As a highschool student with a strong interest in genetics and immunology, the developments of the past few weeks have been exciting and provided much needed hope. Biological sciences to the rescue of humanity – YES! The first two vaccines to receive emergency use authorization by the FDA are both mRNA vaccines. I hope that this marks the beginning of the end of this pandemic that has had such a devastating impact on all of our lives across the globe. For this PBH (philosophy of biology and health) blog post, I want to focus on the Scientific Lens to explain the cause of my excitement. Also, as I zoom out and think about these developments from a broader, multidimensional PBH perspective, I want to share some new questions that have come up.
On December 11, 2020, the FDA authorized for use the Pfizer and BioNTech’s mRNA COVID-19 Vaccine (FDA). The first doses were administered to healthcare workers from December 14, 2020. Just the following week, on December 18th, 2020, Moderna’s mRNA vaccine also received FDA emergency use authorization (FDA). The mRNA vaccines were developed in record time and faster than the traditional vaccines that are yet to be approved by the FDA.
Both of these vaccines have gone through extensive trials, proven to be safe and highly efficacious after two doses. However, many people are still wary about what the new mRNA vaccine entails. A recent survey (WebMD) found that only 60% of the American population are “certain” or “probably certain” they will get the vaccine. To achieve herd immunity, professionals believe 75%-85% of the population will need to be vaccinated. What’s causing this reluctance and lack of faith in modern medicine? Yes, wild conspiracies and fear mongers influence this opinion. However, I think one of the primary causes for this uncertainty is a lack of knowledge about this new vaccine technology. So, what really is the mRNA vaccine, and how does it differ from a conventional vaccine?
Conventional vaccines have been utilized since 1796, when english doctor Edward Jenner produced the first vaccine for the Smallpox disease. This primal vaccine was used by introducing cowpox into a young boy. As cowpox doesn’t produce symptoms for humans, the boy’s immune system was able to learn and fight off the non-threatening virus. When introduced to smallpox, the boy was not affected as now his body had the antibodies to fight off the disease. This was a huge breakthrough for the scientific field, and for over the last 200 years this method has been used to some extent. Now, common vaccinations for diseases such as Chickenpox, measles, and the flu use various forms of this method. Overarchingly, they work by introducing a harmless, denatured version of the virus into the body, allowing the immune system to build the proper antibodies and immune response to fight it off. Then, when exposed to the pathogen in the real world, the body already has it’s defense system built up and prepared to effectively stop the spread of the disease.
mRNA stands for messenger RNA, and it is an important part of the DNA replication process. In DNA replication, the first stage is called transcription. An enzyme called DNA helicase “unzips” the double-stranded DNA, leaving one side of the genetic material exposed. mRNA reads the genetic code of nucleotides A, T, G, and C, creating a complementary strand of mRNA utilizing the nucleotides T, U, C, and G respectively. This strand of mRNA leaves the nucleus and nuclear envelope, carrying the new RNA codes to the cell’s ribosomes. These ribosomes read the mRNA instructions, build the corresponding amino-acid chains, thus producing the specific proteins. Scientists are now able to leverage the role of mRNA to develop new medications and treatments. Synthetic mRNA, precoded for a specific protein, can be distributed to many cells in the body. From there, human biology takes over. The synthetic mRNA is taken up by the ribosomes, continually building up the amino acids and proteins, allowing them to be expressed in the body. This technology has the potential to be applied for many different medical uses, with the most current and notable one being the COVID-19 mRNA vaccines (Moderna).
Early in the outbreak, scientists sequenced the COVID-19 virus and published its genetic code. Scientists discovered that this virus is characterized by “spike proteins” on its surface. Scientists used these protein spikes as the target for vaccines and treatment, as opposed to injecting a fully-structured denatured virus. While BioNTech and Moderna worked on their vaccines separately, there are a lot of similarities in the underlying science. Using the genetic code of the COVID-19 virus, scientists use complementary RNA base-pairs to build strands of synthetic mRNA, with the instructions to build the specific viral spike proteins. The synthetic mRNA strands are delicate, and need assistance entering human cells. They are packaged in a specially designed oily coating, created with lipid nanoparticles. Once injected into the body, these oily capsules bind to some cells and break apart, inserting the mRNA material into the cytoplasm. These mRNA strands make their way to the cell’s ribosomes, where the mRNA sequence is read repeatedly to produce the viral spikes. These viral spikes are then pushed to the surface, protruding from the cell membrane as either displayed fragments or full spikes.
Once the cell ultimately dies, the mRNA is destroyed, disallowing it from spreading and taking over other cell functions. This acts as a safety feature for the vaccine, ensuring that only a select few cells are taken over. Upon the individual cells’ destruction, the protein spikes and debris float throughout the body, unable to do real harm. However, the foreign material attracts the attention of the body’s immune system – specifically antigen-presenting cells and T-cells. The antigen-presenting cells take in the spikes and present at its surface, while helper T-cells can send a signal to the rest of the immune system. This calls another type of immune cell: B-cells. These B-cells can hit and lock into the protein spikes, and with activation from helper T-cells can begin forming antibodies to identify the virus. Lastly, killer T-cells are activated, and trained to recognize and kill the virus upon contact. Memory B and T-cells store this information, offering protection in the long term. This shortens the reaction time of the immune system upon exposure to the virus, allowing it to utilize the “alarm” system and its antibodies to destroy the virus before it can continue to replicate. In this way, the vaccine utilizes the new mRNA technology to protect the vaccinated individual and break the chain of transmission.
These two COVID-19 vaccines are the first ever mRNA based product to be approved by the FDA. This miracle of being able to use the human body as a factory to custom manufacture targeted proteins has the potential to protect humans from other infectious diseases and genetic disorders. I am very excited about the potential this new genetic technology has to do so much good for human health!
From a PBH perspective, as I zoom out beyond the Scientific lense, these promising new scientific developments also raise some important questions and considerations:
- What are some of the other most promising applications of this new mRNA technology?
- How can we make these new, promising mRNA vaccines cheaper and more accessible beyond the rich, developed countries?
- Should the intellectual property (IP) associated with the COVID-19 mRNA vaccines be made freely available to developing and poor countries, at least until this pandemic ends?
There will be other opportunities to address these questions. But for now, I want to take a moment to marvel at this miracle of science!