Category Archives: Science

Pointing to Problems With Pointing

There is one common topic which the followers down the fleet will most often bemoan. Pointing a sailing boat, or rather not being able to point as high as others. In handicap fleets it can get outright nasty this pointing at problems as if they were purely down to fortuiry of boat design and how much lard one helm attracts as his rail ballast.        

                                       In one design fleets it tends to be an issue for all and sundry, especially on the start line or coming off the leeward mark to the subsequent beat. Why  do you not get your boat sailing as high on the wind as a competitor?                                            
           We can divide the answer or rather ‘point you in the right directions’ to coin a pun, into several routes to understanding a shortcoming. Firstly there is rig set up and then there is boat trim and sheeting, finally there is technique. I will touch very briefly on the alternative mentioned above, that some boats do indeed point very much higher by virtue of design.                  

          All boats have a pivot point when their wetted areas are fully immersed to their maximum for each point of sail. In keel boats we find that on the beat, the heeled boat usually has a longer water line and the centre of longditundinal resistance or pivot point moves a little forward. Usually this point on the beat is somewhere between the base of the mast and the trailing tip of the keel. In some boats like the j24, it probably moves too far aft, because the keel is too far back in the design, but because this is quite a high pointing racing boat often sailed in OD fleets, no one really cared that much!

 A boat whose pivot point moves forward will tend to be pushed more by the leverage power of the mainsail along the boom and through the mast. In many 1960 and 70 RORC ‘ton’ designs the boats were built to fit the rule with a large genoa and a relatively small main, and many designs followed this, for example the Contessa 32 and her sister designs. The big genoa becomes an awkward factor as it reaches beyond its optimal wind and starts to fight with the optimal centre of resistance while also heeling the boat and making the waterline even longer and thus more prone to weather helm. This can be very pronounced with over canvassed ton designs fighting themselves out of the ‘groove’ upwind in a cycle of CLR displacement and rounding upon heeling. The answer is to strip down sail early so as to avoid this in gusts, because you cannot depower a genoa very much at all underway.                                          

        Here then we go right out of boat design and into what you do with the boat and how you react to different conditions of both wind and it has to be raised now, sea.  Lets face it, most boat designers know what they are up to and have to comply to safety rules and guidelines when developing a new boat. Ton designs and their Sadler and  David Thomas deriviatives do screw up into the wind when overpowered, but on the beat that is a bit of a safety factor. Impalas were known to tack themselves though after an upwind ‘broach’ so they had to have extra weight on the end of their keels. Even in this example, David Thomas had probably intended that folk should be on a number three and a reef, when in fact they were sailing with full sail in 20 knts wind. Modern designs with rounded hulls and ‘spade’ or bulb  keels and wide transoms tend to hold their waterline better upwind so within reason they are easier to sail however the high volume, flat stern can promote broaching in a boat which is overcanvassed on any point of sail. So correct canvassing is the first step in ‘getting into the groove’ and staying there.               

                       Then we come to rig tune. We happened upon a similar effect with poor pointing on our first trip out in the Melges this year in fact, just last week, and that is what inspired me to write tonight. Way back when about 1998 I sailed a Cumbraes regatta on the very tasty detuned Figaro I, T’jig II owned by the Dryborough brothers. This was a machine with planing potential under its mast head spinnaker,. but on the second start I think it was, we just could not point and ended  up sitting ducks squeezed in by the fleet near the IDM end. We actually won a subsequent race and the overall result gave us a class win or a second place, we collected silverware. They said then the boat just did not really point but in fact later on they had the rig tuned, quite possibly professionally, and the boat could point a lot better. What their issue quite likely was, and very likely what our issue was last wednesday was forestay length and tension.          

   The forestay is really a key measurement on any  standard, bermudan rigged sailing vessel. It controls the mast rake first and foremost, and then how much sag and power there is in the genoa or jib. Too long and you will find the boat develops lee helm, because the mast is going backwards too far and the mainn sails centre of effort goes back, pushing the boat round its pivot point to windward. Very often too long will also mean you are breaking a class measurement or agreed IRC one.  Too short and you will pull the mast too far forward and the boat will loose some ability to point as the centre of effort of the mainsail moves forward. This is a big deal even over the course of two inches on the Melges for example, because it can move the centre of effort far more than just a couple of inches. It messes up the balance. 

