Lest the appearance of this detailed stu_The Propaganda for Reform in Proprietary Medicines, Vol. 2 of 2

rejection of so-called secretin preparations, should be interpreted

(as manufacturers whose products have been rejected have endeavored to

interpret such action) as a case of first condemning a preparation and

then getting the facts, the Council’s methods, and their application

in this case, may be briefly stated. The Council maintains that,

when a manufacturer places a product on the market, the burden of

proof is on that manufacturer to show that the properties of his

product are in accordance with his claims for it. As stated in the

introduction to N. N. R., “it is ... manifestly impossible for the

Council to investigate the composition of every complex pharmaceutical

mixture, or to check thoroughly every therapeutic claim; it can give

only an unbiased judgment on the available evidence.” Acting on this

principle, the Council examined the claims made for Secretogen, an

alleged secretin product manufactured by the G. W. Carnrick Company.

The conclusion was that these claims were in absolute conflict with the

available evidence as to the action of secretin.

It is not necessary to review this subject again. It will suffice to

state that the claims made for Secretogen rest on two fundamental

propositions: (1) that deficiency of secretin (or, rather, of

prosecretin) in the intestinal mucosa is a factor in gastro-intestinal

diseases; (2) that secretin given by the mouth is absorbed and produces

increased secretion of the pancreatic and intestinal juices and of the

bile.

From an examination of the evidence available, including that

submitted by the manufacturers, the Council concluded: “1. No evidence

has been presented that the absence of secretin is a cause of

gastro-intestinal disease. 2. There is no evidence that secretin in

any form is physiologically active when administered by mouth.” That

these conclusions were justified is shown again by the review given

by Carlson of the literature, much of which was also reviewed in the

Council’s previous report.

Since the claims of the Carnrick Company were not supported by any

satisfactory evidence, no further investigation on the Council’s part

was necessary to warrant rejection of the product. The Council did

not undertake to determine, for instance, whether or not Secretogen

and similar products actually contain secretin; the determination of

this point was immaterial here, in view of the conclusiveness of the

evidence that secretin given by mouth has no physiologic action.

Since firms other than the G. W. Carnrick Company are manufacturing

alleged secretin preparations, and since recommendations for the use

of secretin preparations in gastro-intestinal diseases have even crept

into textbooks, it seemed desirable to obtain further information on

certain points. The Council therefore requested Prof. A. J. Carlson

of the University of Chicago to check the results of previous

investigators with regard to the action of secretin administered by

mouth or directly into the intestine, and, in addition, to investigate

the secretin content of certain alleged secretin preparations.

Carlson and his co-workers, like all previous investigators, found that

secretin given by mouth, or introduced even in enormous doses directly

into the intestine, is entirely inactive. They also found that marked

destruction of secretin followed contact for one minute with human

gastric juice and that secretin is rapidly oxidized and rendered inert

in contact with the air.

Further, they were unable to demonstrate the presence of secretin

in samples of Secretogen and another supposed secretin preparation

(Duodenin) bought on the open market. In the case of Secretogen there

was one exception: one bottle was found which contained a little

secretin, but it was necessary to administer (by intravenous injection,

of course) the entire contents of the bottle (100 tablets) to obtain “a

small but unmistakable secretin reaction.”

In these studies the methods employed were those by which secretin was

discovered. It is only by the use of such methods that the presence or

absence of secretin can be determined. Apparently the manufacturers who

place so-called secretin preparations on the market do not make use of

these methods, by which alone even the composition of their products

can be determined.

Carlson and his collaborators conclude:

“There is as yet no reliable evidence that lack of secretin is a

primary or important factor in any disease. Even should this be

established, secretin therapy, to be effective, must be intravenous.

Secretin has not yet been prepared in sufficiently pure state to render

possible intravenous injection in man without injurious effects. And

even when this is attained, the very fleeting action of secretin

will in all probability render secretin therapy as futile in all the

diseases in which it is theoretically indicated as epinephrin therapy

is in Addison’s disease.”

In short, secretin is as ineffective taken by mouth as it would be

rubbed on the skin.

The referee recommends that the work of Professor Carlson be

endorsed.--(_From The Journal A. M. A., Jan. 15, 1916._)

HAS SECRETIN A THERAPEUTIC VALUE?[B]

A. J. Carlson, Ph.D., J. E. Lebensohn, M.S., and S. J. Pearlman, B.S.

Chicago

[B] From the Hull Physiological Laboratory of the University of Chicago.

[B] This investigation was undertaken at the request of the Council on

Pharmacy and Chemistry. The following report, having been submitted

to the Council, received its endorsement (see preceding report of the

Council on Pharmacy and Chemistry, “So-Called Secretin Preparations”).

It is well established that acid chyme in the duodenum is the normal

stimulus to the secretion of pancreatic juice.[31] Interaction of

the acid with the duodenal mucosa liberates into the blood stream a

substance which, circulating through the pancreas, excites the latter

to activity. This exciting substance has been termed “secretin.” It

can be prepared artificially by macerating duodenojejunal mucosa in

0.4 per cent. hydrochloric acid, neutralizing the boiling mixture, and

filtering. A few cubic centimeters of the filtrate injected into a

vein produce invariably a powerful secretion of pancreatic juice.[32]

That a “chemical messenger” is at the basis of the duodenal acid

reflex has been proved by even more crucial experiments--transfusion

(Wertheimer,[33] Enriquez and Hallion[34]), cross circulation

(Fleig,[35] Matuso[36]), and perfusion of the isolated pancreas

(Huston[37]).

[31] Pawlow: The Work of the Digestive Glands, 1912.

[32] Bayliss and Starling: Jour. Physiol. =28=:325, 1902.

[33] Wertheimer: Compt. rend. Soc. de biol. =54=:475, 1902.

[34] Enriquez and Hallion: Compt. rend. Soc. de biol. =55=:233, 363,

1903.

[35] Fleig: Arch. internat. de Physiol., =10=:206, 1910.

[36] Matuso: Jour. Physiol. =45=:477, 1913.

[37] Huston: Ann. et bull. Soc. roy. de sc. méd. et nat. =70=:178, 1912.

PROPERTIES OF SECRETIN

_Prosecretin._--Secretin is soluble in water, yet a watery extract of

intestinal scrapings is without action,[32] even after being submitted

to acid treatment.[38] Starling therefore holds that secretin exists

in the intestinal mucosa in an inactive form, as “prosecretin.” The

content of the intestine in prosecretin decreases from the duodenum

down, so that one is unable to demonstrate any prosecretin in the last

2-1/2 feet of the ileum. Prosecretin is insoluble in water, acetone,

absolute alcohol or ether. Secretin, on the other hand, is readily

soluble in water, normal salt solution and diluted alcohol (70 per

cent.), but likewise insoluble in absolute alcohol and ether.

[38] Starling: Lancet, London =2=:433, 1905.

_Preparation._--All of the more dissociated acids liberate secretin

from intestinal mucosa on boiling. Their action is dependent on

the degree of dissociation,[39] carbonic and boric acids being

inactive.[40] Secretin can also be prepared with strong soaps (from

10 to 30 per cent. sodium oleate), alcohol (70 per cent.,[41] 0.6 per

cent. sodium chlorid[36]). The acid and soap in the duodenum produce

secretion; there is no necessary correspondence between the action of a

substance in the intestine and that obtained by injection after boiling

mucosa with it. The sodium chlorid, bile, maltose and glucose produce

some secretion by the latter method yet none by the former.[36] On the

other hand, ether, chloral and oil of mustard excite secretion when

in the intestine, but no secretin can be prepared from boiled mucosa

by their action. The irritation of the lining cell has produced the

necessary hydrolysis.[38] In well-controlled experiments, Wertheimer

and LePage[42] found that after the introduction of acid, secretion is

secreted into the lumen of the intestine. Matuso[36] confirmed their

results, and found this a satisfactory method for the preparation of

secretin. It is said that secretin can be obtained by merely boiling

the mucosa with water, but the results are inconstant.[43]

[39] Frouin and Lalou: Compt. rend. Soc. de biol., =71=:189, 1911.

[40] Camus: Compt. rend. Soc. de biol., 1902, =54=:442, 1902.

[41] Fleig: Jour. de physiol. et de path. gén. =6=:32, 50, 1904.

[42] Wertheimer and LePage: Jour. de physiol. et de path. gén. =4=:1061,

1070, 1902.

[43] Stepp: Jour. Physiol. =43=:441, 1912.

_Action._--Secretin is an excitant not only of the pancreatic juice

but also of the liver and the intestinal mucosa. The flow of bile is

markedly accelerated (Henri and Portier,[44] Enriquez and Hallion[45]),

likewise that of succus entericus (Delezenne and Frouin,[46] Bottazzi

and Gabrielli[47]), and intestinal peristalsis is stimulated (Enriquez

and Hallion,[48] Falloise[49]). Injections of secretin produce a marked

vasodilatation, but the secretory effect is independent of the blood

pressure changes. The pancreas is not readily fatigued by secretin.

Bayliss and Starling[50] have obtained undiminished flow after eight

hours of continuous injection. Our experience confirms this result.

Also, equal doses of secretin give corresponding results at various

intervals. Moreover, anesthesia does not affect the flow. Secretin

is unrecoverable from the glands even after two hours of continuous

injection.[51] The juice obtained by secretin has been subject to many

studies.[52] It is of high alkalinity (about seventh normal), contains

all the pancreatic ferments, and corresponds in all respects to the

juice obtained in digestion from permanent pancreatic fistulas.[53]

[44] Henri and Portier: Compt. rend. Soc. de biol. =54=:620, 1902.

[45] Enriquez and Hallion: Presse méd. =1=:105, 1903.

[46] Delezenne and Frouin: Compt. rend. Soc. de biol. =56=:319, 1904.

[47] Bottazzi and Gabrielli: Arch. internat. de physiol. =111=:156,

1905.

[48] Enriquez and Hallion: Bull. gén. de thér. =162=:202, 1911.

[49] Falloise: Bull. de l’Acad. roy. de Belgique =5=:945, 1902.

[50] Bayliss and Starling (Note 2). Matuso (Note 6). Arch. internat. de

physiol. =10=:335, 1911.

[51] Dixon and Hamill: Jour. Physiol., 1909, xxxv, 314.

[52] Bayliss and Starling: Jour. Physiol., 1904, xxx, 61. Bierry:

Compt. rend. Soc. de biol., 1907, lxii, 433. Bierry and Terroine:

Compt. rend. Acad. de sc., 1905, cxli, 146. Lalou: Comp. rend. Acad. de

sc., 1910, xxix, 824. Morel: Compt. rend. Soc. de biol., 1909, lxvii,

36. Strassano and Billoro: Compt. rend. Soc. de biol., 1902, liv, 937.

[53] Bayliss and Starling (Note 23).

_Specificity._--In a maceration of the duodenojejunal mucosa, such as

we have in secretin, the known substances are proteoses and peptones,

acid amins, bile salts, beta-imidazolethylamin, cholin, gelatin and

inorganic salts. These substances, individually and severally, together

with their derivatives, are devoid of secretory action. Chemically,

secretin, is then a specific entity. But like epinephrin, in its

distribution, it is nonspecific. Active preparations have been made

from an extraordinary variety of animals among the different classes

of vertebrates (Camus,[54] Bayliss and Starling,[55] Chapman[56]). It

is likewise found in the new-born and in the fetus.[57] Its action,

however, like its chemical composition, is markedly specific. It

stimulates the flow of pancreatic juice, bile and succus entericus.

Its effect on the gastric glands is negative, and on the saliva

likewise.[58] On the other hand, no other extracts produce pancreatic

secretion. Dr. Koch, who, in collaboration with Dr. Keeton and Dr.

Luckhardt, has done the most recent work on gastrin[59] (a substance

that most nearly resembles secretin) and has isolated an extremely

active preparation, finds that gastrin injection has likewise no effect

on the pancreas. Camus and Gley,[60] with crude preparations, had

previously obtained a similar result.

[54] Camus: Jour. de physiol. et de path. gén. =4=:998, 1902.

[55] Bayliss and Starling: Jour. Physiol. =29=:174, 1903.

[56] Chapman: Proc. Linnaean Soc., New South Wales =1=:92, 1905.

[57] Camus: Compt. rend. Soc. de biol. =61=:59, 1906. Hallion and

Lequex: Compt. rend. Soc. de biol. =61=:33, 1906.

[58] Derouaux: Arch. internat. de physiol. =3=:44, 1905. Lambert and

Myer: Compt. rend. Soc. de biol. =54=:1044, 1902. Starling: Lancet,

London =2=:501, 1905.

[59] Keeton and Koch: Am. Jour. Physiol. =37=:481, 1915.

[60] Camus and Gley: Compt. rend. Soc. de biol. =54=:648, 1902.

_Lability._--Neutral secretin is but feebly attacked by a temperature

of 100 C. If heated in an autoclave (so as to prevent oxidation), this

temperature can be continued for thirty minutes without any change

in its activity. Increasing the temperature increases the speed of

destruction, so that at 140 C. the destructive action is marked.[61]

Autoclaving at 15 pounds for fifteen minutes, as an ordinary

sterilization of culture mediums, produces, we found, a distinct though

not serious decrease in activity. Secretin acidified to fifth-normal

with hydrochloric acid loses 60 per cent. of its activity on fifteen

minutes boiling. Secretin, alkalinized to fifth-normal with sodium

hydroxid loses 95 per cent. of its activity in five minutes’ boiling;

decreases to a trace in thirty minutes, and disappears entirely in

sixty minutes. At room temperature, with fifth-normal alkalinity, 80

per cent. of secretin is destroyed in eight hours.[61] The destruction

probably means a secondary cleavage of the secretin molecule itself.

