A Nifty Cartoon About Vaccines

A couple of loyal readers today sent me this cartoon they found informative and amusing.  While I strive to be more detailed and immersed in hard science, like my prior post today, I admire the creators’ excellent storytelling.  It’s effective.

Please keep sharing the story of vaccines.  I hope one day we can get pertussis and measles under control again.

Happy Reading, Patrick Lowder

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Connections to Social Media

Dear Readers:

Thank you for your interest in my blog at patlowder.com.  I have noticed the linked “headlines” in Facebook, LinkedIn, and Twitter occasionally reflect titles I did not choose.  I cannot preview what goes to these social media sites, so I end up surprised by how the posts are published.  I will try to resolve the problem as quickly as I can.  In the meantime, please let me know what you think.

Patrick Lowder

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Pertussis – 2: The Slaughter of The Innocents

In the last post, I discussed the importance of mucus and cilia.  In short, cilia in the trachea and other airways combine with a river of mucus to clean the air we breathe and move it up (yes, against gravity) out of the trachea.

Pertussis is caused by the bacterium Bordetella pertussis.  This organism basically destroys cilia and the epithelial cells from which cilia grow. Here’s a picture of the bacteria lodging themselves between cilia.   The beasts are in greenish-yellow, and the cilia are salmon-colored.  Conveniently rod shaped, see how the pertussis bacteria fit between individual cilia?

PRinc_rm_SEM_of_whooping_cough_bacteria_in_cilia(Picture from WebMD.com)  The pathology of B. pertussis is well-understood.  As the bacteria develop, they a) emit specific toxins that kill the cilia and b) induce a cascade of biochemical responses to further screw up the body’s ability to heal.  Entire regions of cilia are shredded.  Here’s a picture to illustrate this response:

Pertussis infecting cilia

(NB: This pic came from here)  As you can see, the non-ciliated epithelial cells are useless to assist in mucociliary clearance.  I bet you can guess what happens next as the disease develops.  Here it is in an infant girl, courtesy of the Mayo Clinic’s archive.  Warning:  This video is disturbing.  But don’t look away – it dishonors those innocents who suffer and die from this terrible, cruel disease.  Sit with her; count the seconds between her breaths.

Imagine coughing all the time if your cilia couldn’t work.  Really:  imagine it.  Your diaphragm could collapse.  After all, that is the muscle that controls breathing.  Just like any muscle, it has its limits before it is so exhausted it cannot go on.  In a weeks-old infant, that’s exactly what happens.

Here’s what childrens’ hospitals sometimes do when an infant can’t take it anymore.  They have to breathe for them.  Here’s a picture of a baby getting cardio-pulmonary assistance after an attack of pertussis. (You can visit the source page here.)

pertussis-baby-oneImage via the CDC. Infant being treated for severe pertussis infection. She received extracorporeal membrane oxygenation (ECMO), a procedure that can take over the work of the lungs and heart. She also received dialysis to help her kidneys keep working.

You know what is really interesting about B. pertussisHumans are the only known hosts.  The implication is clear: an infant contracts pertussis by exposure to another human harboring it.

Fortunately, the pertussis vaccine is effective in preventing transmission.  However, newborn infants can’t be vaccinated against pertussis until about 6-8 weeks old, and then the infant needs booster vaccinations at 4 months and 6 months to increase immunity.  See this vaccination schedule (the vaccine is called the DTaP vaccine).

So here’s the takeaway risk analysis: In my humble opinion, these simple facts indicate anyone in contact with infants must have the most pertussis immunity they can get.  Breaking it down, those in contact with infants shouldn’t have the germ in them (detectable using modern biotechnology), and they should have detectable pertussis antibodies.  That is a very high level of care.  But while the actual chances of an infant contracting pertussis may be perceived to be low, the consequences of getting it may be fatal, absent extreme medical intervention.

