Epigenetics: Sins of the fathers?

A picture worth a thousand words?

The term, ‘Central Dogma Theory’ was coined soon after the structure of DNA was elucidated back in 1953. In essence, it refers to the flow of genetic information. Thus, as stated by the theory, genetic information flows in one direction: from gene to intermediary RNA molecules, finally culminating in the production of proteins, the building blocks and rate controlling molecules of life. It was anathema to consider information flowing the other way. And the main heresy, in particular, involved the consequence of environmental factors influencing gene expression with heritable consequences. Sane, grown-up biologists would shudder at the very thought. To think so invited the resurrection of Lamarckism, an 18th-century proto-evolutionary theory. This theory, as presented by the French savant, Jean-Baptiste Lamarck, postulated that the environment could influence the genetic form of an organism and hence propagate for posterity. The classic example involved the giraffe. Lamarck’s hypothesis contends that in lean times giraffes would stretch their necks to obtain succulent leaves further up the tree branch. In time the neck would be elongated and this increase in length would be passed on to their offspring. Over generations, an elongated neck would become fixed in the giraffe population. The idea has a certain elegant simplicity especially as it was formulated well before the genetic mechanism had been discovered. However, subsequent experimentation, often involving cutting the tales off mice, showed that Lamarckism was not a viable mechanism for the transmission of genetic information. 

Conventional genetics contends that gene expression can be altered through dynamic mutation. Alteration of the structure of DNA can occur through mutagenic insults from natural radiation, replication errors and chemicals within the cell environment. If this change occurs within the ‘germ cells’, cells responsible for the production of sperm and eggs, this change may be passed on to subsequent offspring and a given mutation may result in the loss of gene function. This underlying mechanism is important for the transmission of genetic disease. If a mutation occurs in cells, other than the gonads (somatic cells), the gene alteration, in certain differentiated cells and in certain genes (oncogenes), may result, or contribute to the initiation of cancer. This model seemed to be all-encompassing with regard to gene expression up to the middle of the last century, but things were about to change.

Let us reminisce to the last Great War. In the latter part of 1944, the Allies seemed poised to liberate the Netherlands and storm into the Third Reich. However, for reasons outside the remit of this post, there was a winter’s pause. The unliberated Dutch folk experienced a period of intense famine during late 1944 and early 1945. Postwar clinical trials exposed an interesting medical trend. Children born to pregnant mothers during this critical 1944/1945 period exhibited relatively high rates of obesity and heart disease in comparison to a control population. Thus, the shade of Lamarckism seemed to emerge from a deep pit of despond, shake off its anachronistic shackles to insinuate on a stunned biological community (Flaxen waxing bollox). Was it conceivable that environmental factors could influence gene expression? Further experimentation and medical trials confirmed the apostasy.

It became quickly established that the initiating event was not due to classical genetic mutation altering the genetic code. Gene expression seemed to be altered by other means not involving a change to DNA base pairs. To cut a long story short, with regard to the Dutch study, it was discovered that a methylation change occurred at a growth factor gene called insulin-like growth factor II (IGF2). The methylation status of a gene controls its expression. In this instance, the IGF2 gene was upregulated. I’m not going to delve into the convoluted biochemistry. My blog with regard to biology is pitched at the intelligent layman/laywomen. For those who would like to know more concerning the fascinating world of genetics, I suggest a Google search. We truly live in wondrous times with information, often erroneous information, a mere click away. Changes in DNA chemistry and DNA conformation resulting in changes in gene expression, influenced by the environment, comes under the auspices of epigenetics. Epigenetic changes can occur in the womb and therefore the mother’s health status appears to be important for subsequent offspring. That said, post birth lifestyle choices may also have an influence on our genetic makeup and heritage.  

What I find fascinating is how the bodily environment can influence genes resulting in the modification of gene expression. I mentioned methylation as an important mechanism in turning genes on and off. The addition of methyl groups to a gene generally prevents the expression of that gene, while the removal of methyl groups promotes expression. Other mechanisms involve a change in the conformational status of the DNA and associated protein complex (histone modification). How change is conveyed at the cellular level is poorly understood at present and much research is being devoted to uncovering the underlying biochemistry. 
Clearly, epigenetic changes are highly important in contributing to our genetic makeup. Individual lifestyle influences (voluntary and involuntary) are only part of the story. The epigenetic status of our parents and grandparents will have a role to play in our genetic milieu. Surely the sins of the fathers will project unto their offspring to the nth generation. Predictably, commercial companies will latch onto the ‘epigenetic phenomenon’. A potion for all our ills will come under the guise of ‘genetic science’. Beware, of the new snake oil. For there is little doubt that companies will take commercial advantage and promote ‘gene modifying’ products supported by baseless pseudoscience. You have been warned.     

