Chapter XXII: Appendix (3)

The Council adopted both the report submitted by the committee and that of the A. M. A. Laboratory and declared “Collosol Cocaine” inadmissible to New and Nonofficial Remedies.--(_From The Journal A. M. A., April 12, 1919._)

CUPRASE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report on Cuprase, sold by the Anglo-French Drug Co., Ltd. The Council’s criticisms of the advertising claims were sent to the firm, December, 1918. The firm made no reply and essentially the same claims are contained in recent advertisements.

W. A. Puckner, Secretary.

“Cuprase” is now being advertised and sold in the United States by the Anglo-French Drug Co., Ltd., the firm which also markets it in England. It is said to be “prepared in the Laboratories of F. Ducatte, 8 Place de la Medeleine, Paris.” According to an advertising circular entitled “The Medical Treatment of Cancer” “Cuprase” is “chemical colloidal copper”; in another place it is “a colloidal copper hydroxid,” which is said to be obtained chemically by the reduction of salts of copper in the presence of albumosic acid.

A box (price $8.50 less 10 per cent. discount) of “Cuprase-Doctor Gaube du Gers” was purchased recently from the Anglo-French Drug Co., Ltd. It contained eight ampules each containing approximately $1 $2$3 of a brownish fluorescent liquid. No information of composition was given on the box, except the line: “Chaque ampoule contient: $1 $2$3 .00121 de Cuivre pur” (Each ampule contains O.00121 gr. of pure copper). The A. M. A. Chemical Laboratory reports that the preparation does contain a small amount of copper, with some protein material and about 1 per cent. sodium chlorid.

The therapeutic claims in the advertising circular are those commonly made for cancer “cures” and are about equally convincing. The publication of such statements and quotations as the following, which appear in a pamphlet “The Medical Treatment in Cancer,” cannot be too strongly condemned in a medicament that at best has only an experimental status:

“A special preparation, Cuprase, has been introduced into
therapeutics which has been remarkably successful. In the history
of the therapeutics of cancer, nothing has been found which can
compare with the effects produced by means of Cuprase. Clinical
facts carry greater weight than theoretical deductions. It
follows, from the clinical observations which I have collected,
that in the large majority of cases Cuprase effects the diminution
or disappearance of the pains, an improvement in the general
condition, a diminution or arrest of the neoplasms, and finally
in certain cases, a cure has been effected. It should be remarked
that all or nearly all the observations refer to inoperable cases
in which the prognosis was unfavorable at an early date. It is
needless to emphasize the practical importance of a preparation
capable of yielding such results, even relative, in the worst
stages of a disease which has always been regarded as absolutely
resisting the action of all internal remedies.”

“To sum up, Cuprase has given positive results in about 94 per
cent. of the cases in which it has been employed for a sufficiently
long period, and some brilliant results in about 20 per cent. of
these cases. Therefore, it may be affirmed, that among the internal
remedies for cancer, Cuprase is the one which has produced the most
successful results, and can, under certain circumstances, compete
with surgical methods, even, so far as the rapidity of their
results are concerned.”

“It is indicated:

(a) apart from all operation, and as a specific and curative
remedy;

(b) before an operation, in order to give tone to the patient,
mobilise the tumor, destroy its toxins;

(c) after the operation, as a tonic and anti-toxic, and in order
to avoid frequent relapses which are always possible.”

Essentially the same statements are made in the more recent advertisements (f. i. Urological and Cutaneous Review, Feb., 1919). Opposed to these loose statements are the results of Richard Weil (The Journal A. M. A., 1913, Sept. 27, p. 1034; ibid, 1915, April 17, p. 1283). Weil avoided pitfalls of subjective impressions and used as the essential criterion of efficiency “the demonstrable reduction in size of a tumor, of a kind not to be attributed to the natural processes of evolution of that tumor or of its associated lesions” (l. c. 1915, p. 1289).

The available evidence for Cuprase is far from meeting this criterion. That published by the manufacturers and agents presents only vague generalities, and no definite data. The evidence gathered by Weil himself permits an estimate of the value of Cuprase and it is entirely unfavorable. He states (l.c. 1915, p. 1288):

“Colloidal copper has been used in recent time for the same purpose by Gaube du Gers and by others. I have recently examined the effects of colloidal copper on malignant tumors in man, and have been unable to find that it has any therapeutic value. Furthermore, a study of the distribution of the copper in tumors obtained at operation or by necropsy from individuals so treated failed to show that the copper had been deposited therein.”

In view of the extravagant and cruelly misleading therapeutic claims, and the indefinite statements of composition, the Council voted Cuprase ineligible to N. N. R., and authorized the publication of this report.--(_From The Journal A. M. A., April 12, 1919._)

COLLOSOL PREPARATIONS

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the report which appears below declaring “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur” inadmissible to New and Nonofficial Remedies, because their composition is uncertain (conflict with Rule 1). In the few cases in which the therapeutic claims for these preparations were examined, the claims were found to be so improbable or exaggerated (conflict with Rules 6 and 10) as to have necessitated the rejection of these products.

W. A. Puckner, Secretary

The Anglo-French Drug Co., Ltd., London and New York, in November, 1918, requested the Council to consider the products “Collosol Argentum,” “Collosol Arsenicum,” “Collosol Cocain,” “Collosol Cuprum,” “Collosol Ferrum,” “Collosol Hydrargyrum,” “Collosol Iodin,” “Collosol Manganese,” “Collosol Quinin” and “Collosol Sulphur.” The term “Collosol” appears to be a group designation for what are claimed to be permanent colloidal solutions, marketed by the Anglo-French Drug Co., Ltd. Were this claim correct, “Collosols” should contain their active constituents in the form of microscopic or ultramicroscopic suspensions, protected against spontaneous precipitation by the presence of proteins or some similar “stabilizers.”

According to the original patent specifications for Collosols, the metals are precipitated or treated with “peptone,” which acts as the suspending or stabilizing agent. The method of using the peptone makes it doubtful, in the first place, whether the major part of the metals is present in colloidal form, or merely in the form of peptonates, i. e., as ordinary salts. Moreover, the later patents indicate that the products have been unsatisfactory; “experience having shown that some metal colloids under certain conditions not yet fully understood have the tendency to break down after a certain period” (U. S. patent No. 1,116,247). Phenol, it is claimed has a tendency to counteract this decomposition, and the patent covers the use of phenol for this purpose.

