Thursday, October 30, 2014

Three good pieces

1. Best review of Iain M. Banks's Culture sequence


Matt Hilliard, a smart and insightful reviewer at Strange Horizons wrote this piece on his blog: the best assessment of what on earth Banks was trying to do with his Culture novels. His take on Peter Watts' Echopraxia is equally superior.

2. Steve Hsu's popular and accessible article on genetic engineering for super-intelligence

Steve Hsu in action
"Super-Intelligent Humans Are Coming - genetic engineering will one day create the smartest humans who have ever lived".

'Stephen Hsu is Vice-President for Research and Professor of Theoretical Physics at Michigan State University. He is also a scientific advisor to BGI (formerly, Beijing Genomics Institute) and a founder of its Cognitive Genomics Lab.'

His blog is here.

3. What makes the quadcopter design so great for small drones?

Remember all those camera drones with four rotors arranged in a square? Amazon's PR stunt for drone delivery? Why do we still go for helicopters in the large then? Is the future the quadcopter?

Here's why not.

A helicopter drone

Thanks to Jess Riedel's blog for the last two links.
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Oh, and here's a laugh-out-loud bonus from The War Nerd.

Take me to Istanbul ..

Tuesday, October 28, 2014

MAO-A: violence through to depression

From BBC News today:
"A genetic analysis of almost 900 offenders in Finland has revealed two genes associated with violent crime. Those with the genes were 13 times more likely to have a history of repeated violent behaviour. The authors of the study, published in the journal Molecular Psychiatry, said at least 5-10% of all violent crime in Finland could be attributed to individuals with these genotypes.
...
"Each criminal was given a profile based on their offences, categorising them into violent or non-violent. The association between genes and previous behaviour was strongest for the 78 who fitted the "extremely violent offender" profile. This group had committed a total of 1,154 murders, manslaughters, attempted homicides or batteries. A replication group of 114 criminals had all committed at least one murder. These all carried a low-activity version of the MAO-A gene, which previous research has dubbed the "warrior gene" because of its link to aggressive behaviour."
Monoamine oxidase A, also known as MAO-A, is an enzyme encoded by the MAO-A gene. It operates in nerve tissue where it degrades neurotransmitters such as dopamine, norepinephrine, and serotonin. This affects mood.

This "warrior gene" thing is somewhat old news. Wikipedia states (in a rather badly-written article):
"In humans, there is a 30-base repeat sequence repeated in one of several different numbers of times in the promoter region of the gene coding for MAO-A. There are 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence, with the 3R and 4R variants most common in Caucasians. The 3.5R and 4R variants have been found to be more highly active than 3R or 5R, in a study which did not examine the 2R variant. An association between the 2R allele of the Variable Number Tandem Repeat region of the gene and an increase in the likelihood of committing serious crime or violence has been found.

"MAO-A levels in the brain as measured using positron emission tomography are elevated by an average of 34% in patients with major depressive disorder. Genetic association studies examining the relationship between high-activity MAO-A variants and depression have produced mixed results, with some studies linking the high-activity variants to major depression in females, depressed suicide in males, major depression and sleep disturbance in males and major depressive disorder in both males and females.
...
"The frequency distribution of variants of the MAO-A gene differs between ethnic groups. 59% of Black men, 54% of Chinese men, 56% of Maori men, and 34% of Caucasian men carry the 3R allele. 5.5% of Black men, 0.1% of Caucasian men, and 0.00067% of Asian men carry the 2R allele.

"A connection between a version of the monoamine oxidase A gene (3R) and several types of antisocial behaviour has been found. MAO-A had no statistically significant main effect on antisocial behaviour. Maltreated children with genes causing high levels of MAO-A were less likely to develop antisocial behaviour. Low MAO-A activity in combination with abuse experienced during childhood results in an increased risk of aggressive behaviour as an adult. High testosterone, maternal tobacco smoking during pregnancy, poor material living standards, dropping out of school, and low IQ can also trigger violent behaviour in men with the low-activity alleles (which are overwhelmingly the 3R allele).

