Chapter XXIII: Part III: Contributions From the Journal: Nostrums (4)

“Chloral and the bromids, before the recognition and advent into
medicine of Pasadyne (Daniel’s Concentrated Tincture of Passiflora
Incarnata), were widely employed in all turbulent states of the
psyche and, notwithstanding their many untoward, even sometimes
dangerous effects, were held in high favor by physicians. For
that matter, they still retain some of their old-time popularity,
but since the superior value of Pasadyne (Daniel’s Concentrated
Tincture of Passiflora Incarnata) has been demonstrated to the
profession’s satisfaction, the erstwhile high esteem in which
chloral and the bromids were held, is fast waning and ere long
Pasadyne will have crowded them out.”

The reasons why the drug passiflora was not deemed of sufficient value and hence, along with the Daniel preparation, was refused recognition, are given in a report of the Council on Pharmacy and Chemistry.--(_Abstracted from The Journal A. M. A., March 8, 1913._)

PAS-AVENA

How Its Formula Evades the Food and Drugs Act

Pas-Avena is a widely advertised “nerve sedative and hypnotic.” The preparation is put on the market by the Pas-Avena Company of New York City. As a headliner the advertisements of the remedy state that the formula has always been on every bottle, and this, The Journal states, has a twofold object: It aims to give the impression that the preparation is non-secret, and it is calculated to inspire confidence in the--apparently--scientific nature of the product. As a matter of fact, it should do neither. The preparation is essentially secret in its composition because of the presence in the formula of an unknown quantity and the liability to change of formula at the whim of the manufacturer. On the bottles some time ago the following formula was given:

Each tablespoonful contains:
Passiflora 20 minims.
Avena sativa 10 minims.
Somnalgesine (C_{30}H_{28}N_{5}O_{6}) 2 grains.

The first two ingredients are plants in whose therapeutic value but little confidence is placed. Somnalgesine, the third constituent, is a secret preparation, the chemical formula of which the manufacturers were kind enough to add. To a chemist, however, the formula is absurd and impossible, and is included either because of the manufacturer’s ignorance or because of an intent to deceive the profession. Since the Food and Drugs Act became law, the label of Pas-Avena has been changed to read:

Alcohol 8.37 per cent. by volume.
Anilipyrine 16.00 grains per fluid ounce.
Guaranteed under the Food and Drugs Act of June 30, 1906.

Substitution of anilpyrine for somnalgesine gives little more information. Chemists may recognize this as a name applied to a mixture said to be formed by the fusion of two molecules of antipyrin and one molecule of acetanilid. To physicians, however, the name carries with it the same mystery as did somnalgesine. Attention is directed to the fact that by publishing the guarantee under the pure food laws the company presumes to disperse all doubt and criticism, assuming that the majority of physicians will be satisfied with the guarantee as it stands. Inasmuch as the preparation contains acetanilid and antipyrin, however, the manufacturers are disregarding that part of the Food and Drugs Act which requires that the name of the parent substance--in this case acetanilid and antipyrin--be put in parenthesis. The laws are so well defined that physicians appear to be content to do nothing, firmly believing that they are safe from the defrauding methods of unscrupulous manufacturers.--(_Abstracted from The Journal A. M. A., March 7, 1908._)

Proprietary House Insolvent--and Physicians Lose?

The Pas-Avena Chemical Company, whose product, Pas-Avena, was exposed in The Journal a few months ago, has recently failed, according to our pharmaceutical exchanges. In recording the fact, one journal says:

“It is reported that considerable stock of this company had been
sold to physicians.”

At this time, when physicians are importuned daily to invest money in various wildcat pharmaceutical concerns, this sentence might well be used “to point a moral or adorn a tale.”

PERTUSSIN

Dr. L. A. Roberts, Dorchester, Mass., writes: “Please tell me what the composition of Pertussin is.”

Pertussin is a proprietary whooping-cough remedy manufactured by the Kommandantan Apotheke, Berlin. A “physician’s sample” bottle of this preparation sent out by Lehn & Fink bears a label on which appears the following:

“100 parts Pertussin contains:
1/2 Ol. Thymi, et Thymol
21-1/2 Ext. Thymi ‘Taeschner’
50 Saccharum
2 Glycerinum
6-1/4 Alcohol
19-3/4 Aqua Destillata”

While it never has had much vogue in this country it has been and still is used in Germany. It belongs to that class of vegetable preparations which, since they contain no distinctive principle, are difficult to analyze--particularly as concerns the “joker” in the formula, in this case “Ol. Thymi, et Thymol” and “Ext. Thymi ‘Taeschner’”--hence there has been much dispute in Germany as to the composition of this nostrum. In general, it appears that whatever virtues it has are due to some preparation of common thyme in a menstruum containing water, sugar and alcohol. At one time the preparation was found to contain potassium bromid; but tests recently made in the A. M. A. Chemical Laboratory indicated the absence of either bromids or iodids.--(_From The Journal A. M. A., March 8, 1913._)

PHENALGIN--A TYPICAL EXAMPLE[AX]

[AX] For reports and articles on other coal-tar preparations, see pp. 9, 115, 244, 268, 305.

Last June[112] we devoted considerable space to the extravagant therapeutic claims made for “Phenalgin” by its venders. At this time we propose to refer to the misinformation--to use a conservative term--that the Etna Chemical Company has promulgated regarding the composition of their preparation.

[112] See The Journal A. M. A., June 24, 1905, p. 1997.

In June, 1905, the Council on Pharmacy and Chemistry officially published to the medical profession of the United States the information that repeated examinations showed that “Phenalgin” is a simple mixture of acetanilid and sodium bicarbonate or ammonium carbonate. So far as we know, no direct denial of the truth of this has been made. There has appeared what we presume is meant as an answer; it is couched in this sentence,

Phenalgin is just what we have always said it to be.

From this expression--which has been repeated in bold, black letters in practically all the advertisements since last June--we presume that we are to understand that in the past they have stated what it is.

It would have been just as easy and more satisfactory if the Phenalgin people, instead of saying: “Phenalgin is just what we have always said it to be,” had said what it is, since the average physician has neither the time nor the inclination to look up their literature.