It is difficult to see how phenol could possibly have such action. In fact, it obviously does not, for a number of the samples of Collosols submitted to the Council had separated. For instance, “Collosol Hydrargyrum” was not a colloidal solution at all, but a suspension of a coarse powder. The ampules of “Collosol Ferrum” contained a considerable quantity of flocculent precipitate. If either of these preparations were injected intravenously as directed, death might result, making the physician morally if not legally liable.

The recklessness of the claims is further illustrated by the advice that these indefinite mixtures of poisonous metals can be injected in unlimited quantities. Thus, Henry Crookes stated (_Chemical News_, May 7, 1914, p. 218) that Collosols “contain so small a proportion of metal, viz., 1 in 2000, that even a poisonous body like arsenic can be used with impunity.” He stated that they may be applied as a lotion, intramuscular or intravenous injection, and that “one pint or more can be injected intravenously.”

In the case of “Collosol Cocain,” as was brought out in the Council’s report published in The Journal, April 12, 1919, the manufacturers have admitted that the product is not what they have claimed--and still claim--for it. The report of the A. M. A. Chemical Laboratory showed that “Collosol Cocain,” instead of containing 1 per cent. cocain as claimed, contained, in fact, at most not more than 0.4 per cent. cocain.

The report of the A. M. A. Chemical Laboratory on the Collosol products was sent by the Council to the New York office of the Anglo-French Drug Co., Ltd., in duplicate in order to facilitate reference to the London office. This was some months ago. The information which the Council requested has not yet been received, nor has the Anglo-French Drug Co., Ltd., indicated its intention of supplying such information. On the other hand, claims to which specific objection have been made, continue to appear in current advertising. Accordingly, the Council authorizes publication of this report, and declares the Collosol preparations previously named ineligible to New and Nonofficial Remedies.

Additional Notes on Collosol Evidence

In addition to the preceding the following notes of the referee on the evidence so far submitted were sent to the Anglo-French Drug Company, Ltd., for consideration:

_Collosol Iodine_: The leaflet which describes Collosol Iodine contains claims that are improbable, not in accord with accepted facts nor substantiated by evidence; for instance:

“This preparation contains Iodine in its most active form ...”

“The disadvantages of ‘iodism’ and nausea frequently associated
with iodides never occur with Collosol Iodine.”

“In the case of Colloidal Iodine the whole of the Iodine is
absorbed and enters into molecular combination with protein to form
an iodo-amino acid and ... exerts a reducing action on the lipoids
producing a different condition of the blood--hence the use of
Iodine as an ‘alterative’.”

“Intravenously the action of Collosol Iodine is more rapid ... in
cases of pyemia ... thus showing its absolute non-toxicity.”

“‘Per se’ Colloidal Iodine is only slightly parasitotropic and
bacteriotropic but micro-organisms are very greatly influenced
by its action, and not only is the effect of a subsequently
administered remedy greatly increased but also the insoluble
colloidal protein of serum itself is reduced to smaller particles,
thus increasing its surface and adsorptive capacity and consequent
germicidal power. In some cases the serum, thus aided, is enabled
to throw off a milk microbial invasion. The above action can be
readily demonstrated ‘in vitro’ by means of the ultramicroscope.”

“In Cancer, the intravenous injection of Collosol Iodine relieves
pain, even where large dosage of morphine is ineffective.”

“In Rheumatism the ionic method of treatment with Collosol Iodine
is strongly advised.”

“In Recovery from Alcoholism the internal administration of
Collosol Iodine restores the normal condition of cell activity,
ensuring rapid recovery.”

_Collosol Hydrargyrum_: This is said to be a preparation of colloidal mercury and would therefore be similar to Electromercurol (New and Nonofficial Remedies, 1919, p. 167). Colloidal mercury preparations have been used to some extent; they appear to have no decided advantage over other, noncolloidal, mercury compounds. They differ sufficiently from them, however, to justify acceptance for New and Nonofficial Remedies, providing that reasonable claims are made for them. The leaflet advertising Collosol Hydrargyrum contains statements that cannot be accepted and require thorough revision to make them acceptable. The following are instances:

“Although--especially locally--the action of mercurials is markedly
antiseptic, when taken internally or injected, it has been stated
by some of the best known authorities, that their action is rather
to increase the natural resisting power of the body to disease,
probably because of stimulation of the oxidases.”

With the soluble mercurials “considerable upset of the normal cell
conditions of the tissues ensues whilst these soluble salts are
being converted to a condition in which the body can make use of
them.”

“The colloidal state ... is stated by some authorities in the case
of mercury to be invariably precedent to absorption.... With the
usual forms of mercury the danger of too great a dose per cell is
considerable, but in the case of colloidal mercury, the diffusion
is extremely rapid and chemical affinity low. Hence the danger
to the individual leucocyte is minimized and the maximum effect
obtained.”

“... absence of pain is usual in the administration of colloidal
preparations and is due to their isomorphism with the colloidal
lipoid and protein of the tissues and body fluids.”

“According to McDonagh,... mercury acts as an oxidizing agent and
that the process of oxidation is more effective in the early stages
of syphilis in producing the death of the causal organism....”

_Collosol Manganese_: The circular submitted to the referee is a reprint of a paper by Sir Malcolm Morris on “The Treatment of Furunculosis and Other Deep-Seated Coccogenic Infections by Collosol Manganese.” It reports four cases of furunculosis, each of which cleared up after the intramuscular injection of a few doses of Collosol Manganese. The author seems to attribute the cure to the manganese but the evidence is not convincing. Even the author admits that, in the treatment of furunculosis in general “when at last the dismal procession ends, this often appears to be less the result of treatment than because the disease has run its natural course.” Unless much better evidence is in existence, the preparation must be considered to conflict with Rule 6, which requires therapeutic claims to be substantiated.

_Collosol Argentum_: The evidence submitted as to actions consists of a single reprint by Roe, which is not convincing, and this fantastic statement by Boys:

“A young girl, aged 18, came to my house with acute inflammation of
one eye with an ulcer on the cornea. Two drops of Collosol Argentum
were dropped in the eye at 7 p. m., and a pad placed over the eye.
When she came next morning the eye was quite well; the ulcer had
disappeared, and there was no inflammation.”

