Recap & Plan

Vaccines and numbers  introduces a new child to the world.  One more.  Addition. A  starting point for maths.  We introduced big numbers like the  over 7 billion (7*10^9 or 7,000,000,000) people who live on our planet.  All of us members of a family that emerged some two hundred thousand (200,000 or 2*10^6) years ago from the Rift Valley in East Africa.

A child born today benefits from life-saving tools. Vaccines, antibiotics, clean water protect children from infection caused by bugs. We now have vaccines against more and more bugs. In New Zealand, children are given vaccines against at least 12 families of bugs.  But what are bugs?

The germ theory of disease introduces you to the idea of bugs.  These are microscopic (tiny) creatures that are too small to be seen by the naked eye.  Some are too small to be seen in normal microscopes.  These many kinds of life forms include  viruses and bacteria, the two  main kins of bugs that  vaccines protect against.

Surprising fact:  some people do not believe or understand germ theory.  Surprisingly many are not even exposed to the idea; their only teaching being religious.  Surprising, because the evidence has been so strong since Pasteur developed the theory  in the late 19th century (1880s).  Today, the evidence is even stronger as we learn about new kinds of bugs, including the Archaea that did not even exist as a separate kingdom of life when I was at school.  And we now have anti-cancer vaccines as we have found  the viruses responsible for liver, cervical, and other cancers.

For me, the idea for Vaccine Logic came from decades dealing with anti-vaccine arguments, prompted by  doing a logic course. A lot of science is needed to understand vaccines.  To learn about vaccines requires understanding many disciplines of the science of our human bodies: medicine, physiology, immunology.

Our   cells of immunity protect us from  bugs.  But our relation with bugs is more complex than a simple war, and may be better thought of as an interplay of another level of our existence; in the same way as we can think of the interplay between the

  • subatomic quarks and electrons that make up all matter
  • molecule machinery of our cells
  • different organs and systems that create our existence and consciousness.
  • individuals who make up a family
  • communities of households and families
  • corporations and nations; religions
  • Gaia, the planetary entity; an almost closed environmental system that has been brewing life for at least 3.8 of its 4.5 billion year life.

Each level can provide some insight to the level above it or below it. For example, the electron dance from the orbit of one atom to that of another, as they seek to find a new partner.  Electrons always want to spin in pairs.

Chemical reactions involve bumping an electron off  to break up and then create a new molecule by shifting the bonds, the shared electrons between the atoms.  This idea helped me understand chemical reactions – but not how to learn about the specific biochemical reactions. Different domains behave by distinct laws.  The social is more plastic.

We do not have the mental machinery to be able to model the quantum world. Why do think we can understand the increasingly complex social one?

Can electron behaviour provide insight into social dynamics?  Humans too seem to need to pair; and to be in society. So, while we don’t need to traverse all the sciences to explain vaccines, perhaps the journey will be more satisfying.

From simple atomic processes, the chemistry of life and the shapes of immunology. To the behaviour of human individuals and populations. It does not matter how effective a vaccine is, unless it is taken up by enough of the population to prevent spread in the community. The impact of vaccines demands population coverage.

With the exception of tetanus, vaccines prevent diseases that are spread person-to-person.  While the protection from a vaccine is to the individual, the impact depends on community coverage.  For some vaccines, when coverage is high enough, the bug will become unable to pass form person-to-person.  This is the ‘herd immunity’ threshold.

The concept of herd immunity is another one that seems to challenge people.  It can be described as derived from a number, that we call R0 (R zero).  The herd immunity threshold is 1 – 1/R0 (one minus the inverse of R zero).  R0 is the average number of people an infected person will pass the disease onto.  Measles has one of the highest know R0, estimated to be between 12-18 in most settings, so the herd immunity threshold is 92-94% immunity.  As no vaccine is 100%, but two doses of measles vaccine give about 99% protection, immunisation coverage needs to be about 95% to prevent spread.

