Sunday, 19 March 2017

Altitude and health – three towns in East Lancashire.


East Lancashire, from the summit of`Pendle Hill

The sun and susceptibility to coronary heart disease – the experience of Lancashire, UK.


Previous Posts have described the well-defined epidemic of coronary heart disease (CHD) that  occurred during the mid and latter parts of the 20th century. Also the Posts have led to the conclusion that the only realistic (and therefore the most probable) cause of the epidemic appears to be an infection. The actual causative organism has not been defined, but it is usual that the recognition of a microbial cause of a disease precedes the identification of its causative organism.

The presence of a disease depends on a combination of its cause plus the susceptibility of an individual or population to  it. This is often a function of immunity.

However the identification of factors leading to susceptibility are of great importance. We need to determine the difference in the incidence of disease, death rates and life expectancy in various places.

A recent Post looked at the much higher incidence of illness and early death in Belfast in Northern Ireland compared to Toulouse in France. The only answer appeared to be a protective effect of the sun acting on the population of Toulouse, which is almost 1000km closer to the equator. Whereas Belfast is at sea level, Toulouse is a slightly higher altitude, 150m above sea level.

Health inequalities in England

A previous Post has looked at health inequalities in Three English Towns, demonstrating higher death rates those in the north of England. There was no explanation other than latitude. Dietary characteristics were the same in all towns. 

It is now well-known that standardised mortality rates are higher in the north-west of England than the UK average, shown in Figure 1. Mortality rates are lowest in the south, and this conforms to a latitude effect. However London has higher mortality rates than the surrounding rural locations.



Figure 1. Mortality rates in England and Wales

Burnley, Nelson and Colne

Burnley is one of the major towns of Lancashire, and Nelson and Colne are smaller towns just 10 and 20 km to the north-east. All grew during the 19th century as cotton and textile manufacturing towns, an industry undergoing major decline during the second half of the 20th century. Like all industrial towns, they have been characterised by significant but relative socio-economic deprivation, with low incomes, poor housing, low average educational achievement and bad health profiles.


Figure 2. The north-west of England, Burnley Nelson & Colne shaded

The particularly interesting aspects of the health profiles are the differences between theses three towns that are geographically so close together and so similar in respect of employment patterns. This is shown in the infant mortality rates in the early years of the 20th century.


Figure 3. Burnley, Nelson and Colne

With the standardised average England & Wales mortality rate (SMR) of 100, that of Burnley was one of the nation’s highest infant mortality rates at 160. But it was significantly lower at 117 in Nelson, and well below the national average at 78 in Colne. The difference is remarkable and no explanation was offered when the data were first published.


Figure 4. Infant mortality rates, 1911-1913

The study was revisited later in the 20th century, this time looking at adult health profiles. During the years 1968–1978, the SMR for “all cause” mortality was high at 121 in Burnley. Nelson was better at 109, and the SMR in Cone was on the national average at 100. So we see the same pattern as was present more than 50 years earlier.


Figure 5. Mortality rates, all causes

When we look at deaths from “bronchitis” we see an overall high mortality rate in Lancashire, a remarkably high SMR of 188 in Burnley. The populations of Nelson and Colne also show high mortality rates, but once again much less than Burnley, with Colne lowest of the three.


Figure 6. Mortality rates, bronchitis

Deaths from pneumonia show the same pattern, Burnley highest of all at 174, Nelson lower at 125, and Colne lower still at 108, just above the national average.


Figure 7. Mortality rates, pneumonia

Deaths from coronary heart disease (CHD) show the same pattern. All are above the national average, but is this expected for towns in the north-west of England. Again, the highest mortality rate of the three is Burnley, Nelson in the middle and the lowest is Colne.


Figure 8. Mortality rates, coronary heart disease

The importance of geography

So how do we explain this? There is no obvious socio-economic difference between the three towns. No formal research has been undertaken in this respect but no significant population  differences can be anticipated, nothing to account for such major differences in death rates. 


Perhaps it is the geography that is important. We saw this in the comparison between Belfast and Toulouse: geography was the only realistic explanation of the much higher mortality rates in Belfast, the higher latitude with a lower intensity of sunlight being the important factor.

