Category: Science

We’ve already discussed the rare clotting disorder associated with COVID-19 vaccinations, resulting in the pause of the Janssen vaccine last month.  It’s time to take a deeper dive to understand more about this disorder. To start, we must learn a little about platelets. It’ll be quick, I promise.

Platelets are bits of cells that circulate in the blood stream looking for leaks.  When a leak is found, platelets are activated and clump together to plug the hole.  There are lots of platelets in blood, so one hole usually isn’t enough to reduce the platelet count.  However, if all the platelets are activated at once, many clumps form, and the count of platelets goes down dramatically.  The reduction of platelet count is called thrombocytopenia. “Thrombocytes” means “platelets” and “penia” means “not enough”, so “thrombocytopenia” simply means “not enough platelets”.

Heparin induced thrombocytopenia (HIT) is a condition in which platelets are activated after the use of heparin, causing a suddenly drop in platelet count.  This is particularly dangerous because, as you may recognize, heparin is a “blood thinner” given to dissolve clots.  The formation of many clots is the opposite of what is desired.  HIT occurs because of an immune response in which antibodies to a molecule that forms when heparin is injected cause activation of platelets throughout the body.  The molecule is called “heparin-platelet factor 4 complexes,” but the name doesn’t matter. Most people don’t have those antibodies to this molecule.  This is a rare but life-threatening complication of heparin therapy.

The rare clotting disorders that have been rarely been observed after the Janssen vaccine have a similar mechanism.  Now referred to as vaccine induced thrombotic thrombocytopenia (VITT), it is like HIT because antibodies develop after vaccine administration that cause platelet activation.  The antibodies are similar enough to HIT antibodies that giving heparin will make the clots worse.  This is why heparin cannot be used to break down those clots.  

This seems to be the same clotting complication that has been observed with the AstraZeneca COVID-19 vaccine, not available in the U.S., but widely available elsewhere.  Both vaccines have in common the use of an adenovirus vector to deliver the vaccine.  A viral vector is not used in the mRNA vaccines. Is VITT related to the adenovirus vector in some vaccines? Nobody knows for sure. Yet.

This is another example of unintended consequences resulting from the use of systems still in the early stages of development.  Life is full of risks; we accept that.  But wisdom demands that risks be acknowledged, quantified, and mitigated as much as possible.  Only the foolish follow science blindly.

In these posts I use my experience as a practicing pathologist to present clear, simple, and understandable explanations of important issues relating to the pandemic amid the noise and misleading half-truths we encounter daily.  When I don’t know, I tell you.  Today, I’m asking you to help me understand something that’s been puzzling me for weeks. Why does the CDC adamantly insist that COVID-19 survivors be vaccinated?

The CDC’s statement is simple enough.  They say that there is a wide range of outcomes to SARS-CoV-2 infection, from no effect to death, and that there is a corresponding range of immune responses to infection.  Those who had mild disease, the argument goes, may not have built up the immunity necessary to fight future infections.  The vaccine, on the other hand, is a measured dose designed to stimulate an adequate immune response.  Furthermore, they assert that there is no data on how long natural immunity may last, saying, “experts do not yet know how long you are protected from getting sick again after recovering from COVID-19.”  So, they conclude, everyone must be vaccinated, even those who have recovered from COVID-19.

Simple enough, yes.  You will find this theory repeated on health websites and in the popular press, often citing compelling studies and medical experts.

But does it make sense?  Before the pandemic, did medical science ever assert that vaccine-induced immunity is superior to natural immunity?  I’ve looked.  I cannot find that assertion from any reputable source, nor can I find that assertion supported by any body of evidence.  I’m not saying that I’ve looked everywhere.  I’m saying I looked and came up empty.  If you know where it is, please tell me. 

