When Martin Chalfie began his first research project as an undergraduate at Harvard it left him so disheartened that he abandoned his scientific career. Luckily, chance events brought him back into the lab for a summer job, and began his journey towards the 2008 Nobel Prize in Chemistry.

Almost 50 years later, Chalfie visited Canada as part of the Nobel Prize Inspiration Initiative and shared his experiences with young scientists. It turns out that many of the reasons he had initially decided not to continue with research were based on misconceptions.

According to Chalfie his first experience with science ended badly because he was too afraid to ask for help. The stories he’d heard about great scientists were of lone geniuses, who made their breakthroughs without the help of others. His conclusion was that, if he was cut out to be a scientist, he should be able to do his experiments entirely by himself.

“I felt that I had to do everything on my own, because asking for help was a sign that I was not intelligent enough,” Chalfie said. “I now see how destructive this attitude was, but then I assumed that this was what I had to do.”

Instead of asking questions and seeking guidance, he persevered on his own even when his experiments were repeatedly failing. Inevitably, his first research project didn’t lead to any results. “I tried doing experiments all summer, but nothing worked,” he said. “I did not enjoy failing and decided that a career in science was not for me.”

He instead went on to teach in a high school where he enjoyed interacting with students. It also meant that his summers were free and, when a fellow teacher introduced him to her friend at Yale Medical School, he found himself back in the lab. This summer job proved to be a revelatory experience. He set up his experiments with help from two other scientists, and this time they worked. Buoyed by his success, Chalfie gave up teaching and took up a full-time position in the lab.

However, this was by no means the end of his failed experiments. He has continued to experience disappointment throughout his time in the lab, though his attitude to failure has completely reversed. For him, anyone who strives for major discoveries will experience a lot of failures. And these failures aren’t just inevitable, they are important. They can take you in new directions, and reveal insights you weren’t expecting.

To illustrate this point, Chalfie tells the story of his co-laureate Osamu Shimomura. Shimomura was studying how organisms emit light, which they do using a variety of different mechanisms. However, he had great trouble in finding the mechanism used by a particular jellyfish species to produce a beautiful ring of green light. He tried repeatedly to extract the substance causing this green glow, but failed again and again. His extract simply didn’t light up.

He spent his days and nights thinking about what he was missing, sometimes going out in a rowing boat so he could think without being disturbed. In the end the answer appeared by accident. One night when he poured the extract away, the sink lit up with a bright blue flash. Seawater from an aquarium overflow was running into the sink – he realised that the seawater had caused the luminescence. Because the composition of seawater is well known, he easily discovered that the luminescence was activated by calcium ions. He was able to purify the protein which is responsible for the light, and it became the first calcium indicator.

However, one mystery still remained. The jellyfish produced green light, yet Shimomura’s sink had glowed blue. He continued with his experiments and found a second protein which converts the blue light into green. We now call this green fluorescent protein, and it is one of the most important tools in biological research. Researchers use it to watch processes that were previously invisible, such as the development of nerve cells or the ways which cancer cells spread. It is this protein, GFP, which gained Chalfie and Shimomura the Nobel Prize, along with co-laureate, Roger Tsien.

Shimomura’s story is a complete contradiction of Chalfie’s early assumptions about how science works. He had believed that scientists were always purposeful in their experiments and knew where they were going. The reality, he discovered, is that many discoveries are accidental, and often come before the hypotheses. The important step comes next – recognising the significance of those discoveries and deciding what to do with them.

These videos were filmed at a Nobel Prize Inspiration Initiative event in Canada, delivered in partnership with AstraZeneca.

First published in November 2019