For the benefit of those who desire to know what the venders of Phenalgin “have said it to be,” we have gone over their advertising literature of the past, with the following results, which are in the form of quotations from their advertisements:

An American Coal-Tar Product--Phenalgin--the only synthetic
stimulant, non-toxic, antipyretic, analgesic and hypnotic.

Phenalgin is the ONLY ammoniated Synthetic Coal-Tar Product made
from Chemically Pure Materials [What have the Ammonol people to say
to this?--Ed.]

A synthetic Coal-Tar Product of the Amido-Benzine series,
containing Nascent Ammonia.

These two chemicals [“stimulant ammonia of coal-tar origin” and
“chemically pure phenylacetamid”] combine under certain conditions
so as to obtain a produce which he [Dr. Cyrus Edson] named
Phenalgin or Ammoniated Phenylacetamide.

Phenalgin is a compound of peculiar character which can not be
extemporaneously made into tablets from the powdered drug, without
seriously changing and impairing its medicinal qualities.

We believe these quotations are sufficient to show what the Etna Chemical Company has “always said it to be.” In going over the literature for several years past we find the above stated in the same, or similar, words in nearly all of it. From the above four statements may be deduced: 1. They have stated that Phenalgin is a synthetic[113] preparation; 2, they have conveyed the impression that Phenalgin is a chemical compound; 3, they have announced repeatedly that it is the “only” preparation of the kind, and 4, they have claimed that Phenalgin is non-toxic.

[113] Dunglison’s Dictionary: “Synthetic--In chemistry the formation of a more complex body by the union of simpler bodies.” Dorland’s Dictionary: “Synthesis--The artificial building up of a chemic compound by the union of its elements.” “Union” is not mixing.

We believe that these four statements represent in plain English what the above quotations mean. They are all absolutely false. Phenalgin is not synthetic; it is not a chemical compound; it is not the only ammoniated phenylacetamide, or the only acetanilid mixture containing carbonate of ammonium--and it is most positively toxic.

In one place it is stated that Dr. Cyrus Edson

Employed his great facilities for chemical research and
opportunities for chemical experiment for the purpose of producing
a formula for a combination of stimulant ammonia of coal-tar origin
(sic) and chemically pure phenylacetamide, also a coal-tar product
... which he named phenalgin, or ammoniated phenylacetamide.

In another place we read that Phenalgin is made

Under the immediate personal supervision of the original inventor
of ammoniated coal-tar products.

By comparing this last quotation--which is from a current--1905--advertisement--with the preceding one it will be noticed that we are asked to believe that Phenalgin is made “under the immediate supervision of” Dr. Cyrus Edson--and yet Dr. Cyrus Edson died Dec. 2, 1903. This is equal to Lydia Pinkham’s prescribing for the suffering women of America when the dear old soul had been dead for over twenty years.

We have before us a full-page advertisement taken from a recent number of a weekly medical journal, which possibly is meant as an answer to the announcement of the Council on Pharmacy and Chemistry that Phenalgin is a simple acetanilid mixture. The advertisement is divided into two parts; the first part is as follows:

+-----------------------------------------------------------+
| FACTS ABOUT ACETANILIDUM (ANCIENT HISTORY) |
| |
| It has long been recognized that Acetanilidum and most |
| other coal-tar products are apt to exert a depressing |
| influence upon the heart, but there has never been any |
| doubt about its great value as a pain reliever and |
| temperature reducer. Its therapeutic value has, however, |
| been practically nullified by the danger of cyanosis and |
| other evils caused by its well-known depressant action |
| and the difficulty of obtaining it in a pure state. It |
| being known that certain deleterious substances are often |
| to be found in Commercial Acetanilidum and that much of |
| the injurious effect attributed to this drug is entirely |
| traceable to these impurities.[114] |
+-----------------------------------------------------------+

[114] This sentence is not complete, but, of course, this is immaterial. Little things like an incomplete sentence do not count.

The above are also falsehoods. The therapeutic value of acetanilid is not “practically nullified ... by the difficulty of obtaining it in a pure state.” Neither is it true that “much of the injurious effect attributed to this drug is entirely traceable to these impurities.” While deleterious substances may be found in _commercial_ acetanilid, they are not found in the substance offered as medicinally pure acetanilid by reputable firms. Pure medicinal acetanilid is a cheap article, costing less than 30 cents a pound, for it is a substance that is easily and cheaply purified. It is a fact that the injurious effects are in the acetanilid itself and not in the impurities it may occasionally contain.

The second half of the advertisement in part is as follows:

+-----------------------------------------------------------+
| FACTS ABOUT PHENALGIN (MODERN SCIENCE) |
| |
| More than a decade ago the late Dr. Cyrus Edson, then |
| Health Commissioner for New York City and New York State, |
| recognizing the value of chemically pure Acetanilidum as |
| a therapeutic agent, if it could be deprived of its |
| depressant quality, employed his great facilities for |
| chemical research and opportunities for chemical |
| experiment for the purpose of producing a formula for a |
| combination of Stimulant Ammonia of coal-tar origin and |
| chemically pure Phenylacetamide, also a coal-tar product. |
| These two chemicals combine under certain conditions so |
| as to obtain a product which he named Phenalgin or |
| Ammoniated Phenylacetamide. |
+-----------------------------------------------------------+

There is more of the same character. In the first place, we call attention to the fact that “Phenylacetamide” is substituted for “Acetanilidum” when it is to go into Phenalgin. To mystify is one of the “tricks of the trade.” Few physicians keep up with chemical terms and, therefore, are not supposed to know that Phenylacetamide is one of the chemical names for Acetanilid.

The reference here to Dr. Cyrus Edson brings up another fact, and that is that the Etna Chemical Company tries to convey the idea that Dr. Edson was the originator of Phenalgin. We have always understood that Dr. Cyrus Edson had something to do with pushing Ammonol and, if we remember rightly, got into some trouble thereby. We do not know the exact facts, but the following letter shows that he had a leaning toward another “ammoniated phenylacetamid.” The letter is dated “New York, Oct. 6, 1894,” and is addressed to the “Ammonol Chemical Company.”