As with Belfast and Toulouse, in Burnley, Nelson and Colne, we are looking not at a case of a disease but of a factor that increases susceptibility to a number of illnesses and results in premature death.

Burnley is located in the valley of the River Calder, a tributary of the River Ribble. The Ribble enters the Irish Sea between Blackpool and Southport. In Burnley the River Calder is joined by the Rivers Brun and Don, and also by Pendle Water. This was an advantage in the pre-steam era, when motive power for factories was provided by gravity acting via running water. 


Figure 9. Burnley

Burnley is therefore relatively low-lying. It is in a valley where four rivers meet, and it is known to be damp. In the industrial era the smoke from domestic and factory chimneys would accumulate in Burnley. When coal and steam came into industrial use, the newer industrial towns of Nelson and Colne could be built away from the rivers. 


Figure 10. Coal mine in Burnley, now closed

Altitude

Burnley lies at 105 metres above sea level. 
Figure 11. Burnley

Nelson is further up the valley of Pendle Water, and is built on higher round above the valley. It lies at 160 metres above sea level. 


Figure 12. Nelson
Colne is even further up the valley and was originally (in the pre-industrial era) a hilltop town, lying at 190 meters above sea level.


Figure 13. Colne

And so here we have the most obvious and the most likely explanation of the variation of indices of health of the populations of the three towns: altitude.


Figure 14. Altitude variation of Burnley, Nelson and Colne

Altitude in the USA

We have seen this phenomenon in a previous post, which described the same feature in the USA. At a latitude of 37–38 degrees north of the equator, between Washington DC and San Fransisco, there is a convincing inverse relationship between altitude and standardised death rates from coronary heart disease (CHD) and cerebro-vascular disease (CVD).
Figure 15: Land mass profile of the USA at 37–38 degrees north, and inverse  CHD/CVD mortality rates

Higher altitude means higher intensity of sunlight at ground level. Of more importance is being above the pollution that is inevitable in an urban environment. An increased altitude of even 30 metres can make a significant difference: the polluted layer of atmosphere is heavier than the atmosphere, and is thus low-lying.

Atmospheric pollution

In a city such as London the polluted layer of atmosphere is only thin, perhaps 20 metres. 


Figure 16. London, looking north from Greenwich

In many cities in China and other rapidly industrialising countries, the atmospheric pollution is very great and its removal by wind and rain is infrequent. The layer of pollution becomes so thick that the sun is totally obscured, despite no natural cloud.


Figure 17. Xian, China, mid-day 

Atmospheric pollution is both chemical and physical. Oxides of nitrogen and sulphur cause irritation to eyes and lungs. These give the chemical component of damage.

The most damaging component is particulate material, tiny particles of dust and unoxidised carbon, giving a physical rather than or as well as a chemical effect. It is the particles that are responsible for the obstruction to the passage of sunlight to ground level.

City versus countryside

It has been known for more than two hundred years that death rates are much higher in people living in industrial cities compared to those living in a rural environment. 


Figure 18. Thomas Percival 1740–1804

It was first demonstrated in a monograph written in 1773 by the Manchester physician Thomas Percival. The monograph was entitled “Observations on the state of the populations of Manchester and other adjacent places”. It recorded that in Manchester (population 27,246) and in Liverpool the death rates were one in 28 of the population each year. This was twice the death rate in surrounding villages in rural locations, one in 56 per year.

It is the same today, standardised death rates being higher in the cities (polluted air) than in rural locations (clean air).


Figure 19. Cloud but clean air in the Ribble Valley, where I live

Conclusion

Life expectancy is greater and death rates lower in the countries of southern Europe compared to countries in northern Europe.

Death rates from a number of diseases are lower with residence at a higher altitude. This demonstrated in the USA and in East Lancashire, UK.

Death rates are lower in rural villages than urban cities.

Pollution blocks the sun much more continuously and much more effectively than natural cloud.

The common factor is that a major determinant of good health and long life is good exposure to the sun. 





Friday, 24 February 2017

The origins of life - rock and water


And now for something completely different....

This is very different from my usual Blog Posts, but I hope you will find the subject as fascinating as I have found it.