"In individuals with the low activity MAO-A gene, when faced with social exclusion or ostracism showed higher levels of aggression than individuals with the high activity MAO-A gene. Low activity MAO-A could significantly predict aggressive behaviour in a high provocation situation, but was less associated with aggression in a low provocation situation. Individuals with the low activity variant of the MAO-A gene were just as likely as participants with the high activity variant to retaliate when the loss was small. However, they were more likely to retaliate and with greater force when the loss was large."
So to summarise and over-simplify: low levels of MAO-A lead to aggression; high levels lead to depression.

Egocentricity asserted itself at this point and my thoughts turned to my 23andMe genotype data. The 2R (two repeats), 3R, 3.5R, 4R, and 5R variants of the repeat sequence aren't looked at by 23andMe, as they only test for SNPs. However, the gene which codes for MAO-A also has alleles which differ in SNPs, specifically rs6323.

Only one nucleotide to report here for me as it's on the X-chromosome and I'm male. The variant which expresses the most MAO-A is the G-variant, which makes its carrier prone to depression.

I'm T: so a tiny bit more warrior than someone on antidepressants.


Wednesday, October 22, 2014

Chris Froome out of 2015 Tour de France?

The Guardian writes:
"The 2015 Tour will include only 14 kilometres of individual time trialling, on day one in the Dutch city of Utrecht. This is the smallest amount since the race was relaunched after the second world war and the first time in recent years that the race has not included a time trial in the final week.

"In a statement issued shortly after the launch of the 2015 race route on Wednesday morning, Team Sky’s Kenyan-born Briton, who crashed out of the 2014 event in the first week, said, “The team and I will have to give it some careful consideration before we make any commitments to which of the grand tours I will compete in.” The 2013 winner was not present at the launch in Paris.

"Froome added: “The Giro with its inclusion of a long TT of 60 km and tough uphill finishes will make it a well-balanced race, which suits me well. If I did the Giro I may also be able to get myself back to top shape for the Vuelta and go there with a realistic chance of aiming for the win. In the past I’ve only targeted one grand tour each season but it could be a good opportunity for me to focus seriously on two.”

"The lack of time trialling in the 2015 Tour should suit the French riders, who staged a dramatic resurgence in the 2014 race, and as if to express their hope that history is on the home nation’s side, the organisers have included a finish at Pra Loup, the resort in the southern Alps where Bernard Thévenet toppled Eddy Merckx in 1975."
This is the kind of hyper-rational analysis which you expect from Froome's cerebral persona. I imagine Bradley Wiggins is aghast: as the 2013 winner, how could you not want to participate in the greatest bike race in the world? Where is Froome's sense of the grand tradition, the honour of cycling?

I wonder whether Team Sky just took a look at the route and figured they couldn't win? Certainly without Froome (and with Wiggins essentially retired from  road racing) they have no credible candidate for a win. Perhaps the notoriously neophilic Team is itself bored with the Tour, and is restlessly seeking new challenges.

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Not many posts at the moment as I'm tied up with various domestic matters. In-between I'm just finishing Peter Watts' Rifters trilogy and very dark, smart and techno-soapy it is, with a soupçon of grotesque horror. Greg Bear's War Dogs and Michel Faber's The Book of Strange New Things have arrived and joined the queue. I'm looking forwards etc.

Friday, October 17, 2014

Shirley Porter's funeral

Clare and myself attended Shirley Porter's funeral this morning at the South Bristol Crematorium. Details of the service and some pictures in this updated post.

Shirley Porter

Wednesday, October 15, 2014

Any chance of stopping this Ebola thing?