However  it is not as simple as that. In a boat like the M24 with swept back spreaders, the cap shrouds are also a major control over rake as they sweep the mast backwards with them as tension is applied through their bottle screws. The mast step limits the amount the mast can pivot as does the maxium bend and compression. Now as the cap shrouds come on even harder the mast compresses and bows forward. We can take some of that out with the inner lower diagonal shrouds,. but not all of it when we are set for mid to heavy weather. Then the forestay is suddenly lieing on a chord now to fixture point which has become shorter, hence the forestay and sail can sag in a leeward curve when close hauled. The net effect is that you cannot actually point as high, because the jib is powering the boat a lot up wind in 12 knots plus with the main being depowered after about 14 knts wind. Your telltales fly early. Now you can on our M24 adjust the forestay on a bottle screw down under the mast, because  it is lead over an axel or wheel in the mast and down to the keel of the boat. This means you can take out this sag and obtain optimal rake. In theory,. However this gets complicated and it is easy to end up either with an out of class illegal mast head to transom measurement, or a mainsail which is hard to trim correctly, or both of course. So later boats were fitted with a fixed legnth forestay, meaning you adjust only the shrouds and you maintain a good balance as the wind builds, while also keeping within your class rules measurement mast top to transom.

                  In many boats though, you can though experiment with legnthening the forestay by a few inches on the bottle screw or pin and rack adjuster. You want to maintain enough tread to have good holding on a bottle screw it has to be said!! 