Let me be clear about my question.  I’m not doubting that vaccine is an important tool in the war against infections generally and SARS-CoV-2 specifically.  Clearly, vaccines provide protection to individuals most vulnerable to bad disease outcomes.  Clearly, vaccines raise the overall immunity within the population, stemming the spread of infection.  An article published in Texas Medicine on the eve of the pandemic advocates for vaccine, especially childhood vaccines—mumps, measles, rubella, and the like—using a simple risk-benefit analysis.  This analysis, and many more like it within the body of traditional medical science, compare the risk of vaccine to the risk of disease.  Acknowledging that vaccines have risk and diseases have risk, vaccines generally have less risk than disease.  This is very different from introducing the risk of vaccine to individuals who have already survived the risks of infection by the virus.

There is a glaring flaw in the CDC’s argument.  True enough, experts do not yet know how long you are protected from getting sick again after recovering from COVID-19.  But neither do experts know how long you are protected from getting sick after completing a vaccine series.  How could they know either?  Neither COVID-19 nor the vaccines have existed long enough to be studied meaningfully, which brings me back to my question.  How can we say vaccine-induced immunity is superior to natural immunity?

I cannot think of any other example of this line of thinking.  We do not insist that children who have had chicken pox get the chicken pox vaccine.  We do not give hepatitis B vaccine to individuals who have had hepatitis B infection.  In fact, before giving a hepatitis B vaccine, we usually test for antibodies to make sure the individual has not been previously infected.  Why expose someone to an additional risk unnecessarily?

Are COVID-19 vaccines different from any other vaccine?  Has a new theory of immunology suddenly replaced years of observation and wisdom?  Why would the CDC, a place I know to be filled with smart, dedicated, and sincere physicians and scientists, be so insistent that COVID-19 survivors be vaccinated?  

If you know the answers, please tell me.  I would love to hear from you.

These blogs advocate caution and skepticism, specifically in response to the COVID pandemic, but more generally in response to all “scientific” proclamations.  Don’t “follow the science” blindly.  Instead use your “smell test” before believing anything labelled as science.  Remember that science does not prove reality.  Instead, science proves what is not real.  We know much less than we would like to believe.

The sudden “pause” in vaccine rollout announced last week by Janssen is a case in point.  The pause follows reports of six cases of unusual blood clots following administration of the vaccine, tragically including one death.   

These unusual blood clots are called cerebral venous sinus thrombosis, or CVST, a condition which blocks the flow of blood out of the brain.  As a result, the blood vessels may burst causing a stroke which may permanently damage brain tissue.  So far, all patients are women under 50 years old with low platelet counts.   

An association between COVID-19 and CVST was noted before the Janssen vaccine was released.  In the August 2020 edition of the American Journal of Neuroradiology, Dr. D. D. Cavalcanti and associates reported three COVID-19 patients under 41 years old who developed CVST; all three patients died.  Others have reported similar associations between CVST and SARS-CoV-2 infection.  

This raises several questions.  Can CVST be caused by COVID-19?  Can CVST be caused by the Janssen vaccine? What about the mRNA vaccines?  And how is it that a vaccine causes a complication of the disease it’s meant to prevent?  Furthermore, six instances of CVST out of 6.8 million doses of the Janssen vaccine administered is a complication rate of less than 1 in 1,000,000.   The rate of anaphylaxis associated with the mRNA vaccines is 10 times as high.  Why so much concern for such a rare complication?

Something doesn’t smell right to me.

To understand how mRNA vaccines work, we must first have a basic understanding of cells and genetics.  Zzzzzzz.  Wait!  Before you go to sleep, we’re going to make this really short and really simple.  Cells are bags of jelly—jellybeans, so to speak—and in those jellybeans is a kernel called a nucleus.  DNA lives in the nucleus, and like the cell’s hard drive, DNA stores and preserves the cell’s genetic code.  Genetic code is a series of nitrogen bases strung together to form nucleic acid.  There are only four possible bases, so just like computer code is a series of 1’s and 0’s, genetic code is a series of A’s, T’s, G’s, and C’s, each letter standing for a different nitrogen base.  DNA is arranged in two complimentary stands—the famous double helix of Watson and Crick—to create code redundancy like mirrored hard drives that protect your data in case of a crash.

