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Precision or personalized medicine based on analysis of patients' genomes is beginning to catch on in Southeast Asia. (Nikkei illustration)
Asia Insight

Cracking ASEAN's code: Inside the push for genomic medicine

Singapore, Malaysia and Thailand doctors seek funds as COVID adds new hurdle

YAO-HUA LAW, Contributing writer | Malaysia

KUALA LUMPUR -- In 1999, pediatrician Vorasuk Shotelersuk was tending the wards at a Thai hospital. A 5-month-old girl had just been admitted in such bad condition that the doctor feared "she would die in less than 24 hours."

Other doctors were unable to make a diagnosis, but Vorasuk recognized symptoms of a rare genetic disorder and saved her. She is now a university student and calls Vorasuk her "medical dad."

The girl survived because her disease happened to match Vorasuk's expertise. "It was good luck," he said. Today, he prefers to leave less to chance.

A clinical geneticist and pediatrician at Bangkok's King Chulalongkorn Memorial Hospital, Vorasuk uses technology that is beginning to catch on in the Association of Southeast Asian Nations bloc as prices drop. For about $1,000, it is possible to reveal a patient's genome -- their complete genetic code of 3 billion pairs of letters -- within days, providing doctors with valuable insights. He said more physicians are opting for "genome first" diagnoses, especially for rare ailments, as part of what is known as "precision" or "personalized" medicine.

Hopes are high but so are the hurdles.

Countries in the region lag behind when it comes to compiling genetic databases. Government support is tentative at best, with doctors struggling to find funding especially given economic pressures from COVID-19. While the cost of reading genomes is falling, other expenses can be prohibitive. And then there are ethical concerns about how the genetic information might be used.

Every day counts. "If we wait," Vorasuk said, "lots of patients would die."

Vorasuk Shotelersuk, a pediatrician at Bangkok's King Chulalongkorn Memorial Hospital: Storing and analyzing genetic data requires plenty of computing power. (Photo courtesy of Vorasuk Shotelersuk)

The foundation of precision medicine lies in cataloging local genomes. When doctors examine a patient's genes for clues to a medical condition, they line up the sample against a reference database to detect differences. These tests can bring forward the diagnosis of a rare condition by years, catch traces of latent illnesses and determine whether a patient might experience severe side effects from certain drugs.

But if the database comes from a different population, the comparisons can yield too many differences, raising the risk of misdiagnosis.

Only a strong local reference database can make precision medicine "meaningful," said geneticist Zilfalil Alwi at Universiti Sains Malaysia. Yet as of 2019, among published studies that scanned genomes for disease signatures, nearly 80% of the samples had European ancestry, while only about 10% were of Asian descent.

The lack of local reference data is "the biggest challenge" for promoting precision medicine in Asia, said Saumya Jamuar, who heads the SingHealth Duke-NUS Genomic Medicine Centre in Singapore and is a geneticist at the KK Women's and Children's Hospital in the city-state. "The pitfall would be if we continue to ignore this problem and not build that local reference database."

Leading nations in precision medicine research, including the U.K., U.S., China, Japan and Saudi Arabia, are compiling large genome collections. Britain appears to be the front-runner with 100,000 genomes cataloged as of 2018; the country now targets 5 million by 2024.

"We want to be in a similar space and we want to be ready as well," said Saumya.

The SingHealth Duke-NUS Institute of Precision Medicine and other institutions in Singapore have teamed up on cataloging and had built a local database of almost 5,000 samples as of 2019, midway to a goal of 10,000.

While bigger databases are needed, even modest steps can make a difference.

Saumya said that when Singaporean patients were compared with overseas databases, the average individual had 2,000 rare variants. But with the new local database, the scope narrowed to about 1,100. "It helped us to filter down more efficiently the variants" that might explain a patient's condition, he said.

Similar projects are underway elsewhere. In Thailand, the government in March 2019 approved a $150 million five-year Genomics Thailand Initiative that will catalog the genomes of 50,000 citizens.

And in neighboring Malaysia, scientists will soon pitch a national precision medicine plan to the government. Rahman Jamal, the geneticist leading the effort, hopes that in five years the country will have logged about 50,000 genomes.

Doctors stress the power of the technology. Rahman noted it is possible to test for any of the 170-odd genes associated with heart disease, for around $500. If the test comes back positive, precautions can be taken.

For diabetes, a common disease among Southeast Asians, studies in the West have found that some medications work well for patients with a certain genetic makeup but not for others. While researchers still need to study this phenomenon in Asia, the findings show that precision medicine provides the knowledge needed to personalize treatment so patients "get the best outcome," Rahman said.

Genetic insights can also make treatment safer. An example: In people of Han Chinese ethnicity, a gene variant known as HLA-B*15:02 makes them tens to hundreds of times more likely to develop a life-threatening skin rash if they take the anti-epilepsy drug carbamazepine. In Singapore and Thailand, about 12% and 6% of the respective populations harbor the variant, and patients are now tested before the medication is prescribed.

