IT’S strange how some things seem to stick in the memory, isn’t it?
I well remember years ago sitting silent and still in the middle of Thetford Forest waiting for the call to start beating: beating to encourage the Muntjac deer to move towards the nets from whence they would be sedated, then provide samples to investigate their reproductive status.
But what was memorable was my companion, Professor John Cooper, sitting equally silent but feverishly writing in his diary to record the event for posterity. It’s something I think he still does with the only notebooks missing being those he had to leave behind when fleeing Rwanda at the height of the horrific genocide years later.
I wonder whether this pattern of daily diary-writing came from his mentor, Dr Edward Elkan, the 120th anniversary of whose birth we celebrated with a wonderful symposium in London recently.
A remarkable career begins
Dr Elkan was a Jewish doctor who fled from the Nazis in 1937, settling in England where he began a remarkable career developing a pregnancy test using the African Clawed Toad, Xenopus laevis. We know of his work not only from research papers but also from his memoirs, recently edited by his family.
The zoologist Lancelot Hogben had discovered in South Africa that Xenopus could be induced to lay hundreds of eggs when exposed to pregnant women’s urine. Elkan optimised this test, using it in place of the Ascheim-Zondek assay, which injected the urine into young mice or rabbits and then dissected them, to determine if ovarian development was produced by the gonadotrophin in the urine.
The test was so widely used that the phrase “the rabbit died” became a euphemism for finding out that one was pregnant. The Xenopus, on the other hand, were no worse the wear after the test and could be used again and again.
Here are the three Rs of reduction, refinement and replacement of experimental animals years before Russell and Birch developed the concept in the late 1950s.
William “Wild Bill” Russell had previously researched amphibian mating behaviour, so perhaps was aware of Elkan’s work. Russell was a remarkable polymath, interested in psychoanalysis, ancient civilisations and opera to name but three of his passions.
He was known to deliver his lectures in rhyming couplets sung in a mellifluous bass-baritone voice. But this little diversion takes me away from Elkan’s Xenopus. In his memoirs, Elkan writes that, reading of Hogben’s discovery while in London at the beginning of the war, he sent a telegram to the zoologist, reading, “Send 100 Xenopus”.
As Elkan notes, this aroused deep suspicions in the authorities who “wondered what kind of dangerous war material I was ordering to the detriment of Old England!?”
Eventually Elkan convinced them why he was asking for these creatures and the tadpoles duly arrived.
He took Hogben’s discovery and turned it into a standardised pregnancy test widely used until the development of the in vitro hCG assay still employed today. But keeping a sizeable colony of Xenopus toads led Edward Elkan to research the anatomy, physiology and pathology of amphibians and reptiles.
His books are still valuable today, linking the pathology exhibited by the animal with its in vivo appearance and behaviour. My favourite picture of Dr Elkan shows him with his microscope, but also with a live chameleon on his hand, linking the living creature with the fixed pathology that shows the disease from which it is suffering.
The Edward Elkan Reference Collection of Lower Vertebrate Pathology contains not only his histopathological slides and gross specimens but also sets of his most wonderful drawings of the lesions he observed.
Forgotten skills
With ready photographic documentation of pathological specimens today, I feel that we have forgotten the art and skill of drawing what we are seeing. And having lost that, we also forego the concentration on the detail which drawing naturally brings with it.
Elkan may have been an early expert in herpetopathology, but he was by no means the first to see amphibians as important experimental models. Over a hundred years earlier the physiologist Marshall Hall (1790- 1857) was insistent that experimental work involving animals should, wherever possible, use animals with as primitive a nervous system as possible, thus reducing detrimental effects of the nociceptive response experienced by the animal.
Hall worked on the damaging effects of blood-letting, then still widely used in human medicine, and for this he exsanguinated several dogs. After this disturbing experience he devised a set of principles of ethical experimentation:
- An experiment should never be performed if the necessary information could be obtained by observations alone.
- No experiment should be performed without a defined and obtainable objective.
- Scientists should be well-informed about the work of their predecessors, thus avoiding unnecessary repetition of experiments.
Key in our understanding of the three Rs today, Hall stated 190 years ago that “justifiable experiments should be carried out with the least possible infliction of suffering often through the use of lower, less sentient animals”.
Finally, he was insistent that “every experiment should be performed under circumstances that would provide the clearest possible results, diminishing the need for repetition of experiments”. Key concepts, yet these lay undiscovered for many years and today his name is all but forgotten.
I started with a memory of Professor Cooper keeping his diary up-to-date. And thankfully, Edward Elkan’s memoirs and those of Marshall Hall, written after his death by his wife, enable us to remember their contributions.
Yet all too often we forget those key figures of the past. Perhaps Dr Winslow died happy that his name would be remembered through his pseudonymous stars in the equine retina or Horner was content to be remembered for his syndrome.
Yet I can find no one who can tell me who on earth Winslow was, and William Keen, who was the first to discover the sympathetic denervation that we now call Horner’s syndrome, is all but forgotten. But those two will have to wait for a future Perambulations, I’m afraid!
