SECRET SINGAPORE

Secret Singapore: Designing The Future Of Wellness

By Marc Almagro
Photos by Alvinn Lim
Video and video editing by Tracey Nguyen
Assisted by Zulfadli Bin Rahman
10 May 2024

More and more answers to questions about the future of health are embedded in our genetic makeup and are emerging from labs where they are examined, identified and applied to prevent or arrest certain types of diseases.

In 2013, international celebrity Angelina Jolie told the press that she had tested positive for BRCA1, a rare genetic mutation with a high probability of developing into breast and ovarian cancer. After genetic counselling, she decided to undergo a preventive double mastectomy and a reconstructive surgery. This is one of several high-profile cases of pre-emptive surgeries that have drawn attention to the tremendous advances in genetic research which supports the development of personalised and predictive medicine. 

Advanced genetic diagnostic and therapeutic research is not only helping scientists predict with consistent accuracy the types of diseases to which humans may be liable, but also producing innovative solutions for the future of medicine. Many of the clues, labs say, are already in our system and, although they have yet to manifest themselves as symptoms, may show up in lab processing.

Personalised (or precision) and predictive medicine employs the molecular and genetic profile of an individual in addressing a disease or managing its symptoms. Using very precise genetic and molecular data from humans and microorganisms such as bacteria, scientists and clinicians can determine an individual’s predisposition to specific illnesses and allow for more precision in patient treatment and prognosis. 

Watch Episode 3 of Secret Singapore: Designing The Future Of Wellness (Segment 1-3)

  • A FIELD LEADER
  • NEXT-GENERATION CELL THERAPIES
  • COMBATTING DRUG-RESISTANT THREAT
  • GUT HEALTH & PREDICTIVE MEDICINE

A Field Leader

Singapore leads in the field of personalised and predictive medicine with a range of scientific labs and medical clinics operating locally. They are conducting research whose results will become building blocks of health regimen or novel approaches to a known illness.

To gain more insight into the subject, we visited three controlled-access facilities that are conducting ground-breaking experiments related to personalised and predictive medicine. The first two, located at the NUS campus – SMART CAMP and SMART AMR – are interdisciplinary research groups (IRGs) that form part of the research enterprise called SMART (Singapore-MIT Alliance for Research and Technology), a partnership between the Massachusetts Institute of Technology in the USA and the National Research Foundation Singapore.  

The third lab, AMILI, is a private microbiome company that is focused on microbiome research for human health applications. Its facility at Singapore Science Park encompasses Southeast Asia’s first and only gut microbiome transplant bank, which serves as the foundation of the world’s largest multi-ethnic Asia gut microbiome database.

  • A FIELD LEADER
  • NEXT-GENERATION CELL THERAPIES
  • COMBATTING DRUG-RESISTANT THREAT
  • GUT HEALTH & PREDICTIVE MEDICINE

Next-Generation Cell Therapies

SMART CAMP IRG is on a mission to help provide more patients with access to next-generation cell therapies, or the use of living cells – such as immune cells and various stem cells – as medicine.

The work requires not only improving the efficiency of manufacturing current cell therapies but also exploring new avenues for improving cell-based approaches in medicine, explains Prof. Jongyoon Han, a professor of Biological Engineering and Electrical Engineering at MIT, and the Co-Lead Principal Investigator at SMART CAMP.

As they develop the technologies that improve various therapies, Prof Han and his team also have to overcome critical bottlenecks in cell therapy manufacturing. A lack of proper measurements to assure quality and safety, known as critical quality attributes (CQA), is a constant problem in cell therapies, Prof Han observes. CAMP IRG is addressing this by developing and testing many CQAs to make manufacturing cell therapies less expensive and more reliable.

Although SMART CAMP does not focus on disease diagnostics, their work aligns with the mission of making next-generation medicine more personalised and predictive. “This is because many approved cell therapies are autologous, that is, they utilise the patient's own cells to make cell therapies.” However, on top of variations in the starting material, i.e., the cells, this process also introduces further variations and deviations, Prof. Han explains. By measuring the CQA of cells at their source, they address and alleviate these variations. Such CQA-based control of manufacturing can also lead to greater consistency in the quality of final cell therapy products, producing better clinical outcomes, he adds.  

SMART CAMP has already developed a revolutionary method using Deterministic Lateral Displacement (DLD) microfluidic technology. “This breakthrough doubles the quantity of MSCs and reduces extraction time to just 20 minutes,” Prof. Han says. Conventional stem cell extraction from bone marrow aspirates (BMA) is time-consuming, inefficient, and often involves complex processes with expensive reagents, which limits accessibility and patient comfort.

SMART CAMP’s label-free cell sorting approach eliminates the need for expensive reagents and simplifies the extraction process, significantly enhancing efficiency in cell therapy manufacturing. The lab is currently conducting research to further enhance the technology, evaluate MSC quality, and optimise sorting speed and resolution.

It has also developed the technology to assess the quality of Mesenchymal Stromal Cells (MSCs).  Identifying cellular senescence – or natural ageing – holds a significant importance in assessing the quality of cell therapy products, including mesenchymal stromal cells (MSCs). “Here, we establish a rapid, live-cell analysis for detecting senescent cells in heterogeneous mesenchymal stromal cell (MSC) cultures,” Prof. Han says. 

The micro-Magnetic Resonance Relaxometry (micro MRR) system used in the work was originally developed at SMART (BioSyM & CAMP IRG) around 2011, shares Prof. Han. Since then, the technology has been applied to many important biomedical detection applications such as malaria (2015) as well as diabetes (2020) monitoring. 