[61] Lalou (Note 21). May: Jour. Physiol. =30=:400, 1904.

Secretin is oxidized readily. If left standing uncovered for a summer’s

day, the preparation will be inactive.[51] Even if kept in the

ice-chest (no other precaution being taken), its activity is lost in

a very few days. Sunlight undoubtedly hastens the oxidative process.

If care is taken as to sterility, however, and the secretin is kept in

the ice-chest, well stoppered and in a dark flask, it will retain its

activity for several weeks.

Dixon and Hamill[51] claimed that secretin disappears quantitatively on

passage through a Berkefeld filter at 5 mm. pressure. Lalou,[62] using

higher pressure, was unable to confirm the finding, but obtained a

marked decrease in activity. Our results are in accord with those of

Lalou.

[62] Launoy: Arch. internat. de Physiol. =3=:62, 1906. Morel and

Terroine: Compt. rend. Soc. de biol. =67=:36, 1909. Zunz: Arch.

internat. de physiol. =8=:181, 1909. Lalou: Jour. de physiol.

=14=:465, 1912.

_Analogy to Epinephrin._--The analogy of secretin to epinephrin

does not generally receive enough emphasis. Both substances are

nonspecific in distribution, but specific chemically, and especially

physiologically, epinephrin acting on the myoneural junctions, secretin

on intestinal digestion. They are both relatively simple substances

of low molecular weight, and subject to rapid oxidation whereby their

properties disappear. The action in both cases is very transient. They

are the two examples of what Starling calls the “acute hormones,” in

which it is essential that reaction take place immediately, and shall

disappear as soon as the exciting cause is removed.[63]

[63] Starling: Proc. Roy. Soc. Med., 8, No. 4, 1914, Therap. and Pharm.

Section, p. 29.

CLINICAL USE OF SECRETIN

_Diabetes Mellitus._--Moore, Edie and Abram[64] were the first to

suggest a therapeutic value for secretin, having obtained favorable

results with secretin administration in diabetes. They argued that the

internal secretion of the pancreas _may_ be stimulated by secretin,

and that some cases of diabetes _may_ be due to lack of this necessary

excitant. Owing to the importance of the question, their announcement

was followed quickly by numerous investigations by other observers.

Previously, Spriggs, at the suggestion of Starling, had tried

intravenous injections of secretin free from depressor substance in a

diabetic patient, and had obtained negative results. Moore, Edie and

Abram gave their secretin by mouth over long periods. Of the five cases

cited in their first paper, two were negative. The third was that of a

man, aged 25, who received daily 30 c.c. of secretin. After a latent

period of three weeks, the sugar suddenly fell, and after four months

the urine was sugar-free. Six months later a relapse occurred with the

development of phthisis and death. The other two patients were a boy,

aged 7, and a girl, aged 9, whose urine in from three to five weeks

became sugar free during the secretin treatment in spite of severe

diabetes. One of these patients later relapsed.[65] Bainbridge and

Beddard[66] gave secretin a thorough trial in three cases with negative

results, and are disposed to attribute the results of Moore to dieting.

Dakin and Ransom[67] cited one case, secretin being given for twelve

weeks, with negative results; Foster,[65] nine cases, all negative;

Charles,[68] three cases, all negative. Crofton,[69] however, gave

secretin a trial in one case with favorable results. Moore, Edie and

Abram, in a later paper,[70] report a large number of cases tried with

the majority of results negative, though in some cases an improvement

in the digestion, and in certain cases an increase of weight was noted.

[64] Moore, Edie and Abram: Biochem. Jour., =1=:28, 1906.

[65] Foster: Jour. Biol. Chem., =2=:297, 1906.

[66] Bainbridge and Beddard: Biochem. Jour., =1=:429, 1906.

[67] Dakin and Ransom: Jour. Biol. Chem., =2=:305, 1906.

[68] Charles: Med. Press and Cir., =133=:578, 1906.

[69] Crofton: Lancet, London, =176=:607, 1909.

[70] Moore, Edie and Abram: Biochem Jour., =3=:82, 1908.

One method of testing the basis of Moore’s theory would be by examining

the prosecretin content of the intestine in diabetics. Bainbridge and

Beddard found, in the paper referred to,[66] that from five of the

six cases of diabetics examined postmortem, little or no secretin

could be prepared; but in a subsequent report of seven cases,[71]

they found only one in which the secretin obtained was scanty. The

failure to obtain secretin in some cases they claim is probably due to

the rapid postmortem degeneration of diabetic tissue. Evans,[72] in

Starling’s laboratory, found that in dogs made recently diabetic by

total pancreatectomy, but little secretin could be obtained. Hedon and

Lisbonne,[73] and Pemberton and Sweet[74] report, on the contrary, that

the duodenum of diabetic dogs is rich in prosecretin. Bainbridge and

Beddard,[71] working on a diabetic cat, likewise found prosecretin to

be present in normal quantity.

[71] Bainbridge and Beddard: Biochem. Jour. =3=:82, 1908.

[72] Evan: Jour. Physiol. =44=:461, 1912.

[73] Hedon: Compt. rend. Soc. de biol. =74=:375, 1913.

[74] Pemberton, Ralph, and Sweet, J. E.: Further Studies on the

Influence of the Ductless Glands on the Pancreas, Arch. Int. Med., May,

1910, p. 466.

_Digestive Disturbances._--Secretin for digestive disturbance was first

used in the “acid duodenal medication” of Enriquez.[75] This consisted

in the giving of tartaric acid in thick keratin capsules, the acid not

being liberated until the duodenum was reached, where it provoked the

formation of secretin. “The secretin mechanism,” he says, “is probably

capable of pathologic disturbance as would result, for example, with

diminished acidity of chyme, disturbance of the normal motility of

the stomach or pylorus, or diminished prosecretin in the mucosa. Such

a condition would produce disturbance of the pancreatic, biliary and

intestinal secretions, and interfere with intestinal movements, with

a clinical syndrome of intestinal dyspepsia as a result, among the

chief and most constant symptoms of which would be constipation.”

“The acid duodenal medication” was submitted to wide clinical use,

and very favorable results in certain obstinate cases of constipation

were reported. In regard to “diminished prosecretin in the mucosa,”

Wentworth[76] has claimed that in infantile atrophy such is the

condition, but Sweet and Pemberton[77] have found that the difficulty

of preparing secretin from human duodenums is such as to render

Wentworth’s findings inconclusive.

[75] Enriquez: Bull. du Lab. de biol. Appliq. 2, No. 2-No. 8, 1904.

[76] Wentworth, A. H.: The Cause of Infantile Atrophy, J. A. M. A.,

July 20, 1907, p. 204.

[77] Sweet, J. E., and Pemberton, Ralph: Experimental Observations on

Secretin, Arch. Int. Med., February, 1908, p. 231.

Beveridge[78] suggests the use of secretin in (_a_) pyloric stenosis,

(_b_) pancreatic insufficiency, (_c_) hepatic stimulation and cirrhosis

of the liver (_d_) to stimulate peristalsis in colonic stasis, (_e_) in

gastro-enterostomy and short-circuiting of the intestines. He claims

to have used it in over a hundred cases with “brilliant results,”

and cites four typical histories. The G. W. Carnrick Company, which

manufactures “Secretogen,” an alleged secretin preparation, cites a

number of authorities[79] as also recommending secretin for digestive

disorders. Harrower, who is or was connected with the Carnrick Company,

in clinical journals[80] has ardently advocated the use of secretin for

a large number of maladies.

[78] Beveridge: Am. Med. =20=:255, 1914.

[79] Lockwood, G. R.: Diseases of Stomach, 1913, Chapter on Achylia.

Bassler, Anthony: Am. Jour. Gastro-Enter., 1914; Kemp, R. C.: Diseases

of Stomach, Intestine and Pancreas, 1912. Reed, Boardman: Am. Jour.

Gastro-Enter., October, 1912. Ewald (Therapie der Gegenwart, 1915,

p. 5) reports favorable results with Secretogen in one of thirteen

cases.

[80] Harrower: Pediatrics =25=:430, 1913; New York M. J. =118=:315,

1913; Arch. f. Verdauungskr. =20=:577, 1914.

PHYSIOLOGIC CONSIDERATIONS

Throughout its clinical use, secretin has been given by mouth; _but

its direct introduction into the intestine of a dog under anesthesia

in even enormous quantities is without effect_. This fact, first

observed by Bayliss and Starling,[32] was confirmed by Fleig,[81] and

Matuso,[36] and our personal experiments have convinced us of its

truth. Matuso found that ordinary secretin and that obtained from

intestinal lumen gave equally negative results. Large quantities of

active secretin, moreover, acidified to 0.2 per cent. hydrochloric

acid, and left in the ileum for fifteen minutes, were still negative.

Wertheimer and Duvillier,[82] in a previous paper on this subject,

had likewise found that acid solutions of secretin (which might be

considered more normal for the intestine than when neutral), when

introduced into the ileum gave negative or inconstant results. They

conclude that it is more likely that the pancreas does not respond to

such minimal stimuli, than that the secretin is not absorbed.

[81] Flieg: Arch. gén. de méd. =191=:1482, 1903.

[82] Wertheimer and Duvillier: Compt. rend. Soc. de biol. =68=:535,

1910.

_The destructive action of the digestive enzymes leads us to believe

that it is in inactive form that secretin is absorbed._ Like

epinephrin, it cannot pass through the digestive tract. Bayliss and

Starling state that it is destroyed by one hour’s tryptic digestion.

Lalou[62] worked with the action on secretin of pepsin, dog’s gastric

juice, pancreatic juice, succus entericus and erepsin, and found in

each case a destructive effect, even almost after mixing; and after

five minutes over 75 per cent. of the activity had disappeared.

Matuso[36] introduced 30 c.c. of active secretin into the intestine,

removed it five minutes later, and found that no activity remained.

Other methods of administration have been tried. Subcutaneous

injections are practically negative (Matuso,[36] Hallion[83])

and intrapleural injections are likewise negligible (Bayliss and

Starling[55]).

[83] Hallion: Presse méd. =20=:433, 1912.

Starling[63] finds that continued intravenous injections of secretin in

a healthy dog produces after a time severe symptoms of collapse, which,

he believes, are due to change in the intestinal mucous membrane caused

by the entry and non-neutralization of the strongly alkaline pancreatic

juice.

Intestinal digestion seems little affected in achylia gastrica

(Stockton,[84] Ehrman and Lederer,[85] Bayliss and Starling[32]). This

may be due to other secretin stimulants as fats, or to the action of

the nervous mechanisms (Meltzer[86]).

[84] Stockton: In Osier and McCrae’s Modern Medicine =3=:19, 1914.

[85] Ehrman and Lederer: Deutsch. med. Wchnschr. =35=:879, 1909.

[86] Meltzer, S. J.: The Factors of Safety in Animal Structure and

Animal Economy, J. A. M. A., Feb. 23, 1907, p. 655.

THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE

We have carried out in detail experiments on the digestive effect of

human gastric juice on secretin. Our results in every respect confirm

the findings of Lalou,[62] who worked with commercial pepsin and dog’s

gastric juice, but are even more striking because of the much superior

quality of pure human gastric juice.

_Methods._--The human gastric juice was obtained from Mr. V., the

gastric fistula case of our laboratory. The chemical and digestive

characters of his juice are discussed in a recent paper.[87] In the

different experiments, different samples of gastric juice were used.

The secretin employed was always freshly prepared. Digestion was

carried out in the incubator at 38 C. with the reaction of 0.4 per

cent. acid, and the end of the period was marked by either boiling

the mixture or (in the first two experiments) by turning the mixture

alkaline. The action of the preparation, we proved, was not influenced

by the method used. The dogs on which the preparations were tested

were prepared for carotid blood pressure, injection into the external

jugular vein, and cannula in the pancreatic duct, essentially the

methods of Bayliss and Starling[32] being employed. The preparations

were injected at body temperature after being neutralized and filtered.

Except for the addition of normal salt solution instead of gastric

juice, the control injections of secretin were submitted to exactly the

same treatment as the other preparations.

[87] Carlson: Am. Jour. Physiol. =38=:248, 1915.

_Results._--Our results are embodied in Table 1. We assured ourselves

before beginning the series that incubation of secretin with _boiled_

gastric juice produced no change. It is to be noted in the table that

each experiment is a unit complete in itself, beginning and ending

with a control injection of secretin. _Special attention is called to

the marked destruction that follows contact of human gastric juice

with secretin for merely one minute._ In Experiment 4, using 1 c.c.

of human gastric juice, the action fell to 14 drops from an original

secretion of 21; in Experiment 5, using 8 c.c. of gastric juice, the

action fell to 6 drops from an original secretion of 20. Of interest

also is the rate at which we get _complete_ destruction of secretin.

This is practically 2 hours for 2 c.c. with secretin giving originally

110 drops (Experiment 2, Fig. 1), or 30 minutes for 5 c.c. with a

secretin giving originally 53 drops (Experiment 6). These results are

practically parallel, though they were obtained with different samples

of gastric juice and in different experiments.