There is no evidence that this preparation acts as catalyzer and assists the natural resisting bodies of the tissues; or that these are “oxygen carriers.” Unless the claims are supported by better evidence, they, in the opinion of the referee, could not be accepted.

There have been submitted to the Council samples of the following metallic Collosols:

COLLOSOL ARGENTUM COLLOSOL FERRUM
COLLOSOL ARSENICUM COLLOSOL HYDRARGYRUM
COLLOSOL CUPRUM COLLOSOL MANGANESE

Also Collosols of Iodine and Sulphur, and finally Collosols of Cocain and Quinin. Of all the above, except sulphur, only three small ampules have been submitted. This does not admit of any chemical examination but a statement of the physical appearance may be of interest.

_Collosol Arsenicum_, 0.2 per cent.: Very turbid with large quantities of a lemon yellow flocculent precipitate. On shaking does not become homogeneous and rapidly separates again.

_Collosol Argentum_, 1-2000: The liquid has a slight opalescence. There is considerable deposit of a heavy black precipitate. Does not become homogeneous on shaking and the black substance quickly separates again.

_Collosol Cuprum_, 0.5 _per cent._: Dark red somewhat opalescent liquid. No precipitate. May be colloidal.

_Collosol Ferrum_, 1-2000: Liquid clear. Large quantities of dark brown flocculent precipitate. The precipitate is not distributed evenly when the mixture is shaken and settles out quickly on standing.

_Collosol Hydrargyrum, 5 per cent._: Milky liquid. Large quantities of white deposit mixed with considerable black. The deposit mixes fairly well but the greater part settles out after standing an hour or two.

_Collosol Manganese_, 2.5-1000: Clear reddish-brown liquid without deposit of any kind. Is not opalescent or fluorescent.

_Collosol Iodin_, 1-500: Very pale straw colored liquid without deposit. Has a slight opalescence.

_Collosol Sulphur_, 1-100: Liquid is opalescent. There is some deposit of yellow particles. A four ounce bottle was also submitted. The liquid in this bottle is milky with considerable deposit of yellow crystals like ordinary crystalline sulphur.

_Collosol Cocain_, 1-100: Transparent, colorless liquid with no deposit. Chemical examination showed 0.4 per cent. of what may have been cocain. This residue gave alkaloidal tests.

_Collosol Quinin_, 1-100: Slightly opalescent, colorless liquid, with no deposit. Gives alkaloidal reactions.--(_From The Journal A. M. A., June 7, 1919._)

PULVOIDS CALCYLATES COMPOUND

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report, not so much because the preparation with which it deals is of any great importance, but as a protest against the large number of similar irrational complex mixtures which are still offered to physicians.

W. A. Puckner, Secretary.

Pulvoids Calcylates Compound (The Drug Products Co., Inc.) are tablets each of which is claimed to contain:

“Calcium and Strontium Disalicylate, 5 grs.; Resin Guaiac, 1/2 gr.;
Digitalis, 1/4 gr.; Cochium [colchicum?] Seed, 1/4 gr.; Squill,
1/4 gr.; Cascarin, 1/16 gr. with aromatics.”

“Pulvoids Calcylates Compound (Sugar coated orange color)” is advertised (_Medical Times_, January, 1919) as being “Analgesic-Antipyretic and Diuretic,” and is included in the preparations designated by the advertiser as “Approved Remedies for LaGrippe and ‘Flu.’” The claim that “Their tolerance is remarkable” refers not to the physicians who tolerate such products, but to the alleged fact that Pulvoids Calcylates are tolerated remarkably well. The advertisement continues:

“May be given persistently and continuously without gastric
disturbances.”

“They are uniformly efficient. More certain in effect than the
ordinary Salicylates.”

It would be difficult to find an advertisement of equal length containing a greater number of misleading or directly false statements than are found in this one. The Journal (April 22, 1916, p. 1307) has called attention to the lack of justification for this absurd mixture of drugs and has discussed the preparation with especial reference to its use in acute rheumatism, in which the salicylates occupy a special field. The advertisement just quoted mentions La Grippe and “Flu” (or Influenza) as special fields of usefulness for this preparation. This, apparently, is merely an attempt to spread the sail for any breeze. Salicylates have a field of usefulness in influenza in that they often afford relief from pain. There is no reason to suppose that a mixture containing calcium and strontium salicylates--the “Calcium and Strontium Disalicylate” of Pulvoids Calcylates is probably a mixture of calcium and strontium salicylate[127]--has any greater salicylic effect than an equal amount of sodium salicylate. On the other hand, it is worse than useless to give colchicum, squill and digitalis for the relief of such pains.

[127] See report, The Journal, Sept. 9, 1916, p. 827.

Should cardiac dilatation develop, and digitalis medication be required it would be impossible to adjust the dose of such a mixture with special reference to the digitalis action, which alone would be indicated for that condition. No educated physician at present would think of giving resin of guaiac merely because his patient required digitalis, nor would he administer “cascarin,” whatever that may be, in fixed doses, every time he gave a dose of salicylate.

It is impossible to recognize the several effects induced by this therapeutic omneity, and the medical profession should consider it an insult to be offered mixtures such as Pulvoids Calcylates Compound.

Pulvoids Calcylates Compound is, per se, of no great importance; it is one of a type. It has been selected as one of the utterly irrational and therefore potentially dangerous mixtures, that may be found by the score or the hundred in the catalogues of practically every pharmaceutical manufacturing firm in the United States.--(_From The Journal A. M. A., June 14, 1919._)

PROTEOGENS OF THE WM. S. MERRELL COMPANY

Report of the Council on Pharmacy and Chemistry

The Council has adopted and authorized publication of the statement which appears below, declaring Proteogen No. 1 (Plantex) for Cancer, Proteogen No. 2 for Rheumatism, Proteogen No. 3 for Tuberculosis, Proteogen No. 4 for Hay Fever and Bronchial Asthma, Proteogen No. 5 for Dermatoses, Proteogen No. 6 for Chlorosis, Proteogen No. 7 for Secondary Anemia, Proteogen No. 8 for Pernicious Anemia, Proteogen No. 9 for Goitre, Proteogen No. 10 for Syphilis, Proteogen No. 11 for Gonorrhea, and Proteogen No. 12 for Influenza and Pneumonia inadmissible to New and Nonofficial Remedies because their composition is secret; because the therapeutic claims made for them are unwarranted; and because the secrecy and complexity of their composition makes the use of these preparations irrational.