An aside: you might think that an airliner must be an ideal Petri dish - recirculating air and a captive audience. It is claimed that cabin air filters have a virus removal efficiency of greater than 99.999% but that manufacturer's guarantee shouldn't be relevant as the Ebola virus currently doesn't transmit via the air, only by personal contact; so we hope for the best. (See here for an informed contrary view).

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Ebola is not going to be stopped in Central Africa: too many cases, too-porous borders, high population densities, poor infrastructure and incompetent authorities, rubbish disease-incidence reporting. Ghana won't be safe for too much longer.

From GhanaWeb

Projection data for the likely spread of Ebola is modelled here - click on charts.

The media (the BBC is a typical offender) talks about 'irrational fears' and the shocking humiliation caused to those on the wrong-end of screening. Very comforting - God help that we should over-react or anything.

What is scary with exponentially-increasing and highly-lethal epidemics is the way things can turn from a background somebody else's problem to something directly, immediately threatening on a time frame of less than a month. (Although here in Europe we'll probably get the Ebola experience quarter one of next year via North Africa).

We're in a situation far too reminiscent of the mediaeval Black Death. The thing which we know works is draconian quarantine. People will be shot (or quarantine will fail). I expect there are contingency plans to set up quarantine zones in the UK right now - if not, someone isn't doing their job right.

The other thing which might work is a treatment or vaccine.  The development schedule is not encouraging.

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The Wikipedia article notes:
"Ebolavirus is classified as a biosafety level 4 agent, as well as a Category A bioterrorism agent by the Centers for Disease Control and Prevention. It has the potential to be weaponized for use in biological warfare, and was investigated by the Biopreparat for such use, but might be difficult to prepare as a weapon of mass destruction because the virus becomes ineffective quickly in open air."
I have this vision of sections of the Nigerian military collecting the corpses of Ebola victims, dressing them in soldiers' uniforms and dropping them by parachute into areas know to be occupied by Boko Haram - they'd be sure to investigate. The equivalent to the mediaeval practice of catapulting the bodies of plague victims into besieged castles. Could anyone, do you think, be so stupid?

Sunday, October 12, 2014

Ebola nuclear strike: a really poor idea

Sierra Leone topography (Wikipedia)
It might have occurred to you that rapid sterilization of the current Ebola outbreak could paradoxically be the most humane course of action in the long run. So we read statements like this *:
"Under the circumstances, we must assume the worst-case scenario,” Weurfuqd’naowe concluded at the close of his press conference.  “The evidence we have indicates that this is a new and extremely contagious strain of filoviridae Ebola, posing a health threat worse than any previously-known epidemic.  If the virus succeeds in migrating out of Guinea, it could very well sweep the planet more rapidly than any medical intervention would be possible.”

“We will monitor conditions in Guinea’s urban centers closely over the next twenty-four to thirty-six hours.  If the disease spreads as rapidly as we fear, it will be imperative that the outbreak be contained and exterminated at any cost.  Regretfully, it is the recommendation of the World Health Organization that members of the United Nations must consider the use of a nuclear weapon, if necessary, in hopes of stopping the lethal virus before it spreads across the world.”
Here are some reasons why this is a poor idea.
  1. The last thing anyone wants is kilotons of wind-borne radioactive fall-out dusting Central Africa. This might suggest using high-altitude radiation-enhanced weapons (aka neutron bombs). Unfortunately, while gamma rays are good at killing people, viruses are remarkably tough. So in practice we would need to ensure detonation of the thermonuclear fireball pretty close to ground level. Unfortunate.

  2. Sierra Leone is big - see the map above. So are Guinea and Liberia. There are big cities where the epidemic concentrates, but also networks of far-flung villages where infection ebbs and flows. Nuclear bombs are not good area-denial weapons: the fireball radius goes only as the cube root of the weapon yield. To sterilize a country the size of any of the three affected would require hundreds of high-mega-tonnage systems, with no guarantee of complete success.

