which the alchemical pharmacists of the sixteenth and seventeenth
centuries sought so eagerly to obtain. Their characteristic property is
that they are basic, that is, that definite salts can be formed from
them by combination with acids. They all contain nitrogen, and have an
alkaline reaction.
Of all the popular vegetable drugs opium was the one more than any
other tortured to yield up its essence. The early laudanums and
extracts of opium aimed at this result, and preparations, such as the
Magisterium Opii of Ludovici of Weimar (born about 1625, and author
of “Dissertations on Pharmacy”), were used in the belief that the
quintessence had been in some degree secured. Robert Boyle experimented
with opium with the object of extracting its essential principle. The
process he adopted was first to treat the drug with calcined tartar
(salt of tartar), and then extract with spirit of wine. By this means
he obtained a solution which would be principally one of morphine.
In 1803 a French manufacturing chemist, working on an idea suggested by
Vauquelin, produced a crystallisable salt which was at first supposed
to be the active ingredient of opium. Experiments on animals seemed
to confirm this opinion, and the salt of opium, or “sel narcotique de
Derosne,” was believed to have solved the long-standing problem. The
product was described in the “Annales de Chimie” of February, 1804.
It was the substance now known as narcotine. Sertürner regarded it as
meconate of morphium, a misapprehension which was corrected by Robiquet.
In December, 1804, Seguin, a chemist who had been a demonstrator
under Fourcroy, and who subsequently got into trouble with Napoleon’s
Government on charges of having enriched himself out of drug supplies
to the Republican armies, read a paper to the Institute in which he
described a process which would yield morphine. For some unexplained
reason that paper was not published until 1814. Meanwhile Friedrich
Wilhelm Adam Sertürner, a pharmacist of Eimbeck, in Hanover, had
been working on Derosne’s salt, and had investigated more accurately
than anyone before him the composition of opium. His first report
was published in 1806, and in that he announced the discovery of
“opium-säure” (opium acid), but in 1816 he named this product “meconic
acid,” and explained how it was combined with an alkaline base which
he called “Morphium.” He described this as analogous to ammonia, and
prepared several salts from it. He came near to losing his life in the
course of his experiments as, misled by the comparative harmlessness of
Derosne’s salt, he had ventured on dangerous doses of his own product.
Consequently he was able to determine very accurately the therapeutics
of morphine at the same time that he announced its discovery.
“I flatter myself,” wrote Sertürner in 1816, “that chemists and
physicians will find that my observations have explained to a
considerable extent the constitution of opium, and that I have
enriched chemistry with a new acid (meconic) and with a new alkaline
base (morphium), a remarkable substance which shows much analogy with
ammonia.”
Sertürner’s discovery excited much interest and emulation, and its
importance was fully endorsed when, in 1831, the French Institute
awarded to him a prize of 2,000 francs “for having opened the way to
important medical discoveries by his isolation of morphine and his
exposition of its character.”
Before Sertürner had definitely established the nature of alkaloids,
Vauquelin had separated from tobacco a substance which he regarded as
its active principle, and which was undoubtedly an impure nicotine.
This was in 1809. The alkaloidal character of this extract was not,
however, recognised until 1828, when Posselt and Reimann produced it in
a pure form.
Vauquelin had in 1812 extracted daphnine from mezereon root, and in
describing his experiments had alluded to its alkaline character. For
this reason the credit of having been the first to have discovered an
organic alkali has been attributed to him; and when in 1818 Pelletier
and Caventou discovered an alkaloid in St. Ignatius’s beans, to which
they gave the name of strychnine, they stated that it had been their
original intention to designate the substance Vauqueline in honour
of the celebrated chemist who had first established the existence
of an organic alkali. It had, however, been pointed out to them by
distinguished members of the Academy that it would have been a doubtful
compliment to associate such an honoured name as that of Vauquelin with
such an evil (_malfaisant_) substance as this new product.
