Category Archives: Genetics

A Bird that Teaches Itself to Sing: The White-crowned Sparrow

White-crowned sparrow ©Tim Jones
White-crowned sparrow (Zonotrichia leucophrys nuttalli) ©Tim Jones

I’ve just finished Richard Dawkins’s self-narrated audiobook of  An Appetite for Wonder: The Making of a Scientist, where, introducing a task given to him by his research supervisor Niko Tinbergen, related to nature versus nurture aspects of animal behaviour, he makes special mention of the White-crowned Sparrow (Zonotrichia leucophrys nuttalli).  As it happens, earlier this year I caught this native of North America pecking at a fig.

White-crowned sparrow ©Tim Jones
White-crowned sparrow (Zonotrichia leucophrys nuttalli) ©Tim Jones

Is behaviour built in at birth – innate and instinctive?  Or is it learned from experience?  One way ethologists, who study animal behaviour, try to answer such questions is to compare the behaviour of subjects artificially deprived of normal early life learning opportunities with those raised in their natural habitat.

Richard DawkinsIn the case of birdsong, tests on Sedge Warblers show they automatically know their song without ever hearing the tune from another bird.  As Dawkins puts it, they ‘fumble’ towards the final song, trying different sounds and sequences from which they assemble a correct version; so the process is innate: it’s all ‘nature’.

The White-crowned Sparrow also teaches itself to sing its unique song by fumbling and picking out the good bits, but, unlike the Sedge Warbler, it needs to have heard its song from another White-crowned sparrow in early life; it needs a prompt to know where it’s going – so to speak.  As for many animal behaviours, including human behaviours, the White-crowned Sparrow’s song is the product of a nature-nurture combo of innate and learned influences.  Dawkins wonders what similar early life deprivation experiments, within ethical bounds, might be made to study the human condition.

You can hear the White-crowned sparrows song here at the Cornell Lab of Ornithology.

Leicester’s Famous Bones

Model of Richard III's Skull at the Leicester Guildhall(Photo: Tim Jones)
Model of Richard III’s Skull at the Leicester Guildhall(Photo: Tim Jones)

Spending time in my original home town of Leicester last week was a chance to get better acquainted with the city’s recently recovered celebrity, King Richard III no less, at an exhibition in the ancient Guildhall.  I also got to visit another of my favourite Leicester museums, The New Walk Museum and Art Gallery, which has its own bones to shout about.

Leicester Guildhall (Photo:Tim Jones)
Leicester Guildhall (Photo:Tim Jones)

Richard III

The search for Richard started in August last year, when the University of Leicester working with the King Richard III Society discovered and recovered a skeleton – everything but its feet – from a central Leicester car park: a car park that overlays the site of the former Greyfriars Priory.

Richard was buried in Greyfriars Priory(Photo:Tim Jones)
Richard was buried in Greyfriars Priory(Photo:Tim Jones)
Plaque to Richard III on Greyfriars, Leicester (Photo:Tim Jones)
Plaque to Richard III on Grey Friars, Leicester (Photo:Tim Jones)

With a barrage of forensic tests and historical interpretation brought to bear over several months, including a DNA match with a living descendant, the remains were finally declared the real deal in February this year.

An unlikely prospect made good for historians and archaeologists, I’m guessing I’m not the only one raised in the city for whom the find has a special fascination.  I lived close to the King Richard’s Road; and as kids we visited nearby Bosworth Field, where Richard fell in 1485; and I can remember some rivalry with the local ‘King Dick’s’ school.   The science labs where I studied for A-Levels were literally a stone’s throw from the burial site.  I’m not suggesting Leicester folk spend all their time sat round thinking about history, but there’s always been a general awareness in the air.

Leicester are proud of their find (Photo:Tim Jones)
Leicester are proud of their find. There are several posters like this around the town (Photo:Tim Jones)

Richard’s character in life, unambiguously portrayed by Shakespeare as one of murderous villainy, is disputed – not least by the splendidly motivated Richard III Society.  But there’s no doubting his popularity in death – not if the queues to the exhibition are anything to go by; I gave up on my first attempt and came back early the next day.

Over a thousand visitors a day (Photo:Tim Jones)
Over a thousand visitors a day (Photo:Tim Jones)

Rather than the real skeleton being on display, there’s a model of the skull and a light-table graphic representation of the bones.  The side-on curved spine characteristic of scoliosis is clearly visible: doubtless the origin of historical reports/myths/exaggerations on Richard’s appearance and gait.

 Skull model and skeleton image (Photo:Tim Jones)
Skull model and skeleton image (Photo:Tim Jones)
 Richard III Exhibition, Guildhall, Leicester (Photo:Tim Jones)
Richard III Exhibition, Guildhall, Leicester (Photo:Tim Jones)

The suite of scientific tests used to characterise the remains included DNA Sequencing for identification, Radiocarbon Dating for age at death (1450-1538), Stable Isotope Analysis (tooth enamel) and Calculus Analysis (tooth plaque) for diet, health and lifestyle.  The Leicester University team successfully matched mitochondrial DNA from Richard’s teeth with that from his living descendant Michael Ibsen.  For more on the science, see Leicester University’s Richard III website.

