NORMAL PHENOL SERUM (CANO) AND METHYL-PHENOL SERUM (CANO) NOT ACCEPTED FOR N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has adopted the following statement declaring Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) ineligible to New and Non­official Remedies.

W. A. Puckner, Secretary.

No statement of the composition of these preparations was submitted to the Council and none appears on the labels of the trade packages. However, the advertising circular contains statements such as:

“... normal phenol serum—phenol with methyl blue dissolved in anaphylactic serum ...”

“... a combination of human or horse serum with Phenol and Methylene-blue, thereby forming a new chemico-biologic product which he termed Methyl-phenol Serum or, chemically, Chloride of Phenol Thionin Tetra­methylene-Seric.”

“Methyl-phenol Serum is a chemico-biological product in which Phenol is the chief factor. Each ampule of 10 c.c. contains the therapeutic equivalent of 0.5 gm. (7.5 grains) of Phenol.”

From the foregoing it appears that both preparations contain phenol and methyl­thionine chloride (methylene blue) and that the second does not contain methyl phenol (cresol) as the name would indicate.

No definite evidence for the value of these preparations is brought forward and even the manufacturer is constrained to caution, “We assume no responsibility for the therapeutic action of the serum....” On the other hand there are a great many statements in the papers of Cano and his colleagues to which exception must be taken. Of these, from among many similar, the following statements are to be cited and commented on:

“Accepting that the gonorrheal infection gives systemic toxemia from absorption of the toxins ...”

It is the general opinion that in the majority of instances there is no systemic toxemia.

“The technique of intraprostatic injection, while less simple than that of the intravenous, is by no means so difficult or complicated as to place it exclusively in the category of the urologist.”

This obviously is an attempt to encourage the general use of these preparations and to minimize the necessity for careful study and special skill in their employment. It is most unwise for one to attempt intraprostatic injections unless he is specially trained in the technique of this procedure.

“This injection to be performed after the 5th or 6th intravenous injection of Methyl-phenol Serum....”

Intravenous injections have a place in sane therapy only when the medicament to be so administered is of known composition and when evidence is available which gives assurance that definite results shall follow its use. In the absence of these conditions it is manifestly unwise and even unexcusable to employ any medicament in this manner, and its repeated use is reprehensible.

“Intravenous injection of Methyl-phenol Serum alternating with intravenous injections of mercury should be given every 48 hours until infection is under control.”

This quotation further emphasizes that the treatment, as advised, carries with it a certain element of danger.

“Methylene blue prevents the phenol from exerting its usual action upon the red blood corpuscles, and ensures rapid elimination through healthy kidneys. It preserves the antiseptic power of the phenol and prevents the phenol from interfering with the chemico-biological function of the white and red blood cells. The serum component favors chemotaxis, it strengthens bodily defense, it prevents anaphylaxis even in debilitated patients, and it replaces the resistance which has been impaired by the demands that have already been made upon it.”

No evidence is submitted to substantiate these claims. It seems strange that phenol should lose its power and that this should be restored by the methylene blue.

“It has a refractory chemico-biological action, and exercises no vicious effect on the red blood corpuscles in the circulation, but, on the contrary, by its inoffensive presence, it wholly preserves all of the physiological properties of the blood.”

What “a refractory chemico-biologic action” is, is not clear, but there is no evidence that this preparation has any action which might be defined as “refractory chemico-biological,” that its presence is inoffensive or that it wholly preserves all the physiologic properties of the blood.

“The treatment of gonorrhea by Cano’s theory ... is firmly based upon chemico-biological facts and accepted authoritative theories and bears the same relation to gonorrhea that intravenous injections of arsenicals bear to syphilis.”

Quite an exaggerated and unwarranted statement. In the same way, objection is taken to the following quotations:

“Phenol administered intravenously in combination with methylene blue, to protect the red-blood globule, undergoes no change, and preserves all of its actual antiseptic effect on the gono­coccus and its toxins as though employed in the test tube.”

“When thus introduced into the human body its elimination is unique, effective, antiseptic, germicidal, being completely and exclusively thrown off through the kidneys in a period varying from one-half to twelve hours without local injury or disturbance to the general economy.”

“Combinations of phenol are unstable, but they do have the advantage of mitigating direct action on the cells and globules. It is also known that ordinary phenol has a coagulant action on the albumins and an oxidizing power on the tissues, which power, if permanent, produces gangrene. By virtue of this dual action it therefore acts as a modifier; by its oxidizing power on the germ it is germicidal, and prevents the growth of the gono­coccus; and by its coagulant power on the toxins it relieves para­gono­coccal lesions (mono- and poly-arthritides) and affections of the serous organs (endo- and pericarditis, meningitis), and some definite systemic disturbances, the pathology of which is often confused with that of other infections.”

