Chapter XXXIII: Part III: Contributions From the Journal: Proprietary Products (1)

NOSTRUMS IN RETROSPECT

A Series of Nine Articles Reviewing Worthless or Unscientific
Proprietary Mixtures Previously Criticized

S. Q. Lapius, M.D.

[FOREWORD.--It is more than twelve years since the Council on Pharmacy and Chemistry of the American Medical Association was created. Since then there have been but few issues of The Journal that have not called the attention of the medical profession to the debasing influence on scientific medicine of unscientific or worthless proprietary mixtures advertised to physicians for their use in prescribing. The Council on Pharmacy and Chemistry has investigated and shown many of these preparations to be fraudulent in one way or another, and these reports have been published in The Journal. In spite of this, these preparations have been advertised continuously to physicians, through medical journals and otherwise, and prescribed by a large number of physicians. One reason for this is that there are many physicians who have never seen these reports--who were not in active practice at the time, or who were not reading The Journal. We probably have among our readers at the present time 35,000 or 40,000 physicians who were not among the readers of The Journal twelve years ago. It is desirable, then, that we should take up, in more or less detail, several of the more widely advertised products that have been the subjects of previous reports. It has been repeatedly stated in The Journal that many of the proprietary mixtures--the so-called ethical proprietaries advertised to physicians--were no better and no worse than “patent medicines” advertised to the public.

Every physician who has the welfare of medicine at heart should put these questions squarely to himself if he has not already taken a firm stand on this whole problem: What is my attitude toward the work of the Council? Are its reports worthy of acceptance? Am I upholding the Council in its efforts to place therapeutics on a rational basis, not by blind faith alone, but by an honestly critical attitude toward it? Am I following the path of indolence by taking the advice of nostrum makers without any serious effort to determine whether they are true or false? In a word, am I really practicing medicine, or am I an unpaid agent and a dupe of nostrum makers? There are other revolutions than political. The public can be wronged just as certainly by the abuse of its confidence in clinicians as by the usurpers of political power, and when the public is thoroughly aroused the heavy hand of retribution is not likely to be too discriminating. That the sins of clinicians are standing out plain for any one who wishes to read is becoming more and more evident. There is but one short and ugly word that properly characterizes the physician who accepts a fee for prescribing that about which he has no more knowledge than has the one for whom he prescribes it. Are you with the nostrum makers or with decent medicine?

The article below is the first of a series written for The Journal by one who is thoroughly conversant with the work of the Council on Pharmacy and Chemistry and can speak authoritatively on questions dealing with the action of drugs and the treatment of diseases. We believe that these articles will prove of interest and profit and that they will help physicians to answer the questions just propounded.]

[ARTICLE I]

Bell-Ans (Pa-Pay-Ans Bell)[H]

[H] See also ????.{sic}

Bell-ans, for years advertised only in medical journals under the name “Pa-pay-ans (Bell),” is now advertised in newspapers as a remedy that “Absolutely Removes Indigestion.” As it is still being advertised to physicians, we propose to analyze the claims made for it with as much care as would be exercised in the discussion of the newest discovery in medicine, because we believe that it is desirable to show the trend of exploitation of a certain type of preparation in the medical press.

In the _New York Medical Journal_ the following advertisement recently appeared on the front cover:

+-------------------------------------------------------------+
| =Acute Indigestion= |
| |
| Yesterday a great soldier and today the head of a big trust |
| succumbed to an attack of Acute Indigestion, and every day |
| we hear from some physician of some case he has saved with |
| BELL-ANS by giving SIX (6) tablets dissolved in a glass of |
| hot water and repeating if necessary. Can any doctor who |
| reads this fail to provide himself with the free supply of |
| BELL-ANS which we will gladly send for his emergency case? |
| |
| Bell & Co. (Inc.) Mfg. Chemists Orangeburg New York U S A |
+-------------------------------------------------------------+

Typical of Bell-ans advertisements as appearing in medical journals.]

A recently purchased package of Bell-ans contained a circular in which it was stated that Bell-ans removes flatulence, vertigo, weakness and other symptoms of indigestion quickly and pleasantly; that it aids the digestion of food and tends to restore the digestive tract to a normal condition; that it relieves vomiting in pregnancy, alcoholism, seasickness and cholera morbus, besides being pleasant, harmless and effective for colic, sour stomach, feverishness, and wakefulness of infants and children. The circular contained paragraphs purporting to be taken from various medical journals, including the _New York Medical Journal_, _Wisconsin Medical Recorder_, the _Lancet Clinic_, _International Journal of Surgery_, and _Massachusetts Medical Journal_. No exact references were given to permit verification or to determine whether or not the quotations were from “reading notices” (advertisements) or from the scientific part of the journals in question. To quote one of the statements given:

“The results from the use of Bell-ans (Pa-Pay-ans Bell) in the
treatment of indigestion are so prompt and so generally good--and
the evidence of this fact is accumulating so rapidly and from such
reliable sources--that we venture to suggest to our readers who
have not tried this remedy that they prescribe one original sealed
package of Bell-ans (Pa-pay-ans Bell) and that they carefully note
the results from its use.

“We suggest an original sealed package because the preparation is
widely and badly imitated, and unless such a package is specified
an imitation of little value may be substituted and the experiment
be thus rendered useless.”

It is possible that Bell-ans has been imitated, but it is not true that it is widely imitated, for no such imitation has ever been called to our attention, and we strongly suspect that the main reason for desiring that an original package be dispensed is that the patient may see for himself the name BELL-ANS plainly blown in the glass.

The circular in question states that there is no derangement of the digestive organs on which the proper dose of Bell-ans will not act quickly and pleasantly! These are samples of the claims made for Bell-ans. Let us inquire into the nature of the conditions for which the preparation is recommended and the treatment advised by well known clinicians.

