Barrington Court (NT)

We were at Barrington Court this last day of August under an autumnal sun, summer already forgotten.

The sun's come back in a semi-serious way

The author, not about to announce a new Apple product

Scary denizens of the Rose Garden pool

She's all pom-pomed out ...

Barrington Court in its fuzzy glory

Recent books

"Under the Skin" by Michel Faber. This is the (excellent) book which was recently art-house filmed with Scarlett Johansson. People say the book is better; I plan to watch the film sometime soon on my tablet, renting - for the first time - from the Google movie store. Moral: think twice before accepting lifts from strange girls with infeasibly large boobs and difficult-to-place accents.

Isserley in action 

"Theological Incorrectness: Why Religious People Believe What They Shouldn't" by Jason Stone.  As recommended by Razib Khan. In the spirit of Scott Atran's "In Gods We Trust" an evo-psych analysis chiefly interesting for its passing analyses of, for example, Buddhism. (Despite what western intellectuals believe, practising Buddhists in the heartlands of that religion deify the Buddha;  ditto with Taoism - which to western despair is full of gods and magic in the east).

"The Rosie Project" by Graeme Simsion. Purporting to tell the tale of the "wife project" undertaken by a partner-free genetics professor, this account of Aspie life is almost convincing. Sadly, success in love is seldom achieved in reality to those as far along the spectrum as our hero. But it's a great story nonetheless.

My next reading treat is that old favourite, "Ringworld" (Larry Niven).

The story on DNA sequencing

One company has transformed the economics of gene-sequencing. Here's the story of Illumina and a taste of where things go next. (h/t Razib Khan's site).

How important is this? Here's a clip from the article.

"... But then Follweiler, a retired financial services professional, found she had another tumor in her bowel. Her doctors opened her up, found it was too big to remove and sent her home. “I was basically throwing in the towel,” she said.

"But one of her physicians sent a tumor sample to Foundation Medicine, a startup backed by Bill Gates and Google Ventures that used Illumina’s sequencers to locate mutations in 236 genes that could help direct drug treatment. As a result of the test she was given Pfizer’s Xalkori, which has made the bowel tumor undetectable and has kept it that way for more than a year. “I feel no different than I felt two and a half years ago,” she says."

23andMe use the Illumina chip; my mother's saliva sample should be arriving at its North Carolina offices later this afternoon.

Family History

We were at the Bristol Records Office and the Bristol Registry Office yesterday hunting down information about my maternal grandfather, William Richard Porter and his mysterious brother George - long disappeared. Here's our data dump so far, mostly based on my mother's recollections (Beryl Seel).

We're still researching, so this may not be the final story.

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William Richard Porter (son of George Samuel Porter)

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George Samuel Porter ("Grandad Porter")

Born: ???
Died: June 1938 aged 75 ??? (or was it Alfred Hewlett died around that time, Beryl's maternal grandfather?)

Address: Salmon Street, Kingsdown, Bristol (now demolished)

Occupation: Docker

Married twice

1. m. ???  and had two daughters Winny and Maisie (died in childbirth with Maisie)
     - Maisie married Reg, a pianist with a band (controversially dyed his hair!).
     - Winnie married George Batten (sp?) they had two girls.

Maisie and Winnie lived next door to each other in Raglan Road, Bishopston, Bristol


2. m. ??? ("Ma Porter") and had three children
    - George Porter  (b. December 1893? - Barton Regis)
                      -- married a non-white girl; banished for ever: disappeared.

    - Florence Porter ['Flo', 'Florrie'] (b. 1895 or 1896? - Barton Regis)
                      -- fat woman, was married (no details), children??

    - William Richard Porter (b. 1st January 1898 - Barton Regis)

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William Richard Porter known as Dick Porter.

Born:  (b. 1st January 1898 - Barton Regis)

Father: George Samuel Porter

Mother: ??? ("Ma Porter")

Wife: Linda Louisa Annie Hewlett.

Death: Oct 30th 1964 in Bristol (aged 66) throat cancer.

Military Medal: awarded in Bristol in 1918.
Private: No. 127338
Invalided out of forces - lost an eye rescuing an officer under enemy fire, hence the medal.

Occupation: Foreman, Wine and Spirits distributor, City Road, St. Pauls, Bristol.

Children: Ray, Beryl, Gordon.