The Council took up the consideration of the Merrell Proteogens because of inquiries received, and on January 27 invited the Merrell Company to aid in the proposed investigation by submitting information in regard to the composition of the preparations, submitting the current advertising, and presenting evidence for the claims that were made for the preparations. While the Merrell Company agreed to submit the requested information, this had not been received at the time the report of the referee to whom the products had been assigned (Referee 1), was adopted. This report was sent to the company on April 4. In reply the Merrell Company protested against the conclusions of the report and submitted considerable material in an attempt to support the claims made for the products. This material was examined by the first referee and then transmitted to a second referee (Referee 2) for consideration. The second referee concluded that the matter submitted offered no evidence that would justify the Council in modifying the report first adopted, and hence recommended that its publication be authorized.

In accordance with this recommendation (report of Referee 2) the Council authorized the publication of the reports of both the first and second referees.

W. A. Puckner, Secretary.

Report of First Referee on Proteogens

“Proteogens,” according to the William S. Merrell Co., are “Polyvalent Proteins of Non-Toxic Plant Origin.” The subject of Proteogens can best be approached by recalling the history of “Autolysin,” an alleged remedy for cancer, originated by A. S. Horowitz, Ph.D. This was exploited some years ago, and was finally shown to be worthless. Proteogens are said to be prepared “under the personal supervision of the originator, Dr. A. S. Horowitz.” The composition of the different Proteogens is essentially secret. The assertion was made at one time, but is not found in the present advertising matter, that Plantex--now called “Proteogen No. 1”--is similar to Autolysin. Now the Proteogens are said to be “prepared by a special process employing various combinations of plants.” Further:

The biologic principles present are chlorophyll, chromoplast,
lipoids and vitamines; these are ferments or enzymes. The vegetable
acids, metalloids and metals present in all plants in colloid form
act biochemically. Among the metalloids are hydrogen, carbon,
manganese, oxygen, sulphur, phosphorus and chlorine; the heavy
metals are iron, potassium, sodium, magnesium and copper. These
biochemic principles are always present in plants as colloids.”

It is claimed by the Merrell Company that:

“Proteogens stimulate the cytogenic mechanism to higher activity;
therefore, indirectly cleave the invading microorganism and
eliminate their special toxins. Proteogens swing the disturbed
metabolism back to normal and, by natural processes, build up
effective defenses against recurrent bacterial attacks.”

Proteogen No. 1 was first introduced as “Plantex,” and at that time the Merrell Company referred to a preparation that was the result of “a series of studies” carried out by a “noted biologist” with a view of “evolving a Cancer remedy” that was “to be autolytic in character,” and announced:

“The House of Merrell always interested in the progress of plant
therapy, began pharmacological experimentations to reproduce this
same substance. The qualitative and quantitative analysis of the
substance as used in New York having been published simplified
matters. A somewhat similar remedy has now been prepared. It
consists of the following substances--Menyanthes trifoliata
[Buckbean], Melilotus officinalis [Yellow sweet clover], Mentha
crispa [Curled mint], Brassica alba [White mustard], Anemone
hepatica [Liver leaf], Viola tricolor [Pansy], Anthemis [Roman
chamomile], Fructus colocynthidis [Colocynth], Lignum quassiæ
[Quassia], Urtica dioica [Nettle], Radix rhei [Rhubarb root], Hedge
hyssop. These substances are in approximately equal proportions
with the exception of the mustard which forms 20 per cent. of the
mixture, and the colocynth fruit which is 5 per cent.”

With respect also to the other Proteogens listed above, study of medical literature revealed no evidence establishing their therapeutic value; in fact, no evidence was found other than that appearing in the advertising matter of the manufacturer. The range of diseases in which Proteogens are recommended is so wide as to make obvious the lack of scientific judgment which characterizes their exploitation. A circular letter, received January, 1919, reminded the physician that about a year ago his attention had been directed to Proteogen No. 1 for cancer, that later developments enabled the firm to recommend for his consideration “a series of Proteogens (Nos. 2 to 9),” and that now “In response to an insistent demand, Dr. A. S. Horowitz has prepared two new Proteogens--No. 10 for Syphilis and No. 11 for Gonorrhea.” A postscript to this circular letter announced another preparation, “Proteogen No. 12 for Influenza and Pneumonia,” a “development out of the present influenza epidemic,” and admitted that “It has not had the clinical experimentation that precedes our introduction of a new product.”

The introduction of No. 12 was effected by means of a special bulletin which consists exclusively of clinical reports from seven physicians, all from Chicago save one, and all purporting to show most favorable results from No. 12. They describe cases which any physician with experience with influenza can duplicate without any special treatment.

It is difficult to give serious consideration to a set of alleged remedies when the only evidence is that furnished by the proponents of the alleged remedies. This is particularly true when the alleged remedy does not make a sufficient appeal to one’s sense of the rational in therapeutics to lead one to feel justified in asking a trial at the hands of careful clinical observers. Considering the grave nature of the diseases for which Proteogens are recommended, particularly cancer, tuberculosis, and pernicious anemia, the want of a rational basis for the method of treatment and the general tenor of the advertising matter, it appears safe to conclude that these agents do not represent any definite advance in therapeutics.

As the use of preparations, secret in composition, and of no established value, is contrary to rational therapy, it is recommended that the Proteogen preparations be declared in conflict with Rules 1, 6 and 10.

Report of Second Referee Reviewing Manufacturers’ Reply

The report declaring the Proteogens of the William S. Merrell Company inadmissible to New and Nonofficial Remedies was adopted by the Council, but before publication it was sent to the Merrell Company for such comments as it might desire to make. In due time the reply of the firm was received. It consisted of two volumes bound in limp morocco, each stamped in gold: “Report Proteogen Therapy Requested by the American Medical Association, 1919; The Wm. S. Merrell Company.” The first volume contained 79 pages of typewritten material; the second volume contained 76 pages of typewritten material and a number of advertising booklets put out by the Wm. S. Merrell Company, exploiting the Proteogens.

Among the typewritten material was a 14-page report on “Proteogen Therapy” by its originator, A. S. Horowitz. Following this there are several pages devoted to what is termed “a short qualitative description of the ingredients of major importance in Proteogens.” Then follows a page describing the advertising of Proteogens, and the remainder of the two books is devoted to testimonials, lauding the benefit of Proteogens in diseases such as cancer, tuberculosis, rheumatism, asthma, influenza, enlarged prostate, rheumatic endocarditis, syphilis, eczema, psoriasis, diabetes, secondary anemia, gonococcic infections, etc. Finally, there are attached samples of advertising pamphlets.