TABLE 1.--THE DESTRUCTION OF SECRETIN BY HUMAN GASTRIC JUICE

=====================================================================

| | Secretion of Pancreatic Juice in Drops

| +--------+--------------------------------------+--------

No. |Quan-|10 C.c.c| The Secretin After Incubation |10 C.c.

of | tity|Secretin| with Human Gastric Juice |Secretin

Exper-|of |Control +-----+------+-----+------+-----+------+Control

|C.c. | | | | | | | |

------+-----+--------+-----+------+-----+------+-----+------+--------

1 | 2 | 28 |6 | 0 |4 | 0 |2 | 0 | 16

2 | 2 | 110 |2 | 7 |1-1/2| 18 |1 | 18 | 41

3 | 2 | 40 |1 | 7 | 3/4| 7 | 1/4 | 8 | 31

4 | 1 | 21 | 1/2| 11 | 1/4| 12 | 1/60| 14 | 18

5 | 8 | 20 | 1/2| 1 | 1/4| 3 | 1/60| 6 | 18

6 | 5 | 53 | 1/2| 2 | .. | .. | .. | .. | ..

------+-----+--------+-----+------+-----+------+-----+------+--------

We also tried the effect of keeping the digestive time _constant_ and

varying the amount of gastric juice employed. Increasing the quantity

of gastric juice used increases the quantity of secretin destroyed

(Table 2).

TABLE 2.--EXPERIMENT 7*

Pancreatic

Preparation Juice Drops

10 c.c. secretin 20

10 c.c. secretin digested with 0.5 c.c. gastric juice 15

10 c.c. secretin digested with 3 c.c. gastric juice 13

10 c.c. secretin digested with 10 c.c. gastric juice 8

* The digestive time was kept constant at fifteen minutes. (The gastric

juice used had been _diluted_ with stomach washings.)

The reader will observe in Table 1 that the results obtained from

the control injection of secretin at the beginning of the experiment

is uniformly greater than that obtained after several injections of

digested secretin.

In view of the established fact that equal quantities of secretin can

generally be relied on to produce results,[21] one might suggest that

the injections of the split products of secretin have inhibited to some

degree the action of the pancreas. We can submit the data in Table 3

in support of this view, showing among other things that the action of

secretin is not influenced by previous injections of inert depressor

substances, though it by the injection of the cleavage products of

secretin. (The various injections in the experiments were made at about

fifteen-minute intervals).

We have carefully analyzed the reaction in blood pressure that follows

the injection of the various preparations. We find no constant effect.

Digested secretin gives a fall in blood pressure that is at times less,

at times equal, and at other times greater (Fig. 1) than that produced

by the original preparation.

Besides the bearing that it has on _the therapeutic use of secretin_,

this destructive action of the digestive enzymes is also of prime

physiologic interest. Failure to realize it has led to misconceptions

as to the intrinsic nature of secretin.

TABLE 3.--EXPERIMENTS 8 AND 9

Pancreatic

Preparations Juice Drops

Experiment 8:

10 c.c. secretin, five injections of inert depressor substances 29

10 c.c. secretin, two injections of completely digested secretin 28

10 c.c. secretin, eight injections of inert depressor substances 16

10 c.c. secretin 16

Experiment 9:

10 c.c. secretin (control, beginning of experiment) 21

10 c.c. secretin, after thirty minutes incubation with 1 c.c.

_boiled_ gastric juice 27

10 c.c. secretin, after thirty minutes incubation with 1 c.c.

_fresh_ gastric juice 11

10 c.c. secretin (control, end of experiment) 18

The findings of Lalou, confirmed by us, explain the anomaly that has

led Delezenne[88] to put forward the antisecretin theory.

[88] Delezenne and Pozerski: Jour. de Physiol., =14=:540, 1912.

SECRETIN HAS NO ACTION WHEN GIVEN BY MOUTH

It is a constant claim that so many and complex are the factors

concerned in physiologic processes, that it is not unusual for clinical

deductions to establish themselves in the face of _a priori_ laboratory

dicta. We considered it desirable, therefore, to test the action of

secretin, orally administered, in the most direct manner, and the one

freest from possible criticism. With this in view, we performed a

series of experiments on normal unanesthetized dogs having permanent

pancreatic fistulas.

_Method._--In the operations for permanent pancreatic fistulas we

followed closely the technic developed by Pawlow,[89] and with

excellent results. The dogs maintain themselves in splendid condition

if proper care is taken. This consists in feeding them only with bread

and milk, and giving sodium bicarbonate daily. The dogs were given

this treatment in the evening so that experimental procedure might be

carried on in the day with empty stomach under constant conditions.

Freshly prepared secretin in large quantities was given by stomach

tube to these dogs, and the response of the pancreas studied and

compared with the response obtained from control preparations. The same

preparation was generally not given on consecutive days.

[89] Pawlow: Ergeb. de Physiol., O., p. 266, 1902.

TABLE 4.--DETAIL OF TYPICAL EXPERIMENTS

Dogs with pancreatic fistulas, showing that secretin given by mouth has

no action on the pancreas

===================================================================

| Rate of Secretion of Pancreatic

| Juice in C.c. per Hr.

+------------------+------------------

| Continuous | Continuous

| Secretion | Secretion

Material Fed by Stomach Tube | Before Feeding | After Feeding

|-----+------+-----+-----+------+-----

-----------------------------+-----+------+-----+-----+------+-----

slightly acid | 6.5| 3.6 | 3.9 | 20.0| 6.0 | 8.0

slightly alkaline | 13.0| 11.0 | 5.0 | 23.0| 26.0 | 12.0

through Berkefeld | 7.8| 7.5 | 7.4 | 23.0| 13.0 | 11.0

150 c.c. extract of colon | 11.6| 12.0 |11.4 | 30.0| 19.6 | 14.8

mucosa | 10.0| 7.0 | 8.0 | 23.0| 7.5 | 4.0

150 c.c. extract of muscle | 6.9| 11.0 | 6.4 | 35.0| 5.0 | 7.0

(diluted to 250 c.c.) | 6.0| 8.0 | 4.0 | 33.0| 36.0 | 17.0

-----------------------------+-----+------+-----+-----+------+-----

_Results._--We have data from six dogs with a total of seventy-six

experiments. As shown in Table 4, the administration of secretin causes

an increase in the flow of pancreatic juice, _but_ the administration

of inert substances as extracts of colon, gastric mucosa or muscle

causes a like increase. The activity of the secretin may be reduced to

a low value by exposure to sunlight, or filtering through a Berkefeld

filter, yet the response of the pancreas is not correspondingly

reduced. The secretion that occurs in the control cases, every one

will admit, is but secondary to the production of gastric juice with

its accompanying hydrochloric acid, that is, excited by virtue of the

extractives and water in the preparations. Such, we can prove, is the

only action of secretin. A mixture of gelatin, peptone and salt water,

the chief incidental constituents of a secretin preparation, gives as

striking results as ever obtained from secretin administration. Yet

the objection may be made that the response of the pancreas that is

due to the incidental constituents of secretin is maximal, and that

the secretin consequently has no opportunity to display its particular

potency. But, as inspection of the accompanying tables illustrate,

the administration of hydrochloric acid shows that the response is by

no means maximal. Let us cite a striking experiment. For three hours

before the administration of hydrochloric acid, the secretion in cubic

centimeters was respectively 29.4, 11.75 and 35.4 c.c.; for the three

hours after, respectively 88.0, 49.0 and 40.5 c.c.

[Illustration: Fig. 1.--Tracings (reduced two-thirds) showing failure

of Secretogen, Elixir Secretogen, and Duodenin to stimulate the flow of

pancreatic juice even when administered intravenously in amounts three

times greater than that recommended to be given by mouth. Dog: light

ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood

pressure; _b_, flow of pancreatic juice in drops; _c_, signal showing

where the intravenous injections were made. Tracing A: Reading from

left to right, the five intravenous injections are: (1) three tablets

of Secretogen digested with 15 c.c. 0.4 per cent. hydrochloric acid

and neutralized; (2) three tablets of Secretogen boiled in 15 c.c.

0.4 per cent. hydrochloric acid and neutralized; (3) three tablets of

Secretogen in 15 c.c. 0.9 per cent. sodium chlorid; (4) three tablets

of Secretogen in 15 c.c. of 70 per cent. alcohol; (5) 15 c.c. Elixir

Secretogen. Tracing B: reading from left to right, the four intravenous

injections are: (1) 5 c.c. secretin made fresh from dog’s duodenal

mucosa; (2) three tablets of Duodenin digested in 15 c.c. 0.4 per cent.

hydrochloric acid and neutralized; (3) three tablets of Duodenin boiled

in 15 c.c. 0.4 per cent. hydrochloric acid and neutralized; (4) three

tablets of Duodenin in 15 c.c. sodium chlorid (0.9 per cent.).]

TABLE 5.--SUMMARY OF EXPERIMENTS

Dogs with pancreatic fistula, weight 14 kg. Secretin given by mouth

====================================================================

| |Rate of Secretion|

| | of Pancreatic |

| | Juice in |

No. of | | C.c. Per Hour |Increase

Experi-| Material Fed +--------+--------+ in

ment | | Three | Three | C.c.

| | Hours | Hours |

| | Before | After |

| |Feeding |Feeding |

-------+---------------------------------+--------+--------+--------

3 |Secretin slightly acid | 5 | 11 | 6

5 |Secretin slightly alkaline | 24 | 30 | 6

4 |Secretin passed through Berkefeld| 18 | 23 | 5

1 |Secretin exposed to sun for 4 hrs| 16 | 29 | 13

2 |Extract of colon (rabbit) | 19 | 29 | 10

3 |Extract of gastric mucosa | 14 | 23 | 9

3 |Extract of muscle | 8 | 16 | 8

2 |Mixture of gelatin, peptone and | 23 | 33 | 10

| salt | | |

1 |1 per cent. peptone solution | 6 | 8 | 2

4 |0.2 per cent. hydrochloric acid | 13 | 37 | 24

3 |Milk and bread | 7 | 20 | 13

-------+---------------------------------+--------+--------+--------

It is possible by large doses of sodium bicarbonate given shortly

before the administration of a preparation so to depress the stomach

that it does not respond with the usual production of hydrochloric

acid. Under these conditions the administration of secretin is

uniformly negative, but the administration of hydrochloric acid on the

contrary still serves to increase the pancreatic secretion (Table 6).

TABLE 6.--SECRETIN IN EXPERIMENTAL “ACHYLIA GASTRICA”

====+=================================================================

| | Rate of Secretion of Pancreatic Juice

| | in C.c. Per Hour

| +--------------------+-------------------

Exp.| Material Fed |Continuous Secretion| Secretion After

No. | | Before Feeding* | Feeding

| +------+------+------+------+------+-----

----+------------------------+------+------+------+------+------+-----

1 |} {| 8.7 | 7.5 | 6.8 | 3.0 | 1.0 | 4.8

2 |} 150 c.c. secretin {| 4.5 | 6.5 | 10.0 | 6.0 | 7.5 | 7.6

3 |} {| 15.6 | 8.1 | 16.0 | 3.9 | 4.9 | 2.9

| | | | | | |

1 |} 150 c.c. 4% HCl {| 9.8 | 7.0 | 6.0 | 65.1 | 28.0 | 7.1

2 |} (diluted to 250 c.c.){| 17.4 | 18.5 | 17.0 | 34.0 | 18.0 | 20.0

----+------------------------+------+------+------+------+------+-----

* Five gm. Na HCO₃ given at beginning of each first two hours.

COMMERCIAL PREPARATIONS OF SECRETIN

_Secretogen and Elixir Secretogen._--The Carnrick Company offers

Secretogen[90] for use in a large number of conditions. The following

indications for the use of the preparation purport to be based on

clinical tests covering a period of several years: dyspepsia, and

the indigestions generally, fermentative disorders, gastric catarrh,

flatulence, nausea; pancreatic insufficiency, intestinal indigestion;

gastric secretory deficiencies, apepsia; constipation and hepatic

torpor; intestinal stasis; diarrhea; infantile diarrhea, “summer

complaint,” marasmus, inanition and malnutrition; gastric atony and

dilatation; cholecystitis and gallstones; nephritis, neurasthenia,

cachexia and cancer; epilepsy and high blood pressure. Testimonials are

presented as to results in most of these conditions.

[90] Secretogen, Report of the Council on Pharmacy and Chemistry,

J. A. M. A., May 1, p. 1518, 1915.

A quantity of “Secretogen” and “Elixir Secretogen” was bought in

the open market, and the preparations were tested on suitably

prepared dogs. The tablets were ground, thoroughly macerated with the

solvent used (water, normal salt solution, alcohol, or 0.4 per cent.

hydrochloric acid), and filtered. If hydrochloric acid was used, the

pulverized tablets were boiled with it, in the manner that secretin is

made from duodenal mucosa, and the preparations neutralized previous

to injection. The injections were made in from 15 to 20 c.c. of the

solvent. All the operations were carried on immediately before the

experiment, and as rapidly as possible, so as to avoid oxidation. The

Elixir Secretogen was injected directly, without dilution.

TABLE 7.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF

SECRETIN IN “SECRETOGEN” AND “ELIXIR SECRETOGEN” EXCEPT IN OCCASIONAL

TESTS WHEN ADMINISTERED IN ENORMOUS DOSES

Dogs under ether anesthesia

=======================================================================

| | Secretion of Pancreatic Juice in Drops,

| Quantity of | Following Intravenous Injection

Exp.| Secretogen +--------+---------------------------+------+--------

| Secretogen |Control +---------+----+-------+----+ |Control

| Used* |10 C.c. |Distilled|0.4%| 70% |0.9%|Elixir|10 C.c.

