Cholera Chloroform and The Science of Medicine A L... - (CHAPTER 6 Chloroform)

Chapter 6
Chloroform
W HEN ANESTHESIOLOGISTS WITH A TASTE FOR the his-

tory of their specialty read John Snow, they generally turn to On
Copyright © 2003. Oxford University Press, Incorporated. All rights reserved.
the Inhalation of Ether or On Chloroform and discover comprehensive, albeit dated,

accounts of these subjects, but reading Snow’s work from the white-hot years 1847 to
1851 is a very different experience. He conducted research on the installment plan,
and he was a serial and accumulative thinker in the golden age of serialization. As the
novel-reading public eagerly awaited the latest installment of David Copperfield in
Household Words, the British medical world followed the latest developments chiefly
via Lancet and LMG. London had learned of ether through articles, bulletins, letters,
and journals. Definitive reference works or compendiums were few and far between.
Most of the real action was taking place in lectures, medical societies, and journals,
and it is in the latter that one finds evidence of Snow’s furiously productive months
of research in 1847 on the properties of ether and the risks of administering it, within
the context of contemporary debates. Often writing in installments, repeating himself
to get new readers up to speed, and modifying as he went, he gradually developed his
views on the subject. Then, as the workaholic Snow raced to keep pace with and ahead
of developments, the ground shifted unexpectedly. Just as a serial novel might have it,
an Edinburgh professor of obstetrics, James Young Simpson, directed the attention of
the Medico–Chirurgical Society of Edinburgh to a new agent termed, with all the
chemical nicety of the day, perchloride of formyle, or chloroform.
140
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Chloroform 141
Pharmaceutical Profiling
Ten days after Simpson’s announcement, Snow was at the Westminster Medical Society
comparing “the new letheon agent” (as the Lancet described it) to the old one, ether. It
was 20 November 1847, only a year since ether’s discovery, but it seemed like an eternity
had passed.1 The early storm of excitement surrounding ether had lulled to a calm. Now
the Scottish announcement created another storm. A local chemist had given Snow a
quantity of chloroform rectified from calcium chloride (expense and ease of production
were important factors that Snow never failed to consider). Snow placed this sample on
the table for the edification of his colleagues and gave them a favorable report. He had
tried chloroform himself and found that it made him no more wretched than ether did.
In advance of his comments at the Westminster, he had placed his watch on a table, sat
down, and begun to inhale. He felt a pleasant inebriation and thought nothing was out
of the ordinary until he noticed that the second hand had disappeared. He found it again
only by pressing his nose up to the face of the watch (ON, 4: 334).2
He told the society that chloroform was preferable to ether in some respects. Chlo-
roform affected the nervous system in the same way that ether did; animal experi-
ments had confirmed this. Less pungent than ether, it was more easily inhaled, pro-
ducing its effects “with great rapidity.” He also noted that it was more economical.
“The quantity of it consumed was curiously small when compared with ether.”2a Pre-
liminary surgical trials indicated superior efficiency. A few days before his presenta-
tion, using his ether inhaler (water bath at 55°F.) he had administered chloroform
for a mastectomy at St. George’s Hospital. The third or fourth degree of “etheriza-
tion” was induced in less than a minute, and the whole operation used one tenth of
what would have been necessary with ether. Snow felt that the speed of its action
might even help to bypass the “preliminary excitement” (hysteria, spasms, or con-
vulsions) commonly encountered in the first stages of ether inhalation. He then pre-
sented a table, just as he had done with ether, that showed the quantity of chloro-
form gas that air would hold in solution at various temperatures (Table 6.1).
Table 6.1. Quantity of chloroform that 100 cubic inches

of air will take up
Temperature ⬚ F. Cubic inches
50 9
55 11
60 14
65 19
70 24
75 29
80 36
85 44
90 55
142 Cholera, Chloroform, and the Science of Medicine
Chloroform was almost twice as heavy as ether but took up one fourth the vol-
ume, and for this reason it neither excluded as much air nor impeded respiration to
the extent that ether did. Simpson administered it by way of a sponge or handker-
chief, but Snow preferred the precision and efficiency of his apparatus. With quiet
confidence Snow proffered his judgment that chloroform, while not without dan-
ger, was faster acting than ether and easier to use.
Discussion followed. Dr. E. W. Murphy (professor of midwifery, University Col-
lege, with whom Snow would work on a number of deliveries in 1848–1849) re-
mained unconvinced. He avoided using ether in labor whenever possible because of
the nervous reactions it seemed to cause “both before and after insensibility,” in-
cluding spasms that resembled “puerperal convulsions.” Murphy feared that the use
of ether in labor might cause hemorrhaging. Did Snow think chloroform caused
similar excitement? No, he replied, this kind of nervous excitement was caused by
the slowness with which it was necessary to give ether. The fast action of chloroform
should mitigate this problem during induction, but the nervous reactions would
likely occur as the patient recovered. He also suggested that patients do not die from
convulsions while inhaling but from continuing to inhale after collapse had appeared
and recommended that two practitioners be present for labor and delivery, one ded-
icated to anesthesia. In other words, Snow admitted that chloroform did cause spasms
similar to those seen with ether, but these were neither to be understood as convul-
sions nor to be dreaded. His recommendation was not to avoid using these drugs
but to bring in a specialist.
Snow was quick to appreciate chloroform’s properties. It seemed to behave like
a concentrated form of ether, generally acting like ether only faster. It fit what was
to Snow’s mind an emerging pharmaceutical profile. Simpson had been empiri-

