Sunday 31 December 2017

XYY Man



Human cell genetics is a relatively new profession. It wasn't until the 1950s that reliable techniques were developed to visualise the morphology and establish the number of chromosomes in the human genome. What followed was a period of rapid advancement during which the major chromosome aneuploidies were described. One of these conditions, Jacobs syndrome, was characterised in 1959. In humans, the presence of the Y chromosome determines maleness. The 'normal male' is bestowed with a single, meagre Y. In truth, the Y chromosome is a stubby nondescript chromosome with very few expressed genes The ever present SRY gene (testes determining factor) is responsible for driving the embryo down the male developmental pathway. In addition, there are genes determining stature and a gene for hairy ears- the bane of every man over 50.

Men with Jacobs syndrome are blessed with not one, but two, Y chromosomes. Unlike most chromosome disorders, men with an extra Y are clinically unremarkable. Most XYY men remain undiagnosed and lie below the clinical radar. They don't suffer major organ defects or look odd. They do have a tendency to tallness due to a double dose of stature genes and their average IQ, as a collective group, is lower (10 to 15 points) than the general male population. For the most part, the IQs of XYY men lie within the normal or low normal range, whilst some may exhibit a degree of mild mental deficit.

When Jacobs syndrome was first discovered, the presence of the extra chromosome gave rise to the unfortunate designation of 'Super male'. If one Y is required for maleness, then surely two would result in a highly masculinised male. This view became reinforced when it was discovered that XYY males were found to be enriched in the prison system. In the general population, the incidence of the condition is about one in a thousand men. However, when we observe the prison population the incidence rises to one in a hundred. Early speculation centred on the possibility that XYY men were highly aggressive and therefore more likely to be involved in violent crime. However, when further investigated it became apparent that the type of crimes committed by these men was no different from the majority of inmates- low-level crime, mostly theft and damage to property Thus it seems that XYY inmates are not 'Super' in any respect, just petty criminals.

The association of the condition with criminality became enshrined in the British consciousness due to a popular television series of the 70s, called 'XYY Man'. The underlying premise throughout the series centres on the main character who is driven to crime as a consequence of his extra Y chromosome. This raises an interesting side issue not pursued by the series: To wit, if the man has no choice in his actions due to innate programming is he considered morally culpable for his wrong doing? If it can be determined that he is unable to restrain his criminal activity because of the extra chromosome, would it be right to punish him for his transgressions? This highlights an interesting ethical conundrum not easily resolved. Sadly, I don't have space in this article to consider the dilemma, here. Digression endeth.

So why is it we see a greater incarceration rate amongst these men? The ultimate answer is rather mundane. When we sample the IQ amongst prison inmates it tends toward 10 to 15 points lower than the general population. Should we be surprised, that stupid folk make stupid decisions in their life? Tis a simple matter of IQ demographics. Ain't dat the sad truth?

It would be wrong to label XYY men as criminals or potential criminals, unless incarcerated. The majority lead uneventful lives and remain, unrecognised by the public, doctors, and the judiciary system. That aside, if one of these 'unremarkable males' appeared in my home, brandishing a pointed stick, or even a bunch of sundry fruit, I would gun him down like a dog and move the corpse to my son in law's pig farm where the unclean and besmirched corpse would become an integral part of the porcine faecal environment. Nuff said.

Monday 25 December 2017

Flaxen's Annual Christmas Address



Tis Christmastide once again. A wondrous time of year when all wars cease, strife is no more and men of all nations come together as one, in harmonious accord.

Families assemble and embark on jolly festivities. Laughter will resonate throughout the abode. Crackers will be pulled and choral harmonies will spontaneously erupt. All will partake of Christmas fayre and no one will drink to excess, limiting their imbibing to a small eggnog and a sweet sherry.

The family will gather around the tree (50 quid from Aldis) and receive gifts according to intrinsic merit. Said gifts will be ornately wrapped in the finest apparel and quaintly tied with ribbons of finest spun gold- no underpants or cheap aftershave shall besmirch the happy occasion.