----+-------------+--------+---------+----+-------+----+------+--------

1 |Secretogen, | | | | | | |

| 1 tablet; | 109 | 0 | 0 | 0 | 0 | 0 | 59

| 15 c.c. | | | | | | |

1 |Secretogen, | | | | | | |

| 6 tablets | ... | .. | 0 | .. | .. | .. | ..

2 |Secretogen, | | | | | | |

| 3 tablets; | 16 | 0 | 0 | 0 | 0 | 1(?)| 16

| 15 c.c. | | | | | | |

3 |Secretogen, | | | | | | |

| 5 tablets | ... | .. |1(?)| .. | .. | .. | ..

4 |Secretogen, | | | | | | |

| 25 tablets | 14 | .. |1(?)| .. | .. | .. | 8

5 |Secretogen, | | | | | | |

| 100 tablets | 110 | .. | .. | .. | 21 | .. | 67

6 |Secretogen, | | | | | | |

| 100 tablets;| 19 | .. | 5 | .. | 1 | 2(?)| 8

| 125 c.c. | | | | | | |

7 |Elixir, | | | | | | |

| 50 c.c. | ... | .. | .. | .. | .. | 1(?)| ..

----+-------------+--------+---------+----+-------+----+------+--------

* One to three tablets is (according to the label) the therapeutic dose

of Secretogen; 4 to 12 c.c. the dose of Elixir Secretogen.

_Results._--In only one case was a slight response obtained, the others

gave none. Small and large doses were equally inert (Table 7, Figs.

2, 3). The preparations, though inert, always produced a depression

in blood pressure, sometimes even greater than that caused by active

secretin. Among our many tests, one bottle was found, however, to be a

little different from the rest (Experiment 4). Its entire content, 100

tablets, had been ground and boiled in 0.9 per cent. sodium chlorid.

The extract on injection was found to have a small but unmistakable

secretin reaction, equivalent to about 2 c.c. of the control secretin

used. But repeated experiments were unable to duplicate this result.

The “Secretogen” and “Elixir Secretogen” were all supposedly fresh

preparations, the retail drug store informing us that a fresh supply

was obtained from the wholesale house each week.

Secretogen, then, contains practically no secretin, and even if it did

contain secretin, it can have no effect on the pancreas when taken by

mouth. The indications for Secretogen, therefore, are based on false

premises, and the testimonials are worthless.

[Illustration: Fig. 2.--Tracings (reduced one-half) showing no

stimulation of the pancreas by Secretogen, Elixir Secretogen, and

Duodenin, even when administered intravenously in quantities one

hundred times greater than the therapeutic dose by mouth. Dog: Light

ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood

pressure; _b_, flow of pancreatic juice in drops. Tracing A: at _x_,

intravenous injection of 10 c.c. secretin prepared from duodenal mucosa

of dog. Tracing B: at _x_, intravenous injection of 100 tablets of

Secretogen digested with 0.4 hydrochloric acid and neutralized. Tracing

C: at _x_, intravenous injection of 100 tablets of Secretogen, prepared

as in Tracing B. Tracing D: at _x_, intravenous injection of 50 c.c.

Elixir Secretogen. Tracing E: at _x_, intravenous injection of 100

tablets of Duodenin (dissolved in 0.9 per cent. sodium chlorid).]

_Duodenin._--This is a preparation manufactured by Armour & Company,

which purports to be “secretin plus enterokinase.” The claims for

this product are similar to those for Secretogen, but somewhat less

sweeping. According to the manufacturers, “Duodenin (Armour) is

recommended in the treatment of intestinal disorders where an increased

flow of pancreatic, hepatic and intestinal secretion is desired. It is

of specific value in proteid digestion on the theory that secretin and

enterokinase stimulate the pancreas and activate its secretion.”

[Illustration: Fig. 3.--Tracings (reduced one-half) showing practically

complete destruction of secretin by the gastric juice. Dog under light

ether anesthesia; cannula in the pancreatic duct; _a_, carotid blood

pressure; _b_, record of flow of pancreatic juice in drops. Time,

twenty-five minutes. Tracing A: intravenous injection of 10 c.c.

secretin (prepared fresh from dog’s duodenal mucosa) at _x_. Tracing B:

intravenous injection (at _x_) of 10 c.c. of the same secretin as in

Tracing A, after being digested in normal human gastric juice at 37 C.

for two hours.]

We bought a quantity of Duodenin in the open market, and carried out on

this product the same series of experiments as that used in the case of

Secretogen. The results were similarly negative (Table 8).

TABLE 8.--SUMMARY OF TYPICAL EXPERIMENTS SHOWING THE ABSENCE OF

SECRETIN IN “DUODENIN”

Dogs under ether anesthesia

=================================================================

| | Secretion of Pancreatic Juice in Drops,

| | Following Intravenous Injection

Exp.| Number +--------+-------------------------------+----------

No. |Duodenin| Control| Duodenin in | Control

| Tablets| 10 C.c.+---------+------+-------+------+ 10 C.c.

| Used |Secretin|Distilled| 0.4% | 70% | 0.9% | Secretin

----+--------+--------+---------+------+-------+------+----------

1 | 3 | 29 | 0 | 0 | 0 | 1(?)| 28

1 | 6 | ... | .. | 1(?)| .. | .. | ..

2 | 18 | 16 | .. | 6 | .. | .. | 16

3 | 5 | 14 | .. | 0 | 0 | 0 | 8

3 | 25 | ... | .. | 1(?)| .. | .. | ..

4 | 100 | 110 | .. | 0 | .. | .. | 67

5 | 150 | 19 | .. | 0 | .. | 0 | 8

----+--------+--------+---------+------+-------+------+----------

In regard to both Secretogen and Duodenin, we assume that the

manufacturers have tried to put secretin in them, but have been unable

because they have failed, in all likelihood, to check their methods

by physiologic standardization. These firms do not give any details

as to the procedure they employed in their manufacture of secretin.

Desiccated secretin of extreme potency has been prepared by various

physiologists,[91] 1 mg. (1/64 grain) of which is active when given

intravenously. It is difficult to conceive that any of these methods

were used in the preparation of Secretogen or Duodenin.

[91] Stepp (Note 13). Dale and Laidlow: Jour. Physiol. =44=:11, 1912.

Launoy and Ochslin: Comp. rend. Soc. de biol., =74=:338, 1913.

CONCLUSIONS

1. Secretin is quickly destroyed by gastric juice and by trypsin.

2. Secretin is not absorbed in active form from the alimentary tract.

3. The presence of secretin or prosecretin cannot be demonstrated in

the commercial preparations “Secretogen,” “Elixir Secretogen” and

“Duodenin” even when the therapeutic dose of the preparations is given

intravenously. In the case of “Secretogen,” intravenous injection of

100 times the therapeutic dose reveals occasionally an insignificant

trace of secretin.

DISCUSSION OF RESULTS

It is, of course, objectionable that preparations containing no

secretin should be advertised to the medical profession as containing

this substance. The more important blunder, however, consists in the

attempt to offer such preparations for oral administration, because

even chemically pure secretin would be equally ineffective when taken

by mouth. There is as yet no reliable evidence that lack of secretin

is a primary or important factor in any disease. Even should this be

established, secretin therapy, to be effective, must be intravenous.

Secretin has not yet been prepared in sufficiently pure state to render

possible intravenous injection in man without injurious effects. And

even when this has been attained, the very fleeting action of secretin

will in all probability render secretin therapy as futile in all the

diseases in which it is theoretically indicated as epinephrin therapy

is in Addison’s disease.

But there remains the alleged favorable effect from secretin therapy

by mouth in various diseases in man. It is, perhaps, impertinent for

laboratory men to comment on these clinical results. The ordinary

“testimonials” need not be considered, but we should like to ask the

serious worker who thinks he has actually obtained good results from

secretin therapy how certain he is of the causal relation between the

giving of secretin or alleged secretin and the abatement of the disease.

When a therapeutic measure not only lacks a positive basis in

physiology and pathology but runs contrary to all the well-established

experimental facts in these fundamental medical sciences, is it too

much to ask that positive clinical findings be subjected to more than

usual critical analysis before acceptance? “_Clinical tests_,” it is

said, “covering a period of several years have proved that neither the

condition in the stomach during digestion nor those in the intestine

prevent the secretin from entering intact into the circulation.” When

we meet claims such as this, should we not scrutinize the “tests” as

well as the men who make them?

We are indebted to Dr. J. H. Moorehead for assistance in part of the

surgical work.--(_From The Journal A. M. A., Jan. 15, 1916._)

ARTICLES REFUSED RECOGNITION

Report of the Council on Pharmacy and Chemistry

Below appear abstracts of the Council’s action on articles refused

recognition which were not deemed of sufficient importance to require

lengthy reports:

Radio-Rem

The Radium Therapy Company, Schieffelin & Co., selling agents,

submitted to the Council radium emanation generators called “Radio-Rem

Outfits,” designed to generate respectively 200, 1,000, 2,000, 5,000

and 10,000 Mache units per twenty-four hours.

Those who are well informed on the subject of radium therapy are of the

opinion that the administration of small amounts of radium emanation

such as generated by certain outfits is without therapeutic value. It

has been stated that at the Radium Institute of London the minimum

preliminary dose is 185 microcuries (500,000 Mache units), and as many

as 555 microcuries (1,500,000 Mache units) are employed.

In consideration of these facts the Council voted not to accept any

radium emanation generator which produces less than 2 microcuries

of emanation during twenty-four hours. Accordingly, while accepting

Radio-Rem Outfit No. 5, claimed to produce 10,000 Mache units (3.7

microcuries) and Radio-Rem Outfit No. 4, claimed to produce 5,000 Mache

units (1.8 microcuries), the Council voted not to accept Radio-Rem

Outfit No. 3, claimed to produce 2,000 Mache units (0.74 microcurie),

Radio-Rem Outfit No. 2, claimed to produce 1,000 Mache units (0.37

microcurie), and Radio-Rem Outfit C, claimed to produce 200 Mache units

(0.07 microcurie).

This report having been submitted to Schieffelin & Co. and their reply

considered, the Council authorized publication of the report. [See also

_Reports of Council on Pharmacy and Chemistry_, 1916, p. 631.]

Olio-Phlogosis

Olio-Phlogosis, a liquid preparation to be applied externally by means

of a cotton pad, is advertised by the Mystic Chemical Company, Kansas

City, Mo., thus:

“Doctor: Don’t fail to use Olio-Phlogosis liberally for Pneumonia,

Bronchitis and Pleurisy. It works quickly. Olio-Phlogosis is as far

ahead of all medicated kaolin plasters as these plasters were ahead

of the old-time moist and soggy poultices.”

A pamphlet advises the use of Olio-Phlogosis in

“... all cases of Inflammation and Congestion, such as Pneumonia,

Bronchitis, Pleurisy, Croup, Boils, Carbuncles, Rheumatism,

Swollen Glands, Peritonitis, Ovaritis, as a Surgical Dressing,

Mamitis [Mastitis (?)] Vaginitis and Metritis (on cotton tampon

to deplete these parts), Septic Wounds, Old Ulcers, Chilblain,

Eczema, Neuralgia, Inflammation of the Eyes and Ears, Alveolar

Inflammation, Burns, Scalds, Etc.”

According to the information sent to the Council by the Mystic Chemical

Company, Olio-Phlogosis has the following composition per gallon:

Ol. Eucalyptus Gaultheria drs. 8

Ol. Abies Canadensis drs. 8

Ol. Abies Canadensis drs. 2

Ol. Thyme (white) drs. 2

Resublimated Iodin crystals grs. 32

Resorcin drs. 1

Acid Boracic C. P. drs. 2

Quinine Bisulphate drs. 4

Sodium Thiosulphate drs. 3-1/2

Glycerin C. P. q. s. ad gal. 1

A nonquantitative formula which appears on the label of a sample bottle

sent to a physician enumerates the same ingredients except the sodium

thiosulphate.

The A. M. A. Chemical Laboratory reports that no free iodin could be

detected in the preparation.

Apparently, then, Olio-Phlogosis is essentially a skin irritant applied

by means of cotton; it can be expected to be just about as effective

as the old-fashioned cotton pneumonia jacket, used in conjunction with

an aromatic skin irritant, such as camphorated oil or wintergreen or

menthol ointment. The odor may have some psychic effect, and it is

possible that some of the oily matter may be absorbed by the skin. That

such small amounts, even if absorbed, can produce any considerable

systemic effect, however, is highly improbable, and the advice that

this preparation be relied on in pneumonia, pleurisy, peritonitis,

etc., is pernicious. In the few cases of pneumonia in which heat is

indicated, the plain cotton pad will usually be found sufficient. If

the physician consider the addition of a skin irritant desirable, it is

easy to select one from the official preparations. It will be far more

rational to do so than to invoke the aid of a mystic name and a complex

formula to which the patient and his family, at least, will be led to

give unmerited credit.

The claims made for Olio-Phlogosis are unwarranted; its composition

is complex and irrational, and the nondescriptive but therapeutically

suggestive name is likely to lead to uncritical use. The Council

voted that the product be refused recognition for conflict with Rules

6, 8 and 10, and that this report be published.--(_From The Journal

A. M. A., Aug. 19, 1916._)

THE HYPOPHOSPHITE FALLACY

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its

publication.

W. A. Puckner, Secretary.

The introduction of hypophosphites into medicine was due to an

erroneous and now discarded theory as to the cause of tuberculosis of

which one Dr. J. F. Churchill of London, and later of Paris, was the

promulgator and propagandist.[92] This theory was that the so-called

“tuberculosis diathesis” was due to a deficiency of phosphorus in

the blood. Believing that the hypophosphites, while nontoxic, were

capable of further oxidation in the organism, Churchill recommended

them as the best means of supplying the supposedly lacking phosphorus.