Maginot Line

  

Aftermath of war

I rarely venture into the Second World War. I’m much happier contemplating and writing about the Great War for reasons I find difficult to articulate. Maybe: To understand the Second Great War you must understand the First.

Today, I would like to make an exception and discuss a topic that I feel has brought forth many misconceptions and downright falsehoods. In popular opinion, and even amongst professional historians, the French Maginot line constructed between 1930 and 1940 was an expensive folly responsible for squandering vast resources and money for no avail. Subsequent events seem to vindicate this harsh analysis as the Germans bypassed the frontier fortifications along the Franco-German border. In mitigation, I would argue that this assessment does not consider France’s strategical, social and political dilemma following the Great War.

Although victorious in the Great War, France suffered greatly at the hands of its German enemy. Her manhood had been stripped bare during the 4-year war resulting in 1,400,000 deaths. In comparison, Germany lost 1,600,000 men. While it is true Germany suffered greater causalities than the French, in terms of proportion of the population the French losses were much larger due to the larger size of the German population. French society was transformed by the loss of a generation of young men and the deep-seated psychological trauma shaped strategic thought leading up to the Second World War.

The problem, from the French perspective, was although Germany had been thoroughly humbled and demilitarised following defeat in November 1918 and hobbled by the Treaty of Versailles, it was recognised that a day would come when Germany would emerge as a powerful European nation. What was not apparent immediately following the war was whether a resurgent Germany would masquerade as friend or foe. Certainly, from past history, the latter possibility seemed most likely. Indeed, sage heads considered the future conflict between the nations inevitable given Germany’s humiliation at the end of the Great War. 

Although not without political opposition or controversy, the French government decided to build a strong line of fortifications along the frontier with Germany. The Maginot line project began in 1930 and continued until France’s defeat in 1940. The Nazi takeover of Germany in 1933 added fresh urgency to the building of the fortifications. The bellicose and expansionist nature of the German National Socialist regime made the prospect of war almost a certainty.   

How was France to respond to a war from a powerful populous neighbour given France’s declining population? Maintaining a military alliance with Britain was part of the solution. But British power would only manifest in a prolonged conflict. Initially, the French would have to bear the brunt of German aggression in any future war. Thus, the concept of border fortifications became a reality.

The line on the German border would not be continuous but consist of a series of mutually supporting forts. In keeping with later First World War doctrine, defence would occur in depth. A series of large forts together with a number of smaller redoubts would form the backbone of the defence. Retractable reinforced turrets were designed to resist the heaviest of bombardment. Great galleries were built to accommodate the men, the ammunition and food.  Anti-tank ditches and extensive barbed wire belts were built to deter and impede the attacker. The cost of the Maginot line exceeded 3 billion francs, not a trifling sum for 1930s France. 

Although France and the international community seemed mightily impressed with the line, Belgium appeared less so. Allied with France during the 20s and up to 1936, Belgium realised that the border fortification almost guaranteed that the next war would involve an invasion of Belgium territory. Perhaps this accounted for Belgium’s decision to become neutral in 1936. However, due to strategic priorities, it would be unlikely that the Germans would refrain from invasion regardless of neutral status.  Belgium was under no illusion how a future war would evolve and her neutral status would ensure that not only would she be invaded by the Germans, but the French and British as well.   

The Maginot line was not perceived as an impenetrable barrier. Lessons from the first war had shown that formidable fortifications and earthworks, although conceived in depth, could eventually be pierced given time, energy and men. The Maginot line was meant to be a temporary stop, designed to occupy the attacking Germans and deflect manpower from more vulnerable sectors if only the Germans would/could oblige. The French hoped that they would buy time and send the bulk of their army to engage and defeat the dreaded Boche in Belgium, or at least form a trench line, again in Belgium. Fettered by doctrine belonging to the First World War, the British and French responded in a predictable manner once Belgium was attacked. For the French, it was vitally important that they did not cede vast swaths of northeastern France, as happened, in the Great War. Mayhap the French were being unduly optimistic or fatalistic, depending on stance.      

