Discovery of Podophyllin.

Selected writings of John King:

The paper which follows was published by Professor John Uri Lloyd in the Western Druggist in December, 1893, and republished in the Eclectic Medical Journal in 1894, We reproduce it here for its historic bearing upon the history of podophyllin and Professor King's connection therewith.

Related entries: Concentrated Medicines - Important Remedies - Discovery of Podophyllin, Etc.

(This manuscript was prepared some years ago. If the same was published I have no record of the fact. It very properly follows the biography of Professor King, connecting the most conspicuous Eclectic remedy with his name.—L.)

DISCOVERY OF PODOPHYLLIN (Resinoid of Podophyllum)—the first Eclectic Resinoid—"As early as 1831 (American Journal of Pharmacy, January, 1832, page 273.) Mr. William Hodgson made a partial analysis of the rhizome of podophyllum, but overlooked the resin. In 1846 (Western Medical Reformer, April, 1846, page 176.) Dr. John King described a resinous substance that he then employed in his practice, identifying it as a resin and calling it a resin, as follows: 'I obtain only the resin, by extracting all that alcohol will take up [by tincturing the drug—Lloyd], then filter the alcoholic tincture, to which add an equal quantity of water, and separate the alcohol by distillation—the resin sinks in the water." (Preceding this, Professor King referred to the resin in the Philosophical Medical Journal of New York, 1844, Vol, 1, page 160.—L.) In 1847 (American Journal of Pharmacy, August, 1847, page 169.) Mr. J. R. Lewis made a good analysis of the drug, describing the resins, and stating that six or eight grains had been taken experimentally, operating as a drastic cathartic, accompanied by vomiting. Thus it is evident that King (1844) and Lewis (1847) independently wrote upon the subject; both referred to the substance under consideration, which King had used for some time preceding his published paper, and both of them called the substance a resin. King, however, preceded Lewis two years. If Lewis was acquainted with the recorded statements of Professor King, he neglected to refer to them. From that early day Professor King energetically and continuously held this resin before his classes, and in his writings advocated the use of resin of podophyllum as the Eclectic substitute for calomel. It became thereby firmly identified as an Eclectic remedy long before the regular' section recognized its value. In connection with this phase of the subject we find that the United States Dispensatory, the standard authority in regular (I use this term as applied to the dominant section of American physicians, because, as a rule, the gentlemen seem to prefer It to Allopathic. The term "Irregular" I do not consider opprobious, as it is used to apply to the minority.—J. U. L.) medicine at that period, preceding its tenth (1854) edition (and indeed thereafter) ignored King as a discoverer, and referred only to Mr. Lewis. In that edition (1854) brief mention is made of the notice Dr. Manlius Smith gave the resin in the American Journal of Pharmacy, 1852. In the eleventh edition (1858) the first reference is made to its then common name (derived from Eclecticism) in commerce as follows: 'It is called podophyllin.' But it was not commended as a therapeutical agent. In the twelfth edition (1865), the resin having become officinal in 1860, a creditable notice is given the substance. In contradistinction, The first edition of the Eclectic Dispensatory, King and Newton, 1852, devotes seven pages to, this drug, which establishes its paternity.

"In an early publication (The College Journal of Medical Science, Cincinnati, 1857, page 557.) Professor King stated that 'My introduction to its therapeutical action having been of a serious character,' and at the solicitation of the writer, who desired information concerning the subject, contributed the following interesting communication. This letter also bears testimony concerning the discovery and introduction of this, important drug:

"'PROF. J. U. LLOYD—Dear Sir: In answer to your request, I will state that my discovery of podophyllin was by no means a pleasant incident, and I will relate it to you as briefly as possible. In the fall of 1835, desiring to make an hydro-alcoholic extract of mandrake root (with the aid of potassa during evaporation) the tincture of the root, and its subsequently made infusion, were mixed together. In order to save as much of the alcohol as possible, this mixture was placed in a distilling apparatus, and when about one-third of the alcohol had been collected by the distillation, the operation was discontinued on account of approaching night. Upon opening the kettle the next morning, and stirring up the now cold mixture, previous to a reapplication of heat and continuation of the distillation, a peculiar substance was found deposited in it, which I at first thought from its appearance was some foreign material that had found its way into the liquid and become burnt or injured by the heat during the distillation of the previous day. While pondering over the matter, and still undetermined as to the nature of this deposit, I decided to investigate its action as a purgative, and accordingly administered about twelve grains (Italicised by the biographer.) to a patient, not supposing it to have much, if any, medicinal action. But I was soon brought to know the reverse. In an hour or two after having taken it the lady was attacked with hyper-catharsis and excessive vomiting, which continued for two or three hours before I was notified. I was truly alarmed at her condition, fully recognized the nature and power of the resin, as well as my responsibility in having permitted her to take a substance concerning the action of which I knew nothing. It was a serious lesson to me which I have never forgotten. I found her in extreme pain and distress, cramps in the stomach and extremities, with coldness and slight lividity of the surface pulse small and weak, almost incessant vomiting and purging, her condition greatly resembling that of one in the latter state of Asiatic cholera; she was apparently sinking rapidly. It is unnecessary to occupy time and space with the treatment pursued; suffice it to state that by a careful and persistent course of medication she recovered, but, unfortunately, was left with a chronic malady of the digestive organs which, as far as I know, was never removed.

"'These serious effects, together with many unpleasant surroundings at the time naturally associated with the event produced a very unfavorable impression concerning the resin, and several years passed before I mustered courage to try it again in smaller doses, and which attempt was greatly owing to a conversation with Prof. W. Tully, M. D., of Yale College, New Haven, Conn., who, upon having related to him my fearful initiation into the use and action of resin of podophyllin, advised me to test it in much smaller closes; during this conversation he informed me that cimicifuga likewise contained a resin, and which I subsequently succeeded in obtaining. After having succeeded in testing podophyllum resin in several varieties of disease, I called attention to it in the Philosophical Medical Journal, of New York, Vol. 1, page 160, 1844. (Also in Western Medical Reformer, April, 1846, page 176.—L.) About a year after this latter publication, being in the drugstore of the late Mr. W. S. Merrell, at that time located at the northwest corner of Court and Plum Streets., Cincinnati, Ohio, he called my attention to two samples, one of podophyllum resin., the other of cimicifuga resin, about an ounce or so of each, which he said were made according to my directions in the Western Medical Reformer, and inquired if they were anything like those I had produced, and I answered that they were, and questioned him whether the Eclectic physicians of Cincinnati had tried them; he stated in reply that he had not been able to prevail on any one of them to prescribe them. According to the promise given to Mr. Merrell, I shortly afterward gave Prof. T. V. Morrow, M. D., a few hints as to the value of these resins, and it was not long before communications appeared from the pens of Professors Morrow, Hill, and others, in which the remedial virtues of these agents were highly lauded; from which time podophyllin, more especially, has been employed extensively by all classes of physicians. Yours truly,

"'Cincinnati, June 14, 1887. JOHN KING, M. D.'

"A careful review of the literature, and an intimate acquaintance with those connected with the introduction and discovery of the substance, enables the writer to say that without a question the foregoing comprises an authentic record of this valuable drug, which is now of world-wide reputation. It was the forerunner of the class of preparations that followed under the name 'resinoid' or 'concentration.'"

The Biographies of King, Howe, and Scudder, 1912, was written by Harvey Wickes Felter, M. D.