Notes and Events 231

That you may be comforted in your great sorrow, and that you may
find solace in the active work of our noble calling is the earnest wish of
yours very sincerely
JOSEPH LISTER

ACKNOWLEDGMENT
I am grateful to Mrs. Mary Yates, Charles Straton's grand-daughter, for her kindness
in presenting these letters to the University of Kansas, and for allowing me to publish
their contents.
L. R. C. AGNEW

On the Nature of Siueet Oil of Vitriol

In the De artificiosis extractionibus of Valerius Cordus, published in
1561 by Conrad Gesner, there appears the first published procedure for
preparing a liquid called by Cordus sweet oil of vitriol ("dulce Vitrioli
oleum") by the distillation of a mixture of alcohol and sulfuric acid. A
translation of Cordus' own description follows:*
Take 6 oz. of strong wine that is very sharp and triply distilled and the
same amount of sour oil of vitriol. Mix in Venetian glass and place in
a small cucurbit with a narrow orifice. Seal the orifice very well with
clay arid leave it thus for a whole month or two. Then pour into a cucur-
bit to which is immediately attached an alembic. Place in a small furnace
and half cover it with ashes. Afterwards attach the receiver, seal the joint
carefully with clay, and extract the 6 oz. of strong wine which you poured
in—indeed for doing this more safely, place it in a hot water bath so that
the wine alone ascends separately from the oil. Now, when by using the
hot water bath you have extracted the 6 oz. of wine that had been added,
place what remains into the furnace so that the sand touches the middle
part of the cucurbit, attach a new, empty receiver (not a large one), and
seal the joint carefully with clay. Then light a gentle fire and gradually
draw out all moisture that is left in the cucurbit until no more is seen in
the bottom. The greatest care and diligence are always applied to moderate
the fire thus, lest the liquid should boil out continually up to the channel
of the alembic. For if the boiling reaches this, it cannot be calmed or
prevented from going over into the receiver and spoiling all the oil. In-
deed, it customarily boils very readily. Now, when you have drawn it
out gradually, immediately withdraw the receiver with its liquid, and you
will see that two things are contained in it, that is to say, a watery liquid
and an oily or fatty one. However, you will immediately separate one from
the other so that none of the watery liquid remains in the oil, for that
water spoils the oil. Also this same oil customarily spreads over the water
for the most part, especially if the wine which was previously added is
completely removed by the hot water bath, but you will be able immedi-
ately to distinguish the oil from the water by touch. For the oil is greasy,
the water not at all so. Then keep the separated oil for use.