The subject of indigestion is discussed by Robert Hutchison and Robert Saundby under the general title of dyspepsia in the “Index of Treatment by Various Writers,” Edition 6, 1912, pp. 260-265. Hutchison says: “In the first place it must be remembered that in many patients who complain of ‘indigestion’ the seat of the trouble is not in the stomach at all.”

+-----------------------------------------------------------------+
| A Philadelphia Doctor writes: |
| |
| “Your BELL-ANS for ingestion do just what you claim and more |
| too. I, personally, had a bad case of intestinal indigestion |
| with gastric vertigo. I had taken almost everything and got no |
| relief, until I commenced to take BELL-ANS--four to six tablets |
| in a large glassful of hot water after each meal. You have my |
| permission to use this statement, with my name and address if |
| you wish. I prescribe BELL-ANS constantly” |
| |
| =BELL-ANS= |
| FOR INDIGESTION |
| 25c package at every drug store in the U. S. |
+-----------------------------------------------------------------+

Newspaper advertisement of Bell-ans, capitalizing the statements of physicians.]

The general principles to be observed in the treatment of functional dyspepsia, as given by Hutchison, are: (1) to remove the cause; (2) to adapt the diet to the impaired functional power of the stomach; (3) to administer such drugs as are calculated to stimulate or correct the particular function or functions which happen to be impaired, or disordered. Proper diet, proper mastication of food, hygiene of the mouth, and constipation are enumerated as deserving attention. Careful attention to securing a proper diet is essential. The choice of drugs depends, of course, on the conditions that give rise to indigestion, and he calls attention to the necessity of avoiding all routine treatment and compiling one’s prescription with an eye to the special disorder or disorders of function, whether secretory, motor or sensory, believed to be present. Hutchison gives the following typical prescriptions to illustrate the use of drugs in the different disorders of function:

FOR HYPERSECRETION (HYPERCHLORHYDRIA, ACID DYSPEPSIA, ETC.)

Sodium bromid 10 grains
Bismuth subcarbonate 15 grains
Chloroform water 1/2 ounce

This mixture to be taken before meals.
Sodium bicarbonate.
Bismuth subcarbonate.
Heavy magnesium carbonate, of each equal parts.
A small teaspoonful of the powder to be taken mixed with a little
water or milk about two hours after meals.

FOR DEFICIENT SECRETION (HYPOCHYLIA, ACHYLIA, GASTRITIS, ETC.)

Sodium bicarbonate 10 grains
Tincture of nux vomica 10 minims
Spirit of chloroform 8 minims
Compound infusion of gentian 1/2 ounce

This mixture to be taken before meals.

Dilute hydrochloric acid and glycerin, of each 15 minims with
enough water to make half an ounce, to be taken about twenty
minutes after meals.

FOR DEFECTIVE MOTILITY (ATONIC DYSPEPSIA, GASTROPTOSIS, ETC.)

Hutchison recommends the use of 10 minims of tincture of nux vomica
in an aromatic vehicle, such as infusion of quassia and compound
tincture of cardamom; but another aromatic bitter, such as the
compound tincture of gentian, will serve quite as well, of course.
This is to be taken before each meal, and for the flatulence that
often accompanies this trouble he gives menthol, aromatic spirit of
ammonia and spirit of chloroform, as may be needed.

FOR ACID DYSPEPSIA

Robert Saundby recommends the following to be used before each
meal for the relief of acid dyspepsia: sodium bicarbonate, bismuth
subcarbonate, magnesium carbonate, of each 10 grains; mucilage of
tragacanth 15 minims, and enough peppermint water to make an ounce.

These are only a few of the conditions that are discussed by Hutchison and Saundby, but they serve to show that the treatment of indigestion by a single prescription or combination is wholly irrational.

Bell-ans, both under its present name and under its older name, “Pa-pay-ans (Bell),” has always been alleged by its manufacturers to contain papain or to be a preparation of the digestive juice from the fruit of _Carica papaya_ (papaw) with other substances. Various chemists have attempted to find papain present and to determine the digestive power of the tablets, but without success. For this reason The Journal suggested that the change of name from “Pa-pay-ans (Bell)” to “Bell-ans” was probably not made entirely for euphonious reasons, as alleged, especially when one considers that the name of a nostrum is its most valuable asset. It is much more likely that as analyses indicated there was not and probably never had been any papain present in the product, the name was changed for fear that some day the misleading term “Pa-pay-ans” might bring the preparation in conflict with the federal Food and Drugs Act.

Pa-pay-ans (Bell) was examined for the Council on Pharmacy and Chemistry in 1909 and the tablets were found to consist of charcoal, sodium bicarbonate, ginger, saccharin and oil of gaultheria. No digestive ferment could be detected in the tablets. Sodium bicarbonate is antacid and serves to dissolve mucus; ginger, if in sufficient amount, causes the expulsion of flatus, and charcoal, while an absorbent in the dry state, is probably useless for any therapeutic purpose whatever after it becomes saturated with gastric juice. Bell-ans, then, has all of the virtues, which are few, and all of the limitations, which are many, of a tablet of sodium bicarbonate and ginger. Its value in the treatment of acute indigestion would be limited to the value of a tablet of such a composition. It is absurd to suppose that it could have the slightest value in the far more serious conditions attended with intestinal indigestion, with the toxemia and autointoxication to which they give rise.

Bell-ans is now advertised directly to the public--but it is no less valuable on that account. True, it is a “patent medicine” in the commonly accepted sense of the term, but it is no more a “patent medicine” today than it was fifteen years ago when it reached the public, not through the direct medium of the newspapers but the more indirect route of the medical journals and undiscriminating physicians. It is true that, in view of the serious nature of many conditions which are loosely spoken of by the public as “indigestion,” its present method of exploitation is likely to make it just that much more dangerous because of the larger publicity that will be given. The point to be borne in mind is that Bell-ans is now in fact what it has always been in essence, a “patent medicine.”