Address: Ray, Beryl were born in a house on Constitution Hill. The family then bought the house at 14 William Street, St Pauls, Bristol.

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Barton Regis was, from 1894 to 1904, a rural district in the English administrative county of Gloucestershire, adjacent to the City of Bristol, comprising:

• Filton
• Henbury
• Shirehampton
• Stoke Gifford
• Westbury-on-Trym
• Winterbourne

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Bristol Record Office
'B' Bond Warehouse
Smeaton Road
Bristol
BS1 6XN

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Bacon reduced at Waitrose

Watched "Horizon should I eat meat?" on BBC2 last night (why is it not yet on YouTube?). The bottom line (so many puns) is that processed meats - bacon, sausages - are the killers: the nitrosamines they contain and produce are carcinogenic.

We predicted there would be a lot of half-price bacon and sausage on the shelves at Waitrose this morning!

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Michael Mosley's self-experiment with extra meat rations was a trifle disingenuous. Presumably he is usually on the 5:2 diet - his physique certainly suggests that. If you then switch to seven day extra-meat-eating for a month, with generous bread rolls, fruit and veg, you are certain to gain 6-7 pounds (3 kg) as he did. Not sure it was the processed meat doing the damage here, doctor!

We got some great shots of a colonoscopy BTW .. I can hardly wait!

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Steve Hsu has an accessible paper here on progress in identifying the many genes (alleles) of small effect which underlie quantitative traits such as height and intelligence. I've been reluctantly* convinced by his argument that fixing the many negative (dysfunctional) alleles in every person could remarkably increase intelligence. Read the paper, skip the harder maths and see if you agree.

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* Why reluctantly? There are a number of brain attributes which presumably contribute to increased general intelligence: specific modes of brain modularisation, optimised brain architecture, increased brain size, larger number of neurons, efficiency of neurons, efficiency of neural-interconnect, density of neural-interconnect .. and so on.

Only some of these are capable of significant change - brain size, for example, is hard to increase given birthing constraints. Steve Hsu's linear additive model seems to imply that (in Sky Pro Cycling terms) there is the possibility of 'aggregation of marginal gains' which would impact all of the attributes mentioned above and more.

And so I have become a reluctant convert.

A Doctor writes ...

From my GP today:

Dear Mr Seel

Thank you for your letter regarding your family history and suggestion for enhanced screening. I think this probably would be a sensible idea and I am sure the family history would fall within the referral guidelines for the enhanced screening. If you would like to go ahead with this please let me know and I can arrange the referral. The enhanced screening involves an endoscopy which is a fibre-optic camera which can look inside the bowel.

If you would like to discuss this in more detail before me making the referral please arrange to speak to me.

Here are some of the highlights from Wikipedia.

"The pain associated with the procedure is not caused by the insertion of the scope but rather by the inflation of the colon in order to do the inspection. The scope itself is essentially a long, flexible tube about a centimetre in diameter, i.e. as big around as the little finger, which is less than the diameter of an average stool.

"The colon is wrinkled and corrugated, somewhat like an accordion or a clothes-dryer exhaust tube, which gives it the large surface area needed for digestion. In order to inspect this surface thoroughly the physician blows it up like a balloon, using an air compressor, in order to get the creases out. The stomach, intestines and colon have a so-called "second brain" wrapped around them, which autonomously runs the chemical factory of digestion. It uses complex hormone signals and nerve signals to communicate with the brain and the rest of the body. Normally a colon's job is to digest food and regulate the intestinal flora. The harmful bacteria in rancid food, for example, creates gas. The colon has distension sensors that can tell when there is unexpected gas pushing the colon walls out—thus the "second brain" tells the person that he or she is having intestinal difficulties by way of the sensation of nausea. Doctors typically recommend either total anaesthesia or a partial twilight sedative to either preclude or to lessen the patient's awareness of pain or discomfort, or just the unusual sensations of the procedure. Once the colon has been inflated, the doctor inspects it with the scope as it is slowly pulled backwards. If any polyps are found they are then cut out for later biopsy.