As in the Melges example, you will need in fact to adjust your shrouds as well because their tension will be altered by slackening the forestay and you want to maintain a tight forestay for poinint high. Your mainsail should still be easy to trim and not start maxing out in how far you can practically sheet in before it or the boom interfere with things, nor do you want too much weather helm. Note your settings in terms of thread screws left on the bottle screws or pin positions on the racks for both forestay and shrouds, and if the backstay has a wheel note there too, or even mark the point at which you tighten it with the rope purchase system if that is fitted. If it is a bad setting with weather helm, note it all the same so that you avoid that failed experiment again.     An example of a boat where experiment showed that an extreme mast rake was best for pointing is the Soling, where the boom meets the deck, very unusual for a boat with a jib and a mainsail and relating to the overall design of the keel and balance of the sails.         
   Getting this rake and sag balance  right before a race or fast passage in a known forecast is just as important for optimal performance as the better known final wee few inches in on the sheets when you want to point high as possible. In some boats you can get away with an average to soft rig setting, and then let the sheeting,kicker, jib track, halyards and cunningham. The modest little Farr Platu 25 could  be sailed like this, using the back stay to first stabilise the rig by tigthening the forestay, and thus achieving good pointing, like a runner in effect, before it and the kicker could be used to depower the sail in the gusts by bending the mast quickly. However given a more definiative blowy forecast, it was better to set things harder on, and reduce rake.              
            The Platu is a good place to move on from righ tuning for rake and discuss balance from sheeting the sails in order to achieve good pointing. Due to a very shord chord keel (fore aft distance) the boat pivots very easily so like in a sailing dinghy, you notice any imbalance between main and jib more than on a spade or long keel.  Too much weather helm and you need to sheet in on the jib a little if you can, or drop the main down the traveller. The Platu can though develop mild lee helm too, when the jib is oversheeted, which is destructive to pointing. Here more main should usually be applied, or the jib sheeted out or opened at the top by moving the cars back and the barber haulers out. A good balance and correct slot angle is key to not only helping pointing by controlling pivoting once the rig is tuned for the race from the above rake techniques, but also main and jib is 2+2=5 . It is more than the sum of its sail area and power alone due to various effects beyond the scope of this essay, just trust me! This nice amount of power leads to speed and that is the next point to raise.                      
             You will hear it said at some point from knowledgeable  sailors that you need speed before pointing, and in a general, non tactical beat this is absolutely critical indeed. There are two things to not here. We are talking about maximal overall boat speed, and the speed at which the keel and rudder, the foils, ‘fly’. A beneteau 25 Platu as mentioned has a very short chord keel of less than  2 feet, so it  flies ie attaches flow and creates lift, at a very low boat speed. That sounds good, you are resisting leeway very soon and able to sail the boat forward, and take the next piece of advice, work the boat smoothly up to close hauled. The trouble with such a short keel is that it  also shakes off attached flow very easily and has eventually quite a narrow groove when the boat is close hauled ie if you point too high or fall off too abruptly it will loose its ‘bite’ in the water, it will stall due  to turbulance. The converse is true of say sailing a Piper or a Loch Long or a 12mR rater. Here you have a need to get up to a higher speed before your keel is flying, because it is so much longer a chord and arc legnth. However  once  flying the flow remains attached as you manoevre up and down from optimal close hauled. In either case below foil flying speed or if the keel or rudder is stalled due  to abrupt movement, you will drift sideways, even if your bow points up towards the wind  more – you will pivot but not gain forward travel.          
           In modern short chord keels though, the flow detaches quickly in abrupt movement of the helm or boat, but reattaches very quickly, whereas if you do shake the flow off a long keel boat, it can take time for it to reattach and you are left with not only leeway, but an ineffective  rudder.      
            Given this foil fly speed and time to reattach if stalled too high on the wind or by abrupt rotational movement in heeling or pivoting towards or away from the wind direction, you can do some simple calculations to build  confidence that you have the keel flying and can  work the boat up to close hauled  in a smooth fashion, maintaining that attached flow and keeping above speed X ie the foil fly speed.                                 Now we can talk about the final luff to close  hauled and sailing the boat  ‘in the groove’. After we get the boat moving on say a beam reach, we understand from the log or the feel that the keel is  flying and the  rudder is  nice and responsive. Then we can work the tiller and sheet the sails in a smooth fashion such that we come up on the wind. *(alternatively you may want to stall the boat to buy time in approaching a start line by abruptly screwing up towards the eye of the wind and thus stalling forward progress)  Your foils are flying but you have now hull speed to think about. This can be roughly calculated by a long standing equation  based on the square root of the water line length but very often there are a sett of ‘target’ polar diagram or table figures available  for popular racing boats. Here we see what boat speed is ptimal for a given wind speed. So when you are close hauled in a modern 35 foot regatta machine your figure maybe between 6.9 and 7.9 knots. In most boats going slower than this is a sign that you are actually sailing too high from optimal close hauled, or of course your boat is not trimmed or rig tuned quite right. In small fast sports boats and dinghies you can actually start to sail a little quicker than hull speed as your boat is light enough to climb its own bow wave in a very early planing mode, even on the beat. However this is actually a sign that you are pointing too low to achieve optimal upwind velocity made good  -VMG , how beneficial the zig zag angle is relative to the  progress right into the  wind direction – until in a dinghy you can actually plane  upwind. The tell tale sign on this is that your stern wave detaches from the aft quarter of your boat. If you point a little higher, you can often see that it reattaches to the hull, and the bow and stern wave stream off in at a parallell angle.These boats tend to be best sailed with a neutral helm ie no weather and no lee, little pressure, just flow over the  rudder and adjustments made by steering to keep the  angle to the wind optimal. Hence this is one way of keeping a boat in the groove if it is a light weight performer.    
    Many of the ton designs and their deriviative mass produced boats have a very prominent weather helm when they are in the groove, this showing that the powerbalance is keeping the boat driving up to wind, and that the lift created  on the rudder itself is helping coutner act leeway. A major element of being in the groove  on what ever boat  is that in fact the boat feels quite settled, still and sometimes it feels slow because it ceases to accelerate and deccerleate. Very often experienced helms rely on the heel and the sensation of water past the leeward gunwhale more than their log and polar diagram as a good  handle as to them being in the groove. Being out of the groove or not maintaining it is the opposite. The boat heels too much, the helm gets imbalanced and loads up or loses influence, the speed is up and down.                 
       So we have learned so far that we need to get the rig set for the expected conditions, we need to balance our sail sheeting, we need to get our foils flying and we want to feel we are in the groove. Now  we are pointing. However we have  those  variable conditions to consider, with the wind being a fickle mistress and waves hindering peachy progress on the beat. Here we come to how we also trim the boat fore aft, to help maintain hull immersion and thus waterline related optimal speed while reducing drag from impact and exit of waves we sail against.
 As the wind builds too we need to discuss a sail change or reef, or try and use the running rigging to depower or power up. In rougher seas with nasty chop many light boats start to be a handful to keep in a high groove and tend to stall up. We need to foot off and steer around the waves, but this also means we never quite sail in the groove – our optimal VMG theory is out the window and we have to sail actively on helm and mainsheet to stop the waves hindering our progress and knocking our keel flow off.  Other heavier boats thrive as the wind builds and once fully powered up can even be pinched up on the wind to depower while still punching through a heavy chop, for example the Bashford Howison 36 and 40 designs.and many older ton and meter designs.
 So now you start to understand perhaps why old sea dogs and medal winners like Dennis Connor still talk about ‘we learned a lot out there today’ after decades of sailing. 

