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Director’s Notebook

The first time I stepped into the National Health Research Institutes (NHRI), it was super hard to keep up with the person I was interviewing, Guann-Yi Yu, as she gave me a glimpse into the mysterious world of a lab that conducts research on viruses. Around every corner, my eyes were filled with gigantic biohazard signs, and I paid witness to their P3 laboratory which hasn’t opened yet. Even when Guann-Yi Yu told me about her daily life as a researcher in her patent gentle voice, images of Yu and her Southbound partners duking it out with viruses kept bubbling up in my mind.

If you’ve ever said that fighting a pandemic is like fighting a war, then the woman standing in front of me was most definitely a hero.

Picture 1: Associate Investigator Guann-Yi Yu at an NHRI lab (Photo: Pei-lin Lin)

Battling Viruses in a P3 Lab 

Since 2019, the world has been in the grips of the COVID-19 pandemic. Therefore, getting a chance to visit NHRI and learn from a virus expert was truly a blessing.

Not long after I met Associate Investigator Guann-Yi Yu she started talking about her research in a cool and collected manner. “I’m a virologist by training. Recently, I’ve been conducting characterizations of novel coronavirus spike proteins. There are many interesting things about this type of research. For instance, why was the Delta variant of COVID-19 more deadly than Omicron, and how are their biochemical properties correlated to toxicity?

In terms of toxicity, Guann-Yi Yu must look at things from a virus’s perspective to break down what makes viruses different and research the key factors in the spread of disease. Researchers can only come up with a prevention strategy when coming across the same or similar viruses. For instance, COVID-19 targets spike proteins. Therefore, researchers must clarify and design more stable antigens and immunity.

When everyone is most scared of a virus is the moment Yu and her colleagues gear up and march into their P3 laboratory (Note 1) to conduct live virus tests. Only 10 people at NHRI have been cleared to enter a P3 lab, and two of those are on Guann-Yi Yu’s team. It’s no wonder that Yu was shocked to hear about a “mobile P3 lab” when working with a team from Malaysia.

Note 1: A P3 lab refers to the third safety ranking of labs that can handle biohazardous materials.

From Dengue Fever to COVID-19, Taiwan and Malaysia Team Up to Fight Disease

Malaysia is home to a mobile P3 lab. Since 2018, NHRI, National Taiwan University, Kaohsiung Medical University, and National Yang Ming Chiao Tung University have worked closely with Universiti Malaya Tropical Infectious Diseases Research & Education Centre Professor Sazaly Abu Bakar. Taiwan-Malaysia research cooperation has explored topics from Zika virus and dengue fever to focusing on how COVID-19 enters the body, its interaction with host cells, and the causes of organ failure. Guann-Yi started out our conversation by talking about the Zika virus, which was previously active in Brazil. The Taiwanese government is currently paying close attention to Zika because there was an instance of an imported case entering the country. Moreover, Zika infections can cause abnormalities, including cerebellar dysfunction, in unborn babies. In addition to disease prevention measures of the Taiwan Centers for Disease Control at the airport, the NHRI National Mosquito-Borne Diseases Control Research Center and Professor Sazaly, who has extensive experience in mosquito-borne diseases, have worked together to develop a model for disease transmission in animals while conducting research on pathogenic mechanisms of viruses.

To address the yellow fever mosquito’s potential to spread dengue fever and Zika virus in Taiwan, a research team led by National Taiwan University Professor Shin-Hong Shaio discovered that a certain molecule can disrupt the insect’s siRNA. This molecule can inhibit the virus from replicating when placed into a yellow fever mosquito. In order to allow more mosquitos to come in contact with siRNA, the team transforms it into a benign form that is carried in Escherichia coli, and then sprays it in areas where there could be mosquitoes with Zika virus. This exciting research is also being conducted in Malaysia. After carrying out multiple tests on mosquitos, the siRNA’s unique qualities have been verified through an observable drop of the pathogenic molecules in yellow fever mosquitos.