Typical of Bell-ans advertisements as appearing in newspapers.]

Again we ask the question: How do you wish to be classified, Doctor--among those who follow blindly the lead of a firm of nostrum makers, or among the intelligent members of the profession who study their cases carefully and prescribe intelligently? The manufacturers of Bell-ans claim that 100,000 American physicians now prescribe Bell-ans, and that 600,000,000 of the tablets are sold annually. If this is even approximately true it is a serious reflection on the medical profession, for the Council examined Bell-ans and reported its findings nearly eight years ago (_J. A. M. A._ =53=:569 [Aug. 14] 1909), and the statements made in that report are as incontrovertible today as they were then.--(_From The Journal A. M. A., Nov. 24, 1917._)

[ARTICLE II]

Anasarcin and Anedemin

“Anasarcin” and “Anedemin” are the twin nostrums of cardiac pseudotherapy. They are dubbed “twin nostrums” not so much because of any similarity in their formulas, that being a minor consideration in the average nostrum, but because of the close similarity in their methods of exploitation, the therapeutic claims made for them, and the time and place of their birth.

It may be remembered that they both claim Winchester, Tenn., as their birthplace, and they appeared on the market at about the same time; furthermore, a comparison of the claims formerly made for both of them indicated that one mind conceived the main idea that lies back of their exploitation. While Anasarcin is especially dealt with in this article, much of the discussion applies with equal force to Anedemin.

A LUSH FIELD FOR NOSTRUMS

Cardiac disease, with its resultant renal involvement, is frequently encountered; and running, as it does, a chronic course, it offers an almost ideal field of exploitation for the typical nostrum vender. By a typical nostrum vender we mean one whose knowledge of his product is far below that of his appreciation of a certain element of human character. On this element rests the whole secret of the nostrum vender’s success. It is variously termed credulity, gullibility and childlike simplicity, but it is that which often causes even the most conscientious clinician to turn aside from the use of the best known and most dependable drugs at his command, in the face of disappointment and failure, and employ some vaunted mixture which, in his saner moments, he scorns to use.

Anedemin is said to consist of a “Scientific Combination of three of the more recently investigated members of the Digitalis Series, with Sambucus”; that is, of apocynum, strophanthus and squill with elder. It is difficult to know just what idea the statement that it is a “scientific combination” of these drugs is intended to convey, for it is unscientific to mix three drugs of this group for use in fixed proportion in a wide range of conditions, if indeed, there is ever any indication for their use.

The great disadvantages of strophanthus and apocynum pertain to the extreme uncertainty of their absorption from the gastro-intestinal tract. Strophanthus is occasionally absorbed promptly, sometimes so slowly that the therapeutic effects are not induced until an amount equal to several times that which would prove fatal if all of it were absorbed into the circulation has been administered, and, unfortunately, one cannot control the absorption which may continue until a fatal effect is induced. This is true to an even greater degree of apocynum, and it was due to the recognition of this fact that apocynum was not admitted to the U. S. Pharmacopeia IX, the committee on dosage having agreed that no safe and effective dose could be given.

THE COUNCIL’S PREVIOUS FINDINGS

In 1907 the Council on Pharmacy and Chemistry examined the literature used in the exploitation of Anasarcin and Anedemin and published its report. Anasarcin tablets, it was pointed out, were said to contain the active principles of _Oxydendron arboreum_ (sour wood), _Sambucus canadensis_ (elder) and _Urginea scilla_ (squill), and the following claims were made for the nostrum:

“Does what dropsy medicaments have hitherto failed to accomplish.”

“Superior to digitalis, strophanthus, scoparius, squills, acetate
of potash and the hydragogue cathartics all put together.”

“The only known relief and permanent cure of dropsies.”

“Unrivaled heart tonic.”

“The most powerful agent known.”

“Safe in administration.”

“Non-toxic as ordinarily administered.”

“Will nauseate some persons,” but “the reaction from the temporary
depression is prompt.”

“In Bright’s disease, both the interstitial and parenchymatous
forms of nephritis, acute or chronic, no remedy ... to equal it in
efficacy.”

“Without increasing the debility of the patient or interfering with
nutrition by producing loss of appetite ...”

“This treatment is to be continued without cessation until all
symptoms of dropsy have disappeared.”

A comparison of the earlier claims with those now being made (see advertisement reproduced from the _New York Medical Journal_) illustrates one of the results of the work of the Council. Today the nostrum exploiter avoids the cruder forms of obvious misstatement, but continues to make, by inference, claims that are equally misleading. It will be observed in this case that a more cautious pen worded the later advertisement, but there is still evident the intent to convince the reader that Anasarcin is superior to the official drugs in the treatment of cardiovascular diseases. The facts are that Anasarcin is at best a dangerous remedy in the hands of the average clinician in the treatment of such conditions, and its use is at all times to be condemned.

No competent investigator has ever investigated the pharmacology of sour wood (_Oxydendron arboreum_), and it appears to have no therapeutic value other than that due to a slight acidulousness. Elder (_Sambucus canadensis_) contains a trace of a volatile oil as its most important constituent, according to the British Pharmaceutical Codex of 1911 (p. 908), but it is difficult to explain why a trace of volatile oil should be considered important. Elder may be dismissed without further consideration in connection with Anasarcin tablets.