Prions, just what the….? 

It has been a good decade since I worked  in biotech and back then there was still a great deal of concern about BSE and CJD as fatal diseases with serious epidemiological consequences and many unanswered questions as to the mode of infection and replication. 

Thirteen years on from BSE gels at Invitrogen being the big thing, Prions remain a bit of a mystery and pose questions about the very origin of life as we know it- invasive, replicating and diversifying!

What Do We Seem to Know About Prions? 

Prions are very odd, they are an enigma to molecular biologists and may prove to be a factor in more disease aetology than we currently know through the more severe and easy to diagnose brain and CNS diseases we know today. In theory a single abbertant protein can precipitate many other proteins in a kind of chain reaction where they then semi crystalise in a new, stable state. This can be described as abberrant and altered protein folding, rather like a slinky *TM spring you are playing with which suddenly gets a little damaged and forms a new shape. 

. As the cell perhaps make more proteins to replace those which lose function, then the chain reaction continues until enough of the cell machinery is either overloaded or the cell is full of prion material and is subject to cell death and lysis. Thus prions are released to infect, or you could say damage other cells, in what many argue is a purely chemical way.

Protein folding is something which happens usually within cells as the peptides are being built on or through the Ribosomes, a nano 3D printer nature happened to fall upon over a billion years ago, or they are meddled with by other entities in the cell,  including  ions and importantly for Prion mechanistics, other proteins with which they form useful big proteins with, like haemoglobin or enzymes. Where as on sister or cousin protein will guide a newly made ‘wobbly’ string of amino acids, a peptide, into being a useful part of the cellular machinery, a Prion will cosey on up to it, and make it fold differently, into long beta sheet folds, which become like fibres in the cell once they start to precipitate. It is theorised that a prions could cause pre-made proteins to fall into a new state, by sliding on up beside them and coaxing them into spreading out and lieing beside them.A chain reaction may then ensue from protein to protein, within fairly specific classes of proteins, which for some reason are usually found in central nervous tissue so far at least,.. These ‘prionised’ proteins become far more stable than other forms, and difficult to get rid of, blocking up the cell and leading to misfunction and eventually cell death.

Ye Cannae Defy the Laws of Physics Jim….

 There is a fundamental bit of philosophy and physics here, that molecules will find a most stable state and persist.  Biological enxymes are inn contrast rather dynamic molecules, where often parts of the molecule act like hinges, or even become temporarily covalently bound to the ‘ligand’ which they are acting upon. Some complex proteins like Haemoglobin, harness both other organic molecules (porphyrins) and metals, iron of course in the case of most higher organisms. These complex proteins then are often not verry stable in terms of structure   or become a little ‘poisoned’ as catalysts. Hence our excrement is brown, as the unstable haemoglobin protein aggregates burn out so-to-speak,  and the more toxic break down product from their catabolism, bilirubin, gets secreted in our guts. 

Plaques they are called then  these aggregates of duff, structurally stabilised  protein, or fibrils to be more precise to mol’biologists. An analogy would be a seed crystal in a salty solution which creates a large, branching crysal, or for example a spec of dust which allows super cooled water in clouds to crystalise and become snow flakes. There is a natural, entropic tendency to assume certain structures and a single, small entity precipitaes out the bigger structure, which may be non homologous or semi homologous in the case of the proteins in animal cells. Without that seeding entity, there is no crystalisation. 