The dissertation by A. S. Horowitz contains little actual information concerning these substances, but is concerned principally with discussion of foreign proteins, “antiferments,” “non-specific proteins,” “anti-virolins” and speculations on their hypothetical actions and interactions on each other and on the organs of the body and on bacteria. The report contains many questionable statements.

One finds in this report but few definite statements of facts which are known to be accurate or which could be accepted without question. The qualitative description of the proteins and their components is as vague as the previous discussion. The differentiation between the various Proteogens is extremely indefinite; that for Tuberculosis, No. 3 is described as “polyvalent, non-specific protein which rapidly attacks the acid-fast, encapsulated tubercle bacilli”; Proteogen No. 10 for syphilis is said to be a combination of “non-specific plant proteins and different chemicals which has the power to paralyze and destroy living spirochete.” It is stated that Proteogens are scientific preparations based on standard ingredients and that the standardization is more accurate than in serums, vaccines or toxins, etc. The report gives no proof of such statements.

The testimonials that are submitted are typical of “reports” that manufacturers are able to obtain from some physicians, to prove the efficacy of almost any preparation in any disease. Each consists, practically, of the opinion of the individual who has employed the Proteogens or the opinion of the patient who has been treated. Few data are given in these reports from which an impartial conclusion might be drawn. A few of the testimonials presented by the William S. Merrell Company follow. The valuelessness of such material as scientific evidence is obvious:

RHEUMATISM:--_Proteogen No. 2._--The Doctor has one case being
treated with No. 2. She has improved so rapidly she cannot express
her pleasure, and will continue for some time on the treatments.
She is a patient who was confined during the time she suffered from
a rheumatic illness, and it seemed to affect her mental condition.
This condition is clearing up also, very much to the pleasure of
both patient and doctor.--November 27, 1918.

INFLUENZA:--_Proteogen No. 12._--First day, temperature 102,
gave 1 c.c. Proteogen No. 12; second day, temperature 100,
gave 1 c.c. Proteogen No. 12; third day, temperature 98.8,
gave 1 c.c. Proteogen No. 12, and then discharged the case as
recovered.--October 31, 1918.

ASTHMA:--_Proteogen No. 4._--Splendid results obtained from a
sample of Proteogen No. 4. Three ampoules affected [effected?]
complete recovery.--October 9, 1918.

CANCER:--_Proteogen No. 1._--Mrs. B. pronounced recovered from
Cancer by Dr. O. W. A., of Catlin, after having injections of
Proteogen No. 1 for some time.--October 4, 1918.

ECZEMA:--_Proteogen No. 5._--Tried No. 5 on a patient with
eczema, and with happy results. Have not done anything for him
for about five months--and he is now at his business. Proteogen
No. 5 also RELIEVED HIM OF CONSTIPATION AND WHAT HE CLAIMED A
TRAUMATIC STRICTURE OF THE LOWER PORTION OF SIGMOID FLEXURE.
He is sure pleased and recommending them to his friends.
(Proteogens).--February 17, 1919.

SYPHILIS:--_Proteogen No. 10._--I am getting such excellent results
with the No. 10 Proteogen for Syphilis that I am badly in need of
more, as I am treating so many cases. Please send me four dozen
C. O. D.--October 9, 1918.

ENLARGED PROSTATE:--_Proteogen No. 1._--Have used Plantex in four
cases, with good results in each case. One of them his father, an
elderly man.--April 25, 1918.

LOBAR PNEUMONIA:--_Proteogen No. 12._--The only case I have used
Proteogen No. 12, was a man who had Lobar Pneumonia of left lung
following Influenza. After crisis came, patient continued to have
slight rise in temperature, cough, and after using 10 doses of your
Proteogen No. 12, temperature was normal, cough very much better,
patient began to take on flesh and is still improving.--December
26, 1918.

TUBERCULOSIS:--_Proteogen No. 3._--The Doctor writes: The Proteogen
No. 3 sent me worked wonders in my patient. The case came under my
care when he was too far gone for anything to benefit him a great
deal, but the Proteogen did for him more than anyone could have
expected, yet he died leaving me with a few ampoules to try on the
next patient.--September 20, 1918.

GONORRHEAL CYSTITIS:--_Proteogen No. 11._--My patient has taken
two boxes of your Proteogen No. 11 given for gonorrheal cystitis
of probably two years’ standing and at this writing I consider
her almost, if not entirely, cured which I think speaks very
highly of your remedy. I expect to use more of your preparations
in the future.--April 12, 1919. [This testimonial, either by
clerical error, or because the results were considered remarkable,
was repeated elsewhere in the material submitted by the Merrell
Company.]

ACUTE GONORRHEA:--_Proteogen No. 11._--Mr. A. E. R., age 65, weight
140 pounds. First attack. Had had no previous treatment. Came to me
January 2, 1919. Had discharge, all acute symptoms, burning, etc.
Gave seventeen injections of Proteogen No. 11, also mild antiseptic
urethral wash. Discharged on February 15, 1919, clinically
cured.--April 11, 1919.

EPITHELIOMA OF BUTTOCK.--_Proteogen No. 1._--I used Proteogen No.
1 on an epithelioma of buttock some six months ago with favorable
results and no return of symptoms as yet.--April 13, 1919.

It is obvious that the Proteogen preparations are in conflict with Rules 1, 6 and 10, and should not be admitted to “New and Nonofficial Remedies.” It is recommended that the previous action of the Council be allowed to stand and that publication of both reports be authorized.--(_From The Journal A. M. A., July 12, 1919_)

“ARSENOVEN S. S.” AND “ARSENO-METH-HYD”

Report of the Council on Pharmacy and Chemistry

The Council authorizes publication of the following report. This report declares Arsenoven S. S. of the S. S. Products Company and Solution of Arsenic and Mercury (formerly called Arseno-Meth-Hyd) of the New York Intravenous Laboratory, inadmissible to New and Nonofficial Remedies. The Council takes this opportunity to repeat its warning against the abuses--often dangerous--to which patients are frequently subjected when “intravenous therapy” is employed.