“During the past six or eight months I have used Ammonol
extensively in my private practice. I have found it excellent
in the treatment of neuralgias and for rheumatism. I have also
verified your statement in two cases that were suffering from
alcoholism. My experience justifies me in saying that it is the
safest and best of the analgesic coal-tar derivatives.

“Very truly yours,
Cyrus Edson, M.D.”

It may be of interest to know that the principal member of the firm of the Etna Chemical Company was at one time a member of the Ammonol Company, and it is usually understood, we believe, that Phenalgin is practically the same as Ammonol--in fact, the analyses published regarding the two preparations show this to be a fact.

We must make one more quotation:

It makes little difference to a physician whether Phenalgin is
a mixture or a compound or a synthetic, with a name that would
destroy the orthographic balance of the universe, provided it is
just what he has always found it to be.

Very complimentary to the intelligence and common sense of physicians, is it not?

Suppose some fellow should get up a scheme to exploit a mixture of quinin and some cheap, harmless substance, say, starch--equal parts of each. Suppose he gives it a fanciful name, puts it on the market at a high price, say $1.25 an ounce, and announces it as a new synthetic with wonderful therapeutic qualities. Suppose that the schemer then adopts the nostrum vender’s methods of fooling physicians into using his product by getting some to give testimonials, others to furnish write-ups, and then subsidizes medical journals through liberal advertising to print both the testimonials and the write-ups. The preparation would, of course, prove to be a good thing if it were used in liberal quantities where quinin would ordinarily be used, and some patients using it would get well even if quinin were not indicated. Then with the psychologic effect of the testimonials, the write-ups, and good, strong claims rightly pushed, unthinking physicians would do the rest. And then, after a while, when the schemer had gotten to the point where, each year, he was making a fortune out of his preparation, suppose some “self-appointed chemists” should examine into the preparation and discover that it was nothing but quinin and starch, and so announce to the doctors of the country; what would the doctors say? That it makes little difference “provided it is just what he has always found it to be!”

This analogy is not far-fetched, for it is practically what has been done with Phenalgin. One difference is that since quinin costs as much per ounce as acetanilid does per pound, the profits on the acetanilid mixture would be sixteen times greater than that of our imaginary preparation. Another difference is that acetanilid is really a dangerous drug, unless used with care, both in its immediate and in its remote effects; quinin is far less so.

“Little difference” indeed, whether we are being buncoed or not! Evidently!

In conclusion, we charge the Etna Chemical Company with intentionally misleading and deceiving the members of the medical profession, in that the said company has in its literature and its advertisements conveyed the impression (whether directly stated or not): First, that its preparation, Phenalgin, is a synthetic compound; second, that Phenalgin requires special skill in its preparation; third, that Phenalgin has therapeutic values which it does not possess; and, fourth, that Phenalgin is non-toxic.

We also charge that on account of these and other misrepresentations, this company has inveigled physicians into prescribing and using a simple mechanical mixture of common well-known cheap drugs--for which an extravagantly high price is charged--under the supposition that this combination of cheap drugs is a chemical compound of special and peculiar merit as a therapeutic agent, and, therefore, worthy of their confidence.

Our object in again giving space to this preparation--and practically all we have said applies to the other acetanilid mixtures that are exploited under fictitious names or as chemical compounds (such as ammonol, antikamnia and salacetin or sal-codeia--Bell)--is to impress on physicians, by a typical example, the shamefulness of the deceptions practiced on them by nostrum manufacturers to the great injury of the public and of the medical profession.

A Pharmaceutical Secret Which Should Not Be Lost

Dr. Gregory Costigan, New York City, writes under date of January 21, as follows:

“I have been carefully reading and enthusiastically approving your
articles on the nostrum evil, and have been impressed more than usual
on the existence of quack advertising in medical journals as set
forth in last paragraph and quotation on page 206, bottom of first
column, of your issue of Jan. 20, 1906.

“In _Merck’s Archives_, page 11, we are told in an advertisement on
‘Phenalgin’ that it ‘is a compound of peculiar character which cannot
be extemporaneously made from powdered drug’ and ‘our process of
manufacturing tablets is coincident with the manufacture of Phenalgin
and is the result of a long series of careful experiments by which
we are able to produce tablets of Phenalgin in a friable condition
without losing any of its _volatile_ constituents or undergoing
chemical changes from heat or moisture’! Inasmuch as Phenalgin
tablets are not covered with a waterproof coating I think this is
a remarkable statement to make, and the manufacturing of a drug
coincident with the manufacture of a tablet must be a very remarkable
performance, especially because it ‘retains the full therapeutic
value of the drug unimpaired’ while the advertisement asserts that no
other manufacturer is cognizant of this wonderful method. This ad. is
for the perusal of physicians only. The Etna Chemical Company owes it
to the medical and pharmaceutical world not to let this secret die
with the company’s dissolution. It owes it as a duty to the coming
generations of science immediately to jot down the full data of this
wonderful performance, to put it away in an age-proof safe and not
allow it to be lost to humanity as were a great many other arts that
were well known to the ancients. Let them keep it secret now and
profit by it, but do not let it be lost to posterity.”--(_From The
Journal A. M. A., Jan. 13, 1906, and Jan. 29, 1906._)

An Ethical (?) Proprietary Exploited Under Fraudulent
and Lying Claims

+-------------------------------------------------------------+
| “PHENALGIN IS JUST WHAT WE HAVE |
| ALWAYS SAID IT TO BE.” |
| --_Etna Chemical Co. in 1905._ |
| |
| “Phenalgin is a synthetic “Unlike the coal-tar synthetic, |
| coal-tar product.” phenalgin is a stimulant |
| --_Etna Chem. Co. in 1898._ rather than a depressant.” |
| --_Etna Chem. Co. in 1910._ |
| |
| TEMPUS OMNIA REVELAT! |
+-------------------------------------------------------------+

“Phenalgin is a synthetic coal-tar product”--thus ran the advertisements some years ago, when the medical profession was willing to take--or was compelled to take--the word of the manufacturer of proprietary remedies at its face value. Then the Council on Pharmacy and Chemistry was brought into existence. One of the first pieces of work done by the Council was the publication of the results of a number of analyses of headache powders. Phenalgin was among them. Analysis showed that Phenalgin was not a synthetic but a simple mixture of the following ingredients in the proportions given:

Acetanilid 57 parts
Sodium bicarbonate 29 parts
Ammonium carbonate 10 parts

The Etna Chemical Company, which puts out this product, was considerably disturbed by the Council’s exposure. It “came back” at the American Medical Association with the slogan “Phenalgin is just what we have always said it to be.” What, up to that time, the Etna Chemical Company had “always said” Phenalgin to be, was:

1.--Phenalgin is a synthetic.
2.--Phenalgin is the only preparation of the kind.
3.--Phenalgin is non-toxic.