The Germans had other plans based on their concept of ‘Blitz Krieg’. On the 10^th May 1940, the German army made a predictable advance into Belgium taking in the Netherlands as an afterthought. However, the main armoured thrust occurred through the supposedly impenetrable Ardennes. When the Germans debouched from the Ardennes the French army was outflanked and outmanoeuvred. This is something the Allies hadn’t anticipated or could respond to- France was defeated within 6 weeks and the Maginot line was bypassed and rendered useless.   

The Maginot line should have worked if the Germans had envisaged a future war as the French did. The French hadn’t prepared for a war of movement spearheaded by concentrated tank thrusts combined with tactical air power. Both powers appeared to have learned important lessons from the Great War, however, only one power appeared to have looked beyond the tactics of that war. Vae Victis.   

     

Eureka

Can't help notice that my posts have become heavy and serious of late. So when I spotted this cartoon I couldn't help but appropriate it for the blog. There is something about the cartoon which appeals to my sense of humour. Arse. 

Normal service is to be resumed shortly

Martin Luther and the Protestant Reformation

Apparently, he was a very naughty boy

It is difficult for us living in the 21^st century to contemplate the sheer secular power and authority held by the Pope and the Catholic church in the Middle Ages. It could be said that the collapse of this authority or at least the beginning of its decline was largely down to the energies of one man, a German Monk, called Martin Luther who initiated the Protestant Reformation. Before the Reformation, virtually all Christians, at least in Western Europe, belonged to the Universal or Catholic church. And at the top of this theological edifice sat the supreme arbiter of religious doctrine, the Pope.   

You may ask why an atheist such as myself should be consumed with things theological. Regardless of individual beliefs, religious belief has proved important in society both ancient and modern and religious beliefs have been overwhelming in shaping world history and culture. Thus, if we want to understand the world we live in today it is important that we take a glance at theology and religion even if that glance is achieved with a tired and jaundiced eye. 

Setting the Scene/Schism

Not only was the Catholic Church incredibly wealthy back in the Middle Ages, but it also had a monopoly on the social services of the time. It ran the orphanages and gave alms to the destitute. Monks were literate in an illiterate society and therefore were responsible for interpreting Christianity’s sacred literature, the Bible. And this interpretation was strictly controlled by the Catholic hierarchy. What little medical care was available was often administered by the Monastery. Importantly, the Church was the caretaker of the human soul and had a great influence over whether a person would eventually abide in eternal bliss or suffer the eternal fires of hell. The parish priest was a pivotal entity in the community providing spiritual guidance, confession and presided over a succession of life’s important punctuations such as baptism, marriage and finally the full stop, last rites.

So how did a chronically constipated Monk set forth a chain of events which proved the Catholic Church’s undoing? Back in 1517, Luther was a resident at Wittenberg University and was already an outspoken and turbulent priest. However, the flame that engulfed Christianity was kindled by a spark in the incandescent form of an itinerant friar, named John Tetzel. When John arrived in town he began to sell indulgences to the town’s folk. An indulgence remitted the time spent in ‘cleansing’ purgatory after death. A necessary intermediate step before advancing unto eternal paradise. As purgatory involved extreme agony, perhaps through burning, it was something that most folk would like to omit or at least minimise. Consequently, ‘indulgence’ was a big revenue spinner for the Church at a price of 3 marks per soul- about 6 months income for the average sinner. 

Luther was outraged at what he saw as a blatant ploy to exploit the flock through fear. Luther opined that Salvation could only be attained by faith, not by good works, revelation, prayer and certainly not by paying a toll. His anger was propelled by a righteous appreciation of how corrupt and venal the Church had become; no different from a money-grubbing extortion racket. Indignation propelled Luther to dramatically nail his 95 Theses, against indulgences, to the gates of the local church, on 31st October 1517, for all to see, but not all to read.  Opposition against the Church was a big thing and Luther’s action provoked much debate amongst the clergy and the literate (mostly the same thing). 

