conte crayon

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The rocks mark, in our distant past, when multicellular organisms evolved guts and first crapped on the sea bed.  It was a critical step, that we might no longer be sessile but could instead migrate, carrying within us the bacteria, the compost, that enables us to digest food. Each of us is an ecosystem comprising many millions of organisms in shifting relationships.  The technology now exists to profile the diversity of organisms within us and understand their relationship to health.  There are many conditions in which illness is caused through inflammation.  What part does our individual internal ecological diversity play in that, I wonder?

I spend so much of my free time trying to wrap my head round these complex biological interactions that I am culturally and artistically ignorant.  The exhibition “Rubens and his legacy” at the Royal Academy was for me a trove of work I did not know.  Here are two simple memories from that show.  First, there were connections shown between landscapes ranging from Rubens through to Gainsborough and Constable.  This visual impact was of deep rich toiling red shadows in the foreground and cool blue and green distances in the left upper panel like a view into an ethereal other land.  The second memory was the masterly, deceptively simple, descriptions of the human form in red black and white chalks.

My humble sketches above were simple landscapes in conte crayon, done on site in woodland and, as evening fell, from a footbridge over a small stream on my cycle route.  I have an idea to work over the woodland scene in thin acrylic glazes.  The second picture is much smaller, done on a scrap of tinted paper lodged in my sketchbook.  I worked further on this in crayon on my return home, to better capture the forms and reflections.

Complex systems

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This weekend, I have been thinking about complex adaptive systems.

Wikipedia tells me that complex adaptive systems contain multiple diverse interacting components and that the system is structured such that it adapts and learns from experience.  At least, it appear to learn.  The system is not conscious or reflective on its experience.  An ecosystem can be seen as a complex adaptive system.

In a cancer, the malignant cells are themselves diverse: some dividing, others resting; some forming a tumour, others infiltrating adjacent tissues, others again invading blood vessels and migrating.  Then there are the array of non-malignant cells: those forming blood vessels; inflammatory cells responding as if this were a healing wound; immune cells perhaps recognising and killing cancer cells, perhaps exciting such killer cells, perhaps damping the immune response.  All these various cells are in communication with each other, sending short range messages by direct contact or chemical signals.  This complex adaptive system is called the immune microenvironment of the cancer.

I am not prone to hyperbole.  Still, I think we* sit on the threshold of a major shift in how cancer can be treated, using new drugs to manipulate the immune microenvironment of cancers.  The drugs are becoming available.  The challenge is to understand the immune microenvironment sufficiently so we use the drugs effectively.

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This piece started with a layer of charcoal, the images driven by recent reading and current music.  I tore into the dampened paper creating highlights and texture.  This was then obscured by layers of gouache and acrylic paint, allowing charcoal and sea salt to disperse slowly, suspended in the very wet washes.   After a week or so looking at it, turning it one way and another, eventually I saw in it a narrative suggesting a complex system.

 

*”we sit on the threshold of a major shift in how cancer can be treated” – by “we” I mean the worldwide cancer community – patients, carers, researchers, clinicians, health care providers, research institutions, industry and those who commission and fund cancer care

traditionally …

I am marking the assessments on clinical trials for our MSc course. Candidates repeatedly use the word “traditionally” to describe clinical trial designs.  Tradition means we do things this way because this is the way we have always done them.  The one thing trials should not be is “traditional”.  Each experiment that relies on human participation must be designed anew to reflect unique circumstances – this population, that drug, these objectives and so on.  Clinical trials are rigorous experiments.  They have to be.  Our model of human experimentation has been forged in the fire of scientific rationalism and shaped by the hammer of human rights.

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One reason for me to watch and draw birds is as icons of slow but inexorable change across deep time.  I can never forget that this group living all around us is allied closely with the venerable titans that dominated the Mesozoic Era.  Conversely, the patterns of behaviour I try to capture today have been repeated year on year, millennium on millennium and were probably similar when humans used rocks as tools and themselves drew the wildlife in charcoal and ochre.

Above, a herring gull casually displaced a black headed gull.  The smaller bird rose and made a show of defiance which was observed without concern by the invader.  Below, a juvenile black headed gull entered the space of an adult, which threw itself backwards to drive away the youngster.

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Periodically, birds dropped from the air and the relationships of the pairs and rivals were re-established by displays of dipping heads, inverted arched necks and spread wings.

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Double dactyls: African memory

African sky

I follow an erudite blog posted by a graduate student in zoology that mixes good science in plain language with great photos and quirky amusement.

Recently she posted  about a poetical form unknown to me, the double dactyl.  I got hooked trying to make one up for myself.  I followed her lead, writing verse about science.

Reading this, you should be aware that three lines are each constructed of a pair of triple rhythms  like “higglety pigglety” whereas the fourth line stops on the fourth, stressed, syllable.   A sign of poetic failure is probably having to italicise the stressed words:

Epstein-Barr virus was

Found in a cell line that

Came from a cancer that

Grows in the jaw.

Intell’gent surgeon that

Spotted conundrum that

Chronic Plasmodium makes

Virus do more.

