The Cold-Cure Merry-Go-Round
The common cold, as DR. DAVID D. RUTSTEIN says, is the most common disease of mankind. Year after year the American public has been offered miracle drugs, and again and again the people have been disappointed. How does this come about? Head of the Department of Preventive Medicine at Harvard Medical School, Dr. Rutstein is a member of the staff of Massachusetts General Hospital and five other Boston hospitals.
by DAVID D. RUTSTEIN, M.D.
MOST a sure of us way would to prevent be willing or cure to pay the common a lot for cold. In fact, as a nation we do spend millions of dollars every year on highly touted medicines which neither cure our colds nor keep us from getting new ones. Every once in a while we are invited to take a new ride on the old cold-cure merry-go-round, and for a short time we hope that the real answer has at last been found.We have had two such invitations in recent years: first, for the antihistamine drugs, and later for the bioflavonoids. To be sure, they were not labeled cold cures, but the implication was clear.
The common cold is well named, since it is the most common disease of mankind. Although it may be a seedbed for other infections, it is rarely serious except in small infants and in people with chronic illness, particularly of the heart and the lungs. But it is a terrible nuisance. It recurs in the same person again and again. It is the largest cause of absenteeism, responsible for an annual loss of well over a hundred million workdays and a cost of over a billion dollars to our economy every year.
The symptoms of the common cold we know only too well. A scratchy throat, a runny nose, sneezing, coughing, and an achy or “knocked out" feeling plague most of us three or four times a year. The mere relief of cold symptoms is inexpensive. Drugs such as aspirin relieve the aches, while syrups and lozenges suppress the cough. Bed rest and hot drinks will make us feel better. But we know that none of these either prevent or cure the cold. So we pay a lot more for a new ride on the cold-cure merry-go-round, hoping that this time we will get the brass ring. Since these new cold cures often relieve some of our symptoms the ride may not be loo unpleasant, but we always end where we began, in time for the next cold to come along.
The antihistamine merry-go-round which began in 1947 is now grinding to a halt. It is possible to examine the full cycle and try to measure its el feet all of us. As its name indicates, an antihistamine drug blocks the effect on the body of histamine and histamine-like substances which are released in certain allergic diseases. When we have the hives these histamine substances are liberated in the skin as they are in the respiratory tract during an attack of hay fever. The antihistamine drugs usually relieve such allergic symptoms.
In the fall of 1947, Dr. J. M. Brewster, then a captain in the United States Navy, made the startling announcement that an antihistamine drug given for colds to sailors and their families had “been found to completely abort 10 percent of such cases and to shorten the course and afford marked subjective relief to 95 percent of all cases.”Dr. Brewster explained this benefit on the ground that the early symptoms of the common cold were allergic in nature. This assertion was based on only suggestive evidence from previous research that histamine may be found in the nasal tissues of people suffering from colds. A year later, a report with similar resells was published from Charlotte, North Carolina, by Dr. J. S. Gordon.
In 1949, five more reports recommending antihistamine treatment for colds were published in medical journals. The claims varied from those of simple relief of symptoms to actual shortening of the duration of the cold. One of the reports was a second study at the Great Lakes Naval Training Station in Chicago by Brewster confirming his previous findings. Another study not only reported benefit in the treatment of colds, but indicated that colds could be prevented if antihist amine drugs were taken prior to infection. Two of the studies were made in industry, and the new treatment gave promise of a sharp decrease in absenteeism.
There was, however, in 1949 one disquieting report on the use of antihistamines in the prevention and cure of colds. In May of that year the Lancet, one of the two great medical journals of England, published a letter from the Common Cold Research Unit at the Harvard Red Cross Hospital in Salisbury, England. The letter indicated that in a small but well-designed experiment this research group was not able to find any benefit from antihistamine drugs in the prevention or cure of the common cold. This report was particularly important because the research workers were thoroughly experienced. The British experiment contradicted the favorable results from antihistamine drugs which had been reported by relatively inexperienced workers.
In September of this same year, 1919, the Federal Food and Drug Administration certified the overthe-counter sale, without prescription, of three antihistamine drugs to be dispensed in tablets containing not more than one half of the usual dose. This limitation was imposed because there was evidence that with the usual dosage, side effects such as drowsiness occurred. These are potentially hazardous in automobile drivers and in those working with dangerous machinery.