cally searching for other anesthetics when he hit upon chloroform, but Snow rec-
ognized ether and chloroform as constituting a family of anesthetic agents in
which similar chemical composition and properties indicated similar physiolog-
ical action. It was a matter of calibrating safe dosages for the new drug. There
were differences, but chloroform conformed to the pharmacokinetic model (how
drugs are absorbed, distributed, metabolized and excreted) that Snow had devel-
oped for ether. There were undoubtedly other agents with similar properties wait-
ing to be tested. As early as February of 1847 Jacob Bell, editor of Pharmaceuti-
cal Journal, had tested chloric ether (which consists of chloroform in wine spirits)
with some success.3 Snow and others returned with fresh eyes to Robert M.
Glover’s Harvean Prize essay for 1842 that described bromoform, chloroform, and
iodoform. According to Glover, “Great resemblance exists among the properties
of this class of bodies, which appear to form a new order of poisonous substances,
uniting in themselves physiological properties which are not found united in any
other known class of poisons.”4 Snow realized that the medical miracle of
ether and chloroform was made possible by a beneficial side effect of a family of
toxins.
Chloroform 143
In a scant ten days chloroform had moved to the center of Snow’s research, which
meant to the center of his life. The extant Case Books of his practice begin in July
1848 (CB, 3), and they chart a widening circle of anesthesia from teaching hospi-
tals and Soho environs to virtually every quarter of London and beyond. Chloro-
form moved to the center of his thoughts about anesthesia, as he proceeded to
make it the basis of his pharmaceutical profile and to build a family of agents
around it (as the title of his last work, On Chloroform and Other Anesthetics, indi-
cates). Whatever risks chloroform presented were clearly outweighed, in Snow’s
mind, by its benefits. He believed that anyone who followed his methods could
work with it safely. Although he would greatly amplify, complicate, and qualify his
understanding of chloroform in the ensuing decade, he remained within the par-
adigm created in 1848. According to Richardson, Snow recalled a talk in which he
stated that “in his opinion sulphuric ether was a safer narcotic than chloroform.
Why, then, said a listener, do you not use ether? I use chloroform, he resumed, for
the same reason that you use phosphorous matches instead of the tinder box. An
occasional risk never stands in the way of ready applicability.”5 Snow’s attitude was
representative of British medical opinion at the time; according to Richardson,
chloroform “was immediately used everywhere to a greater extent than ether had
been,” rapidly becoming the anesthetic of choice (OC, 22).6 In 1848 Snow would
follow Glover’s lead and expand the range of his investigations beyond one or two
specific agents toward a larger concept of a family of drugs that fit the same phar-
maceutical profile. His approach was both bold and prudent—bold in its confi-
dence, prudent in the way it controlled the dosage. Chloroform’s very virtues, its
power and convenience, made it dangerous, even though many doctors had the
impression (largely thanks to Simpson) that chloroform was safer than ether (OC,
22). Within months of its discovery its risks would become all too real; the eu-
phoria of national pride at the Scottish breakthrough that rivaled, perhaps even
surpassed American self-satisfaction at having “discovered” ether, gave way, like a
serial novel, to death and doubt.
Hannah Greener
On 22 October 1847 a fifteen-year-old girl named Hannah Greener was admitted to
the Newcastle Infirmary suffering from an ingrown toenail on the big toe of her left
foot. The big toe on her right foot was also affected, but less so. She had not had
much of an appetite lately but was otherwise healthy. A few days later the surgeon
to the infirmary, H. G. Potter, operated to remove the left toenail. Ether was to be
used, but the first two inhalers failed to produce the desired effect. A third inhaler
(designed by Hooper) did the trick. According to Potter, the patient “screamed dur-
ing the operation but did not feel any pain.” She had not cried or laughed or ex-
hibited any “hysterical symptoms.” She never paled. Her pulse did weaken but then
regained strength. Thirty minutes afterward, sans toenail, she was fine, said that she
felt no pain, and “was asleep the whole time.”7
On 28 January 1848 Greener’s feet were still giving her trouble, and her family de-
cided to have another surgeon pay a visit to their home in Winlaton (near Newcas-
tle) to have the other nail removed. Thomas Meggison and his assistant, Mr. Lloyd,
arrived and found the girl in a fairly agitated state. She began crying from the mo-
ment that they walked in and continued to weep as they seated her in a chair and
began to administer chloroform.8 Meggison poured about a teaspoonful of chloro-
form on a “tablecloth” and held it to her nose. After drawing two breaths she pulled
his hand down. He told her to keep her hands on her knees and breathe quietly. The
girl complied, and in about thirty seconds he observed rigidity in her arm. Her
breathing quickened but was not stertorous. Her pulse was fainter than normal but
steady. Lloyd began the operation making a semicircular incision in the toe, and
Greener’s leg gave a sudden jerk. Meggison thought she might need more chloro-
form and was about to give her the cloth again when he lifted her eyelids and they
stayed open. Then the patient’s face and lips turned white, and she moaned or splut-
tered. The sound, he later explained, was “similar to the expiration in epilepsy or
hysteria.” He dropped the cloth and dashed water in her face. It was no use. He gave
her some brandy, laid her down, and tried to bleed her. He opened a vein in her arm
but nothing flowed. He tried her jugular with the same result. In total, about a fluid
drachm, or three and a half milliliters, of chloroform was used. The elapsed time of
the entire process of inhalation, operation, venesection, and death: two to three
minutes.9
The next day Sir John Fife and Dr. R. M. Glover conducted a postmortem exam-
ination. They attributed the cause of death to “congestion in the lungs” caused by
the inhalation of chloroform in combination with the idiosyncrasy of the patient.
Meggison and Lloyd were not held responsible for Greener’s death. Dr. Fife argued
that “no human foresight, no human knowledge, no degree of science, could have
forewarned any man against the use of chloroform in this case.” The jury convened
at the coroner’s inquest unanimously agreed,10 but would juries continue to agree if
more cases of sudden death occurred? This was both a crisis of medical knowledge
and a public relations nightmare for chloroform and doctors, like Snow, who pro-
moted its use. Pain relief was a blessing, but it had its limits. Whatever went wrong
had yet to be determined, but it was clear that a procedure to remove an ingrown
toenail should not result in the death of a fifteen-year-old girl. In the months that
followed the press was full of analyses of the case and soul-searching about the ben-
efits and dangers of chloroform. The same page of the Lancet that carried a report
of the inquest into Greener’s death contained an account of Professor William
Brande’s lecture on the chemical properties of ether and chloroform. It ended, the
report tells us, with a demonstration of Snow’s inhaler and Brande’s endorsement
of these chemicals as “of the greatest benefit to the medical profession and to hu-
manity.” Following the account of this well-attended lecture, the Lancet chose to run
Chloroform 145
an editorial that scolded Brande for killing a guinea pig during his demonstration
of the effects of chloroform. The performance seemed to confirm chloroform’s dan-
gers rather than to highlight its beneficent powers, and this was the last thing the
general public needed to see. There were ladies in the audience.11
Reports of other deaths from chloroform began to proliferate.12 In the general
press there were calls for abandoning its use. In its “Medical News” column the Lancet
reprinted an account from the Scotsman dated 12 February of a young man in his
late teens from Aberdeen who had been given to joy-popping chloroform and had
been found dead.13 A letter to the Lancet from a Robert Selby musing on the bene-
fits and dangers of chloroform admitted to nearly killing a nine-year-old boy.13a In
February in a dental parlor in Cincinnati, Ohio, a thirty-five-year-old mother of six
died under chloroform. A Boston man died in March. In May a thirty-year-old
woman in Boulogne, France, succumbed. Snow, who assiduously collected and scru-
tinized every case of death involving the medical use of chloroform, counted thir-
teen fatal or allegedly fatal cases for 1848. By the end of his career in 1858, these
would number more than fifty (OC, 120–222).
Doctors using ether and chloroform generally reacted defensively to these adverse
reactions and suggested that the proper stewardship of these drugs was the most press-
ing issue. It was most commonly argued that the agents could be used safely but must
be administered by informed, competent professionals. The letters in the Lancet were
quick to remind readers that toenail surgery is intensely painful, fully mandating the
use of anesthetics despite the fatality that occurred. Simpson led the way with a de-
fense of chloroform. Two weeks after Greener’s death he reviewed the facts of the case
and the autopsy as reported in the Lancet, concluding that she must have died of as-
phyxia; he believed the dose was “so small as to render it exceedingly improbable that
it could have been the essential cause of the death of the patient.”14 She appeared to
have fainted (syncope) at a critical moment. The water and the brandy used to restore
her, Simpson argued, inadvertently caused her to choke and cut off her air, but he did
not blame Dr. Meggison for using these techniques, because he had no way of know-
ing their dangers in the treatment of chloroformed patients.15
Reactions to Simpson’s analysis were generally sympathetic, with important dis-
tinctions that reveal the uncertainty surrounding the chloroform-related emergen-
cies. One correspondent agreed that the cause of death could not have been chloro-
form but believed “that the girl Greener died from the shock of the surgical
operation,” not efforts to revive her.16 David Davies, the house surgeon at Lough-
borough Dispensary, disagreed with Simpson’s analysis. Simpson’s account did not
jibe with his or Marshall Hall’s understanding of how anesthetic agents paralyze the
nerves. “Would it not have been more physiological to have said,” he wondered, “that
this poor woman’s death was owing to the power which anæsthetic agents have, in
some very rare instances, of destroying the functions of the spinal and ganglionic
systems of nerves.”17 Davies felt that Simpson needed to be more critical of the agent
he had discovered.
Like Davies, Snow disagreed with Simpson as to the cause of death, and he also
disagreed with the coroner’s conclusion. Snow sent a letter to the Lancet, stating that
the evidence did not support the thesis of syncope followed by asphyxia. While he
agreed with Simpson that brandy and water were not wise in this case, he could not
agree that they had asphyxiated the girl. Congestion of the lungs and heart, as was
found with Greener, was not compatible with fainting prior to asphyxiation. Snow,
who was lecturer on forensic medicine at Aldersgate School of Medicine, pointed
out that “a certain number of those who are drowned” do not have congestion in
the heart and lungs, and it is believed that “those persons have fainted on falling into
the water.” The autopsy did not support Simpson’s account and pointed back toward
the chloroform and, to Snow’s thinking, toward Simpson’s preferred way of giving
it, the hanky. There is a note of accusation in Snow’s critique. “For if anyone could
prevent his patient from getting into a state which cannot be looked on otherwise
than as one of imminent peril, it would be the authority who introduced that agent,
and recommended this method of its administration.”18
Snow wrote Meggison seeking clarification on a number of points and then pub-
lished his opinion in the LMG. He reasoned that if chloroform had caused death in
the manner concluded at the inquest, it “would necessarily invest the inhalation with
some degree of danger, however small, and would entail some anxiety on both the
operator and the patient. My view of the matter holds out more hope for the future.
I look on the result as only what was to be apprehended from the over-rapid action
of chloroform when administered on a handkerchief.”19 He believed that the hand-
kerchief had induced a much deeper degree of anesthesia than had been supposed,
and the rapid action of the chloroform was carried too far too fast, to the point that
it put a stop to Greener’s respiration. Snow had found that the effects of chloroform,
unlike ether, seemed to increase for twenty seconds or so after leaving off inhalation,
and this would account for the acceleration into a lethal degree. He argued that ex-
periments had shown that a teaspoonful of chloroform was sufficient to induce dan-
gerous levels of anesthesia in a large man, and this would therefore also be possible
in a smaller, younger female, even if given in the inefficient handkerchief.
In his letter to Meggison Snow asked for details about time and Greener’s symp-
toms in order to correlate them with the degrees of “etherization” he had established
the year before. What was “the nature of the breathing after the inhalation was
stopped?” “How long did the patient breathe after the removal of the cloth?” What
was the exact nature of the moan? From Meggison’s reply Snow reasoned that the
rigidity of the patient’s arm placed her in the third degree. From that position he in-
terpreted all subsequent symptoms as acceleration to the fifth degree. He argued that
the overdose stopped respiration and then the circulation, and this was the funda-
mental cause of death. This was a key moment in the development of Snow’s thought.
He noted that some of his more recent animal experiments indicated that in some
cases “the respiration and circulation seem to cease together.”20 By October 1848
he would go even further and claim that chloroform at this strength “paralyzes the
Chloroform 147
action of the heart at the same time as the respiratory movements.”21 In the ten years
of using chloroform that followed this investigation, Snow would elaborate on his
theory, especially in response to the commentary of Francis Sibson, who pointed to
the heart as the key to the trouble and also mentioned fear as a factor.22 Snow would
discuss more cases and complications, but he would never essentially depart from
his conclusions in the Greener case.
Concerns: On Narcotism
As he had done with ether, Snow looked to the mode of administration as the source
of the problem. He concluded that with ether problems typically eventuated in an
underdose; with chloroform, however, the danger was an inadvertent overdose. This
assessment would turn out to be only part of the story, but in 1848 there were too
many other basic questions that needed answering before subtler complications could
be pinpointed. He needed to find a way to explain the effects of chloroform and
ether in general, and he needed to detail the emerging pharmaceutical profile. What
was the appropriate name for it? His former term, etherization, was obsolete. Anes-
thesia was useful, but it placed the emphasis on the absence of sensation and dis-
tracted attention from other phenomena associated with these agents that should be
scrutinized. He settled on narcotism, because ether and chloroform closely resem-
bled narcotico-irritants (the Greek narco encompassed both stupor and numbness).
Strange as it may sound to modern ears, narcotism in the mid-nineteenth century
referred exclusively to narcotic vapors. In an era before the availability of nerve-
blocking local anesthetics, anesthetists were using gases that produced unconscious-
ness or stupor. Today, we tend to keep the pain relief derived from anesthetics sep-
arate from that produced by narcotics like morphine and heroin, which carry an
association with addiction. We also tend to distinguish the main property of a drug
from its side effects, which frequently suggest more about a drug’s common appli-
cation than its properties. For Snow, however, narcotism seemed the most compre-
hensive term for the entire range of phenomena, and his usage resonates with the
term narcosis.
In February 1848, with the notes to fifty chloroform cases carefully logged, he an-
nounced the next plank in his research agenda. Having established to his own satis-
faction that chloroform conformed to the five degrees of etherization, he concluded
that there “can be no doubt that these degrees of narcotism correspond with differ-
ent proportions of vapour which are dissolved in the blood at the time—propor-
tions which I hope to be able to determine.”23 Narcotism was the total effect of the
drug on the system, and anesthesia was just one consequence.
These drugs could be measured against each other with respect to blood satura-
tion levels, anesthetic and narcotic power, and various other effects. Snow used
Flourens’s theory of the cessation of neurological function as a working model of
narcotism. “A certain quantity of vapour disturbs the functions of the cerebral hemi-
spheres; an additional quantity appears altogether to suspend these functions, and
to impair those of the spinal cord, and probably of the cerebellum; a still larger quan-
tity to suspend their latter functions, but to leave the medulla oblongata more or less
unaffected.”24 As the gas escapes the lungs, the sequence is reversed.
With this model in mind, Snow began his pioneering study, “On narcotism by the
inhalation of vapours,” published in eighteen installments by LMG between May
1848 and December 1851. He completed twelve installments by August 1849, when
he interrupted his research to develop his theory of cholera. He completed four more
installments between the spring of 1850 and the spring of 1851 and finished his se-
rialization that December, just before LMG amalgamated with MT to become MTG.
“On narcotism” (ON) placed his earlier work on ether in a broader context of nar-
cotic and anesthetic phenomena. It is studded with examples of outstanding scien-
tific observation and problem solving. Snow laid out the significance of saturated
vapor pressure. He expressed his rule of thumb that the amount of an agent needed
to produce anesthesia was inversely related to its solubility in blood. He identified a
family of agents that worked in this way, gauging their potencies relative to one an-
other. He added further considerations to his ether study on the mechanics of in-
halation. He discussed oxidation, closed-circuit techniques, and tests to detect chlo-
roform in air, blood, and tissues.25 It was an evolving study, written in periods of
great activity and energy and responsive to emerging controversies about deaths while
patients were under chloroform. In sum, the installments of ON reveal the reach of
Snow’s mind, the patterns of his thinking, and his ability to incorporate develop-
ments on practical, experimental, and theoretical levels.
His basic goal in ON was to determine the exact correspondence among precise
doses of ether or chloroform, degrees of narcotism, and quantity in the bloodstream,
but first Snow needed to show experimentally what was already plain: ether and chlo-
roform enter the blood via respiration. To show this he “passed a tame mouse”
through a mercury trough and into a graduated jar containing a mixture of ether
and air. After a short while he removed the mouse from the first jar and placed it in
a second graduated container containing only air. He then removed the mouse from
the second jar, let both jars return to the starting temperature, and observed that in
the first jar the mercury rose a good deal while in the second it fell somewhat (ON,
1: 850). With relatively simple techniques of chemical analysis he had demonstrated
that the mouse had inhaled ether from the first jar and exhaled it into the second.
Even so, how could he determine the precise amount the mouse had inhaled and
the minimum required to induce the five degrees of narcotism? In 1847 Jean-Louis
Lassaigne and Andrew Buchanan had made crude estimates of how much ether was
required to fully anesthetize an adult. Snow was prepared to offer a more accurate
method. Rehearsing the laws of proportion for gas mixtures and liquids that he had
confirmed in 1847, he explained that when gases like ether or chloroform come in
contact with a liquid like blood or water, the gas is absorbed into the liquid until
Chloroform 149
equilibrium is established. At a given temperature and pressure, equilibrium occurs
when both the gas and the liquid contain “the same relative proportion to the quan-
tity which would be required to saturate them” (ON, 1: 850). If one knows the con-
centration of the gas, the concentration at which that gas saturates air (at the tem-
perature of the air in the alveoli), and the concentration at which that gas saturates
blood (at the same temperature), then one can calculate the concentration of the gas
in the blood. He expected to find that, if one started with a three percent concen-
tration of gas to air at equilibrium, the blood would contain a one per-
cent concentration of the gas (assuming thirty percent was required for air satura-
tion and ten percent for blood saturation). That is, the ratio of anesthetic gas to air
would be proportionate to the ratio of gas to blood. In Snow’s words, “As the pro-
portion of vapour in the air breathed is to the proportion that the air, or the space
occupied by it, would contain if saturated at the temperature of the blood, so is the
proportion of vapour absorbed into the blood to the proportion the blood would
dissolve” (ON, 1: 850). For the sake of clarity, this rule was perhaps best not con-
densed into one sentence, but Snow’s formulation gives us a sense of how he saw the
problem. To regulate the dosage, he created an inhaler, which was a temperature-
and volume-controlled environment for gas–air mixtures. To calculate the quantity
absorbed in the blood, the dosage had to be adjusted for alveolar temperature. Once
saturation levels were established and concentrations known, determining the
amount of the drug absorbed in the blood became a matter of solving for X. Snow
had come to see temperature, volume, and saturation as the keys to controlling con-
centration and concentration as the key to understanding the physiology of narco-
tism and the process of anesthesia.
The first series of experiments described in ON dealt with chloroform; he had de-
cided to use the new drug, not ether, to build the database of narcotism. Using min-
imal doses and allowing enough time to see that the drug’s effect no longer increased,
Snow combined his acute powers of clinical observation with the numerical preci-
sion of chemistry to determine the quantity of chloroform necessary to induce a par-
ticular degree of narcotism. Working from a chemical and physiological perspective,
Snow was practicing modern scientific medicine. He placed guinea pigs, mice,
chaffinches, green linnets, and frogs in jars with different quantities of chloroform,
allowed the effects to run their course, and monitored the animals for symptoms. In
the course of the first sixteen experiments, Snow pinched the guinea pigs and
chaffinches to see if they would flinch and made his notes. Table 6.2 summarizes his
findings. The medical model enabled a new kind accuracy in his estimates. The se-
lection of rodents, birds, and frogs afforded a variety of sizes and respiratory rates,
allowing for a range of differences in reactions while supporting the general valid-
ity of the blood concentration model.
To prove this last point, Snow concluded the first installment by recounting the
experiments he was invited to perform at the Royal College of Physicians for James
Arthur Wilson’s Lumleian Lectures (29 March 1848). In a very large jar (almost 1000
Table 6.2. Snow’s early experiments with chloroform

