I got my first shot of the COVID-19 (Moderna) vaccine, and to celebrate this event I thought I would write about the vaccine and how societies in general reacted to vaccines in the past. Before COVID-19 we were spoiled. The massive success of vaccination in eradicating or diminishing disease had made it possible for people to enjoy the luxury of dabbling in antivaxxer pseudoscience and indulging in vaccine hesitancy. Until COVID-19 hit us, many people had not experienced the fear for their loved ones that people had experienced in the times before vaccines were available during epidemics of diseases such as polio. Nowadays few people remember the peace of mind and hope that vaccines brought to humanity. The bliss experienced by people finally rid of the scourge of certain diseases such as smallpox, which periodically decimated entire communities, is difficult to describe today. To give you an idea, let me just present below a translation of a stanza of the poem Oda a La Vacuna (Ode to the Vaccine) by the Venezuelan poet Andres Bello written in 1804 (he mentions Jenner, the discoverer of the smallpox vaccine, and Carlos, the King of Spain who promoted the distribution of the vaccine). “Supreme Providence, the tearful echoes of the disheartened man at last arrived to your abode, and you raised your righteous arm from his neck; admirable and amazing in your resources, you gave the man medicine, wounding the herds with contagious plague; you opened for us new springs of health in the sores, and you stamped upon our flesh a miraculous seal that the black pox respected. Jenner is the one who discovered under the roof of the shepherds such a precious find. He joyfully published to the universe the happy news, and Carlos distributes to earth the gift of heaven.”
Although many individuals today are too far gone down the rabbit hole of antivaxxer irrationality to be redeemed, now that science has delivered for humanity an effective vaccine against COVID-19 in record time, I hope that many people will regain a measure of gratefulness and respect for vaccines and for scientists. The COVID-19 vaccine has an amazing history involving failure, tragedy, perseverance, and triumph that is worth reading about. This vaccine was made possible by a remarkable confluence of several technologies produced by numerous discoveries in basic and applied science. Others have already reported in depth on these stories, so here I will provide a summary of the most salient points with references. A couple of decades ago, the scientific establishment was skeptical of the concept on which the Moderna and Pfizer vaccines are based: using mRNA to direct the production of a viral protein and generate an immune response. This was mostly due to the fact that the mRNA triggered an immune response against itself that interfered with its effectiveness. A Hungarian born scientist in the United States, Dr. Katalin Karikó, spent many years fighting against this skepticism and paying dearly for it in terms of stress, remuneration, and career advancement. Finally in 2005, Dr. Karikó and a collaborator, Dr. Drew Weissman, succeeded in modifying the molecule to make it more stable. Two emerging biotech companies, Moderna (founded in 2010) and BioNTech (founded in 2008) licensed the technology from Karikó and Weissman and began working on a series of applications for the modified mRNA. When the COVID-19 pandemic broke out, they were ready to hit the ground running with the technology. In 1966, a trial of a vaccine against a virus called respiratory syncytial virus (RSV) went horribly wrong. The vaccine not only was unsuccessful in protecting immunized children, but it actually worsened their response to the virus with 21 children being hospitalized and 2 dying. Dr. Barney Graham, an American virologist, devoted his career to finding out what had happened. Finally, he and his colleagues figured out that the protein the viruses use to fuse with human cells changes shape in the process. Antibodies against the pre-fusion protein were effective against the virus, whereas antibodies against the post-fusion form were not and actually made things worse. Dr. Graham and his colleagues applied this knowledge to develop a vaccine against a type of coronavirus that appeared back in 2012 called Middle East Respiratory Syndrome (MERS) which could not be tested because the disease did not reach epidemic levels. However, by 2017 they had figured out how to develop a vaccine against coronaviruses in general. Graham teamed up with Moderna to incorporate his research into the design of mRNA vaccines. When the COVID-19 pandemic began, Graham’s research and experience with coronaviruses allowed Moderna and other companies to design a vaccine for the right form of the protein. A seldom mentioned issue is that the mRNA in the vaccines is a large and fragile molecule that is easily degraded once inside the body and which does not cross cell membranes. The reason the vaccine mRNA is effective, is that the molecule is packed into vesicles called lipid nanoparticles (LNPs) which protect the molecule and allow its efficient delivery into cells. When Moderna and BioNTech began their work to find the right LNPs to deliver their vaccine mRNA, they benefited from the experience of decades of hit and miss research conducted by multiple labs that painstakingly combined different lipid components, tweaked their proportions, and tested them in cell, animal, and humans studies for effectiveness and toxicity. When the pandemic started, both companies had already produced working LNPs to deliver mRNA. And finally, there are multiple discoveries that resulted in technologies that made possible the day to day practical and theoretical work of scientists. Among these are the advances in genetic sequencing technology, which allowed the quick elucidation of the genome of the virus, and the advances in computing and bioinformatics, which allowed the visualization and analysis of sequences and molecular structures, and the quick sharing of information among scientists worldwide. A lot of things have improved in our societies since Andres Bello published his poem back in 1804. Science has spearheaded a revolution that has increased human lifespan and quality of life, and vaccines such as the COVID-19 vaccine have been an essential part of this process. Sadly, one of the things that has changed for the worst is that today poetry is no longer an art cultivated by the younger generations which consider it something old fashioned. But I am grateful for this gift that science has given to us, and I hope somebody considers composing an ode to the COVID-19 vaccine! The photograph is property of the author and can only be sued with permission.
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