Guest Author: Dr Naveen Surendran
An invisible enemy taking over the planet killing the old, poor and the vulnerable while locking up the rest. Superheroes in white coats fighting day and night to rescue the world – sounds straight out of a science-fiction thriller, right? Except this was the reality of the world for the past almost two years. The world suddenly became disrupted and dysfunctional for too many people – disbeliefs, denials, discomfort and deaths. As of this writing 266 million people got infected and 5.27 million people died. An observer from space though wouldn’t realize it with manmade structures intact and no major natural disasters. Death and devastation laid bare the weaknesses of the most sophisticated human generation. However the past two years has been a case in point showcasing the resilience, resourcefulness and resolve of humanity to overcome any adversities.
Thanks to an extraordinary period of science reporting and myth busting through media – lock downs, quarantines, PCR tests and viral variants became routine discussions in our conversations. Suddenly an obscure epidemiological term R0 value, average number of people that one COVID-19+ person can infect, became an everyday jargon in the early days of COVID. COVID-19 taught the entire population the fundamentals on disease transmission, public health, how vaccines are developed so much so that even toddlers started reminding adults of mask wearing and hand washing. This is the first pandemic in a digitally attuned world and all stories beyond borders played real time in our phones. More than the health and wellbeing of people, this pandemic had social and economic devastation on its wake wiping out >5% of global GDP.
Remember the early days when the news broke about the illness in Wuhan, initial hopes in vain that it wouldn’t spread from human to human and then the short-lived optimism about the spread will be limited in a few countries as happened with the previous 2003 SARS epidemic. Contrary to all those beliefs and calculations, in a well-connected world the disease spread like wildfire.
It was quite a remarkable time to be a scientist especially in the area of vaccine development. Suddenly being an immunologist, virologist, epidemiologist and/or an infectious diseases expert became much cooler than being a sports celebrity or a movie star. We read countless heroic stories of doctors/nurses/first responders who saved millions of COVID patients. Here, I want to mark a few milestones on the scientists’ incredible journey to understand the mysterious illness, identify the cause, publish the genetic code, develop the diagnostic test and finally to launch a lifesaving vaccine.
In December 2019 there were reports of an outbreak of pneumonia in Wuhan, China caused by what was then called 2019 novel corona virus (2019-nCoV). As the cases rose it was Professor Zhang Yongzhen who sequenced and published the viral genome on January 11, 2020. This helped Scientists around the world to learn more about the virus and establish that this virus was different from the one that caused the 2003 SARS outbreak. By February more and more countries reported cases and it looked like the world was bracing for a pandemic. On February 11, the new virus was renamed as SARS-CoV-2.
The world has seen pandemics before but this time the scale, speed of its spread and its peculiar epidemiological characteristics – that it affects the elderly and vulnerable more than others – made it look particularly worse. The need for a vaccine was clear but this time we needed it faster. This was the scenario that the scientists were predicting would happen and that we need international collaborations on disease surveillance, information sharing and infrastructure development to quickly control the spread of any pandemic. Luckily this time we saw a new technology in vaccine development that was getting ready for prime time to accept that challenge – mRNA vaccines. Messenger Ribonucleic Acid, mRNA are essentially messengers with genetic information that tell the cells in our body which proteins to make. However, for a successful COVID-19 mRNA vaccine, scientists needed to be ready with 3 things – the right SARS-CoV-2 immunogen (protein that elicit an immune response in humans), stable mRNA platform and a lipid nanoparticle delivery system.
The mRNA technology was long time in the making. First discovered in 1960 there were no tools available to synthesize mRNA in the laboratory until 1984 when an RNA synthesis enzyme was developed to make biologically active mRNA. It was 4 years later in January 11, 1988 (exactly 32 years earlier to the publication of SARS-CoV-2 genome) when Robert Malone, a PhD student, mixed mRNA strands with fat droplets and poured on to human cells making the observation that those human cells absorbed mRNA and started producing proteins encoded by them – first observation that mRNAs can be passed on to living cells to produce proteins. But mRNA degrades so fast and it was expensive to deliver them as a vaccine or drug. Separately scientists from late 1970s were trying to develop fatty membranes called liposomes to transport mRNA without degradation to cells. It took another 5 years before demonstrating mRNA encapsulated in a liposome can generate immune response in mice against flu virus in 1993. But the cost to optimize the mRNA platform for large scale manufacturing was prohibitive and many companies focused on DNA vaccines instead. Breakthrough came in early 2000s when it was discovered that modified mRNA can evade body’s immune response to avoid inflammatory reactions to mRNA. This key finding came in 2005 from the work of Katalin Kariko and Drew Weissman at the University of Pennsylvania after years of failed experiments to transform mRNA into a drug platform. Around the same time researchers Pieter Cullis, Thomas Madden and Ian MacLachlan developed a 4-component lipid nanoparticle scalable delivery system that can deliver mRNA efficiently. Both these findings made an impact and gave momentum for many mRNA companies to spring up and human clinical trials for mRNA vaccines to start.
Scientists knew that the SARS-CoV-2 virus used spike protein to attach and get into human cells to cause disease from the previous SARS outbreak in 2003. As soon as Professor Yongzhen published the SARS-CoV-2 genome, researchers Barney Graham and Jason McLellan used structure based vaccine design to develop stabilized versions of spike protein (immunogen) and mRNA constructs for the immunogen were made by various vaccine companies. So the scientific field was ready to tackle SARS-CoV-2 when the World Health Organization declared COVID-19 as a global pandemic on March 11, 2020. The rest is history. Within 8 months by conducting pre-clinical and clinical trials in parallel, leading vaccine companies could show the safety and impressive efficacy of COVID-19 mRNA vaccines – the first licensed mRNA vaccine ever. Thousands of scientists across the globe worked day and night to achieve this goal and to save millions of lives. The fight continues as the virus mutates while spreading with new variants emerging and the only way to stop it is by getting the most people vaccinated around the globe.
Looking back, this is an extraordinary story of human determination, scientific prowess and international co-operation. Currently the largest vaccination campaign in history is underway with 8.18 billion doses delivered in 184 countries. As Louis Pasteur once said ‘Chance favors the prepared mind’ and scientists were prepared to take on this chance.