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COVID-19 Update December 10, 2020: The Gene, The Protein, and the Miracle of the COVID Vaccine

By Dr. Arthur Lavin

Glossary

  • Virus– a type of germ that consists solely of a bit of genetic material (DNA or RNA) wrapped in a protein coat.  The coat gets the genes into the target cell where the genes force the cell to make zillions of new viruses, and on it goes.
  • Coronavirus– a species name of a number of different viruses.  Called corona because its protein coat is studded with spike shapes that form a crown, halo, or corona of spikes
  • SARS-CoV-2– the specific name of the new coronavirus
  • COVID-19-the name of the illness that the new coronavirus is causing
  • Endemic– an illness always present in a region.  One could say strep throat is endemic in the US
  • Epidemic– a sudden burst of an illness that comes and goes over a limited time
  • Pandemic– an epidemic that bursts across the world not just one region
  • Spreadability– how contagious is the disease, how many people will end up infected
  • Symptoms- the experience of being ill, for example- fever, cough, headaches, loss of smell etc.
    • Asymptomatic– literally means “without symptoms”.  For COVID-19 it refers a person infected with the virus but has no and will have not symptoms
    • Presymptomatic– This is a person who was infected with SARS-CoV-2, and will feel sick, but hasn’t yet
  • Severity– what harm does the disease cause, in terms of  how sick you get and how many it will kill
  • Mask- a mask is a loose-fitting cloth or textile that covers the mouth and nose loosely.  A surgical mask is a mask used in surgery
  • Respirator-  for the purposes of the COVID-19 pandemic and other respiratory illnesses, a respirator is a mask that fits very snugly or tightly to the user’s face.  An N95 mask is a respirator.
  • Personal Protective Equipment (PPE)- PPE are any item that covers any part of the body with the design and intent of keeping viruses in the environment from infecting the wearer of the PPE. PPE’s include all masks (which includes respirators), face shields, eye shields, gloves, gowns.
  • Ventilator- a ventilator is a machine that can force a person unable to breathe to inhale and exhale and control both effectively.  They are sometimes called respirators, but during this pandemic the word respirator is now reserved for reference to a tightly fit mask.
  • Live Virus Swab– this is the swab which attempts to swipe live virus from one’s nose or throat to see if you are currently infected.
  • Antibody Test- (aka serology test) this is the blood test which looks for antibody to the SARS-CoV-2 virus to see if you have been infected in the past.
  • Vaccine Terms
    • Vaccine or Immunization– a dose of a substance that activates your immune system, as if you have the actual infection you are hoping to prevent, leaving you in fact protected from having that infection.
    • Efficacy– the percentage of people immunized with a particular vaccine who will not get infected if exposed to the target infection.  For example, a COVID-19 vaccine will be said to be 95% effective if 95% of people immunized with that particular COVID-19 vaccine will not get COVID-19 if exposed to COVID-19
    • mRNA– DNA works by dictating exactly which proteins your cell will make.  The message on how to construct each protein is delivered to the cell machinery that makes proteins by a piece of genetic material called messenger RNA, or mRNA
    • mRNA vaccine– an mRNA vaccine places a small bit of mRNA code that makes your cells make a protein that is the protein from a virus that alerts your immune system and activates it to make protections against you being infected
    • Viral vector vaccine– a viral vector vaccine takes a harmless virus that is known to infect people reliably and places that weakened virus in a person where that virus will in fact infect the person.  The virus is not only weakened, but also attached to a set of genes  that makes your cells make a protein that is the protein from a virus that alerts your immune system and activates it to make protections against you being infected.

 

The Gene, The Protein, and The COVID Vaccine Story

On December 8, 2020, the first person in the world received a COVID-19 vaccine as part of regular care, not as part of a study.

This moment ushers in an extraordinary moment in the history of all humanity- many, many years of searching for a path to develop vaccines for dangerous diseases that burst on the scene has led to a truly monumental success, and at the same time what may prove to be a historic refusal to save lives.

To understand the nature of the dramatic breakthrough we are living in right now, we need to talk about the basic strategy of an immunization and how all depends on one type of molecule- the protein.

The Protein

The word protein comes from the Greek word protos which means first, and it’s a good name for this sort of molecule, because in many ways, it is the first foundation of all of life.  We tend to give that eminence to our DNA, our genes, but genes only exist to create proteins.   It is proteins that deliver all the major functions of life, directing and making happen essentially every chemical reaction that defines life itself.

How do proteins manage the chemistries of life?  The secret lies in their remarkable structure.  Proteins are astounding sculptures, and they carry the functions of life literally in their shape.

Their nearly infinite variety of shapes derive from a very simple underlying structure.  Every protein, from virus, to tree, to your cousin, is a long, long chain of amino acids.

