Features

It takes years of study to create a chance discovery, writes Ashley Hay.

An ecologist stops beside a puddle he’s driven past scores of times and samples its water. An historian orders up drawings from the French National Archive and is brought the wrong thing. A chemist forgets to wash his hands after a day working with coal tar and tastes an unusual sweetness as he eats dinner.

The discovery of a new species of shrimp; the only extant drawings of France’s first theatre; penicillin and saccharin; the fluorescence of jellyfish: these are all moments of serendipity, confluences of knowledge, experiment and happy accident that touch the word as Horace Walpole coined it in 1754. Serendipity, he stated, was “accidental sagacity”.

Everyone loves an extraordinary find, an unlookedfor twist and often scientists find themselves on new paths because of serendipitous moments.

“Researchers are often encouraged to offer a breakthrough like this,” says Dr Richard Corkish, head of UNSW’s School of Photovoltaic and Renewable Energy Engineering (SPREE), “both to attract funding, and to encourage high expectations.” Some become so well known as to be almost clichéd: the penicillin in Alexander Fleming’s petri dish; the sweet saccharin Constantin Fahlberg tasted on his unwashed hands. Yet two of this year’s peak Australian scientific awards – the Science Minister’s Prize for Life Scientist and the Prime Minister’s Prize for Science – were awarded to researchers who found something they weren’t looking for: a new kind of chlorophyll, and the means of controlling the movement of molecules in polymers.

“I always say to grad students, when you come across something that doesn’t make sense, keep an open mind,” says Professor Ary Hoffmann, a geneticist at the University of Melbourne. “The unexpected pushes things through, and serendipity in science is a wonderful thing. We try to pretend sometimes that many of our major discoveries are not associated with serendipity, but of course they often are.”

In Hoffman’s case, one such moment came just as he thought he’d found a major flaw in a new control strategy for dengue. The idea was to shorten the life of the mosquitoes that transmit dengue by infecting them with Wolbachia, a naturally occurring bacteria. One of the attractions of the approach was that Wolbachia would be inherited by any offspring of those infected mosquitoes – meaning the Wolbachia infection would perpetuate itself through generations, rather than requiring the ongoing release of infected mosquitoes. Then Hoffmann’s team discovered that while the mosquitoes could “spread pretty well in the wet season, in the dry season, they came to a grinding halt”. If releases had to be ongoing, one of the strategy’s major advantages was undermined.

Around the same time, fortuitously and incidentally, the project’s team discovered Wolbachia effectively vaccinated mosquitoes against transmitting dengue – irrespective of how long the mosquito lived – and they found a strain of the bacteria that allowed the mosquitoes to breed on through the dry.

“That was my serendipity moment,” says Scott O’Neill, leader of the Eliminate Dengue project and Dean of Science at Monash University. “Of course, we write up a paper, we make it tell a story about science. This was the idea; we went and tested it; and we did it. But usually, you were doing something completely different and this fell out … nearly all science is like that.”

Professor Philip Hogg, Director of the Lowy Cancer Research Centre at UNSW, agrees: “The reality is it won’t have unfolded as a story; it will be an odd result that you saw here, which you then tried to understand, and you end up finding something new. That’s serendipity. But when you read the paper you think, these guys are pretty smart – they knew it was going to be like this.”

Unravelling some of these narratives is part of the impetus behind the Journal of Serendipitous and Unexpected Results ( JSUR), recently initiated by an editorial team including Assistant Professor Ryan Lilien from the Department of Computer Science at the University of Toronto and Assistant Professor Ramgopal Mettu from the Department of Electric and Computer Engineering at the University of Massachusetts.

“It’s important to have the perspective of how research takes twists and turns,” says Mettu. “You don’t often get that in plenary talks by famous people: what you get there is a very nice and beautiful story about what they did. It would be great for grad students to see how people do things, in a principled way, and how they deal with the situation when an experiment doesn’t work, or when something they tried doesn’t go the way they expected.”