A number of chemists narrowly missed the discovery of quinine. As
early as 1746 Count Claude de la Garaye obtained from cinchona bark a
crystalline salt which he termed sel essentiel de quinquina. Two other
French chemists, Buquet and Cornette, subsequently introduced another
sel essentiel de quinquina. Both these products were simply kinate
of lime. A Swedish physician named Westerling announced in 1782 that
he had discovered the active principle of cinchona, and he gave it
the designation of vis coriaria. His product was in fact cinchotannic
acid. Seguin perhaps made the worst mistake of all the investigators
in coming to the conclusion that what was precipitated by tannin was
the essence of cinchona from a medicinal point of view, and he actually
recommended that gelatin should be substituted for cinchona in cases
when price was an object. Fourcroy made several attempts to ascertain
the true chemical constitution of the bark. In 1790 he separated a
resinous principle, mixed with some colouring matter, since called
cinchonic red. This he at first supposed was the essential medical
constituent of the bark. Vauquelin later adopted this erroneous
theory, and so missed his way. In 1792 Fourcroy got nearer to the truth
when he observed incidentally that the water in which the bark had been
macerated turned litmus paper green; and he also remarked that lime
water caused a greenish precipitate in the infusion. He did not pursue
the investigation, but his comment on what he had stated is noteworthy.
“These researches,” he said, “will no doubt lead to the discovery one
day of an anti-periodic febrifuge, which once known may be extracted
from various vegetables.” Berthollet followed on Fourcroy’s lines,
but came to the conclusion that the precipitate which lime water gave
with decoctions of cinchona was magnesia, which he believed was a
constituent of the bark in combination with hydrochloric acid.
In 1811 Gomez, of Lisbon, described a crystalline substance which Dr.
Duncan, of Edinburgh, had obtained from certain species of cinchona,
and gave to this product the name of cinchonine. Lambert later prepared
it in a state of considerable purity. But neither of these chemists
suspected its alkaline nature. In 1820 Pelletier and Caventou studied
the whole chemistry of cinchona and succeeded in showing that the
cinchonine of Gomez was a mixture of two alkaloids, to the second of
which they gave the name of quinine. Quinidine was isolated by Henry
and Delondre in 1833, and cinchonidine by Winckler in 1844, but the
name of the latter was given by Pasteur in 1853. Pasteur also produced
the alkaloidal derivatives cinchonicine and quinicine.
Robiquet had the idea that as the coffee plant belongs to the same
family of plants as the cinchonas it might be possible to find quinine
in coffee. In searching for it he isolated caffeine. This was in 1821.
In 1827 Oudry found an alkaloid in tea and called it theine. Jobst and
Mulder in 1838 proved that these alkaloids are identical. It is now
recognised that the alkaloids of cocoa, of guarana, and of Paraguay tea
are all the same substance, or closely related.
Pelletier and Caventou isolated strychnine from the St. Ignatius
beans in 1818, and brucine from false angostura bark (_Brucæa
anti-dysenterica_) in 1819; in the same years they obtained
veratrine from cevadilla seeds and white hellebore root; but it would
appear that in their investigation of cevadilla seeds, which was the
first to yield the alkaloid, they were preceded by a very short time by
Meissner. Pelletier and Magendie produced emetine from ipecacuanha in
1817, and Pelletier alone is credited with narceine in 1832. Codeine
was discovered by Robiquet in 1821 when he was examining a new process
for obtaining morphine which had been suggested by Dr. William Gregory,
of Edinburgh. Belladonna had been studied by Vauquelin and many
chemists after him, but it was not until 1833 that atropine in a state
of purity was isolated from it. This was accomplished simultaneously by
Geiger and Hess, two German chemists, and by Mein, a German pharmacist.
ANÆSTHETICS.
The greatest triumph achieved in any department of medicine, and
worthy, perhaps, to be described as almost, if not quite, the most
beneficent discovery in the world’s history, is that of the successful
employment of anæsthetics. This great glory belongs to the nineteenth
century. Indian hemp had been employed for centuries in the East,
mandragora had a classical reputation, and from time to time the
possibilities of hypnotism had been expounded by one or another of
its professors. But it is only within the past sixty years that the
terrible anxiety and suffering associated with surgical operations
have been so far mitigated as largely to increase the prospects of
success, and to annihilate the pain. To Sir Humphry Davy is due the
credit of first suggesting the line of advance towards this precious
goal by describing his experiences of the inhalation of nitrous oxide
gas which he found had the effect of relieving toothache and other
pains; “uneasiness swallowed up for a few minutes by pleasure,” were
his own words; and he foresaw the possibility of this agent being
employed as an inhalation “in such surgical operations as involved no
great effusion of blood.” That was in the year 1800. About 1830 Faraday
observed and noted the effect of ether on the nervous system, which he
stated was similar to that of nitrous oxide gas.