We will then take a diversion to reflect on what is happening with measles in New Zealand as we get close to this level of immunity, before starting to address the various anti-vax arguments, and from this to learn about the different types of logical flaws.  Here we need to be very careful, as it is surprisingly easy to be trapped by faulty logic.

With that caution, we can then look further at the individual versus population view of the risks and benefits of immunisation.  Through this to see if we can test and strengthen the logical proof that vaccination is an act of love for others, in addition to ours.

Please let me know if you have some other suggestions.

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Love & Logic

Time for a philosophical break on this journey.  I started Vaccine Logic to see if I could teach vaccines and mathematical tools including logic. But as Aristotle said, “Educating the mind without educating the heart is no education at all.”  And I realised that learning about vaccines and immunisation is also about emotion.  We are emotional and not rational creatures, by instinct.

But we can and do over-ride instinct routinely.  Isn’t that what it means to be civilised: to do what is moral rather than what instinct or pleasure dictates to meet self-interest?  To over-ride our natural prejudices with deliberate logic.  We can recognise our biases and address them if we choose, but it is hard work!  Discipline and practice.

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Love requires empathy, a feeling for others. “When parents use empathy and don’t react negatively to a child, they help the child stay in the upstairs part of the brain (more rational part) and not the downstairs (emotional).”

It is wrong to think of love as a purely human attribute. Love emerges in the animal kingdom with mammals and birds, who care for their young.  Fish spawn and move on. Reptiles will carefully hide their eggs then leave them.  Love starts with the care of the mother for the child; and there are many kinds of love.  An army unit works as well as its members love each and will protect each other.  At heart is the care for the other, and willingness to sacrifice for them.

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The primate love instinct that we inherited has gone metaphysical: a love not just of other people, but also of ideas.  Continue reading

Cells of immunity

 

My biology lessons started with cells: the building blocks of life. About 200 types of cells make up a human body, but the number depends on how you define ‘type’. It is hard to measure, but a recent estimate was the human body is composed of some 30 trillion human cells.

One trillion is a thousand billion or a million million or 1 with 12 zeros: 1,000,000,000,000.  A simpler way to write it out is to use the power of exponents: 10^12 (ten to the power of twelve).  There are also the estimated 39 trillion (39*10^9; 39,000,000,000,000) bugs that are part of each healthy adult human body; slightly more than the estimated human cells!

There are skin cells, liver cells, brain cells and so so, each adapted to its purpose. Blood cells come in three varieties:  white, red and broken.  Platelets are the remnants of broken cells that help form blood clots in response to a cut.  Red Blood Cells (RBCs) carry oxygen from your lungs to every cell in the body. The picture  below shows that blood below is mostly RBCs; they are doughnut shaped to maximise the amount of oxygen that they carry.  The shape results from  a spherical cell whose nucleus has been removed.  The RBC is thus not like other cells in that it is without a nucleus, and serves to transport Haemoglobin.  This is a protein molecule with iron at its core that binds the oxygen molecule when it passes through the lung and then deposits it in the tissues.

 

sem_blood_cellsWhite Blood Cells (WBCs) are the main cells of immunity, in particular the lymphocytes.  Another type of WBC includes the macrophage (‘Big Eater’), a general-purpose soldier, that removes all kinds of cellular debris and foreign matter.  In contrast lymphocytes provide immunity to a specific organism.  We learn about two types of specific immunity: from antibodies (humoral) and cells (cellular), with  B and T lymphocytes the responsible cells, respectively.

The reality is that is a simplification of a very complex system, with multiple different cell types, proteins, and chemical messengers involved.  For our purpose of understanding vaccines, the key point is that it is easy to measure humoral immunity: test for antibodies in the blood.  But testing for cellular immunity is harder, , and is not usually needed.  And when tests of immunity are done, it is usually use humoral immunity that is tested: antibodies.  In some cases (such as measles), the antibody provides a reasonable, but not perfect indication of protection.  For pertussis (whooping cough), we can measure various antibodies to the different parts of the bug, but not sure what level of which means protection.