That’s why I advocate universal vaccination.  Otherwise, there are significant, perhaps upsetting, social consequences.  Family members or friends who are not immunized or refuse to be vaccinated may need to be excluded from contact with a newborn.  This can lead to some very tough conversations. But when the life of an infant is at risk, the limits of these relationships have to be considered.

I conclude by asking this question: by not adhering to some simple rules like those suggested, are we knowingly exposing innocent infants to suffering and death?  I say we are.  So getting a pertussis vaccine is tantamount to “doing unto the least of these my brethren.” I’d like to not have to explain otherwise on the day of judgment.

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Pertussis – 1: The Creepy Beauty of Mucus

As a chemist, mucus is fascinating stuff.  It turns out that mucus is quite difficult to chemically characterize.  Mucus is a “non-Newtonian” fluid.  It does not act like a “predictable” fluid, water, for example.  When you pour a bucket of water, it seems to all pour as a single quantity.  Mucus, on the other hand, is a rubbery (viscoelastic) material: it can be compressed and relaxed, stirred, and sheared to thin it.  Basically it’s a mixture of water, salts, and mucin proteins that are sometimes cross-linked to form polymers of varying sizes.  The type of proteins in mucus, their concentrations and the amount of protein-crosslinking often determines mucus viscosity.  (Note: all of the technical information and the two pictures in this post (not the Zombie)  is from Michael M. Norton’s Master of Mechanical Engineering Thesis entitled Modeling Problems in Mucus Viscoelasticity and Mucociliary Clearance. Any errors in summarizing this excellent work are mine)

Observationally, mucus seems to have a life of its own.  It’s literally and figuratively creepy.   Zombies always seem to be expurgating copious amounts of it, mixed with the blood of their victims.  You know the story.

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Imitation Zombie

While morbidly fascinating, mucus is critical for many bodily functions, and breathing is the function for the moment.  Breathing air, getting oxygen to our blood and expelling carbon dioxide is a dirty business.  Air is full of contaminants for humans: tiny particulates, viruses, bacteria, allergens, trash, plastics, you name it.  Anyone who says that the country has pure clean air is probably trying to sell you something, because they’re just blowing smoke.  Mucus traps the contaminants for us.  How we get the mucus and contaminants out of us is the important part.

Humans move the mucus by something called the mucociliary transport system.  This is a beautiful mechanism.  Tiny structures called cilia beat almost synchronously with neighboring cilia on a dense grid.  The cilia are bathed in a watery periciliary fluid.  The periciliary fluid layer is about as thick as the cilia are long (estimated about 5-7 microns in humans), and the fluid is held between cilia strands by capillary action. A layer of the much denser, viscous mucus floats on top of the cilia/periciliary fluid layer.  Here’s a cross-sectional view of this arrangement in a rabbit trachea.  The mucus layer boundary runs right through the middle of the picture.  It looks like the cilia strands are supporting it.

mucus-cilia-rabbitCilia have a mechanically fascinating structure.  A single strand has two central columns, surrounded by 9 symmetrically spaced outer vertical structures, that move parallel to each other to whip the tip.  The tip has a cap structured to “grab” the upper mucus with each whipping stroke through the watery periciliary fluid.  (The top right inset photo is the “cap” and the top left inset shows the cross-sectional structure.)

Cilia frondsSince the mucus is viscoelastic, each stroke of the cilia “nudges” the mucus, for lack of a better term, by compressing it and allowing it to relax in the direction of movement.  While one or two little strands won’t move much, millions of them can move a river of mucus in what looks like a stadium wave.  If you imagine that each strand is a person, you’ll get it.  Here’s a great video that illustrates this movement.  Start watching at the 1:30 mark and end at about 3:30.

The microscopy video of cilia moving crap out of the trachea shows how efficient it is.  Imagine if a section of the cilia just weren’t there.  And that’s what can happen when the bacteria Bortedela pertussis infects vulnerable humans.  Stay tuned for the next installment. . . .