THE PHARMACOLOGY OF SQUILL

This leaves only squill among the constituents of Anasarcin for consideration. Sollmann (Manual of Pharmacology, 1917, p. 409) in discussing the advantages claimed for squill over other drugs of the digitalis group, says: “Dixon, 1906, points out that any superiority is outweighed by its disadvantages: uncertain absorption; strong gastro-intestinal irritation.” Squill was formerly used as an expectorant and diuretic, the activity having been attributed to two amorphous glucosids, scillipicrin and scillitoxin, but Ewins, 1911, found these to be impure mixtures. A later investigator claimed to have isolated two glucosidal agents from squill, but similar claims have often been made only to be disproved later, and we know of no confirmation of the claims regarding the isolation of any pure principles from squill having any true typical digitalis action.

The statement quoted from Sollmann is accepted by practically all pharmacologists, and we may say with certainty that squill is decidedly inferior to digitalis in the treatment of cardiovascular, and cardiorenal diseases, and certainly no active principles of squill were known to the scientific world at a time that the remarkable claims were first made for Anasarcin by an obscure pharmacist of Winchester, Tenn. Indeed, if Anasarcin were all that it was claimed to be, its discovery would have made Winchester as famous as a certain Wisconsin city was said to have been made by a popular beverage.

It has been abundantly demonstrated, and it is now almost universally accepted among well informed pharmacologists and clinicians, that all digitalis principles exert the same kind of action on the heart after they enter the circulation in effective doses, though they differ to an extraordinary degree in the intensity of their action and in their undesired sideactions, such as nausea and vomiting. When the use of Anasarcin (squill) is followed by immediate improvement after digitalis has failed, it merely shows that the dosage of digitalis was insufficient or that it was discontinued and the squill mixture was substituted before the full therapeutic effects of the digitalis developed.

WHEN THE DIGITALIS GROUP IS CONTRAINDICATED

If the administration of a sufficient dose of digitalis is not followed by improvement in the circulation, it shows that the heart is incapable of responding to such treatment and the further use of any of the drugs of this group is distinctly contraindicated. This is confirmed by the experience of nearly every competent observer of digitalis therapy, and numerous fatalities have resulted from the failure to appreciate this fact and further administer some other member of the group, such as strophanthus or squill.

It is now well known that the cardiac effects of toxic doses of squill, and other members of the group, resemble closely those of cardiac disease, and it is often impossible to determine whether the behavior of the heart in a given case is attributable to insufficient dosage, to excessive dosage, or to the progress of the cardiac disease itself. If this occurs when one uses the best known members of the group, it is certain that it occurs even more frequently when others that are less understood are employed. In the light of this knowledge of the dangers attending the incautious use of any member of the digitalis group, and more especially the use of impure principles, such as are commonly obtained from squill, it is impossible to condemn sufficiently the recommendation that the use of Anasarcin should be continued without cessation until all symptoms of dropsy have disappeared.

Digitalis bodies are not suited for the treatment of all cardiac disturbances, and it is, of course, self-evident that a time must come in the treatment of chronic cardiac disease when the heart is incapable of responding to any form of treatment with improvement. But, unfortunately, it never loses its response to toxic doses, and to push the administration of any drug or mixture containing any drug of the entire digitalis group--and especially those, like squill, in which the side actions are most prominent--beyond the point of tolerance is to court certain disaster.

THE TREATMENT OF CARDIAC DROPSY

While it is quite certain that many lives have been sacrificed to the failure to understand this phase of cardiac therapy, it is equally certain that many lives have been sacrificed because of insufficient dosage, and one can steer a safe course between these dangers only by using the best known preparation available; and in the present state of our knowledge it is indisputable that digitalis and the tincture of digitalis are best suited for the treatment of cardiac disease except in those few cases in which intramuscular or intravenous administration must be employed temporarily for immediate effect.

The secret of prescribing successfully for the relief of dropsy in cardiac disease consists in understanding the effects of digitalis on the heart, in administering it until these effects indicate that the desired object has been obtained, and stopping, or interrupting, the administration at that point until the effects begin to wear off. Cumulation, so called, is a positive advantage in such cases. It merely means that the desired therapeutic effects once induced persist for a time, and that further medication is unnecessary during such persistence of action. Eggleston has recently shown (_Arch. Int. Med._ =16=:1 [July] 1915; abstr., _J. A. M. A._ =44=:459 [July 31] 1915) that the full therapeutic effects of digitalis can be induced in suitable cases within a few hours even with oral administration.

We are not aware of a single publication in which a careful, detailed clinical study of Anasarcin has been reported. The claims made for Anasarcin, past and present, indicate either a deliberate purpose to mislead or crass ignorance of the rudiments of pharmacology and therapeutics. The exploiters of the nostrum claim that thousands of physicians have found Anasarcin tablets of unsurpassed remedial value in the treatment of disorders of the circulatory system and of ascitic conditions.[244] It must be admitted that too many physicians have prescribed Anasarcin, otherwise the manufacturers would not have continued to spend thousands of dollars in advertising it in medical journals during a period of more than ten years.

[244] Former estimates of the number of physicians who prescribed Anasarcin appear to have been too high, possibly based on the ratio obtaining in Winchester, Tenn. Inquiry at five fairly busy drug stores in a large eastern city showed that in no instance was the pharmacist even acquainted with the name. One pretended to be, and manifested pity for the inquirer’s ignorance in supposing that it could be imported during the war! He was obviously merely less honest than the others, who frankly admitted they had never heard of it.