An amino acid is a small molecule defined by having two ends- an amino end, and an acid end.  Without getting too technical, it will be noted that the amino end is essentially one nitrogen atom.  And the acid end is essentially a carbon dioxide molecule.   Between them is where the amino acid is defined.  Some amino acids in our body have names that are familiar:  glutamine, lysine, phenylalanine.  Others less so.

In our human bodies, all the myriad proteins are made up of just 20 amino acids.   But those 20 basic units can combine in limitless ways.  I like to think of a protein as a word with hundreds of letters, and the amino acids are the 20-letter alphabet that can write any book.

To give you an idea of scale and function, take a most familiar protein- hemoglobin.  Hemoglobin is a protein with four chains of amino acids, each chain has nearly 150 amino acids linked together, so the hemoglobin protein has nearly 500 amino acids linked together.  Each amino acid has its own shape, and so every chain of amino acids has a unique shape.   The nearly 500 amino acids gathered to make hemoglobin create a shape that uniquely is suited to hold 4 atoms of iron.  It holds them in a way that lets the whole assembly grab oxygen in the lung, and deliver it to tissue.  These nearly 500 amino acids line up in just the right very complex 3-D sculpture to hold atoms of iron so well that we can breathe and live!

Such magnificent sculptures are also seen in our immune system.  It is the shape of protein chains that determine if a protein we call an antibody will attach to, that is recognize, a protein on the surface of a germ.  No recognition, no immunity, germ wins.

How an Immunization Relies on the Sculptural Uniqueness of  a Protein to Work

Every immunization that has ever existed uses this fact to work.  The basic point is since proteins come in such a truly infinite variety, every type of cell and virus literally has its own unique set of proteins on its surface.   And our immune system basically operates by looking for unusual such identifying proteins on the surface of alien cells or viruses, aka germs.

The other amazing property of proteins is that our immune system can craft a sculpted protein that can match trillions and trillions of proteins.  Take any germ, any new or old germ, virus, bacteria, or parasite, and our immune system can craft a protein to match each germ’s unique protein on its surface.  This matching protein creates the antibody unique to that germ, but the same sculpted protein is what helps one’s T-cells create a whole system of immunity to destroy that germ whenever it dares to appear.

It is a truth that when we say someone is immune to a particular germ, what is really going on is that our immune system has put together a very specific, unique chain of amino acids, in just the right sequence so that the crafted protein folds into a sculpture that will bind to that germ’s identifying protein on its surface.

And so an immunization, until very recently, has always involved placing the identifying protein from a germ’s surface into a body, and stimulating that body to create the immune system protein that will allow it to make antibodies, T-cells, and all other attack modes to wipe out the germ.

That’s how the tetanus, meningitis, polio, hepatitis, HPV, all immunizations work.  All of them.  The only twist is that a small number of immunizations actually place a live germ in the body.  This is the story of measles and chickenpox immunizations.  A weakened form of these viruses is injected, and the vaccine virus grows, exposing our immune system to all the proteins on its surface, and once again, doing what all immunizations do- stimulate our immune system to make the signature protein that our system will use to create antibodies and T-cells to bind, recognize and destroy anything with the germs signature protein on its surface.

We know this sequence works.  Find the signature protein of the germ in question, place it in the body, have the body’s immune system make its recognition protein to attack the germ.  The result?  No one in most of the world has polio anymore.  Immunizations have eliminated smallpox from humanity.  Measles could be wiped out if we wanted to.  The idea works, and works well.

The Problem with the Standard Model of Immunizations, the Protein Model

As noted, every immunization ever used has relied on placing the germ’s unique identifying protein into the body to activate the exact immune response to keep us from ever getting infected with that germ.

The problem with this approach is that we have to have the germ’s unique identifying protein in hand to inject.   If we don’t have enough of that protein, we will not have an immunization.

It turns out we cannot make proteins, they are too complex.   We are 100% dependent on the germ to make its own protein.   So to make an immunization, we have been forced to accomplish one of these two processes:

  1. Find a way to create a weakened virus that can be injected, grow in the body, and expose our body to the germ’s unique identifying protein.
  2. Find a way to figure out what is the key identifying protein, or proteins, on the surface of the germ, grow vast quantities of the germ, and purify those identifying proteins, and inject that as the immunization.

Now, here’s the problem.  You have to do one of these two processes for any immunization from a new disease from scratch.  Knowing how to identify the right protein on the tetanus germ and purify it, and turn it into an immunization doesn’t help you do the same for hepatitis, or any other germ.

So when a new germ shows up, it takes years to do either step 1 (live viral immunization) or step 2 (dead germ immunization).

That’s why it has taken over 4 years to create any other vaccine across history, until now.

