Trekking in the Himalayas was when this big Twitter fan first caught wind of a new virus.
Twenty-twenty is going to be an amazing year, Dr Ruklanthi — or Rukie — de Alwis remembers thinking as she and her husband trekked in the Himalayas in late 2019, even as their Twitter feeds started carrying news of a pneumonia of unknown cause. Soon, the cause began to be attributed to a SARS-like virus.
De Alwis, a then-senior research fellow with Duke-NUS’ Emerging Infectious Diseases Programme, was looking forward to studying the human antibody response to viruses that cause neglected tropical diseases like chikungunya and dengue, and advance the search for effective vaccines against these scourges.
In particular, she was keen to shed light on the different signals that emanate from the stems of Y-shaped antibody molecules; signals that beckon other parts of the immune system to help protect against infection. At least that’s how they are supposed to work.
“The plot thickens because that stem portion can either protect or make the infection more severe,” says de Alwis, who also held an appointment with the Viral Research and Experimental Medicine Centre at SingHealth Duke-NUS (ViREMiCS). “And that is something that has not been very closely studied.”
But as the first weeks of January rolled by, the novel coronavirus started to take root in Singapore, spreading beyond holidaymakers to the community.
As de Alwis watched cases creeping up, she felt agitated, an urgency to lend her skills had built in her. Sitting dispirited at the café at Duke-NUS, she was spotted by a principal investigator (PI) whom she admires.
“When I confided in this PI, she told me to just ask and gave me that push that I needed,” recalls de Alwis who works closely with Professor Ooi Eng Eong and then Associate Professor Jenny Low.
Plucking up the courage, de Alwis approached Ooi.
“I was sure I could help out somehow as we knew nothing about the antibody response patients were having,” says de Alwis, who had been developing a series of antibody tests using her National Medical Research Council Young Individual Research grant.
“I had these easily adaptable tests ready,” she adds.
Yes, of course! was Ooi’s response and de Alwis plunged into the planning and preparatory work for a new vaccine project as the contract for the work was being finalised between Arcturus Therapeutics and Duke-NUS.
Stepping on the rollercoaster
The weeks and months that followed were a blur of activity, filled with scientific discussions on what and how many constructs to test, reading up on the literature from SARS to find the best leads, organising reagents and ensuring all the necessary supplies were on hand for the moment the contract was signed.
While they waited for the go-ahead, de Alwis and Ooi delved into a concern that niggled in their minds: Some early reports of preclinical studies had hinted at antibodies possibly going rogue, sending signals — or effector functions as they are known — that helped the invading pathogen. Similar effects had been observed in preclinical work for some vaccine constructs that had been developed against the SARS-CoV-1 coronavirus.
“There were some reports that instead of having all these beautifully protective effector functions, the virus uses the same portion of the antibody to get into an immune cell, causing an infection in the immune cell,” she explains. “And at that point we knew very little about SARS-CoV-2.”
Reflecting on the resulting review, de Alwis is glad that the antibody-dependent enhancement effect didn’t materialise in subsequent studies.
“We didn’t see the same effect in our preclinical vaccine studies, fortunately,” she says.
Just as Singapore entered the Circuit Breaker, the vaccine work unfurled in earnest, setting de Alwis and her colleagues off on a rollercoaster ride. With limited reagents and even less time, de Alwis and the team were under pressure to make every experiment count. Frequent and detailed discussions with the whole team and their partners were the norm.
So, despite being assigned to the afternoon shift, de Alwis’ day started early, her morning filled with meetings with teams in the US, analysing the latest data and planning the next steps.
Around 2pm, she would begin her shift in the lab.
“Sometimes, there were days, when I’d stay till 1am or 2am,” she recalls. “We were running on adrenaline.”
One bright spark during those sleep-scarce rollercoaster days was the company of her family. Based in Sri Lanka, which is two-and-a-half hours behind Singapore, she would videocall them as she worked late into the night, the gentle chatter helping her stay focused on her work.
Like the joy her family brought, the shared excitement and enthusiasm from the team in Singapore was another source of happiness.
“It was nice to have the team to discuss the data with. For the vaccine development project, seeing any signal was so exciting, we were (literally) jumping. That doesn’t happen in peacetime,” laughs de Alwis.
Emerging from the pandemic
While excitement ran high, the need to validate the science — that required the team to run the same experiments for each clinical trial participant at different time points to ensure they had a complete picture — meant that the team had to stay focused.
“I’m very much an academic scientist,” admits de Alwis. “So, if there is something super interesting, I want to follow it. But when you’re doing a clinical trial, there is one goal and you got to stay focused.”
“That was the hardest part of it.”
They didn’t just have to stay focused on the goal, they also had to meticulously document every sample and each step of their experiments.
“It was a highly stressful time,” says de Alwis. “But I also learnt a lot in the process and it showed me that I had skills that I could contribute which made it a very fulfilling experience.”
Her — and the wider team’s — experience was immortalised through the documentary “The Vaccine Quest”. Like the vaccine development project, it was another new experience for de Alwis, who would in the past have passed on such an opportunity; valuing her privacy more.
“I was thinking that if sharing my experience motivates more young scientists to do this sort of thing, then why not,” says de Alwis, who is determined to continue to engage with a wider audience about science.
As for her scientific ambitions, the pandemic lent a wider focus.
“It has increased my focus on regional development,” shares de Alwis, who realised that to see a vaccine through its full development journey she would have to find a role that takes her beyond Singapore. Because by the time Phase III trials were due to start, Singapore had implemented an effective nationwide vaccination programme and successfully lowered its community transmission rates; essentially making Singapore no longer a suitable location for testing a COVID-19 vaccine in Phase III trials.
This thought sparked another dormant passion of de Alwis’: a desire to give back.
“I come from Sri Lanka, and I really want to be able to give back all that I’ve learnt,” said de Alwis.
When she learnt that Duke-NUS was setting up a new centre — a centre that would work with low-resourced partners around Asia to ensure humanity’s defences against the next outbreak are strengthened — she saw a perfect opportunity.
“The pandemic showed us that we have a long way to go before everyone has equal access to health care,” she says. “And right now, we have an opportunity to strengthen the region in terms of tracking diseases, developing vaccines and fortifying our regional health security.”
The Centre’s director Professor Paul Pronyk was keen to bring her on board and within days, had offered her a new appointment: as an assistant professor with the Emerging Infectious Diseases (EID) Programme at Duke-NUS and the new Centre for Outbreak Preparedness as its deputy director, effective from third quarter of 2022.
“With these two complementary roles, I now act like a bridge, helping our EID folks translate their discoveries into meaningful impact through our partners across the Asian region,” she explains, “a bit like a matchmaker.”
“I do miss lab research, but this is just as exciting. I’m creating research opportunities, opportunities that I’ve benefitted from for others.”