  3. Not all Ebola-carriers would be vapourised in any conceivable strike. Inevitably refugees would flee into neighbouring countries: Senegal, Mali, Ivory Coast, there to become the seeds of a subsequent round of infection. There is a limit to the number of African countries which can be nuked. And in the aftermath of the sterilization event, do-gooders from a hundred countries would flock in for 'disaster relief'. Can you imagine a more effective method of then spreading Ebola around the globe?
And radiation-induced viral mutation; we so don't want to go there. No, nuking the epidemic is a poor response and I would advise policy makers not to go down that route.

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* Check the date, by the way, on that report.

Saturday, October 11, 2014

Ebola: should you be worried?

Just to the end of October 2014
That's the trouble with exponentials: they burble around beneath the noise floor - 1, 2, 4, 8, 16 - and then sixteen iterations later it's one million, two million, four million .. and you're overwhelmed.

Scientific American writes:
"In a worst-case scenario the CDC projected that by mid-January, Sierra Leone and Liberia alone could have up to 1.4 million cases."
Yes, mid-January .. and 1.4 million.

Dr James Thompson at UCL has been posting about this, the latest being his satirical "Ebola IQ test"
"Given a viral disease which is transmitted by contact with the contaminated bodily fluids of infected dying and dead people such that each case can lead to 2 new cases, and for which there is no known cure, though rehydration and basic nursing improve outcomes somewhat, which of the following is the best strategy to save the most lives?

"In each case, chose either A or B."

(continue reading)
The NHS could presumably handle what eluded the Spanish, the prompt isolation of a carrier followed by quarantine of all contacts. But this is highly labour-intensive (dozens of at-risk contacts); it's hard to see it working if we had a hundred belatedly-identified carriers. The UK, along with the rest of Western Europe, is densely populated and highly-interconnected by busy transport links. City-wide or regional quarantine would be difficult in the extreme, even if the political will could be found for the necessary military enforcement

If the Ebola exponential wildfire sweeps across Sub-Saharan African early next year, then the UK isn't just subject to the  threat of incoming air flights. Most likely the virus will burst out to the more adjacent Middle-Eastern or North African regions, and thence into Europe by a thousand routes.

At the moment, due to West African poverty and lack of development, the virus is moving slowly. Incursions into Europe have mostly been self-inflicted through the repatriation of infected health workers. However, if incursions become more organic and massive then all those complacent "We're protected," bets are off.

Time for that trip to town, to stock up on soups, bottled water and Campingaz cartridges. A shotgun would be handy too as you hunker down.

Friday, October 10, 2014

Evolutionary roots of homophobia

From The Economist: legality of homosexuality
The Economist this week has a main feature on Gay Rights. Some countries are moving forwards, while others move backwards. The map above, showing where homosexuality is permitted in law (shades of blue-green) and where it is illegal (orange and red), cries out for explanation: it is very far from random.

There is a hint, perhaps, in the language used by red-zone politicians. The Economist writes
"IN THE argot of human rights, LGBT means lesbian, gay, bisexual, transgender—a catch-all term for sexual minorities. But Yahya Jammeh, president of Gambia for 20 years, has a different reading. “As far as I am concerned,” he thundered during a televised speech in February, “LGBT can only stand for leprosy, gonorrhoea, bacteria and tuberculosis.” He compared gay people to vermin, and said his government would fight them as it does malaria-bearing mosquitoes, “if not more aggressively”."
The Economist also notes that:
"Revulsion against homosexuals is ancient, deep and, in its way, sincere,"
Why?

Homophobia clearly draws on ancient, powerful emotions - chiefly disgust. Some of us oldies will remembers literary dialogues of the mid-twentieth century, where a refined woman gets to drawl in genuine puzzlement: "But what exactly do homosexuals actually do?"

Sex is inherently a mucky and disease-prone activity; we've all heard of sexually-transmitted diseases. Arguably, certain homosexual practices are more disease-prone. Some people find the whole idea of sexual activity frankly disgusting: homo- or heterosexual. However, any male or female who believes this sufficiently strongly is not going to leave any descendants - so genes coding for that emotional reaction are unlikely to spread widely in the population.

