Written: September 2022
Humans have been very fortunate to have been protected by vaccines for more than two centuries. The path to get from the identification of an infectious disease to have an effective vaccine is complex, to put it mildly. The issues include research and development to get the right recipe, testing, regulatory approvals, procurement of dependable funding, scaleable manufacturing, equitable and efficient distribution, assured safety, management of public fears of inoculation, and global political considerations. Despite the complexity, what used to take years, now takes months. Politicians pushing to go faster may have helped, but it mostly has to do with bioinformatics, genomics, AI, machine learning, cloud computing, and synthetic biology. As I have written before, I believe the transition from years to months will continue to days and maybe even hours.
At one point, there were nearly 100 vaccines under development for COVID-19. About 20% of them are based on DNA or RNA. The RNA approach has shown to be best for speedy development. Efficacy of the two leading vaccines has shown to be more than 90%, compared to 60% for flu vaccine. Safety data has been very good.
The long-term implication of the RNA development and manufacturing platform is the potential to respond quickly to new variants and even new viruses. An antigen from a new virus or variant can be sequenced in hours, and the genetic code for a vaccine can be manufactured using a tested and pre-approved platform. If so, it would eliminate the traditional lengthy process for developing a new vaccine. The current pandemic became a testbed for the next generation of vaccine technologies.
But what is RNA? Let’s start with DNA to put things in perspective. DNA is material found in nearly every cell of every living organism. The structure of DNA is the famed double-stranded helix which some say looks like a twisted ladder. Our DNA contains genetic information which acts like a recipe enabling us to develop, grow, and reproduce. Although our environment, lifestyle, and nutrition have an influence, our DNA is primarily responsible for our development. The recipe informs our cells how to produce the tens of thousands of human proteins which form our cells, tissues, and organs.
Gregor Mendel has been called the “Father of Genetics”. Like Vint Cerf, who has been called one of the fathers of the Internet, there were several fathers of genetics. It started in 1866 when Mendel was the first to note human characteristics get passed down from generation to generation. He coined the terms of dominant and recessive. Numerous discoveries about DNA occurred over the next 87 years. In 1953, Watson and Crick published a detailed paper about DNA’s double helix structure which has become symbolic.
As early as 1939 scientists suspected there was something special which provided the recipe. The something was RNA. There are three types of RNA, but the one most relevant in the current vaccine development is messenger RNA, or mRNA. Using a process called transcription, mRNA copies genetic code to ribosomes, which act like a kitchen where the production of proteins take place.
Scientists have dreamed about the endless possibilities of synthetic mRNA. Researchers understood its role as a recipe book for the body’s trillions of cells, but their efforts to expand the menu have come in fits and starts. The concept: By making precise tweaks to synthetic mRNA and injecting people with it, any cell in the body could be transformed into an on-demand drug factory.
Moderna and Pfizer BioNTech are quite different companies but, in both cases, there were dedicated researchers with a passion and a vision about mRNA. The government pouring huge amounts of money into the research was no guarantee, but it certainly helped. The idea was to inject the synthetic mRNA into a patient, and the patient’s cells would create a protein which would fight the virus. The challenge was the patient’s body would treat the mRNA as a bad actor. The two companies, in different ways, devised a tailoring of the mRNA so it could get past the patient’s rejection. The results were 90% efficacy.
As of September 4, 2022, a total of 12.5 billion vaccine doses have been administered. This was no small feat. The ingredients list contains a lot of syllables and unpronounceable names. Unfortunately, there is a lot of misinformation on the Internet and some media outlets about what is in the vaccines. Following is a high-level summary of things which are not in the mRNA vaccines. No preservatives, no antibiotics, no medicines or therapeutics, no tissues like aborted fetal cells or any materials from any animal, no food proteins, no metals, no latex, and no manufactured products like microelectronics, electrodes, carbon nanotubes or other nanostructures, or nanowire semiconductors. The vaccines are not manufactured in facilities which produce food products. The vial stoppers used to hold the vaccine do not contain latex.
What are the ingredients? The various mRNA vaccines such as made by Pfizer BioNTech and Moderna contain about a dozen similar ingredients. Moderna ingredients fall in three categories. The mRNA provides instructions the body uses to build a harmless piece of a protein from the virus which causes COVID-19. This protein causes an immune response which helps protect the body from getting sick with COVID-19 in the future.
The second category is lipid nanoparticles. These are spherical vesicles, a thin-walled sac filled with a fluid, which help deliver the mRNA to the cells. This is a technology new to mass production and is incredibly complex. The vesicles must be small enough to enter our cells. When I say small, I mean on the order of 100 nanometers. There are 25,400,000 nanometers in one inch. A human hair is approximately 80,000- 100,000 nanometers wide.
The third category includes a half dozen salt, sugar, acid, and acid stabilizer ingredients. These ingredients work together to help keep the vaccine molecules stable while the vaccine is manufactured, frozen, shipped, and stored until it is ready to be given to a vaccine recipient. After the body produces an immune response, it discards all the vaccine ingredients, just as it would discard any substance that cells no longer need. This process is a part of normal body functioning.
The process to put all this together and make it safe and effective is mind boggling to me. Groups of scientists, doctors, researchers, and engineers made it happen for the 12.5 billion doses with many more to come. The best news is the manufacturing process has been tested, validated, and approved. When a new variant or virus comes along, and they will, the companies can do the genetic sequencing, tweak the recipe, and start manufacturing very quickly. I expect we will have one annual vaccination which will protect us from all known viruses and variants which can attack our respiratory system. Looks likely a year from now.
In the meantime, next week, I will get the new bivalent booster plus a quadrivalent flu shot. The bivalent booster protects against the original COVID virus plus Omicron and other variants. The quadrivalent flu vaccine protects against four different flu viruses, including two influenza A viruses and two influenza B viruses.
Epilogue: The more I read and learn about genetics, the amount I don’t know grows more rapidly. I plan to take an MIT biology course online at edX.org.