Enter the Gene 

Remember we mentioned that all proteins are chains of amino acids, connected into a very long line of amino acids that once assembled folds into a unique sculpture, whose shape gives it a unique function?  And, that we tend to give DNA all the glory, the blueprint of life?

Well behind every protein is a gene, no exception.  This is an ironclad rule of all life.  This is because what DNA, or genes do, is tell a cell what sequence of amino acids to link together.  That is what a gene does, it is essentially all it does.  Set the sequence of amino acids, and you set the exact protein you make.

Now our genes are made up of either DNA or RNA, both of which are almost the same thing.  Like proteins, DNA and RNA are long chains of basic units.  Proteins are very long words made up of the 20 letter amino acid alphabet.   DNA and RNA are long words made up of a 4 letter alphabet.

For DNA and RNA the letters are not amino acids, they are very small molecules and are referred to by their initials.  For human DNA the initials are A, C, G, or T.  For human RNA the initials A, C, G, or U.  That’s it!   For both DNA and RNA any three letter combinations tell the cell to plug in a very specific one of 20 amino acids when it constructs its protein.

Enter the Gene in the Vaccine

Now think about it.  It should be dramatically easier for someone in a lab to make a series of these small molecules, than a protein, and it is.  We now have the power to take bottles of the A, C, G, or U molecules, and attach machine that will create a long chain of them.  That would be a molecule of RNA.  And, if we specify what order the A, C, G, and U molecules gather into the big chain of RNA, then we have an RNA instruction manual.

Add this RNA to a cell, and the order of the A, C, G, and U’s will dictate that cell to make a particular protein.

Can you see what this has to do with vaccine creation?

With the right long sequence made of these 4 letters, one can create a small bit of RNA that can be injected like a vaccine, that then gets your own cells to make the identifying protein of the target germ, granting you full immunity.

The Gene, the Protein, and the Challenge of New Viruses

So how does all this biology explain how we, humanity, created a whole new vaccine in months instead of years?

It goes to the emergence of new germs that have been literally plaguing humanity.  All of life dances with germs, even bacteria get viral infections.    This dance has been going on for over 3 billion years, over which time, the germ changes to get the upper hand, the target cell changes to block the new germ, and on it goes.

But as we all know, as humanity crowds the Earth, we are crossing paths with more and more animals and plants, touching and eating more types of viruses.  And the viruses have crossed over from their usual hosts, animals like bats, ducks, chickens, pigs, pangolins, chimpanzees.   Many, many times.  The list includes HIV, Ebola, West Nile, Zika, MERS, the first SARS, and now the second SARS the one that causes COVID-19.

As HIV, Ebola, Zika, and others began to crop up more and more frequently, it became obvious that humanity could no longer afford to wait 4 years to develop protein vaccines.

The search was on to find a new approach to making a brand new vaccine for any brand new virus.  Science knew that if a new virus appeared, it would take years to create a new protein-based vaccine.  And, that creating a small strip of RNA could allow very rapid creation of a new vaccine for any new virus that came to infect humanity.

Now, there are various forms of RNA, the key form is that taken by strips of genetic RNA material that carry the information of the body’s DNA to the cell’s protein manufacturing machinery.  That form of RNA is called messenger RNA, or mRNA.

mRNA Vaccines Began Their Development Many Years Ago

This new idea was NOT created in response to COVID-19.  The idea was thought of many years ago, and the first demonstration that giving viral RNA to a cell could cause that cell to make the desired protein happened 31 years ago in 1989.  A key team labored for 15 years to show how this could be done in human cells, in a human body successfully and safely achieving proof of concept 15 years ago in 2005.  Ten years ago a company called Moderna was founded to create mRNA vaccines to allow rapid creation of a vaccine to any new virus.  I am very pleased to share that a co-founder of Moderna was my previous mentor, Dr. Robert Langer, whose lab I was honored to be in at MIT in the 1980’s.  Around the same time, other such companies were founded for the same purpose, with one called BioNTech founded in seven years ago.

The point here is critical to know.  The COVID-19 vaccines being used did not begin their development a few months ago, not at all!  The technology of using mRNA to deliver the genetic code of a viral protein that will trigger one’s immune system to make one immune began in earnest over 30 years ago.

This means this vaccine is the result of decades of painstaking, likely Nobel Prize winning, work.  Work that tested ideas with extreme care, day after day, year after year.  This was not related in way shape or form to any President, any Party, or any Congress.  It was related to a constant level of support for research by all Presidents, Parties, and Congresses to fund the National Institutes of Health, but that is the only connection to our government.

After so many years of development, the breakthroughs began accumulating, and as a result, science started to be able to create mRNA vaccines by 2010-2013, about 7-10 years ago.