When the genetic code needs to be accessed, a specific portion of the DNA untwists, exposing a segment of code which is copied onto a new strand of messenger RNA (mRNA).  Unlike DNA, RNA is only a single strand of nucleic acid and much less stable.  The mRNA floats into the cell jelly, the cytoplasm, where ribosomes attach and move along the strand, coupling together amino acids as they go.  Every sequence of three bases on the mRNA, known as a codon, codes for a specific amino acid.  For example, GCA codes for alanine, CAA codes for glutamine, and so on.  There are 20 different amino acids, each with its own codon or codons (some have more than one).   Put together according to the sequence of bases on the mRNA, the amino acid chains become a protein.  Out of the trillions of possible amino acid combinations, the proteins formed by your genetic code define the shape of your nose, the length of your bones, the complexion of your skin and everything else that makes you you.  Once the right number of proteins have been made, the mRNA disintegrates into the cytoplasm of the cell.  The process starts again in the nucleus, and a new protein is created as called for by the cell.

What if mRNA could be injected directly into cytoplasm without first being created in the nucleus?  Then the cell’s machinery could create a protein that wasn’t part of the cell’s genetic code.  That’s exactly the hypothesis behind mRNA vaccines.  After the vaccine delivers mRNA into the cytoplasm of muscle cells in the arm, those cells begin forming the protein coded by the mRNA in the vaccine—in the case of COVID vaccines, one of the spike proteins known to exist on the SARS-CoV-2 viral capsule—and those proteins make their way to the surface of the cell where the immune system forms antibodies which are memorized by the body for future use.  How cool is that!

Various companies have been working on mRNA vaccines for over a decade, but none made it to production until the pandemic demanded rapid vaccine development.  Although never been used on a large scale before, mRNA vaccine technology is appealing for several reasons:

1. Molecular sequencing systems makes creation of mRNA almost as easy as writing a computer script.  
2. Once sequenced, mRNA can be mass produced easily and cheaply.  
3. There is no danger from viable pathogens in the vaccine production.  
4. There are no infectious agents or toxins injected into the vaccine recipient.  
5. Once the delivery system is perfected, vaccinations for many different pathogens can be created by simply altering the mRNA sequence, making it possible for vaccines to respond quickly to emerging viral variants. 

Before we anoint mRNA vaccines as our pandemic savior, we should first listen to voices urging caution about this new technology.  For example, in a recent New England Journal of Medicine publication, Dr. Mariana Castells and Dr. Elizabeth Phillips note that the incidence of anaphylaxis, a serious, sometimes fatal allergic reaction, associated with the Pfizer SARS-CoV-2 mRNA vaccine is “10 times as high as the incidence reported with all previous vaccines, at approximately 1 in 100,000, as compared 1 in 1,000,000.”  Why?  And moreover, what are our expectations of vaccination?  Do vaccines prevent COVID or simply reduce COVID complications?  How long will immunity last?  Who should NOT get the vaccine?  Answers to these and other questions are not readily apparent, not because of a failure of diligence, but because there has simply not been enough time to collect, compile and analyze the data that will eventually yield answers. 

The Center for Evidence Based Practice at the University of Pennsylvania recently published a review of the adverse effects of mRNA vaccines.  Among their findings are the following:

1. There are no specific guidelines for use of messenger RNA (mRNA) vaccines or contraindications to mRNA vaccines. 
2. No large trials of any mRNA vaccine have been completed yet. 
3. The only evidence on safety of mRNA vaccines comes from small phase I and phase II trials of SARS-CoV-2 vaccines, with follow-up typically less than two months. 
4. Systemic adverse events such as fatigue, muscle aches, headache, and chills are common 
5. The rate and severity of adverse events appears to be higher for the second dose of vaccine than for the first. 
6. Higher vaccine doses appear to increase the rate and severity of adverse events.
7. Larger trials of SARS-CoV-2 vaccines are in progress, with results expected in mid-2021.
8. There is not sufficient evidence to support any conclusions on the comparative safety of different mRNA vaccines. 
9. Direct evidence on the comparative safety of mRNA vaccines and other vaccines is lacking. 