It is now known that tuberculosis is not due to a deficiency of

phosphorus. Of more importance is the fact, now known, that little

phosphorus, if any, is assimilated from the hypophosphites--far

less than from phosphorus compounds of ordinary food.[93] There is

no justification for giving hypophosphites for the sake of their

phosphorus content. For various reasons, however--partly from force of

habit and partly because of the power of advertising--many physicians

still prescribe hypophosphite preparations, and consequently, they

are still included in the Pharmacopeia and in textbooks on materia

medica and therapeutics. They are put out in the form of “specialties”

and of proprietary preparations, and are lauded extravagantly by the

manufacturers of the latter.

[92] Churchill, J. F.: De la cause immédiate et du traitement

spécifique de la phthisie pulmonaire et des maladies tuberculeuses,

Paris, 1858.

[93] The Hypophosphite Fallacy, J. A. M. A., April 25, 1914, p. 1346.

Although the overwhelming weight of evidence was against the

probability that the hypophosphite preparations are of value as

therapeutic agents, the Council thought it well to investigate the

subject. Dr. W. McKim Marriott of Baltimore was therefore requested to

review the evidence for and against the therapeutic usefulness of the

hypophosphites and to conduct such experiments as seemed necessary. His

report has already appeared in The Journal.[94]

[94] Marriott, W. McKim: The Therapeutic Value of the Hypophosphites,

J. A. M. A., Feb. 12, 1916, p. 486.

Dr. Marriott found that nine observers (Paquelin and Joly, Vermeulen,

Boddaert, Massol and Gamel, Panzer, Delaini and Berg), who endeavored

to test the alleged utilization of the hypophosphites in the organism,

reported that there is complete, or practically complete, elimination

of hypophosphites in the urine, with little or no effect on the body.

Only one experimenter (Patta) claimed that a considerable amount

of ingested hypophosphite was retained in the body; however, he

used a method now known to be inaccurate and made obvious errors in

calculation, so that his conclusions were unwarranted.

Since the evidence was even to this extent contradictory, Marriott

performed a series of experiments. The methods of this study and

details of results are described in his paper, in which he also

discusses the experiments of some other observers. Marriott writes:

“None of the subjects of the experiment [Marriott’s] experienced

any effect whatsoever from the administration of the drug....

Almost all of the ingested hypophosphite is promptly eliminated

unchanged....

“These experiments [Forbes’] demonstrate conclusively that the

hypophosphites possess no specific value as a source of phosphorus

for the body. This is not to be wondered at in view of the fact

that 85 per cent. of the phosphorus ingested in the form of

hypophosphite is excreted unchanged, and there is no proof that

even the remaining 15 per cent. is available to the organism. It is

doubtful if there are any conditions in which the body suffers from

lack of phosphorus. Even should such conditions exist, phosphorus,

in the form that it occurs in the ordinary foods, or as phosphates,

is more efficient in supplying the deficit than hypophosphites

that must be oxidized before utilization and which are only about

15 per cent. oxidized, if at all. For example, half a glass of

milk contains more available phosphorus than three large doses of

hypophosphites of 15 grains each, as great a dosage as is usually

given.

“What, then, is the therapeutic value of hypophosphites? There is

no reliable evidence that they exert a physiologic effect; it has

not been demonstrated that they influence any pathologic process;

they are not ‘foods.’ If they are of any use, that use has never

been discovered.”

In view of the foregoing, it seemed to the Council advisable to

examine the claims under which a few of the proprietary hypophosphite

preparations are marketed. The following are representative:

FELLOWS’ SYRUP OF HYPOPHOSPHITES

No very exact information concerning the composition is furnished by

the manufacturers (Fellows Medical Mfg. Co., New York). They say that

the product

“... contains the chemically pure hypophosphites of iron, quinin,

strychnin, calcium, manganese and potassium, agreeably blended

in the form of a bland, stable syrup with a slightly alkaline

reaction....

“Each fluid drachm contains the equivalent of 1-64th of a grain of

pure strychnin.”

The Fellows’ Hypophosphites advertising furnishes something like a

barometer of the popular status of hypophosphites. In one circular

(undated, but, from certain references contained in it, presumably

issued ten or fifteen years ago) we read:

“It is an indubitable fact that the hypophosphites have earned

the distinction of having their therapeutic value more completely

established than have any other remedial agents.... it is only by

accepting the current view, which was originally advanced by Mr.

Fellows, that we can satisfactorily account for the incontestable

fact that the hypophosphites are of supreme importance in the

treatment of a very extensive variety of affections.... the

hypophosphites increase the consumption of oxygen and the

elimination of carbon dioxide. In this manner, they stimulate

nutrition and promote constructive metamorphosis.... It is

now universally conceded that the widespread utility of the

hypophosphites is due to the fact that they substantially improve

metabolic processes, thus increasing the disease-resisting capacity

of all the tissues.”

The circular, continuing, emphasizes the “incomparable

phosphorus-contributing properties” of Fellows’ Syrup, its

“extraordinary reconstructive properties” and “the magnificent results

which invariably attend its employment in the treatment of anemia,

chronic bronchitis, chlorosis, neurasthenia, mollities ossium, delayed

union of fractures, rickets, convalescence,” etc.

A circular bearing the copyright date 1914, on the other hand, admits

that:

“The theories for the favorable action of Fellows Syrup of

Hypophosphites have undergone several changes.”

The same circular further maintains, however, that:

“... the fact has never been challenged that in Fellows Syrup of

Hypophosphites we have one of the most efficient, most complete,

most all-around tonics and roborants in the materia medica.”

No attempt is made to base this assertion on the therapeutic action

of the constituents. In other words, the old theory, which formed the

basis for the popularity of Fellows’ Syrup, has been thrown overboard,

but no substitute is deemed necessary; the momentum already acquired is

apparently regarded as sufficient to insure its continued sale.

Fellows’ Syrup of Hypophosphites is a semisecret, unscientific

preparation--an affront to sound therapy--exploited by means of

extravagant and misleading statements.

SYRUPUS ROBORANS (SYRUP HYPOPHOSPHITES COMP. WITH QUININ,

STRYCHNIN AND MANGANESE)

Little information concerning this preparation seems to be furnished

at present by the manufacturers, Arthur Peter & Co., Louisville, Ky.

According to an old circular, it contains, in each fluidounce,

Grains

“Hypophos. Potass. 1-1/2

Hypophos. Manganese 1

Hypophos. Lime 1

Hypophos. Iron 1-1/2

Hypophos. Quinin 6/16

Hypophos. Strichnin 1/16

“1/128 grain Strychnia to Teaspoonful.”

Further, according to the same circular:

“The Hypophosphites are especially useful in all diseases where

there is a lack of nutrition.... They are the best of all remedies

in Rachitis, non-union of fractures, Osteomalacia and Syphilitic

Periostitis.”

As for Syrupus Roborans itself:

“This elegant preparation is ... the best general tonic and

reconstructive known.”

The unwarranted therapeutic claims formerly made for it seem to be no

longer circulated. Syrupus Roborans is an unscientific, shotgun mixture.

SCHLOTTERBECK’S SOLUTION HYPOPHOSPHITES OF LIME AND SODA (LIQ.

HYPOPHOSPHITUM, SCHLOTTERBECK’S)

The Schlotterbeck & Foss Co., Portland, Maine, the manufacturers, say

of their preparation:

“This solution contains 30 grains of the combined Hypophosphites of

Lime and Soda to the ounce. It contains No Sugar, No Acid and it is

Perfectly Neutral.”

“Indications for use.--Galactostasis, Imperfect Metabolism,

Neurasthenia, Nervous Dyspepsia, Insomnia, Convalescence,

Acetonuria, Cyclic Vomiting in Infants, Diabetes, Starvation,

Deficiency of Lime, Mother’s Teeth during Pregnancy, Dentition of

Infants, Rachitis, Furunculosis, Vomiting of Pregnancy, Obesity.”

“Migraine is often caused by conditions for which this Solution is

one of the most satisfactory remedies:”

“In Insomnia due to advancing age, it will often act as a

hypnotic....”

Of the hypophosphites the Schlotterbeck & Foss Company say:

“If ‘damning it with faint praise’ on the part of some of the

leading medical authorities, or utterly condemning it as useless,

on the part of others, would kill a medicine, the Hypophosphites

would long since have disappeared as medicinal agents. Negative

testimony in regard to the value of a drug does not settle

anything.”

Of their own preparation they say:

“When we get the results that ought to follow the administration of

Hypophosphites, we have proved that Schlotterbeck’s Solution enters

the system unchanged.”

“This Solution is primarily a blood and nerve tonic and chemical

food.”

Schlotterbeck’s Solution of Hypophosphites of Lime and Soda is a

semisecret preparation marketed under claims that are both unwarranted

and misleading.

ROBINSON’S HYPOPHOSPHITES

According to the manufacturers, the Robinson-Pettet Company,

Louisville, Ky., each fluidounce of this preparation contains:

“Hypophosphites Soda 2 gr.

Hypophosphites Lime 1-1/2 gr.

Hypophosphites Iron 1-1/2 gr.

Hypophosphites Quinin 3/4 gr.

Hypophosphites Strychnine 1/16 gr.”

It is claimed to be

“Nutritive, Tonic Alterative. A Standard Remedy in the treatment of

Pulmonary Phthisis, Bronchitis, Scrofulous Taint, General Debility,

etc. Stimulates Digestion, promotes Assimilation.”

The declared composition of the preparation is unscientific, and the

therapeutic claims are unwarranted.

EUPEPTIC HYPOPHOSPHITES

Nelson, Baker & Co., Detroit, Mich., who market Eupeptic

Hypophosphites, call this preparation:

“A superior combination containing the Hypophosphites of Potassium,

Calcium, Iron and Manganese, and the bitter tonics, Quinin and

Strychnin, agreeably associated with natural digestive ferments

of the pancreatic secretion. It is thus a general reconstructive

tonic.... The remedy is of especial value in the treatment of

mental and nervous affections.... It is indicated in pulmonary

tuberculosis, in all wasting diseases, in debilitated conditions

generally and in all exhaustion from over work.”

On the basis of the manufacturer’s statement, Eupeptic Hypophosphites

must be regarded as a semisecret, unscientific, shotgun preparation,

exploited through unwarranted therapeutic claims.

MCARTHUR’S SYRUP OF THE HYPOPHOSPHITES COMP. (LIME AND SODA)

So far as the recent literature and trade package are concerned, no

information as to the composition of this product is furnished beyond

what is conveyed in the name. The advertising for McArthur’s Syrup,

like that for Fellows’ Syrup and Peters’ Syrupus Roborans, has been

modified as time has passed. A few years ago it was advertised under

such claims as the following:

“... Has Stood the Test during many years for unequaled efficacy

in the treatment of Tuberculosis.... Indicated also as a Tonic and

Tissue Builder in convalescence from Fevers, in Nervous Diseases,

Rickets, Senile Debility and Bronchitis.”

“Its use is indicated in ... diseases of the chest, chronic cough,

throat affections, general debility, brain exhaustion, cholera

infantum and wasting diseases of children.”

At present no definite claims seem to be made for it; the manufacturers

evidently find the magic name of hypophosphites sufficient to evoke

the spell for which the advertisement writer’s aid was once sought.

A testimonial contained in a circular which seems to be still used

illustrates both the kind of aura which surrounds hypophosphites in

the minds of physicians who are still living in the past, and the kind

of logic which has made the reputation of this and many other equally

worthless preparations.

“Just about six years ago I had a severe attack of La Grippe which

almost killed me. Left me with Asthma (Catarrh) and a severe cough.

Did not get out of the house for three months. Took over a dozen

bottles McArthur’s Hypophos.--came out all right and since then

worked hard, but last Fall took another cold, but worked on, used

McArthur’s Hypophos., am using it now, am on my 12th bottle.

“I have five or six patients whom I have put on McArthur’s

Hypophos., but I do not prescribe the single bottle, but

_wholesale_ no less than half dozen bottles. One patient is on

his 24th bottle with orders to get another half dozen and keep it

up all winter. I have given the same order to all (keep it up all

winter) and I myself intend to do the same, for with its use I have

lost no time--rain or shine I am doing my work. I know what it has

done for me and what it is doing for my patients.”

It would be hard to find a more characteristic example of the naïve

mental processes of the simple folk who in all good faith write

testimonials for worthless medicines. This well-meaning practitioner

(a homeopath, by the way), because he “came out all right” after an

attack of grip, returns all praise to McArthur’s Hypophosphites, which

he has taken “wholesale.” Not the faintest doubt of the validity of

his _post hoc ergo propter hoc_ argument seems to glimmer across his

consciousness.

McArthur’s Syrup of the Hypophosphites is an irrational preparation.

While its faults are fewer and less glaring than those of some other

proprietaries, the circulation of such a testimonial as the one just

quoted is sufficient of itself to cast suspicion on the product.

