Lucky scientists rule?

When sharing scientific discoveries (especially groundbreaking ones) with colleagues in fika-time conversations, I quite often end up in deep philosophical discussions about conducting research, and of course the publication system which everyone sort of complains a little bit about. But one other interesting topic that frequently pops up is serendipity in scientific progression.

Over the years, I have come across views residing at both ends of the spectrum. Slightly pessimistic colleagues would say ‘luck’ definitely plays an enormous role, and that such eureka moments will become less and less likely nowadays as scientists cannot afford distractions under the current grant-hunting and publishing climate. Others, who are more positive, would insist that only the most clever and meticulous are able to seize the opportunity as slim as thin air brushing by.

I honestly do not have a strong opinion as I see a point in either argument. What I definitely agree, though, is it always boils down to the scientist’s attitude towards any ‘unexpected finding’, which can sometimes be a synonym for ‘negative finding’, or even ‘opposite finding’ that might, at most, prompt another round of the same experiment before a reluctant focus switch due to pragmatic reasons. Nevertheless, I cannot help but imagine how I would have responded if such ‘miraculous moments’ ever occur to me.

Serendipity in science – simply luck?

Almost everyone knows how Alexander Fleming accidentally discovered penicillin. He left an uncovered Petri dish containing potentially deadly bacteria by the window for two weeks. That definitely qualifies as poor laboratory practice. I for sure would frown with every facial muscle if one of my students did that, and would ask him/her to clean up the mess immediately without even looking at the dish. And… there goes the Nobel prize.

Would you throw these away immediately or examine the mould carefully as did Fleming?
(from pixabay.com)

Decades earlier, the critical role of calcium ion (Ca2+) in muscle contraction was discovered through equally careless practice in the laboratory. In this less known story, Sydney Ringer’s lab technician inadvertently used tap water to incubate a rat heart to study its contraction, as opposed to using distilled water as instructed by Ringer. The rat heart contracted beautifully and continuously. When Ringer tried to repeat the results with distilled water, he saw a much weaker response that did not last at all. That marked the birth of Ca2+ signalling research field.

In both stories, serendipity was technically a direct result of unacceptably sloppy practice. What really should not be neglected, however, is that penicillin was only able to save millions of lives thanks to the robust work (discussed below) by Ernst Chain and Howard Florey, who shared the Nobel Prize with Fleming.
And in the latter story, Ringer did not simply disregard whatever the careless technician had done. Instead, he not only managed to comprehend the importance of Ca2+, but also came up with the famous Ringer’s solution. To keep the rat heart beating, this solution has to contain roughly 1% potassium chloride, 0.75% sodium chloride, 0.5% sodium bicarbonate and, you guessed it, 0.1% calcium chloride. This is a magical recipe that is hardly optimised further since the 1880s, not to mention Ringer’s team did not have a pH metre, digital balance or modern pipettes to assist in this alchemist feat. Simply relying on luck would clearly have brought Ringer nowhere.

Goal-oriented serendipity

More often, though, serendipity in science does not simply fall out of the sky, particularly for findings that are progressive rather than game-changing.

For Barry Marshall, the 2005 Nobel laureate who was brave enough to swallow a culture of H. pylori, courage was the catalyst for deciphering the puzzling link between gastric inflammation and bacteria in the stomach. But it certainly took a little bit more luck than analysis for him and Robin Warren, who shared the Nobel prize, to arrive at that point1. After failing repeatedly to culture the bacteria, they got distracted by a busy schedule and, like Fleming, totally forgot about the culture dish over a long weekend. This finally allowed sufficient time for H. pylori to grow for the first time in a laboratory.

Yet another example of problematic behaviour that ended up winning a lottery, some say. But given their intense focus on H. pylori at the time, realising the trick to grow the bacteria is just a matter of time. And as I was contemplating serendipity in science, I found a whole list of ‘accidental’ discoveries. Looking through it, one will notice that most if not all of these discoveries were nothing more than mistakes or distractions during the pursuit of a loosely relevant but predefined scientific goal. They would not have been popularised without sagacious insight followed by industrious efforts.

Serendipitous only in retrospect

When Fleming published his findings about penicillin in 1928, it did not shake the world. In fact, it did not even stir up any significant interest in the field. It was 11 years later when Florey at Oxford University accepted Chain’s proposal and assembled a specialised team to try and synthesise the silver bullet properly2. They spent two more years to validate its unbelievable anti-bacterial efficacy repeatedly in both animals and humans. Yet even with such power, penicillin still could not attract international attention without going through a series of dramatic events2, including a stealthy journey to the United States, as well as the subsequent laborious experimentations that finally allowed penicillin’s mass production. That was another two years later at the height of the war.

As summarised1 by Samantha Copeland, who has examined serendipity systematically, scientific revolutions are only perceived retrospectively. Indeed, all the a-ha! moments are typically part of everyday life for the discoverers, and every event following that moment is equivalently important to the discovery. In other words, anything you see today, no matter how ridiculous or boring, could some day be described as the eureka moment by your successors without even asking for your permission. Who knows, right?

Making astute observations and asking the right questions

I believe what scientific serendipities had in common is how their discoverers made astute observations of otherwise nonsense phenomena, and subsequently asked the right question. And to achieve these, the cause of the unexpected phenomenon has to be traceable, or a ‘controlled sloppiness‘, which was true for the vast majority of serendipitous discoveries.

We may not be lottery winners in a laboratory, but we can keep an open mind as well as be more vigilant about details, so that we are hopefully better prepared to tackle unexpected findings in a more constructive way.

I always remember that one practical class I attended as an undergraduate back in the UK. We were instructed to perform a molecular cloning exercise (which involved using Petri dishes containing agar gel like those Fleming had used!). Out of all important steps, our team of three was arguing for more than 15 minutes about whether the Petri dishes should be facing up or down in the incubator.
Prof Jonathan Hodgkin, supervisor of the practical class then, walked by and stood there to watch the comedy show with a silent smile. Finally, one of us said, ‘Alright then, place it all you like, but all dishes will have to face the same way!’ Before the two of us responded, the professor suddenly interrupted and said, ‘Yep, yep! That is good thinking. That will be enough.’ He then walked off.
That brief encounter was intriguing then, but enlightening much later on. It would not matter how we placed the dishes. We could even have tilted the dishes at an angle in the incubator for fun, as long as we had proper controls and were being consistent, or at least noted down what we did to each of them. Only by doing so, would we be able to explain why, in case we managed to grow a mushroom in the dish.

Remarks

Reflecting on myself, once as a student and now as a mentor, I have asked and received countless funny questions in the lab, both scientific and technical. Sometimes there is a definitive answer with sound scientific support, other times we just follow the standard practice and dismiss the curious enquiry. Are we ready for exciting stimuli disguised as distractions? Well, I guess I will have to work on it more anyway.

What are your thoughts?

p.s. Trained as a biologist, I am always curious about how bioinformaticians progress in their fields. Are there any similarly unintended a-ha! moments that led to breakthroughs in the coding world too?

References
1. Synthese 196,2385-2406 (2019)
2. Emerg Infect Dis 23(5):849-853 (2017)

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