This relates to discoveries in the 1950s when Denis Burkitt, missionary surgeon in Uganda, biopsied the continent, probing the geographical limits of the previously unknown lymphoma that now bears his name.  His prepared mind worked out that this cancer must be associated with a virus spread by an insect vector, ideas that led to Tony Epstein finding his eponymous virus within a cell line from a Burkitt’s lymphoma.  Confusingly, it was then shown that the virus is ubiquitous among humans and spread in our saliva not by insects at all.  Others showed that Burkitt’s lymphoma is driven by the coincidence of children acquiring Epstein Barr virus very early in life plus suffering repeated bouts of falciparum malaria (Plasmodium falciparum is of course spread by mosquitoes and wreaks enormous injury on exposed populations).  So Burkitt did not fit the final pieces together but it was his enquiring mind and observation in the field that founded areas of science that have been enormously productive in understanding cancer.

Just before I started my own doctoral work in this field, I had the chance to visit Uganda.  I was not painting then.  Later, when I was just starting to use  watercolour, I had no reference photo to remind me.  Thus my painting carries my memories of where I was first based, on the shore of Lake Victoria, but I copied someone else’s composition – from a book or the net I cannot remember.  From Entebbe, I flew to the West Nile (where Burkitt had made his observations some 30 years earlier) in a tiny plane through vast confectionary clouds, piloted by a slightly mad guy with a Biggles moustache.  The hospital was on the Congo border by virgin jungle filled with the whoops of apes.

Sixth floor, Holiday Inn, Edinburgh: dawn.

I was invited to Edinburgh to give a talk about Merkel cell carcinoma

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This skin cancer is more aggressive than melanoma but occurs more rarely.

It occurs more frequently as we age or in people with damaged immunity.  Sometimes it nestles in the same tissue with other cancer types.

Fascinatingly, in 2008, Drs Moore and Chang discovered that Merkel cell carcinoma harbours a novel virus.  Merkel cell polyomavirus turned out to be a common harmless inhabitant on our skin.  It gets into the predecessor of the cancer cell by an unhappy accident, perhaps helped by ultraviolet light.  When it does so, it is crippled, no longer able to make new viral progeny, forever integrated in stunted form in the cellular DNA. It encodes four genes and makes just six proteins.   Just one of these genes, mutated and truncated, contributes to the cancer.  The virus subverts its hosting cell but is itself subverted to drive and shape an evolving cancer.

Cancer is complex, driven by a myriad of dysfunctional and  repurposed pathways.  How do you break the Enigma, the encrypted cipher, the code of the Merkel cell carcinoma?  We need a crib or key: a simple message we already understand as a way in.  Merkel cell polyomavirus provides us with that key.

Spring

Today it was my privilege to be the invited speaker at a local event raising funds for Cancer Research UK, our leading cancer research charity in the UK.  I picked on work that is currently in the news (not work I am involved in personally).  Try this excellent lay person’s summary from the CR-UK website http://scienceblog.cancerresearchuk.org/2012/04/18/increasing-the-resolution-on-breast-cancer-the-metabric-study/.  This illustrates so many points.

At its heart was an international collaboration dissecting the molecular events underpinning breast cancer.  This depended on the painstaking building of tissue collections.  It linked these to patients’ data.  Analysis coupled these to high-throughput assays and statistical methods capable of handling so many data.  The result was reclassification of this disease into 10 subtypes with different outcomes.  So the molecular signature impacted on prognosis.  Understanding this may lead to new treatments.  This is the foundation of what is now called stratified or personalised medicine: the recognition at a fundamental level of the individuality of a patient, a cancer and a treatment plan.

Cancer Research UK is building the infrastructure for more work like this through its Experimental Cancer Medicine Centres and the Stratified Medicine Programme across the UK.

I also talked about the politics of cancer science, partly in response to an earnest question about the iniquities of the pharmaceutical industry.

I believe that scientific research and understanding are at the heart of what it is to live in a free, accountable and democratic country. Charitable and public funding  create the framework for transparency and peer review and spread of excellent information to non-specialists.  Science thrives on challenge.  Publicly funded cancer research identify and address patients’ needs, balancing the drive for profits in industry.   These values are the core of what makes good science, the very opposite of arbitrary authority, domination by the wealthy, dogma and the rote learning of an accepted canon.

Without public and charitable money, research would all be owned by the pharmaceutical industry.  In partnership, industry is harnessed to need.  What is being done here is a quiet revolution: in the terms of the day, a Cancer Spring.

Metaphor

I painted this a few months back.  I began with water in the middle of the page and dropped ink for the fun of watching it spread and then dry, pulled to the edge of the shape.  I dragged a brush through it and built in the colour and lines, taking my rhythms from the sounds of Philip Glass’ dance pieces “In the Upper Room”.

In our bodies, in the tissues, are cells sampling and consuming  the detritus of life.  On meeting a microbial threat or cellular damage, they undergo a radical change, migrating and activating so that on reaching their destination they spread out thousands of tiny dendritic tendrils to contact the many soldiers of the immune system.  They have taken up, processed and now present fragments of the threatening material along with signals to say … get angry.

We can harness these dendritic cells to fight cancer.