Researchers at the Perelman School of Medicine were preparing for COVID-19 long before it arrived last year.
With the appearance of the SARS-CoV pandemic in China in 2003, events similar to those of 2020 occurred there and in 20 other countries. A similar series of events occurred in 2012, when MERS appeared near the Arabian peninsula. In what would become a familiar tableau, scientists and researchers recorded and assimilated the genesis story in animal vectors, the spread of the disease from its point of origin to other populations, elevated death rates in the old and debilitated, early alarms and mandates for public safety, and the parsing of a virus to define and clarify its infectious capacities.
There were differences between these diseases and COVID-19, of course. Both were more deadly; SARS, though highly infectious, was relatively quickly contained; MERS was limited to individuals who worked or kept infected dromedaries, and seems to have spread only among families.
If there is a fortunate iota to be derived from SARS and MERS, it's that the diseases provided an incentive for continued research in the coronaviruses and vaccine development. Notably, the platform for both of these undertakings existed at the University of Pennsylvania School of Medicine (now the Perelman School of Medicine) long before the words coronavirus and COVID-19 entered the public realm.
Now leading the Penn Center for Research on Coronavirus and Other Emerging Pathogens at Penn, Dr. Susan Weiss proposed in 2004 that SARS be considered an emerging pathogen--an official designation granted by the National Institute of Allergy and Infectious Diseases to nearly appeared pathogens that are rapidly increasing in incidence. Dr. Weiss urged, as well, that future research on SARS be based on the collected knowledge that coronavirologists had generated over more than 30 years of prior experience with the viruses.
Dr. Weiss, whose early career included work on the genetic composition of virus-specific RNA in cells producing defective deletion mutants, was drawn to coronavirus research in the early 1980s. In a career retrospective that essentially parallels the evolution of coronavirus research, she writes of mapping the viral tropism and virulence factors that contributed to the pathogenesis of the coronaviruses, and the discovery that genes outside the spike protein had a role in tissue tropism.
This means, she wrote, that the pathogenesis of the virus cannot be inferred from knowledge of the spike protein and receptor alone, adding that future studies of SARS-CoV-2 would define whether its tissue tropism parallels that of its predecessor. Subsequently, Dr. Weiss and research partner Dr. Julien Liebowitz, described research on the interaction of the protease TMPRSS2 with ACE2 in SARS, findings that suggest that cleavage by this protease may be a determinant of viral tropism and pathogenesis during the initiation of SARS-CoV infection in vivo. Many reports of the interaction of TMPRSS2 with ACE2, the receptor of choice for SARS-CoV-2, have been published since January 2020.
At about the same time that Dr. Weiss was reporting on the emerging status of SARS, Drew Weissman, MD, PhD, at the Perelman School of Medicine was describing RNA-based vaccines as a potential alternative to DNA vaccines. More than a decade later, he would propose mRNA technology as a platform for vaccination against epidemic and pandemic infection.
Between these events, Dr Weissman and research partner Katalin Karikó, PhD, discovered the means to overcome a major obstacle to mRNA therapy — an obstacle so recalcitrant that it drove researchers away from the field. RNA is a natural carrier for genetic information, but for practical use, must be synthesized. For all of its promise, however, something in synthetic mRNA was causing the immune system to mount a prolific inflammatory response.
After a decade of research, Karikó and Weissman discovered that the problem was an errant nucleoside that, when swapped out for a hybrid, eliminated the body's immune reaction to mRNA.
According to the History of Vaccines, the much-honored website created by the College of Physicians of Philadelphia, the normal course of vaccine development takes between 10 to 15 years to complete. It is not beyond reasonable presumption to conclude that the above-mentioned efforts at Penn played no small part in abbreviating that timespan to create a safe, effective COVID-19 vaccine in less than a year's time — the fastest turnaround for a vaccine in history.
More information about the current vaccine and the history of its development is available on Penn Medicine's COVID-19 Vaccine Page.