Pique the Geek 20110227: Polio

Anterior poliomyelitis, mainly called polio (the old name was infantile paralysis) was a scourge for centuries, but was not recognized as a specific disease until comparatively recently.  This piece is in honor of the huge immunization program that was begun 56 years ago last week in the United States, that fact kindly pointed out by our good friend ek hornbeck at TheStarsHollowGazette.com a couple of days ago.

Most people do not know anyone who was infected with the paralytic form of this disease these days, partly because they either died or got better, but mostly because of the most successful vaccination program against an infectious disease ever attempted.  I have first hand experience with two cases, and will turn 54 on this coming Wednesday.  Few people younger than about my age will have known anyone who had it.

The intent with this installment of Pique the Geek is fourfold:  first, to educate people about what was probably the most feared disease by parents in the 1940s and 1950s for their children; second, to give my personal experiences with the two people that I knew that suffered from it; third, to describe the incredibly top drawer work done by two research groups in creating vaccines, Drs. Salk and Sabin respectively, and finally to make the point that, even there are probably some risks associated with vaccines, it is folly not to have children vaccinated.  The last point is likely to elicit some strong disagreement, but that is OK.

It was only in 1840 that polio was recognized as a specific disease, and the main reason for that was epidemics were not very common then, so it was not studied that much.  The German physician Jakob Heine first described it then, and in 1909 the Austrian Karl Landsteiner identified the virus that caused it.  He became a Nobel Prize winner for medicine, having also identified the Rh factor, the tag on your blood type that is either positive or negative.  Quite a guy he was.

In the late 19th century, due to increasing urbanization for the most part, polio epidemics began to occur.  The reason for that was not understood for a long time, but it turns out that there is not really a natural vector for infection except for houseflies, and that is a weak vector.  The reasons for that will become clear in a few minutes, but first a little about the agent that causes it.

Polio is causes by a virus, Poliovirus, of which there are three serotypes, I (formerly known as the Brunhilde), II (formerly known as Lansing), and III (formerly known as Leon).  Interestingly, they are primitive viruses, small even for viruses and with RNA rather than DNA as their genetic information carrier.  It may be that this is the smallest RNA virus to cause human infection with HIV being also a contender.  However, their mechanism of transcription differs so they are not really in the same class.  The virus is quite resilient and not easily destroyed.

Because of the resilience and the fact that the virus mainly is transmitted by an enteric mechanism (to be blunt, feces to mouth transmission), as urbanization became widespread, water was contaminated with the virus because of poor sanitation in urban areas.  Human waste was disposed of in ways that we would not even imagine back then, often just “thrown into the creek”.  Lots of times, those creeks were the source of drinking water not far downstream.  As urbanization became more important, so did polio epidemics.

Let us dispel a myth right now.  Polio is not, and was not ever, a disease confined only to children.  However, it is know known that an infection is likely to provide lifetime immunity, and around 90% or more of infections do not lead the the paralytic syndrome, so in the day most adults had already produced antibodies to the virus, and so were immune.  However, with three serotypes, having one strain does not produce immunity to the other two.  One of the most famous cases of polio in adults was that of our President, Franklin D. Roosevelt, who contracted it long after adulthood.  I have a theory, and it has to do with class.

He was a child of immense wealth, and did not have to drink creek water.  Thus, he was never exposed in childhood and so did not develop immunity.  When, as an adult, he was exposed, he was one of the unlucky ones who developed the paralytic form.  Sometimes being elite is not a good thing.  It turns out that in very young children the risk for developing the paralytic form of the infection is only about 0.1%, depending on the serotype, but in adults can be as high as 1.3%, thus before the vaccine became available the best defense was to become infected at a very early age.

Because of the water borne nature of the infection, that well over 90% of people only get a mild, enteric infection, and the lifetime immunity acquired explain most of the mystery of why it was not recognized as a particular disease until comparatively recently.  The symptoms only add to the mystery.  Most polio cases feel lots like a bad cold or dysentery, with a mild fever, headache, sore throat, perhaps diarrhea, and a general feeling of not being well.  The fever never gets really high, so the constellation of symptoms are similar to that of many other, harmless but annoying, “bugs”.

Even with the paralytic form, the symptoms are very much like the flu, with muscle aches and pains, like a stiff neck and sore joints are not really anything to put it on red alert status.  In other words, it just feels like any other acute viral infection.  That is really why it was never conclusively identified until 1840 (although some workers were beginning to home in on it before then); it just feels like you are sick, but nothing specific.

