Asia’s Scientific Trailblazers: Patrick Casey

By Rebecca Tan

When Singapore launched the Biomedical Sciences initiative in 2000, the need for clinician scientists who could bridge the gap between bench and bedside was immediately felt. In response, the National University of Singapore (NUS) sought out an international partner to launch Singapore's second medical school that would take in graduates and focus on training them to conduct urgently needed clinical research.

Prof Patrick Casey

“In addition to practicing medicine, we teach students how to do research and train them in leadership because we expect them to be out there improving the practice of medicine in many different ways – through research, leadership, clinical trials, etc.”

- Prof Patrick Casey

Duke University, a research powerhouse, fits the bill. Thus the Duke-NUS Graduate Medical School Singapore (Duke-NUS) was born. Although the mission of Duke-NUS was clear, it was not immediately obvious how the challenges of developing a brand new university should be tackled, and who would be the most suitable person for the job.

Patrick Casey, a cancer biology expert and the James B. Duke Professor of Pharmacology and Cancer Biology at Duke, rose to the occasion. Involved right from the beginning, the Senior Vice Dean of Research at Duke-NUS saw the potential in the fledgling medical school, and moved both his family and his laboratory over to Singapore in 2005.

Ten years on, Duke-NUS has established itself as a leading research institution, with its researchers publishing in brand-name journals and winning fellowships, grants and awards. Recently, Duke-NUS researchers were also involved in developing ETC-159, the first made-in-Singapore cancer drug. In this interview for Asia's Scientific Trailblazers, Professor Casey shares with us his ongoing research, what it takes to build a medical school and where medical education in Singapore is headed.

As a G protein researcher, what has been your most exciting research finding to date?

Personally, it was discovering that Ras proteins and other G proteins are modified by lipids in the process ‘prenylation’, which is required for protein function. One of our major contributions to the field was to identify the enzymes that attach these lipids, and embarking on programmes to find inhibitors of these enzymes for development as novel therapeutic agents.

What are some of the clinical applications of your research?

The first enzyme that we identified, farnesyltransferase (FTase), was a major development in the 1990s, and thousands of patients were treated with developed FTase inhibitors. Unfortunately, the response rates were very low, partly because there’s another enzyme, geranylgeranyltransferase (GGTase-1), that can step in and restore function when FTase is inhibited. So we are developing GGTase-1 inhibitors, thinking that with the two together, we might get better responses.

Currently, most of our attention is on another enzyme, isoprenylcysteine carboxyl methyltransferase (ICMT), which methylates all of the different prenylated proteins. My wife, Mei Wang, is a clinician scientist here and we work together on this programme, focusing our attention on the methylation step and to develop agents to inhibit it.

What was your biggest challenge in building up the medical school?

The biggest challenge was trying to ensure that we were meeting the needs and expectations of the multiple stakeholders – Ministry of Health, Ministry of Education, A*STAR, NUS, Duke University and SingHealth. Every one of these entities were excited about the possibilities and what this school could do, but they all had different ideas of what it should be. So it was really about balancing all of these expectations and staying on course, but the great commitment by all parties for the school to be successful really helped us to get through that period.

In your opinion, what is the most important determinant of success in a medical school?

I’d say first and foremost, you have to train good doctors. In addition to practicing medicine, we teach students how to do research and train them in leadership because we expect them to be out there improving the practice of medicine in many different ways – through research, leadership, clinical trials, etc. But foremost, they have to be good doctors!

You’ve been in Singapore for about a decade, where do you see the Duke-NUS Graduate Medical School heading in the next decade?

From the school’s standpoint, there is a greater alignment and integration with our major health system partner, SingHealth, such that it is seamless between Duke-NUS and SingHealth. There’s going to be a complete continuum, research-wise and clinically, between the medical school and health system so that it looks like the academic medical centre that Duke University is in the US.

What impact do you foresee Duke-NUS graduates making?

First and foremost, of course, would be those who have become clinician scientists. They train in medicine and in research, and at the end of their ten years, they would be faculty in the medical school or clinician scientists in the health system.

And then there’s another cadre that is primarily delivering medical care, but still actively engaged in research and leadership aspects. Their research is particularly on clinical trials and clinical research development.

And then I’m quite sure we’ll have a small cadre that trains in medicine, and then transitions to the private sector. They will become the medical directors of biotech companies and assume leadership roles in aspects of medicine and medical research, be it in the public or private sectors.

If you look 20 years ahead from now, you’ll see several of our graduates occupying key roles in the ministries or in the public service organisations.

When Duke-NUS opened, it changed the landscape of medical education in Singapore. How do you see that landscape changing now that there are three medical schools?

There is a great need for medical professionals in Singapore. Even with three medical schools, you’re just barely keeping up with the country’s needs. There is a bit of dynamic tension and competitiveness between the schools, but I’ve been impressed with how much collaboration there is across institutions in Singapore and I expect that to continue. By having more than one school, people feel that they continually need to refresh and energise their approaches, making sure that they don’t stagnate in their careers.

Are there any areas in Singapore that you feel that are in need of development or strengthening?

I think most areas are developed very well here. We’re a little concerned that there’s going to be too much emphasis on applied and directly commercialisable research. That is OK, as long as we make sure that we don’t lose sight of the fact that it’s the firm foundation in the basic science that made it all possible. If you don’t maintain that firm foundation, the layers you built on it – commercially-oriented research – aren’t sustainable. We need to ensure that there’s adequate funding for translationally-oriented scientists too.

First published in Asian Scientist Magazine: www.asianscientist.com