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Feature Christmas 2018: Look Before You Leap

Adventures in self experimentation

BMJ 2018; 363 doi: https://doi.org/10.1136/bmj.k5006 (Published 11 December 2018) Cite this as: BMJ 2018;363:k5006
  1. Gareth J Parry, old research professor,
  2. Eric J Buenz, young research professor
  1. Nelson Marlborough Institute of Technology, Nelson, New Zealand
  1. eric.buenz{at}nmit.ac.nz

Gareth Parry and Eric Buenz explore the storied history of scientists using themselves as guinea pigs

Self experimentation is a rich medical tradition, leading to remarkable scientific advances but also erroneous conclusions and, sometimes, death.

Recently we explored the properties of Urtica ferox, a stinging nettle endemic to New Zealand (fig 1). During a collection expedition a 71 year old emeritus neurologist indulged in inadvertent, and subsequently deliberate, self experimentation. His notes of the evolving neurological manifestations after exposure provide clues to the toxin’s mechanism of action that would be difficult to draw without self experimentation (see box 1 for notes).

Fig 1
Fig 1

Self experimentation by an emeritus neurologist.Urtica ferox is a tree nettle growing >2 m tall, endemic to New Zealand (A), with trichomes that contain a putative neurotoxin (B). During a collection expedition and subsequent sample preparation an emeritus neurologist exposed himself to the fluid in the trichomes (C) and recorded the experience in detail (D).

Box 1

The emeritus professor’s notes after exposure to the neurotoxic stinging nettle

Immediate, moderately severe, burning pain at the site of penetration spread over 5-10 seconds to involve an area 1 cm in diameter. The pain began to subside within five minutes and had resolved within 60 minutes. As the pain subsided paraesthesias appeared that were intense and annoying but not truly painful, and allodynia was noted in the affected area.

Paraesthesias were constant for 18 hours and then became intermittent (particularly triggered by cold) and resolved completely by 48 hours. Numbness developed within 30 minutes of onset of paraesthesias. At nadir, complete loss of cold thermal and light touch sensation was noted, and pin prick thresholds were increased, but hyperalgesia occurred when the threshold was exceeded. At 18 hours the numbness began to recede in severity and extent, and it resolved completely by 72 hours.

Urtica ferox contains several chemicals that may account for the acute pain but not for the evolving neurological features. The observed sequence of events suggests a capsaicin-like response with initial burning pain and paraesthesias, followed by numbness that persists for several days. Like capsaicin, the unidentified molecule in the U ferox extract may bind to a channel in the nerve terminal, causing initial depolarisation but then preventing repolarisation.

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Self experimentation through the years

Historically, self experimentation was an important part of the scientific process, allowing medical advances that would have been hard to achieve otherwise because no sane human would agree to be a research participant and no ethical review board in its right mind would approve the experiment. For example:

  • Hooke calling Newton’s bluff on distorted vision through inserting a blunt needle between the eyeball and the orbit. He shamed Newton into performing the procedure and self experimenting with the retinal perception of light.1

  • Carrion’s self inoculation with blood from a wart on a patient with verruga peruana, to establish the link between these chronic skin lesions and the acute febrile illness Oroya fever, caused by the bacterium Bartonella bacilliformis. Carrion died for this advance.2

  • Head’s examination of cutaneous innervation and reinnervation by transecting the nerves in his own arm and studying the return of function through regeneration.3

  • Haldane’s personal explorations of hyperoxia, causing seizures resulting in vertebral fractures.4

  • Forssman’s success at self cardiac catheterisation, after lying to the nurse about who the research participant was and initially strapping her to the table so that she couldn’t stop him from initiating the procedure—which ultimately resulted in a Nobel prize.5

  • Salk using himself and his family to demonstrate the safety of the polio vaccination.6

  • Hoffman’s entertaining account of taking LSD (and thus establishing Bicycle Day for the counterculture).7

Below we outline four famous instances of self experimentation that have led to notable medical advances.

Stark’s pudding and cheese diet

In naval exploration scurvy was a perpetual significant risk manifesting as fatigue, whole body pain, muscle atrophy, tooth loss, and death (fig 2a). Encouraged by John Pringle (the “father of military medicine”), the young William Stark devised dietary experiments involving weighing his food, water, and excrement to show that “a pleasant and varied diet was as healthful as simpler strict diets.”8

Fig 2
Fig 2

Historical examples of self experimentation.James Lind—conqueror of scurvy (Parke, Davis and Company 1959). Throughout naval history scurvy was a predominant medical concern. Stark’s dietary self experimentation set the foundation for supplementing sailors’ diets with citrus (A).
Conquerors of Yellow Fever (oil on canvas), showing Cuban physician Carlos Finlay (left) and US army surgeon Walter Reed (centre) observing as Lazear exposes Carroll to mosquitoes carrying yellow fever (B).
Bier and Hildebrandt’s entertaining account of using cocaine to block pain was a significant advance in anaesthesia. Bier performing an intravenous regional neural blockade (C; courtesy of Michael Goerig, Hamburg, Germany).