Poliovirus is not primarily an infection of neurons, but rather of the GI tract.   After exposure, anywhere from just a few days to five weeks can elapse while the virus replicates in the GI tract, and the patient is consequently shedding virus for that entire time.  After symptoms occur, several more weeks may be required for final clearance of all virus particles, so infected patients are contagious for a long, long time.  The virus is also present in saliva, so the old adage of not to “eat after someone” actually had a good deal of truth in it in Grandmum’s day.  It is still unclear why the virus sometimes invades the nervous system, although a few connexions are known.  Tonsillectomy is a known positive contributor to neural involvement.

The virus has a higher affinity for motor neurons than for others.  Once a neuron is infected, it dies and is not generally replaced.  If only a few motor neurons are damaged in a particular location, the remaining ones can take up the slack, for a while.  Decades later, after apparent recovery from paralysis, weakness can return due to overtaxing the remaining motor neurons.

There are three primary types of paralytic infection:  spinal, bulbospinal (aka respiratory), and bulbar.   My personal experience is with people who the first (the most common) and the third (the rarest).  A man who used to work for me who was about 35 or so at the time, was not vaccinated when he was a child.  He told me that he had been sick one week when he was about 14, and everyone thought that he had the flu.  He awakened one morning and found that he could not move his legs.  This patient of spinal polio to this day walks with leg braces and elbow crutches.

Bulbospinal polio affects areas higher up than just the spinal cord alone.  This motor neurons in this region are the ones that control the diaphragm, and the destruction of them caused respiratory failure.  I am sure that most folks have heard of the “iron lung”, a device in which the entire body except for the head and neck are sealed in an airtight chamber, with a motor operating a bellows to expand and contract the lungs.  Often patients would get enough function back (as remaining neurons retrained to take up the slack), but some patients were confined for life, and usually that was not all that long.  In addition to breathing, coughing and sneezing are also impossible and most patients finally died of pneumonia because they could not clear their lungs.

The bulbar type is only about 2% of the total, but that is the other type with which I have personal experience.  When I was only about five or six years old, we lived in North Little Rock, Arkansas.  My parents knew some people who had a child about my age who had had essentially all three types simultaneously.  He could not walk because of the muscle wasting in his legs, had gotten out of the iron lung, but still presented with the characteristic symptoms of bulbar polio, and this region controls functions like swallowing and clearing of the throat as well as speech.  Rex had a permanent tracheotomy and had to hold his finger over the opening to try to talk, which he did with difficulty.  He also had extreme difficulty eating.  The reason that I knew him was that he and his parents would stay with us as they took him the Arkansas Children’s Hospital in Little Rock for evaluation and treatment.  He lived only a couple of years.

It was cases like that which terrorized parents back in the early to middle part of the 20th century.  In addition, from a normal situation of about 20,000 cases per year, in 1952 there were about 58,000 cases and in 1953 35,000, all in the United States alone.  Since the virus was so pervasive, and to this day there is no really effective treatment after symptoms appear, it was essential to develop a vaccine to prevent the infection in the first place.  Actually, polio was one of the biggest driving factors in the development of modern virology that existed.  Early work had to do with a passive vaccination made by extracting antibodies from the blood of polio survivors and injecting them into patients.  While this does work, it is fraught with problems.

First of all, getting enough serum from survivors was no small feat, and that fraction of blood is also extremely useful for other conditions.  Second, it confers only a passive immunity, meaning that one’s own body does not “learn” to produce the antibodies, so after a few months they are gone and there is no mechanism for the body to recognize the virus and produce new antibodies of their own.

The trick is to get the body to recognize that the virus is bad and to produce antibodies.  This can be done only by exposing the body to the virus itself, or pieces of it that are large enough for it to recognize.  The first real vaccine was made with a live virus that had been attenuated (weakened) by successive passes through nonhuman hosts until it is no longer infective to motor neurons, but is infective towards the GI tract.  This was developed in 1950 a group led by Hilary Koprowski, but since he had to use rat brains to grow the virus, along with the fear involved with using a live one, never really caught on very well.

The first real success was by the group led by Jonas Salk which in 1952 announced a vaccine based on inactivated (killed) virus.  This eliminated the possibility of the the vaccine causing the disease, and Salk’s group also had the advantage of a new technique to grow virus, this time in flasks containing living monkey kidney cells that were infected.  Each serotype was cultivated separately, and when the population of virus is high, the cells are disrupted and the virus particles removed (rather simple in concept since the virus particles are so much small than the cell fragments).  The purified virus particles were then treated with formaldehyde to inactivate them, and after a number of other steps, all three serotypes were combined into a single injection.