The inorganic origins of organic life

Moonset over London - a long way from the origin of life

Creation

The “Big Bang” story of the start of the Universe 14 billion years ago is rather dull: there was nothing and then in less than a microsecond later there was everything. The Book of Genesis is much more interesting; it says the same thing but with a longer time-scale. There are countless other similar and imaginative creation stories composed by the many groups of people in the world.  


Creation – The Ancient of Days. William Blake

After or during creation, “everything” had be be remodelled into things that we can see and things that we cannot see – matter and anti-matter, visible energy and dark energy.

The Earth itself appears to have been created 4.5 billion years ago, and a lot has happened since then. 


The evolution of the Universe during 14 billion years


Evolution

The Just So Stories” (Rudyard Kipling 1865–1936) have given colourful suggestions of the evolutionary origins of some advanced animal species, but these would have been in comparatively recent years. The great mystery is how and where life itself originated. 


Eukaryotes (cells with nuclei), the cellular building blocks of the advanced forms of life, appeared about 1.6 billion years ago. Before this, there were just bacteria and archaeadiscovered only recently. 

But life had its very earliest origins 4.5 billion years ago. 

Panspermia

There is a suggestion of panspermia, the seeding of life from comets into a receptive Earth environment, bringing the fundamentals of life from great distances. 



The concept of panspermia  has its origins in the 5th century BC writings of the Greek philosopher Anaxagoras, with further suggestions in the 19th century. Fred Hoyle (1915–2001) and Chandra Wickramasinghe (born 1939) have proposed panspermia in modern times. 



Hoyle and Wickramasinghe have suggested that recent pandemics of “flu” might have been due to viral DNA or RNA seeded from comets. This is an interesting but untestable hypothesis.

An acceptance of panspermia only begs the question of the mechanism of the origins of life elsewhere. It also acknowledges that evolution still had to take place on Earth: man and other advanced animal life could hardly have arrived by cometary transport.

Although panspermia cannot be excluded totally, it is perhaps more likely that life on Earth originated on Earth.

Zircons

Zircons are usually tiny mineral deposits less than a millimetre in diameter, but there are lager examples that can be fashioned into attractive jewellery. The important thing about zircons is that they can be dated back to times shortly after the creation of the Earth.

The chemical composition of zircons is basically zirconium silicate, ZrSiO4. However zircons contain several impurities, which give the gem-stones a variety of colours. 



One of the major impurities is uranium. This is of course radioactive and it decays to lead. The more recently the zircon was formed, the higher the ratio of uranium to lead. But in practice the ratio of lead is high, indicating a very ancient time for the formation of zircons. They can be dated to the very origins of the Earth.

The detailed analysis of zircons indicates that at the time of their formation, more than 4 billion years ago, the atmosphere contained water vapour, nitrogen and carbon dioxide. There was between 100 and 1000 time as much carbon dioxide as at present, as there was of course no plant life to absorb carbon dioxide and to release oxygen. Oxygen is a highly reactive element and all oxygen was in the form of oxides of carbon, hydrogen, and many metals. There was ample liquid water, indicating that temperatures were similar to what they are today.

There have been many major cataclysms disrupting the surface of the Earth and its atmosphere, but the sea bed remained much more stable.

The chemical constituents of life

The formation of life had to start off with the components that were already present 4.5 billion years ago. 

Life is fundamentally composed of carbon, hydrogen, oxygen and nitrogen. These are available as combinations in the forms of water (H2O), carbon dioxide (CO2), methane (CH4) and nitrogen. 
Methane

Nitrogen is found as a gaseous atomic dimer (N2), which is free in the atmosphere. Oxides of nitrogen (NO, NO2, N2O) are gaseous but form solid compounds as nitrates and nitrites.

The other important simple compound is hydrogen sulphide (H2S), which is a gas at a temperature of the freezing point of water. Water (H2O) is unique as a simple low molecular weight compound, being in liquid form at ambient temperatures (20–40 degrees Celsius). At normal atmospheric pressure it becomes a gas at the relatively high temperature of 100o Celcius.

Carbon, hydrogen and oxygen will form fats and carbohydrates (sugars). Nitrogen is necessary in addition to form amino acids, the basis of proteins and nucleic acids (RNA, DNA).