"Some doctors prefer to work with totally anesthetized patients inasmuch as the lack of any perceived pain or discomfort allows for a leisurely examination. Twilight sedation is, however, inherently safer than general anesthesia; it also allows the patients to follow simple commands and even to watch the procedure on a closed-circuit monitor. For these reasons it is generally best to request twilight sedation and ask the doctor to take his or her time despite any discomfort which the procedure may entail. Tens of millions of adults annually need to have colonoscopies, and yet many don't because of concerns about the procedure.

"It is worth noting that in many hospitals (for instance St. Mark's Hospital, London, which specialises in intestinal and colorectal medicine) colonoscopies are carried out without any sedation. This allows the patient to shift his or her body position to help the doctor carry out the procedure and significantly reduces recovery time and side-effects. Although there is some discomfort when the colon is distended with air, this is not usually particularly painful and it passes relatively quickly. Patients can then be released from hospital on their own very swiftly without any feelings of nausea."

Something to look forward to before Christmas! Here is what my 23andMe health report has to say about my Colorectal Cancer risk.

Nigel Seel
4.2 out of 100 men of European ethnicity who share Nigel Seel's genotype will develop Colorectal Cancer between the ages of 15 and 79.

Average
5.6 out of 100 men of European ethnicity will develop Colorectal Cancer between the ages of 15 and 79.

And here's the caveat.

The 23andMe Odds Calculator only takes into account effects of markers with known associations that are also on our genotyping chip. Keep in mind that aside from genetics, environment and lifestyle may also contribute to one's risk for Colorectal Cancer.

Can you be too super-secret?

In Terry Hayes' excellent and scary thriller "I Am Pilgrim", the hero works for a super-secret and totally deniable organisation called 'The Department'. Basically it audits the spies - with few restrictions on what it can do.

In China Miéville's wonderful "The City and the City" there's a super-secret organisation called Breach which has almost unlimited power in its bizarre domain.

Operatives of these super-secret organisations have a problem, it seems to me. Probably no-one has heard of their secret organisation, nor are they permitted to identify themselves with it.

So how then do they gain authority to interview people, task military/police assets and generally grab the logistical resources they need?

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Semi-spoiler: I'm still wondering how easy it would be to create from scratch a synthetic version of a deadly virus. Once fabricated, the deployment mechanism in "I Am Pilgrim" seems horribly plausible.

Westhay Moor and Nature Reserve

We visited Westhay Moor Nature Reserve this morning, about 15 minutes from Wells on the Somerset Levels.

Ponies at Westhay Moor

Flies on the face

The author with birds

The author's wife with pony

The high priests are out again

From The Times today.

"A British writer is facing global protests from scientists for suggesting that there are biological differences between races that could explain the success of European nations and make African societies prone to poverty and violence.

"Nicholas Wade had expressed the hope that his book, A Troublesome Inheritance, would “draw some of the tension from this fraught subject by showing that the understanding of genetic differences between human groups does not lead to racism”.

"The book, which speculates on whether differences between societies and nations are based on genetic variations, has caused uproar in academia and allegations that its author is doing the very thing he said he was seeking to avoid and encouraging racism.

"In a letter to The New York Times books section, 143 geneticists from universities in Europe and the US protest that his book “juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in IQ test results, political institutions and economic development.”

"The scientists rejected “Wade’s implication that our findings substantiate his guesswork”, adding that “there is no support from the field of population genetics for Wade’s conjectures.”

"Besides a chapter speculating on an evolutionary basis for “Jewish intelligence” and passages suggesting that genetic traits had led Africans to fail to “develop the ingrained behaviours of trust, non-violence and thrift that a productive economy requires,” Wade examines whether a genetic variation could predispose young African-Americans towards aggressive behaviour.

"He notes that 5 per cent of African-Americans in a study had the mutation as against 0.1 per cent of Caucasians. African-Americans with the genetic variation were “significantly more likely to have been arrested and imprisoned.”

"He says “a large number of genes are evidently involved in controlling aggression” and that even if African-Americans were more likely to possess one particular mutation, Caucasians may carry other mutations."

I reviewed Nicholas Wade's book here.

In other news, leading scientists confirm that the sun does indeed circle the earth, and that the world was created in 4004 BC.

Why bother with 23andMe?

The genetics company 23andMe is no longer permitted (under a current US FDA ruling) to provide you with health advice based on sequencing your own DNA sample. In practice this is not an issue since you simply go to Promethease and import to them your raw data from 23andMe (as described here). For some reason this is not forbidden.