A rather large study was done in 1954, and in 1955 the efficacy of the vaccine was conclusively proved.  The vaccine was approved in 1955, and a huge campaign to raise awareness was undertaken.  by the year of my birth, 1957, the US number of cases had dropped to 5,600.  By the 1960s the numbers were only in the low hundreds.  A disadvantage of the Salk vaccine is that it does not prevent actual infection in the GI tract, but does prevent the virus from entering the bloodstream to that it can not attack motor neurons.  There is an important corollary to this to be brought out later.

A new attenuated vaccine was being developed by Albert Sabin’s group in the late 1950s, became available in 1961 and 1962, each one a separate serotype.  In 1963 the combination of all three serotypes came to market, and it rapidly replaced the Salk vaccine since it was orally administered.  Many of you may remember the sugar cubes at school that were given out to administer this vaccine.  Attenuated virus tend to be a bit more effective in producing an immune response since the person being immunized actually develops a real infection, and in that respect the Sabin vaccine was actually better than the Salk one.  There is another advantage:  in areas where polio has not been eradicated, mixing the attenuated strains with the “wild” ones can confer immunity without serious infection due to poor sanitation practices.

A real, but very small possibility is that an attenuated vaccine will produce an actual neuronal infection.  In children with normal immune systems this seems to be just a little more than one case in 1,000,000, but is higher in adults.  This is not surprising since adults tend to develop paralysis at a higher rate with wild strains.  However, in immune compromised recipients,  the rate can be thousands of times greater.  There are more ramifications as well.  If an immunocompromised sibling, or even an adult, is present in close contact with the child that was vaccinated, there is a chance of that individual contracting the paralytic form.  Remember, polio is spread by feces and saliva, and babies have lots of both, often contaminating the local environment.

Modern practice is to use attenuated vaccines in areas where wild polio is still present in the environment, and to use inactivated ones in areas declared free of endogenous polio.  Newer inactivated products produce a very high level of immunity, and are the standard in most developed countries.

Like with any other medical product, there are other risks as well.  The original Salk vaccines, at least some of them, had a simian virus (SV 40) from the kidney cells used to grow the polio.  This has been a cause of concern, because SV 40 has been found in certain human cancers, although it is not yet known if the SV 40 causes the condition or is just there as a coincidence.  However, that was an inactivated virus product, so the likelihood is that the SV 40 was also inactivated.  Perhaps, by accident, those batches were also SV 40 vaccines!

The bottom line, at least for me, is this:  immunizations are important for each child, unless there is an overwhelming medical reason, to receive on schedule until the full compliment has been received.  The “link” betwixt autism and the MMR vaccine has now been shown to the the result of outright fraud, not real data.  If you want to demonstrate for yourself how important childhood vaccines are, drive to any cemetery that is over 120 years or so old, and just count the number of grave markers for children under 15 from 1890 to 1910, then do the same for the number from 1990 to 2010.  I rest my case.

From last week’s installment, Kossack docmidwest had the following observations where I got it wrong.  Since the comment period had elapsed, I am adding a copy of his message to me.  If anyone wishes (and docmidwest indicates that he will try to be here tonight), we can discuss them.

I just got around to “following” Scitech, and saw your diary. I know this is a little obnoxious, but there were some basic mistakes in it. This comment was posted belatedly.

Sorry, I should have noticed this diary sooner, but some of the basic points here are all messed up.

1. At the phase transition point, the net change in free energy is exactly zero. That’s why the two phases are in equilibrium. Therefore the enthalpy term is not much bigger than the entropy term. They have exactly the same magnitude and opposite signs. If you’ve seen something that “often ignored” the entropy term, that’s either because it was crap or, more likely, because the author assumed that it was understood that T*delta_S=delta_H at the phase transition, so that the two quantities didn’t need to be listed separately.

2. The supercritical regime is not a separate phase. There is in general no phase transition between it and either the liquid or gas phases. Yes, that means that there’s a path through p-T space to go from liquid to gas without a phase transition. SInce these are phases of the same symmetry, that’s perfectly possible.

Sorry to be picky, but these are the basic ingredients of the science, especially the free energy issue.

Well, you have done it again!  You have wasted many more einsteins of perfectly good photons in reading this sick piece!  And even though Brigitte Gabriel quits shouting like a banshee she reads me say it, I always learn much more than I could ever hope to teach by writing this series, so keep those questions, comments, corrections, and other feedback coming.  The comments are always the best part of this post.  I shall stay around as long as comments are coming tonight, and shall return for Review Time tomorrow around 9:00 PM Eastern.

Warmest regards,

Doc

Crossposted at Antemedius.com, DAilykos.com, Docudharma.com, and Fireflydreaming.com.