BORCHERDT’S MALT OLIVE WITH HYPOPHOSPHITES, MALTZYME WITH

HYPOPHOSPHITES AND MALTINE WITH OLIVE OIL AND HYPOPHOSPHITES

These preparations are now described in the appendix to New and

Nonofficial Remedies. Borcherdt’s Malt Olive with Hypophosphites

(Borcherdt Malt Extract Company, Chicago) is said to contain in each

100 c.c., 0.64 gm. each of calcium and sodium hypophosphites, with

malt extract, olive oil and glycerine. Maltzyme with Hypophosphites

(Malt-Diastase Company, New York) is said to contain, in each

100 c.c., 0.4 gm. each of calcium, sodium and potassium hypophosphites

and 0.005 gm. each of iron and manganese hypophosphites, with

maltzyme. Maltine with Hypophosphites (Maltine Company, Brooklyn,

N. Y.) is said to contain in each 100 c.c., 0.64 gm. each of calcium

and sodium hypophosphites and 0.42 gm. of iron hypophosphite, with

maltine. Maltine with Olive Oil and Hypophosphites (Maltine Company,

Brooklyn, N. Y.) is said to contain, in each 100 c.c., 0.6 gm. each

of calcium and sodium hypophosphites, with maltine and olive oil. In

general, no therapeutic claims are made for these mixtures so far as

the hypophosphites are concerned. The addition of hypophosphites to

such mixtures is irrational and, since it tends to perpetuate the

hypophosphite fallacy, detrimental to sound therapeutics.

THE COUNCIL’S ACTION

The Council endorsed the conclusions of the work of Dr. Marriott

referred to above, and noted: (1) that the therapeutic use of

hypophosphites (except possibly in some cases as a convenient means of

administering the positive element in the salt, as ammonium in ammonium

hypophosphite or calcium in calcium hypophosphite) is irrational; (2)

that the merits of each hypophosphite salt submitted for consideration

under the foregoing exception must be judged individually, and (3)

that Fellows’ Syrup of Hypophosphites, Peters’ Syrupus Roborans,

Schlotterbeck’s Solution Hypophosphites of Lime and Soda, Robinson’s

Hypophosphites, the Eupeptic Hypophosphites of Nelson, Baker &

Co., and McArthur’s Syrup of the Hypophosphites are ineligible for

inclusion in New and Nonofficial Remedies, and that Borcherdt’s Malt

Olive with Hypophosphites, Maltzyme with Hypophosphites, Maltine

with Hypophosphites, and Maltine with Olive Oil and Hypophosphites

be deleted from the appendix of N. N. R. Of these preparations,

all are in conflict with Rule 10; Fellows’ Syrup, Schlotterbeck’s

Solution, Robinson’s Hypophosphites and Nelson, Baker & Co.’s Eupeptic

Hypophosphites are in conflict with Rule 6; the Fellows, Schlotterbeck,

and Nelson, Baker preparations are also in conflict with Rule

1.--(_From The Journal A. M. A., Sept. 2, 1916._)

PULVOIDS CALCYLATES

Report of the Council on Pharmacy and Chemistry

Pulvoids Calcylates 5 grains was submitted by the Drug Products

Company, Inc., New York, under the following claims as to composition:

“When ingested represents the following chemical formulas:

OH)

C₆H₄ COO)₂ Ca.2H₂O + Sr.(C₇H₅O₃)₂ + 2H₂O.”

“Strontium Di-Salicylate 2-1/2 grs. and our especially prepared

Salt of Calcium and Acid Salicylic adjusted in such nascent form,

that these pulvoids upon ingestion will promptly form Calcium

Neutral Di-Salicylate 2-1/2 gr.”

“A combination of Calcium and Strontium Di-Salicylate, in seemingly

true chemical union.”

These statements are rather vague, possibly because they are an attempt

to mystify. The product, however, may be assumed to be a mixture (not a

chemical combination) of calcium salicylate and strontium salicylate.

The therapeutic claims made for the preparation are:

“Superior to ordinary salicylates. Can be taken continuously

and indefinitely without gastric irritation, insuring maximum

efficiency.”

“Reports show surprisingly good results, even where the sodium salt

fails.”

As there is no evidence to show that strontium salicylate, calcium

salicylate or a mixture of the two salts has any advantage over

sodium salicylate, these claims cannot be accepted. The name and the

statement of composition are objectionable in that they do not reveal

the identity of the drugs in “Calcylates” and in suggesting that this

preparation possesses radical advantages over salicylates in other

forms.

The Drug Products Company was told that the facts just mentioned

rendered “Pulvoids Calcylates” ineligible for New and Nonofficial

Remedies. The company in its reply objected to the Council’s

conclusions, and in support of its position submitted testimonials from

a number of physicians. The reply of the company embodied no facts or

arguments which had not been considered by the Council’s referee, and

the testimonials from physicians contained no evidence to show that the

combination has any real advantage over sodium salicylate.

The Council therefore declared “Pulvoids Calcylates” ineligible for

New and Nonofficial Remedies for the following reasons: Unwarranted

therapeutic claims are made for the mixture (Rule 6); the name does not

describe the composition (Rule 8), and the mixture is an unessential

modification of an established remedy (sodium salicylate) (Rule

10).--(_From The Journal A. M. A., Sept. 9, 1916._)

SULFURYL MONAL

Report of the Council on Pharmacy and Chemistry

Sulfuryl Monal is said to be manufactured by Monal Frères,

manufacturing chemists of Nancy, France. It is sold in the United

States by George J. Wallau, Inc., New York City. According to the label:

{Contains: Sulfuryl (combined polysulphurets)

{ = 0.35 centigr.”

“Each Pastille {

{Liberates: Nascent sulphurretted Hydrogen

{ = 2 cub. cent.”

The Chemical Laboratory of the American Medical Association was

requested to check the amount of available hydrogen sulphid. An

original bottle of Sulfuryl Monal was used; this contained tablets

having the taste of licorice extract and an odor of hydrogen sulphid.

The tablets were found to liberate about 6 c.c. hydrogen sulphid to

each tablet.

Among the claims made for the preparation are:

“Dissolved by the saliva, Sulfuryl Monal reaches the stomach

where, under the influence of the gastric juice, it generates

nascent sulphuretted hydrogen. Professor Albert Robin’s remarkable

researches have proven that it is in the nascent state that drugs

produce the greatest effect with the smallest dose.... Being thus

eliminated by the entire respiratory tract: the lungs, bronchi and

the throat, the sulphurretted hydrogen passes from the interior to

the exterior, that is to say, goes right through these organs which

are, as a consequence, thoroughly cleansed, antisepticized and

freed of the pathogenic micro-organisms.... Then, again, part of

the sulphuretted hydrogen, liberated in the stomach, is eliminated

by the mouth and acts as an antiseptic and disinfectant of the

mucous membranes of the throat and mouth. Hence Sulfuryl Monal is a

perfect protective agent against contagious diseases.... Numerous

clinical tests have demonstrated its real efficacy in diseases of

the throat and of the respiratory tract: laryngitis, pharyngitis,

hoarseness, granulations, tonsillitis, colds, bronchitis, pulmonary

catarrh, asthma, emphysema, grippe, whooping cough, simple

and infectious pneumonia, and in the first stage of pulmonary

tuberculosis.”

The sulphids are practically ignored in modern textbooks. There is a

rather extensive clinical literature on the subject, particularly in

connection with sulphur waters; this, however, offers no good evidence

for the therapeutic value of sulphids. Probably the tradition in their

favor is largely due to the old popular idea that a disagreeable taste

or odor is a mark of a good remedy.[95]

[95] Liquid Sulphur--Sulphume, J. A. M. A., Dec. 2, 1911, p. 1853.

When hydrogen sulphid is introduced into the body, the small amounts

that appear in the expired air are insufficient for quantitative

demonstration and it is highly improbable that the amount thus excreted

has any germicidal action, or that enough is excreted in the lungs to

cause irritation and a reaction. The claim that Sulfuryl Monal is “a

perfect protective agent against contagious diseases” is unwarranted;

the recommendation for its use in “simple and infectious pneumonia, and

in the first stage of pulmonary tuberculosis” is dangerous and vicious.

The Council declared Sulfuryl Monal ineligible for New and Nonofficial

Remedies and authorized publication of this report.

[Editorial Note..--With one exception, this product does not appear to

be advertised in medical journals. We find, however, in the gallery

of nostrums that grace the advertising pages of the _International

Journal of Surgery_, that Sulfuryl Monal has its place. According to an

advertisement that has been running some months in this publication,

“affections of the throat and respiratory organs respond promptly” to

Sulfuryl Monal whose “effects are rapid and certain” even in “incipient

tuberculosis.” This preposterous pronouncement is no worse than many

others appearing in the same journal, but it is bad enough to indicate

how uncritical must be the physicians who support--by subscription

or contribution--publications that are still debasing scientific

medicine.]--(_From The Journal A. M A., Sept. 16, 1916._)

MARK WHITE GOITER SERUM AND MARK WHITE IODINIZED OIL

Report of the Council on Pharmacy and Chemistry

The “Mark White Goiter Serum Laboratories” of Chicago asked the Council

to consider its products “Mark White Goiter Serum” and “Mark White

Iodinized Oil.” The “serum” was claimed to be an “antibody blood serum

from a goat with thyroidosis” while the “Iodinized Oil” was said to

contain “about 4 grains of iodin” to “each c.c.” The therapeutic

indications for the treatment were given as:

“Simple or Exophthalmic Goiter, Hyperthyroidism-dosis, Thyrosis,

Thyroidosis, Thyrotoxicosis, Dementia.”

An ampule (2 c.c.) of the “serum” is to be injected into the thyroid

to be followed one week later by an ampule (2 c.c.) of the “Iodinized

Oil.” Repetition of this “treatment” once or twice a month is advised.

The Council asked for more specific information as to the composition

of the remedies, particularly as to the preparation and nature of the

serum; it also asked for evidence of the therapeutic value of the

preparations. In reply, Mark White wrote:

“All that I can say regarding the serum is that it is made from the

blood of goats with thyroid affection, and it has been found that

the serum from these goats has antibodies which control, or has

curative effect upon thyroid affections when injected into thyroid

glands of either humans or animals. As to the iodinised oil, it

is only an adjunct or side treatment which is not always used or

indicated, and will only be furnished to the physician for use in

case in his judgment his patient needs it. We shall also advise the

use of quinin ... when indicated....”

The Council was referred for further information to a paper by Rachel

Watkins, M.D., published in the _Illinois Medical Journal_. It is to

be noted, incidentally, that the letterheads used by White in his

correspondence bore in one corner the notation “Rachel Watkins, M.D.,

Practice Limited to Goiter and Other Disorders of the Thyroid Glands,”

and in the other, “Mark White, Goiter Research.”

The information regarding the composition of this goiter treatment, as

furnished in Dr. Watkins’ paper, was to this effect:

“The medical treatment consists of the administration of a blood

serum derived from a thyrodized goat. Formula: Iodine 0.16 grams

[according to a correction by Mark White, this should read 0.26

gm.], oil 0.25 c.c., serum q. s. 1 c.c.”

This description of the treatment differs from that furnished to the

Council by Mark White in that here the iodin and oil appear to be

combined with the serum. Dr. Watkins’ “formula” implies that the iodin

is a routine medication, thus contradicting White’s statement, which,

in turn, is at variance with the statements made in submitting the

treatment.

[Illustration: Photographic reproductions (greatly reduced) of some of

the letterheads used by the Mark White concern during the past five

years.]

The Council does not accept any biologic product until its sale in

interstate commerce has been authorized by the secretary of the

treasury in accordance with the federal law regulating the sale of

viruses, serums, toxins and analogous products. The sale of the Mark

White Goiter Serum has not been so authorized; consequently even if the

preparation complied with other rules of the Council it could not be

accepted.

In addition, however, this treatment conflicts with other Council

rules. The statements regarding its composition are indefinite

and contradictory (Rule 1); the evidence presented to support the

therapeutic claims is insufficient in itself and does not appear to

have been checked by any disinterested authority (Rule 6). Moreover,

the recognized variation in the morphology and pathology of the types

of goiter render it impracticable to treat cases of goiter by any

routine procedure.

The foregoing report was submitted to the Mark White Goiter Serum

Laboratory. In reply, a letter signed “Mark White, V.M.D.,” was

received, which read, in part:

“... we hope at some future time to be able to give you more

detailed information, but as you possibly appreciate that we

have experienced for some time a demand on the part of many

physicians that we furnish to them our therapy, which necessitates

us furnishing it before all the detailed work has yet been

accomplished, and I trust that you will be so kind as to bear

patiently with us until we are better in a position to make a

complete scientific application and report to you.”

White wrote further:

“The serum and iodized oil may be mixed for immediate use, but

could not be put up only separate for the use of the profession and

the therapy furnished Dr. Watkins she mixed as used.”

This statement throws no light on the discrepancies in the statements

with regard to the place of the iodinized oil in the treatment, namely:

(_a_) the original statement that the oil was to be given a week after

the serum; (_b_) White’s statement (quoted earlier in this report) that

the oil “is only an adjunct or side treatment” and “is not always used

or indicated”; (_c_) the statement in Dr. Watkins’ paper that the oil

and the serum are given in combination.

The Council declared the Mark White Goiter Serum and Mark White

Iodinized Oil ineligible for New and Nonofficial Remedies and

authorized publication of this report.

Editorial Note on the Mark White “Serum”

As some of our readers will remember, on April 26, 1913, The Journal

called attention to the Mark White preparation which at that time was

being exploited from Denver. The Propaganda Department has in its files

a number of letters sent out from the Mark White concern at various

times. One mailed in May, 1911, on the embossed stationery of “The Mark

White Goiter Institute,” Exchange Building, Denver, was evidently a

general letter sent to physicians, calling their attention to “the most

important medical discovery of the age.” “Dr. Mark White, a graduate

of the University of Pennsylvania,” said the letter, had discovered “a

simple and harmless remedy” that would cure goiter. “Because of the

desire to preserve the secrecy of this remedy it is given only at the

office here.” It was then suggested that the doctor might send those

of his patients who were suffering from thyroidism to the “Mark White

Goitre Institute.” If he would do so he would be “given a commission

of $10, in cases of the $50 fee with the additional $5 for each $50

increase.” It closed with some casuistic arguments, presumably for the

purpose of overcoming the physician’s scruples, summing up the matter

with the statement:

“No right thinking man will allow a narrow and self-seeking system

of ethics to stand between him and his duty to the sick and

suffering.”