Cysteine, a simple amino acid, made up of hydrogen, oxygen, sulphur, nitrogen


All these constituents were readily available 4 billion years ago, as they are today. It is likely that they have been available on other planets. But more than just the atomic building blocks of life were necessary for life to begin.

Polymers and the development of organic compounds

Two other things were necessary for simple organic molecules to be created, and for them to be assembled into complex molecules. 

Life is composed of simple sugars, fats, amino acids and nucleotides, but these must be polymerised, built up into long chains. 


Pentane, a 5-carbon polymer of methane
Polymers of glucose form starch as an energy store in plants, glycogen as a similar energy store in animals, and cellulose, a structural polymer in plants. Various long-chain fats  are polymers of methane. Complex proteins are polymers of amino acids. DNA and RNA are polymers of nucleotides.

The need for sustained energy

For the synthesis of simple and then complex organic molecules, a source of constant energy was necessary. 

There has been the suggestion that life started from an atmospheric chemical “soup” with the energy input being from flashes of lightning. However lightning does not provide the constant and manageable energy flow that would have been necessary. The surface of the Earth would not have been sufficiently stable for life to develop, and zircon analysis indicates that the atmosphere would not have been suitable.

The source of constant energy has been found in structures deep in the oceans.

Deep sea alkaline vents

Lost City, 60 metres tall


It is now thought that life started in deep sea alkaline vents. These are not the superheated hot smokers that we are more aware of, but rather less dramatic structures that have been discovered more recently. Water at moderate temperatures emerges from deep sea alkaline vents into rock structures with heights up 60 meters. The most famous of these structures is known as “Lost City”. 

The important features are that the water emerging is not very hot, is alkaline, and contains dissolved hydrogen and methane. 4 billion years ago the sea was much more acid than today, as the result of much more carbon dioxide in the atmosphere.

Lost City and similar alkaline vents are high towers of a sponge-like arrangement of the mineral olivine (Magnesium Iron Silicate). Olivine is hydrated into serpentine, a common mineral that polishes well and has been used in many buildings, such as the Empire State Building. 


Alkaline water with pH 9–11 percolated through a sponge-like matrix, with at the time acid sea water  with pH 5–7 on the other side of the porous rock plates that make up the “sponge”, rock as thin as one micrometer. This separation of acid and alkaline created an electro-chemical gradient, not unlike a battery, with a difference of proton concentration 1,000 to 100,000-fold. This was the constant source of energy that was necessary for the creation of organic molecules and ultimately life. This was the environment in which "protocells" (the forerunners of free-living cells) developed within the pores of the thin rock plates of the sponge matrix.


Catalysts and enzymes

The second necessity to enable a chemical reaction to take place is a catalyst, something that accelerates a chemical reaction but is not consumed by it. This is provided in the alkaline vents by the many metals that are found within the rock, in particular iron. Many other metals such as nickel and copper also act as catalysts. Think also of platinum in the catalytic convertor of a car exhaust system. 

Tiny metal clusters became incorporated into the rock and in particular into the walls of the pores in the rock. They were thus in a strategic position to catalyse chemical processes.

Olivine
As organic life developed the iron (and other metal) atoms became incorporated into highly complex protein enzymes, enzymes being biological (organic) catalysts. They are still within us today, the metal atoms from the very beginnings of life. An example is the iron atoms at the core of the complex protein haemoglobin, which carries oxygen within our blood.

The complex proteins that make up enzymes are concerned mainly with the flow of negatively charged electrons and positive charged protons (nuclei of hydrogen atoms). This is fundamental to the control of electro-chemical energy within living organisms.
Serpentine (polished)

Although magnesium and iron are the most common metals to be found in the important olivine and serpentine rock, nickel, aluminium, zinc and manganese can also be found in the silicates that make up the serpentine family of minerals. They all add to the range of catalysts, becoming essential trace-elements incorporated into the complex enzymes that were synthesised throughout the evolution of a wide range of life forms. It was the Dutchman Albert Kluyver (1888–1956) who demonstrated that similar biochemical processes are present from “bacteria to elephants”.

LUCA

LUCA was the Last Universal Common Ancestor of all life today, the great and unlikely accident in the development of the Earth.