Doctor, this article is meant to be a candid discussion with you, whether you use Anasarcin or not, because every clinician is vitally interested in the customs that obtain in the practice of medicine, and we wish to put a hypothetic question to you. Answer it, at least to yourself, in exactly the spirit in which it is put. Suppose that you prescribe Anasarcin for a patient who is critically ill with cardiac disease. He dies. Are you willing to tell the relatives frankly just what you used and the nature of the evidence on which you based your choice of this nostrum? Let the supposition be carried further and say that the case was hopeless, and agree that digitalis and all other drugs would have been equally ineffective. Granting all this, would your explanation satisfy? Would you in all candor dare to offer such an explanation? Try it as a hypothetic case before you are forced to apply it.--(_From The Journal A. M. A., Dec. 8, 1917._)

[ARTICLE III]

Pepto-Mangan

It would be interesting, and even instructive, to know how many educated physicians, if any, are now prescribing Pepto-Mangan (Gude): interesting as indicating the number who have neglected to avail themselves of the work of the Council on Pharmacy and Chemistry, especially the earlier work; instructive in that it would show how many are still prescribing by the rule of thumb, and who are taking their therapeutic instructions from purely commercial sources instead of striving to learn how to choose those drugs that are most effective in the treatment of disease.

It has been pointed out many times in the pages of The Journal that many nostrums are advertised first to physicians, and that after physicians have served as the unpaid agents of the manufacturers in introducing the preparations, their exploitation is then commonly continued by means of advertisements in the public press. This plan has been followed successfully in so many cases that we have now come to look on it as the regular course. It is in keeping with this rule that we find Pepto-Mangan now advertised in the public press, the physicians having served the manufacturer’s purpose.

DISCARDED THEORIES OF IRON MEDICATION

It will be recalled that many years ago the theory was held that hydrogen sulphid (sulphureted hydrogen) interfered with the absorption of the iron of the food, and that the administration of medicinal iron prevented this interference by neutralizing the hydrogen sulphid (sulphureted hydrogen). It was only a short step to argue that manganese might replace the medicinal iron in combining with the hydrogen sulphid, permitting the food iron to be absorbed, and it was held that only food iron could be utilized in the formation of hemoglobin.

It is hardly necessary to remind the reader that this theory rests on numerous fallacies. There is no hydrogen sulphid worth mentioning in the small intestine where iron is absorbed; food iron cannot be utilized directly in the formation of hemoglobin but must be broken into simple forms for absorption; and, further, inorganic iron, such as ferrous carbonate, serves the purpose admirably when iron is indicated. With the acceptance of these well established facts, all possible excuse for the therapeutic employment of Pepto-Mangan in place of iron vanished; but as plain and simple as this fact is, the unnecessary and expensive Pepto-Mangan continues to be prescribed by physicians who will not take the slight trouble to investigate the claims for this nostrum.

FALSE AND MISLEADING CLAIMS

There is not merely a difference of opinion between the exploiters and the Council, but there has been also actual misrepresentation in the exploitation of this nostrum to physicians. This has been shown on more than one occasion. About twelve years ago, the M. J. Breitenbach Company, the proprietors of Pepto-Mangan, claimed that the report of the commission that had been appointed for the investigation of anemia in Porto Rico “would alone suffice to establish Pepto-Mangan at once as the foremost hematinic known.” Examination of the report showed that the commission made no such claims; on the contrary the commission protested against this misrepresentation (_J. A. M. A._ =45=:1099 [Oct. 7] 1905).

Undaunted by this exposure of their methods, the Breitenbach Company later sent out a statement of results purporting to have been obtained by one Mateo M. Gillen, in the treatment of infantile anemia on Randall’s Island in New York City. At the instance of The Journal the hospital records in these cases were examined, and it was found that the pretended report was little more than a tissue of falsehood (_J. A. M. A._ =48=:1197 [April 6] 1907).

About two years ago the Council reported that while the statements just referred to were no longer made, they had never been definitely admitted by the Breitenbach Company to be erroneous, and that Pepto-Mangan was then being exploited to the public indirectly. (Council Reports, 1914, p. 121.)

We reproduce an advertisement that has been appearing weekly in the _New York Medical Journal_ for several months. One can only suppose that this advertisement was intended to mislead physicians, and it would be an insult to the intelligence of the average reader to attempt any detailed discussion of it, but enough has been said to show how misleading the statements are. One should note particularly the advice--old as the nostrum business itself--contained in the advertisement, to prescribe an original bottle. The reason for such advice is simple. Experience has shown that when original bottles are dispensed patients soon learn to buy the nostrum without consulting the physician, for they shrewdly suspect that he knows no more about the preparation than they, and that he gets his information from precisely the same sources that are available to them. They are obviously right. In truth, the physician who prescribes Pepto-Mangan as a hematinic shows ignorance of the most rudimentary facts of iron therapy, and the intelligent patient soon perceives his limitations.

THE PROBLEM OF IRON THERAPY

The investigation of the problems of iron therapy and its utilization in the formation of hemoglobin forms one of the most brilliant chapters in pharmacologic research, and there is no better established fact in therapeutics than that any organic or inorganic preparation of iron that does not irritate the stomach may be employed effectively when the administration of iron is indicated. “Useful Drugs” contains a list of iron preparations that are suitable for all conditions which call for iron, and the clinician may rest assured that he will never have occasion to go outside that list to prescribe any substitute.

As a matter of fact, it seems probable that the very number of available iron preparations has served to cause confusion, thus affording an opportunity for the nostrum maker to introduce his superfluous compounds. It may be difficult at times to select the preparation of iron best suited to the individual patient; and it is this difficulty that has led the clinician to listen to the seductive claims made for the various pretended substitutes for iron. One should approach the question of choosing the proper form of iron for therapeutic use with the recognition of the fact that there is no such thing as a substitute for iron in the formation of hemoglobin, that there are no ideal forms of iron other than those found in the foodstuffs. Further, the clinician cannot avoid the disadvantages inherent in all forms of iron that he can prescribe, and he must therefore seek that which seems best suited for the individual patient.