Chloroform/
Degree of narcotism Quantity of chloroform/air blood concentration
2nd 1 grain (64.8 mg)/100 cubic inches air 1/16,285
3rd 1.5 grains (97.2 mg)/100 cubic inches air 1/10,857
4th 2 grains (129.6 mg) /100 cubic inches air 1/28
5th 2.5 grains (162 mg) /100 cubic inches air 1/22
cubic inches) Snow had placed a frog and a chaffinch (in a small cage) and then in-
troduced five grains of chloroform. In less than ten minutes the frog was insensible
whereas the bird was perfectly conscious. He inserted another frog and chaffinch in
a much smaller jar (200 cubic inches) and added five grains of chloroform. In ninety
seconds the bird was insensible, but the frog was still very conscious (ON, 1: 854).
These demonstrations showed how crucial dilution, respiration rate, and blood tem-
perature were in the process of narcotism. In the first case the dilution was too great
for the small, warm-blooded chaffinch to be affected despite its quick respiration,
but the cold-blooded, slowly respiring frog was affected because the lower temper-
ature of its blood meant that it did not require as high a concentration to achieve
saturation. In the second case the greater concentration worked quickly on the bird,
but ninety seconds was not long enough for the slow-breathing frog. Snow added
further confirmation by demonstrating that a warmed frog ceased to be affected by
diluted gases that would narcotize it at low temperatures.
The second installment of ON analyzed ether, using the same approach as he had
done with chloroform, and then compared the two agents. Snow found that the sec-
ond degree of narcotism corresponded to .000875, or 1/1,142 proportion of ether in
the blood at 100° F., and that the fourth degree corresponded to .00175 or 1/572. He
compared these results to his experience with human subjects. Working from Gabriel
Valentin’s calculations of the weight of the blood in the adult human (about thirty
pounds, equivalent to 410 fluid ounces), Snow calculated that the total quantity of
chloroform in the blood was 12 minims (.71 ml) for the second degree and 24 min-
ims (1.42 ml) for the fourth. For ether, the corresponding numbers were 171.84 min-
ims (10.17 ml) and 340.8 minims (20.17 ml). He found these to correspond very
nearly with his experiences when administering both agents: “a considerable portion
is not absorbed, being thrown out again when it has proceeded no further than the
trachea, the mouth and nostrils, or even the face-piece” (ON, 2: 895). He confirmed
this hypothesis by breathing chloroform over and over again from a balloon (as with
nitrous oxide). Using this recycling technique, he found twelve minims sufficient to
induce the second degree.
He was particularly sensitive to the role temperature played in the administration
of vapors, both in the apparatus and the alveoli. He noted that birds “were found to
Chloroform 151
require nearly twice as much” ether as were mice to render them insensible, while
this was not the case with chloroform. Because these birds generally maintained a
temperature of 110° F., he reasoned that the blood serum at that temperature would
dissolve much less ether than at 100° (the temperature of Snow’s mice), and there-
fore the birds would require greater concentrations to achieve the same degree of
saturation. Snow also began to consider the impact of ether and chloroform on an-
imal temperature, not merely noting the difference between warm-blooded and cold-
blooded creatures but as a physiological process. Snow came across Jean Nicholas
Demarquay and Auguste Dumeril’s statements that these agents lower body tem-
perature during inhalation. Several ether experiments on linnets confirmed this, reg-
istering drops of as much as eight degrees in fifteen minutes (ON, 2: 893–94).
This was John Snow in early 1848—poking guinea pigs, pinching chaffinches, pass-
ing mice through quicksilver, and warming frogs near the fire in the name of med-
ical science. His medical model focused on narcotic symptoms, concentration, volatil-
ity, respiration, time, and temperature. Differences in species and individuals now
came down to measurable differences of minutes, minims, cubic inches, degrees
Fahrenheit, degrees of saturation, and degrees of narcotism. Through the alembic of
this medical model, he transformed a narcotized menagerie of experimental animals
into reliable data on blood concentrations. To our knowledge no one else took such
a comprehensive numerical approach to these drugs, nor did anyone else wed chem-
ical analysis to a physiological progression with such consistency.
After establishing a baseline with chloroform and ether, Snow concerned himself
with broadening the spectrum of vapors that might have narcotic properties and
might be inhaled for anesthetic purposes. Through the spring and summer of 1848,
when he published the third and fourth installments, he investigated six other agents:
nitric ether (ethyl nitrate, C2H5ONO2), bisulphuret of carbon (carbon disulphide
CS2), benzin (benzene C6H6 [Snow gives it as C12H6]), bromoform (HCBr3) ethyl
bromide (C2H5Br), and Dutch liquid (1,2-dichloroethane C2H4Cl2). He had begun
to compile a systematic pharmacology of inhaled anesthetics. Whereas many were
engaged in the search for better anesthetic agents (Simpson and Thomas Nunnely
from Leeds, for example, experimented with many of the same agents), and medical
journals were filled with suggestions for new agents, Snow established a method of
comparison based on general principles of anesthetic and narcotic action. “His grand
search,” according to Richardson, “was for a narcotic vapour which, having the phys-
ical properties and practicability of chloroform, should, in its physiological effects,
resemble ether in not producing, by any accident of administration, paralysis of the
heart.”26 No doubt that would have been a desirable practical outcome from Snow’s
research, but this was actually Richardson’s project.
For Snow, the grand search was for “the ‘perfect’ anaesthetic” as well as a general
theory of narcotism itself.27 That was why he went to the trouble of calculating the
blood saturation levels for substances like bisulphuret of carbon, when all of his ev-
idence showed that it was too powerful, noxious, and dangerous; it caused convul-
sive tremors in mice (ON, 3: 1076–77). He never really considered this agent a vi-
able substitute for ether or chloroform, but he studied it because he wished to place
it on a continuum of inhaled agents that induced narcotism in the same way as did
ether and chloroform. In particular, he was looking for extremes to set the endpoints
on this continuum. He was careful to point out that not all narcotics functioned like
ether and chloroform, and he mentioned hydrocyanic acid (prussic acid) as an ex-
ample of one that did not. He was only interested in those narcotics “producing ef-
fects analogous to what are produced by ether,” “and having . . . a similar mode of
action.” However, he regretted that he was not “able at present to define them bet-
ter than by calling them, that group of narcotics whose strength is inversely as their
solubility in water (and consequently in the blood)” (ON, 4: 333). The analogical,
deductive pattern of his thought is evident; similar substances producing analogous
effects implied similar pharmacodynamic mechanisms. In this manner he invented
a family of volatile liquids where formerly there had been only individual agents. He
linked blood solubility with the narcotic power, rated by the minimum concentra-
tion in the blood, necessary to induce the second degree. He considered nitric ether
a promising candidate, and he asked one of his regular chemists to make him a sam-
ple. When he tried it on himself (“on two or three occasions”), a small amount
“caused a disagreeable feeling of sickness each time” (ON, 3: 1075). In May 1848 he
used it with encouraging results in a tooth extraction at St.George’s Hospital, but he
never used it again, clinically, despite evidence that it was an effective painkiller. He
was also interested in benzene, despite its tendency to cause convulsive tremors. Tri-
als showed it to be nearly as efficient as chloroform, but its effects “are not so rap-
idly produced as the effects of chloroform, on account of its lesser volatility.” He tried
benzene on human subjects at St. George’s Hospital, with success in minor opera-
tions, but in an “amputation, where its effects were carried further, the patient had
violent convulsive tremors for about a minute, which, although not followed by any
ill consequences, were sufficiently disagreeable to deter me from using it again, or
recommending it in the larger operations” (ON, 3: 1078). Snow was a cautious prac-
titioner, and it is admirable that he stopped using benzene. At the same time, given
his reaction to the carbon compound, which also caused convulsions, one may won-
der why he bothered to put benzene to clinical trial at all, or, for that matter, why
he never pursued nitric ether, despite its promise. Convulsions alone would not have
dissuaded him; both ether and chloroform could produce spasms.
He was deeply invested in the model of narcotism he had constructed around
chloroform, and it shaped his theoretical and practical considerations of related
agents. He probably did not pursue nitric ether because it was a weaker and more
expensive agent than was chloroform.28 In the case of benzene, the potential of hav-
ing a drug as economical and efficient as chloroform that acted less quickly (Snow
considered gradual induction desirable) made it worth trying until convulsions
proved too violent. The sulfur–carbon compound was too fast acting to control ef-
fectively, so it held no clinical interest for him. Snow synthesized his own bromo-
Chloroform 153
form, a substance with a molecular formula similar to chloroform and now known
to cause kidney and liver damage in animals. He found it “very pleasant to inhale”
but too costly to produce (ON, 4: 330). He found ethyl bromide to be too volatile,
requiring very high concentrations to be effective, so he never bothered to get an ex-
perimental reading of its blood solubility. Dutch liquid tasted “at once sweet and
hot,” and Simpson considered it too caustic to be inhaled by most patients (ON, 4:
331). Snow determined that it required 46 minims (2.7 ml) of Dutch liquid to cre-
ate 1/50th relative saturation of the blood to induce the second degree of narcotism.
He was not particularly sanguine on its prospects as an anesthetic agent for addi-
tional reasons: Two mice died after trials, and postmortem examinations revealed
that their lungs were congested, their hearts swollen, and the blood coagulated and
dark.
Snow would continue for the rest of his life making trials of all kinds of hydro-
carbon inhalants, but his main concern in 1848 was to confirm and reconfirm that
degrees of narcotism corresponded to the quantity of the substance in the blood. He
believed that this quantity was a proportion of “what the blood would dissolve—a
proportion that is almost exactly the same for all of ” these substances. The actual
differences in quantity were accounted for by differences in solubility: “When the
amount of saturation of the blood is the same, then it follows that the quantity of
vapour required to produce the effect must increase with the solubility, and the ef-
fect produced by a given quantity must be in the inverse ratio of the solubility” (ON,
4: 332). Snow included acetone, pyroxilic spirit, and alcohol on his list, even though
they are infinitely soluble in blood, because they shared properties with the other
volatile liquids and were proportionately less potent, which seemed to prove his rule.
In this fourth installment of ON, he again described the degrees of narcotism, using
chloroform as his model, began to make observations about chloroform and mid-
wifery (a subject that would increasingly preoccupy him), and put forward an idea
that he had not previously mentioned: “The division into degrees is made accord-
ing to symptoms, which, I believe, depend entirely on the state of the nervous cen-
tres, and not according to the amount of anesthæsia, which I shall give good reason
for believing depends very much on local narcotism of the nerves” (ON, 4: 334). It
turns out that Snow’s last opinion was incorrect, but it reveals the general pattern of
his thought. Painlessness was, for Snow, a local epiphenomenon of narcotism.
Narcotism’s Reach
In these early installments Snow established the pharmacology of narcotism and a
model of how the body responds to relative quantities of narcotics. The fifth and
sixth installments addressed the general physiological effects of chloroform, how the
nerves were affected, how death could occur, and what autopsies on animals revealed.
After reviewing the dangers of chloroform in part seven, he made a case for its safe
use with a slightly modified version of the temperature-controlled chloroform in-