Molecular Intelligence or Pure Chance Entropic Effect ?

One of the main lines of thought is that Prions are a purely chance phenomenom which has arisen through a classic of evolution: perpetuation by surviving, accumulating and replicating. In that though there is a fundamental dileman or even oxymoron. Do Prions really replicate via a protein to protein route or is there as many suspect a viral type of nucleic acid vector? 

In theory though we could be looking at something which occurs by pure chance and is related to some fundamentals of the thermodynamics and entropy of protein folding. It could be that there is a weird chain reaction which is purely physical in nature, and propagates purely by re-release of ‘prionised’ proteins into the infected creature and then out into other  creatures. This is no bad stance to take on the theory, because it is known that CJD is spread from cattle to humans via consumption or exposure to body fluids and materials at work. 

However that stance is equally as enticing for an infectiious agent which uses a nucleic acid. Or as was propsed by some headline grabbers at the time, that there was a new route to replication of proteins outside the central dogma of DNA-RNA-Peptides. That a single protein agent could instruct the cell’s DNA , or mRNA to do something odd and cause proteins to build up and kill the cell, thus perpetuating the ‘species’.

. At one point it was believed that the Prion acted like a virus, devoid of nucleic acid code, but with a kind of proxy message – it could perhaps turn on genes which favoured certain protein production which then lead to more prionisation and inevitably, some proteolysis would create new prions. Or even more sinister, that the seediing Prion could both kill the cell having made more of itself by directly controlling the nucleic acid pathways. This would point to a most uncomfortable ideom for geneticists, the instructive method of gene control, where proteins tell the cell how to change, and the cell line alters, rather than the mechanism of natural selection being at work. There are though some special cases where this happens, in immunogenetics at least as far as I know, perhaps elsewhere, but that is for very specific purposes. Is there then a dastardly signal and almost alien life form mechanism behind Prion replication? 

No Signs of Message So Far?

More than a decade on from the BSE -CJD – Scrapie Pie scare in the UK and around the world, researchers have not found any nucleic acid or other set of instructions encoded in protein or anything else which would point to a little mastermind of an infectios agent behind the Prions. It could be though on the one hand that they just havent been looking in the right places or something has been taken for granted. 

On the other hand it could just be that we have that grain of sand in the mother of pearl, which makes a pearl in the one cell that is, which then bursts down to a million new grains of sand and is infective and replicative that way. Furthermore, if this latter be the case, it could be purely the fortuity of probability,  that these fibril bodies are proteolysed by cellular immune systems or post cell death, and a very few become ‘ seed prions’ as a matter of due course, given enough of them. .

Prions Are Perhaps a Clue to the Origins of Life 

We get back into the concept of the very origins of life, especially when the space ship Cassini finds liquid water and organic compounds on a moon of Saturn, and Mars , well is NASA holding back on us a bit here?  

Prions exist and propagate because they can exist and propagate. This is very much the kind of concept of very early life, when it has been hypothetised that peptides predated nucleic acids as the means of firstly ‘precipitating’ enough material so as to be able to replicate, and then to do this replication accurately enough to spread the proto organism. Proteins (peptides) very often naturally ligate metal ions, which then create a lot of useful and immensely powerful chemistry – the power to split water, carbon dioxide, oxygen dimolecules and nitrogen, phosphorous and sulphur compounds. to other thermodynamically useful ends. More replication, more accumulation of building blocks, more interesting things being built, chance  events. 

The ‘primeval soup’ then gets lumpier and lumpier as a string of chance events favoured by thermodynamics snow ball into ‘species’ of proto-organisms, which then either compete with each other, perhaps eating each other, or cooperate with each other. It is theorised now due to the deep hot volcanic vents of the ocean floor, that life could have evolved in many places on earth to the single celled forms. The idea of the miracle, the genesis event only once in the universe, is really put up against the possibility that carbon /nitrogen/phosophorous life is an inevitability if you have the right chemical buiolding blocks and environment. 