For myself, I will spend the day with my family, sweltering in the New Zealand summer heat. So gentle readers have fun, be well acquainted, and don't burn down your neighbour's house in a fit of misplaced pique (Arse).  


Thursday 21 December 2017

The Raven Paradox


The scientific process is based on the condition of induction. For the uninitiated, this is a fancy term for 'observation' and any initial scientific hypothesis is always based on input from our senses. Consider the hypothesis: 'All Ravens are black'. After many observations of seeing only black ravens, let us say 2,000, it would be reasonable to accept the prior hypothesis. The more black ravens we encounter, the more our hypothesis stands firm and eventually moves from the status of hypothesis into the realm of 'law'. There are two points to be made here: One, it is impossible to sample all ravens, past and present. Most ravens that have existed are no more, and therefore beyond mortal tally. Other ravens remain beyond scrutiny due to their location in remote, or difficult to access geographic environments. The second point is self-evident. The observation of one non-black raven is all that is required to tumble our 'law' and destroy its scientific credibility. From a practical point, our hypothesis was never really on sound ground. Indeed, it is known that about 1 in 10,000 ravens are born albino. Very few of these mutant birds make it to adulthood as they are sickly and because of their lack of pigment, prone to predation. A dedicated bird watcher might spend a lifetime 'twitching' and not see a single albino Raven, and yet they exist.

This simple scenario undermines one of the great tenets of science- the notion of falsifcation. True scientists should not only be gathering data to reinforce their beloved theory but also, if he/she is scrupulously honest, be actively seeking evidence to undermine the theory. This, of course, is the counsel of perfection. The concept of 'falsification' was made famous due to the work of the great science commentator, Karl Popper. You can view my commentary on his propositions, hereThis simple mind game exposes a fundamental flaw in the design of the scientific method. Although the falsification of a hypothesis, or theory, is technically feasible, in practical terms, the necessary data may not be readily accessible.

The second part of the paradox is more interesting and instructive and concerns the deductive aspect of the scientific method. In logic when we posit: ‘All ravens are black’ we must accept the contrapositive statement: ‘Everything that is not black is not a raven’.  Seems fair enough, don’t you think? So, any non-black object is denied the possibility of being a raven- in logic this is irrefutable, given the original premise. Thus, any non-black object supports our hypothesis, even a green  apple. Surely the data set in this instance is bordering on the infinite and the trivial at the same time, but the underlying logical principle is sound. Here we illustrate a basic dichotomy between induction and deduction. In this instance, induction is responsible for our logical posit. But as we have seen previously, 'All ravens are black' is a false hypothesis and logic based on a falsehood will give an incorrect answer even though the logical process is impeccably valid.  

Does all this sophistry destroy the scientific method as a means of obtaining knowledge? Of course not, it would be stupid to propose or advance such a notion. The scientific method clearly works or our technological civilisation would and could not exist. Science must be getting something right. Remember, science does not give infallible knowledge and is bound by the principle of improvement.

The Raven paradox is a philosophical tool for the prudent scientist to apply in order to examine each step of the scientific inductive process with intellectual rigour. In many day to day scientific endeavours the raven's paradox will not apply. The paradox should not be viewed as a means to cripple science, but as a hobble, gently applied. A process to limit scientific hubris and to place the inductive method, with its limitations, within the canon of available knowledge. 




Thursday 14 December 2017

Huntington



Is there a more terrible disease than Huntington disease? Huntington is a neurodegenerative disorder with an incidence of 1 in 20,000 and is inherited as an autosomal dominant. An autosomal dominant condition ensures that if you carry a single mutant gene you inevitably develop the condition- a mutant gene which is passed onto 50% of your offspring. Huntington disease strikes in the prime years of life (30-40) and slowly destroys your motor and cognitive powers resulting in death, typically 15 to 20 years after developing initial symptoms. Consequently, due to the disease's late onset,  you are likely to pass it on to your children before you develop symptoms yourself. 

