Friday 21 February 2014

Relaxing the pancreas

It's Rag Week at The Institute  . . . except it's not.  Other colleges are getting a mid-term break but we have a policy that classes will go ahead regardless of the fact that 80-100% of the students are off-site.  Some of them are doing traditional Rag Week things - pushing bedsteads about the country or washing car-windscreens for some Good Cause.  Others are just going down to the offy, buying a slab of tinnies and getting hammered.  Having very short classes means that I've had time to prep a bit of teaching material for the medium-term future, so that when things return to normal I'll have something sensible to say about, say, ductless glands.  A key difference in classifying the wobbly bits of human physiology is whether a gland has a duct (tube) through which it delivers its product: these are called exocrine glands.  The bits that seep their stuff directly into the bloodstream (and thus ductless) are called endocrine glands.

The pancreas, a body about the size and shape of a parsnip and found tucked in under the stomach, is both exocrine and endocrine.  The pancreatic ducts empty into the gut and push digestive enzymes like trypsin into the top of the duodenum to make a start breaking down the proteins in the food.  The rest of the organ is taken up with little clusters of cells, evocatively called the Islets of Langerhans, which make a number of hormones.  The most well-know of these is insulin which, with its complement glucagon, regulates the amount of glucose circulating in the bloodstream.  Lack of insulin is the basic cause of diabetes which is getting ever more prevalent in our society.

In the early 1920s insulin was discovered and purified as an alcoholic extract with demonstrable efficacy against diabetes in humans by two young Canadian biochemists Banting and Best.  Fred Banting was born in 1891, qualified as a doctor and joined the Canadian Army Medical Corps where he won a medal for tirelessly helping wounded soldiers at the Battle of Cambrai despite being shot himself.  So he had that in common with Francois Jacob.  After WWI, he returned to medical research, intrigued by what he'd read about a protein supposedly secreted from the pancreas that regulated the levels of blood sugar.  The problem was that all efforts to purify this active principal mobilised the trypsin which digested the protein before it's effectiveness could be measured.  In the Summer of 1921, Banting borrowed some lab space and a research assistant from University of Toronto's Professor of Physiology J.J.R. MacLeod.  MacLeod promptly left for an extended European vacation. The 22 year-old research assistant turned out to be Charles Best, who despite his youth had also done a wartime stint in the Canadian Army.  Between the two of them, they cracked the problem, obtained an alcoholic extract of the insulin, tested it with success on diabetic dogs and later on a diabetic boy.

This was a revolutionary break-through and the Nobel Prize was awarded about as quickly as it was possible to do so in 1923, to . . .  Banting and MacLeod.  Despite the frequent assertions of lazy-arsed 'researchers' in the history of science, it is not true to say that MacLeod's contribution to the project was that of an absentee landlord of the rooms where the experiments were carried out.  On his return from vacation, he was instrumental in improving the quality of the insulin with better extraction and purification procedures, getting Biochemistry Professor James Collip to oversee this aspect of the work.  But the exclusion of young Best from the winners (three is the maximum number of ways a single Prize can be split) struck many people then and since as unfair. It was probably just ageism: Banting, at 32, is still the youngest winner of a Nobel in Physiology & Medicine: maybe it was inconceivable to a committee of Swedish silverbacks that 'a mere boy' of 22 (who could drive a tank!) could have contributed substantively to the discovery. It's quite a neat antidote to the story of non-Nobellist Jocelyn Bell Burnell - exclusion from credit due is not the prerogative only of young women in science.  Like Burnell (N = 21), Best later got a rash (N = 18) of honorary degrees as consolation prizes.  Banting was sufficiently annoyed with the slight to his Effective that he shared his own prize money with him.  That induced a similar gesture from Professor MacLeod who shared his loot with fellow Professor Collip, keeping the money at the correct level in the hierarchy.  The list of exclusions might include Clark Nobel the other potential lab-assistant to Banting - he lost a coin-toss with Best for first dibs in the Banting laboratory.  Other people feel that B&B were pretty well scooped by Romanian physiologist Nicolae Paulescu who had treated diabetic dogs with his pancreatic extracts as early 1916.  But Banting's team were the first to successfully treat human diabetes with insulin.  Everyone seems to like and respect Banting.  He died on 21st February 1941 in a plane-crash en route to war-torn Europe (again!) to test another life-saving invention.

The discovery and purification of insulin started an industry removing the pancreas from every pig that went to slaughter and purifying porcine insulin to medical-grade injectible material.  The pig protein is 88% identical to the human product which was not enough to trigger a "this is foreign" immune response but was sufficiently different that diabetics on that treatment felt a little off when they needed an insulin boost.  Later this abbatoir-based biochemical solution to insulin availability was replaced with genetically modified microbes that grew human insulin in vats.  With the new product diabetics didn't get the tell-tale pre-crisis indications which made management of the disease a little more difficult.

Some years ago, The Beloved persuaded me and the girls to spend a week in the South of France on a Buddhist Retreat for Scientists. It was a little out of my comfort zone (except for the getting up before first light to not-think) but was a pretty wonderful experience.  There were 1000 people on the Retreat but the actual Scientists were very thin on the ground. In that world iridologists, chakra-boffins and crystal-therapists identify their whoo-wah as a branch of science. One of the techniques employed at such events is whole-body relaxation where everyone lies down warm-and-comfy on the floor and listens to somebody quietly, relentlessly, urging you to relax each part of your body in turn starting with the toes.  It's a bit "your toe bone's connected to your foot bone; your foot bone connected to your ankle bone . . ." but before we'd reached the hip there were wholly-relaxed snores in the room.  I was feeling a little dozy myself when I heard " . . . relax your pancreas . . .".  "WTF," I thought, "I'm sure I'm the only person here who could point to his pancreas, let alone relax it".

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