Nobel Prizes: The Good, Bad, and the Completely Unexpected

It was the summer of 1961. The end of yet another day of unsuccessful experiments for Osamu Shimomura, a young researcher who was trying to understand the science of the Aequorea jellyfish’s green glow. With a sigh, he chucked his sample into the sink, intending to head home, when he noticed something unexpected. A bright flash of light inside the sink, and not just that, the glow was … blue?

If Shimomura had brushed off the unexplained glow as a freak accident, his life – and very possibly ours –may have looked a lot different today. Fortunately, he dug deeper and ended up not only solving the mystery of the jellyfish’s glow but also discovered a very important molecule called Green Fluorescent Protein (GFP).

More than two decades later, an unsuspecting roundworm scientist heard a mention of GFP at a seminar and he was instantly bewitched. By 1994, the scientist, Martin Chalfie, published the paper that would revolutionize the use of GFP as a tool to visualize vital bioprocesses that were once invisible – such as the spread of cancers, the development of Alzheimer’s disease, and the growth of pathogens. Nobody was surprised when Shimomura, Chalfie and Roger Tsien were jointly awarded the Nobel Prize in Chemistry in 2008.

Happy Accidents

“Serendipity has defined much of my career,” said Morten Meldal, during the Agora Talk on ‘The Joy of Unexpected Discovery’ that he delivered alongside Chalfie during the 74^th Lindau Nobel Laureate Meeting. He substantiated this statement with a slew of examples from his own life that made him go “Wow, something is going on!”. The most famous of these involved a routine chemical reaction between an alkyne and an acyl halide turning up an unexpected product, and eventually kickstarting a method of chemical synthesis called click chemistry. This would eventually win Meldal a Nobel Prize in Chemistry in 2022.

So how does a scientist make unexpected discoveries? Or as Chalfie put it (tongue-in-cheek) “increase serendipity”. He offered a number of tips, starting with the most obvious: do many experiments, do many controls and question everything. But he also invoked physicist Max Delbruck’s “principle of limited sloppiness”, warning that over-controlling experiments could come in the way of stumbling upon surprising observations. Perhaps there is such a thing as too much perfection?

With all this endorsement of serendipity in science, Meldal made sure to emphasise the role of a healthy academic environment. “We need the youth to go into chemistry and for that research should have no constraints. We need them to use serendipity as a research principle and there needs to be freedom to do that,” he asserted.

Life Before and After a Nobel

If serendipity does strike and good science comes out of it, there are enough examples to suggest that a Nobel Prize is a possibility. But there’s usually a wait involved. For Chalfie it was 14 years, and for Frances H. Arnold it was nearly 30! She conducted the first directed evolution of enzymes in 1993, a feat that would go on to transform the world of catalysts, pharmaceuticals, and renewable fuels. A Nobel for this followed in 2018. As glamorous as the recognition can seem, Arnold emphasised that the work that went into it was much less so. “I remember I was so tired. I had three little kids, I was an assistant professor… Winning was definitely a high point, but the work was definitely not.”

Arnold and Chalfie were part of a panel discussion on “Consequences of the Nobel Prize” along with John M.  Jumper on the opening day of the meeting. The panel was moderated by science historian Nils Hansson, who intriguingly conducted the session in the format of a game show. While the three laureates echoed in their view that prizes largely have a positive impact on scientists and science, Hansson prompted them to open up about the challenges.

It can get disconcerting, conceded Arnold. “We don’t suddenly become smarter or more well-informed on December 10, but the consequence of getting the prize is that people think you know everything.” Jumper, who won a 2024 Nobel Prize in Chemistry, admitted to struggling with balancing his roles as a scientist and an ambassador of science. “I feel this tension between science as the thing you do and science as the enablement of others to do science,” he remarked.

A Noble Goal?

The panellists spent a few fascinating minutes in debate about whether or not it was a good idea to work towards a Nobel Prize. Jumper suggested that there was value in doing research that “could” win a Nobel because for him these kinds of work serve as examples of science changing the world.” Chalfie, however, questioned this. “A surprising number of Nobel Prizes started with serendipitous research … so that means we don’t actually know how to get one” he pointed out, foreshadowing the essence of his upcoming Agora Talk.

Interestingly, Arnold was opposed to the idea of scientists working towards the goal of winning a Nobel. “I think it’s a terrible goal,” she retorted strongly. “It takes away the fun of doing science and it’s very greedy.” Jumper accepted his co-panellists’ arguments graciously, agreeing that a Nobel Prize should never be the criteria for success. “But what I love about science is the power it gives us over things like disease. There is someone who may know nothing about biology who will go back home from the hospital [thanks to science]. For me, that is the motivation, and the Nobel Prize is an acknowledgement of this fact,” he concluded.