These, in brief, were the three things that Phenalgin had been asserted to be. Each statement has been proved to be a definite and unequivocal falsehood. Phenalgin is not and never was a “synthetic.” Phenalgin is not and never was the only acetanilid mixture containing carbonate of ammonium. Phenalgin is not and never was in any sense of the word non-toxic. Phenalgin, in short, possesses the properties--both good and bad--that are common to acetanilid. It is a mixture that the merest tyro in pharmacy could dispense and for which any sophomore medical student could write a prescription without stopping to think. Acetanilid sells at 8 cents an ounce wholesale; Phenalgin at $1.00 an ounce, wholesale.

All these facts and many more were given to the profession by the Council on Pharmacy and Chemistry in The Journal more than six years ago--before even the Food and Drugs Act came into effect. After that law became operative, the Etna Chemical Company was compelled to say something on the label that it had never said before, namely, that Phenalgin contained 50 per cent. acetanilid. But the law not only required them to add a fact to their label, but it also compelled them to remove a falsehood. When the pure food law went into effect, Phenalgin was labeled a “malaria germicide.” It is not a malaria germicide and never was a malaria germicide, and the Etna Chemical Company dared not risk taking the question into court so it removed the statement.

Unfortunately the Food and Drugs Act exercises no control over the lying statements that may be made for drugs elsewhere than on the label. So it is that physicians within the last two or three weeks have received a booklet on Phenalgin containing the following assertions for this acetanilid mixture:

“Without the slightest harm, injury or depressing effect.”

“Is never followed by depression.”

“Its prolonged administration does not give rise to destructive
blood metamorphosis.”

“Is of great value in the treatment of neuralgia (especially in the
anemic.)”

“Freedom from the deleterious action or habit-forming tendencies of
the opiates.”

“It aids in destroying the malarial parasite.”

“Safest and most dependable of analgesics.”

It will be seen by this that while the Food and Drugs Act has forced a certain degree of truthfulness on the Phenalgin labels, the advertising matter is as fraudulent and as untruthful as ever it was. It is true that the assertion that it is a synthetic is no longer made, possibly because the medical profession has been so thoroughly enlightened on the much-overworked “synthetic” fraud that the falsehood is no longer profitable. In other respects, the assertions are just as false as ever. It is said to have no depressing effect--and yet it is acetanilid. It is said to produce no habit--and yet it is acetanilid. It is said to have no injurious effect on the blood--and yet it is acetanilid. It is said to be the safest analgesic--and yet it is acetanilid. How long will the medical profession continue to be hoodwinked by means of such transparent falsehoods?

The Phenalgin concern takes much credit to itself because on the cartons in which the bottles of Phenalgin come, it is stated that the product is “for dispensing purposes only.” Yet, as a matter of fact, practically any layman can go to any drug store and obtain this product, for the druggist appraises this spectacular piece of Pecksniffian virtue at its face value--a joke. Why, if intended only for physicians, would it be necessary to include with every bottle a circular naming the diseases, for which this acetanilid mixture is supposed to be good--“headache,” “colds,” “lumbago,” “scanty menstruation,” “pain in any part of the body”--and why is the name of the product and of the firm making it blown into the bottle?

To sum up then, Phenalgin is as big a humbug as Peruna ever was. It is sold to-day under claims that are just as false as those used six years ago. The Etna Chemical Company is perpetrating a stupendous fraud on the medical profession to-day and it is doing it not only through the agency of the United States mail, but with the aid and support of the following medical journals--and others--in which the Phenalgin advertisement appears:

_Medical Record_
_New York Medical Journal_
_Pediatrics_
_Lancet-Clinic_
_American Journal of Surgery_
_International Journal of Surgery_
_American Medicine_
_American Journal of Obstetrics_
_Medical Century_
_Pacific Medical Journal_
_Dietetic and Hygienic Gazette_
_Medical Standard_
_Eclectic Medical Journal_
_Am. Jour. of Clinical Medicine_

It is conceivable that in some cases it is not easy for those editors and publishers of medical journals who insist on relying on their own judgment to satisfy themselves that certain preparations are not worthy of being advertised. No such difficulty occurs in the case of Phenalgin. Here the issues are clear cut. The product is exploited under claims that are both false and vicious and their falsity and viciousness are perfectly evident to any freshman medical student. The only charitable explanation of the appearance of the Phenalgin advertisements in the medical journals listed is that the editors and publishers have not given the subject the attention it deserves and to which their readers are entitled. Perhaps it would help if their attention were called to the matter by their subscribers.--(_From The Journal A. M. A., Jan. 27, 1912._)

PHENO-BROMATE

An analysis of this preparation made at the instance of the New Haven Medical Association, by its chemist, and sent by Dr. Charles J. Foote of New Haven to The Journal is in part as follows:

The package was marked “Sample package, Pheno-Bromate. The
Pheno-Bromate Company, New York, U. S. A.” The box contained a number
of tablets and a package of powders in papers marked, “Physicians’
10 grain powders, Pheno-Bromate.” The substance in the papers was a
white crystalline powder not homogeneous. It was completely soluble
in hot water. The hot water solution on cooling yielded a mass of
thin crystalline plates. This material was found to melt at 113.5 C.
It gave no color with ferric chlorid and a positive isonitril test.
The portion insoluble in ether amounted to 49.8 per cent. of the
powder and consisted of potassium bromid. Quantitative determinations
of potassium and bromin in the original solution confirmed this
result. In my opinion, the powder consists of approximately equal
quantities of acetanilid and potassium bromid. Qualitative tests of
the tablets indicated that they had the same composition except for a
small quantity of some excipient not entirely soluble in water. Yours
truly,

Herbert E. Smith,
Chemist New Haven Medical Association.