Clearly, mRNA vaccines offer an attractive, promising alternative to other vaccine technology, especially when a new vaccine is needed quickly.  However, it is a new technology associated with risks of the unknown.  Many unanswered questions remain, demanding a sober examination of the evidence for and against vaccine safety.  Since the risk-to-benefit ratio from taking a COVID vaccine varies individually, I urge individual decisions, not collective ones. The Infectious Diseases Society of America recently published a comprehensive FAQ on vaccine safety which you may find to be a valuable great resource for making an individual decision.  

Although paved with good intentions, the early path of new technologies is frequently littered with unintended consequences.  Next time, I will tell a story of good intentions that ended tragically for many.

Spoiler alert: This essay contains an unpopular conclusion, and you may disagree.  It’s okay if you do, because you’ll probably be in the company of many of my colleagues who disagree with me too.  Today I’m going to talk about when we can trust science.  To do that, I’m going to pretend to be a scientist and a philosopher.  This is dangerous because, as I have said before, I am neither a scientist nor a philosopher.  Instead, I am a practitioner, applying science to the problems of diagnostic medicine.  As a practitioner, I must know when science is applicable and when it is not.  I know just enough about science and philosophy to be dangerous.

Our experience tells us to trust science, and the explosion of technology during our lifetimes tells us we can.  But science is a process, not a product.  Not everything labelled as science is science.  To understand the difference, let’s consider how science works.

The scientific method begins with a hypothesis.  A hypothesis is just an educated guess about some aspect of reality.  It is proposed by a scientist as a fact of the world, something that can be relied on to be always true within certain conditions.  If the conditions are true, the hypothesis can be used to predict the future and tell us about the past.  

Once formed, the hypothesis is communicated to other scientists, who test the hypothesis by experiment.  The objective of an experiment is not to prove the hypothesis true; rather, the objective of an experiment is to prove the hypothesis false.  If successfully proven false, the hypothesis is rejected.  This is the fate of most hypotheses.  The path of science is littered by the half-truths of discarded hypotheses.  On the other hand, if the hypothesis survives the challenges of repeated experimentation, it becomes elevated by the community of scientists to the status of theory, and its predictions become part of scientific knowledge.  This is a relatively rare phenomenon.  

The falsification objective of the scientific method is a commonly misunderstood aspect of the process, but it is fundamentally important.  It gives science its power over other means of understanding reality, but it also gives science its pace.  It takes time to test hypotheses.  The proof of a hypothesis can be shortened by increasing the number of simultaneous experiments, but only to a point.  Science, like fine wine, requires adequate aging.  

For all its power, the elevation of hypothesis to theory illustrates another weakness of the method: theories are created by scientists.  Scientists are people, and people make mistakes. Scientists have made many.  We can review examples of the most spectacular blunders of scientists later.  The point is that the mistakes of science are the mistakes of people, not fallacies in the method.

So why do we trust science?  Because, despite its flaws and weaknesses, science has increased our understanding of the world exponentially.  But can we be misled by science?  Of course we can, and we are most vulnerable when products labeled as science are not developed with strict adherence to the scientific method.

This brings us to the controversial part.  Most of everything we have learned and developed in the war against COVID-19, including the tests, the treatments, and the vaccines, should not be trusted as science.  In the middle of this emergency, there has not been enough time to fully study the virus and the disease by the scientific method.  Rather, what we have so far are merely hypotheses: the best guesses of the smartest and brightest people in the land.  To be sure, these hypotheses are our best hope in this fight against pandemic, but they should not be labeled science.  There has not been strict adherence to the scientific method.  So, what should we trust, what should we view skeptically, and how can we tell the difference?  We will address these questions next time.