Saturday, 24 September 2016

Dawkins' and Pinker's gene

The two biggest problems for Dawkins' and Pinker's interpretation of what the gene means as a heritable "element" that affects phenotype. Is that first it is most often not an element but a system of non-local and interacting elements and secondly and most importantly it will not follow Mendelian genetics. It will not be segregating and discrete. There will be a myriad of variations depending on how the system responds to the environment it finds itself.

Mendel was lucky with the characteristics he chose to examine and when you do have genes that segregate then you do have a gene as described by the molecular biologist and geneticist, of they type that Pinker riles against. They are just different alleles corresponding to an expressed region of DNA or possibly their cis regulatory regions. They are not the nefarious and indeterminate objects defined by Pinker and Dawkins. If we are to take their views seriously then we have to go back to before the modern synthesis and try again.

Now that we know that most of the genome can be defined as loosely functional, even if just in terms of spacing between coding regions, then perhaps we do need to look at what the term gene means.

Thursday, 22 September 2016

I finally understand what Dawkins means by gene

I was reading a short article by Steven Pinker in the book "This Idea Must Die". There Pinker was saying about how molecular biologists have a different view, a very restrictive view of what a gene is. They only consider the protein encoding region of the DNA as the gene.

That was a Eureka moment as I finally understand what Dawkins was trying to say. He shares exactly the same view as Pinker. To him a gene is a heritable element that produces a phenotype. This is a much older view of the gene than the view I was brought up with. It predates knowing anything about DNA at all.

To the atomistic and DNA based molecular biologists and geneticists this means the sections of DNA that produce the protein that is responsible for the phenotype. That piece of DNA when expressed causes the phenotype. This is why the molecular biologists got such a shock when they found that there were only 20-30 thousand protein expressing segments, genes in their words, in the human genome. This looks the same as Dawkins' gene but it is completely different. Dawkins because he knows very little about genetics and molecular biology is living in the world view before the modern synthesis which linked DNA to genes. Pinker shares the same anti-reductionist perspective. Even though both would consider themselves materialist and reductionist scientists.

Their view of the gene would include all of the regulatory elements, both local and non-local in the genome. It would also include all of the mechanisms for regulation and post-translational modification, for localisation and for every other modifier that affects the process of taking that section of DNA or those multiple sections of DNA to produce a phenotype. In Dawkins' view there are no multi-gene effects to produce a phenotype because the genetic atom is actually that complete system that relates DNA and phenotype.

That is what makes me so strongly critical of Dawkins' work because he has no appreciation of the system at the molecular level. I work with proteins and how they fold and I even dislike DNA. I see the disconnect between the DNA code that can be mutated and the proteins that they produce. There is a huge non-linearity in their connection. The effects of mutations are almost impossible to predict. But if you take Dawkins' and Pinker's way of specifying a gene just as a heritable element then their writing makes a lot more sense.

It makes more sense but they still ignore the fundamental problems with this view. That is that these "atomic entities" these genes are not atomic. They are overlapping, intertwined, non-local and non-linear systems that cannot be approximated by some atomic genetic theory. In each cell-type the networks of connections between regulatory elements and expressed regions is different and that is not even considering spatial effects.

In their world each cell type would have its own set of genes, because each have their own phenotype and own system of expression. Even each of my tissues would become a collective organism and and animal would become a collective of collectives. It is this decision to ignore the relationships between the parts and to impose an artificial genetic atomism on these heritable elements that makes it unrealistic as a view. Playing with my sons' Lego makes it clear. I have all those bricks which are the genes of the model. But unless I put those bits together in the right way I never get my car or my space ship. If you don't think at the systems level you can never understand biology. Atomism and reductionism are doomed to failure.

Saturday, 3 September 2016

Big Government should Amazon and Starbucks pay more tax?

Yesterday I posted about beggar my neighbour and why the Ireland/Apple tax case matters for democracy and stability. Today Amazon and Starbucks are he focus of attention. These are two more in a very long list that will also include Google, Vodafone. Microsoft and many others who use their global clout to minimise regulation and taxation.

What was amusing is the posts on social media by neo-cons about the companies being justified because the governments waste money and so they should keep avoiding the tax.

What do governments spend their money on? A lot of it is social security and a lot of that is pensions (much more than unemployment in the UK). So shall we cut pensions because Amazon and Starbucks don't pay up? Should those Daily Mail reading baby boomers who support the neo-con illusion get shafted by their own stupidity? Should we allow them to poke themselves in the eye? Sounds good to me but maybe not.