Early in November, newspaper advertising of antihistamines appeared, first for lnhiston, followed within a week by Anahist. According to the New York Herald Tribune of November 30, 1949, in the first month of promotion the sales of Anahist increased from zero to one million dollars. Radio advertising began at about the same time. In December, the Anahist company sponsored the radio series “Counterspy” on the national radio network of the Mutual Broadcasting System. The merry-go-round was well under way.
The peak of enthusiasm for the control of colds with antihistamines was expressed by Paul de Kruif in an article in the Reader’s Digest in December, 1949, entitled “Is This, At Last, Good-Bye to the Common Cold?” He stated that “the new coldkiller is no tantalizing laboratory curiosity; it’s available to everybody. It is safe, and it is not limited to expensive prescriptions; the federal government permits its direct sale to the public in drug stores. . . . Thus it seems within the range of possibility at last to wipe out the curse of the cold in the head.”
The year 1950 was the big one for sales of antihistamine drugs for the prevention and cure of colds. National promotion of these drugs was begun in magazines. In January an advertisement in Look magazine promised “Anahist Can Stop Cold Symptoms in a Single Day.” Another in February said “ Reader’s Digest Reports Clinical Proof That It’s Anahist for Colds.” Nation’s Business for February, 1950, carried an advertisement which said “Now You Can Stop Colds in Your Business with the lnhiston Cold Control Plan.” This advertisement also offered an attractive lnhiston dispenser of 1000-tablet capacity to be mounted conveniently near a drinking fountain. In 1917, total sales of antihistamine drugs amounted to 2 million dollars; by 1950 total sales reached 30 million dollars. Almost half of this total, or 14 million dollars, came from nonprescription, overthe-counter sales.
In late February, 1950, stimulated by the extreme advertising claims, the Council on Pharmacy and Chemistry of the American Medical Association published a “status report” on the antihistamine drugs. The common cold is a variable disease with unpredictable occurrence, severity, and duration in any particular person. Therefore, the results of prevention or treatment can be evaluated only by careful comparison with results in a group of similar persons, a control group, not receiving antihistamine drugs. The AMA report stated that three of the six favorable studies, including the original Brewster report, made no comparable observations on a control group and that the rest had other faults in their experimental design. In some, the diagnosis of a cold was made by the patient himself. In others the results were based only on the patient’s own statement of improvement without actual examination by the investigator. Such subjective statements are known to be unreliable because in other well-designed studies on the common cold many persons given sugar pills disguised as cold tablets claimed great benefit. Mention was also made of the possible toxic effects of the continued use of antihistamine drugs. The AMA committee delivered the Scotch verdict of “not proven” and urged further experimentation.
FOLLOWING the American Medical Association report, the Federal Trade Commission in April, May, and June of 1950, on the basis of undocumented advertising claims, brought complaints against five manufacturers of the antihistamine drugs — Anahist, lnhiston, Kripton, Resistab, and Antimine. In June, the complaints were settled and the five companies agreed not to claim cure, prevention, abortion, elimination, or shortening of colds by the use of antihistamine drugs. They were stiil permitted to claim the checking, stopping, or relief of symptoms.
During 1950, the published reports in medical journals of the use of antihistamine drugs in colds were no longer favorable. Eleven more studies appeared that year, but only two of them showed beneficial effects in the prevention or cure of colds, although some of the others found relief of certain symptoms, particularly sneezing and amount of nasal discharge. By this time, many well-established and experienced common cold research teams had been forced to put aside some of their long-range research on the cause, nature, and control of the common cold, to investigate the antihistamine drugs. Among the nine reports unfavorable to the antihistamine drugs in that year were those from the respiratory disease research learns at the University of Minnesota and Western Reserve University and from the U.S. Naval Medical Research Unit No. 4, and in England from the research unit under the auspices of the Medical Research Council. The diversion of scientific effort and manpower is corroborated by the statement of the Medical Research Council in the British Medical Journal: “In view of the great practical importance of the favourable findings, if confirmed, the Medical Research Council undertook, at the request of the Ministry of Health, to investigate in this country the value of the treatment. A special committee was appointed early in 1950, and the results of the tests arranged by the committee arc reported here.”That report, showed that the antihistamine drugs were worthless for the prevention or cure of colds. The report of the Naval Medical Research Unit was of particular interest. This well-recognized respiratory disease research unit attempted to confirm Brewster’s results under the same conditions at the same place — the Great Lakes Naval Training Station in Chicago. In a series of four well-controlled experiments, they found no evidence that the antihistamine drugs prevented or cured colds.