Bunge estimated the amounts of iron present in various foods; and a table based on this, and other data, is given in “Pharmacology of Useful Drugs” (published by the American Medical Association). Ordinary foods in an ample diet contain enough iron to supply the normal daily loss, which amounts to only a few milligrams, but many persons who have poor appetites take an insufficient amount of iron in their food and become anemic. In such cases the additional iron required can be supplied best by adding spinach, eggs, apples, or other iron-rich food to the dietary.

SOME IRON COMBINATIONS

William Hunter discusses the subject of anemia and its treatment at considerable length in the “Index of Treatment,” Ed. 6, pp. 17-37, and gives many prescriptions containing iron for use under different conditions; and while it is unnecessary to reproduce all of these here, a few may be given in order to suggest suitable methods of prescribing iron when it cannot be given in sufficient amounts in the food.

In chlorosis Hunter advises that that form of iron which experience has shown to be least disturbing to the patient’s stomach should be used, and he suggests separate stomachic mixtures to be used simultaneously, not mixed with the iron itself. When constipation exists--and this is a very common accompaniment of chlorosis--he gives the following aperient iron combination:

Gm. or c.c.

℞  Ferrous sulphate |25 gr. iv
Magnesium sulphate 4| Ʒ i
Aromatic sulphuric acid |5 ♏ vii
Tincture of ginger |7 ♏ x
Compound infusion of gentian (B. P.) q. s., ad 30| ℥ i

This, constituting a single dose, is to be taken twice daily--at 11 a. m. and 6 p. m. A little compound tincture of gentian and water may be used in place of the compound infusion of the British Pharmacopeia. He modifies this somewhat as occasion demands by using sodium sulphate and adding sodium bicarbonate (which converts the sulphate of iron into ferrous carbonate) and adds 10 minims of spirit of chloroform to act as a stomachic.

Hunter also suggests the use of pills of aloes and iron in place of the mixture described above, and when constipation has been corrected, the aloes may be omitted and the pill of ferrous carbonate alone may be used for the iron. Hunter’s comment regarding this pill is, “very satisfactory.”

The same form of iron is available in the compound iron mixture, formerly official, which Hunter says is exceedingly good. In this country the compound solution of iron and ammonium acetate, Basham’s mixture, so called, has long enjoyed a wide reputation as causing very little disturbance of the stomach, and the homely tincture of ferric chlorid is probably useful in a large majority of cases in which the stomach is not especially irritable.

We may say with assurance that one of the forms suggested here will suffice for practically every case in which it is necessary to reinforce the amount of iron available in the food by some pharmaceutical preparation. If these do not satisfy your requirements, consult a really competent pharmacist and enlist his aid in devising a mixture especially suited to your individual patient.--(_From the Journal A. M. A., Dec. 29, 1917._)

[ARTICLE IV]

Cactina Pillets

This preparation may be considered briefly in view of the recent discussion in this series of articles of the pharmacology of the digitalis group and the principles of treatment in cardiovascular disease. The manufacturers maintain that cactina is wholly unlike digitalis, and that is the truth, as we shall show; but since they claim that it is useful in certain conditions of the heart in which digitalis is commonly employed by well informed clinicians, it is necessary to consider its cardiac actions--or its lack of them! It is difficult to determine just what action cactina is supposed to exert on the heart. For example, one advertisement contains the following:

“Cactina Pillets. A gentle cardiac tonic that supports and sustains
the heart through its capacity to improve cardiac nutrition.”

Just how the cardiac nutrition is to be improved without an improved coronary circulation is not explained. It would be interesting to know in what other way this is to be accomplished, and how an improved coronary circulation can be induced without acting on the heart or vessels. But that is what digitalis does, and you should remember that cactina is so very different from digitalis! Then again:

“Cactina Pillets. A remedy that steadies and strengthens the heart
by imparting tone to the heart muscle.”

That is a pretty direct statement, but digitalis imparts tone; and we must not forget that “cactina” is wholly unlike digitalis, and we are told that “cactina” is:

“Invaluable in all functional cardiac disorders such as
tachycardia, palpitation, arrhythmia, and whenever the heart’s
action needs regulating or support.”

If these are merely functional disorders of the heart, it is highly desirable to know what are the symptoms of really serious cardiac disease! Since the manufacturers give us no information concerning the mode of action of “cactina” we will turn to the literature of disinterested observers. If one attempts to discover the origin of “cactina,” he will probably meet with disappointment, for various bibliographies fail to mention the name of Sultan, who is said to have isolated “cactina” from _Cactus grandiflorus_. It seems that Sultan worked with _Cactus_, or some other plant, when a student of pharmacy, and it is to be remembered that Cactina Pillets are manufactured by the Sultan Drug Company.

It is doubtful whether Sultan actually worked with genuine _Cactus grandiflorus_; and, in fact, there is good reason for thinking that he did not, for all subsequent workers who have taken pains to secure genuine _Cactus grandiflorus_ have failed to detect the presence of any active principle, except possible traces that are of no therapeutic importance whatever.

WHAT THE COUNCIL FOUND

The Council on Pharmacy and Chemistry examined the literature relating to cactus and certain proprietary preparations, including Cactina Pillets, alleged to be made from cactus, and has reported the results of its investigation (_J. A. M. A._ =54=:888 [March 12] 1910) and we will quote from that report.

“The therapeutic value of this plant has been variously estimated by
different observers. Experimental evidence as to its action is scanty
and no complete chemical examination has ever been made.

“Reputable men have testified that some of the plants of the cactus
family contain very active principles, but so far experiments seem to
prove that _Cactus grandiflorus_ has neither the action of digitalis
nor that of strychnin. The principal contributions, clinical and
experimental, for and against the drug are set out below.”

