The Race to Resolve COVID-19: Invisible Steps for Extraordinary Progress

A s a scientist, it has been amazing to watch the release of paper after paper offering more information about the coronavirus and how to fight it. In just the last year, 198 vaccine candidates, 2,388 clinical trials, and 120,000 peer-reviewed publications emerged in response to COVID-19. To give you an idea of the rapidity with which research is progressing, the entire genome of the virus causing COVID-19 was sequenced within the first two months of the virus being identified. In comparison, the Human Genome Project was a thirteen-year study.

By finding the virus’s genetic code, scientists have revealed all the viral machinery that they could target in order to disrupt the virus’s function. Within a month of mapping its genetic code, scientists had uncovered the 3D structure of the physical component of the virus that enables it to invade human cells. Solving this structure equipped scientists with a perfectly detailed picture of what would become the target for a large proportion of future therapeutics.

After this, the research field exploded with new advances: massive studies were (and continue to be) carried out to rapidly screen, in a single experiment, huge numbers of possible drug candidates for the virus. Super high throughput methods were used to quickly characterize recovered patients’ antibodies to find one that could be repurposed as a virus-neutralizing drug. Tons of vaccine platforms were quickly redesigned for COVID-19. Innovative diagnostic platforms were reworked within a matter of weeks to detect the virus.

From the vantage point of the general public, these proceedings may have felt hasty, especially as the media warped scientific findings with catchy titles or misconstrued descriptions. But from the vantage point of a scientist, it is astonishing to behold. As someone with knowledge of the data beyond the titles, I have watched these technologies unfold over time. In fact, most of the advancements of the COVID-19 pandemic were years, even decades, in the making.

Consider antibody drugs. Within mere months of the identification of COVID-19, there are already at least eight antibody drug candidates proceeding to clinical trials. And yet, the tools that enable this date back to 1975. Before then, scientists had to discover what an antibody was in the first place, figure out its function, determine how it was made, and then create ways to detect and measure it. It was only a Nobel prize-winning discovery in 1975 that gave us the technological ability to produce specific antibodies that bind to a desired target in vitro. Even then, it took another decade for the first antibody drug to enter the market. Since then, countless techniques have been developed to produce antibody drugs more quickly, with better binding to its desired target, and more effective function in the body.

Behind the scientific community’s incredibly rapid response to the pandemic is the accumulation of decades of meticulous, collaborative work. Contained in the apparently dizzying pace of scientific advance today is the collection of so many individual moments of inspiration, hours of torturous thought, weeks of grueling experiments to yield a single ounce of insight, and years of effort to develop the scientific tools necessary for each subsequent advance. It is only the combined effort and achievements of countless scientists over the years that has prepared the scientific community as a whole to be this impressively responsive in the face of the COVID-19 pandemic.

The importance of that work seems so clear to us now, but the truly important advancements came with no one there to applaud the incremental steps. Certainly, those scientists working throughout the years had some inkling of an idea that their work could impact humanity; still, there must also have been times when they felt like they were going nowhere. In the heat of any scientific pursuit, it can be difficult to see the progress being made.

I think of AstraZeneca's ChadOx1 vaccine as an example of this reality. It is one of the leading COVID-19 vaccine candidates and the one with the oldest characterization and closest match to the hypothesized optimal immune response. The design of this particular vaccine was studied for protection against MERS coronavirus, Ebola virus, Chikungunya virus, and tuberculosis. It has been extensively studied in animals, from mice all the way up to non-human primates, which is the next-best thing to actual human trials. This design has also been thoroughly characterized for the type of immune response it generates. Just like there are different branches in the military that specialize in different tactics, there are different branches in the immune system that defend better against some pathogens than others. This is especially true for COVID-19; the type of tactics used by the immune system to clear the virus can be the difference between recovery and death.

By virtue of their prior research, scientists had already determined before the COVID-19 pandemic which branches of the immune system were activated by the ChadOx1 vaccine, and how strong those immune responses were. They spent years slowly advancing this vaccine design long before anyone had ever heard of COVID-19. Without such foundational understanding, the record speed of vaccines progressing through clinical trials would have been impossible. In the middle of their research, however, scientists couldn't fully know how their advancements would matter in this unanticipated pandemic.

In biomedical science, dramatic progress is made in liminal space. That progress comes from graduate students pipetting clear liquids for hours. It comes from lab assistants rising daily at six in the morning to check the saturation levels on a soil sample. It comes from young researchers pouring through spreadsheet after spreadsheet of data as the coffee pot brews in the corner. Just like the key developments for the ChadOx1 vaccine came prior to its use during the COVID-19 pandemic, breakthroughs aren’t completely recognized until the work crosses over the threshold of discovery. And in this sense, biomedical science is like life.

When, hopefully soon, we enter a post-COVID period, we will find ourselves in a transitional space navigating towards a new normal. Biomedical science reminds us that, though that space can be discouraging, it is also powerful. There will be times when growth is made but not felt. In those times, we should take heart in knowing that the full extent of our advancement can only be realized once we are able to look back and recognize the strides that we’ve made. Then, we will see that what we’ve accomplished during this time was truly profound.