Prions – Does Nothing Direct Them, Other Than Thermodynamic Fate?

Personally I am kind of on the fence, just in case because they may well find an infective agent when and where they least expected  it. If Prion ‘seed’ proteins are only needed in small qauntities for the disease to progress, and there is then an advantage to the dark knight infective agent behind the scenes to use this, then it may be that the little nasty thing is a real lurker, or in fact nothing described by science so far – a protein only virus perhaps? On the other side of the fence, there is the pure entropic beauty of a self propagating protein system, which has no forward looking ambition, there is no design in its madness, it purely is a phenomenom because it can be one due to the laws of physics and chemistry. 

Here then we get back to the origins of life and how a ‘soup’ of what ever nutrients and metal ions, could kind of simmer for a while and start to do interesting, large molecule based chemistry which replicated itself. If you replicate something by chance, you get more of it, it accumulates, it propagates. In a more complex way, but yes you can say like a nuclear chain reaction in a fission neutron reactor. Over time we see that which persists, that which thrives, that which adapts. Most of all we see the mechanisms of the universe and life are fundamental and undeniable.

Perhaps indeed Prions are either a very old hang over from the earliest forms of life, which nature never quite managed to kill off. Or perhaps prions are an example of  co-evolution, a secondary meta-genesis event fortuitated by some vagiaries of proteins in brain tissues in particular.  These particular protein systems which were not present in earlier evolution when DNA based systems were kind a pressure to select against Prion type activity as being dangerous and competitive to the new, robust and ‘blindly intelligent’DNA driven core of life to come. Hence perhaps prions can do their dirty work and spread purely because they damn well can, it is an inevitability given the right set of factors.. 

Questions Around Allelic Exclusion, 30 Years On

It’s 28 years since I studied allelic exclusion in B lymphocytes as my paper based undergrad’ thesis. I kind of fell upon the concept, as it always bothered me from the first days of understanding simple Mendelian genetics – how does it all work with two copies of a gene yet only one phenotype?

Well Mendel of course, cheated. He actually ignored strains of peas whose flowers bred through to pink, instead of those which bred pure white or red. Genetics is always throwing up complexity around some central simplicities, and as with the Human Genome Project, scientists go off on keep-it-stupid-simple at their hazard.

In allelic exclusion in certain types of  white blood cells, there is some very interesting genetic engineering, and sorry dear creationist, you can see evolution happening in your own bodies if you care to study the molecular mechanisms. At some point a white blood cell decides                                                                                                                                                                                                                                   to make one very specific antibody which has the purpose of             very specifically locking onto a potential  disease causing agent. This is then locked and in effect it becomes a memory cell if you like, which can then explode in a clonal type way to produce thousands of these cells all of which are identical to fight a disease currently threatening the body, or doing so in future. Earlier on in the story, the cells have undergone some degree of evolution, firstly by being selected as fairly good matches for that ‘pathogen’ or antigen to be more accurate, and then having to select which one of two versions of the gene for the antibody will be the one which is most suited to the job at hand after in fact the cell induces some very specific mutations, or internatl genetic engineering, to alter small parts of the antibody such that it may become more specific and thereby the antibodies will bind better and discriminate between this specific threat and others in a manner much enhanced over the earlier incarnation of the cell line.

So one gene gets switched roundly off, while the other copy, which is a little different due to this ‘hyper mutation’ is kept for the life of the new cell line. If i remember correctly, there was only one iteration of this process, but of course it occurs over a population of white B lymphocytes and other related antibody producing cells, so that a diversity is then honed down into a more targeted set of cells which can tackle disease better. So we see natural selection at work, every day , in our own bodies with mechanisms of molecular directed evolution to boot!

Now this was thought to be a very specific mechanism, the exclusion of one of the two copies from further use in the cell. However back to Mendel. It seems to be very wasteful to have one copy of the gene which is recessive, or presumably non functional? White flowers it seems are default no colour when two copies of the white, failed gene are present. It just seems a waste of space.