haler (Fig. 6.1). In part eight he described the various conditions that influence the
action of chloroform such as age, strength, debility, disease, diet, hysteria, epilepsy,
renal convulsions, and diseases of the heart, lungs, and brain. In parts nine and ten
he analyzed the data for amputation and other procedures under chloroform. Next
(parts eleven and twelve), he considered various mixtures of chloroform and ether,
and described an alternative mode of administration via a balloon and a valved face
piece. He made a few more trials of Dutch liquid and in 1849, as cholera raged in
London, Snow evaluated it as a potential treatment. A seven-year-old girl was in the
throes of the disease, constantly vomiting and evacuating and in jactitation from
horrific cramps. He had used chloroform in a number of cholera cases that year, and
he found that it offered some relief by inducing sleep free “from sickness and spasm.”
For this girl, however, he administered Dutch liquid, which gave her only a few min-
utes’ respite, although she did recover (ON, 12: 277). In June 1849 Snow continued
to experiment with his growing armamentarium of pain relievers in the face of
Figure 6.1. The modified chloroform inhaler and mouthpiece from November 1848
(Adapted from ON, 7: 843).
Chloroform 155
cholera. Sometimes he was able to give patients enough rest to make a recovery,
sometimes he simply eased the suffering of the dying. In the process it must have
become clear to him that giving chloroform and Dutch liquid to cholera victims was
only a stop-gap measure.
Chlorophobia
On a night in early January 1850, a Lime Street solicitor named Frederick Hardy Jew-
ett was walking along the bustling Whitechapel Road in the East End. Suddenly,
someone put a felt rag or handkerchief over his mouth. The next thing he remem-
bered was waking up the next morning in the filthy bed of a lodging house in Thrawl
Street, Spitalfields. When he attempted to leave, he found the door locked from the
outside. He was naked, covered with rags, and most of his valuables had been stolen.
Two young women, Margaret Higgins and Elizabeth Smith, were arrested, tried, con-
victed, and sentenced to fifteen years. At one of their hearings Catherine Donovan,
the wife of a local grocer, testified that Higgins had confessed to the crime and told
her that the man with whom she lived had been operated on at a London hospital.
They gave him “some stuff to send him to sleep,” and afterwards he had managed to
steal some of it. Higgins had used this “stuff ” in the Whitechapel Road mugging.
About the same time, a man was walking along the Borough Road, south of the
Thames, toward London Bridge when a woman passed a handkerchief across his
face. He immediately felt indisposed, and the woman helped him into a nearby pub
for a tumbler of brandy. Her name was Charlotte Wilson. Ten minutes later the man
was unconscious, and she left the pub with his hat and scarf in hand. Wilson was
soon apprehended. In the opinion of the court, she had used “some deleterious ar-
ticle such as chloroform,” and she received ten years for robbery.29 It was not just a
problem of women attacking men. In April 1850 a young man named Charles Jopling
and his girlfriend walked home from a pub dance near Marylebone. He beckoned
her to follow him into a mews, where he poured the contents of a vial on a hanky
and tried to smother her. Repulsed by the wet hanky and the pungent odor, she cried
out for help. A policeman on his beat heard the screams and took the man into cus-
tody. Jopling paid bail and married his girlfriend, and she dropped the charges against
him.30 This was not exactly news. As early as November 1847, when Simpson’s new
agent was first publicized, there had been reports of chloroform described as a rape
drug.31 There were a few reports of street robberies in 1849, but in the aftermath of
Hannah Greener’s death the medical risks of chloroform received more press than
its criminal potential.32
In 1850 and 1851, however, chlorophobia swept the country, as the agent intended
for medical purposes was increasingly perceived as an alleged agent of crime, rob-
bery, rape, and murder. An old man asleep in a hotel room was attacked with chlo-
roform by a man hiding under his bed. Prostitutes were charged with hocussing by
way of chloroform, using it to lace the drinks of unsuspecting johns and then rob-
bing them. In France a dentist raped a female patient while she was under its influ-
ence.33 Chloroform’s fast action, incompletely reported in the press and experienced
by growing numbers of patients, led to a sensational misunderstanding of its pow-
ers in the public and popular imagination. Long before the chloroformed handker-
chief became a staple of fictional abductions—the kidnapper’s method of choice for
surreptitiously overpowering victims—the powers of chloroform were mythologized
on the streets and in the criminal courts.
Things came to a head in February 1851, when Lord Campbell, the recently ap-
pointed chief justice of the Court of Queen’s Bench, proposed An Act for the Better
Prevention of Offences that called special attention to the use of chloroform for crim-
inal purposes. Lord Campbell believed that British criminal law was too liberal and
that too many criminals were able to skirt whatever law did exist. He lobbied for
stricter sentences as a deterrent. He wanted to make possession of tools of criminal
trades (e.g., picklocks) an offence for which the punishment was deportation. A
clause in Lord Campbell’s bill depicted chloroform as a potential tool in the crimi-
nal’s trade: “And whereas it is expedient to make further provision for the punish-
ment of persons using Chloroform, or other stupefying things, in order the better
to enable them to commit felonies: be it enacted, that if any person shall unlawfully
apply or administer, to any other person, any Chloroform, Laudanum, or other stu-
pefying or overpowering drug . . . every such offender shall be guilty of felony, and
being convicted thereof shall be liable, at the discretion of the Court, to be trans-
ported [to Australia] for life, or for any term not less than seven years.”34
Snow believed Lord Campbell’s bill was unnecessary and unfairly targeted chlo-
roform. In his opinion, “It ill becomes the gravity of the law, and is, I feel assured,
far from your Lordship’s intention, that a legal enactment should be made on a false
alarm, or to meet a trivial and unsuccessful innovation in the mode of attempting
a crime: to legislate on this matter would revive the groundless fears of the public.”35
Snow was skeptical of public reporting on the purported uses of chloroform to com-
mit crimes. Most descriptions did not conform to the known properties of the agent.
The drug was far too pungent to be inhaled unawares. To force it upon someone re-
quired smothering, or “burking”—a felony for which the law already provided. Per-
haps Lord Campbell was cracking down in advance of the Great Exhibition of 1851,
when tourists were expected in London. The bill had a distinct animus against the
working class, especially with its stiff sentencing. Snow thought social hypocrisy ex-
plained much of the chlorophobia: “Persons who have been dead drunk are very un-
willing to admit, even to themselves, that the result was the consequence of their
own voluntary potations, and still less willing to admit it to the world, when they
have to complain of having been robbed whilst in bad company.”36 The editorial staff
of the Pharmaceutical Journal concurred, stating that, “It may be a convenient sub-
terfuge for a man who finds himself in a scrape . . . to conjure up a mysterious
and exciting story about chloroform and a handkerchief, for the purpose of throw-
Chloroform 157
ing dust in the eyes of the magistrate, and working upon the prejudices of the jury.
[This act] may be the means of entailing an unjustly severe punishment for a com-
paratively trifling offence.”37 Snow’s letter was discussed in the House of Lords. The
Times reported that “a most respectable physician” had done Lord Campbell the
honor of writing him a letter, stating that the fear of using chloroform in this way
was “altogether imaginary.” Nonetheless, Campbell kept the provision and hoped that
anyone convicted would “be guilty of a felony, and liable to be transported beyond
the seas.” To which his fellow lords replied, “Hear! Hear!”38 The act passed in June
1851.
Narcotism’s MO
When Snow resumed publication of ON in April of 1850, he apologized for the in-
terruption. He justified it on the grounds that he needed to “repeat many experi-
ments and institute fresh ones,” but his study of cholera in 1849 may have been an
additional factor (ON, 13: 622). The new installments reflect a shift in thinking. Ear-
lier, his goal was to establish a pharmaceutical profile of narcotism, to measure in-
verse ratios of solubility, and to describe the benefits of various agents in amputa-
tion and dentistry. Now, in 1850, he concerned himself with the underlying
physiological mechanisms, or, as he called it, “the modus operandi of ether and chlo-
roform” (ON, 13: 622). He began to tackle complex questions involving the bio-
transformation of these drugs as they circulated in the body.39 This approach would
push him beyond the pharmacokinetics of narcotic agents into thornier issues of
pharmacodynamics (how drugs interact at cellular and molecular levels). It was terra
incognita. Where to begin? His cholera research had led him deeper into patho-
physiology to Liebig’s Animal Chemistry, especially Liebig’s descriptions of how car-
bon and hydrogen in fat, starch, sugar and gum “combine with oxygen in the blood,
and are given off as carbonic acid gas and water” (ON, 13: 627). Based on this gen-
eral model, Liebig also offered an “explanation of the physiological action of alco-
hol,” that is, how it was metabolized in the system (ON, 13: 626). When ether came
along, Snow observed, “many persons were inclined to extend” Liebig’s alcohol the-
sis to ether (because of its chemical similarity to alcohol). Snow would begin by test-
ing the validity of Liebig’s theory of the physiology of alcohol to see what he might
learn about the physiology of narcotism.
Snow began by reconfirming what his blood solubility table had shown: a family
relation between alcohol, chloroform, and ether.40 He showed that alcohol did, in-
deed, correspond to the pharmaceutical profile he had set up for narcotism. It obeyed
the inverse ratio rule of blood solubility. He also extended his analysis by confirm-
ing that its clinical effects corresponded to his model of degrees. This was not easy
to do because the effects of alcohol last so much longer than those of chloroform or
ether. He concluded that “ordinary drunkenness does not exceed the second degree
of narcotism; the popular term of dead drunk being often applied to a state of sleep
from which an individual is still capable of being roused to a state of incoherent con-
sciousness.” He calculated the blood-alcohol level for this condition (fifteen ounces
of proof spirit) and asserted that less than twice this amount taken all at once on an
empty stomach ought “to prove fatal” (ON, 13: 625). The result corresponded well
with common experience and his established degrees of narcotism (and today’s
blood-alcohol standards). Snow concluded that the “amount of anesthesia from al-
cohol is apparently as great, in proportion to the narcotism, of the nervous centres
attending it, as from chloroform and ether,” but it does not yield enough vapor at
room temperature to cause insensibility in a reasonable amount of time (ON, 13:
626). Were it a more practical anesthetic, the teetotaler Snow mused, alcohol would
be in public opinion “as praiseworthy as it is disgraceful when resorted to for the
purpose of supposed enjoyment, or to satisfy a craving which has resulted from a
pernicious habit” (ON, 13: 626). Alcohol, a substance he had opposed his entire adult
life, was actually a cousin to ether and chloroform, substances he championed and
sources of his livelihood.
Snow concluded that alcohol was a narcotic, for which Liebig had supplied a thick
description of its physiological action. According to Snow, Liebig argued that obser-
vation had led him to conclude that “neither the expired air, nor the pers-
piration, nor the urine, contains any trace of alcohol after indulgence in spiritous
liquors . . . ; that the elements of alcohol combine with oxygen in the body, and
that its carbon and hydrogen are given off as carbonic acid and water; that the ele-