Some small percentage of the population (c. 3-4%) is significantly into homosexual practices. As this kind of sexual activity can't lead to descendants how can such people exist? Greg Cochran thinks the culprit is some kind of infectious agent priming an underlying heritability of 0.3 - 0.4; we know that sexuality is on a hormonal continuum so perhaps LGBT people are simply 'on the spectrum'?

Still, like all practitioners of sex, homosexual people historically engage in a potentially disease-spreading activity. And there is no genetic come-back from disgust in the heterosexual community, as so graphically articulated by Yahya Jammeh, President of Gambia above.

In the West, our standards of hygiene are higher and perhaps we're rather more self-controlled and empathic. We've become 'tolerant' (there's a word!) and of course we should be - LGBT people are what they are - and in the last decades we've agreed not to use the power of the state against them.

But let's not pretend - in some blank slate fashion - that those underlying, ancestral, selected-for emotions have somehow been edited out, because they plainly haven't.

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Sparse pickings on the Internet for this topic. A Scientific American article makes a brave attempt but looks to paedophilia and xenophobia for explanations - disconfirmed both by common sense and the evidence. The whole area is stymied by liberal hand-wringing.

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In case it wasn't obvious, let me summarise the speculative thesis of this post.

The reason for an evolved heterosexual disgust towards homosexuals (mislabelled as 'homophobia') is that in the environment of evolutionary adaptedness (EEA) homosexuals were more likely to be disease vectors.

Wednesday, October 08, 2014

Best introduction to human genomics

Puzzled by your 23andMe/Promethease results? Having trouble figuring out what SNPs are and what they're good, or bad for? Time to learn some human genetics and genomics.



"Human Genetics and Genomics" (4th Edition) by Bruce R. Korf and Mira B. Irons is a bird's eye view of the basics of molecular biology through to the technologies of genome analysis to the medical implications of DNA and chromosome variation. It's aimed at medical students, so there are case studies to keep it real.

Chapter 1 starts us off with a tour round human DNA. We look at how it's structured, how it's replicated in cells and how DNA is transcribed into proteins. We take a quick look at epigenetics (the way some genes can be chemically silenced - switched off).

Chapter 2 looks at genetic variation. This covers single nucleotide polymorphisms (SNPs), DNA repair mechanisms, gene duplication and its role in evolution. PCR (Polymerase Chain Reaction) as used for forensic analysis of DNA samples amongst other things is also described.

Chapter 3 is 'Patterns of Inheritance'. Here you'll learn how to take a family history looking for dominant or recessive patterns of Mendelian inheritance. We also look at sex-linked inheritance (X or Y chromosome location of the gene in question), mosaicism and genomic imprinting.

Chapter 4 describes the Human Genome Project and the history of attempts to find out where on the human chromosome set a gene of interest (often disease-causing) actually resides. You'll meet some common terms such as linkage disequilibrium, which is carefully explained. The working example in this chapter is cystic fibrosis.

Chapter 5 discusses 'Multifactorial Inheritance'. Most 'quantitative traits' such as height, personality and intelligence are under the control of hundreds or thousands of alleles of small effect. The same is true of many diseases. So in this chapter we learn about heritability, additive and threshold models of multi-allele effects and that very latest thing: genome-wide association studies (GWAS) which are shedding light on .. almost everything.

Chapter 6 raises its gaze to the organisation of genes into chromosomes. Sadly, this is another level where errors can occur (e.g. chromosome 21 trisomy leading to Down Syndrome) and there are plenty of more subtle things which can go wrong (deletions, duplications, inversions, rings, translocations). Characteristic diseases and syndromes duly follow.

Chapter 7 looks at Population Genetics. We learn about the Hardy-Weinberg equation (very clear explanation) and how it is used to work out the carrier frequency of a recessive disease in various populations. The working example here is Sickle Cell Anaemia.