How useful are these reports? To be honest, I believe they're of bounded interest, and here's why.

"A number of commercial firms offer targeted or extensive genotyping to anyone who wants to submit a saliva specimen and pay a fee. Some of the reasons suggested for doing this include identification of ancestral background, relationship certification and most commonly, detection of genetic susceptibilities to disease.

"The latter are almost entirely based on GWAS that have associated specific single nucleotide polymorphisms (SNP) with an increased (or decreased) likelihood of developing a particular common disease. In almost all such GWAS-based analyses, the association with disease is highly statistically significant but of remarkably little predictive value. In other words, the relative risks of developing a disease based on having one of these markers is typically in the range of 1.1–1.4.

"Moreover, virtually no research has been done to examine the clinical utility of being identified as having one of these risk markers. For example, is someone with the 9p21-linked SNP that has no known biologic function but is associated with a slightly greater risk of developing an atherosclerosis-related condition more likely to alter their lifestyle, change their diet, or stop smoking? "

In addition, there are many other sources of error in the genetic code which can have profound medical implications - but are not SNPs - such as (from the same report):

"Translocation results from an exchange of parts of two chromosomes.

"Deletion is loss of chromosomal material.

"Duplication is the presence of two or more copies of the same region of a given chromosome. The redundancy may occur in the same chromosome or in a nonhomologous chromosome. In the latter case, a translocation will also have occurred."

So most health reports tell you that you have some SNPs which increase, or decrease your susceptibility to this or that condition, but in the current state of the research it's not known how many other SNPs or distinct genetic modifications could also affect the likelihood of acquiring it. Early days indeed!

One of the things 23andMe ask you is whether you permit them to keep your sample for ten years (I guess in liquid nitrogen or something). I imagine that in a decade the cost of a complete genome sequencing will have come down to something affordable and 23andMe will then be able to offer a much more sophisticated analysis/diagnostic service based on your complete genome (FDA willing!).

Assuming we will also by then understand a lot more about how the genome ties in to phenotypic traits such as health, intelligence, personality, appearance, sports potential and so on, the report in 2024 might be quite informative, and the one in 2034 even more so.

One generation down-track from now, everyone will have their genome transcribed for health reasons, and moreover we'll understand it. One of our remote descendants may well be interested in their ancestors, bewailing the fact that they never got genotyped.

But wait!

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Steve Hsu has more to say here:

"... given sufficient phenotype|genotype data, genomic prediction of traits such as cognitive ability will be possible. If, for example, 0.6 or 0.7 of total population variance is captured by the predictor, the accuracy will be roughly plus or minus half a standard deviation (e.g., a few cm of height, or 8 IQ points). The required sample size to extract a model of this accuracy is probably on the order of a million individuals. As genotyping costs continue to decline, it seems likely that we will reach this threshold within five years for easily acquired phenotypes like height (self-reported height is reasonably accurate), and perhaps within the next decade for more difficult phenotypes such as cognitive ability. At the time of this writing SNP genotyping costs are below $50 USD per individual, meaning that a single super-wealthy benefactor could independently fund a crash program for less than $100 million.

"Once predictive models are available, they can be used in reproductive applications, ranging from embryo selection (choosing which IVF zygote to implant) to active genetic editing (e.g., using powerful new CRISPR techniques). In the former case, parents choosing between 10 or so zygotes could improve their expected phenotype value by a population standard deviation. For typical parents, choosing the best out of 10 might mean the difference between a child who struggles in school, versus one who is able to complete a good college degree. Zygote genotyping from single cell extraction is already technically well developed, so the last remaining capability required for embryo selection is complex phenotype prediction. The cost of these procedures would be less than tuition at many private kindergartens, and of course the consequences will extend over a lifetime and beyond.

"The corresponding ethical issues are complex and deserve serious attention in what may be a relatively short interval before these capabilities become a reality. Each society will decide for itself where to draw the line on human genetic engineering, but we can expect a diversity of perspectives. Almost certainly, some countries will allow genetic engineering, thereby opening the door for global elites who can afford to travel for access to reproductive technology. As with most technologies, the rich and powerful will be the first beneficiaries. Eventually, though, I believe many countries will not only legalize human genetic engineering, but even make it a (voluntary) part of their national healthcare systems. The alternative would be inequality of a kind never before experienced in human history."