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Apologetics

Before I jump into some planned topics, I thought it was important to tell you about me to the extent it helps you understand my thinking and conclusions:

After being raised in a small North Carolina town by two damned intelligent parents who sent me to Wake Forest University, where I met my wife (Valerie Coe Lowder, the editor of this stuff) I got a Ph.D. in Organic Chemistry from Indiana University (1991).  I worked as a research chemist in two multinational companies before becoming a patent agent, and ultimately a patent attorney.  I got my law degree from North Carolina Central University School of Law at night.  I’ve practiced in state and federal court and before the United States Patent and Trademark Office.  I am standing on the shoulders of many giants, my wife and parents, and their ancestors.  Not to mention the countless scientists and lawyers before and after me.  I have plenty of friends who know biology well enough to correct my errors, and I call on them to set me straight if needed.

I view the world through the eyes of a chemist, a lawyer, and a Christian.  It would be intellectually dishonest if I did not state that I call upon my Christian faith and the teachings of Jesus as I view the world.  For those of you who would not take me seriously because of that apology, then I point you to my last blog post.  More than anything, I try to practice mercy, particularly toward the most vulnerable and downtrodden, as Jesus has commanded, and to love one another, even as he loved us.

And that’s where I’m coming from as I blog.  As I present facts and my interpretations, try to keep this in mind.

Pro Humanitate, y’all.

Happy Reading, Patrick Lowder

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Typos, Peer Review, and Cold Fusion

coldfusiontime_2

That is a strange title for a vaccines blog.  But it’s timely.  I published the entry Smallpox 2: Serendipity without an unbiased reviewer having proofed it.  And that’s where the problem lay.  I substituted “utter” for “udder.”  Oops.  Thanks to my mother for pointing this out.  I’m sure she wondered what her life’s work had come to.  Sigh.  (Fortunately for you faithful readers, Valerie Coe Lowder, my wonderful wife, has your back.  She’s agreed to edit my work as long as she can stand it.)

My unfortunate typo is a silly example of a significant human fallacy.  Humans are predisposed to see what they wish to see, or to understand.  This tendency is well known as confirmation bias.  From “Self-Proofreading” in this Wikipedia entry:

Primary examples include job seekers’ own résumés and student term-papers. Proofreading this kind of material presents a special challenge, first because the proofreader/editor is usually the author; second because such authors are usually unaware of the inevitability of errors and the effort required to find them; and third, as finding any final errors often occurs just when stress levels are highest and time shortest, readers’ minds resist identifying them as errors. Under these conditions, proofreaders tend to see only what they want to see.

See what I mean?  Confirmation bias happens to the best of humans, and brilliant scientists are no exception.  A famous example in chemistry and physics occurred with Cold Fusion.  I was a graduate student at Indiana University on March 23, 1989 when Professor Stanley Pons announced in a seminar there that he and Martin Fleischmann had discovered this previously unrealized, but hoped-for, event.  I recall Professor Pons announcing that his team had filed thirty-plus patent applications to claim (monopolize) every aspect of the phenomenon.  I have no doubt that the inventors were imagining a Nobel Prize and some higher-learning institutions were salivating over the prospective cash inflows.  Now there’s some confirmation bias.

The announcement stunned the physics and chemistry world.  Most scientists were in disbelief.  My brother, Douglas Lowder, a University of California Berkeley physics doctoral candidate at the time, described the general reaction: everyone put down his own work to reproduce the Pons/Fleischmann experiments.  Pons and Fleischmann swore they had recorded a massive exothermic reaction when pressurizing hydrogen adsorbed onto a metal (layman’s terms: it got real hot).  But nobody else could reproduce the exotherm, along with some missing gamma rays, as I indistinctly recall.  Because and the inventors and their respective universities had the patent-rights-driven incentive to keep the technology secret prior to filing the patent applications, no one outside the Pons/Fleischmann research labs ever had the opportunity to reproduce the experiments prior to the announcement.  That’s called “peer review” in academic circles.  Such is life and the consequence of such a strategy.  In a final note on this sad story, Cold Fusion-based inventions appear to be considered highly suspect, if not outright unpatentable as a matter of law, by the United States Patent and Trademark Office.  See the Manual of Patent Examining Procedure, section 2107.01 and In re Swartz, 232 F.3d 862 (Fed. Cir. 2000).