The last major pandemic to afflict the world erupted in 2009, the H1N1 swine flu pandemic, before the mRNA technology was ready to go.

After 2013, the world of science stood ready, waiting to see if the new mRNA approach to vaccine development could work in the setting of a new, dangerous pandemic.  During this time, the path to doing this when the alarm was raised.  During this time, steps to streamline the steps necessary to take knowing the genetic code of a new virus to a new, safe, effective mRNA vaccine were honed.

By this year, 2020, science had done its over 30 years of work, and stood ready.

The Gene, The Protein, The Pandemic

So by January of 2020, when the world knew a deadly, historic pandemic was exploding across the globe, all mRNA vaccine pioneers knew this was a true alarm and they stood ready.

The result?  In January, 2020, China made public the genetic code of the SARS-CoV-2 virus.  The virus’ genes are not in the form of DNA like ours, but RNA, like many respiratory viruses.

Very rapidly afterwards, scientists around the world began to decode the COVID RNA to determine what each segment of this deadly virus’s RNA codes for.   This was done in weeks, allowing all to know the exact sequence of the 4 RNA letters (A, C, G, and U) coded for the key protein on the surface of SARS-CoV-2- the famous spike protein.  That spike protein is the spiky element seen in every picture of this coronavirus, and in fact, the crown that it forms gives this virus its name.

Soon it was established that if a body makes the right antibodies to this spike protein, they will be immune to COVID-19, they will be safe from this dangerous infection.

Now we know the key identifying protein the immune system would construct its protection against the virus, and the RNA code that makes this protein.

The stage, carefully constructed over 30 years was set, and ready to go.

And those years of work paid off.  The concept was put into place and worked!   The RNA code for the virus’ identifying protein was crafted into a bit of mRNA that was injected into tens of thousands of people, and at least 95% made antibody to the spike protein of the COVID-19 virus enough to keep them from getting COVID-19!

This was not a rushed job.  This was the result of decades of painstaking work, done so well that when the moment of truth arrived, science was ready.  The time from the identification of the new virus to vaccine was short, not because of shortcuts, but because a very carefully constructed road to being able to do this was built over many, many years of very, very hard and careful work.

Congratulations and Hopes

We close with a hearty congratulations and high hopes.

The congratulations go out to all of humanity.  It was our combined effort that funded the work of the great scientists who created this new path.  A new path that can now create a brand new vaccine for any virus that rises up to threaten us.

The congratulations go to the scientists who learned what a protein is, what a gene is, how viral genes make viral proteins, how to find out which protein on a virus is the protein our immune system will use to craft our antibodies and T-cells to keep us from being infected, and how to make the short strip of mRNA and inject it into us to have our immune system do just that.

And congratulations to all of humanity, for being able to look forward to using COVID-19, mRNA based vaccines, to end this nightmare in the coming months!

The high hopes go to all of us.   It is the hope that everyone will know, these COVID-19 vaccines are not a rushed product, based on flimsy evidence.  It is the hope that everyone will know, it took decades of very intense and painstaking work to create a path that allows us to make vaccines to new dangers so much more rapidly.

We hope that everyone will know enough to realize the speed of these new vaccines is the final fruit of over 30 years of work to allow such vaccines to be developed in time to save lives, effectively and safely.

It appears that all that stands in our way is the choice to fear rather than to know, to stand in opposition to life-saving facts, rather than accept those facts and save millions of lives.

BOTTOM LINES

  1. December 8, 2020 will be a major day in the history of humanity.  It will forever be the first day that a person received an mRNA to keep a deadly new virus from infecting her as part of routine care, not a study.
  2. This day is only possible as the result of over 30 years of careful, steady, painstaking work to create a new path to making vaccines.  A path that allows any new virus to tell us its genetic code that makes its identifying protein, and then create a little strip of mRNA that codes for that protein.  And then turn that small strip of mRNA into a new mRNA vaccine in a matter of months, not years.
  3. It may seem the new COVID-19 mRNA vaccines from Pfizer and Moderna and others came out of nowhere in just a few months.   But only the last steps took a few months.  The ability to create a new vaccine in a few months will always represent decades and decades of careful work.
  4. We have far more to celebrate than raise worry about.  The science is very, very solid.  The processes to get here are very, very reliable.
  5. Now we need to gather together, celebrate the goods that science has so carefully cultivated overy the last 30 years, and take its fruit to save our lives and the lives of those we love.

My Takeaway – In One Sentence:

The COVID-19 mRNA vaccines are based on work across many, many years, which are now proven technologies, allowing new vaccines against new viruses to be produced rapidly; it is time for all of us to get ready to be immunized against COVID-19, and soon.

To your health,
Dr. Arthur Lavin

 

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