The specific immune system requires exposure to learn. With a virus like measles, once the immune system has been exposed to an infection the immune memory that develops prevents further infection.  We develop life-long immunity, once we have recovered from the initial illness.  A virus like influenza is constantly changing so that it can escape detection by the immune system and cause infections many times.

The development of immune memory involves the selection of B and T cells. Those cells that are most effective through a match between antibody – a protein that will ‘fit’, like a lock and key, an ‘antigen’.  The antigen is usually a specific part of a protein or other component.  The antibody can ‘lock on’ to the antigen with relative degrees of good fit.  Those cells that produce the best fitting ones to circulating viruses are naturally selected.  The best ones proliferate to produce both the immediate attack on the bug, and a small number are retained as memory cells.  These are the ones that remain long-term ready to be reactivated, as well as those that continue to produce antibodies.

So, now we are ready to understand how a vaccine works…

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The germ theory of disease

Your immune system protects you from bugs: harmful micro-organisms. These are tiny living organisms that can infect and sicken us. There are many types, including:  viruses, bacteria, fungi, protozoa.  It might surprise you to know that it is a very modern idea that germs – another word for bugs – cause disease.  The germ theory has only been widely accepted since the second half of the 19th century, and is still not accepted by some.

Please allow me an arithmetic deviation. When was the 19th century?  Our calendar starts with Jesus.  A century is 100 years, so we describe the first 100 years after His birth as the first century.  So the 19th century are the years from 1800 to 1899, or the 1800s.  In 2016, we are living in the 21st century: science fiction for me,  growing up in mid-20th century.

Wikipedia tells me that germ theory was originally proposed by Girolamo Fracastoro in the year 1546. (I wonder if there has been adequate credit given to earlier Chinese or Greek thinking.  Most ideas can be found in these classical sources,   confirming the biblical verse that ‘there is nothing new under the sun’. ) The microscope was only developed in the 16th century, and it was not till 1676 that  Antonie van Leeuwenhoek discovered micro-organisms.  He had developed a microscope with up to 300 times magnification and  discovered red blood cells and spermatozoa (or sperm, if you remember where you come from).

The role of micro-organisms, or bugs, in causing disease remained controversial until medical science advanced. As these bugs are too small to be seen, they were not discovered until we had microscopes.  Viruses are much smaller than bacteria, and cannot be seen with a light microscope.  An electron microscope  allows us to see viruses, but we can also see the effect of viruses on the cells they infect on a lab dish.  The first virus was only isolated in 1898, influenza virus in 1933.

The cartoon above shows the key features of the influenza virus: the two proteins that it uses to get into and out of the cell it infects and takes over, preparing billions of copies of itself in the infected cells.  Below, you can see these two proteins as well as the 8 strands of its genetic code, each coding for the proteins that make up the virus.  Influenza is an RNA virus, meaning its code is made of RiboNucleic Acid.  In contrast, bacteria and humans use DNA, or DeoxyRiboNucleic Acid, as our genetic code, in each of our cells.

 

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The influenza virus 

Source: http://www.twiv.tv/virus-structure/  where you can see other types of virus.

Our understanding of the immune system is even more recent than of bugs.  Many different types of viruses cause disease; and even more so for bacteria. For most viruses, including influenza the symptoms we get are not from the infection itself, but from the body’s attempt to remove an invader that has breached the initial defence barriers of skin, gut, or vagina.  This is why many viruses will cause an influenza-like illness.

Other viruses, like measles, polio, or Ebola each have distinctive patterns of illness, that still is the reflection of the battle between the virus and the specific tissues that that virus has a propensity to attack. In addition to an acute infection, some vaccines can be carried for a long time to be reactivated as shingles or cancer. hepatitis B and human papilloma virus cause cancer of the liver and cervical cancer, respectively.

