Pontifications on Poison
Being some ramblings on events associated with poisonous plants.
Wednesday 18th January 2012
I was reading a paper about the effect of giving calcium to someone suffering digoxin poisoning. It turns out that what ‘every doctor knows’, giving calcium to a person with a digoxin overdose is inevitably fatal, isn’t so. The paper was written for doctors and much of it went well over my head but it got me thinking about William Withering.
Dr. Withering is a hero of mine and I often mention him in my talks when comparing historic beliefs about plants and their effects, based on folklore and superstition, with modern scientific discoveries. Withering was the first to document the effects of using Digitalis plants, foxgloves and I believe his 1785 ‘An Account of the Foxglove’ is the first publication of a systematic trial of a substance.
I have a copy of the privately printed 1979 facsimile edition and it is one of the treasures of my library. Withering gives over 150 case histories of his own plus a great many other cases that doctors wrote to him about once his interest was known. Foxglove had been used for a while, though often as a folk remedy given by a village’s ‘wise woman’, but no-one had tried to define how it should be prepared and what dose should be used.
I’m not much of a one for prefaces and forwards so it was only today that I read Withering’s preface and discovered just how ‘modern’ his views were. In describing what should be taken from his work, he raises many of the issues that are still of concern when it comes to medical trials and the assessment of novel remedies.
Take the question of only publishing positive trials and suppressing unhelpful results. Withering writes;
‘It would have been an easy task to have given select cases, whose successful treatment would have spoken strongly in favour of the medicine, and perhaps been flattering to my own reputation. But Truth and Science would condemn the procedure. I have therefore mentioned every case…successful or otherwise.’
Then there is the matter of replication. It is not enough for a trial to make some discovery, others must be able to repeat the results. After saying that he understands some people will be doubtful of all he has to say he suggests that they;
‘…attend only to the communications from correspondents, because they cannot be supposed to possess any unjust predilection in favour of the medicine.’
But, in writing about the ‘correspondents’ he returns to the danger of positive bias and, whilst defending the reputations of those who have sent him their experience with foxglove, warns;
‘…the cases they have sent me are, with some exceptions, too much selected. They are not upon this account less valuable in themselves, but they are not the proper premises from which to draw permanent conclusions.’
He even touches on one of the most contentious issues in modern clinical trials whether it is enough to compare a novel remedy with placebo or whether it should be measured, in all respects, against existing treatments.
*Withering was looking to use foxglove to treat the dropsy, a condition where fluid built up in the soft tissue. He thought Digitalis was acting as a diuretic to remove the fluid. We now know that the dropsy is a form of heart disease where an under-performing heart leads to a build-up of fluid and the digoxin in the foxglove acts on the heart.
‘…it is not my intention merely to introduce a new diuretic* to [the reader’s] acquaintance, but one which, though not infallible, I believe to be more certain than any other in present use.’
After detailing his own trials and reproducing the correspondence he has received, Withering gives a guide to preparing and using the new medicine. Interestingly, he notes that different people will respond differently especially in terms of the first observed effect of the medication. Some will experience nausea and vomiting, some will pass urine freely and frequently and others will exhibit a very slow pulse.
Those differences show that Withering knew what the paper I referred to earlier was pointing out, you cannot be certain that the action of a substance will be the same in every patient.