“That’s also true in articles,” adds Lilien. “But we take a quote from [American physicist] Richard Feynman about the pitfalls and blind alleys encountered during a particular line of inquiry – those are all really important.”

There are four kinds of communications in JSUR’s remit: those dealing with serendipity or “compelling curiosities”; those that contradict prevailing wisdom; follow-up papers on earlier unexpected results; and perspectives or reviews.

“Of course,” says Lilien, “we don’t want to put the message out that most of science is random happenstance; you play round in the lab and something works. Mostly that’s not the case – and you can’t fund that model of science.”

“But then the standard model of science isn’t that fundable either,” adds Mettu, laughing. “Mostly what you’d be saying is, this probably isn’t going to work, but we’re going to try it, and we might learn something that isn’t exactly what we’re looking for, but I promise we’ll learn something. If grant proposals told the exact truth about how science went, they’d look more like that. We need to say that there’s a lot of hard work involved in discovery and exploration, and people try a lot of other things before they come across something successful – not that that successful thing is just lucky.”

The journal’s website is bannered by a quote from Isaac Asimov: “The most exciting phrase to hear in science, the one that heralds new discoveries, is not ‘Eureka!’, but ‘That’s funny …’.”

For John Golder, a visiting senior research fellow in UNSW’s School of English, Media and Performing Arts, the language of discovery was not so polite. Realising the material the French Archives had mistakenly delivered was sketches of France’s first theatre, the Hotel de Bourgogne – a place thought to have left no extant drawings, and a place he’d been studying for more than three decades – “the hairs on the back of my neck bristled”, he says, “ just as they do now as I recall the moment”. Realising subsequently, on the Metro, that one exquisitely coloured piece he’d dismissed was from the same place, “I was shaking with excitement”, he recalls. He thinks he probably swore aloud, given that everyone else in the carriage was staring. “These things just don’t happen to you very often.”

The world of research might be best described by Donald Rumsfeld: it’s a world of “known unknowns” – the questions you believe you can answer by the methods you have to hand – and “unknown unknowns” – the questions you don’t know how to answer, or the questions you haven’t yet thought to ask. If that sounds incomprehensible to those of us who never enter it, it’s only slightly less so to many of its newest arrivals, the students moving from structured undergraduate courses to the open landscape of postgraduate research.

“When you do a coursework program, you know the length of the courses, you undertake an exam on a certain date, and then you go to the pub,” says Professor Laura Poole-Warren, UNSW’s Dean of Graduate Research. “Research isn’t like that.”

“Because it’s the unknown,” says Hogg, “it’s very hard to put timelines around it. Being selfdriven really freaks some people out because you just don’t have the comfort of knowing what you have to do when you get into work. And to do something worthwhile can take a long time, and can be a struggle. The notion that you might need to work for three years before you see the results – that’s something some people have difficulty with.” He has seen more than one graduate student baulk at the timelines, and walk away.

The disconnect between funding timelines and the realities of research is well known: in a recent opinion piece for The Australian Financial Review, UNSW Vice-Chancellor Professor Fred Hilmer and Deputy-Vice Chancellor (Research) Professor Les Field called for the time frames for the research funding system to be reset. “With success rates for grant applications sitting at around 20 per cent, a 12-month application process and a three-year funding cycle, it’s no exaggeration to say that two out of four research years can be lost to jumping funding hurdles,” they wrote.

How then to keep the unexpected, the new opportunities – or what Hogg calls “the crazy ideas” – moving forward? Most do as Hogg did when he began investigating the way protein function is controlled and the influence on this of disulphide bonds. “When I first started telling people about this, more often than not they did think I was crazy,” he laughs. “I used to quarantine some funds [from other grants] and, with the best people working with me at the time, we’d explore this idea. That’s how we do it. There’s a saying that I think is quite apt: as a researcher you do what you need to do to be able to do what you want to do.” With the ongoing support of two or three senior academics at the time, the idea got off the ground.