W. A. Puckner, Secretary.

Because of inquiries received, the Council took up the consideration of Arsenoven S. S. and Arseno-Meth-Hyd (now sold as Solution of Arsenic and Mercury). The preparations having been referred to a committee for consideration, this committee reported:

ARSENOVEN S. S.

“Arsenoven S. S.” is a preparation put out by the S. S. Products Company, Philadelphia. The claims are made that it is “a simplified office treatment for syphilis” and is “a combination of arsenic and mercury for office use, offering maximum efficiency, safety and convenience.” According to the company, “Arsenoven S. S.” contains Dimethylarsenin 15.4 grains, Mercury biniodid 1/10 grain, Sodium iodid 1/2 grain. With regard to the identity of “dimethylarsenin” the company claims: “This product is a compound of cacodylic acid similar to sodium cacodylate but with a more pronounced therapeutic action.” The committee recommends to the Council that “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because of unwarranted therapeutic claims.

ARSENO-METH-HYD

“Arseno-Meth-Hyd,” is sold by the New York Intravenous Laboratory, New York City, for the treatment of syphilis. It comes in three dosages, 2 gm., 1.5 gm., and 0.7 gm., respectively. The claim is made that “Arseno-Meth-Hyd 2 gm.” contains “2 gm. (31 grains) of Sodium Dimethylarsenate (Cacodylate), U. S. P.. and Mercury Iodid 5 mg. (1/12 grain)” in 5 c.c. of solution. Physicians are told:

“In primary and early secondary case administer Arseno-Meth-Hyd
2 gm. every sixth day and Mercury Oxycyanide .008 (1/8 grain)
intravenously between each injection.”

“In Tertiary cases and those of long standing alternate with
intravenous injection of Sodium Iodid 2 gm.”

The following claims are made for the alleged effectiveness and safety of the cacodylate:

“This methyl compound of arsenic has come into almost universal use
for syphilis. On account of lack of toxicity an aggressive routine
can be carried on. The simple technic and absence of reactions
make it most desirable for the regular practitioner. This large
dose gives more uniform results both as healing manifestations and
negative Wassermann’s.”

“Much discussion has surrounded the use of Methyl Compounds of
Arsenic and it has been demonstrated beyond doubt that Cacodylate
of Soda proves an effective remedy for syphilis provided that it is
properly administered.” [sic]

“The low toxicity of this Methyl compound of arsenic is remarkable.
It is contraindicated only where a decided idiosyncrasy for even
small doses of arsenic exists.”

These statements are essentially false and misleading. Cacodylate has _not_ come into universal use in the treatment of syphilis, nor has its usefulness been “demonstrated beyond doubt.” On the contrary, H. N. Cole (The Journal, Dec. 30, 1916, p. 2012) has shown that doses so large as to produce renal injury were almost totally ineffective against syphilis. Obviously, “effective doses” if such exist, are not harmless. The dosage advised for Arseno-Meth-Hyd may not produce acute toxic symptoms; nevertheless smaller doses have produced nephritic phenomena. The “Arseno-Meth-Hyd” treatment includes the intravenous injection of about 1/4 grain of a mercury salt. Although this is less than the usual dose (about 1 grain per week), the mercury is probably more effective than the cacodylate.

The committee recommends to the Council that, because of the unwarranted therapeutic claims, “Arseno-Meth-Hyd” be held inadmissible to New and Nonofficial Remedies.

The Council adopted both reports of the committee and declared “Arsenoven S. S.” and “Solution of Arsenic and Mercury” (“Arseno-Meth-Hyd”) inadmissible to New and Nonofficial Remedies. The committee’s reports on these two products impel the Council again to call attention to the undesirable and dangerous abuses to which “Intravenous Therapy” lends itself. There is a distinct field for the intravenous administration of drugs in those cases in which immediate drug action is necessary, or when the medicament is likely to be changed if absorbed through the ordinary channels. Unless such indications exist, however, intravenous administration involves not only inconvenience and expense to the patient, but what is more important, unnecessary danger. The fact that indiscriminate intravenous administration is peculiarly profitable to certain manufacturing houses makes it all the more necessary for the medical profession to be on its guard in this matter.

In this connection it is well worth while to quote the closing paragraph from an editorial on “Intravenous Therapy” that appeared in The Journal, Nov. 11, 1916. It is as true today as when it appeared:

“Intravenous therapy will be most securely advanced if its employment is restricted to such well defined fields. [As those mentioned above.] These fields can be satisfactorily determined only by a scientific pharmacologic study of the action of these drugs when so administered in animals, as well as in man, under conditions in which the results are carefully controlled. The intravenous method is an impressive one, approaching in preparation almost to that which goes with a surgical operation. The patient is usually interested and impressed by this new, and, to him, mysterious method. There is a psychic element in his reaction to the injection which is not a factor in his reaction to the same drug when given by mouth. The intravenous injection of a complex mixture would appear to be particularly reprehensible. Little is known, as has been stated, of the results to be expected from intravenous therapy, even with simple substances. The use of complex mixtures will without doubt react against the proper use of the method.”

After the report on Arseno-Meth-Hyd had been presented to the Council, a letter was received from the New York Intravenous Laboratory announcing that the preparation “Arseno-Meth-Hyd” was now called “Solution of Arsenic and Mercury” and expressing a desire to have its products accepted for inclusion in New and Nonofficial Remedies. In view of this letter, the committee’s report on “Arseno-Meth-Hyd” and the Council’s protest against promiscuous intravenous therapy were sent the New York Intravenous Laboratory for consideration.

The reply of the New York Intravenous Laboratory contained nothing which permitted a revision of the preceding report. The change of the name of “Arseno-Meth-Hyd” to “Solution of Arsenic and Mercury” means little as the name still does not disclose the important fact that the arsenic is present as sodium cacodylate, nor does it tell the character of the mercury compound. The Council voted that “Solution of Arsenic and Mercury” and “Arsenoven S. S.” be declared inadmissible to New and Nonofficial Remedies because the therapeutic claims advanced for them are unwarranted (Rule 6) and because the names of these pharmaceutical preparations are not descriptive of their composition (Rule 8).

In filing its reply with the Council, the New York Intravenous Laboratory announced that that document would be circulated to the medical profession. This is of course the firm’s privilege. The Council notes, however, with interest, that the reply is devoted almost entirely to points which were not raised by the Council and that it fails to discuss the objections which were actually made.