Before the Food and Drugs Act Pheno-Bromate was advertised as “a synthetic combination of the phenetidin and bromid groups, and not, as is the case with many analgesics and antipyretics, a mixture of various coal-tar derivatives” and as “the safest and best of all sedatives.” The dose recommended in most cases is 20 grains--equal to 10 grains each of acetanilid and potassium bromid. Since the Food and Drugs Act has gone into effect its label states that it is “a perfect combination of a phenol and bromin derivative containing 282 grains of acetphenetidin, U. S. P., per ounce.” What a boon it was to mendacious manufacturers that the patent rights on phenacetin expired before the Food and Drugs Act went into effect.--(_Abstracted from The Journal A. M. A., July 14, 1906, and April 18, 1908._)

PHENOLPHTHALEIN

Phenolphthalein has long been used as an indicator in chemical reactions, but its use as a therapeutic agent[115] is comparatively new. When its laxative properties were first discovered it was exploited as a proprietary in Germany, and it was not long before the enterprising manufacturers in this country saw in it a potential gold mine and now nearly every proprietary drug manufacturer in this country has coined a proprietary name for it and is exploiting it, either alone or in combination with one or more other laxatives, and with more or less unwarranted claims.

[115] Those who wish to study the action and use of this drug further will find references to articles in The Journal as follows: The Journal, Jan. 5, 1907, pp. 64 and 70; March 30, 1907, p. 1133; April 20, 1907, p. 1351; Nov. 21, 1908, p. 1782; Nov. 28, 1908, p. 1886. The first page mentioned discusses the introduction of phenolphthalein into medicine.

Phenolphthalein itself has certain pretty well defined properties, but when a little of some other drug has been added wonderful therapeutic possibilities are claimed for the combination. The drug also has a definite market value and the pure substance in the form of powder, tablets or pills could not be sold at a price greatly in excess of the market value. Thus manufacturers, from business policy, add to it other drugs. There are now on the market numerous more or less secret and “fancy” preparations of phenolphthalein for which a price is charged out of all proportion to the value of the preparation. Among these are:

Phenolphthalein Laxative (_El Zernac Co._).
Exurgine (_Bischoff & Co._).
Probilin (_Schering & Glatz_).
Prunoids (_Sultan Drug Co._).
Laxine (_Columbus Pharmacal Co._).
Phenolax Wafers (_Upjohn Co._).
Laxaphen (_Parke, Davis & Co._).
Phenalein (_Pax Chemical Co._).
Thalosen (_Abbott Alkaloidal Co._).
Laxothalen Tablets (_Pitman-Myers Co._).
Veracolate (_Marcy Co._).

And additional preparations are still coming out! Some of the preparations contain only the phenolphthalein with a coined non-descriptive proprietary name attached, but most of them contain in addition one or more of such drugs as cascara, sulphur, prune, senna, salicylic acid, ipecac and aromatics. The exploitation of phenolphthalein in this way gives opportunity to the manufacturers to make all sorts of strong claims, some of them directly contradictory, for their preparations. For instance, Phenolax, which is said to contain phenolphthalein and cane sugar, is claimed to be “a great success for all forms of constipation, intestinal atony and hepatic torpor.” Of Laxothalen, which is said to contain phenolphthalein, aromatics and sugar, it is stated that “its action is confined to the bowel and it has practically no hepatic action.” Of Prunoids, which is said to contain phenolphthalein, cascara, de-emetized ipecac and prunes, we have the old familiar statement that “the harmonious blending of the several ingredients will give results that cannot be obtained through their use separately, nor will their use be followed by after-constipation.”

At the time phenolphthalein was beginning to be exploited in this country The Journal[116] suggested that physicians who wished to try the remedy should prescribe it under its own name and not under fancy, coined names. Since phenolphthalein occurs in the form of an insoluble and tasteless powder there is no reason why special pharmaceutical preparations of it should be placed on the market. It can be prescribed in powder form, in pills, capsules or tablets. Thus given, the true therapeutic action of the drug would be apparent and its actual value arrived at.

[116] The Journal, March 30, 1907, p. 1133.

The vice of this unscientific habit of prescribing names instead of drugs is stated in a forcible way in a letter received from Dr. V. E. Simpson, a teacher of materia medica and therapeutics in the medical department of the University of Louisville. He says:

“Recently P. D. & Co.’s representative left on my desk a sample
labeled ‘Laxaphen.’ The formula given is: phenolphthalein, gr. viii;
salicylic acid, gr. 3/5, in each fluidounce, ‘incorporated in a
palatable chocolate base.’ Now, in the first place, this name is one
that the public will easily learn and will soon call for; in the
second place, it is not a name that carries with it even a suggestion
of its contents; and, finally, the physician acquires the habit of
mechanically prescribing names instead of drugs, and in the burdening
of his memory with the myriad of fantastic labelings he finds it
impossible to remember even the drugs any one contains, much less the
exact proportions of those drugs. Then suppose that a consultation
is had; the consultant asks what is being given and the attendant
answers that he is giving ‘laxaphen.’ The consultant, perhaps, has
not been sampled and inquires about it; the attendant must answer.
‘Oh, it contains some phenolphthalein and a salicylate, but I have
forgotten the exact proportions. I have the literature on my desk.’
Had he used U. S. P. and N. F. remedies, which the consultant and
every other doctor in the land has access to and should have some
knowledge of, this embarrassment would not occur.”