The report then proceeds to analyze the work of O. H. Myers, R. A. Hatcher, Boinet and Boy-Teissier, Sayre, Gordon Sharp, S. A. Matthews, P. W. Williams, Aulde and Ellingwood, and comes to conclusions that are set forth as follows, in brief:

1. It is uncertain what part of the plant contains the active principle, if any such principle exists.

2. Part of the experimental and clinical work has been published under proprietary auspices.

3. The value of clinical evidence when unsupported by animal experimentation is much diminished by the tendency of enthusiastic and untrained observers to attribute to the drug given the effect really due to general remedial measures, psychic suggestion and so forth.

In other words, the literature does not afford a report of a single piece of careful painstaking work the results of which lend support to the claims made for Cactina Pillets as stated above, for it is obvious that if _Cactus grandiflorus_ contains no active principle, no active principle can be extracted from it. Some time after the report of the Council was published, Hatcher and Bailey secured genuine _Cactus grandiflorus_ directly from a competent botanist, Dr. C. A. Purpus, of Vera Cruz, Mexico, and studied it experimentally. They reported (_J. A. M. A._ =56=:26 [Jan. 7] 1911) in part as follows:

“We have been unable to obtain any evidence that the true Mexican
_Cactus grandiflorus_ possesses any pharmacologic action whatever;
but, on the contrary, it appears to be a singularly inert substance
when administered either by the mouth or by the vein.”

When colossal doses of _Cactus grandiflorus_ are given by the vein, they sometimes--but not always--appear to exert an extremely feeble action on the heart; but this action is so slight that its nature could not be determined. Even the most colossal doses of _Cactus grandiflorus_ administered by the mouth to cats, dogs and frogs exert no perceptible effect.

Sollmann thus satirizes the absurd claims made by the exploiters of proprietary forms of cactus: “Should the heart be too slow, cactus quickens it; if the heart is too fast, cactus slows it; should the heart be too weak, cactus strengthens it; if the heart is too strong, cactus weakens it; does the heart wobble, cactus steadies it; if the heart is normal, cactus does not meddle with it” (_J. A. M. A._ =51=:52 [July 4] 1908).

Will physicians continue to accept the statements of an interested nostrum vender--who submits not a shred of evidence to support his claims, but who has a financial interest in convincing them--even when his statements are diametrically opposed to all the evidence that the Council on Pharmacy and Chemistry has been able to secure?--(_From The Journal A. M. A., Jan. 19, 1918._)

[ARTICLE V]

Ammonol and Phenalgin

At the time that synthetic chemical drugs were coming into fame and when every manufacturer who launched a new headache mixture claimed to have achieved another triumph in synthetic chemistry, Ammonol and Phenalgin were born. Of course, these twins of analgesic pseudotherapy were claimed to be synthetics and were duly christened with “formulas.” They were among the first of the nostrums examined for the Council on Pharmacy and Chemistry, and the false claims made for them were exposed.

The analyses made for the Council showed that Ammonol and Phenalgin were simple mixtures, having the following composition:

ACETANILID SODIUM BICARBONATE AMMONIUM CARBONATE
AMMONOL 50 25 20
PHENALGIN 57 20 10

The reports of the Council on, and numerous references to, these two nostrums may be found in The Journal of various dates.[245] The reports will prove interesting to those who are not familiar with, or have forgotten, the methods of nostrum exploiters at the time the Council was formed. Following the Council’s exposure of the false claims made by the manufacturers of Phenalgin, the _Medical Record_ published an advertisement of that nostrum in which an attempt was made to discredit the Council’s report. The editor of the _Medical Record_ was requested by the Council to publish the facts in the case but he refused to do so.

[245] J. A. M. A. 44: 1791 (June 3) 1905; ibid. 44: 1997 (June 24) 1905; ibid. 45: 935 (Sept. 23) 1905; ibid. 46: 134 (Jan. 13) 1906; ibid. 46: 290 (Jan. 27) 1906; ibid. 58: 280 (Jan. 27) 1912.

Long after the death of Dr. Cyrus Edson, the claim was made that Phenalgin was made under his direction and that it was his “discovery.” As a matter of fact, Dr. Edson had favored the use of Ammonol at one time, and when the Council exposed the false claims then being made for Phenalgin, The Journal charged that a fraud was being perpetrated on the medical profession. Despite the exposure of the methods used in exploiting Ammonol and Phenalgin, one finds just as glaringly false statements made in the advertisements of Phenalgin today as were made in its unsavory past. This would seem to indicate either that physicians have short memories or that they are strangely indifferent to the welfare of their patients, to their own reputations and to the good name of medicine.

The _New York Medical Journal_ of Dec. 22, 1917, contained an advertisement of Phenalgin--it has been running for months--from which the following is quoted:

“For the relief of PAIN the ‘logical supplanter of opium and
other habit-forming drugs’ is PHENALGIN. No matter how severe or
where located pain is promptly and satisfactorily controlled by
this effective anodyne--and without disturbing the digestion,
suppressing the secretions, causing constipation or inducing a drug
habit.

“This is why Phenalgin has superseded opium and its derivatives
for relieving HEADACHES, RHEUMATISM, GOUT, LA GRIPPE, LUMBAGO,
NEURALGIA, DISORDERS OF THE FEMALE, DYSMENORRHEA, AND PAINFUL
CONDITIONS GENERALLY. To thousands of physicians Phenalgin ‘is the
one dependable analgesic--the logical supplanter of opium.’”