About 1912 the name of the concern seems to have been changed, for we

have in our files a letter addressed to a layman on the stationery of

the “Mark White Goitre Treatment Company.” According to this letterhead

the product this concern had for sale was “Goitreine” discovered by

Mark White, “President and General Manager.” Mr. White’s letter to the

sufferer from goiter assured him that if he would take “Goitreine”

he might “be practically sure of an immediate and permanent cure.”

“Goitreine,” according to White, “has absolutely and permanently cured

90 per cent.” of all cases of goiter in which it has been used--“and

the other ten showed remarkable improvement.” It was efficacious for

all forms of goiter and “cannot possibly harm.”

The person who received this assurance might have had his confidence in

it shaken had he seen a copy of the Denver _News_ for May 23, 1911, in

which was reported a case of collapse and death in a woman following

an injection given in White’s office. The paper stated that the death

certificate was signed by one W. A. Gray and gave “fatty degeneration

of the heart and goiter” as the cause of death. Gray, it seems, was the

licensed physician employed by Mark White to administer “Goitreine”--if

that is what White happened to be calling his product at that time.

For here it may be stated, parenthetically, that Mark White is not a

physician; he is a veterinarian.

In February, 1913, Mark White sent a circular letter to a number of

medical publications with the request that it be printed in full in

the next issue, “to cover one full page of space.” The letter White

wanted printed was addressed to doctors offering to “enter into a

copartnership agreement” with such physicians who would be willing to

treat “patients with goiter affections on a 50 per cent. commission

basis.”

“You would be expected to make a cash charge to the patient for the

treatment, remitting on the same day our 50 per cent. to us, when

ordering the treatment, giving the treatment in no cases for less

than $50.00.”

About the same time that Mark White made this “fifty-fifty” offer,

he sent in an advertisement to be published in the classified column

of The Journal. At that time he was told his advertisement was not

acceptable; we now reprint it, however, free of charge. Here it is:

“WANTED--ONE OR MORE PHYSICIANS

in each vicinity to administer and represent our new medical

treatment for GOITER. Good margin of profit. Write for copy of

contract. The Mark White Goitre Treatment Co., Denver, Colo.”

In 1914, White moved to Chicago. At least the card which we reproduce

so indicates. At that time, as will be seen, “Dr. Mark White” was

“personally associated” with Peter S. Clark, M.D. According to the

same card Dr. F. D. Paul of Rock Island, Ill., seems to have been his

“associate” for that particular locality. In this connection, it is

worth noting that a Rock Island paper, in one of its issues during

July, 1913, devoted a good deal of space to “Dr. Mark White” who

was at that time in Rock Island “directing Dr. Frank D. Paul in the

administering of the treatment.” There was nothing to indicate that

this notice was an advertisement or that the editorial appearing in the

same issue puffing White’s “important cure,” was paid for.

[Illustration: When exploited from Denver the Mark White “goiter cure”

was advertised in the daily papers. Here is a photographic reproduction

(reduced) of an advertisement that appeared in the Denver _Post_, Sept.

1, 1912.]

Dr. W. A. Gray, who has already been mentioned as White’s associate

in Denver, seems to have been doing business in Illinois some time in

1913 and a Princeton (Ill.) paper had some uncomplimentary things to

say about him. Finally in July, 1913, this item appeared in a Princeton

paper.

“Dr. W. A. Gray, the goiter specialist who operated last winter

at Princeton and Walnut until he became embroiled with Dr. Mark

White, a Denver veterinary and originator of the cure, over a

division of the spoils, has opened a goiter institute in Chicago

under his own name. Advertisements of the Dr. Gray Goiter Institute

appeared Sunday morning in the Chicago _Examiner_ and other morning

papers. Dr. Gray and Mark White broke off their relations after

their disagreement at Walnut, and Dr. Gray slightly changed the

ingredients of the goiter cure and started off on his own hook.”

One of Gray’s advertisements in Chicago newspapers made the claim that

“Dr. Gray’s New Medical Treatment removes the cause of goiter in seven

days.”

[Illustration: Photographic reproduction (reduced) of the

“professional” card used by “Dr. Mark White” after he came to Chicago.]

The Tulsa (Okla.) associate of “Dr.” White seems to have been Dr.

J. H. Morgan and the Tulsa papers of June, 1914, tell of “Dr.” White’s

visit to that city “for the purpose of instructing Dr. J. H. Morgan in

the technique of his new medical treatment for nervous disorders and

goiter.” Some months later--in December, 1915--the following little

item appeared in a Tulsa paper:

“Dr. Mark White was found guilty in the county court yesterday of

practicing medicine without a license and was fined $50. Doctor

White is a goiter specialist.”

In September, 1915, Mr. Thomas S. Hogan, the efficient counsel for the

Illinois State Board of Health, instituted action against Mark White

for practicing medicine without a license. The case was tried Oct. 15,

1915, and the jury, after being out four hours, returned a verdict

of “not guilty.” Attorney Hogan attributes the failure to obtain a

conviction to the testimony of Dr. Rachel Watkins, who said she had a

partnership arrangement with White in carrying on the medical business.

It was about this time that Mark White seems to have issued some new

letterheads. These bore in their upper left hand corner the device

“Rachel Watkins, M. D., Practice Limited to Goiter and Other Disorders

of the Thyroid Glands,” while the upper right hand corner read “Mark

White, Goiter Research.”

On Dec. 9, 1915, Rachel Watkins, M. D., of Chicago, read a paper

entitled “A Serum Treatment for Physiologically Defective Thyroids,

With Clinical Reports” before the Stock Yards Branch of the Chicago

Medical Society. The “serum treatment” discussed was Mark White’s

“Goitreine” which, in the course of its checkered career, had lost its

original name by the wayside. This paper appeared in the December,

1915, issue of the _Illinois Medical Journal_.

Probably emboldened by the ease with which a component part of the

American Medical Association “fell for” a paper exploiting a “goiter

cure,” Dr. Watkins requested that she be permitted to read a paper on

the same subject before the Section on Pharmacology and Therapeutics at

the Detroit meeting of the American Medical Association last June. The

request was refused. Dr. Watkins is apparently no longer connected with

White and in fact has protested against the use of her name by White in

connection with his “goiter cure.”

[After the above was in type and ready for the pages of The Journal,

attention was called to the _Official Bulletin of the Chicago Medical

Society_ of Sept. 16, 1916. This _Bulletin_ contained a full page

advertisement of the Mark White “goiter cure.” The advertiser referred

to the preparation as having been “announced to the Chicago Medical

Society” and declared it to be “an ethical therapeutic agent.”

Mark White was described as “a medical research student” but no

hint was given that he is a veterinarian. After again emphasizing

that “this therapy is ethically proven” physicians were invited

to “visit our goats when convenient” and the advertisement closed

with the modest claim that “this thyroid therapy has equal curative

therapeutic value in these cases as quinin in malaria.” And this sort

of pseudo-scientific claptrap is presented to a presumably learned

profession through its own official Bulletin--but what’s the use of

commenting!]--(_From The Journal A. M. A., Sept. 23, 1916._)

KORA-KONIA

Report of the Council on Pharmacy and Chemistry

Kora-Konia is a “dusting powder” which at present is advertised to the

medical profession through medical journals, circulars, post cards and

sample packages. It is put out by the “House of Mennen,” which sells

various toilet preparations such as talcum powder, shaving soap, etc.

On the trade package is the statement:

“Indicated in the treatment of Acne, Dermatitis, Eczema Intertrigo;

in obstinate cases of chafing, prickly heat, nettle rash, chicken

pox, measles, scarlatina and irritations of the skin; as a soothing

absorbent and antiseptic dusting powder and as an umbilical

dressing.”

While a circular asserts that:

“Kora-konia is indicated in the treatment of acne, dermatitis,

eczema and eczematous conditions of the utmost severity,...

eruptive fevers,...”

What purports to be a physician’s testimonial reads:

“I used Kora-Konia in a new born case of inherited syphilis and the

eruption soon cleared up.”

Germicidal powers are claimed for Kora Konia in a medical journal

advertisement. In view of the various claims made and the fact that it

is advertised to the medical profession, the Chemical Laboratory of the

American Medical Association was asked to analyze Kora-Konia. This was

done and the chemists reported as follows:

LABORATORY REPORT

Kora-Konia is a white powder, slightly greasy to the touch. Qualitative

tests showed the presence of boric acid, zinc, magnesium, a solid fatty

acid and material insoluble in hydrochloric acid containing magnesium

and aluminum. Starch was not found. Quantitative determinations gave

the following results:

Acid-insoluble material (talc) 48.3 per cent.

Magnesium (Mg++) soluble in dilute acid 1.2 per cent.

Zinc (Zn++) 4.5 per cent.

Stearic acid (impure) 39.2 per cent.

Boric acid 3.0 per cent.

Carbon dioxide (CO₂) 1.5 per cent.

From this analysis it is concluded that Kora-Konia has essentially the

following composition:

Zinc stearate U. S. P. 44 per cent.

Talc 48 per cent.

Magnesium carbonate U. S. P. 5.0 per cent.

Boric acid 3.0 per cent.

Essentially this dusting powder consists of the well-known substances

talc and zinc stearate in about equal proportions to which small

quantities of magnesium carbonate and boric acid have been added.

Inasmuch as the claim is made, by inference at least, that Kora-Konia

represents original investigation carried out “with the cooperation of

the medical profession” it should be stated that the preparation of

commercial zinc stearate was described and recommended as a dusting and

toilet powder nearly twenty-five years ago.[96]

[96] Proc. Am. Pharm. A. =40=:488, 1892.

There is nothing new or original in any one of these substances or in

the combination. The extravagant and unwarranted claims made for this

simple dusting powder are undoubtedly leading the public as well as

some thoughtless physicians, to place undeserved confidence in it.

In view of the small amount of boric acid present in the powder, its

antiseptic powers must be slight and its germicidal powers almost nil.

The Council declared Kora-Konia ineligible for New and Nonofficial

Remedies and authorized publication of this report.--(_From The Journal

A. M. A., Sept. 30, 1916._)

THE THERAPEUTIC VALUE OF THE GLYCEROPHOSPHATES

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following report and authorized its

publication.

W. A. Puckner, Secretary.

Glycerophosphates are the salts of glycerophosphoric acid,

H₂[C₃H₅(OH)₂]PO₄. This acid is produced by the interaction of glycerin

and phosphoric acid. In general, only sodium glycerophosphate,

Na₂[C₃H₅(OH)₂]PO₄ + 5-1/2H₂O, and calcium glycerophosphate,

Ca[C₃H₅(OH)₂]PO₄ + H₂O, are used in medicine, though the

glycerophosphates of lithium, potassium, manganese, magnesium, iron,

quinin and strychnin are claimed as constituents of proprietary

preparations. At a time when certain disorders were assumed to be due

to a deficiency of phosphorus in the nerve structure in the body,

glycerophosphates were introduced as “nerve foods” and “tonics” on the

theory that they would be assimilated more readily than hypophosphites

or ordinary phosphates. What led to this assumption was the fact that

the lecithins, which form a part of the nerve structure, were known to

contain the glycerophosphate radical in the molecule. The belief that

inorganic phosphates cannot supply the body’s need of phosphorus is

implied or expressed in most of the “literature” devoted to proprietary

phosphorus preparations.

Thus, Schering and Glatz quote G. Meillière as saying that “the

organism is incapable of assimilating inorganic forms of phosphorus.”

Again, when exploiters of glycerophosphates admit that the body can

synthesize its phosphorus compounds from inorganic phosphates, they

attempt to counterbalance the admission by contending that the use

of organic compounds “spares” the system the necessity of making

such synthesis. This assumption rests on the theory that the organic

phosphorus compounds are absorbed and stored as such.

This theory is contradicted by evidence which has been presented[97]

that the organic phosphorus compounds are split up into inorganic

phosphates before absorption.

[97] McCollum and Hart, Grosser and Husler, Plimmer, and Bayliss and

Plimmer, quoted by Marshall (Note 2).

The Council requested E. K. Marshall, Jr., to review the evidence for

and against the therapeutic value of organic phosphorus compounds.

Marshall’s study[98] brings out the following points:

[98] Marshall, E. K.: The Therapeutic Value of Organic Phosphorus

Compounds, J. A. M. A., Feb. 13, 1915, p. 573.

1. In various tissues of the animal body, enzymes have been found which

hydrolyze complex organic phosphorus compounds so as to liberate the

phosphorus in the form of inorganic phosphates.

2. Metabolism studies of the phosphorus balance with diets containing

inorganic phosphorus compounds, as compared with diets containing

organically bound phosphorus, are somewhat conflicting in their

results. The balance of evidence, however, is in favor of the view that

there is no difference between organically combined phosphorus and

inorganic salts with respect to the phosphorus balance.

3. Experiments indicate that the organism thrives on and supplies its

phosphorus needs quite as well from inorganic phosphorus compounds as

from organically bound phosphorus.