ments of alcohol appropriate the oxygen of the arterial blood, which would other-
wise have combined with the matter of the tissues, or with that formed by the meta-
morphosis of the tissues: and that thus the change of the tissues . . . are diminished”
(ON, 13: 626). Snow believed this description was largely incorrect and, as any Breath-
alyzer will reveal, he was right, and Liebig was wrong. Whereas Snow concurred that
alcohol and other narcotic vapors diminish or suspend “molecular change” (Liebig’s
catchall for chemical and biochemical interactions) of the affected tissues, it was not
the result of “appropriating the oxygen in the blood” (ON, 13: 626–27). While oxy-
gen may combine with hydrocarbons in fat, starch, sugar, and gum, yielding carbon
dioxide and water, none of these substances were in any degree narcotic. Second, the
amount of carbon and hydrogen present in enough chloroform to render someone
completely insensible was “totally insignificant” compared to the amount of oxygen
absorbed in the lungs (ON, 13: 627). Alcohol has a very similar action to chloroform
and therefore could not, as Liebig argues, appropriate very much oxygen in the blood-
stream. Third, if alcohol did indeed create its narcotic effect by appropriating oxygen,
then supplying more oxygen should prevent or diminish the narcotic effect, but this
was not the case. Snow had observed patients in states of complete insensibility whose
skin turned “bright vermillion” with excess oxygen coursing through their arteries.
Through the summer of 1850 Snow demonstrated how to detect the presence of
chloroform, ether, and alcohol excreted in the breath. Consulting with Dr. Alfred
Chloroform 159
Taylor of Guy’s Hospital, he refined a test for the presence of chloroform in the blood
in the Journal de Chemie Medicale (March 1849). By inhaling chloroform and breath-
ing into a heated tube lined with silver nitrate, Snow obtained precipitates of silver
chloride crystals that corresponded to the amount of chloroform taken. He showed
how this method could detect chlorine in urine and tissue samples as well. Snow was
careful to qualify his analysis, reminding his readers that the process did not “prove
the presence of chloroform itself, but only that of a volatile [at the heat of boiling
water] compound containing chlorine” (ON, 14: 326).41 This meant that only the
compounds in the family he had been studying were likely candidates, of which only
chloroform was commonly used.
Snow devised a parallel series of experiments to detect traces of ether and alco-
hol in the breath. He had smelled ether on the breath of patients in the same way
one smells alcohol on the breath, but, as with chloroform, he sought quantitative
chemical confirmation. In both cases he took the drugs himself, trapped his respi-
ration in a balloon, and was able to rectify pure ether and alcohol from the breath.
Braving the perils of intoxication in the name of science, the temperance advocate
manfully took his measured dose of spirits with bread and butter, became mildly in-
toxicated, and breathed into a spiral tube connected to a small bath of sulfuric acid.
Trapping the alcohol vapor in the acid, he developed a process of heating the mix-
ture to obtain alcohol in a pure state (ON, 15: 751–53).
This was classic Snow. The implications of his research spun off, like a serial novel,
in social and medical directions. He wished to demonstrate that Liebig was wrong
about alcohol. He had also devised tests for detecting both alcohol and ether that
were more conclusive than was the test he devised for chloroform, yet he began the
discussion with chloroform because it had become the baseline for all his research
on narcotism. He was also highly sensitive to the social uproar surrounding chloro-
form in 1850. Snow’s test would be very useful in forensic investigations in which
chloroform was suspected. There was no pressing social need to detect alcohol or
ether on the breath, so he did not bother to develop a socially useful test for them.
He continued to investigate alcohol and ether in order to solidify his claim of the
family relations of narcotic agents, to further his physiological theory, and to prove
Liebig wrong.
The detection of chloroform, ether, and alcohol yielded a key physiological insight
rather than the modus operandi of narcotism per se. “I have assumed from the first,”
he explained, “that the speedy subsidence of chloroform and ether, in comparison
with that from alcohol and other narcotics, depends on the volatility of the former
substances, which allows of their ready exit by the expired air. Indeed, the effects of
these medicines usually subside in the period which a calculation founded on this
view would assign to them” (ON, 15: 753). Snow preferred the term degrees of nar-
cotism to stages because degrees suggested the passage of time on the face of a clock.
The duration of the effects of narcotism were determined by solubility and volatil-
ity: how much of the narcotic gas was absorbed by the blood, how fast the blood
circulated, and, once the narcotic gas was left off, how quickly the air removed the
gas from the blood. With their quicker circulation and respiration, children went un-
der and came out more quickly than did the slow-breathing elderly. He suggested
that diffusion of the agent to smaller vessels and tissues could play an ancillary role
in “allowing the brain to resume its functions” (ON, 15: 753). Ether was more volatile
than was chloroform but much more soluble, so the quantity absorbed by the blood
was much greater. Greater solubility compensated for the lesser volatility, Snow rea-
soned, and therefore ether wore off more slowly than did chloroform. It followed
that alcohol, with even greater solubility and less volatility than ether, lasted even
longer.
It also followed that one could prolong the effects of a narcotic by recirculating
the expired breath. Snow devised an autoexperiment, based on an attempt to relieve
the sufferings of a cholera victim in 1849, in which he first filled a balloon with pure
oxygen. Using a glass condensing coil, he connected the balloon to his ether inhaler,
which was filled with a “solution of potassa” (potassium monoxide) and attached
this setup to a valveless mouthpiece.42 After inhaling as much chloroform as possi-
ble without passing out, he breathed and rebreathed from the balloon–inhaler de-
vice; the oxygen he inhaled became mixed with the air already present in the inhaler,
while the potassium solution absorbed his CO2. He reported that the narcotism,
which ordinarily would have passed off in three to four minutes, lasted a full ten
minutes, with feelings persisting for approximately thirty minutes afterwards. It
worked for ether as well (ON, 15: 754). The potassium solution permitted him to
quantify the amount of CO2 produced while he was under the influence of narcotic
gasses.43
Oxidation–Asphyxia Theory
In April 1851 Snow presented a theory that explained how narcotic vapors worked.
It was based on two fundamental observations: The inhalation of narcotic gases re-
duces “the amount of carbonic acid formed in the system,” and “chloroform and
ether are exhaled unchanged from the blood” (ON, 16: 626). These agents, defined
as “the volatile narcotic substances not containing nitrogen, or those subsances whose
power was found to be in the inverse ratio of their solubility in water and the serum
of the blood,” have “the effect of limiting those combinations between the oxygen of
the arterial blood and the tissues of the body which are essential to sensation, voli-
tion, and, in short, all the animal functions” (ON, 16: 626). They “modify, and in
larger quantities arrest, the animal functions, in the same way, and by the same power,
that they modify and arrest combustion, the slow oxidation of phosphorous, and
other kinds of oxidation unconnected with the living body” (ON, 16: 626). He ar-
ticulated his theory of narcotism in the form of twelve propositions. The first was
an assumption that the life force is a variation of basic laws of physics: “Sensation,
Chloroform 161
motion, thought, and indeed all the strictly animal functions, are as closely con-
nected with certain processes of oxidation going on in the body, as the light and heat
of flame are connected with the oxidation of the burning materials” (ON, 16: 626).
Propositions two through six summarized the clinical and experimental findings
detailed in earlier installments. The seventh was a conclusion drawn from his long-
standing research into respiration: “The different parts of the nervous system lose
their power under the influence of the narcotics we are considering, in the same or-
der as in asphyxia—the privation of oxygen, as was observed by M. Flourens with
respect to ether, in 1847” (ON, 16: 627). The last five propositions summarized ear-
lier comments on the effects of narcotic vapors on muscular irritability, ordinary
combustion and oxidation, and putrefaction, as well as the narcotic parallel pro-
duced by a reduction in body temperature.
In Snow’s theory narcotic gases were an unusual kind of antioxidant that slowed
down the body’s oxidizing processes without combining with the blood’s oxygen. In
other words, the narcotized body behaved as if it were being asphyxiated; the body
could not make use of the oxygen present. Asphyxia and narcotism enjoyed a par-
allel relationship with respect to the molecular action of oxygen: “The relation be-
tween asphyxia and narcotism is this—that in asphyxia there is an absence of oxy-
gen, whilst in narcotism the oxygen is present, but is prevented from acting by the
influence of the narcotic” (ON, 17: 1053). In both conditions body temperature
dropped, nervous centers lost power in the same sequence, and the heart continued
to beat after breathing had stopped. When robust athletic individuals were narco-
tized or asphyxiated suddenly, convulsions or rigidity frequently occurred. When ei-
ther occurred gradually, convulsions tended not to take place. Both states were ac-
companied by delirium and languor. He noted that acute bronchitis, in which the
patient could not breathe, often produced delirium, strange visions, and dreams. He
speculated that the languid movement of the fetus in utero was due to the reduced
level of oxygen available via the placenta. And, as Snow had long known from his
efforts to resuscitate guinea pigs, muscular irritability was reduced by asphyxia and
suspended by narcotics.
In the final part of ON, he suggested that the antiseptic power of chloroform,
ether, and alcohol could result from their antioxidant properties. In those pre–germ
theory days, Snow reasoned that preventing oxidation functioned to prevent, or at
least inhibit, putrefaction. Essential oils, like lemon and peppermint oil, that pos-
sessed narcotic properties might be used to preserve meat. A dead rabbit that he in-
jected with lemon oil “kept very well for seventeen days” (ON, 18: 1091). Oxidation
was the key for Snow, and he considered biochemical oxidation similar to what took
place outside the body. According to Richardson, Snow believed he “could illustrate
all the meaning of this great practical discovery of narcotism on a farthing candle”
by showing the flame subdued but glowing under the influence of chloroform.44 In
Snow’s metaphor, narcotic vapors did not only inhibit combustion (oxidation) of a
candle flame, they inhibited the oxidation of bodily tissues. It was an analogy born
of experience and theory. In his 1841 paper “On asphyxia and the resuscitation of
still-born children” he had compared respiration with combustion and the lungs to
a furnace: “The whole body ought to be compared to the furnace, and the lungs to
the draught and chimney department—a view which better explains the uniform
diffusion of warmth throughout the body.”45 Respiration was combustion fueled by
oxygen, whereas asphyxia was deoxygenation of the blood. Years before he ever
learned of the properties of ether or chloroform, he had formulated the basics of ox-
idation and asphyxia that would inform the physiological model in his theory of nar-
cotism. He had witnessed, time and again, the incandescence of respiration under
chloroform. He had seen his patients’ breathing grow stertorous and sputter. He had
seen their skin glow red with unignited oxygen. Small wonder that most of the agents
he experimented with were potential fuels or coolants. Keeping someone under dur-
ing anesthesia was like knowing how to stoke a fire or run a combustion engine.
Chemical Affinity/A Balance of Forces

