inhibitors that cut off this supply and cause tumors to shrink. These breakthroughs in understanding the cellular oxygen-sensing mechanism augur well for new treatments for cancer, anemia, and more.

That's about the shortest possible version of the genius discoveries that led to Dr. Kaelin's Nobel Prize. And with that background, let's look at five lessons to help all of us unlock more innovation.

Lesson #1: Find An Important Issue

It might seem tautological, but if you want big innovations, you usually need to tackle big (or frequent) problems. Innovating a fix for a process that fails one out of every ten thousand times won't garner nearly as much support or attention as solving a problem that occurs every day.

Why then did Kaelin focus his work on the rare von Hippel-Lindau disease? When he started his work, he notes that "it seemed like most of the examples where we had fascinating glimpses into the cause of a particular cancer involved cancers that were epidemiologically pretty rare. But it was clear that if we were going to make a dent in cancer mortality, we had to start making progress in one of the top ten cancers in terms of incidence. Most of those are what I would call the big, bad epithelial cancers, including lung, breast, colon, prostate, and kidney cancer. And knowing that von Hippel-Lindau disease gave rise to a number of cancers, including kidney cancer, why not work on a common cancer rather than uncommon cancer?"

A clear takeaway is that Kaelin's focus was on achieving maximum benefits for large numbers of patients. And given his training as a physician, that's not surprising. But there's another benefit to his strategy: Funding.

Curing cancer is obviously not easy; it hasn't happened yet, and it will continue to require time, patience, attention and funding. Kaelin notes that "Because I was working on genes that were linked to human diseases, I didn't worry so much about whether I'd be able to patch together funding. By contrast, I do worry about the brilliant researchers working on more obscure biological and biochemical phenomenon, where maybe the link to human disease isn't so clear. Their research is vital, and short-sightedness with their funding is a very real risk to all of us."

While most of us aren't working to cure cancer or other diseases, support and funding are not immutable. Budgets get cut, advocates get transferred, and corporate priorities change. While those shocks aren't always easy to predict, some areas weather cutbacks better than others. (A quick look at a company's financial priorities over the past few years generally provides some quick clues as to what they do and don't value). I'm not suggesting you avoid working on less popular issues, but at least be aware of the challenges.

Lesson #2: Explore Something Underexplored

A hallmark of great innovators is their predilection for solving novel problems. They're far more likely to take the road less traveled; preferring the charting of new territories to coloring and detailing maps that already exist.

In Dr. Kaelin's case, he shared with me, "When you isolate a new gene, one of the first things you do is go to the computer and ask,' does this look like any other genes that I've seen before?' In the case of the VHL gene, it didn't look like a gene that we had seen before. Even looking for recognizable structural motifs, it appeared to be quite featureless. There were no clues about what it was going to do, so for me, this was a great puzzle to work on."

When you talk to or read about great innovators, a common theme you'll uncover is their love of solving puzzles. And for many scientists, innovators, and inventors, solving puzzles is the fuel that drives their resilience as they plow through frustrations and setbacks.

Lesson #3: Leverage Your Existing Expertise

While Kaelin's VHL puzzle was a new one, he wasn't a neophyte when it came to solving puzzles. As a postdoc under David Livingston, himself a renowned researcher, Kaelin worked on the retinoblastoma tumor suppressor, developing and honing the skills he would employ to great success with the VHL gene.

He told me that "while the VHL protein didn't look like something we'd seen before, I assumed that some of the techniques that were useful in studying the retinoblastoma protein would be useful in studying VHL. If you look at the experiments that led to the Nobel prize, we didn't need a big technical advance. We added little wrinkles, but the underlying technologies we needed to solve the puzzle were already available."

It's not just okay to use your existing skills; it's a great way to maximize the speed and size of your innovations. If you've mastered certain skills, there's no law against developing new and different skills; but there's also no law against using those same skills to solve different problems. Teflon's first applications were military, including artillery shell fuses, while now, through a bit of creative reapplication, that same material coats much of our cookware. Temper Foam was first developed to help astronauts survive intense g-forces; now, many of us sleep on Tempur-Pedic mattresses.

Lesson #4: Embrace A Reductionist Mindset

If you call someone reductionist, there's a chance they'll hear it as an insult. But for scientists, and innovators in general, that word has a much more nuanced meaning. In its simplest formulation, it really just means reducing explanations to the smallest possible entities (in biology, for example, that could mean focusing on the biochemical and molecular processes that cause a particular biological phenomenon).

The reductionist mindset is quite common amongst great innovators. Dr. Kaelin explains his approach by saying, "Once we had the cloned VHL gene in hand, we did classical roll up your sleeves, reductionist biology. We wanted to understand what the protein encoded by this gene did in biochemical terms. And to understand why, when the protein was abnormal, kidney tumors developed. And why were those tumors rich in blood vessels? And so on. Essentially, we did classical reductionist biology."

This idea of taking things apart, dissecting a problem down to its smallest entities, and uncovering the essence of a tough question, is a remarkably helpful approach. And that approach is especially helpful when innovators are awash in data and the latest whiz-bang technologies. It's hard enough to generate brilliant innovations; ironically, that problem can sometimes become more difficult when we're confronted with an insurmountable amount of data and a panoply of new science technologies (“shiny new toys” as Kaelin describes them) that run the risk of diverting our attention without providing deeper insight. As the saying (sort of) goes, lots of people have information, but not many have insight.

Lesson #5: Take The Detours

Many great innovations are not easily foreseeable; in fact, it's likely that most are not. If you really want to increase your chances of serendipitous and game-changing breakthroughs, Dr. Kaelin strongly recommends you "follow the unexpected findings, because that's where so many truly transformative discoveries arise."

As he told me in a previous conversation, "Many of the recent breakthroughs I'm most excited about weren't initially foreseeable. But some scientist who was properly resourced, and given the time and trust to follow their curiosity and instincts, discovered something that turned out to be incredibly useful."

Forbes