The culprit is a mutation affecting a gene which manufactures the huntingtin protein. Although the exact biological function of this protein is not fully known, it is likely that it plays a critical role in nerve function and development. The mutant protein undergoes an altered configuration causing chains of protein aggregates. The aberrant 'strings' of protein accumulate within the brain where they progressively destroy nerve tissue. Whole families are ravaged and destroyed by the disease. If you carry the mutant gene you linger under a death sentence without reprieve. It is no wonder that the suicide rate amongst Huntington families is high. 

Imagine being in your 20s watching your mother, or father, falter and decline both physically and mentally and knowing there is no hope of recovery; and that you have a 1 in 2 chance of being affected yourself. Genetic testing is available, however, some potential sufferers choose not to be tested. For those who choose diagnostic testing, a positive result is a hard psychological burden to bear, although reactions differ depending on temperament and circumstance. Even those testing negative are not spared as they must reconcile their good fortune with the knowledge that their siblings may not have faired so well. 

The only treatment to date has been palliative; no more than keeping the patient as comfortable as is possible until demise. However, recent research at University College London has focussed on a drug which blocks the formation of the aberrant protein and initial trials on Huntington patients have been very encouraging. The drug is injected into the spinal cord and interacts with messenger RNA from the damaged gene. This messenger RNA would then go on to direct the formation of the mutant protein. However, in the presence of the experimental drug the RNA molecule is rendered non-functional and therefore the damaged protein can no longer be manufactured. During the first human trial, it was demonstrated that the levels of the abnormal protein were substantially reduced.  

Is this a cure? Probably not. A reduction in the protein would have to be correlated with an improvement in the clinical condition. This will take further trials and many years work. Current work has been undertaken on patients already showing symptoms of the disease. Long term work will be necessary to see if the disease can be stabilised and even reversed. Perhaps the most enticing and exciting prospect will be to treat asymptomatic carriers of Huntington to see if the disease can be prevented from developing later in life. 

The use of drugs to target gene expression in combating genetic disease is not a new approach and has found a particular application in cancer. It is hoped that a similar approach can be adapted to treat other neurodegenerative conditions where a build up of protein is responsible for brain cell death. Alzheimer is one such condition where the deposit of protein plaques result in neural tissue destruction. 

The next wave of genetic research will herald a ‘golden age’ for disease treatment. Unlike many neurodevelopmental conditions, most autosomal disorders manifest at birth. The key, therefore, is to implement drug intervention in the womb, ideally early in embryo development. The goal will be to modify gene expression to prevent or ameliorate the condition. The rub, of course, is that sophisticated genetic therapy will not come cheap and therefore as a society, we may face the real dilemma of withholding effective treatment because of prohibitive cost. Tis indeed a brave new world.   

Just a comment: Astute readers will have noticed that I have not used the possessive apostrophe for Huntington disease. It is no longer considered correct form to refer to the disease as Huntington's disease (Huntington's chorea is right out). In the same way, Down's syndrome is rendered Down syndrome. As for the old tag, 'Mongol', this is deemed totally unacceptable in any polite medical lexicon.



Saturday 9 December 2017

Bloody Christmas Songs

Tis nearly the time of year when goodwill and serene tranquillity overfloweth and everyone is full of good cheer and eggnog. Engaging, quaint and ragged urchins gather to sing carols in pitch-perfect harmony. The snow lays crisp and deep and Jack Frost nibbles at deliciously exposed, pink and plump nether regions…….