What else does the government pay for? Healthcare is a big spend as well. We could allow Amazon and Starbucks to use their tax avoided cash to invest in sponsored hospitals and to reproduce the philanthropy of Carnegie or Rockerfeller. Look at Oracle and the billions of Larry Ellison as an example he used all that cash to build - the most expensive racing yacht in history. So maybe expecting billionaires to give away their money is not such a good idea (I know Bill Gates has done amazing things and George Lucas and Warren Buffett as well but they do not run countries).

The government also spends money on defence. From an evidence based view this is often a waste of money and the social media post is correct. Britain is building two stupid carriers to fight the types of war that no longer exist against enemies that are no longer there. We are about the renew nuclear weapons that nobody will ever use and that are also a waste of time. Oddly enough I suspect that the person who made the media post would say that this is NOT a waste of government money as the neo-cons are easily deceived by Eisenhower's military industrial complex that sells what nobody needs at an extortionate price.

Then there is education. We could all do with a lot less of that so that we can all be as stupid as the Daily Mail readers and the neo-con social media enthusiasts. That keeps people from questioning. Yes you need to train an elite to run your business and keep globalisation going but an ignorant population is good for business.

What about the infrastructure paid for by taxes? The roads etc. Well there is lots of mis-mangement of funds there, but is is caused by the neo-con push to privatise all services and to have the market find the best price. Just ask Halliburton how this works for them in the US and ask any local government how it has worked out in the UK. Higher price poorer service and don't mention PPI.

So yes Amazon, Starbucks etc. should be paying taxes and while sometimes government does waste money it is a lot better than the alternative.

Friday, 2 September 2016

Beggar my neighbour: Apple's Tax Problem in Ireland

There is well known economic rule called "beggar your neighbour". It is important in behavioural economics when you consider the model of the repeated Prisoner's dilemma. In that case beggar my neighbour represents the defection strategy. There is also a connection to companies seeking countries with the minimum regulation/taxation. This is when the companies are defecting.

Companies have a duty to shareholders which in the short term and when you do not expect there to be a repeat of the circumstances means that defection is the preferred strategy and politicians often think the same way. This is sib-optimal capitalism. It is sub-optimal because in reality we have longer term interactions and repeat business which are undermined by defection. Axelrod has shown that the best strategy as proposed by Rappaport is Tit-for-tat. You respond to defection by defecting and then you go back to a position of trust. Trust is the essential feature that makes the system optimal. You have to maximise the trust to reduce the costs of regulation and defection.

At a national level a defecting country is one that offers a lower level of regulation and taxation compared to all the other countries as business will move to that country and not pay taxes where they actually are active. This is how the Swiss canton of Zugg has become the European HQ of many multi-nationals. Zugg has a tax rate of 5% which is very attractive to global business. Given the size of the canton this minimal amount of tax from a large number of corporations raises more than enough for the infra-structure and services that the canton has to pay for. In fact they should be making a considerable profit. Levels of taxation elsewhere have to be larger because nations are expensive and levels of tax are set to avoid a deficit. This is why Zugg is beggaring its neighbours and why Ireland with its Apple tax deal was also beggaring its neighbours by removing tax revenues from other countries where Apple was doing business. Apple was unlucky enough to be the first company that was brought to court but it will not be the last and Google and Amazon are two more big names that stand out.

Ireland with a much smaller economy can survive without all the tax that is owed but this deficit is pushed onto all the other EU nations. That is why this sort of tax deal is illegal and why the UK deal with Vodafone also  needs to be investigated. Governments do this because they want to keep the jobs in their countries but if I did this as a small business or as an individual even if I did not do my duty well enough only in the expectation of a future benefit I would be in jail for up to 12 years and face an unlimited fine under UK law. In fact the recent report about the possible dropping of the investigation of BHS in return for Sir Philip Green paying a large sum to the pension fund is also bordering on illegal under the Bribery Act 2010. I begin to see why an Italian mafia judge called the UK the most corrupt country in Europe.

Ireland has been caught cheating but both Ireland and Apple are going to seek to contest the judgement. The only way that you can prevent beggar my neighbour is if we go beyond short term interests or if we promote supra-national agreements. We call these trade deals and although TTIP is a dirty word at the minute there are many others that we rely on everyday. The WTO is the largest agreement to make sure that nations do not deliberately cause economic hardship for each other. But the most successful is the European Union and that is why Ireland and Apple in the end have to lose if we are to have any faith in nations and democracies and if we want to live in a world which has not been taken over by corporations.