After four years of research, Snow had found the handle to a complex process, but
a fundamental question remained unsolved. “Having traced the narcotic action of
ether and other bodies to the more general law of their power of preventing oxida-
tion under a great variety of circumstances,” his “mind naturally inquire[d] by what
kind of power oxidation is thus prevented” (ON, 18: 1092). His hypothesis, offered
with “considerable diffidence,” was that
chemical attraction or affinity is a constantly acting force, by which each atom

of matter exerts an influence on all other atoms within the sphere of its attrac-
tion, . . . varying with the respective nature of the substances, and the physical
conditions in which they are placed. In this point of view, it will be seen that any
two substances in a condition to unite together might be prevented from doing
so by the intervention of a third body possessing a sufficient attraction for ei-
ther of the others; and it would not be necessary that this third body should en-
ter into chemical combination; for a balance of forces might be established, so
that the three substances would remain exerting reciprocal attractions for each
other, but unable to enter into more intimate union.
ON, 18: 1092
Snow reasoned that narcotic gases entered into the bloodstream and attracted the
oxygen with a force insufficient to bond with it. Even so, the force was strong enough
to counter the attraction between oxygen and “certain constituents of the blood and
tissues of the organs,” thereby inhibiting or preventing (depending on the dosage)
“those changes which are, in a manner, the essence of all the animal functions” (ON,
18: 1093). Although this hypothesis did not pan out, Snow proposed that chemical
affinity explained the stalemate he considered characteristic of narcotism: oxygen,
Chloroform 163
chloroform (or any other narcotic gas), and the materials of the body were coursing
through the bloodstream in a state of suspended molecular animation. He consid-
ered it possible that counteraffinity was a form of molecular anesthesia in which the
forces that explain normal oxygenation were neutralized.
He was pushing his theory of narcotism into a speculative realm well beyond what
anyone at the time could demonstrate in the laboratory. The Medical Society of Lon-
don (successor to the Westminster) would select him as their orator for 1853. The
address he delivered, entitled On Continuous Molecular Changes, contained a grand
theory of biochemistry that included speculations on the basic mechanisms of nar-
cotic vapors and the nature of epidemic diseases, chiefly cholera. Since the fall of
1848, an understanding of that dreaded disease and how to prevent its communica-
tion had rivaled inhalation anesthesia as major medical concerns in London.
Notes
1. Simpson’s announcement took place at a meeting on 10 November 1847; LMG 40 (19
November 1847): 906 contained a brief notice, but Snow already knew about it. During a mas-
tectomy at St. George’s Hospital on November 18, “The chloroform was administered by Dr.
Snow with his ether apparatus”; “Operations without Pain,” Lancet 2 (1847): 661. For Snow’s
remarks at the Westminster Medical Society on 20 November 1847, see LMG 40 (1847):
1030–31; and Lancet 2 (1847): 575–76.
2. Snow, “On narcotism by the inhalation of vapours,” 4: 334. Citations to the original se-
ries in LMG are placed parenthetically in the text as ON, indicating part number and pages.
2a. Lancet 2 (1847): 575. Subsequent quotations from this meeting taken from Ibid., 575–76.
3. PharJ 6 (1847): 357. Snow contributed a version of his ether saturation table to this is-
sue and made mention of Bell’s experimentation in OC, 20.

