Thursday 28 July 2016

Mosquito flight and laser knockdown

How can a laser shoot down mosquitoes?

In order to use lasers in the fight against Zika and malaria, it's important to understand the biology of mosquito breeding and flight. 

High speed cameras need to be used to detect insects and identify mosquitoes. 
Here's an example of slow motion capture of a mosquito in flight captured by Intellectual ventures.

Mosquitoes beat their wings 250-1000 times a second, so this footage is amazingly slowed down.
 Astonishingly, this method claims to be able to distinguish male and female mosquitoes.
As you can imagine, the differences are subtle when the insect is in flight. Apparently female mosquitoes choose a mate based on the frequency of their wing beat.
Here's a video of the mosquito-killing laser in action:

Tuesday 28 June 2016

Anti-scientific bias of 'scientific' animations

How does personalising cells destroy the magic?

A review of anatomy and physiology videos


Naturally, blood is typically represented as red, as here. The function of Red Cells [Anatomy World]. Red cells are enlarged and spread out to make them visible. We are used to such distortions to make cells visible; perhaps you think I'm being pedantic but a dilution of blood cells like this would be incompatible with life. Anyway, depth is implied by showing artificial incident light and variation in scale and usually the cells are rushing past us to suggest cells propelled by the pumping of the heart and suspended in plasma.


In this video, Red cells are given human features in order to describe: A Day in the Life of red blood cell [Digital disasters] . Red is the obvious colour although in the absence of light, ie inside the body, blood is black but so is everything else. 
Each red cell is given a face, a personality and a voice.
To me, giving faces to organs and cells creates a childish, fairy tale atmosphere which is patronising, deceptive and inaccurate.
If we personalise our organs, we overlook the way they can sometimes fight each other, harbour cancer or weather faster than we would like.  

Darwinian evolution implies that there is no organising intelligence, just an incredible interplay of ultimately autonomous physiological processes which sustain life by constantly maintaining temperature, oxygen, acidity and glucose within a narrow range to sustain the miracle of life. 

Here's a contrasting film: Haematology - Red Blod Cells [Armando Hasudungan]
Perhaps this errs on the opposite end of the scale: the microscopic laboratory vision with conventional ignoring of scale. The danger here is that anatomy is only part of the picture. At heart it is a question of what we want people, medical students, doctors to know of all the facts that have been discovered about blood. This video poses as a scientific account but is only a partial view.

One variant of the red video is in fuchsia pink with contrasting light blue, here used to show the adhesion of platelets to a clot.


Blood, Part 1 - True Blood: Crash Course A&P #29 [CrashCourse]
Blood vessels are usually shown as diagrammatic cylinders, as here. Again, red cells are massively enlarged and widely spaced out. Even this largely 'scientific' film veers into characterisation of whicte blood cells as people:




 This feels sentimental and old-fashioned. Can the audience bear to live in an existential world where our function depends on ingrained, automated reactions to random variation? There is a creepy angle to personalising cells: what if, like people, they become argumentative, temperamental, self-destructive? But this unsettling option is rarely evoked. Most videos would like us to bathe in the comforting image of our tissues and cells constantly working lovingly to help us live our lives with a smiley face.


Sunday 26 June 2016

How medical illustration distorts the facts

How medical illustration distorts the facts

As soon as art is used to explain science a rift opens up between reality and the image.  

This happens in human biology for a variety of reasons.
  1. Biological events happen in complete darkness: hormone secretion, clot formation and the pumping of the heart happen deep inside the body where there is no light and no convenient gaps between the organs. The heart is wrapped around by the lungs, the pancreas is beside the liver and the duodenum. In order to see the actions of a single organ you need to isolate it from its surroundings but the movement of the lungs influences the emptying of the heart. Even an endoscope inside a blood vessel cannot see the vessel wall unless the blood is flushed out of the system. That's why radiologists use contrast medium to create a 3D image of the circulation.
  2. Most biological events are too small to see with the naked eye or the optical microscope, so we need to construct an image to describe what is happening on a scale of nanometers [one millionth of a meter] or molecular events at the level of picometers, maybe sometimes at a sub-atomic layer in the case of changes in quantum physics which occur inside the body. 

  3. When events like clotting are scaled up so we can observe them there are deliberate mistakes in scale; to show platelets and the vessel wall in the same image, one molecule of haemoglobin is made to look huge in comparison to one red cell.