A recently founded US-based start-up, Larmor Biosystems, has licensed the technology. The company is currently collaborating with at least two major pharmaceutical companies to evaluate the device’s efficacy in diagnostics and drug discovery applications.  

SMART CAMP brings together faculty members from various institutions (MIT and Singaporean universities), different departments (various engineering and science departments), and different intellectual and professional backgrounds (early-stage science vs. mature engineering), into a single group where they can collectively tackle the challenging problems of the industry that does not belong to any one department or discipline,” Prof Han shares. 

“This way, every researcher at CAMP is challenged to go beyond their comfort zone in approaching topics and issues that may lie outside their field of expertise, and this intersectional, interdisciplinary collaboration and research is what makes CAMP truly unique.”

  • A FIELD LEADER
  • NEXT-GENERATION CELL THERAPIES
  • COMBATTING DRUG-RESISTANT THREAT
  • GUT HEALTH & PREDICTIVE MEDICINE

Combatting Drug-Resistant Threat

Germs sometimes reach a point when they beat the drugs that are designed to remove them – a situation known as antimicrobial resistance or AMR – and a lab is dedicated to addressing this. Called the SMART AMR IRG, it is a translational research and entrepreneurial programme that applies theoretical discoveries to the further development of practical applications. 

“We aim to tackle AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections,” Dr Megan McBee, Senior Scientific Director, explains. “By conducting research on the resistance mechanisms of bacteria and advancing novel technologies to tackle this challenge, we aim to pave the way for a healthier world for future generations,” says Dr McBee.

Some of SMART AMR’s works are linked to predictive medicine, among them evaluating existing and new drugs for their ability to remove or inhibit the growth of bacteria, detecting bacteria through various lab procedures, and exploring new and alternative strategies to resolve the antimicrobial resistance.

SMART AMR has, to date, identified a new therapy for combating VRE infections – VRE is a highly resilient bacterium notorious for causing severe bloodstream infections, urinary tract infections, and wounds associated with catheters and surgical procedures. It has also discovered a new way to combine the antibiotics clarithromycin and rifaximin to improve their ability to remove a species of rapidly growing multidrug-resistant mycobacteria that is a common soil and water contaminant. 

“This pioneering development holds great promise for surmounting the challenges associated with NTM infections,” notes Dr McBee. NTM (non-tuberculosis mycobacteria) are multi-drug resistant opportunistic pathogens for which certain groups, including those with lung disease or suppressed immune systems, are at increased risk.

SMART AMR researchers have also discovered a new stress signalling system that enables bacteria cells to adapt and protect themselves against the immune system and certain antibiotics. “The discovery opens the door to developing drugs that can thwart the adaptive response, ensuring that pathogens maintain their sensitivity to antibiotics,” Dr McBee elaborates.

SMART AMR works collaboratively as one research group and leverages the scientific and clinical strengths of MIT and Singapore, Dr McBee adds. “Our interdisciplinary teams work across research and innovation and the projects address the threat of drug-resistant microbes by developing diagnostics and drugs based on synthetic biology; defining new resistance mechanisms in biofilms and dormant infections; developing anti-resistance drugs and drug delivery strategies; and exploiting host immunity to combat resistant microbes.”

SMART AMR is unique in many ways. It is among the few labs dedicated to both AMR-related research and innovation. A translational-focused research lab, it is fully equipped to perform both diagnostics and therapeutics development.

  • A FIELD LEADER
  • NEXT-GENERATION CELL THERAPIES
  • COMBATTING DRUG-RESISTANT THREAT
  • GUT HEALTH & PREDICTIVE MEDICINE

Gut Health & Predictive Medicine

“We are now able to study your gut microbiome by doing something as simple as a stool test. Knowing the composition and diversity of your gut microbiome can help us predict your future risk of disease and suggest preventative changes you can take to rectify this,” says Dr Melvin Look, an upper gastrointestinal surgeon and medical director of Pan Asia Surgery Group.

According to Dr Look, only 43 per cent of the cells in our body are made up of human cells; the rest comprises trillions of microbes that live on our skin and in our internal organs. “The most important ones reside in our gut where you will find an astounding diversity of bacteria, viruses, fungi and other microbes.” Collectively, this group is called a microbiome.

“Advances in genomics, proteomics, and epigenomics open up new understanding in the role our microbiota plays in gut health. We also now know that the quality of your gut microbiota, and the effect on it by your dietary, environment and lifestyle choices, may affect your health far beyond the gut itself,” he explains. 

A loss in microbiota diversity can lead to an increased permeability in the intestines, Dr Look explains, a condition known as ‘leaky gut’ which allows substances such as undigested food particles, toxins, waste and bacteria to enter the bloodstream and causes an autoimmune, allergic or inflammatory reaction in the body. “Your gut health can therefore be intricately linked to systems as diverse as your cardiovascular health and your brain health,” he emphasises. 

Dr Look collaborates with the private microbiome lab AMILI to obtain key microbiome information. AMILI offers gut microbiome sequencing services and probiotic formulations. 

At the AMILI facility, stool samples are processed to obtain valuable insights and products. Following rigorous processing, the samples are transformed into raw data with manifold applications in optimised food and nutraceutical manufacture. They also serve as powerful tool in the sample donor’s quest for better nutrition and personalised medicine through probiotic formulation or even microbiome transplantation.

This feature is not a medical assessment and does not seek to endorse any type of genetic therapy, personalised (precision) or predictive medicine. 

Read & watch the first instalment of Secret Singapore, "Protecting The National Patrimony", here.

Read & watch the second instalment of Secret Singapore, "Your Money Where Your Art Is", here.