New Walk Museum

Passing on Richard’s queue that first day gave me plenty of time to explore Leicester’s New Walk Museum and Art Gallery.

 New Walk Museum and Art Gallery (Photo:Tim Jones)
New Walk Museum and Art Gallery (Photo:Tim Jones)

New Walk Museum & Art Gallery

I’m spoilt for museums in London, but still have a soft spot for Leicester’s New Walk.  It was the first museum I visited as a child: with an indoor goldfish pond and scary Egyptian mummies standing at the top of the stairs as you went in.  The fish have gone, but the mummies are still there, better contextualised now in a special ancient Egypt exhibit.  And overall they’ve done a great job of keeping up with the times.

On this occasion, supporting a special exhibition on DNA,  I caught a lunchtime lecture on the human genome, by Dr Ed Hollox, a Leicester University geneticist whose talk focused on the genetic basis and geographical distribution of milk (lactose) intolerance.

Part of the interactive Inside DNA exhibition at New Walk Museum (Photo:Tim Jones)
Part of the interactive Inside DNA exhibition at New Walk Museum (Photo:Tim Jones)

The Leicester group have also printed a 130 volume hard copy of the entire human genome – as a communication exercise in getting over the sheer size of the thing.  The volumes, printed in tiny 4 point font, are on display at New Walk.

 Printed in 4 point text 130 Volume Hard Copy of the Human Genome (Photo:Tim Jones at New Walk Museum, Leicester)
Printed in 4 point text 130 Volume Hard Copy of the Human Genome (Photo:Tim Jones at New Walk Museum, Leicester)
130 Volume Hard Copy of the Human Genome (Photo:Tim Jones at New Walk Museum, Leicester)
130 Volume Hard Copy of the Human Genome (Photo:Tim Jones at New Walk Museum, Leicester)

The Rutland Dinosaur

Back to the bones, and this c.168 million year old Ceteosaurus Oxoniensis , known as The Rutland Dinosaur.

The Rutland Dinosaur, Cetiosaurus, at Leicester's New Walk Museum (Photo:Tim Jones)
The Rutland Dinosaur, Cetiosaurus, at Leicester’s New Walk Museum (Photo:Tim Jones)
The Rutland Dinosaur, Cetiosaurus, at Leicester's New Walk Museum (Photo:Tim Jones)
The Rutland Dinosaur, Cetiosaurus, at Leicester’s New Walk Museum (Photo:Tim Jones)

The long-necked herbivore’s fossilised remains, recovered in 1968 from Great Casterton, Rutland – the county just East of Leicestershire – have a special claim as the most complete (about 40%)  Sauropod found in the United Kingdom.

Connections

I’m not alone in my childhood memories of New Walk Museum.  In this video, Sir David Attenborough, who hails from Leicester and stays close to the museum, recalls his early impressions.  Incidentally, the chair he mentions, belonging to the giant Daniel Lambert, is now in Leicester’s Newarke Houses Museum – but that’s a different story.

Let’s not forget too that one of the oldest fossils in the world is kept at New Walk: the pre-Cambrian Charnia fossil, as featured in Attenborough’s First Life series (for more on that, see Return to the Land of Charnia).

All of which lets me finish on a nice obscure link, almost as unlikely as finding Richard III in a car park.  Which is to realise the roof tiles from the Greyfriars Priory, recovered from the excavation and featured in the Guildhall exhibition, come from the very same Swithland slate quarry where Charnia was found.

Swithland slate roof tiles recovered from Greyfriars Priory (Photo: Tim Jones)
Swithland slate roof tiles recovered from Greyfriars Priory (Photo: Tim Jones)

Book Review – Here Is a Human Being, by Misha Angrist

Here Is a Human Being

  • Hardcover: 352 pages
  • Publisher: HarperCollins; 1 edition (1 Dec 2010)
  • Language English
  • ISBN-10: 0061628336
  • ISBN-13: 978-0061628337
  • Product Dimensions: 15.2 x 2.9 x 22.9 cm

 

 

 

Between 2006 and 2010, half a million 40-69 year olds, including yours truly, joined the UKBioBank project.  We agreed to share lifestyle and medical information – not to mention blood, saliva, and urine samples – all to help researchers get a better handle on the incidence, cause, and treatment of disease.  With enough subjects, the logic goes, associations between an individual’s characteristics and their health can inform our understanding and treatment of the wider population.

No surprise then that only a few pages in to Misha Angrist’s  Here Is a Human Being: At the Dawn of Personal Genomics I spotted the obvious link between his experience as the fourth subject in Harvard Medical School’s Personal Genome Project (‘PGP) – the theme of his book – and my own humble contribution to medicine.  Both projects are based on ideas around association, to one degree or another involve genomics in support of healthcare goals, and as James Watson said to Angrist on the value of personal genomics, they create “a more compassionate, better society”.