  4. Biological events, like the pumping of the heart are dynamic, changing in a rhythmic cycle over seconds, hours and a whole day. So to capture what's happening you can opt for a snapshot like a sagittal CT scan or use ultrasound to record an echocardiogram over several seconds to observe dynamic emptying and filling. Either way, it's a compromise between accurate anatomy and indicators of function.
  5. Biological events such as brain activity involve multiple processes which all happen simultaneously. During brain activity the blood supply increases, brain cells fire off electrical impulses, chemicals: neurotransmitters are released and the whole process goes on an anatomical structure which is unique to every individual. The brain cells are bathed by a constantly changing symphony of locally released and systemic hormones. But we can only measure one change at once; measuring the electrical activity would disturb the magnetic radiation scan of the brain. The constantly changing level of transmitters is not recordable in life.  
For all these reasons, the medical imagery used in videos is based on distortions: at the macro level by the results of dissection of dead bodies, X-rays, ultrasound and at the micro level by laboratory studies of tissues and cellular processes.
My point is that none of these methods of illustration can be explanatory of daily events in the human body such as breathing, clotting, fatigue and thinking.  It's not the fault of illustrators; it's a result of the hyper-specialism of scientists who can only attribute health or disease to a factor within their specialty: a single electronic charge, a neurotransmitter, a change in structure or a pretty pattern on scans and not combinations of several of them simultaneously which our cells take for granted.

Friday 24 June 2016

What does Zika look like?

What does Zika virus look like?

 Viruses are small

Very small. Smaller than a speck of dust, smaller than a germ like E coli. Between 20 and 300nm [there are one million nanometers in a millimeter]. So we can't just take a photo of them. 
Here are some 3D renderings of viruses such as this one: Hepatitis C

It looks like a studio portrait, with two lights from above and a backlight helping it standing out from the monotone background. 

But it is nothing of the sort. It's made-up.


Viruses can only survive deep in body tissues, usually inside cells. If we could film viruses in the blood stream they would be like flotsam washing along the arteries and veins, dwarfed by thousands of giant red cells and a few even larger white cells. But we can't. Light microscopes can only reach a resolution of 200nm so even a giant virus is a minute dot.

But the electron microscope has a resolution of 50pm [there are a thousand picometers in one nanometer]. The problem is that the smallest electron microscope is about the size of a PC.  Here it is:

So it won't fit inside any living body. As a result for transmission electron microscopy you need to:

  • Take a sample
  • bring it to the lab
  • fix the structure with formaldehyde
  • freeze it quickly in liquid ethane and keep it frozen
  • take fine slices 
  • place the sample in a vacuum 
  • direct electron beams at the sample

You'll be familiar with the resulting gray scale em photos like this:


Here is our first sight of Zika virus in frozen section.

It looks spherical and transparent. There is no colour. The only way we can see coloured images is by adding stains to the sample. And the only way we can see the 3D structure of the virus is by using a scanning electron microscope, which can work with thicker sections but you may have to:
  • bathe the sample in electron dense solution
  • dry it
  • freeze fracture it to examine the broken off edge
  • embed it with epoxy resin
  • blow metal vapour such as platinum across it to create shadows
  • take an imprint of the structures with carbon vapour
  • stain it with heavy metals: lead, tungsten or uranium
As you can imagine, any of these processes may interfere with the sample to cause artefacts. So it's necessary to compare the results of several different methods to get an accurate picture.
Since viruses are essentially colourless, artificial colour is added in the staining process or in illustrating the virus structure in order to make it visible. It's guesswork:



From these sudies we know that Zika virus has a smooth surface but develops projections when it is attacked by acid inside the cell. The projections are exaggerated in some illustrations to create a more beautiful/sinister image:





 This image of Zika virus homing in on a human embryo [much reduced in size is particularly unsettling:

For me, the image which best captures the structure of Zika is this diagram: 




Wednesday 11 May 2016

Top Zika virus quizzes

Choose the best quiz above

Zika Quiz sites are important as a measure of what people have learnt about Zika

Test your knowledge of Zika virus with these on-line quizzes.
Which one is best?


Zika Quiz site           number 
                            of questions


Medicine Net         9             Correct answers given immediately, includes prevention 3/5

WHO                     6             Very basic, answers given at the end, easy 1/5

PRI                        5             Answers given immediately, a bit pedantic, difficult 2/5

Washington Post 18             Thoughtful, imediate answers, scientifically sound 4/5

Stuff                     10             Short, intelligent, immediate answers and bar charts 5/5

Outlook               10              Answers at end, no explanatrion,ambiguous questions 2/5

My favourite is the Stuff.co.nz quiz because it shows [briefly] which options most people have chosen. From that you can work out the discriminant questions; in planning education, you need to focus on the answers that most people get wrong.
But what is important to know?
In the Stuff quiz most people knew when Zika was first detected, the vector of Zika, and its gender, the status of a vaccine, the proportion of people with no symptoms and the duration of symptoms.

People weren't so sure about where Zika was found and what symptoms it causes.  But which facts are the most important? How to protect yourself is relatively under-represented here.



Why is Zika vaccine taking so long to develop? 8 Reasons

Zika Virus

Zika belongs to the flavivirus group that is spread by arthropods: Yellow Fever virus [YFV], Japanese Encephalitis Virus [JEV], Tick-borne encaphalitis virus [TBEV] Dengue [DEN] and West Nile Virus [WNV]. 