[Illustration: HORACE WELLS.]
The possibility of painless operations began to be imagined about
this time, but not much serious experimental work seems to have been
attempted. In 1842, Dr. Long, of Athens, Georgia, U.S.A., claimed to
have removed a tumour from a patient under the influence of ether, and
about the same time Dr. Jackson, of Boston, U.S.A., also professed to
have carried out successfully a similar operation. These experiments
have not been rigorously established, but there is no question about
the authenticity of the next. Horace Wells, a dentist of Hartford,
Connecticut, U.S.A., suffering from toothache, resolved to experiment
on himself. He induced a colleague named Rigg to draw a molar while
he was under the influence of nitrous oxide gas, and did not feel the
pain of the extraction. This was in 1844. Wells then, in association
with another dentist, named William Thomas Green Morton, started
to demonstrate the discovery publicly. The first exhibition was an
ignominious failure, and the two pioneers were derided as impostors.
Wells suffered so severely from his disappointment on this occasion
that he died insane a few years later. Morton, however, continued
his investigations, and he and the Dr. Jackson already mentioned
worked together on ether, and assured themselves of its anæsthetic
powers by experiments on animals. Morton then inhaled it himself on
September 30, 1846, and awoke from deep unconsciousness a few minutes
later, convinced of the reality of his discovery. Just then a patient
rang the bell. It was towards evening, but the visitor was shown
into the surgery. He was in agony with the toothache, and begged
the doctor to mesmerise him in the hope of getting some relief. The
nerve was so sore, he said, that he could not summon up courage
to have the tooth drawn. Morton, greatly excited, told his patient
that he could do better for him than mesmerising him. He could take
the tooth out without pain if he would consent. The sufferer agreed
eagerly, and Morton, with two assistants, proceeded to operate. A
handkerchief, saturated with ether, was applied to the mouth and
nostrils, and unconsciousness was produced almost immediately. A
tooth, a firmly-rooted bicuspid, was extracted without arousing the
patient. Then followed a minute of intense fear. The man remained
motionless, and Morton felt convinced he was dead. Seizing a glass of
water he dashed it into the face of this first subject, who at once
revived. “Are you ready to have your tooth drawn?” asked Morton. Rather
hesitating assent was given, and then the extracted tooth was shown to
the patient in the chair. His name, which ought to be recorded in the
annals of surgery, was Eben Frost.
On October 16, 1846, a tumour was removed from a patient at the
Massachusetts General Hospital, Boston. Morton administered the ether,
and Dr. Collins Warren, the senior surgeon, operated. The patient made
no sound, and after he recovered consciousness declared that he had
experienced no pain. “Gentlemen, this is no humbug,” said Dr. Warren to
the other surgeons who had witnessed the operation. Morton died in 1868.
The first operation under ether in Great Britain was performed by
Liston at University College Hospital in December, 1846. In January,
1847, James Young Simpson commenced to employ it in midwifery cases
in Edinburgh. Simpson had already acquired a high reputation as a
gynecologist, and was an enthusiast in his profession. Delighted though
he was with the results of his trials of ether, he felt sure that an
anæsthetic with more lasting effect could be found or made, and with
characteristic courage and pertinacity he and his two assistants,
Drs. Keith and Duncan, carried on personal experiments at Simpson’s
private house on such evenings as they could spare. At the same time
the scientific world was appealed to for suggestions. About this time
David Waldie, a Scotch pharmacist then settled in Liverpool, where
he was manager of the Liverpool Apothecaries Company, was visiting
Edinburgh and had a conversation with Simpson on his absorbing topic.