The reply constantly confuses the efficiency of cacodylate in anemia and in syphilis. The Council’s report on “Arseno-Meth-Hyd” does not discuss or even touch on the question of cacodylates in anemia. It is confined to a discussion of the disappointing results obtained with cacodylates as such (i. e., without mercury) in the treatment of syphilis. This attempt on the part of the New York Intravenous Laboratory to confuse the issue and to attribute to the Council an opinion that it has never stated or held is an inexcusable misrepresentation. The company in its reply said:

“We believe that you have previously stated that a solution
cacodylate of soda possesses no more action than so much water. In
other words, it was inert. Now you try to show that it produces
renal injury.”

The Council has never declared that cacodylates are inert. In the report it is merely stated “that doses so large as to produce renal injury were almost totally ineffective against syphilis.” Neither has the Council stated that cacodylate is “peculiarly dangerous.” In fact the absolute toxicity of cacodylates is low but Cole’s results were quoted as a caution that “effective” doses are not harmless. A great portion of the remainder of the reply is devoted to disparaging arsphenamin--a product that is not involved in this action of the Council, and one about which the physician is amply informed.

Amongst other wholly extraneous matters, the firm’s “reply” tried to resurrect the pepsin pancreatin controversy. This also has nothing to do with the efficiency or harmlessness of sodium cacodylate. In order to dispose of the matter, however, it may be pointed out that the implications are entirely misleading. The work which is quoted against the Council was undertaken by the Council itself, to clarify obscurities in the older data. The outcome of these new investigations showed the essential correctness of the deductions from the older work, namely, that pancreatin is destroyed by pepsin-hydrochloric acid. Dr. Long’s work to which the firm’s reply evidently refers, showed that under favorable conditions, namely, when protected by an excess of protein, some trypsin may escape destruction in the stomach; but it fully confirmed the original conclusion that pepsin and pancreatin mixtures as ordinarily administered are practically worthless (J. H. Long, _Jour. Amer. Pharmaco. Assoc._, Sept. 19, 1917).

As regards the editorial on intravenous therapy, a concession may be made the New York Intravenous Laboratory: intravenous injections are no longer quite as “impressive” as in 1916, but that does not alter the fact that they should be used only when a distinct advantage is to be gained.--(_From The Journal A. M. A., Aug. 2, 1919_)

HORMOTONE AND HORMOTONE WITHOUT POST-PITUITARY

Report of the Council on Pharmacy and Chemistry.

“Hormotone,” of the G. W. Carnrick Company, is advertised as “A pluriglandular tonic for asthenic conditions.” “Hormotone Without Post-Pituitary” is recommended for use “in neurasthenic conditions associated with high blood pressure.” These preparations are sold in the form of tablets for oral administration. The Council declares these preparations inadmissible to New and Nonofficial Remedies because: (1) Their composition is semisecret (Rule 1); (2) the therapeutic claims are unwarranted (Rule 6); (3) they are sold under names not descriptive of their composition but suggestive of indiscriminate use as “tonics” (Rule 8); (4) in the light of our present knowledge the routine administration of polyglandular mixtures is irrational (Rule 10). In explanation of this action, the Council authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Each tablet of “Hormotone” (G. W. Carnrick Co., New York City) is said to contain 1/10 grain of desiccated thyroid and 1/20 grain of entire pituitary, together with the hormones of the ovary and testes--the amounts and the form in which the latter are supposed to be present are not given. From this it will be seen that the only definite information given to the medical profession regarding the composition of Hormotone is that it is a weak thyroid and a still weaker pituitary preparation.

What results can be anticipated from one or two tablets three times daily (the recommended dose of Hormotone) each containing 1/10 grain of thyroid and 1/20 grain entire pituitary? Such doses of thyroid may, of course, have a beneficial action in a limited number of cases of myxedema and cretinism. An extract of the posterior lobe of the pituitary (Liquor Hypophysis, U. S. P., for example) will, _when injected subcutaneously or intramuscularly_, have a pronounced effect on the parturient uterus; its action on certain other forms of smooth muscle will be much less certain. But the _oral administration_ (for which Hormotone is recommended) of the posterior lobe of the pituitary has not been shown to have any such effect. The use of the anterior lobe in doses of 1 to 4 grains (doses very many times larger than those recommended for the entire gland in Hormotone) is in the experimental stage and its only probable value seems to be in those cases of known gland deficiency.

As to the other alleged ingredients of Hormotone--hormones of the ovary and testes, amounts not stated: all physicians know the uncertainties attending the use of ovarian preparations and the serious question as to whether testicular extracts have any therapeutic value. Whatever may be the physicians views as to the probable therapeutic value of these organs, the first thing he desires to know is how much of the substance he is giving and from what part of the gland it is obtained.

So much for the facts; yet the physician is asked to jump from this region of solid fact into a sea of hypothesis; to believe that small amounts of the well-known drugs thyroid and pituitary, plus an unknown amount of unknown hormones of the testes and ovary are of great value in conditions that in themselves are often purely hypothetical. He is asked to believe that this combination has virtues in such conditions as “hypofunction of the adrenal system,” neurasthenia, the “fatigue syndrome,” amenorrhea, dysmenorrhea, “natural and artificial menopause,” sexual neuroses, cold extremities, cardiac asthenia, low blood pressure, infantilism, sterility, melancholic conditions, obesity, anorexia, anemia, slow metabolism, constipation, psychasthenia, lowered virility and the sexual neuroses of the unmarried, hysteria following functional exhaustion of the nerve centers, frigidity, etc., etc., especially if he guesses that the trouble is due to a “pluriglandular disturbance,” “glandular hypofunction,” an “adreno-pituitary deficiency,” suboxidation, etc.

The physician is invited to use Hormotone because, among other reasons, each alleged constituent is said to be “in physiologic sympathy and therapeutic harmony with the others,” and further, because:

“Pluriglandular therapy has the endorsement of high authorities,
is both logical and effective and Hormotone is a splendid example
of it. It will be seen at its best where the patient lacks snap
and vim and vigor. Asthenic conditions necessarily indicate
hypofunction of the adrenal system ...” etc.

“The use of gland extracts in the treatment of aplasias of the
pluriglandular system has become an established therapeutic measure
of miraculous potency (Bayard Holmes: The Internal Secretory
Glands, _Lancet-Clinic_, Sept. 19, 1914).”