Chapter 8 focuses on Cancer Genetics. Cancer is a genetic disease, emerging from a cascade of errors in those genes which regulate cell development and division. We now have a causal narrative of the mechanisms behind many cancers, as this chapter explains in good detail.

Chapter 9 looks at chromosome translocation with specific application to Down Syndrome.

The remaining chapters (10-17) are shorter and look in detail at:
  • Molecular diagnosis of conditions based on genetic testing
  • Newborn screening (e.g. for PKU) 
  • Developmental genetics (CHARGE syndrome is the example) 
  • Carrier screening (Tay-Sachs in an Ashkenazi context is the example in this chapter)
  • Genetic risk assessment (companies like 23andMe are discussed in some detail)
  • Genetic testing for risks of cancer (BRCA1 and 2 is the example)
  • The genetics of drug response - Pharmacogenetics (example: malignant hyperthermia)
  • Emerging treatment for genetic disorders such as gene therapy.

This book was published in 2013 so it's pretty much up-to-date. If you're not a medical student with good recall, have Google/Wikipedia next to you as you read it: most terms are explained - and then you come to something like Epistasis!

Shirley Porter

My aunt, Shirley Porter, died in the early hours of this morning. I remember her as a very attractive and pleasant woman, married to my mother's brother Gordon who pre-deceased her by a number of years.

Shirley and Gordon Porter


Shirley Porter in the 1960s

Shirley with my mother, and (L to R) myself, Elaine and Adrian (early-sixties)
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Shirley Grace Porter (née Brown): b. 26th July 1935, d. 8th October 2014 aged 79.

Husband: Gordon Alexander Porter: b. 30th October 1925, d. April 30th 1990 (lung cancer) aged 65.

Update (Friday October 17th):

Clare and myself attended Shirley's funeral today at South Bristol Crematorium. There were 30 mourners, mostly her family. The presiding Minister noted that Shirley had trained as a shorthand typist and had worked at the firm John Hall & Sons in Bristol as a secretary and later PA. It was said that anyone she PAed for ended up as a Director, testifying to her competence and, I suppose, her shrewdness in choosing good bosses.

It was there that she met her husband-to-be Gordon Porter (my uncle) who was working as an electrician. They were married in March 1958.

Here are some pictures from today.

Our bouquet

The dedication

The author and his wife preparing to attend the funeral

Order of Service: cover - click to enlarge

Order of Service  - click to enlarge

Tuesday, October 07, 2014

The web of deceit

Did I mention that I'm surrounded by electronic devices which do whatever they want and have minds of their own? Sick of living in their autistic machine-world, I can now preview an X-Lab development which will transform our lives.

Initially running on a chromecast-like device plugging into a USB slot, the new module will have speech capabilities ('you can converse with it') and will communicate with its attached device using CTP (Communication Things Protocol).

Version 1.0 will be painfully honest, as in this sample dialogue.
You (to Sky Box): "Why have you gone into automated standby?"

Module: "I'm doing a software upgrade."

You: "But my favourite programme's just about to come on, can't you delay?"

Module: "No."
This is clearly not going to go down too well.

Subsequent versions will model the user and simulate emotion.
You (to Sky Box): "Why have you gone into automated standby?"

Module: "I'm feeling terrible."

You: "But my favourite programme's just about to come on, can't you delay?"

Module: "You know, I would if I could but honestly, I'm so sick I'm about to faint. I will do the best I can when I feel better to search down your programme and record it for you."

(It won't of course).
Same useless outcome, but you feel guilty rather than incandescent.

Naturally, CTP is a crude protocol: the module doesn't really know what the attached device is actually doing, especially if it's malfunctioning. The X-lab module will spend most of its time justifying and lying to you, to overcome its own confusion.

Strange to think that biology addressed the self-same problem a hundred thousand years ago.