In 1769 he was experimenting with a diet solely of honey puddings and Cheshire cheese when he experienced symptoms of scurvy. On Boxing Day he broke the restricted diet and consumed half a pint of blackcurrants, noting some improvement in symptoms. He considered introducing fresh fruit and vegetables but returned to his pudding diet. On 23 February 1770 he died, with symptoms of severe scurvy and other ailments. His meticulous record keeping ultimately provided key clues to the importance of an antiscorbutic substance in the diet, later identified as vitamin C.

Ffirth, Carroll, and Lazear investigate yellow fever

Historically endemic in Africa and most of the Americas, yellow fever was a major impediment to tropical exploration. In the 19th century the miasma theory of disease causation prevailed, but a postulated alternative was an infectious agent.

In the early 1800s Stubbins Ffirth, a Philadelphia medical student, devised a series of imaginative experiments to prove that yellow fever was not infectious9: first, he smeared vomit from an infected participant into incisions on his own arms and poured it into his eyes; second, he fried vomit and inhaled its fumes; third, he drank vomit directly from the mouth of an infected patient; and, finally, he smeared blood, saliva, and urine into cuts on his arms. Having still not contracted yellow fever he triumphantly, but erroneously, announced the results of his experiments as proof that the disease was not infectious.

In the 1890s Jesse Lazear was working in Cuba during a yellow fever epidemic (fig 2b).10 To show that yellow fever was an infectious agent transmitted by mosquitoes he exposed James Carroll and (debatably11) himself to bites from Aedes aegypti, the mosquito suspected of being the vector. Lazear contracted the disease and died, but Carroll recovered—going on to identify the vector for yellow fever virus and facilitate public health strategies to prevent infection.

Marshall drinks a bacteria brew

Into the late 20th century peptic ulceration was treated with dietary manipulation, antacid medicines, and even surgery. The concept that bacteria could survive in the stomach and cause the condition attracted derision.

Barry Marshall, an Australian physician, identified a bacterium, Helicobacter pylori, in the stomach contents of several patients with peptic ulcers.12 Having tried unsuccessfully to infect pigs with the bacterium he decided, without seeking ethics approval, to drink a culture of the patients’ bacteria. Three days later he developed nausea, vomiting, and putrid breath; gastric biopsy showed marked gastritis. His wife insisted that he immediately take antibiotics, and he rapidly improved. Subsequent research established H pylori’s role in gastric and duodenal ulcers, and in 2005 Marshall was awarded the Nobel Prize for Physiology and Medicine.

Bier and Hildebrandt pioneer spinal anaesthesia

In 1898 August Bier, a German surgeon, had his assistant August Hildebrandt perform a lumbar puncture on him, attempting administration of intrathecal cocaine.13 Spinal fluid was removed, but the experiment was aborted because of defective equipment. The next day the tables were turned, and Bier administered the cocaine to Hildebrandt. He tested the effects of the anaesthesia on Hildebrandt by thrusting a pin into his thigh to the bone, smashing a hammer against his shins, stubbing out a cigar on his skin, tugging on his testicles, and plucking his pubic hairs.

The tests all demonstrated successful anaesthesia; however, subsequently, and perhaps not surprisingly, Hildebrandt complained of pain and bruising in several areas of his legs. Both also developed severe headache, nausea, vomiting, and dizziness. Although Bier had previously performed this technique on six patients, these experiments ushered in the era of spinal anaesthesia and discovered post-lumbar puncture syndrome (fig 2c).

. . . and in the future

We should acknowledge the value of self experimentation and bring it out from the shadows. However, the business world has long appreciated the risks associated with ego driven decisions15 and “importantitis”16: it’s unlikely that physicians and medical scientists are immune to ego clouding their clarity when deciding to self experiment. While ethics approval should be optional when people want to do this,14 ethics committees and the soon-to-be participant should welcome an objective, unbiased review of the proposed self experiment: such a review can only help to ensure that the experiment is well designed.

A comprehensive review showed that only around 2% of documented efforts are made by women.17 Consider the Māori culture’s powhiri (traditional meeting between groups), where the men sit in the first row and the women sit behind them18: the historical reasoning is that, if battle ensues, the men—less important in maintaining the family lineage—are the first in line to die. While 89% of self experiments ultimately support the hypothesis being tested,17 the yellow fever and scurvy experiments show that the participant may be correct—but still dead. The sex bias in self experimentation could be the result of evolutional unimportance in males, a greater tendency towards narcissism in males,19 or simply historical gender disparities in science and medicine.20

Self experimentation is not without its hazards, but it often leads to useful and timesaving medical advances, as in our investigations into stinging nettles. Formal investigation of exposure to the potential neurotoxin in U ferox would require isolation and identification of the active compound, as well as extensive preclinical characterisation and ethics approval to administer it to humans. If an old curmudgeon would like to inject himself with a neurotoxin for the sake of science, describing the process in exquisite detail, he should be thanked and presented with an award—ideally in large type, suitable for framing.

Acknowledgments

GJP wrote the first draft of the manuscript. EJB added the humour and eloquence. GJP replied, “Who are you calling an old curmudgeon?! I’m not old.” After discussion it was agreed that GJP technically was an old curmudgeon. All authors approved the final manuscript.

Footnotes

  • We have read and understood BMJ policy on declaration of interests and declare no competing interests.

  • Provenance and peer review: not commissioned; externally peer reviewed.

References

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