Luther’s theological stance began to evolve and became more radical with time culminating with the denial of Papal and Church infallibility. Furthermore, he stated that the Church lacked any spiritual authority. This was an extremely bold condemnation requiring a bold reaction from the Church and ruling elite. In 1521 Luther was called before the Holy Roman Emperor, Charles V, at Worms to explain his theological position. Needless to say, others had criticised the Catholic Church before Luther (cf John Wycliffe) without causing catastrophic and irrevocable damage to this teetering power structure/stricture. However, new to the mix was the power of the newly arrived, printing press. This allowed a wide dissemination of Luther’s tracts and pamphlets enabling large numbers of literate folk to access and consume Luther’s revisionist ideas. Over two thousand editions of his work appeared between 1517-1526. This volume of work, greatly propagated, introduced the literate clergy to criticism of the Catholic Church. For many, this proved a novel and intellectually refreshing experience. Of equal importance, Luther translated the Latin Bible into German. For the first time, non-priests could read the Bible for themselves- hundreds of thousands of copies were printed. Lay people could now discuss the meaning and interpret Biblical passages for themselves. The genie was out of the bottle. Once scripture became widely available coupled with the injunction that anyone’s interpretation was as valid as the Pope's you arrive at alternative interpretations of scripture only limited by the imagination of the beholder. Catholicism was no longer all-inclusive. 

Alternative views resulted in a shattering of doctrine culminating in the formation of numerous and diverse Protestant churches each with their own religious understanding and ‘truth’. Then, of course, the fractured/fractious religious groups started to fight amongst themselves and the Catholic Church fomenting social discord and violence. Years of religious strife and intolerance ensued. What started as a doctrinal dispute transformed into a peasant’s revolt in 1525 involving 300,000 people. People applying Luther’s ideas and methodology not only criticised the Church but the landowners and rulers as well. The German peasant revolt was eventually crushed with great loss of life, but Protestantism was here for good and soon found favour with various rulers of Europe and not just because Lutheran doctrine proved theologically attractive. It also gave rulers an excuse to appropriate Church lands and money if they could. Certainly, King Henry VIII profited greatly from appropriations and this is why the Queen of England, Elizabeth II, is the greatest landowner in England today. 

Consequently, the Reformation was not just a religious revolution, it proved a potent force for political and social change. Thus, European civilisation lurched toward the modern era and this is why today we have only one Catholic Church and  200 of the Protestant persuasion.  Arse.    

 

 

Thales

Thales: Note the noble brow

Oddly enough, the birth of philosophy can be accurately dated to 585 BC. Twas in this year that the Greek philosopher, Thales, predicted an eclipse using mathematics and astronomy. No mean feat for the 6^th century BC. 

What had been happening in the world and particularly Greece, prior to this event? Surely Thales did not emerge from an intellectual void. Sadly, much has been lost to time and conjecture is our only comfort. Other civilisations existed, many with an ancient pedigree, however, their speculations never veered beyond explanations ascribed to gods. Although the Egyptians had developed ‘rule of thumb’ geometric techniques for their monumental building projects they never seemed to be able to shift from the practical to the abstract. Thus, we turn to the Ancient Greeks for the development of abstract concepts and true mathematics. And indeed, the well-travelled Thales is considered to have brought geometry to the Greeks by way of Egypt.  

Thales hailed from Miletus in Asia Minor and therefore was part of the Hellenic diaspora.  All philosophy is said to have begun with this man. If his antecedents thought in the abstract as he did, we will never know as history has left us no record. I’m inclined to think that Thales was an innovator in thought because his faltering beginnings seem to us moderns as banal and rather silly. I’ll need to qualify this remark later in this post.  

It can seem rather worrying to the new student of philosophy that the founder of Greek philosophy and hence Western thought, considered that all was composed of water.  Actually, as a hypothesis, this is a reasonable start.  There is nothing wrong in stating a ridiculous hypothesis, especially if we don’t recognise it as such; from a thousand ideas, only one is destined to be great. 

We are apt to forget that we are the product of 2,500 years of intellectual endeavour, admittedly subject to fits and starts which attend all progress. If we are diligent in our studies and not thick, there is the potential, if we so desire, to progress in intellectual thought and drench thoroughly in the wisdom of those great men who preceded us. The shortcut to true knowledge is the legacy of our ancestors, if only if we can be bothered to take heed. Inquisitive Thales had no store of great knowledge or wisdom to guide his intellect. His originality was to seek non-miraculous causal mechanisms to describe nature. Ultimately this was Thales’s insight and fundamental genius. His predecessors and contemporaries could not make this intellectual leap and divorce themselves from explanations based on supernatural agencies. 