* A complete translation of the thiid part of the De artificiosis extractionibus

has been published by G. K.. Tallmadge (Isis, 1925, 7, 394-411). The translation which
follows was made independently and then compared with Dr. Tallmadge's. No difference
in interpretation was apparent, but where certain of Dr. Tallmadge's expressions seemed
more pleasing, slight adjustments were made.
232 Journal of the History of Medicine: APRIL 1959
The importance of this passage is that it has been called the first pub-
lished description of the preparation of ethyl ether, and Cordus has been
credited with being the discoverer of ether.34 On the other hand, SudhofF
has argued persuasively that Paracelsus was the first to prepare ether; and
Darmstaedter1 has claimed that the procedure described by Cordus would
not result in the formation of ether at all but would yield instead diethyl
sulfate.
The properties ascribed by Cordus to his product do not agree well
with those either of diethyl sulfate or of ether. His sweet oil of vitriol
was described as floating on water and readily volatile, both of which
properties fit ether well but diethyl sulfate not at all. On the other hand,
Cordus also described it as oily ("pingue") and spoiled ("perdit") by
water, observations applicable to diethyl sulfate but not to ether. Leake:!
has emphasized the first two properties to bolster his argument and Darm-
staedter1 the second two to support his. It is indeed satisfying to be able
to report here that Cordus really did know what he was talking about,
that his product did have all four of these properties, and that, as in many
similar cases, the truth lies somewhere between the two opposing positions.*
The problem has been resolved merely by repeating the experiment,
following the directions given by Cordus. The only discrepancy to be
noted is that no distillate could be collected by heating on a hot" water
bath. It was necessary to reach a minimum temperature of 1250 C. before'
any liquid distilled over. Possibly Cordus was only speculating that a
water bath would be a good way to do this; or else his reagents may have
been considerably less anhydrous than our present-day ethanol and sulfuric
acid so that a large amount of unreacted, distillable alcohol remained in
the equilibrium mixture. To a temperature of 140° C. the primary prod-
uct in the distillate was found to be ethyl ether, notwithstanding Darm-
staedter's opinion that this could not form under these conditions. As the
temperature increased, diethyl sulfate could also be identified in the dis-
tillate, and finally above 1750 C. water distilled over.
The liquid collected between 1400 and 175° C. apparently represents
Cordus' sweet oil of vitriol. By virtue of its being a mixture of ether and
diethyl sulfate, it possesses the four properties observed by him which fit
neither component singly. It contains enough ether to be lighter than
water and enough diethyl sulfate to feel oily. It is spoiled on standing
with water since the ester is hydrolyzed. (Most likely what Cordus noticed
was the disappearance of the distinctive odor of diethyl sulfate.) It appears
to evaporate rapidly although, in truth, it is only its ether component
which does so. The only additional observation which should be made is
that Cordus probably lost much of the ether component and obtained a
product richer in diethyl sulfate than that obtained by using the efficient,
water-cooled condensers of today.
• Editor's Note: Dr. Robinson's conclusions as expressed in this note have been sub-
mitted to Dr. Leake, who has reported his hearty approval of them.
 Notes and Events 233
The argument, then, appears to be settled. Cordus did prepare ether;
but to say merely this seems to miss an important point. The significance
of any discovery can be judged only in its context. It must be stressed
that the later history of sweet oil of vitriol parallels and to a great extent
is independent of the history of ethyl ether and anesthesia. It was the
same sort of discovery as the discovery of America by Leif Ericsson—it did
not lead to the consequences which today we consider the important ones.
Nevertheless, sweet oil of vitriol has a long and distinguished history
in pharmacy, extending nearly to the present day. It was investigated
jointly by Robert Boyle and Isaac Newton.2 In the seventeenth century it
was known by many names, such as aqua Lulliana, aqua iemperata, and
oleum dulce Paracelsi. Finally it achieved lasting fame as Hoffmann's
anodyne (liquor anodyni mineralis Hoffmannii) when prepared and pub-
licized by the German physician, Friedrich Hoffmann (1660-1742). William
Lewis in his Materia Medico? of 1761 described the preparation of Hoff-
mann's anodyne by essentially the same procedure as that used by Cordus
two hundred years earlier, and he understood it to be a mixture of two
products, one oily and one very volatile. By 1818 the London Dispensatory
directed that Hoffmann's anodyne should be prepared by mixing together
specified quantities of its two components rather than obtaining the ill-
defined mixture in a single distillation. At the end of the nineteenth cen-
tury this preparation was still considered a very valuable one for preventing
nausea and as an anodyne and tranquillizer.8 It survived into the 1950
edition of the U. S. Dispensatory1' and disappeared only with the 1955
edition. This is a long history for any drug; and rather than thinking of
Cordus as paving the way for ether anesthesia, it seems appropriate in this
Miltown age to regard him as the first man to synthesize a tranquillizer.
Finally, let me stress again, the sweet oil of vitriol of the early chemical
literature cannot reasonably be regarded as a single compound. It makes
sense only to consider it a mixture of diethyl ether and diethyl sulfate.
TREVOR ROBINSON

REFERENCES
1. DARMSTAEDTER, F. Zur Geschichtc dcs Athers. J. prnkl. Chem., 1928, 120, 74-88.
s. LA WALL, C. H. Four thousand years of pharmacy. Philadelphia, J. B. Lippincott Co.,
1927, pp. 349-350.
3. LEAKE, C. D. Valerius Cordus and ihc discovery of ether. Isis, 1925, 7, 14-24.
4. LEAKE, C. D. Historical notes on the pharmacology o£ anesthesia. ]. Hist. Med., 1946,
', r>73-582-
5. LEWIS, WILLIAM. An experimental hislor\ of the materia mcAica or of the natural
and artificial substances made use of in medicine. London, H. Baldwin, for the
author, 1761, pp. 581-582.
6. OSOL, ARTHUR and FARRAR, G. E. Dispensatory of the United States of America. Phila-
delphia, J. B. Lippincott Co., 1950, p. 445.
7. SUDHOFF, KARL. Valerius Cordus, der Ather und Theophrast von Hohenheim. Sud-
hoffs Arch. Gesch. Med., ig2g, 21, 121-130.
8. WOOD, G. B. and BACHE, FRANKLIN. The Dispensatory of the United States of Amer-
ica. Philadelphia, J. B. Lippincott & Co., 1895, pp. 1266-1267.