Those two or three colleagues exemplify elements most people identify in the making of a good researcher: the importance of mentors, and the importance of input on your ideas from beyond your own world.

“Finding your independence as a researcher, that’s key,” says Poole- Warren, “but it’s also key to have good, strong mentors. At UNSW we have early career researcher (ECR) programs that pair ECRs with a mentor who’s outside their normal sphere of operation. If that works, it works well.”

“It’s always important to keep your ears open, to be aware of what other people are doing,” says Corkish. “In a perfect world, in a university, you’d have the resources and the leisure to be listening to talks in physics at lunchtime, and them coming to us at SPREE, and we would pop down and see material sciences every so often. But that’s a more gentle world than the one we have, so those things don’t happen enough.”

What is important, says Associate Professor Darren Curnoe, head of UNSW’s Human Evolutionary Biology Lab, is knowing how to maximise your chances of serendipity. At one international conference, he was invited to China to meet some fellow academics, “to see if it might be possible to do some work together”. He made the trip, met the researchers and saw some of their material. To find yourself looking at something you suspect will tell you a great story, he says, “that’s an amazing thing”. He pauses. “Five years later, we find ourselves submitting papers to high-profile journals – the serendipity of meeting someone at a conference, the serendipity of the particular fossils you’re allowed to work on, of ascertaining whether or not they’re internationally significant …” You might not be able to predict or depend on the appearance of such inspirations, such situations, but Curnoe advocates increasing their chances of occurring – by putting yourself in the way of as many people as possible, and being willing to head down the paths that open up behind them.

Professor Brian Timms from UNSW’s Australian Rivers and Wetlands Centre, calculates he’s visited Far North Queensland’s Paroo River almost 100 times in the past 20 years, sampling aquatic life from the temporary pools that spring up after rain. For most of that time, he’d driven past one pool of water on a flood plain figuring that most pools on flood plains host fish that would have eaten the shrimp he was interested in. “One day, for some reason, I stopped and sampled it,” he says, “and lo and behold, there were shrimp in it – it was filled with rainwater, not flood water.”

That shrimp turned out to be a new species: “Branchinella clandestina I called it,” says Timms, “because there it was, living this clandestine existence, right under my very nose, just waiting for me to discover it. That’s what I call serendipity.”

Often, however, serendipity springs from a collision between older research and newer questions, the connection of dots from disparate places across long periods of time – O’Neill’s Wolbachia work built on a PhD thesis completed in 1971 that sat, unutilised, for another 20 years. And Osamu Shimomura’s serendipitous extraction of luminous material from a jellyfish (see box, opposite) was all the more resonant for its profound impact on other research fields. More than 30 years later, researchers realised its potential as a genetic marker – it could be attached to anything inserted into a gene, and then made to fluoresce to indicate the insertion was successful. Green fluorescent protein is now used in cell and molecular biology, cryobiology, microscopy and transgenics.

In a similar vein, the surprises in photovoltaics spring more commonly from realising discoveries in one area of research are highly useful to others, says Corkish. “Technology from our third-generation group, based on quantum physics, is now applied on thin-film or secondgeneration solar cells. And an ink-jet printing method developed for use on our thin-film cells is used on our original solar cells. These crossovers are surprising sometimes, but maybe that’s not serendipity; maybe it’s something that happens if you’re looking in the right places.”

In the vastly disparate places that traffic in original thought, settling on one definition of serendipity is as unlikely as settling on one description of research – research is everything from test tubes and soil plots, to muddy puddles, high-tech equipment, lines of genetic code and scribbled notes on scrappy paper. “Think of researchers in the humanities,” says Poole-Warren, “they are the virtual bench.”

“[Research is] a fantastic job,” says Hogg. “I love it, and it’s a privilege to do it. Most of us recognise we’re lucky to be able to do this job. Yes, most of us survive on three-year, five-year grants – there’s no security – but that’s the trade-off for working in an area that’s a big unknown. You have to be creative and innovative, good enough to discover new things or gain new insights. If you can do that consistently, you can stay in the business.”