Clearly, there must be differences, otherwise I’d have got to write the book and hang out with the likes of Stephen Pinker – with Angrist settling for the return bus fare to a medical testing center in Croydon.  The distinction is mainly down to issues of privacy, plus the fact that Angrist’s genome was sequenced when it was still a big expensive deal to do that.

UKBiobank data is anonymised.  Even the researchers working with my genome (if and when it’s ever sequenced) won’t know my name .  Angrist’s PGP data, however, is public: genome, life style, medical history; it’s just out there – totally, with his name on it.  To take part in PGP you have to take an exam to show you know what you’re doing; those in the spearhead PGP-10 group required a Masters level training in genetics.  More importantly, as Angrist gets to see his own stuff under the PGP rules, he can share the motivations, emotions, excitement and anxieties that go with that kind of exposure and self-knowledge.  (How effective promises of confidentiality in programs that have them really are is a whole different, but related, topic.)

Human genomics is a young field.  The first composite human genome was published by the U.S. government’s Human Genome Project (HGP) in 2003.  A parallel commercial project led by Craig Venter and the Celera Corporation published Venter’s personal genome in 2007.   Early processes were slow and costs correspondingly high; but the promise, particularly for medicine, was great.  Now, as the dream of a medical revolution fades, and free-falling costs open the way for mass genomic profiling, attention has turned more to protecting the public from what some see as a useless, possibly dangerous, product of an immature science – peddled by an exploitative industry.  Insurance companies circle round the latest hot tool for risk minimisation, ready to turn our genome against us.   Bridging the exclusive and commodity phases on the human gemonics timeline, Angrist brings an insiders eye to bear on an uncertain period.  As he says “I had arrived at the theatre early enough to grab a good seat, but the carpenters were still building the sets.”

It’s fashionable to talk about personal genomics in terms of its profound complexities and limitations, and not its useful applications.  You can see why though.  In predicting disease, genes tell only part of the story alongside environmental factors.  As Angrist says, we need to link environment (was a child exposed to lead paint), phenotype (how much did it weigh), and lifestyle (what did I have for breakfast) with personal genomic profiles.  He cites rheumatoid arthritis as an example where from twin studies we know the risk is only 50% genome related.  Disease  is sometimes associated with single defective genes, but more often is the combined expression of many genes interacting with each other and the environment.  Relevant genes may exist anywhere throughout the genome, requiring researchers to search the whole smash – with no clues on appearance or location.  To complicate things further, the same disease is caused by different gene combinations in different people.

That’s not to say some genetic associations don’t give personal genome candidates pause for thought.  When, in a separate study, James Watson’s genome was sequenced, he chose not to know his risk of the incurable Altzheimer’s disease; Angrist’s fellow PGPer Stephen Pinker made the same choice.  As interesting perhaps is the fact that many people do want to know their Altzheimer’s risk – despite the disease’s incurability, and that studies show they can handle the knowledge.  Angrist has a special interest in the breast cancer gene variants BRCA1 and BRCA2, as his daughters would be at an 80% life-time risk were he to pass on defective versions; it seems personal genomes aren’t so personal after all.  In one of the most human moments in the book, Angrist sits  alone with his genome report, about to discover this type of information for the first time.

Angrist is at pains to show where human genomics contributes beyond disease prediction, pointing to work on: drug efficacy across ethnic groups and individuals (testing for hyper-sensitivity to warfarin blood thinner), resolution of paternity disputes (10% of  fathers are not biological), donor screening (of blood and sperm), and identification of lost racial origins or heritance.  One company specialises in providing genome-based nutritional advice, perhaps advising someone whose gene mix inhibits calcium absorption to consider taking a supplement.  Ethically intriguing applications include the use of genetic selection to identify our ideal partner or love match.  These on top of the widely used law enforcement applications of DNA we know and love from TV shows like CSI.

Angrist weaves plenty of historical, technical, and commercial detail into his personal story, much of it original and drawn from interviews with fellow PGP’ers (a truly mixed bag of characters and motivations in their own right), PGP Founder George Church, and a host of specialists in genomics and medicine – including some insightful tid-bits from former HGP Director Francis Collins and James Watson.

You won’t retain it all – I sometimes lost track of who exactly developed what, when, and where; who went bust and reappeared again, etc. – but the main take-away is clear enough.  That despite any limitations and historical hype – “the marketing of personal genomics has outpaced the science” – personal human genomics is far from valueless, and has great potential if we hang in with it.  Specifically, Angrist believes the tangled complexity of genotype-phenotype associations may unravel if a sufficiently large sample of cross-referenced data is available.  And with over a thousand active participants in the PGP in 2012, and thousands more in the queue, it looks like that might just happen.

RECOMMENDED.

Misha Angrist blogs at GenomeBoy.

 

Also of interest:

http://thednaexchange.com/2013/11/29/the-fda-calls-a-penalty-on-23andme/