Necessity and research are the mothers of invention

Scientist Joyce Rubothen looks at the trials and triumphs that go with a career in research

‘Crystal Dragon’ by Keith J Flanagan and Marc Kielmann, an entry for the Science Research Image Competition 2017.
‘Crystal Dragon’ by Keith J Flanagan and Marc Kielmann, an entry for the Science Research Image Competition 2017.

Research opportunities for Irish Science graduates have never been better. Ireland is now home to some of the world’s largest biotech and pharma companies. After nearly 10 years studying to achieve a doctorate in science however, many graduates lack the inclination to make a switch from academia to corporate. These academic researchers fill our university laboratories and lecture halls.

Academic research is fundamental research; knowledge-driven and motivated by the basic human desire to learn something new. The knowledge acquired is always valuable and can subsequently be applied to improve lives. During Science Week 2017, it is timely to outline how this kind of research happens and relates to the wider world.

Dr Conor Breen, a researcher at Maynooth University notes "even when the commercial potential of a project isn't obvious, by solving problems that arise through research, it can lead to discoveries that have commercial applications".

Dr Breen cites the work carried out by Prof Isidor Isaac in his molecular beam laboratory at Columbia University during the 1930s. His fundamental research lead to the development of the technology that is now used for magnetic resonance imaging or MRI scanning.

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Researchers working in universities face different challenges to their pharma counter-parts. Time scales and resources for individual projects are completely different to those observed in the laboratories of private drug companies.

Life in academia is enriching, it’s not so much a career as a vocation. “Like getting paid to do your hobby,” a researcher I worked with once admitted.

There is the excitement of exploring and pitching your own ideas to funding agencies. Going to work, eager to know if your overnight incubation was a success. Maybe this time you’d cracked it.

Or maybe not this time. There are frustrations and difficulties too. It’s not for the fainthearted. Chronic experimental failures and disappointments are an essential part of the work. A grinding repetitiveness prevails when an experiment must be done over and over again in order to achieve perfect accuracy.

Success takes time but is so much the sweeter when it comes.

Academic scientists usually follow their own individual research path. Every project has a history of its own. The work quickly becomes very personal; your project is your baby.

Letting go of an apparently unsuccessful research project can be impossible. Researchers regularly work unpaid between grants. They believe in the project even when none of the funding bodies do.

Many scientific breakthroughs owe a debt to a tenacious researcher who kept working against odds and advice.

Mixed-bag

University research groups are a mixed-bag, made up of scientists of varying experience-levels, all working together. The head of a group is the Principal Investigator; his or her name will be on the door.

The managerial structure in university laboratories is familial rather than corporate. Most researchers have teaching obligations. Teaching introduces a special dynamic into academic laboratories. There is a continuous exchange between established researchers and the new generation of young undergraduates.

For several months of each year undergraduate students in the final year of their degree join the laboratory. These are the babies of the science family. It’s a busy time for research groups as they squeeze in extra, inexperienced students into their laboratory space.

Next up on the generational ladder are the PhD students. The long road to a PhD in science is as much a psychological challenge as an academic one. No research is ever finished and the PhD student’s most arduous task can be finding a good place to stop researching and write the thesis.

Those who stay on the academic path after a PhD become post-doctoral researchers. Post-doctoral work is contract-based with contracts usually ranging from two to five years. Publishing research in peer-reviewed journals is the only way to secure another contract, maybe even a permanent job. Maybe.

There is immense pressure on and competition among senior post-doctoral researchers who scramble to obtain one of the few permanent posts available in university laboratories.

Irish researcher Dr Conor Breen began his research career in the laboratory of Prof Paul Voorheis in Trinity College. He completed his undergraduate research project and subsequent PhD with Prof Voorheis.

Fifteen years later they continue to collaborate with success on the same project. Last year their ground-breaking research was published in the Nature Publication Scientific Reports.

Dr Breen recalls how their research idea came about; he was trying, unsuccessfully to measure the binding of a particular protein to cells. The traditional method of doing so involved using radioactivity to measure binding. The protein in question was available for purchase, already radioactively labelled. There was however an obstacle.

Without the facilities, the licence or the funding to use radioactivity Dr Breen had hit a dead-end. As PhD students do, he sought the advice of his supervisor. Prof Voorheis did not hold back with his thought-provoking guidance; “find another way, use fluorescence instead of radioactivity”.

Fluorescence involves the use of light-emitting probes, when they bind they emit light not radioactivity. The idea of replacing radioactive probes with fluorescent probes was ground-breaking.

Since the 1970's researchers had been using radioactive probes to quantify protein binding to cells. The technique was developed by Robert Lefkowitz who subsequently won a Nobel Prize for his work in the area.

Dr Breen remembers wondering why, if developing fluorescence as an alternative to the traditional radioactive method was such a good idea no one had done so by now. He hesitated over how much time and energy he could afford to risk on this unheard-of notion.

Fifteen years was just the right amount of time. Thanks to the success of his research a new technique for measuring protein binding to cells now exists. Because it does not involve the use of radioactivity, his method is cheaper and safer than its predecessor.

It transpires that Dr Breen's novel method has potential for measuring uptake and specificity of certain drugs into cells. He is currently working with Enterprise Ireland to develop this technique for the purposes of drug-target studies.

If Dr Breen’s story tells us nothing else, it confirms that academic research can and does deliver. That, and necessity truly is the mother of invention.

Joyce Rubotham is a doctor of molecular biology who has worked in academic science for over 10 years in the Department of Biochemistry and Immunology, Trinity College and University of Brussels in Belgium