The benefits are "very clear," said Surakameth Mahasirimongkol, director of genomics medicine and innovation support at Thailand's Ministry of Public Health. Incidents of severe skin rash reactions to carbamazepine have dropped to about 30% of 2009 levels.

Genome sequencing data shows the variations within an individual’s genes. (Image courtesy of SingHealth Duke-NUS Institute of Precision Medicine)

Even so, doctors in Southeast Asia have struggled to convince policymakers to promote nationwide precision medicine programs. Budgetary constraints are a concern. Vorasuk rattled off a list of expenses besides the declining cost of reading genomes, including database construction, software and computer scientists to analyze the data and genetic experts to interpret the results.

Universiti Sains Malaysia's Zilfalil -- who leads the country's participation in the Human Variome Project, a global drive to catalog genetic variations -- admitted the infrastructure requires "lots of money."

"I think somehow the government does not see it as a priority," he said, noting academic institutes conduct most of the nation's genetic research. Zilfalil thinks a big push from the Ministry of Health is necessary to "help the country to jump forward into precision medicine."

Rahman agreed that the ministry and its 146 hospitals could play key roles. The ministry "would formulate policies in terms of approving [free] genetic testing for certain diseases." At least, he said, precision medicine is included in the ministry's strategic planning.

"I believe the buy-in is there," Rahman said.

But COVID-19 has only made it harder to obtain public funding. Malaysia's economy contracted over 17% in the April-June quarter, and the government has pledged tens of billions of dollars to cushion the impact.

"If you start by saying that I want 100 million ringgit ($24 million) to start this project, I believe we will fail," Rahman said. He thinks a better approach is to focus on how precision medicine can improve public wellness, longevity and productivity, all of which can be converted into economic gains and government savings.

This could "justify easily the return on investment," he said.

Thailand, where the economy contracted 12.2% in the April-June period, has slashed next year's allocation for the Genomics Thailand Initiative, according to the health ministry's Surakameth. But the total five-year budget remains $150 million and "we can keep requesting the budget until the plan is finished," he said.

The ministry aims to extend Thai life expectancy from 75 to 85 years by 2040, and many of the deadliest diseases -- cancers, tuberculosis -- are "easier to control with genetic testing," Surakameth said. "So that is how we establish the system."

Another challenge will be developing a clinical workflow to deliver precision care, according to Saumya at SingHealth Duke-NUS Genomics Medicine Center.

The basic idea is that patients would, after giving informed consent, provide DNA samples for testing and analysis. The results would then be interpreted by doctors, who would provide the appropriate advice and treatments.

But experts recognize that genetic testing is not just a checkup. It goes far deeper, probing the very nature of ourselves. A crucial link in the delivery of precision medicine services are counselors who can help patients understand and cope with the implications for themselves and their families.

Yasmin Bylstra, principle genetic counselor at the SingHealth Duke-NUS Institute of Precision Medicine, explains that genetic information can have "psychological, medical, social and practical" ramifications, including possible impacts on insurance coverage and even employment.

Genetic counselors like Yasmin Bylstra, right, are crucial to help patients understand the implications of genetic tests. (Photo courtesy of SingHealth)

Counselors like her and other precision medicine specialists are in short supply in Southeast Asia, however, according to a 2018 study.

While Bylstra could not say how many counselors there are in Singapore now, she did say the number is growing, with more than 10 at SingHealth institutes alone. In Thailand, where the 2018 review found none, the Genomics Thailand Initiative aims to train around 100, Surakameth said.

Many say it will take more than counseling.

Since genetic tests can reveal the risks of developing diseases, the information can save lives but also theoretically hurt a patient's future opportunities. Southeast Asia lacks legal protections against insurance or employment discrimination based on genetics.

Malaysia needs the "proper legislation for precision medicine," Zilfalil said. Rahman agreed there should be safeguards so people who undergo genetic testing are not "put at a disadvantage."

Bylstra explained that in Singapore "it's all up to the individual [insurance] policies." If patients are worried, she recommends they buy coverage before getting tested. When it comes to job prospects, she helps her patients decide which is more important -- "the fact that you might face employment issues in the future" or "that you learn more about your condition."

For Vorasuk, although he saved the 5-month-old girl, he cannot help but think of the not-so-lucky ones -- patients with similar diseases who are diagnosed too late or not at all.

If that baby in 1999 "had another disease that didn't fall in my specialty, she would have died already," he said. But now, "we want these rare and undiagnosed disease patients to be diagnosed."

"What we want to do," he said, "is to change luck into a system."

Yao-Hua Law won the 2019 International Journalism Competition on Personalized Medicine organized by the Switzerland-based SantePerSo Initiative. The initiative aims to further public discussion of personalized medicine.

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