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For the Love of Science: The Long and Rewarding PhD Journey

For Milly Choy, the culmination of having defended her thesis – the final examination that marks the end of her PhD journey – is much like the finale of a symphony, the satisfying sense of fulfilment that follows a crescendo of sound and activity. As for her peer, Nicodemus Oey, the thesis defence has been a humbling opportunity to present the work one has toiled on for four long years. The process of being able to offer something new to advance the field, he said, “is a necessary step to become a true discoverer of science.”

For every PhD student, four to five years of work culminates in a public seminar in which the candidate provides evidence for his/her claim(s) in front of examiners, experts in their fields, and the public at large, who may question or refute these claims. This defence is the milestone that caps a myriad of other criteria: the completion of 25 credits of full-time coursework, a Qualifying Examination, the pursuit of getting these discoveries published in a peer-reviewed journal and the writing of a 200 to 400 page PhD dissertation. For each PhD candidate, it closes a chapter of their journey in medical science whilst opening another as they embark on a new path.

Unique PhD Experience

Milly, who graduated from Nanyang Technological University in 2010 with a BSc Hons in Biological Sciences, is part of the pioneer batch of the Duke-NUS PhD programme. Her work on the interaction of dengue virus with its hosts, the Aedes aegypti mosquito and humans, seeks to identify a potential antiviral drug. “My thesis investigates the role of a pathway that is critical for protein degradation in cells in the dengue virus life cycle,” she explained. “We show that inhibition of this pathway, the ubiquitin proteasome pathway, is able to reduce dengue virus production in human cell lines and mosquitoes, as well as ameliorate signs of dengue in a wild type mouse model.”

Working with luminaries in the field, Professor Duane J Gubler and Associate Professor Ooi Eng Eong, she has benefitted greatly from their expertise. “Dr. Gubler has spent more than 50 years working on vector-borne diseases around the world, and his research has contributed greatly to our understanding of dengue,” she pointed out. “His dedication to his work is something I strive to emulate.” She also expressed gratitude for the mentorship she has received from all her professors. “The collective nature of the Emerging Infectious Diseases programme was a huge plus point for me, as all the professors were ever so willing to share their experiences and knowledge with PhD students,” she said.

Looking back on her PhD experience, Milly, who will go on to work as a research fellow in Genome Institute of Singapore, A*STAR, reflected how preparation and partnership with others has aided her in her work. “To me, the work starts from the first day you step into the lab,” she said. “If you planned all your experiments well, and engage in frequent discussions with professors and fellow colleagues about your work, you should be able to write a good thesis. Having said that, a thorough understanding of what you are doing is essential for a successful defence!”

A Dream Made Reality

The eight-year long road to becoming an MD-PhD has been the fruition of a childhood ambition for Nicodemus Oey. Born in Padang, Indonesia, the young Nicodemus, who won a National Biology Scholarship to study in the University of Toronto, never had any doubt that he wanted to become a clinician scientist. This led him to join Duke-NUS. “Its vision of being an academic medical centre to train future clinician-scientists was a huge factor of my decision to apply,” he said.

His thesis on the molecular mechanisms involved in memory formation, is one he has spent four and a half years on, learning about a particular protein called PHF8 found in the nervous system. He ended up discovering a fundamental epigenetic ‘switch’ that turns genes on and off in response to neural activity. “If we are what we think, then my hope is that my work has contributed to understanding the very process by which we are able to do so,” he explained. “This has implications in the discovery of novel treatments for extremely debilitating diseases such as Alzheimer’s and Parkinson’s, where patients’ memories fail them.”

It was a long journey towards the discovery, he shared. “In the beginning I was too busy trying to learn basic techniques, doing laboratory bench work, and just training to be a scientist. Over time as I grew more confident with my skills and ability to contribute results and insights, I started developing collaborations with prominent scientists and clinicians with a range of expertise.” His mentors include Drs. Patrick Tan, Zhou Lei, Roger Beuerman, Helen Zhou, Ng Yee Sien and Sarah Lisanby. “They all have enriched my training immensely and have given meaning to the research I contribute to.”

In particular, he credits his achievements to his mentor, Associate Professor Antonius Van Dongen, an expert in molecular, cellular, and systems neurobiology. Nicodemus is grateful for the support and encouragement he received under Dr. Van Dongen’s tutelage. “I can’t remember how many times I have been stumped, at a total loss for how to make sense of the results that I see in front of me, but I do remember the numerous instances he has helped me through those tough times; every single time. I cannot thank Dr. Van Dongen and his wife, Margon, enough for their unwavering support through these years, without which I highly doubt I could have even survived my first year as a budding scientist.”

Describing his four years of medical school and four years of PhD work as a “long and arduous road full of dangers lurking in every corner,” Nicodemus nevertheless said that it was all worth the slog. “Not one single drug has ever been approved without the years of hard work and dedication of researchers working well late into the night in laboratories. Not one single innovation has ever been made without the blood, sweat, and tears of the clinician or basic scientists putting their hearts and souls into what they do.”

With the rise in dementia due to the rapidly ageing population, it is his hope of stopping what is a currently incurable, though highly debilitating disease, that drives him. “It is what makes me get up every morning and come back to the lab every day of the week.” Already, his work in uncovering the mechanism that may alter the course of memory-impairing diseases has resulted in several direct applications. He has worked with Dr. Ng Yee Sien from Singapore General Hospital in a successful pilot clinical trial of a new combinational therapy for stroke rehabilitation. Dr. Sarah Lisanby, head of Duke University Hospital’s Department of Psychiatry and Behavioral Sciences, has also expressed interest in developing new medications for treating memory impairment in depressed patients based on his work.

With his scientific journey far from over, Nicodemus reflects, “I remember being a first-year medical student in a young, new medical school, being asked to write a short sentence about my aspirations as a future doctor. I said: ‘I aspire to contribute to making discoveries that benefit patient care, with Duke-NUS as the spearhead of advancement in basic and translational medical scientific progress.’ I feel that I have been true to this goal, and hope to continue to keep this aspiration in mind as I go forward.”

Photo: Kenneth Goh 

This story was first published in Vital Science (April 2015). Nicodemus is the first from the school to graduate with an MD/PhD degree this Academic Year.