The immune system does not only protect us from these infections, but we can teach the immune system so that it can defeat an infection before it sickens us.  But to understand the immune system, we first need to understand cells….

 

 

 

 

Diversion on dates:

So, was Jesus born in Year zero or one? Probably neither, but in 4BC – which means four years before Christ is born, so how can that be?  The problem was this new calendar, called Annus Domini (AD) , was not established till some hundreds of years later.    The issue of whether to choose zero or one as the starting point is a computer coding question too.  Are you 0-day or 1-day old on the day your are born?  The zero itself was not born till seventh century India, around 650 AD (7th century), though did not reach Europe till the 12th century I hope by now you will recognise is the seventh century after His birth.  And that in 2016, we are living in the 21st century.  Can you believe it?

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Does Logic Work? Anti-Vax arguments to teach thinking…

I have this dream.  An educational resource to teach children to think: numeracy, logic, and how different an issue seems from an individual versus a population perspective.  In part, this is my response to anti-vaccine arguments that flourished following a 1998 Lancet article; but are as old as the first vaccine:

In 1796, Edward Jenner demonstrated that prior ‘vaccination’ with cowpox would lead to protection against smallpox.  Smallpox was one of the worst scourges of humanity, until eradicated in 1977 through a global immunization programme, led by the World Health Organization.

Anti-vaccine arguments date back to Jenner:  like most vaccines smallpox can cause serious adverse reactions, but it does not turn anybody into a cow – as depicted in the first image of the anti-vaccine movement.

I don’t know if anybody seriously believed that smallpox vaccine – cowpox that has been altered through multiple generations of human transmission – could turn one into a cow.  But the list of ills caused by modern vaccines, according to some anti-vaxxers, covers a large range of human illnesses for which we either have not yet defined the cause or there are multiple causes.

In fact, smallpox vaccine has amongst the worst safety profiles of vaccines.  Luckily for humans, this is now only of historical interest.  Smallpox was the first disease eradicated by a vaccine; though some anti-vaxxers can provide entertaining accounts of why it really has not been eradicated, or that its eradication was purely coincidental to the vaccine programme.

In 1999, I was invited to write WHO guidance on adverse events following immunisation.  The AEFI is a carefully crafted concept that requires understanding of the logical fallacy of post hoc, ergo propter hoc.  This is Latin for mis-attributing to coincidence a causal relation: when event A happens after event B, we can say that B caused A.

In reading through the science of AEFI, we classified events that happened after as being possibly, but not necessarily caused, by the vaccine.  The event could be from an error in storing, preparing or giving the vaccine: a programme error.  These remain too common in developing countries, the main audience for the WHO manual.  Injection and anxiety related reactions are relatively common, especially in poorly planned mass campaigns. But coincidental events are the main problem for immunisation programmes are those that just happen to occur after immunisation.  So, why is my claim for an event being coincidental stronger than the claim around smallpox eradication?

Of course, some AEFIs are caused by the vaccine. The known vaccine reactions have been well defined during initial trials; rarer events require wide-scale use in programmes to become evident. During my time leading the NZ immunisation programme, I found it ironic that the vaccine with the most severe known reaction (roughly 1 in a million risk of paralysis) was the one that caused the least public concern about vaccine risks. Perhaps because it was the only oral vaccine in the national immunisation schedule at that time.

In contrast, there is roughly a 1 in 200 risk of paralysis from infection with the poliovirus.  The risk difference between disease and vaccine is why immunisation improves health.  But human cognition is not well designed to compare risks.  For example, we worry more about getting on an airplane than in a car; while on a tropical beach we fear sharks more than a coconut falling on our head. (I hope that you know the first risks are statistically much lower than latter.)

