Professor S.S. Vasan (’91 Batch) has been working on the COVID-19 response at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) in Australia. The English Press Club and the Alumni Relations Cell reached out to him for an interview regarding his team’s efforts and his time in Pilani. They also talked about Sandhya Mitra, Star Wars, playing Antakshari, eigenvalues, Oxford dinner table conversations, and potential journeys after Pilani.

COVID-19 Efforts

Let’s start with the present. You are head of the Dangerous Pathogens Team for Australia’s science agency CSIRO. What is unique about the high-security laboratory where you are based?

CSIRO’s Australian Centre for Disease Preparedness in Geelong is the world’s largest operational high-containment facility where in vivo studies on small and large animals can be performed under Good Laboratory Practice conditions. My team is suit-trained and work on some of the deadliest viruses including Ebola, Hendra and Nipah.

You and your team have been mentioned by the journal ‘Nature’ thrice recently. What are some of your key achievements in relation to COVID-19 vaccines?

We were the first to make working stocks of this virus outside China and initiate preclinical research. We showed, for the first time, that ferrets are susceptible to SARS-CoV-2, and with funding from a global body called CEPI (Coalition for Epidemic Preparedness Innovations), I am running the world’s first multi-vaccine animal efficacy studies. With the Oxford vaccine, I am also investigating if giving it intranasally is better than the current plan of intramuscular injection. Inovio’s candidate is equally interesting because there is currently no DNA vaccine licensed for human use. We are also down-selecting promising and repurposed therapeutics across our in vitro, ex vivo and in vivo systems.

How rapidly do you think the current scenario can be changed by the availability of a vaccine for COVID-19, given that it should be accessible to people all across the world?

There are some 115 vaccines under development, 22 listed as promising by the journal ‘Nature Biotechnology’. CEPI is funding 8 of these and are committed to equitable access around the world. Vaccines alone won’t solve this pandemic but will be critical to bring it under control.

Why are your preclinical studies important and time-critical?

Usually it takes 10-15 years to develop and validate vaccines. Scientists around the world are trying to achieve this in 10-15 months without compromising on safety and rigour.

In an unprecedented development, several leading vaccines (including the ones I am evaluating) have entered Phase 1 safety studies in healthy volunteers, and are due to enter human efficacy trials (Phase 2/3). Before approving the latter, regulators would like to see safety signals and efficacy data from animal studies (in addition to Phase 1 output), hence we are against the clock.

You are the senior author on the first peer-reviewed study on how the SARS-CoV-2 virus is mutating. What did you learn? Does the ‘D614G’ mutation render vaccines ineffective?

We analysed the genome sequences of this virus published on GISAID, which totalled 181 at that time (now there are over 31,000). We have developed phylogenetic as well as alignment-free sequence analysis using multi-variate techniques to visualise how the virus quasispecies exist as clouds of variants. An RNA virus such as this, even with a proof-reading mechanism, will mutate, but that is not a cause for panic per se. We are unlikely to require annual vaccines similar to seasonal influenza, nevertheless, we are keeping a close eye on the virus evolution. We have called for deidentified patient metadata to accompany sequences uploaded on GISAID, so we can make sense of all the data. I am also doing some experiments to ensure that the D614G mutation will not affect the vaccines that target the spike region.

Pilani Days

Let’s talk about your days in Pilani. If you were to describe your time in BITS using three words, what would they be and why?

“Training in Dagobah” — if I may use the Star Wars analogy. An unspoilt world where The Force is very strong… Jedi Masters continuing to believe in your potential although we frequently disappoint them with our antics, distracted performance, impatience, and occasional curiosity about the Dark Side… ?

Who was your greatest inspiration on campus? What were some of the biggest lessons that you learnt as a college student and how have they impacted on the way you work?

My interest in molecular biology research was piqued by Professor Sandhya Mitra. We were lucky as the last batch she could teach. There were many dons — especially Dr Alka Kurup, Professor V.N. Sharma, Professor G. Sundar, Dr Anuradha Tandon and Professor R.P. Vaid, who demonstrated that being empathetic is as important as being brilliant in one’s subject.

I found it humbling and inspiring that my batchmates were better than me at most things. I learned a lot from them and that experience, which helped me to find and focus on my own niche. I also realised that the institute’s broad-based education is our greatest strength. For instance, how many second year students in India are as comfortable as BITSians with RNA mutations, eigenvalues and coding? All three are key to my journal paper you refer to.

There was another funny lesson we learnt. We were taken inside a clean room, but before Dr Tandon could explain how it works she was called away. A bunch of us (I won’t name, they know who they are!) were stuck inside for an hour or two, so we played ‘antakshari’. Dr Tandon was horrified when she returned and the whole place had to be decontaminated.

How can BITS sustain its competitive position amongst Indian universities? How can the institute do cutting edge research on topics like COVID-19?

No university can sustain a high rank in the long run without excellence in research. In my days, the institute was in the same league as the five oldest IITs. Currently, BITS is 16th in research publications output, which requires urgent corrective action, so we can be back in the Top 5. There are private institutions with fewer faculty and considerably less 3-year total expenditure that have managed to publish more, so it can’t all be due to lack of government funding. That said, more funding always helps, and the institute badly needs a Biosafety Level 3+ (BSL3+) laboratory to do impactful work on COVID-19, TB, etc.

What did our seniors do after graduation in your days? What did you do and why?

Many of my batchmates preferred to take up sought-after jobs in the IT sector. Others gave CAT or GRE and joined the IIMs or US universities. A handful of us chose to pursue postgraduation within India by giving GATE or similar national entrance tests; I took this route and joined the Indian Institute of Science Bangalore for my masters. I was inspired by Professor Vaid (also an IISc alumnus) and the fact that the ‘Tata Institute’ is research-intensive compared to the IITs.

You are the first BITSian to win the prestigious Rhodes scholarship to Oxford. How was that experience different from BITS or IISc? What was your doctorate on?

BITS, IISc and the IITs are elite science and technology schools similar to the École Polytechnique in France or the ETH in Zürich. It is unfair to compare them with the likes of Oxford, Harvard, etc. which are consummate universities. At my Trinity College dinner table, I could learn about the Byzantine Empire, Jamaican dance hall music, lack of ‘brown children’ in Indian kindergarten textbooks, and still debate on ontology, epistemology and the latest developments in computational fluid dynamics. For my doctorate, I developed and validated a set of analytical equations that describe what happens when charged macromolecules approach very close to a charged membrane.

Where did you work before the CSIRO? What aspects of being a scientist do you find most challenging/rewarding?

After Oxford I was a McKinsey biopharma consultant in USA, then returned to Oxford’s spin-out Oxitec as Head of Public Health to work on arboviral diseases. I then worked for the UK’s equivalent high-containment facility in Porton Down, before moving to Australia.

The most challenging and rewarding aspect is to understand and address the social science context of the scientific problem we are trying to solve. For instance, safety and efficacy are necessary but not sufficient conditions for a vaccine to be successful. Unless they address unmet needs of the society in a timely and cost-effective manner, they won’t be rolled out. I have two daughters (the youngest we adopted), so my other challenge is maintaining work-life balance, especially in the midst of responding to a pandemic.