Marshall concludes:

“We see that the evidence is very convincing of the view that the

animal organism can synthesize its complex organic phosphorus

constituents from inorganic phosphates, and that organic phosphorus is

of no more value as a food than inorganic.”

In view of this report, the Council deemed it advisable to take up the

consideration of certain glycerophosphate preparations on the market.

As the therapeutic claims are all similar, it is not necessary to quote

them extensively.

TONOLS (SCHERING’S GLYCEROPHOSPHATES)

Tonols (Schering and Glatz, New York) comprise iron, lime, lithium,

magnesium, manganese, potassium, quinin, sodium and strychnin “Tonols”

or glycerophosphates; also Duotonol Tablets, said to contain equal

parts of calcium and sodium glycerophosphates; Triotonol Tablets,

each said to contain “Sodium Tonol 2-1/2 grains, Lime-Tonol 2-1/2

grains, Strychnine-Tonol 1/60 grain”; Quartonol Tablets, said to

contain “Sodium and Lime-Tonols, each 2-1/4 grains, Quinine Tonol

1/2 grain, Strychnine-Tonol 1/200 grain”; Sextonol Tablets, said to

contain “Sodium and Lime-Tonols, each 2 grains, Iron-Tonol, 1/2 grain,

Manganese and Quinine-Tonols, each 1/4 grain, Strychnine-Tonol, 1/200

grain.”

The name “Tonols” is objectionable in that it is not only

nondescriptive of the composition, but also therapeutically (and

falsely) suggestive. The composition of the more elaborate Tonols is

particularly unscientific; there is no justification for combining

quinin, strychnin, iron, manganese, etc., in one formula.

PHOSPHORCIN COMPOUND

Phosphorcin Compound, called “The Elementary Phosphorus indicated in

all forms of Nervous Diseases” and the “Perfect Formula,” is said to

be manufactured by the Organic Products Company, Wetzlar an der Lahn,

Germany, and Greenwich, Conn. It is sold in the United States by Eimer

and Amend, New York, according to whom:

“Each two fluidrachms contain:

“Acidulated Bone Phosphor O. P. Co. 2 grains

“Calcium Glycerinophosphate, Merck & Co. 1-1/2 grains

“Magnesium Glycerinophosphate, Merck & Co. 1-1/2 grains

“Sodium Glycerinophosphate, Merck & Co. 2-1/2 grains

“Lactated Pepsin 2 grains

“Ignatia Extract 1/20 grain

“C. P. Glycerin (Special Process) O. P. Co. 50 per cent.

“Acidulated bone phosphor” presumably is acid phosphate of calcium.

This formula is an unscientific shotgun combination.

ROBINOL

Robinol, manufactured by John Wyeth and Brother, Philadelphia, is

called a “Universal Tonic.” It is said to be:

“A preparation of the glycerophosphates of lithium, calcium,

sodium, iron, manganese, quinine, with 1-16 gr. strychnine

glycerophosphate in each fluidounce.”

This is a semisecret preparation, since the quantities of most of the

ingredients are not given and the vehicle is not named. This complex

combination, too, is unwarranted.

PHOSPHOGLYCERATE OF LIME (CHAPOTEAUT)

This is said to be prepared by the Laboratories de Pharmacologie

Générale, Dr. Ph. Chapelle, Paris and New York. It is sold in this

country by E. Fougera and Co., Inc., New York. It is offered in several

forms, especially in that of wine, which is called the “Medicinal Wine

and Tonic Par Excellence.” The alcohol is no doubt the constituent

to which this preparation is indebted for such popularity as it has

attained, for it is much more freely advertised than the syrup,

capsules or granulated form. The usual claims are made with regard to

the efficacy of calcium glycerophosphate “during convalescence, in

cases of enfeebled vitality, and nervous affections associated with an

excessive elimination of phosphates.”

ELIXIR GLYCEROPHOSPHATES, NUX VOMICA AND DAMIANA

This is manufactured by Sharp and Dohme, Baltimore. The manufacturers’

statement of composition is:

“Each fluidounce represents Nux Vomica 8 grains, Damiana 64 grains,

combined with Glycerophosphates of Calcium and Sodium.”

“Alcohol 20 per cent.”

Sharp and Dohme call this mixture a “Reconstructive Nerve Stimulant,

Aphrodisiac,” and claim that:

“Phosphorus in elemental form has long been prescribed under the

title of Elixir Phosphorus, Nux Vomica and Damiana, but due to the

rapidity of chemical change occurring in preparations containing

this form of Phosphorus, much of the Physiologic action is lost.

The Glycerophosphates present Phosphorus in its most available

form--the form in which it exists in the brain and nervous system.

They powerfully stimulate the functions of nutrition and are

rapidly assimilated by the system.

“Nux Vomica is a general Nerve Tonic. Damiana exerts a stimulant

effect upon the sexual appetite and function.”

The claim that the glycerophosphates may be substituted for elementary

phosphorus is, at least, novel.

The elixir is an unscientific semisecret combination.

RECOMMENDATIONS

All of the preparations mentioned violate Rule 6 (unwarranted

therapeutic claims). In addition, Robinol and Elixir Glycerophosphates,

Nux Vomica and Damiana violate Rule 1 (secrecy of composition) in

that not all the quantities of the ingredients are declared; Tonols,

Phosphorcin Compound and Robinol violate Rule 8 (objectionable names).

It is recommended that the Council endorse Marshall’s findings[98] and

declare that Tonols (Schering and Glatz), Phosphorcin Compound (Eimer

and Amend), Robinol (John Wyeth and Brother), Phosphoglycerate of

Lime Chapoteaut (E. Fougera and Co.), and Elixir Glycerophosphates,

Nux Vomica and Damiana (Sharp and Dohme) are ineligible for New and

Nonofficial Remedies.--(_From The Journal A. M. A., Sept. 30, 1916._)

HYDRAS

Report of the Council on Pharmacy and Chemistry

Hydras, sold by John Wyeth and Brother, Philadelphia, is one of the

many proprietary, so-called “uterine tonics.” It is said to contain

“Cramp Bark, Helonias Root, Hydrastis, Scutellaria, Dogwood and

Aromatics,” but as the amounts of the several ingredients are not

given the statement regarding its composition is valueless. The label

declares the presence of 24 per cent. alcohol.

The name “Hydras,” taken in connection with the statement of

composition, would suggest that hydrastis (golden-seal) is an important

constituent. The report of the Chemical Laboratory of the American

Medical Association, however, indicates that hydrastis is present in

unimportant amounts:

“The hydrastin content of Hydras was determined by extraction with

immiscible solvents (_Pharm. Review_, May, 1908, p. 132). Twenty-five

c.c. was found to yield an alkaloid residue of 0.0160 gm. The

preparation contains, therefore, not more than 0.064 gm. ‘hydrastin’

per 100 c.c. Inasmuch as hydrastis is required to contain about 2.5

per cent. ‘hydrastin,’ hydras contains an equivalent of not more than

2.56 gm. hydrastis (golden seal) in 100 c.c. and the stated dose of

Hydras--one dessertspoonful (8 c.c.)--represents not more than 0.2 gm.

or 1/10 of the U. S. P. average dose of hydrastis.”

The label of a recently purchased bottle of Hydras bears the following

recommendations for its use:

“Indicated in treatment of Dysmenorrhea, Menorrhagia Anti-Abortive,

with anodyne and tonic properties.”

“For dysmenorrhea, suppressed menses, etc., a dessertspoonful three

times daily, before or after meals.”

“To relieve pain due to uterine disorders, a dessertspoonful every

three hours, or increased to a tablespoonful, at the discretion of

the attending physician.”

A circular wrapped around the bottle declares that Hydras is:

“A valuable preparation to the physician in the treatment of

dysmenorrhea, colic, cramps, spasm, palpitation incident to

pregnancy, and the various pains resulting from diseases of the

female sexual organs.”

It is further claimed that:

“In the dysmenorrhea of young girls due to some mechanical

difficulty, as anteflexion or of a congestive character, of

suppressed menses from exposure to cold and other causes of

a similar character, Hydras will prove efficient and can be

administered freely without danger.”

The value of hydrastis in the treatment of the diseases and conditions

mentioned is problematical at best, and the small amount present in

Hydras is wholly useless. As for the other constituents, cramp bark

(_Viburnum opulus_), helonias (false unicorn--_Chamælirium luteum_

or _Helonias dioica_) and scutellaria (skullcap--_Scutellaria

lateriflora_) are drugs which are practically ignored by most writers

on materia medica and therapeutics.[99] Dogwood (_Cornus florida_) is

a mildly astringent aromatic bitter for the use of which there is no

scientific evidence.[100]

[99] See reports of the Council, J. A. M. A., Jan. 9, 1915, p. 165;

Jan. 23, 1915, p. 359; Nov. 27, 1919, p. 1836; March 27, 1915, p. 1093.

[100] See Reports Council Pharm. and Chem., 1912, p. 36.

To sum up: Of the five ingredients of Hydras (aside from alcohol and

aromatics), one (hydrastis), which apparently gives the preparation its

name, is present in unimportant amounts; three (cramp bark, helonias

and scutellaria) are therapeutically unimportant; the fifth (dogwood)

has never been shown to have any specific action on the uterus. The

potent constituent, therefore, appears to be the alcohol.

But, even if every one of the several drugs said to be contained in

Hydras were possessed of distinct therapeutic properties, and if each

were present in known and therapeutically active amounts, still the

combination in fixed proportion would be irrational. No one could

foresee the joint effect of the five drugs in the several conditions

for which the mixture is advertised. Hydras is evidently meant to

appeal to the thoughtless and to be used at random; witness the

suggestion made in the advertising that

“Owing to its palatability, it is acceptable to patients with

impaired digestion, and will serve as a stomachic tonic, promoting

appetite and digestion.”

A useless alcoholic nostrum “administered freely” to women and girls

is as dangerous as the recommendation for such administration is

reprehensible.

This preparation is semisecret. The recommendations for its use in

specified diseases which appear on the label and in the advertising

accompanying the bottle are sure to lead to its ill-advised use by the

public. The claims made for its curative properties are exaggerated

and unwarranted. The name, in view of the small content of hydrastis,

is misleading. Finally, the combination of five drugs, even if

individually they were of therapeutic value, is irrational. Hydras,

consequently, is inadmissible to New and Nonofficial Remedies for

conflict with Rules 1, 4, 6, 8 and 10, and publication of this report

is authorized.

[Editorial Comment.--Products like “Hydras” are the bane of scientific

medicine. The physician who prescribes them could with just as much

reason prescribe any of the various alcoholic “patent medicines” of

the “women’s tonic” type. In fact, his patients would be running less

risk of contracting the alcohol habit if he prescribed the “patent

medicines,” as these nostrums usually have less alcohol than is

contained in their “ethical” prototypes--and alcohol is the only really

important drug in practically all of them. Whatever one may think of

reputable pharmaceutical houses who put out products of the “Hydras”

type, the fault really lies with the profession which tolerates such

therapeutic monstrosities.]--(_From The Journal A. M. A., Oct. 7,

1916._)

BROMIN-IODIN COMPOUND

Report of the Council on Pharmacy and Chemistry

“Bromin-Iodin Compound,” according to the Bromin-Iodin Chemical

Company, San Diego, Calif., has the following “formula”:

Iodin Gr. 1

Bromin Gr. 1/4

Phosphorus Gr. 1/100

Thymol Gr. 2/3

Menthol Gr. 2/3

Sterilized Oil Gr. 1

The only statement regarding its method of preparation is the line

“Solution in Cod Liver Oil, Norwegian.” According to the promoters,

“Bromin-Iodin” is:

“A Powerful Anti-Tubercular Agent for Hypodermic Use in Pulmonary

and Laryngeal Tuberculosis. Useful in other forms of Tubercular

Diseases, and in Non-Tubercular Pulmonary Diseases of a Sub-Acute

or Chronic Nature.”

The “formula,” in the form in which the manufacturers publish it, is

either impossible or meaningless, according to the interpretation that

may be given. It is impossible if it is intended to indicate the actual

composition of the product because that would mean that the oil is

alleged to contain free or uncombined iodin, bromin and phosphorus.

Both on theoretical grounds and also in the light of the findings of

the Chemical Laboratory of the American Medical Association, it is

not possible that all these constituents can be present in the free

state. The formula is meaningless if it is intended to convey the idea,

merely, that iodin, bromin, phosphorus, thymol, menthol and sterilized

oil are combined to form “Bromin-Iodin.” In the absence of any details

of the method of manufacture, it is futile to attempt to pass judgment

on the actual composition of the preparation.

The use of an almost identical product (said, however, to contain

only 1/2 grain iodin to each fluidram) was described in 1908 by Dr.

Ingraham of Binghamton, N. Y., in “Five Years Successful Experience

with a Special Mode of Treating Pulmonary Tuberculosis.” In 1910 The

Journal[1] characterized the preparation as “one of the innumerable

‘treatments’ for pulmonary tuberculosis that have arisen, had their

day and, more or less gracefully, retired.” If the preparation had

value for the purpose for which it is recommended, its use during these

twelve years should have secured its general recognition. There is no

satisfactory evidence of its therapeutic efficacy. The Council refused

recognition to Bromin-Iodin Comp. and, after submitting this report to

the Bromin-Iodin Chemical Company, authorized its publication.--(_From

The Journal A. M. A., Dec. 23, 1916._)

AMMONIUM HYPOPHOSPHITE OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Propaganda for Reform in Proprietary Medicines, Vol. 2 of 2 · 第 3 / 20 章

Lest the appearance of this detailed study of secretin, after the