Number 1 Scientific Breakthrough of 2020: The mRNA Vaccine
If you haven’t yet, check out our countdown of the Macromoltek team’s top 9 favorite scientific breakthroughs of 2020 here. Our top pick is:
01. The Development and Approval of The SARS-CoV-2 mRNA Vaccine
Without a doubt, everyone in the world was affected by the COVID-19 pandemic. Scientists in academia and industry changed gears on the spot to tackle this problem from all possible angles. To our advantage, coronaviruses were first discovered in 1965 as the causative agent of mild respiratory illness or the common cold, and scientists have been studying them ever since. Moreover, these RNA-based viruses have caused other epidemics in the past — discussed here in greater detail — which have provided us with valuable insights that made a difference this time around.
In historically record time, vaccines were developed and entered distribution. There are multiple key elements that came into play to allow scientist to create this vaccine promptly:
A. The rapid DNA sequencing of the virus
DNA sequencing is a pillar in modern biotechnology. The possibility of reading the genetic material of living organisms was not always as accessible as it is today. Both in terms of cost and efficiency, nucleic acid sequencing used to be out of reach for most research facilities. From the 2000s to the present time, genome sequencing has leaped in technological advancement by incorporating: microfluidics, PCR reaction methods, fluorescent molecule markers, and robotics to increase the efficiency, accuracy, and sample volume capabilities of sequencing machines. These advancements were incredibly important to allow scientists to obtain a full ‘map’ of the SARS-CoV-2 genome in less than 1 month at a relatively low cost.
B. The structure determination of the spike protein
Since coronaviruses had caused epidemics in the past, scientists were aware of which proteins to look for when designing a treatment or vaccine. Dr. Jason McLelland and his group at our hometown university, The University of Texas at Austin, were quite knowledgeable of the molecular structure of coronavirus proteins. As soon as the genomic information was made available, they were ready to get to work. Utilizing Cryo-EM and their previous knowledge of other coronavirus spike proteins, they determined the structure of the SARS-CoV-2 Spike protein 1 and published their findings within the first quarter of the year. Many efforts in testing potential therapeutics, including both small molecules and biologics, as well as vaccine development efforts, required this information to move forward.
C. Advancements in mRNA vaccines
Vaccines have been an important tool for humanity, with early inoculations dated as far back as 200 BCE and their widespread use starting around the 17th century. The main concept in their mechanism of action is giving the human body ‘a sample’ of the disease, which stimulates our immune system until we develop antibodies to fight off the infection once we become exposed. These ‘disease samples’ started out being rather rustic, exposing patients to infected skin flakes or scabs. Later, techniques were developed to create inactivated or live-attenuated pathogens, as well as more refined techniques where a tiny piece of the pathogen, such as purified protein, is the main component of the vaccine.
For decades, scientists have investigated if vaccines can be reduced to their simplest form: nucleic acids. If DNA were to represent a ‘cookbook’ for how to make an organism, mRNA would be a single recipe within that book, and the dish would be the protein. The idea that we could introduce a ‘recipe’ of how to make a tiny piece of a pathogen to allow our immune system to read it, ‘train’, and develop immunity sounds simple enough. The main problem is that our bodies know how to recognize recipes that are not from our cookbook, meaning that any foreign mRNA molecule would get destroyed before it produces the pathogenic protein that would train our body. Dr. Katalin Kariko, senior vice president at BioNTech, spearheaded many mRNA studies since the 1990s that were vital for the development of the COVID vaccine. Particularly, in 2005, Dr. Kariko published a study that delineated the mechanism through which our bodies recognize foreign mRNA and found a simple solution to safely introduce mRNA into our bodies. If we go back to our recipe analogy, this would look like a recipe with a post-it note specifying it is not a ‘human’ recipe, in the case of mRNA it meant having a methyl modification. The solution being the removal of that chemical modification. This discovery became the foundation for the development of safe mRNA therapeutics.
There are numerous advantages of mRNA vaccines over traditional vaccines. Traditional vaccines can take months to years to develop, while mRNA vaccines can be designed within weeks of obtaining the DNA sequence — as was the case for COVID-19. Conventional vaccines are grown in chicken eggs or mammalian cells, while mRNA vaccines can be synthesized rapidly in a lab. Compared to growing live pathogens, producing a nucleic acid molecule provides improved biosafety conditions during manufacturing. Importantly, mRNA vaccines have the flexibility to be quickly modified to be effective against new strains without changing the production pipeline. In fact, most of the teams who worked on the mRNA vaccine development from multiple companies are already taking action and proactively designing COVID-19 vaccines that may be effective towards a broader range of viral variants.
Years of mRNA research, advances in lipid nanoparticles, pathogen characterization techniques, and improvements in technology converged to bring a solution to this global crisis.
Concluding remarks
We are living in exciting times. Many fields of study are intersecting each other to create technologies that used to only exist in scientists’ wildest dreams. Interdisciplinary advances, such as the ones highlighted here, come after decades, or even centuries of work, and have proved essential during this unforeseen crisis. We cannot help but wonder how these recent breakthroughs will come together in the future. Will we be taking DNA synthesizers on our planetary explorations? Will there be a future where superconductors and artificial intelligence allow medical imaging to give you an accurate diagnosis within minutes? Will we clean our oceans with biotechnology? Will solving the protein folding problem open the door to a new era of drug and enzyme design?
What a wonderful thing science is.
