Panacea or Pandora’s Box?

The COVID-19 pandemic has thrusted two extreme ends of the healthcare spectrum into a head-on collision with each other. At one end is experimentation and research, where novel, innovative ideas are born and nurtured. A good example of this would be a new treatment for cancer. There may be known and unknown side effects, but the disease is severe enough to justify the risk. A lot of medicine falls in this category as well; doctors are prescribing treatments for individuals who have a disease already. At the other end of the spectrum is public health, which is about preventing illness among those who are healthy to start with. One example of a public health intervention is adding fluoride to drinking water. Because we are dealing with healthy individuals and a large of number of them (i.e., everyone in the general public) the intervention has to be utmost safe. ANY side effects are generally unacceptable since the exposed individuals are already healthy prior to the intervention.

So is the new mRNA vaccine a potential panacea for a near endless list of diseases or a so-called Pandora’s box?  What is an mRNA vaccine and how does it work?

The most obvious application of this nascent technology is in the field of prevention against infectious diseases.  Traditional vaccines involve exposing the immune system to a foreign protein that belongs to a virus or other pathogenic organism.  A properly working immune system will mount an attack on the foreign protein, create memory, and be ready to defend the body against it in the future.  This approach has been tested and proven, as protein vaccines have been in use for over two centuries.  All subsequent advances have been in how the foreign protein is obtained.  From laboriously harvesting proteins from viruses raised on living cells grown on plates, science has progressed and discovered how to make proteins of choice with living “factories” (commonly genetically engineered bacteria like E. coli).  The most recent breakthrough recruits the patient’s own body to make the desired protein.  Enter mRNA vaccines.  But first what is mRNA?  mRNA is similar to DNA, and it provides instructions to a cell, for example, “make this protein or that protein.” Making mRNA is incomparably easier than making proteins.  Synthesizing mRNA (in vitro transcription) is almost like actual photocopying, in a test tube with a DNA template, enzyme, and nucleotides.  A living system is not required.  To understand this huge advancement in industry, imagine comparing 3-D printing a filet mignon steak (if this were possible) to having to raise and eventually slaughter the cows to obtain that same filet mignon steak.  Think of the resources that go into raising cattle.  This is truly an industrial revolution.

Another interesting way to look at this amazing new technology is from the perspective of our bodies. Traditional protein-based vaccines entail the injection of a specific pre-determined dose or specific number of protein particles. It is fixed and finite. The body then breaks down the protein particles, and that’s it. On the other hand, the mRNA vaccine involves delivering “instructions” into cells and reprogramming cells in the body to make the protein of interest. Here is the interesting part. Each individual is unique, and one cannot predict with certainty how many or which of your cells will be reprogrammed, nor how much of the protein will be made by each reprogrammed cell, nor for how long. If the old-fashioned vaccine is like giving somebody a hundred $1 bills, the new high-tech vaccine is like leaving the U.S. Mint printing plates for the $1 bill on a sidewalk. Who will take the plates, and how many bills will the person print, and for how long? It’s a little had to say.

There are many other unanswered questions about the mRNA vaccine. If the NEW (i.e., haven’t had a chance to do long-term human studies) mRNA vaccine becomes mandatory as a public health intervention, then it will be quite interesting to see what comes out of the huge collisional experiment.

Photo credit: http://www.hhs.gov

Interesting reads: Coronavius-Induced Autoimmunity, Integration of SARS-CoV-2 RNA into Human Genome by Reverse Transcription, Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery.

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