Giraffe

Sometimes scientific and clinical experiments need a brand.

I am pre-occupied with writing a funding proposal for a clinical trial whose title includes the words “Gastro-intestinal Immune-RelAted side efFFEcts”.  From this my clever colleagues extracted and highlighted the letters to spell Giraffe which is now the trial’s name.  I drew a quick sketch to serve as the logo, at least for now.  I presented the rationale and scientific design at a national workshop last week – but the name is what grabbed attention first.

Rectangles

Ravenshaw Lane is on a regular short cycle route for me, one I usually take when light is failing but I need to get out for an hour or so.  At one end is an industrial unit, set in parkland, making large metal waste tankers called whales.  The lane is tarmacked at either end but in the middle dwindles to a footpath and a narrow wooden bridge across the river.  Standing on the bridge, I watched the fading sunlight filter through hanging rusted foliage in a garden above the brook.  I managed only to get the bones of this sketch onto paper before darkness fell.  I finished it at home from memory.  Initially, I drew in the fence posts and plants scrambling up the bank and fence in high key, but muted them as the what light there was came from behind the fence: I wanted to emphasise the backlit curtain of brown foliage.

This was drawn in conte crayon then watercolour laid over this.

The next day, I went to Liverpool.  I have been privileged to be the person who has taken an exciting piece of science into the clinic.  The whole project, from its inception long before I was involved through to the current trials, was recognised with a prize.

Complex systems

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

Double dactyls: African memory

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

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.