4. R. M. Glover, “On the properties of bromide and chloride of olefiant gas of bromoform,
chloroform, iodoform,” Edinburgh Medical and Surgical Journal 58 (1842). The essay was ex-
cerpted in PharJ 7 (1848): 348–49. For Snow’s citation, see OC, 112.
5. Richardson, L, xxxv.
6. For support of Snow’s observation, see Duncum, Inhalation Anesthesia, 178–81; Davi-
son, Evolution of Anesthesia, 137.
7. Potter, “Late fatal case at Newcastle,” Lancet 1 (1848): 214.
8. Although this detail does not appear in the inquest, it does appear in Snow’s definitive
account; see OC, 124.
9. This account is drawn from several sources: “Fatal application of chloroform,” Lancet 1
(1848): 161–62; J. Y. Simpson, “Remarks on the alleged case of death from the action of chlo-
roform,” Lancet 1 (1848): 175–76; “Fatal case of inhalation of chloroform,” LMG 41 (1848):
255. Snow, “Fatal chloroform case at Newcastle”(1848); “Remarks on the fatal case of inhala-
tion of chloroform (1848); and OC, 124.
10. “Fatal application of chloroform,” Lancet 1 (1848): 161–62.
11. “Royal Institution,” and “Experiment with chloroform at the Royal Institution,” Lancet
1 (1848): 162–63. Quotation from 163.
12. Times (3 February 1848) reprinted the report from the inquest.
13. “Medical news—another death from chloroform,” Lancet 1 (1848): 218–19. See also
“Fatal effects of chloroform,” Times (14 February 1848), 6.
13a. “Chloroform—its benefits and its dangers,” Lancet 1 (1848): 190.
14. “Remarks on the alleged case of death from the action of chloroform,” Lancet 1 (12
February 1848): 176.
15. Ibid., 175–76.
16. “The alleged death from chloroform at Newcastle,” Lancet 1 (1848): 240.
17. “The Fatal Chloroform Case at Newcastle,” Lancet 1 (1848): 296.
18. Snow, “Fatal chloroform case at Newcastle” (1848).
19. Snow, “Remarks on the fatal case of inhalation of chloroform” (1848), 277. See also
“Westminster Medical Society,” Lancet 1 (1848): 312.
20. Ibid., 277–78.
21. Snow, “On the discussion respecting chloroform in the Académie de Médecine of Paris”
(1849), 324. See also Snow, ON, 6: 614–19.
22. For example, see OC, 120–27.
23. Snow, “On the inhalation of chloroform and ether, with description of an apparatus”
(1848), 178.
24. Ibid.
25. For a longer summary and interpetation, see Ellis, introduction to reprint of ON.
26. Richardson, L, xxviii.
27. Duncum, Inhalation Anesthesia, 208.
28. Nitric ether was apparently difficult to obtain and required 1.5 drachms (5.3 ml) to
reach the second degree, whereas chloroform required only .71 ml to reach the same state.
Snow was quick to suggest that the anesthetic power of nitric ether was not unique: “I do not
look on [it] as a peculiarity of nitric ether, for I have met with it occasionally from chloro-
form and sulphuric ether when the vapour was introduced slowly” (ON, 3: 1076).
29. For accounts of the case, see “Police—Higgins, Margaret, and another, for stealing,”
Times (25 January 1850); Times (1 February 1850); and “Criminal trials—Higgins, Margaret,
and another, for robbery,” Times (9 February 1850).
30. “Police—Jopling, Chas., for attempted rape,” Times (1 May 1850).
31. “New crime, rape on young girls under chloroform,” Times (5 November 1847).
32. “Chloroform, use of, by thieves,” Times (5 October 1849).
33. Snow, “A letter to Lord Campbell” (1851), 13.