Let us track back to Thales’s original notion that ‘all is water’ and examine it for intrinsic merit. This is not to be judged by modern epistemological standards. Instead, to be fair, we must erase our current knowledge base and knowledge accretion and imagine that we are at the dawn of rational enquiry. Thales observed that life is dependant upon water and Aristotle thought that Thales came up with this revolutionary idea ‘from seeing that the nutrient of all things is moist’. We have no clue as to why he thought this way. What’s important, I think, is that Thales’s idea was not arbitrary and required effort and contemplation. His attempt to understand and unify the complex with a simple construct is sound. However, parsimony in thought is not necessarily the root of all wisdom and clearly, in this regard, Thales was completely and irrevocably wrong. However, for a first attempt to rationalise the natural world, it was a bold and imaginative effort.

Are you convinced of Thales’s wisdom? Of course not. It is virtually impossible to free our minds of the ‘modern scientific paradigm’ unless you are a fundamentalist Christian from the Deep South of the US or a Catholic theologian. 

Finally, I will finish with an anecdote ascribed to Thales. Whether it is true or not, I have no idea. It is said that Thales attended a dinner party. After a while, and probably after imbibing much wine, Thales decided to wander into the garden to stargaze whereupon he promptly fell into a ditch. An elderly woman present was heard to comment: “how could someone who cannot see what is under his own feet presume to understand and see the heavens’’.  Quite so.

Ted and Rowan

Dead Cute

Brief and very boring post……. 

Last Saturday on a glorious Wairarapa afternoon, our ‘neighbours’ dropped off our new livestock, Ted and Rowan, the Alpacas. They were led by halter to the ‘South Field’ where they quickly settled in but not before a little mock fighting. Within 15 minutes they had sorted out any dominance issues and began to graze on our lush pasture. Alpacas are hardy creatures and low maintenance. They require no specialised shelter and by preference are happy to brave the elements. Our only concern is the Wairarapa Summer which is notoriously hot and dry. Temperatures in the high 30s are not uncommon. Luckily, we have an extensive tree line of tall Aussie Gum trees to provide shelter from the heat of the day. Also, we shall have them sheared of their fine fleece. Apparently, Alpaca wool is of high quality and much sort after. So far, our new additions appear content to stay in their allotted field although the top end is not fenced off from the rest of the property. I suspect they will prefer their pasture due to the thick grass cover. All other grassy areas are kept short and manageable. If they do decide to go ‘walkabout’ they will not be able to vacate the property because of an unbroken perimeter fence. However, we are not sure whether the little buggers will take a culinary fancy to our extensive and well-groomed flower beds. More importantly, I’m a little worried that they might graze our veggie gardens. If it becomes a problem I’ll have to get off my lazy arse and secure the field at the Eastern end.

So, there we have it. Livestock at last with the option to add another Alpaca. I suspect we will take on the third critter as they appear easy to maintain. Next on the list is a brace of chucks. Just need to clear out the hen house prior to introducing chickens. I reckon four will keep the two of us awash in eggs for a lifetime. The intention is to become self-sufficient in vegetables, fruit and salad with the odd rabbit or two to fulfil our craving for free meat. Well, that’s the plan unless I completely screw it all up- let’s wait and see.    

The End is Nigh.....Again

Dis ain't da one

Yea, and so it came to pass……

"Speak unto the, children of Israel that they bring thee a red heifer without spot, wherein is no blemish, and upon which never came yoke". (Numbers 19:2)

 Apparently, a Jewish sect has been awaiting the birth of a ritually pure ‘Red Heifer’. The appearance of said heifer heralds the reinstating of Biblical purity to the world (no shit). If that wasn’t enough, the event will initiate the building of the Third Temple inaugurating the end of the world (bugger, I’ve just retired!). The Messiah will also turn up and unrepentant sinners will be judged. Now some may say that the Messiah turned up some 2,000 years ago, but the Jews have never recognised Jesus Christ as such. Regardless, if the prophesy holds truth then the likes of me and ilk are in for a bad time. Now I’m not saying I’m unredeemable, it is just that I’ve never lived an exemplary existence and on occasion have been a bit naughty. Hopefully, this ‘Red Heifer’ will turn into a ‘Red Herring’ and not live up to the rigid criteria demanded. Previous candidates have not fulfilled their initial promise as the presence of only two black hairs results in disqualification. Only after a stringent physical examination will the pronouncement be announced on the current heifer. I’m holding my breath that the ‘miraculous beast’ will have too many of the non-red variety of hairs.

Now here is the rub. It seems as if the Jewish brethren have been giving nature and prophecy
a bit of a nudge. For several years past the sect have utilised embryos transferred from Red Angus cattle into the native Israeli cattle. What can I say? Orthodox religious Jews embracing science to force a doomsday prophecy- O, the irony!