“Lymphocytosis is often persistent in some individuals in whom the internal secretions and the processes of assimilation and disassimilation are deficient; and because of the lack of these the organic physiological ferments are insufficient for the mechanism of nutrition and the phenomena of hematopoiesis.”

Until proof is available showing that phenol, administered intravenously in the quantities employed in Cano’s Normal Phenol Serum and Cano’s Methyl-Phenol Serum, acts as a germicide and methyl­thionine chloride (“methylene blue”) prevents the deleterious effects of phenol on the red blood corpuscles; that repeated intravenous injections of phenol and mercury are without danger; that there is no danger of anaphylaxis; that the physiologic properties of the blood are preserved by these medicaments; and, finally, that these preparations have an effect on gonorrhea and its complications, these substances Normal Phenol Serum (Cano) and Methyl-Phenol (Cano), are inadmissible to New and Non­official Remedies.

The following quotations taken from the circular are admissions that these preparations are not innocuous:

“That the economy will tolerate to a surprising degree substances directly introduced through the blood stream is now well known. By the intravenous injection of 10 c.c. of methyl-phenol serum we throw into the human body a massive dose of an alien substance. The immediate effect of this injection is upon the central nervous system. The recipient usually becomes either pale or suffused, he has a ringing in his ears, has a sensation of great altitude, and occasionally has a dryness of the fauces and a metallic or a garlic taste.”

“In some patients secondary reactions occur in from one to four hours after injection. The phenomena we have observed in these secondary reactions are pronounced chill and rigor ...”

There is no doubt that considerable harm may be done by the intravenous and by the intraprostatic administration of these preparations and until there is good evidence showing the therapeutic value of the treatment, the routine use of these preparations, except perhaps at hospitals in selected and well controlled and carefully guarded cases, is to be strongly discouraged.

When the foregoing statement was sent to the Mulford Company for comment, the firm submitted a letter from Dr. Perry Townsend to the Mulford Company in which he declared that the results obtained with the Cano preparations had been satisfactory and without untoward results. In this letter, Dr. Townsend proposed that a series of injections with these preparations be carried out under the observation of members of the Council and the supervision of Dr. Cano or himself.

The report of the Council, the letter from the Mulford Company and that of Dr. Townsend were sent to a number of urologists for their opinion concerning this whole matter. It was explained that the referee held that no reason had been presented which would warrant the Council to depart from its customary procedure, namely, to require that clinical evidence be submitted in the form of published reports which permit investigation and verification by independent observers but that, before making further recommendation to the Council, he desired the opinion of urologists of recognized standing concerning the report submitted to the Mulford Company. All replies received approved the Council’s position.

The following is one of the replies received:

Your letter in regard to Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) received. I wish to state that I have read the correspondence between the Council and H. K. Mulford Co. and in my opinion the referee and the Council are quite correct in their attitude in the matter. In my opinion I would emphasize the following:

(1) There is absolutely nothing about the remedies directed specifically against the gono­coccus and no evidence to show that any action against them is obtained. As we know there are certain states of normal serum which are highly toxic and any normal serum from another animal will produce disturbances in man when injected intravenously—particularly if repeated. The addition of substances to serum normal or otherwise is apt to and frequently does render that serum highly toxic! The substances added in the instances referred to—phenol and methylene blue are not in any way calculated to lessen the toxicity of serum. The element of danger existing in the indiscriminate use of serums intravenously is, in my opinion, increased by the addition of the substances mentioned, and it would be unwise to encourage the general use of any such remedies. Furthermore the products are condemned by the very evidence of the originators and their admissions are quite sufficient to deter anyone from using the products as they suggest.

As to the intraprostatic injections with the serums it does not at all meet my views; although the introduction of serums by this route have been frequently advocated and I have personally carried this mode out I cannot allow the impression to go out that it could be done in a routine manner—nor that no ill results could follow—for I have seen otherwise. Furthermore from theoretical standpoint serums need not be given in this way.

In consideration of the opinion expressed by the Council’s consultants the referee recommended that Normal Phenol Serum (Cano) and Methyl-Phenol Serum (Cano) be declared ineligible for New and Non­official Remedies because of conflict with Rule 6 (unwarranted therapeutic claims) without considering possible conflicts with other rules, and that publication of the report be authorized.—(From Reports of Council on Pharmacy and Chemistry, 1919, p. 85.)