And then we have the obligatory Christmas song release. How could we endure the season without ‘Snoopy’s Christmas song’ or the dulcet tones of Cliff Richard as he belts out ‘Mistletoe and Wine’.  A time when every crooner, past and present, hits the music scene with a Christmas song, hoping to catch the mug punter with deep pockets and nostalgia in their hearts. Although there have been a few memorable Christmas inspired tunes, the majority are just hastily cobbled together crap replete with banal predictable lyrics allied with ridiculous and hackneyed, sentimental tunes of sick, syrupy mulch. For every Bing Crosby's 'White Christmas' there are 1,000 forgettable melodies. Do you recall the engaging: ‘Santa Claus Has Got the Aids This Year’ by the late lamented, Tiny Tim? Of course, you don’t- the whole effort was a pathetic attempt to cash in on the weirdly eccentric and pathetic, Tiny Tim.

So in the gentle spirit of Christmas, I would like to nominate my top five piss awful Christmas refrains. I’m quite aware that the selection is in some way arbitrary and prone to my own bizarre brand of subjective taste. In fact, there are so many bad Christmas songs that compiling a worthwhile list is virtually impossible. A music nerd, in 2014, scoured the song catalogues and came up with 914,047 tracks of Christmas themed songs. I’m sure the current inventory is in excess of a million and the vast majority will be complete and utter dross.      

5. Dominick the Donkey by Lou Monte




The lyrics to this particularly annoying song are pure unadulterated crap accompanied by a tune that will stick in your head turning your brain into spaghetti. Moma Mia!

4. This Christmas (I'll burn it to the ground)




The only saving grace of this cacophony is that it panders to my sick proclivity for 'burning stuff' and underlying nihilism. Other than that it is utter and absolute shite. At least you won't carry this tune in your head once the 'music' stops. Although to be fair I couldn't listen to this all the way to the end.

3. Mistletoe and Wine by Cliff Richard  




This list must contain at least one of Harry Webb's Christmas warbles. Our Cliff has knocked out 17 festive songs in his long career. Once touted as Britain's answer to Elvis Presley back in the 50s and early 60s he quickly morphed into the saccharine 'Peter Pan' of pop. Grandmas loved him and everyone else detested his smug self-righteous persona. I'm starting to digress. My own particular nemesis is 'Mistletoe and Wine'. A sticky sweet tune backed with trite lyrics. A mismatch of pagan 'Mid-Winter Festival' with supposed Christian sentiment.

2. Wonderful Christmas Time by Paul McCartney



I must confess, I’m not a fan of Paul McCartney’s post-Beatles work. And let’s be honest, ‘Wings’ were piss poor. Do you think Paul employed his wife  in the band because she was an  exceptional musician? Tis a wonder he didn’t put his dog on bongos. My particular nip of venom is reserved for the simpering sweet bubble-gum number, ‘Wonderful Christmas Time’. Here is a judicious selection of the insipid caramel lyrics:  “The party’s on, the feeling’s here that only comes, this time of year”. Perhaps I’m being a tad unfair to the man who wrote ‘Yesterday’, but the jarring muzak quality of the melody has me reaching for the petrol and matches. 

At last, we come to my personal choice for worst Christmas song. Many are called, but only one is chosen.

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1. Do they know its Christmas


This may be a controversial choice. Those amongst you may aver that there are worse jingles out there jangling with discord on the harmonic waves. And of course, you would be right. Tis all a matter of criteria and I confess that I have not applied any stringent or consistent filter process. This list comprises those wretched songs which grate and gnaw at my very fibre. After masticating fully they spit the remnants on a bright white canvas. A pristine canvas despoiled and left sullied with ochre blotches of doom…..

Some will rave that the sentiment behind the enterprise was laudable and helped to raise money for Africa’s starving, seething masses. But when has sending gelt to Africa done any good? Most likely the aid will end up in the sticky fingers of the local War Lord/Chief/local corrupt government officials/Despot. And when has largesse ever been a sustainable manner to provide a stable economic base for a country? Surely this is a job for the elected government to address?

The original line up contained the ‘scourge of god’, Bob Geldof and Bono and a hastily thrown together line of, musicians of the time. The lyrics are predictably nauseating and reek of paternalism - what more needs to be said?        

To calm the fever in my blood I have added the following.  The heaving breast is stilled once more.