Guann-Yi went on to explain, “Cross-border tests are necessary. It’s the only way to verify “uniqueness.” Mosquitoes and people are the same. siRNA has specific sequences that only impact yellow fever mosquitos. However, we can’t disrupt the overall ecosystem too much because mosquitos play an important role. A lot of things would happen if we were to kill off all the mosquitos.

Making a Virus “Library” During the Pandemic

Guann-Yi also brought up the trial-by-fire that was the COVID-19 pandemic, which made people rethink the way they did things, including research on viruses. It’s hard for most people to imagine that for NHRI to buy one virus, they need to spend upwards of two or three months. From the application documents to flight cancellations during the pandemic, every step along the way is full of uncertainty. Contrary to what you’d think, developing a reagent to test “uniqueness” requires having other viruses. Moreover, an experiment is forced to stop if the research team can’t get the control group material on time.

Therefore, the Ministry of Health and Welfare had NHRI establish a “library” that collects viruses in order to get us better prepared in dealing with current infectious diseases and ones that we might potentially encounter in the future. This “library” is like Noah’s Ark with advanced storage capabilities that allow research teams to get the right virus when they need them without looking around. Moreover, it eliminates the risk of obtaining the wrong virus, delaying research, or stalling the development of new vaccines. Just like how ice can preserve seeds, keeping viruses on hand is a type of proactive defense that can serve as a bud of hope one day in the future.

Combating Ever-Changing Viruses amidst Climate Change through Regional Cooperation

Research topics supported by the NSTC’s “Taiwan Significant Emerging Infectious Disease Research Project” include viruses that have been active in Taiwan such as COVID-19 and mosquito-borne viruses like dengue fever and chrysanthemum virus.

Regardless of whether a virus has been active in Taiwan, these disease prevention heroes pay attention to them as long as the WHO classifies them as significant emerging infectious diseases.

Not many Taiwanese people know that Nipah virus has two strains: Bangladeshi and Malaysian. Guann-Yi said, “Universiti Malaya identified the Malaysian strain, mainly which comes from the date tree habitats of bats. People or pigs can get infected when consuming the juice or fruit from a date palm tree that’s been infected by a bat with the virus. In addition, a transmission pathway sometimes forms when pigs pass the virus on to people. This year, we’ve invited Professor Sazaly to come to Taiwan to give a lecture on Nipah virus. 

In closing, Guann-Yi reminded me that every year, Taiwan has a new wave of dengue fever, which tends to ease up in the winter. However, climate change has impacted seasons, temperatures, and rainfall, which in turn, may also lead to changes in the rise of different viruses. Therefore, establishing a virus “library” and long-term research partners across the globe will help determine the best response in the shortest amount of time whenever the next pandemic arises. Regional cooperation and safety aren’t just strategic considerations. In the face of invisible viruses, we need to establish solid academic and research partnerships to fight disease.

Picture 2: Team members conduct virus-related research (Photo: Pei-lin Lin)

Picture 3: Dr. Sazaly of Universiti Malaya (Right) and his team come to Taiwan for an exchange (Photo: Guann-Yi Yu)

Columnist

Pei-lin Lin

Pei-lin Lin obtained her B.A. in Philosophy from Fu Jen University and her M.A in Political Science from National Taiwan University. Lin embodies a humanistic literacy and political sensibility. In recent years, Lin has collaborated with the Taiwanese government to shoot videos promoting various policies. Currently, Lin splits her time between running a Chan Lands Ltd., Zongdipan, making documentary films and hosting the podcast “Human Translation Machine.” In the past, Lin has been a reporter for several media outlets and the anchor of shows on TVBS, CBC and Da Ai Television. While at Da Ai Television, Lin’s piece “Muhammad Yunus- Savior of the Poor,” was nominated at the First Taiwan Golden Wheel Awards for Outstanding Television News Feature.