So why does not being able to beggar your neighbour matter? History shows that wars are usually about resources and as a response to internal economic challenges. Harming another countries economy has political and social consequences and not just economic ones. If we want a more peaceful and equal world we have to get beyond Brexit and Beggar my Neighbour and start understanding the long term benefits of working together.

Monday, 20 June 2016


I have just received the EU Myth Buster from the Brexiteers. Firstly it still has the already proven wrong 350 million a week claim, as well as the nonsense about expansion to new members including Turkey. This is all scare mongering and the gall of the Brexiteers to claim it is Remain that are using economic fear to win the argument is just nonsense.

On the back the great and the good making their arguments. I wanted to go through them one at a time.

1) Sir Richard Dearlove - former chief of MI6.

"Brexit would bring about two potentially important security gains: the ability to dump the European Convention on Human Rights ... and more importantly, greater control over immigration from the European Union."

Sorry but this makes me very worried when a former head of the security service thinks that not having human rights is a good thing. This is the person who was in charge during 9/11 and then the dodgy dossier fiasco. Regarding his second statement, is the EU a source of terror threats to the UK? The 7/7 attacks were home grown and we do control immigration from outside the EU. He is also on record as stating that the media have exaggerated the threat from Islamic terrorists. So maybe he thinks the French farmers have been radicalised and are a threat?

2) Tim Martin - chairman of Weatherspoons

"The EU places tariffs on goods from outside the EU, which is bad for British shoppers and the developing world. And the EU forces us to charge VAT on goods, pushing up bills for working families."

By his argument leaving the EU and becoming one of those countries outside this is going to be good because now we are subject to those tariffs he is talking about. The levels of taxation are set by governments and they are to make sure that the finances of the country are in good order. The UK sets its own levels of VAT. These had to be increased because of the banking crisis not the EU. When we face tariffs because we are outside of the EU tax levels are likely to rise even more.

3) Nigel Lawson - former Chancellor of the Exchequer.

"As Chancellor, I became increasingly aware that, in economic terms, membership of the EU did us more harm than good. Outside the EU, we would prosper, we would be free and we would stand tall."

Sorry Nigel but this is pure rhetoric without a single shred of evidence or valid argument. He was last Chancellor in 1989 before the Berlin wall had fallen. The world has changed a bit since then and certainly the economy has changed beyond all recognition. Free and tall are not economic arguments, they are useful for boxers and cage fighters but they do not secure wealth for nations.

4) John Longworth Director of the British Chambers of Commerce.

"The EU interferes with UK firms and stacks the rules in favour of a select number of big businesses. It we Vote Leave jobs will be safer. We can have faster growth and greater prosperity in the future."

The EU spends a very large amount of its business spending on what are called SMEs and not the very large firms. Big business and big interests are very effective at lobbying the EU. My dad was a lobbyist for the Cattle Breeders Association and the UK farming industry which is hardly a big business. He would have never dreamed of voting out. The EU actually is more effective than the UK in dealing with the excesses of global business such as Microsoft and Google. These are companies that individual nations do not take on. In fact the UK government is noticeable in its reticence to get involved in taxing many of these businesses (Vodaphone is a high profile example) which get special tax deals that are certainly not given to small UK firms. Exactly the opposite to his claims is closer to reality.

5) Gisela Stuart Labour MP

"The rights we have won for British workers came from our Parliament, not the EU. The EU is run in the interests of the big corporations who spend billions lobbying to make it work for them."

I think that billions is an exaggeration. Even big business cannot spend that much on a Parliament that has so little legislative authority. I seem to remember the Conservatives opposing EU legislation precisely because it did protect worker's rights and asking for opt-out clauses. I seem to remember the social charter causing uproar from Mrs Thatcher, which does not agree with the MP's claims. It was only finally accepted in 1998 by a Labour government. I was also discussing this issue and where Deutsche Bank would move to if there was Brexit and the wife of one of their employees said not back to Frankfurt because they are only allowed to work a 37 hour week in Germany because of the EU legislation (that has not bee adopted by the UK) whereas her husband has a 67 hour week here.

It is amazing that in 5 quotes there is not a single good reason to Brexit. There is nothing there that is not fabricated, untrue or not pure fallacy. If that is the best they have got in their arguments then the Remain camp have very little to worry about.