Waldie had had some special experience with chloric ether at Liverpool,
and had made experiments on its chemical character, which had led him
to the conclusion that the chloric ether then used was chemically only
a mixture of chloroform with some undecomposed spirit. Chloroform, it
must be remembered, was then but little known. Dr. Samuel Guthrie,
formerly an army surgeon, but later practising at Jewelsville,
Jefferson County, N.Y., published an account of a chloric ether he had
made from alcohol and chloride of lime in May, 1831. In October of the
same year Soubeiran in France, and a month later Liebig in Germany,
announced the discovery of a similar compound. None of these products
was an absolute chloroform, but all were heavy substances. Dr. Guthrie
called his chloric ether, and familiarly sweet whisky, Soubeiran’s was
a bichloric ether, and Liebig described his as a trichloride of carbon,
but Dumas showed in 1834 that the essential substance was a trichloride
of formyl, HCCl_{3} and a substitution product of marsh gas. He
invented the name chloroform. It appears too that another French
chemist, Flourens, in March, 1847, reported to the Academy of Sciences
of Paris some experiments he had made with chloroform on animals,
which indicated its anæsthetic properties; but probably neither Simpson
nor Waldie was aware of this paper. This was the chemical which
Waldie recommended to Simpson in the summer of 1847, and the chemist
promised to send some to Simpson on his return to Liverpool. A fire
in the laboratory of his establishment prevented the fulfilment of
this promise, and also, Waldie said, prevented him from experimenting
on himself with chloroform, as he had intended to do. Simpson got
chloroform from Duncan and Flockhart in Edinburgh, but did not expect
it would answer on account of its density. The sample was set aside
for some time, but on November 4, 1847, he and Duncan and Keith
resolved to test it. They all inhaled some from a tumbler, and almost
immediately became loquacious and hilarious. Then unconsciousness came
on, and Simpson, who was the first to recover, found Duncan under the
table, eyes staring, and snoring vigorously, while Keith was kicking at
the supper table. The experiment was repeated a few evenings later, and
this time a niece of Simpson was induced to take a turn. After inhaling
the vapour she fell asleep, murmuring “I’m an angel; I’m an angel.”
Simpson at once began the use of chloroform in his practice, and his
great reputation and powerful advocacy soon caused its general adoption.
[Illustration: SIR JAMES YOUNG SIMPSON, M.D.
(From a drawing by T. M. Pape, lent by the publishers of the _Century
Magazine_.)]
A MYSTERIOUS ANÆSTHETIC.
A strange and little known story is told by Professor Franck. Van
Swieten was a Dutch physician, a pupil of Boerhaave. He did not succeed
in his native land so well as he ought to have done, for he was a
devout Catholic. He went to Vienna, where he attained the highest
medical position and the utmost esteem from his patroness, the Empress
Maria Theresa. On May 1, 1771, three young gentlemen called on Van
Swieten and were shown into his study. The professor was then an old
man, 71 years of age.
“What do you desire, my children?” he asked, as he fingered his beads.
“We come to teach Van Swieten what he knows not,” answered one of the
young men.
“That is not difficult,” replied the veteran. Then they told him they
wished to show him a medicine new to the world, and as the doctor
smiled incredulously, one of his visitors added:
“Like the philosopher of old, we will say to Pain:--Thou art but an
idle word.”
Van Swieten was doubtful, but after further explanation he invited
them to come to his hospital the next morning and demonstrate their
secret. When they were gone he went to Maria Theresa and told her of
the interview. The Empress declared her intention of being present at
the experiment.
The next day when the three young men appeared at the hospital they
found Van Swieten and a veiled lady awaiting them. Certain chemicals
had previously been placed in retorts by them, and a mastiff was made
to inhale the product. The animal exhibited symptoms of inebriation,
and soon fell on the floor unconscious. One of the strangers made
a deep incision into the dog’s chest and covered the wound with a
surgical dressing. The animal showed no sign of pain, and shortly
afterwards recovered consciousness, got on his feet, and walked about
as if nothing had happened.
“This is indeed a miracle,” said the Empress.
“Would you dare to operate thus on a patient?” asked Van Swieten.