If we are to suppose that the composition of Phenalgin is today essentially the same as when it was examined, the claims just quoted are obviously false for, of course, such a mixture must have the properties of acetanilid with all of its drawbacks and limitations. We may contrast the statements made in the advertisement just quoted with those made in Bulletin 126 of the Bureau of Chemistry of the U. S. Department of Agriculture. This bulletin on “The Harmful Effects of Acetanilid, Antipyrin and Phenacetin” summarizes the replies received from 400 physicians to whom a questionnaire had been sent. The information thus gained was tabulated and the figures that follow are from these tables. There were reported no fewer than 614 cases of poisoning by acetanilid with 16 deaths and 112 cases of its habitual use. The larger number of cases of poisoning followed the administration of the drug, by physicians, in doses larger than those now regarded as fairly safe. This large number reported by only 400 physicians indicated an excessively large number in the whole country. Since the questionnaire was sent to nearly a thousand physicians, of whom about 500 failed to reply, it may be assumed that had it been sent to the entire 130,000 physicians in the country, at least 75,000 cases of poisoning would have been reported.

Prior to the passage of the federal Food and Drugs Act (the “Pure Food Law”) many nostrum makers had declared that their preparations contained no acetanilid. When that law went into effect, some of these manufacturers triumphantly pointed to the fact that they were still able to make the same claim without conflicting with the requirements of the law. This was accomplished in fact by changing the formula and substituting acetphenetidin (phenacetin) for the acetanilid. While acetphenetidin is somewhat less toxic than acetanilid, bulk for bulk, the toxicity and therapeutic activity of the two drugs are nearly proportional.

The claim made by many proprietary medicine manufacturers that they are “strictly ethical” because they advertise only to physicians is mere verbal camouflage. There may be no more certain way of insuring the continued use of a nostrum by the public than to have it prescribed by physicians; and none know this better than the makers of nostrums. A proprietary individuality is obtained by giving some special form to the tablets and package or a special coloring to the capsules (“Specify ‘Phenalgin Pink Top Capsules’”) so as to indicate the identity of the products in such a way that the patient may in the future procure them without the advice or warning of the physician. When a proprietary preparation with the name or initials stamped on it or attached to it is prescribed, the patient immediately is aware of the fact, and his respect for the physician’s intelligence and wisdom is naturally lessened.

The physician should never place such dangerous drugs as acetanilid and acetphenetidin, or ready made mixtures of them, in the hands of the patient in such a way that they can be employed without his supervision or control. He should never prescribe more than is needed at the time and should not form the habit of using fixed doses or combinations of drugs without a special reference to the particular needs of the individual.

Certain forms of headache yield more readily to a mixture of caffein and acetanilid or caffein and acetphenetidin than to either acetanilid or acetphenetidin alone. When the physician wishes to prescribe such a mixture he may combine 1 grain of caffein or 2 grains of citrated caffein with 3 grains of acetanilid or 4 grains of acetphenetidin in a powder or capsule. Under supervision such a dose may be repeated at intervals of from two to four hours if necessary to control pain. It is necessary to remember, however, that when small doses fail to give relief, increase in the dose is useless. This fact is especially important, and disregard or ignorance of it has been responsible for many cases of poisoning. Further, it should be remembered that while it was taught for many years that the admixture of caffein with acetanilid lessened the effect of the latter drug on the heart, Hale has shown that this is not the case and such mixtures must be used with special caution.--(_From The Journal A. M. A., Feb. 2, 1918._)

[ARTICLE VI]

Fellows’ Syrup, and Other Preparations of the Hypophosphites

We hope that it is clear to those who have read the several articles of this series that their purpose is to present evidence that will enable the reader to form a correct estimate of the literature employed in the exploitation of various nostrums. The distinction between mere assertion--however plausible, and from however eminent an authority--and evidence should again be emphasized. Satisfactory evidence rests on careful observation by those who are capable of accurately determining to what extent any changes that may be observed are due to the therapeutic agent employed and not mere accompaniments of such treatment.

When the Council on Pharmacy and Chemistry was organized in 1905, the greater part of the literature of the nostrums was so palpably misleading, the statements often so ludicrously false, that it was only necessary to call attention to this fact to have those claims collapse. As a result of the Council’s work, the exploiters of worthless nostrums have developed a greater degree of shrewdness in avoiding the easily exploded falsehoods. This has made it increasingly difficult to point out the exact statements on which many of the false claims now rest, even though the exploitation as a whole is as inherently dishonest as before. If a nostrum is worthless, any exploitation must be false and misleading in effect, even though not one single false direct statement is made.

A platitude may be given an appearance of importance if uttered in an impressive manner, and it may be employed to suggest far more than it categorically affirms. These two facts are appreciated by many nostrum exploiters and we find that they have adopted the impressive manner to secure attention, and the platitude to suggest far more than they could defend in direct statement. Thus we have the “lie with circumstance.”

FELLOWS’ SYRUP

A full page advertisement, which has been appearing regularly for about a year and which must represent a good deal of money, is used to give an appearance of importance to a few words which, if printed in ordinary type, would either pass wholly unnoticed or would lead one to assume that something essential to the full meaning had been omitted. The statement, in full reads:

“Fellows’ Syrup differs from other preparations of the
hypophosphites. Leading clinicians in all parts of the world have
long recognized this important fact. Have you? To insure results,
prescribe the genuine ℞ Syr. Hypophos. Comp. Fellows’. Reject cheap
and inefficient substitutes. Reject preparations ‘just as good.’”

The only direct statement contained in the advertisement is to the effect that many clinicians have observed that Fellows’ syrup and other preparations of the hypophosphites are not alike. In truth, Fellows’ is not like the better preparations of this type, since after standing it contains a muddy looking deposit that any pharmaceutical tyro would be ashamed of. Technically, then, the statement is true, but it is hardly credible that the manufacturer is paying for an entire page in a medical journal to make this statement without any attempt to suggest something else.

The advertising pages of six medical journals were examined in the order in which they chanced to come to hand. In five of these, the entire advertisement of Fellows’ syrup was in the words just quoted; not a single word more. In one there was the further statement:

“Not a new-born prodigy or an untried experiment, but a remedy
whose usefulness has been fully demonstrated during half a century
of clinical application.”