Wednesday, 13 April 2016

Thoughts on Heritability

Using Waddington's idea of canalisation. This is the related to the width of the canalisation - this is the maximum variation between a pure in bred low phenotype and a pure in bred high phenotype. This is the variance in that characteristic which is attributable to the genes.

This is going to be very hard to measure unless you do it for a genuine population. If you have a non representative sample then that will have its own variability and the variation in that characteristic will depend on the state of all the different end points you are starting from in a normal mating population carrying all of its history and variation. Think of dogs the dog population includes all the breeds but the variation within breeds is very low, the same with horses but with humans you have Usain Bolt and me to compare for our 100 metres performance.

The width of the canals is important as it shows the plasticity in response to environment. How far does it need to be pushed to get someone outside the normal bounds. The genes make the landscape and they do not determine the outcome except in pure bred lines where the canals are very narrow. 

High heritability could actually signify large canals and low determinism because we are very far from a pure bred line and everyone is close to the middle of a large canal. But it could also indicate low variation and a multi-modal population - mixing of species, comparing apples and oranges. Conversely low heritability measures would mean that there is low variation with very narrow canals and it is very strongly inherited.

The concept of heritability implies that you can have a pure bred line for a specific phenotypic characteristic and so that characteristic must be inheritable. So my reason for questioning the paper rejecting Haidt and heritability is that why would his classifications be capable of being bred for? Can I breed someone who believes in justice over everything? Can I breed someone who finds disgust in the unclean their biggest driving force? Can any of these higher human constructs be embedded into genes or are they more accurately modelled at the meme/cultural evolutionary level? This is what I meant by there being strong determinism - that you could breed for it and that the genes would determine the effect. 

My opinion is that they are at the cultural evolutionary level and only the very simplest of behaviours is canalised at the genetic level. This would be probably things like higher level reasoning, personal identity, desire to reproduce, desire for satisfaction etc. The advantage of the cultural/meme level is that it is NOT Darwinian. It develops during lifetimes and is directly passed on to the next generation. It is Lamarckian and not wasteful random exploration. It builds on what we already have and is rapidly modified. It is much faster than genetic evolution. 

Sunday, 20 March 2016

Spectator Review of Not in Your Genes

This is the spectator review by a post-doc in psychology.

Now there are some good references in the beginning but sadly the complaints and understanding also decline as it goes on. In particular it descends into an ad hominem attack against the author and not his work. If you are convinced of your argument why go after James and his media appearances?

The first few references seem fine about birth order and the 10,000 hours effects. Then is goes down hill. So what if 80% of genes are expressed in the brain - this tells you nothing more than the 20% that are not cannot have any effect on the brain. Why does this mean anything? Lots are house keeping genes that just keep cells alive.

The ample evidence is a meta analysis of twin studies. The problem with twin studies if the author had bothered to check is that epidemiologists now suspect that they might be flawed as they have the same exposures and circumstances. I have two children who are not twins but they share lots of views and personality traits because of their upbringing not because of their genes. It is very hard unless you separate twins to actually get good evidence for genetic as opposed to environmental effects and even then epigenetic effects might be larger than genetic effects (these follow Lamarck and not Darwin - they are "Just So Story" modifications that are directly heritable)

I will need to look at GCTA and think about how to weight that evidence.

Then there is a look at GWAS which again the review author just talks about a review chapter. I have seen the people who lead some of the major GWAS studies of disease speak and there conclusions are that the effects of genes are SO SMALL THAT THEY CANNOT BE STATISTICALLY DETECTED. The effect sizes are tiny in diabetes, heart disease and lots of less complex phenomena than learning and personality. This is because it is gene interactions that produce the effects and not single genes. This talk was from the same lecturer who cast doubt on the twin studies. The review author might like to read Prof. David Clayton's work.

Then for basic statistics he cites wikipedia. While I like wikipedia this is all credibility lost. Power calculations are a tautology. You need to know effect size and population standard deviation in order to calculate the population size that you need to use to detect the effect. This is knowing the answer before you ask the question. The last references from the Journal of Irreproducible Results (Nature) is from the News and View section, an unrefereed section where the great and the good get to spout garbage on a weekly basis.

So apart from the possible evidence from GCTA there is actually as little to support the reviewers assertions of genetic links as there is for James support that there are no genetic links. The final result is a 0-0 draw.