34. Quoted in Ibid., 14.
35. Ibid., 4.
36. Ibid., 14–15.
37. “The use of chloroform for criminal purposes,” PharJ 10 (1851): 488–89.
38. “Parliamentary proceedings—Prevention of Offences Bill,” Times (15 March 1851).
39. Shephard, JS, 136.
40. Snow included the other two agents from his table in this series of experiments, py-
roxilic spirit (methyl, or wood, alcohol) and acetone, but his main focus was on ethyl alcohol
(ON, 13).
41. See also the description in A. Taylor, Medical Jurisprudence, 320.
42. ON, 15: 753–54. In a footnote Snow wrote, “I used the same arrangement in giving
oxygen gas last year, at the request of Dr. Wilson, to a cholera patient in St.George’s Hospital.
The patient, who was in a state of collapse, was not saved or relieved by it.”
43. In 1851, using an apparatus devised by Regnault and Reiset described in the Annales
de Chemie et de Physique (1849), he confirmed his findings from autoexperiments on chlo-
roform, ether, and alcohol with extensive animal experimentation; ON, 16: 622–26.
44. Richardson, L, xvii.
45. Snow, “On asphyxia and the resuscitation of still-born children,”(1841), 223–24.

Cholera Chloroform and The Science of Medicine A L... - (CHAPTER 6 Chloroform)

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Chapter 6

W HEN ANESTHESIOLOGISTS WITH A TASTE FOR the his-

the Inhalation of Ether or On Chloroform and discover comprehensive, albeit dated,

Table 6.1. Quantity of chloroform that 100 cubic inches

to Snow’s mind an emerging pharmaceutical profile. Simpson had been empiri-

Table 6.2. Snow’s early experiments with chloroform

use with a slightly modified version of the temperature-controlled chloroform in-

Chemical Affinity/A Balance of Forces

chemical attraction or affinity is a constantly acting force, by which each atom

sue and made mention of Bell’s experimentation in OC, 20.

33. Snow, “A letter to Lord Campbell” (1851), 13.

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