All of the above should remind the physician that he should write simple prescriptions, for drugs whose action he knows, adapted to the particular case and not for money-making combinations under fanciful, non-descriptive names exploited by the proprietary manufacturers. In this way he will not only save money for himself and his patients, but he will be giving them exact and effective treatment, he will know exactly what he is giving and learn for himself its effect, and he will be following the only method which entitles him to be called a scientific physician.--(_From The Journal A. M. A., April 30, 1910._)

MIXED VACCINE AND PHYLACOGENS[AY]

[AY] A reprint of articles on the subject of Phylacogens originally published in The Journal is issued under the title “The Phylacogens: A Menace to Rational Therapy.”

The noted advance in therapeutics shown in the development of vaccine therapy has brought with it grave dangers as well as advantages. We have, on a number of occasions, discussed in special articles and in editorials the dangers which threatened from the rapid commercialization of this new method. The unscientific character of mixed vaccines and of the mixed filtered products of a number of vaccines marketed as “Phylacogens” has been especially emphasized and the danger from their indiscriminate use pointed out. A little over a year ago we published a series of articles dealing with the whole subject in which the nature of mixed vaccines was described[117] as follows:

[117] Bacterial Vaccine Therapy: Its Indications and Limitations, p. 37, reprinted from The Journal A. M. A., April 26 June 28, 1913, price 10 cents.

“The mixed stock vaccine of commerce is a makeshift. It is offered
as a substitute for correct diagnosis. Like all such makeshifts
in science, it is doomed to failure.... A burden is being forced
on the profession which will speedily assume the proportions
attained by proprietary drug combinations. The menace cannot be
counteracted unless physicians will accept the guidance of unselfish,
non-commercial interests and refuse to purchase and use mixed
commercial vaccines.”

This admonition to seek the guidance of unbiased scientific observers is deserving of special emphasis at the present time. Five weeks ago we published the address of the chairman of the Section on Pharmacology and Therapeutics, Dr. John F. Anderson,[118] one of our foremost workers in this branch of biologic science, in which attention was very forcibly drawn to the dangers involved in the use of biologic products of non-specific character. He says:

[118] Anderson, John F.: Some Unhealthy Tendencies in Therapeutics, The Journal A. M. A., July 4, 1914, p. 1.

“Bacterial therapy undoubtedly in some cases is a most valuable
method of treatment; but when the claim is made that a combination
of the dead bodies or the filtered products of a number of different
bacteria are useful for the treatment of certain diseases with a
different specific cause, it would seem that the suggestion closely
approaches quackery.”

Further he says:

“Aside from the doubtful practice of the indiscriminate use of
unproved methods of treatment, it has seemed to me that a great
injustice is done the patient by their use, since some of the
preparations that have been widely exploited have been shown to
be harmful in certain instances and even to have caused death. So
the first step in attempting to remedy conditions is to awaken the
physician to the importance of ignoring the claims of those who are
pushing these new methods until their usefulness and harmlessness has
been clearly demonstrated by those best in a position to do so.”

As a result of scientific methods in teaching therapeutics, physicians have gradually given up almost entirely the use of “shotgun” prescriptions and now prescribe a drug or a combination of a few drugs, each given for the purpose of exerting a definite action. On the other hand, the purveyors of bacterial vaccines have gradually increased the number of different bacteria in their mixed vaccines until some of those now advertised for sale contain as many as seven different kinds of bacteria, and some of the “Phylacogens” contain the filtered products of at least eleven bacterial species!

Under the present federal laws there does not seem to be any way in which the federal government can do more than is being done at present. It is a case in which the physician becomes the sole guardian of the patient committed to his care. He is the one and the only responsible individual. He cannot throw the blame for bad results back to the manufacturer. When he subjects his patient to the possibility of harm by the use of these unscientific and dangerous preparations, the physician assumes the responsibility, whether he wants to or not.

If physicians would report their failures when these vaccines are used, and especially report the fatalities consequent on their use, with the name of the manufacturer of the particular product used, we are quite sure there would result lessening in the enthusiasm of the purveyors of these products.

When tempted by the optimistic statements of the interested manufacturer of these mixtures to give them a trial the physician should remember that the warnings of disinterested scientists are of far more value than uncritical clinical reports put out under commercial auspices.

This we quote from a recent book by Victor C. Vaughan,[119] President of the American Medical Association:

[119] Vaughan, Victor C.: Protein Split Products in Relation to Immunity and Disease, 1913, p. 226.

“Every time an unbroken protein is introduced into the body it
carries with it, and as a part of it, a poison. From the very
careless, rash, and unwarranted way in which ‘vaccines’ of most
diverse origin and composition are now used in the treatment of
disease, this matter certainly cannot be understood or its danger
appreciated by those who subject their patients to such risk. It
should be clearly understood that all proteins contain a poisonous
group--a substance which in a dose of 0.5 mg. injected intravenously
kills a guinea-pig. This poison is present in all the so-called
‘vaccines’ now so largely used, and it is not strange that death
occasionally follows the use of ‘Phylacogen’ or similar preparations.
Not only do these proteins contain a poison, but when introduced
parenterally the poison is set free, not in the stomach, from which
it may be removed, but in the blood and tissues. It is possible
that vaccine therapy may become of great service in the treatment
of disease. Even now there are occasional brilliant results which
are reported while the failures and disasters are not so widely
advertised.”

Such a warning as this quotation contains, from a man so eminent as Dr. Vaughan, merits and should receive the careful attention of medical men; at least it should have as much weight as the “clinical evidence” spread broadcast among our profession by commercial houses.--(_From The Journal A. M. A., Aug. 29, 1914._)

THE DANGER IN PROTONUCLEIN, A PREPARATION CONTAINING THYROID

Protonuclein was the subject of a little article in our Queries and Minor Notes Department, Nov. 16, 1912, page 1812. Dr. Reid Hunt, Washington, D. C., writes:

“_To the Editor_:--I have been requested by a physician to call your
attention to certain statements which might well have been added
to your reply to J. A. C. in regard to Protonuclein. Dr. Seidell
and I examined several samples of Protonuclein some time ago[120]
and by chemical and physiologic tests found that they contained the
equivalent of 10 per cent. thyroid of 0.1 per cent. iodin strength
(the actual amount of thyroid may have been greater or less for
we did not know the percentage of iodin in the thyroid used). The
dose recommended on the bottle was 6 to 12 grains every three or
four hours; this represents from 0.6 to 1.2 grains of some of the
commercial thyroid powders, and is sufficient to cause pronounced
thyroid effects in many conditions. Protonuclein was advertised as a
‘perfectly harmless antitoxin, tissue-builder,’ etc., although the
dose of thyroid did not differ materially from that in ‘Rengo’ and
‘Marmola,’ two anti-fat nostrums which we examined at the same time.
We called attention to the danger of using thyroid, the most powerful
tissue-destroying drug known, in cases of typhoid, phthisis, etc.,
for which protonuclein was recommended, though these are conditions
in which the physician is supposed to be exerting every effort to
build up the tissues.