Well in fact recent research amongst relatively inbred populations including Iceland and an area in Pakistan, show that in fact humans in such small gene pools harbour upto 7% inactive gene copies. It may seem that prevalence then of genetic diseases would be much higher, but althouugh some typical genetic linked diseases like Huntingdons are present, there is actually not a correspondingly higher rate of disease in accordance with the inbreeding and this high percentage of ‘knocked out’ genes.

Here we see again that a simple route can reveal complexities and the golden rules can and are broken, wihtout perhaps the exeptions quite proving the rule. We find that a gene in the genome, on the chromosome, can be swithced on and off intermittantly, or more locked away and this can vary between copies, sometimes the paternal is less likely to be switched on than the maternal copy. The simply methylation of chromosomal DNA can affect this. Also the gene product need not be a protein, but can be an intermediary control element. And if there is a final protien as in the good old central dogma of genetics, then it can vary in how it is constructed from the one gene, or be made up of several genes spliced together at the messenger RNA level. 

Oh dear, Genetics is big and scary and the Human Genome Project to some extent, only confused us more. There were fewer genes than expected, and a now it seems there may be more inactive, fautly genes that first thought. Also there may be redundancy of alleles, or multiple alleles of the same gene, or perhaps gene products can be cobbled together to make up for a K/O’ed gene at the mRNA level. It suddenly became important to study diversity between individual genomes so as to try and understand what was going on. 

From my point of view then I always said that in Genetics and molecular biology, there is simplicity to be found in diversity, and that the abnormal informs the normal. There is a fundamental truth that in studying one fairly obscure genetic phenomenon, we find a universal truth, yet we cannot understand a universal trith fully without considering diversity.

Big science has kind of speeded things up, but also quite possibly used up huge resources in uncovering issues which were already there as in the last paragraph . We need to look at the detail but also how varied each detail is. So if you follow one obscure detail, like allelic exclusion in B cells, then you find out a lot about it, in fact so much that in this case specifically, it seems it is just an obscure mechanism . for time being. If you give yourself a bigger job, then yes you get more done in terms of this diveristy, but you are building a bigger stick to beat yourself with as that diversity then starts to obscure the universality in mechanisms. However Big Science came with a lot of public and private funding so we cannot complain from that point of view, and a lot of processes which were tedious and manual when I was working in labs (with the first commercially available multi well PCR thermal cycler with digital control) have been either fully- or semi/automated and results are as likely to be read on a computer screen than in a ‘petri dish’so to speak.

The older, more patient and pedantic me would suit being a scientist today because I am quite computer literate and like solving puzzles,. At the same time being locked into using standard equipment means that you perhaps loose some pioneer spirit and perhaps come up with less new technique innovation, which is also very enabling in terms of being able to do new things, if not do the same thing thousands of times over accurately and automated. 

We come back to the whole simple argument which is really about sex. Why have diploid organisms which breed sexually? Well in fact those industrious and ingenious little B cells have the answer. We need diversity to survive and evolve. Without diversity there would be no real selective evolution, one species would tend to get whiped out, as we saw with for example the potatoe blight of the 1800s which was from all plants stemming from a tiny number  brought back from S. America. We need sexual reproduction and sexes because it means we can recombine good survival packages of genes to then meet the challenges of the environment. Sex speeds up evolution by this mixing up of genes too. Some new combinations fall by the way side, while other quire surprising genes come to be quite common, such as the odd case of sickle cell anemia, a simple point mutation, which you would have thought would be bread out due to the higher morbiitiy and mortality of having the double dose. But the single dose confers a protection from malaria, which hides in red blood corpuscles, which then split open upon infection. Here we see a perfect example of the opposite of my thesis area, where there is no exlcusion what so ever, there is a neutral inclusion of both gene expressions. 

 I could hypothesise then that we will find that some gene alleles have one favoured all or most of the time, while others just arent important enough. Some alleles can be compensated for by other gene alleles or qausi alleles. Some gene alleles have one of the pair long term down tuned  via methylations, and that can be tissue specific. Some genes may well be turned more on at one of the pair copies. Some genes will be then later tuned or eliminated at their RNA level as far as getting stuck onto the ribosome protein factories. Sometimes we may need multiple copies of the gene on at any time to make enough protein or gene product. 

Allelic exclusuion in the context of a secually reproducing multicellular  organism is a high risk strategy in some