“Willingly, Master,” was the reply.
“Then operate on me,” said the Professor.
To this proposal, however, they demurred, and the Empress supported
their objection. An appointment for further experiment a few days later
was made, but when the day arrived Van Swieten was ill. He died on May
18, and Maria Theresa was at the time immersed in political troubles.
The sequel to that strange history has never been told, but some of the
old books tell of the “Holland Oil,” which is believed to have been
the mysterious medicament employed. Professor Franck thinks one of the
strangers was Gautier Van Decoren, a physician of Flemish Holland.
SYNTHETIC REMEDIES.
EARLY DISTINCTION BETWEEN INORGANIC AND ORGANIC CHEMISTRY.
The development of organic chemistry in the course of the nineteenth
century is a subject so vast that it is mentioned in this place with
something approaching despair. The great chemists who, in the latter
part of the eighteenth and in the early years of the nineteenth
century, had rescued their science from the superstitious and fantastic
theories and conceits which had encumbered it, Lavoisier, Priestley,
Scheele, Cavendish, Dalton, Fourcroy, Berzelius, and many others
who might be named, distinguished sharply between the products of
the mineral kingdom and those which they called organic, that is,
substances of vegetable or animal origin, combined, it was agreed,
under the influence of what was described as vital force. This force,
it was considered, inherent in living bodies, could never be imitated
in the laboratory, and its achievements were beyond human skill. It was
even doubted whether the elements composing organic substances were
subject to the same laws of combination as were those of the mineral
world.
Lavoisier, it is true, regarded organic bodies as consisting of
radical compounds, hydrocarbon radicals, as he called them, instead
of the metallic bases. His last scientific work was the investigation
of the statics of organic chemistry, and on this subject his clear
vision would probably have enabled him to anticipate many modern
conclusions. He had already recognised some of the transformations
of sugar, had analysed alcohol, and had declared that in animal and
vegetable chemistry no less than in the inorganic kingdom nothing is
ever destroyed, but that vegetation and animalisation are only inverse
phenomena of combustion and putrefaction.
SYNTHETIC ORGANIC COMPOUNDS.
Some isolated results of the artificial productions of organic
substances are recorded which do not seem to have been recognised as
challenging the reign of vital force. Scheele, in 1786, formed oxalic
acid by oxidising sugar by nitric acid; and in 1822 Döbereiner produced
formic acid, previously known as a distillate of ants, by oxidising
tartaric acid. In both these cases, however, the transformation was
essentially one from a previous organic substance.
The inauguration of synthetic chemistry is understood to date from
the year 1828 when Wöhler, then a professor of chemistry at Berlin,
produced a supposed cyanate of ammonium by the action of ammonium
chloride on silver cyanate. Wöhler was surprised to find the cyanate of
ammonium which he had obtained did not correspond with other ammonium
salts, but resembled, and as he afterwards proved, was identical with
the organic substance, urea, a crystalline compound which constitutes
about half of the solid matter dissolved in urine. Wöhler and Liebig
next collaborated in a study of organic substances, and one of the
early results of their investigations was the discovery of the compound
radical, benzoyl, as they termed it, C_{7}H_{5}O, which they found
could be combined with chlorine, bromine, iodine, sulphur, ammonium,
and other substances, always retaining its own individuality. It was,
in fact, a compound radical, and though it has never been isolated,
its compounds prove its character. Berzelius was so struck by this
discovery that he suggested the name of proine or orthrine, either
meaning the dawn, in substitution for benzoyl.
[Illustration: FRIEDRICH WÖHLER.
(From the Royal Collection of Etchings at Munich.)
Born at Eschersheim, near Frankfort, 1800; died at Göttingen,
1882. Wöhler’s notable discovery of the artificial production
of urea in 1828 is famous as the starting point of synthetic
chemistry.
]
Henceforward discoveries and theories based on them, or propounded to
explain them, so crowd the field that even in bulky volumes the story
is only told in outline. But several of the famous theories or laws or
expositions, on which modern chemistry relies, have been so fertile in
consequences that they must be very briefly mentioned.
SUBSTITUTION.