Confirmation bias is a serious concern in a modern debate on the importance of vaccines.  If you are convinced or predisposed a) you don’t need them, or b) the danger of vaccines far outweighs the benefits to you or others,  it’s easy to miss other facts or the logic of another view.  And this goes for the pro-vaccine community in reverse: many anti-vaxers are suffering through raising an autistic child or a child they sincerely believe is damaged by “chemicals.”  Their concerns may seem imagined, but are real to them.  That’s important to hear.  My point is, in the end, if you are totally, e.g., doctrinally, predisposed to one view, you might imagine (or miss) an important exotherm, just like Pons and Fleischmann did.

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Smallpox – 2: Serendipity

So, continuing.  Smallpox was around for a long time, until about 1979, when the World Health Organization declared the disease completely eradicated.  Who can you thank for this? Edward Jenner.

The above Wikipedia link is extensive, so here’s what he did, simplified.  Really, it was simple.  It was known during Jenner’s time that cowpox (a Vaccinia virus) could impart immunity to smallpox (a Variola virus) by innoculation, but nobody knew how.  Mankind got incredibly lucky, hence my title.  Jenner hypothesized that pus from a cowpox pustule did the trick.  That’s because milkmaids were known to be immune to smallpox.  Here’s an engraving of a cow utter with cowpox.  Lovely isn’t it?  (The pictures are from the Wellcome Image Library, and I encourage you to explore the site.)

Cowpox_Engraving_(detail)

So, Jenner took a pointy ivory stick

L0057751 Edward Jenner's ivory vaccination points, England, 1821

stuck it into a cowpox pustule from a milkmaid, and scraped the pus into the skin of his gardener’s son.  Lucky him – lucky for us.  (The Dowager might have approved the working class being guinea pigs, but I digress.)  After recovering from the cowpox illness, Jenner purposely infected the boy with smallpox.  This is known in modern medicine as a “challenge,” but was not out of the ordinary back then.  It was common to infect people with smallpox on purpose so they’d be immune when the next epidemic hit.  Life was a bitch, for sure.

This seems horrible to a modern sensibility. But this is just risk management, the essence of vaccination.  One endures the unpleasantness and (finite) risk of prevention in order to stave off a catastrophe.  It’s a biological insurance policy.  And side-by-side, here’s a brilliant illustration of the relative risks: These are drawings from 1803 of a smallpox innoculation and a cowpox innoculation.  The pictures start on Day 2 and end on Day 14.  Which side would you rather be on?  If a picture says a thousand words, well, I’ve said enough.

                                    Smallpox                                                        Cowpox

L0039159 Smallpox (left) & cowpox inoculation, day 2L0039160 Smallpox (left) & cowpox inoculation, day 3L0039161 Smallpox (left) & cowpox inoculation, day 4L0039162 Smallpox (left) & cowpox inoculation, day 5L0039163 Smallpox (left) & cowpox inoculation, day 6L0039164 Smallpox (left) & cowpox inoculation, day 7L0039165 Smallpox (left) & cowpox inoculation, day 8L0039166 Smallpox (left) & cowpox inoculation, day 9L0039167 Smallpox (left) & cowpox inoculation, day 10 L0039168 Smallpox (left) & cowpox inoculation, day 11L0039169 Smallpox (left) & cowpox inoculation, day 12L0039170 Smallpox (left) & cowpox inoculation, day 13L0039171 Smallpox (left) & cowpox inoculation, day 14L0039172 Smallpox (left) & cowpox inoculation, day 15L0039173 Smallpox (left) & cowpox inoculation, day 16

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