Each of these viruses has a wide and growing distribution, due to international travel and climate change favouring spread of infected people and mosquitoes:

Why is Zika virus vaccine taking so long?

1. Because Zika virus seemed to be harmless

Zika was isolated from Rhesus macaque monkeys in Zika Forest, Uganda in 1947. When human infections with Zika were detected in the 1950's, the symptoms were mild: flu-like transient fever, headache and muscle pains. 
However since then two changes have occurred. Transmission of the virus by mosquitoes and the development of Pacific strain associated with microcephaly and Guillain Barre Syndrome [GBS: a neuropathy, or nerve disease]. 
Spread of the virus has been aided by international travel and climate change favouring the spread of Aedes aegypti, the main mosquito vector. Other mosquito species such as Aedes albopictus are capable of harbouring Zika which would be a serious development.

2. Because most Zika infections go unnoticed

Zika infections usually have no symptoms. In any case flu-like symptoms are so common they are rarely investigated. However older people are at higher risk of GBS after Zika infection and the dangers to unborn children are extremely severe, especially in the first three months of pregnancy.
Japanese encephalitis virus is similar to Zika. Most JEV infections go unnoticed but one case in a thousand progresses to brain infection. A mouse brain derived vaccine is available with 80-95% efficacy and vaccination in affected countries has led to a fall in incidence since 1960. A cell-grown strain appears to be safer and more effective. A two dose regime is suggested to match the conversion rate of other vaccines.

3. Because Zika virus is constantly changing

Viruses are the fastest evolving organisms on earth. They exist in multiple forms so that drug resistant strains are already present before the drugs are even developed. Viruses exchange genetic material and switch genetic code frequently leading to multiple mutant strains, some of which survive and come to dominate the population. This is illustrated by the current change in Zika to become much more invasive and adapted to life in a mosquito.
The RNA of flaviviruses can be read backwards or start from a different base pair and still produce viable organisms. They are the masters of improvisation.
Like most viruses, JEV has shown changes in the dominant strain from genotype 3 to genotype 1 however immunisation with one strain has been shown to protect humans from all strains. 

4. Because Zika virus rapidly enters human cells

Zika's ability to penetrate human cells is the key to its success. Once inside the cell the virus is protected from the body's defences. Zika deconstructs itself and the RNA component hijacks the cell into making more viruses, ultimately leading to cell death and release of mature virus particles.
Survival inside the cell means that viral infections such as Herpes can persist for long periods. A vaccine needs to target the immediate entry of viruses in the blood stream before they enter human cells. 

5. Because Zika virus survives in other animals

YFV cannot be eradicated because a reservoir exists in non-human primates, and tropical birds and mammals 'the sylvatic cycle', in towns YFV is spread from person to person by Aedes aegypti the 'urban cycle'. In addition some mosquitoes target humans and non-human primates 'the intermediate cycle'.

Despite the wide availablity of vaccine, outbreaks still occur. So far YFV has not become endemic in Asia but a current outbreak in Angola [April 2016] increases the risk via migrant workers returning to Asia.



6. Because of the danger of brain complications from the vaccine


The first YFV vaccine was made in the 1930's and substrains of the YFV-17D vaccine, are used nowadays to protect against infection. >98% of people have an immune response to a single dose and because antibodies are detectable 30 years later, a follow-up at ten years is no longer recommended. 
However the early vaccine was complicated by brain and spine complications and the current vaccine has an adverse rate is 38/100,000. Some people are allergic to gelatin or chicken egg protein,however 1/100,000 reactions are dangerous: encephalitis or multiple organ failure.
These complications can't be detected until the vaccine is tested in a large human population. Scientists are understandably cautious about introducing the vaccine until they are sure that the vaccine is effective and safe.

7. Because detecting Zika is difficult

Host response to the Zika virus, antibodies, are only detectable in the blood of infected people briefly. Antibodies are detected in the urine for longer.  However immunity to YFV may interact with the result, complicating the issue. 
The most sensitive test  is to isolate the Zika virus itself by RT-PCR but this requires deep refridgeration at -80C to preserve the virus, which isn't widely available.

8. Despite years of study, there is no vaccine to Dengue virus

Like Zika, closely related Dengue is spread by mosquitoes and as the map shows, it's the most widespread and the most dangerous flavivirus, causing 50m infections and 20,000 deaths a year. Antibody-dependent enhancement [ADE] explains Dengue's resistance to vaccines. The body's response to infection creates an army of monocytes and macrophages that ultimately spread the infection.This may explain why second infections in an individual can provoke dangerous Dengue Haemorrhagic Fever [DHF]
Dengue has four subtypes, so a vaccine must protect against all four otherwise it might be associated with DHF. Conversion rates of 40% against all 4 serotypes are reported and 70% after two immunisations, however the risk of DHF has halted some testing.