So, you can see that our intuitive risk meter is off; but we can correct this through deliberate process of logical thinking together with careful review of the available evidence.  What I want is an education resource that helps children understand how to think in that deliberate process.  Which involves understanding numbers and logic, as well as the inevitable flaws in all kinds of data.  And the challenge of how to carefully appraise the evidence.  So, what does this education resource look like?

I look forward to contribution, as I explore these ideas, starting with the number one and how 1+1 can equal 0,1,2 or 3 – and the intrinsic ‘slipperiness’ of numbers.

 

 

 

Vaccines and numbers

The story of vaccines starts with a new child (is it you?) arriving into our strange quantum world; where particles come into and out of existence, by charm, spin or whim.

Each of the seven billion, or so, human beings alive at this space-time have this shared story.  It starts, when one (1) sperm joins one (1) egg & become (1) you. Did I just prove that 1+1 = 1?

But, 1+1=2.   Can both be true?  Yes, 1+1=2, has to result if the 1 refers to the same thing.  If not, it can also be 1+1= 3:  (1) Mum + (1) Dad  become a family of three, when you are born. And more as the family grows.

It all depends on both numbers counting the same thing.  In the case of sperm and egg, this is a special relation where both become a new thing: you!  There is also matter and anti-matter that together become nothing (1+1=0). (Strangely, this means that from nothing we can get something in the reverse process that is constantly happening in the sub-atomic world of this strange  quantum physics…

 

Why all this? To torture numbers?  The number is only valid, if the logic is correct.   If the logic is incorrect, the number is either meaningless, or can even mean the opposite.  It helps to understand numbers, if you want to understand vaccines.  Numbers can be used to confuse as well as illuminate.

In Propositional Logic, a statement of fact, or proposition, has Truth Value of  ‘1’ if ‘True’, and ‘0’ if ‘False’ . In Fuzzy Logic, numbers can also between 0 and 1, as this can better describe the world than the sharp categories that our minds make up.

So, what does number ‘1’ mean?  It defines the unit, the thing.  It is also the space between numbers – a unique role.  I hope you know all your numbers, but if you keep adding 1 you will never get to infinity, just a bigger number.  If you like big numbers let be introduce you to the Googol (10^100 or 1 with 100 zeroes after it) and Googolplex (10^Googol). The Googol alone is so unimaginably large that it exceeds the dimension of the known universe, nearly whatever units one uses.

So, you are 1 in 7 billion and more living breathing human beings on planet Earth-today.  One billion is a huge number:  (10^9 1,000,000,000).  It is biologically unprecedented for a single species to cover the entire planet. All of us from a small family that arose in Africa about 200,000 years ago, and survived climate change to emerge smarter.  Prof. Harari suggests that the Cognitive Revolution, about 70,000 years ago, led us to outcompete the other human species: at least half a dozen (which is 12; i.e., 6) that existed around that time.  From Africa, our ancestors left  about 50,000 years to progressively cover the planet, making countless species extinct as we rose to the top of the food chain through the organising capacity of language.

These are some numbers that can give you a perspective of your life, which is so short compared to these numbers, even smaller compared to the estimated age of Earth at 4.5 billion years.  The Bible gives us  ‘three score and ten’ or 70 years  (so how much is a ‘score’ – an old English measure?)  But increasing numbers of people are living over 80 or even 100 years; many in good health.  How long have you been here for?  And how long would you like to stay?  I often wonder if we go back to the place we came from, or this life is some small part of something that we cannot even comprehend.

Now, back to the start of your story.  A child is conceived (from the sperm and egg), grows in its mother’s womb for about 38 weeks and is then born on this planet.  The womb nourishes and protects you as that first cell divides and divides to become the trillions (10^12 or 1 with 12 zeroes).  Once born into the world, you are now exposed to the  risk of  bugs: microbial infections: bacteria, viruses and other parasites. You are born with natural defences against these, and also an immune system  that can be ‘trained’ to protect against specific bugs.

This is what vaccines do.  But first we must understand a bit more about bugs, and the germ theory of disease.