[120] Hunt, Reid, and Seidell, Atherton: Commercial Thyroid
Preparations and Suggestions as to the Standardization of Thyroid,
The Journal A. M. A., Oct. 24, 1908, p. 1385.

“You also speak of the ‘high’ nuclein content (0.28 per cent.
phosphorus): the largest recommended dose would contain only about
1/3 grain of nucleic acid--an amount which probably has not the
slightest effect, especially when given by the mouth.

“A sample of ‘Protonuclein Special’ was found to have twice as much
thyroid as the ordinary Protonuclein; this also was stated to be
‘perfectly harmless.’”--(_From The Journal A. M. A., Feb. 1, 1913._)

PURGEN

The physicians of the United States are receiving a neat package containing samples of a German proprietary--Purgen. The container is an ingenious one and, besides the tablets, includes a circular in English, although mailed in Europe, describing the remarkable virtues of this “new synthetic aperient.” It has been considered strange that this proprietary, which has been advertised so thoroughly in Europe, Australia, etc., should not have made its appearance in this country. Now it is here, and it is well that physicians should know what Purgen is and not be mystified and misled by the literature that they may receive regarding the preparation.

The following appeared in The Journal, Jan. 5, 1907, page 64, and is reprinted now as being especially timely:

The report of a case of poisoning by Purgen (phenolphthalein) is
the occasion for some pertinent observations by Dr. G. Brasch as to
the proper introduction of such remedies to the medical profession
(_Ztschrift für Medizinalbeamte, Abst. in Apotheker-Zeitung_,
No. 59, 1906). He agrees with Best that all such remedies should
first receive a thorough trial in an institution subject to state
supervision, before they are advertised to the medical profession,
so that their harmlessness in appropriate doses may be ascertained
by a method free from liability to error. The manner in which the
manufacturers introduced Purgen to the profession and the laity is to
be condemned, and probably led to the symptoms of poisoning exhibited
in the case of Dr. Best and tends to discredit a remedy which is
harmless and efficient if used in proper doses. The manufacturer
of such a preparation is inclined, for obvious reasons, to put the
dose of his preparation much too high. The most important point,
however, is the objectionable character of the names given to such
articles. The organic compound phenolphthalein has been known for a
long time and has been widely used as an indicator. Accidentally it
was discovered that phenolphthalein possessed laxative properties
and thereon it was proposed (1901) as a medicine under the name
“Purgen.” It is sold in tablets containing 0.05, 0.1 and 0.5 grain
phenolphthalein mixed with sugar and flavored with vanilla. The
author says: “But it is very desirable--and I regard this as the
most important part of my communication--that phenolphthalein
should be received into the materia medica under its own name. The
addition of vanilla and sugar is to the highest degree superfluous
and the arbitrary dosage in three strengths with the ridiculous
designations, ‘baby,’ ‘for adults,’ ‘for patients confined to bed,’
are merely calculated to prejudice the physician who is accustomed
to individualize in his prescriptions, against a remedy which is in
itself an excellent one.”

As explanatory to the last sentence, it should be stated that in Europe Purgen is put up in three dosage forms, “infant Purgen for children,” containing 3/4 of a grain; “adult Purgen for chronic constipation,” containing 1-1/2 grains, and “strong Purgen for invalids,” containing 7-1/2 grains. The form in which it is being sampled in this country is in the medium dose, 1-1/2 grains.

Physicians should remember that the promoters of Purgen are simply introducing a chemical well known to laboratory workers for the last twenty years, which has been recognized as an aperient for at least seven years, and which can be purchased for 40 cents an ounce, whereas an ounce of phenolphthalein in the form of Purgen will cost $3.20 wholesale. The enthusiastic praise of the remedy, found in the advertising circulars, should be subjected to critical judgment on account of its source and motives.

It is undoubtedly true, however, as we have previously stated, that phenolphthalein is worthy of a trial. In the _British Medical Journal_, Oct. 18, 1902, F. W. Tunnicliffe speaks of the virtues of phenolphthalein, and the conclusions reached by him were that it is a useful aperient, without irritating action on the kidneys, and is especially valuable in jaundice, its depressing action on the circulation being less than sulphate of magnesia.

Phenolphthalein is not in the Pharmacopeia, but has been included in “New and Nonofficial Remedies” by the Council on Pharmacy and Chemistry. From this we quote:

_Actions and Uses._--Phenolphthalein acts as a purgative, but appears
to possess no further physiologic action. A case of poisoning from
taking 1 gm. (15 grains) is reported. _Dosage._--For adults the
average dose is 0.1 to 0.2 gm. (1.5 to 3 grains) given as powder, in
cachets, capsules or pills. It may be given with safety in doses of
0.5 gm. (8 grains), and these doses seem to be necessary to secure
its effects in bedridden patients or in obstinate cases.

We have gone into this matter again so that our readers may have some knowledge of this remedy, and we hope that if they conclude to try it they will use the chemical itself and under its own name.--(_From The Journal A. M. A., Sept. 14, 1907._)

PYO-ATOXIN

“_To the Editor_:--I am sending you a sample of a proprietary
preparation that for the past two or three years has been largely
retailed in the South and Southwest as a new combination that
liberates larger amounts of formaldehyd, etc., in the genito-urinary
tract than any known agent, that it is a methylene-formate, entirely
new, etc.