The G. W. Carnrick Company also advertises a “Hormotone Without Post-Pituitary,” each tablet of which is said to contain 1/10 grain desiccated thyroid, and to “present” “hormone bearing extracts of thyroid, anterior pituitary, ovary, and testes.” This product is just as irrational as “Hormotone.”--(_From The Journal A. M. A., Aug. 16, 1919_)

FORMALDEHYDE LOZENGES

Report of the Council on Pharmacy and Chemistry

The Council has voted Hex-Iodin (Daggett and Miller Co., Inc., Providence, R. I.), Formitol Tablets (E. L. Patch Co., Boston), and Cin-U-Form Lozenges (McKesson and Robbins, New York City) inadmissible to New and Nonofficial Remedies, and authorized publication of the report which appears below.

W. A. Puckner, Secretary.

Some years ago, the Council published (The Journal A. M. A., Aug. 28, 1915, p. 816) a report on Formamint, a proprietary medicine widely exploited as a peculiar chemical compound of sugar of milk and formaldehyde. The formaldehyde was said to be liberated slowly by the action of the saliva, and because of this liberation of formaldehyde, Formamint was claimed to be a powerful germicide. Extravagant claims were made for its curative and prophylactic effects. The Council found that the therapeutic claims were grossly unwarranted and that its exploitation to the public was a public danger.

During the recent epidemic of influenza, a variety of tablets or lozenges were advertised, and are still being advertised, having formaldehyde, in some form or other, as the nucleus around which revolve the therapeutic claims. In some cases, the advertising clearly indicates the character of the formaldehyde compound that is claimed to be present; in others the statements are vague and indefinite or misleading.

It is hardly necessary to remind physicians that the use of tablets containing hexamethylenamin or other formaldehyde compounds can neither cure respiratory infections, nor even confer protection against such infections. To be effective, formaldehyde would need to be supplied to the entire respiratory tract continuously for some time or else in concentrations that would be distinctly irritant and damaging to the tissues. Saliva-dissolved tablets, obviously cannot reach the nasal or tracheal mucosae directly; and the application of quickly acting concentrations of formaldehyde is out of the question. This altogether aside from the fact that hexamethylenamin, the basis of some of these tablets, does not liberate formaldehyde in the mouth, and for this reason alone would be quite useless for this purpose! (See Hanzlik and Collins, _Archives of Internal Medicine_, November, 1913.)

An inefficient antiseptic is more than merely useless; it is a menace to public safety, in that it tends to lead to the neglect of rational and effective protective measures. It therefore seems advisable for the Council again to call the attention of physicians to the subject. Accordingly, three specimens of these products were purchased and examined in the Association’s Chemical Laboratory.

Hex-Iodin

Hex-Iodin (Hexamethylenetetramine and Iodum) Lozenges are manufactured by Daggett and Miller Company, Inc., Providence, R. I. They weigh 15-1/2 grs. each, are sweetened and are flavored with mint or menthol. The package and circulars do not contain a definite statement of composition. The rather indefinite synonyms “Hexameth. and Iodine Comp.” and “Hexamethylenetetramine and Iodum” suggest that the lozenges contain hexamethylenamin and free iodin. The further statement that they “contain the combined medicinal antiseptic and prophylactic properties of Hexamethylenetetramine and Iodum” is also rather indefinite. The therapeutic action claimed for the lozenges, however, could only be produced by free iodin and by liberated formaldehyde.

It is unnecessary to discuss in detail the extravagant claims made for these lozenges. The inefficiency of hexamethylenamin has already been referred to; the limitations of iodin, free or combined, in lozenge form, need not be discussed because the examination made in the A. M. A. Chemical Laboratory showed that Hex-Iodin lozenges contained no free iodin, and only traces of combined iodin. Neither formaldehyde nor paraformaldehyde was present; hexamethylenamin was present but, the lozenges being neutral no formaldehyde is generated in contact with water or with the alkaline saliva.

Thus Hex-Iodin is shown to be worthless for the purpose for which it is advertised. Of the two important ingredients said to be present, iodin and hexamethylenamin, only traces could be found of the former while the latter, as has been shown, is incapable of exerting any effect when used as the manufacturers direct.

Formitol Tablets

These tablets are prepared by the E. L. Patch Co., Boston. Each tablet weighs 13-1/2 grs. They have the odor of thymol or menthol and an acid taste and reaction. They are, according to the label:

“For the throat and mouth. Soothing, Astringent, Antiseptic.
Rapidly destroys germs of infection, preventing and relieving sore
throat and mouth.”

In a circular, it is stated, that one of the qualities of Formitol:

“... is the generation of formaldehyde when in contact with water
or the saliva.”

“Besides generating formaldehyde, Formitol, Patch contains
astringent, demulcent and soothing ingredients which render the
combination unusually effective.”

A bacteriologic report is given in this circular in which it is stated that, in 2-1/2 minutes one Formitol Tablet rendered sterile a plate culture of a “characteristic throat micrococci.” The instructions are to dissolve a tablet in the mouth, slowly, once an hour or a half-tablet every half hour.

The A. M. A. Chemical Laboratory reported that Formitol Tablets contained formaldehyde (or paraformaldehyde), and ammonium compound, and some hexamethylenamin. It is probable that the formaldehyde (or paraformaldehyde) was produced by the decomposition of hexamethylenamin originally present in the tablets but decomposed by long contact with the acid.[128]

[128] The E. L. Patch Company declares that “no hexamethylenamine has ever been used in the manufacture of Formitol tablets,” and that ammonium chloride and paraformaldehyde are among the ingredients used in the manufacture of these tablets. The hexamethylenamine present in the tablets, therefore, must have been produced by interaction of the paraformaldehyde and ammonium chloride. This does not alter the laboratory findings regarding the composition of the tablets, namely, that they “contain formaldehyde (or paraformaldehyde), an ammonium compound and some hexamethylenamine.”

These tablets differ from Hex-Iodin in that they really contain active formaldehyde and, therefore, possibly produce antiseptic effect in test-tube cultures. The conditions in the mouth, however, are very different from those in the test-tube, since in the mouth the formaldehyde would be immediately “bound” or absorbed. The claimed absence of irritation indicates sufficiently the absence of efficient quantities of formaldehyde under clinical conditions.

Cin-U-Form Lozenges