Thought Leader Feature: Prof Patrick Tan

Powering the Next Generation of Biomedical Research

Singapore’s National Precision Medicine Strategy will not only improve healthcare within the country but enable the next wave of healthcare innovations, says Professor Patrick Tan, Executive Director of PRECISE.

In October 1990, researchers across the globe embarked on The Human Genome Project—allowing us to read the complete genetic blueprint of a human being and changing our understanding of who we are forever. But that was only the beginning, the next step is applying that information to treating diseases and improving lives.

Thirty years on, there remain gaps in our understanding of the human genome. To address the lack of Asian genomic data, researchers in Singapore began sequencing 10,000 Singaporean genomes in the SG10K_Health study. The first of three phases, SG10K_Health is now the largest multi-ethnic Asian database to date.

As the cost of genome sequencing falls, Singapore began the National Precision Medicine Strategy to shift the focus from treating disease to maintaining health. To coordinate this national move, PRECISE was incorporated as a central entity to drive data-driven healthcare in Singapore. With phase two of the strategy in process and phase three not far off, Executive Director of PRECISE, Professor Patrick Tan, shares the complex challenges, important lessons and great potential of precision medicine in Singapore.

What is your vision for precision medicine and what difference will it make, both for Singapore and the whole world?

In Singapore, we have been blessed with a very good healthcare system. But there are many pressures that are challenging our ability to deliver high-quality medical care at affordable cost. For example, we have an aging population with increasing cases of chronic disease, and many elderly will unfortunately likely spend their last years in ill health. To address this, the Ministry of Health is looking at innovative ways to deliver healthcare differently, to maintain health.

One option is precision medicine, where we use data—genetic data, environmental data, clinical data and lifestyle data—to move medicine away from this one-size-fits-all regimen towards more tailored management approaches. We want to help Singapore’s patients by predicting disease before it happens, diagnosing patients more accurately, and treating them in a more refined way for certain drugs to work better and identifying those at risk of experiencing side effects.

Taking a step out to the larger world, the impact of our work can extend to many countries in Asia. Most genomic data currently comes from Western countries like the US and Europe, but there are several disease conditions that affect Asians differently. To apply precision medicine to the Singapore population we mapped three major ethnic groups: Chinese, Malays, Indians. In doing that, we could potentially contribute towards the application of precision medicine in other Asian countries where these populations are prevalent as well.


What are some trends that you have noticed in precision medicine happening worldwide and how do these trends affect Asia?

I think there are a few trends—some of them good and some of them more challenging. There is now a greater appreciation for data-driven healthcare because of advances in technology, such as decreasing genome sequencing costs, the use of wearable trackers that can monitor heart rate and other data, and new applications including artificial intelligence.

The other trend that’s important, and is worldwide, is a growing recognition that medicine and healthcare now needs to focus should be on intercepting disease before it manifests at later stages. If we can predict for you or your family members which diseases you will get and intercept them early, we can forestall later complications.

On the other hand, I think there are certain trends that are less supportive. We are beginning to see more concern about the exchange of data across borders. However, this information needs to be interoperable and shared among different countries to maximise its benefits. I think with new technologies that are coming up in computing and privacy we will be able to have exchange, while recognising the data sovereignty of these different databases.


What makes PRECISE different from other national genetics programmes that are happening around the world?

Singapore is one of the few countries that has a mix of different ethnic groups living in one place. It’s a small country, which means that you don’t lose individuals in terms of their clinical journey, which would allow monitoring of health trends over one’s lifetime. And we have a unique identifier for every individual that allows us to link data pieces. Moving forward, we need to work with industry partners to achieve these capabilities that we want to build.

Over the years, a number of things have happened that have made doing something at this scale reasonable in terms of costs, time and money and manpower. To sequence a genome at the time of The Human Genome Project cost about US$3 billion; today you can have your entire genome sequenced for under US$1,000. Platforms like cloud computing and nearly infinitely scalable computing allow us to crunch all of this data; these were not available until only a few years ago. Furthermore, the pervasiveness of the internet allows monitoring longitudinally, rather than only when you come to the hospital. All of those things help to bring together the different factors that contribute to your health and influence your future.


The National Precision Medicine Strategy is currently in phase two, what were some barriers faced in phase one, and what are key challenges that you want to overcome in phase two?

I’m going to use an analogy to explain the first barrier. To diagnose diabetes, we look for elevated blood sugar, but to know what is considered elevated you first need to know what is normal, which can be different for different people. When we started, we did not know what was a ‘normal’ Asian genome. If a patient with symptoms has a particular gene variant in his or her sequence and I compared it to a Western database, it may appear that this is the disease causing variant when it actually is not. There have been cases where patients from under-represented populations that have been misdiagnosed and treated wrongly, simply because they were compared against the wrong reference database.

Creating a database of Asian genetic normality was thus one of the key goals for phase one. When we accomplished it we found millions of variants that are common in Asia but not present in Western databases. That data is now being used by clinicians in Singapore as a reference standard to identify true disease-causing mutations.

The second area we are working on is developing the right workforce to be able to build this program at scale and make it mainstream. We’ve started working with the Ministry of Health training programmes for genetic counseling and medical geneticists to increase that cadre of skilled people that can then go on to the different hospitals.


The SG10K database has already made waves as the world’s largest multi-ethnic Asian genetic database. As the database grows, what are some tangible outcomes we can expect from this database?

Soon we will be able to identify gene variants, pathway and insights into disease mechanisms that are relevant to Asia. This is the short-term impact.

Looking ahead, we will now have well-powered longitudinal population cohort of Singapore. These large-scale population cohorts are the best way to distinguish between cause and effect and understand early cues of disease. For the next five to ten years, this will be our goal.

The third part is extremely exciting to me. Through this process, we will establish a data platform where data from consenting individuals can be linked up. Once this platform is set up, it will also open for use for many other studies that are now being funded through public funds. That data can then be returned to that platform for researchers to access information from various studies at the press of a button. That will completely change the way biomedical research is done and enable studies that were simply not possible before, for future generations of Singapore biomedical scientists and clinicians.