The important steps in the early evolution of life

LUCA  was formed within the serpentine based sponge-like rock of the alkaline vents. It was not free living, but it was an entity that had become metabolically active. Its later developments were along two distinct and very long pathways, the bacteria and archaea. Their antecedents could only be released from the rock once they had developed protective cell walls. They also required metabolically active energy systems to replace the energy supply that sustained LUCA in the alkaline vents. In addition they required the more complex enzymes and genetic control proteins. These developments occurred during the course of half a billion years.

The development of cells

Cell walls were developed from droplets of oil, a relatively simple process involving the polymerisation of methane and also its hydroxylation to glycerol. 

The cells later absorbed what were initially free-living entities and these added much to the cell function. They included: ribosomes, for protein synthesis; mitochondria, for energy production; cyanobacteria, to enable photosynthesis in plants; spirochaetes, to form flagella that enable motility.

Mitochondria

Mitochondria transformed cellular life through a huge increase in energy production. Without mitochondria complex life could not have developed.

Mitochondrion

Mitochondria were initially free-living bacteria that developed membranes that enabled the production of large amounts of energy. This was through the Krebs cycle of energy from the oxidation of glucose the energy being stored as ATP (adenosine tri-phosphate, a simple organic compound), with water and carbon dioxide as waste products. 

The next stage was endosymbiosis, mitochondria becoming incorporated within cells for mutual benefit. A cell can contain up to 40,000 mitochondria, which reproduce to enable cell division without mitochondrial loss. The complex protein enzymes of mitochondria include atoms of iron from the earliest origins of life. Imagine 4 billion years after the creation of life, 40,000 mitochondria in each of 10 trillion cells in our body.

To give an idea of the power of mitochondria. I quote from Nick Lane (see below):


“A single cell consumes around 10 million molecules of ATP every second! The number is breathtaking. There are about 40 trillion cells in the human body, giving a total turnover of ATP of around 60–100 kilograms per day – roughly our own body weight. In fact, we contain only about 60 grams of ATP, so we know that every molecule of ATP is recharged once or twice a minute.”

"There is an electrochemical potential difference across the membrane, in the order of 150 to 200 millivolts. Because the membrane is very thin (around 6 nm thick) this charge is extremely intense across a short distance.... the field strength is 30 million volts per metre, equal to a bolt of lightning, or a thousand times the capacity of normal household wiring."

Nick Lane

The importance of simple inorganic gases

Interesting new research has investigated the role of mitochondrial “down-regulation” in mammalian hibernation, with a shut-down of energy and heat production. There is great curiosity concerning what can restore (switch on) normal mitochondrial function, and this is relevant to human illness in which there might be mitochondrial down-regulation. Studies of hibernating mammals suggest that hydrogen sulphide (H2S) might be responsible for inducing hibernation and for reactivating mitochondria. 

Other functions of hydrogen sulphide are also suspected. This is relevant to the origin of life four billion years ago as hydrogen sulphide is a simple gas, common and present undersea geothermal vents, especially in the “smoking chimneys”. However today it appears that hydrogen sulphide is produced in the body from the sulphur-contianing amino acid cysteine.

Incidentally, I before retirement I had great interest and considerable experience in patients with chronic fatigue syndromes (CFS, ME, SEID). I came to understand that the basis of the illness was a physiological down-regulation of mitochondria during an acute illness, but failure of restoration of normal mitochondrial function when the acute illness (usually infection) had settled. I had no curative treatment to offer, but the recognition of the importance of hydrogen sulphide might well provide a therapeutic opportunity in the future.

Nitric oxide (NO) is another simple gas with early origins that has important physiological actions today. One is the control of blood pressure and other cardiovascular effects. Nitric oxide is produced in the body by the action of sunlight on nitrates from the diet, as the blood circulates through the skin. This is one reason why the sun has effects greater than can be observed from vitamin D supplements.

…………………..


But these are different stories. The important message from this Post is to draw attention to how life was originally formed from the interaction of water and rock.

Our complex biology is based on simple inorganic origins that remain of great importance today.


The ages of the Earth


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The writing of this Post would not have been possible without the information contained in the remarkable book "The Vital Question", by Nick Lane, Reader in Evolutionary Biochemistry, University College London. 


I recommend it to those with a deeper interest in the subject of the inorganic origin of life.