“I asked the representative why he had not submitted a specimen to
the Council, and his reply was that like Wyeth and others they did
not get a fair report, or something to this effect. My reasons for
trying to find the truth for their claims is that quite a number of
general practitioners have asked me regarding this Pyo-Atoxin.

“W. P. Dey, M.D., Jacksonville, Fla.”

Dr. Dey sent with the foregoing letter a box of Pyo-Atoxin which bore this label:

Pyo-Atoxin
Reg. in U. S. Pat. Office
(Capsules)
(Pheno-Methylene-Formate)
“Hurley”
An Antitoxic Agent Indicated in
Gonorrhoea, Cystitis, Pyelitis and
Bacteriuric Conditions.
DOSE: One capsule four to six times daily,
Followed by large glass of water.
Guaranteed by
H. O. Hurley,
Manufacturing Pharmacist,
Louisville, Ky.
Under the Food and Drugs Act, June 30, 1906
Serial No. 1710.

The pseudoscientific synonym “pheno-methylene-formate” carries the idea that Pyo-Atoxin is a definite chemical substance. It is unnecessary to say that the term “pheno-methylene-formate” is a meaningless one and its use reminds one of those preparations exploited seven or eight years ago before the Council began to expose these mixtures masquerading as definite chemical compounds.

The chemical laboratory was asked to investigate this preparation and the following is a report of the chemists:

“The box contained thirty gelatin capsules coated with some black
substance giving them the appearance of some of the popular gonorrhea
nostrums. When the capsules were opened they were found to contain
a powder--about 0.35 gm. or 5 grains per capsule--composed of large
white or colorless crystals mixed with a smaller amount of a fine
dark powder. The crystals when separated out and dissolved yielded
the characteristic tests for hexamethylenamin. A solution of the
entire capsule content was deep blue and responded to the U. S. P.
tests for methylene blue.

“As a result of these and other tests it was concluded
that Pyo-Atoxin consisted essentially of two pharmacopeial
drugs--hexamethylenamin and methylene blue. A quantitative
determination of the constituents was considered unnecessary. From
its general appearance and properties, however, the hexamethylenamin
probably constitutes approximately from 60 to 80 per cent. of the
preparation.”

It thus appears that the capsules contain a mixture consisting essentially of two well-known official substances, the value and particularly the limitations of which should be known by physicians by this time. This nostrum is simply another example of how physicians are being humbugged.--(_From The Journal A. M. A., Feb. 14, 1914._)

RESINOL

The Philadelphia branch of the American Pharmaceutical Association issued a pamphlet some two years ago in which the following appeared relative to Resinol and similar products:

“Within recent years there have been introduced a number of compound
ointments that in their supposed range of therapeutic usefulness are
scarcely equaled and certainly not excelled by the magic unguents
of the quacks and charlatans of continental Europe, who, several
centuries ago, essayed to cure all manner of disease by inunction or
the simple application of compound ointments of secret composition.

“As typical of this modern class of panaceas we may mention
Resinol. This preparation is being widely advertised at the present
time in the daily papers as a valuable adjunct to Resinol Soap
in the treatment of all kinds and varieties of diseases of the
skin. The makers of this particular mixture, in the form of an
ointment, modestly assert that it will cure all skin diseases, and
is also ‘Specific for Pruritus Ani, Itching Piles, and Pruritus
Vulvæ.’”--(_From The Journal A. M. A., Nov. 6, 1909._)

RESOR-BISNOL

Resor-Bisnol was considered by the Council and refused recognition. The following formula for Resor-Bisnol was at one time given in advertisements in a number of medical journals:

“A scientific combination, in nicely balanced proportions of
Bismuth Salts of antiseptic acids of the aromatic series, and
Resorcin.

“Each 100 parts contains 20 parts Resorcin, and 52 parts Bismuth
Oxid, combined with antiseptic acids.”

Besides this formula other “formulas” equally indefinite, vague and misleading have been given in lieu of an actual statement of composition, thus:

“---- is a mixture of resorcin and bismuth salts of phenic acids
such as salicylates, etc., and an aromatic alcoholate. Its
composition is as follows.

Bismuth salts of phenic acids 60 per cent.
Aromatic alcoholate of bismuth 20 per cent.
Resorcin 20 per cent.”

The product was recently analyzed in our chemical laboratory. The chemists report as follows:

“A specimen of Resor-Bisnol examined by us consisted of a light
brown powder possessing a characteristic odor and a taste at first
sweetish and then bitter. It was found to be only partially soluble
in water. The examination indicates that Resor-Bisnol is probably a
mixture consisting essentially of a basic bismuth salicylate (bismuth
subsalicylate), a basic gallate of bismuth (bismuth subgallate),
a basic compound of beta-naphthol (bismuth betanaphtholate) and
resorcinol (resorcin).”

It thus appears that Resor-Bisnol is probably a simple mixture of well-known substances. In other words, the Resor-Bisnol advertising and literature are typical of that issued by various nostrum houses: it conceals the truth in a mass of semi-scientific verbiage, and while not frankly false, it deceives by what is left unsaid rather than by what is said.--(_From The Journal A. M. A., June 1, 1912._)

ROBINOL AND SEVETOL

Revamping Discarded Theories for Commercial Purposes

It is astonishing how rapidly medical hypotheses become theories and theories are accepted for established facts, when such alleged facts are favorable to commercial enterprise. Yet, as a matter of fact, the manufacturers of proprietary preparations are under a moral obligation, at least, to tell the truth with reference to the scientific basis for their claims. To draw from exploded theories reasons for the use of proprietary preparations is reprehensible, not only because it may lead physicians to use preparations which are worthless, but also because it tends to confirm in the physician’s mind opinions which science has discarded.

Robinol

John Wyeth and Brother put up a mixture of glycerophosphates which they call Robinol. In their description of the properties of this mixture they say:

“Phosphorus exists in the brain, nervous system, and vital organs
as lecithin, of which glycerophosphoric acid is the most important
constituent and is essential to the vital processes for the
reproduction of life and maintenance of metabolism in old age,
impotence, etc.”