Since 1950, the antihistamine merry-go-round has been slowing down. Most of the scientific reports published thereafter failed to document the early claims, and in 1951, total estimated sales had dropped to 21 million dollars. Of this amount, 6 to 7 million were from nonprescription over-thecounter sales. In 1952, total sales remained at about the same level, but the nonprescription sales were decreased to about 4 to 5 million dollars. These changes probably reflect a decreasing use of antihistamine drugs for the common cold with a continuing or possibly increasing use in those allergic diseases in which the antihistamine drugs are known to be effective.
By January, 1957, only one antihistamine drug, Superanahist, was still extensively advertised. But now reliance is placed on a combination of five ingredients of which the antihistamine drug is only one. The others include vitamin C, which has been repeatedly shown, even in large doses, to be of no value in the prevention or treatment of the common cold. The advertisements make the potentially dangerous statement, again with no scientific evidence, that the five ingredients may take the place of bed rest in the control of colds.
IN MID meantime, the bioflavonoid merry-go-round has been picking up speed. This substance has a distinguished ancestry unrelated to the common cold. Dr. Albert Szent-Gyorgyi, then of Hungary, received the Nobel prize in 1937 for his discovery that it helps to maintain the integrity of the walls of our capillaries. It is found in large amounts in fruit and other foods in the American diet.
The use of the bioflavonoids for the common cold was first suggested in 1954. Drs. S. N. Biskind of Westport, Connecticut, and W. C. Marlin of New York City, in two reports of uncontrolled observations on 22 patients in 1954 and 46 patients in 1955, told of striking benefits in the treatment of colds with an average dose equivalent to the amount of bioflavonoid found, for example, in three ounces of orange juice or in eighteen large grapes.
In December, 1955, using what the Sew England Journal of Medicine has referred to as the “D-Day Technique,”the Clayton Laboratories of Saint Louis, Missouri, promoted large newspaper advertisements of Citroid Compound, a mixture of bioflavonoid, vitamin C, and aspirin. Each capsule contains bioflavonoid equivalent in amount to that found in one-half ounce of orange juice or in three prunes. The vitamin C is less than one tenth of the amount demonstrated in 1950 at the University of Minnesota to have no effect whatsoever on colds. Each capsule also contains less aspirin than is found in the ordinary five-grain tablet. These Citroid Compound advertisements promised that starting treatment early with two capsules will “block the cold virus from spreading through the system" and “prevent complications.”Even the uncontrolled favorable studies were more modest in their claims. The net result of all this was that sales of bioflavonoids increased about ten times from 1954 to 1955.
In November, 1956, three more studies on the use of bioflavonoids in colds were reported. One from the McDonnell Aircraft Company in Saint Louis showed benefit. Two carefully controlled studies published in the Journal of the American Medical Association were negative, one from Dartmouth Medical School in New Hampshire and the other from a group of industrial plants in the midAtlantic area. The latter study, a very extensive one on 1976 persons, concluded: “No appreciable effects were observed after three days on subjective or objective improvement; on disappearance of running nose, sneezing, cough, hoarseness, malaise, headache, post nasal drip, or sore throat; on decrease in nasal secretions or obstruction or pharyngitis; or in time lost from work.”
In the light of this conflicting evidence, one is forced to ask. Should experienced research learns, once again, give up some of their basic research on the common cold in order to investigate, this time, the effects of Citroid Compound on colds? We know that there is no theoretical basis for the use of this material either in the prevention or the treatment of colds. We recognize that all of the evidence for the use of Citroid Compound depends on two uncontrolled studies by the same authors, on one small controlled study, and on the hardhitting Citroid Compound advertisements. Yet it is likely that research on the common cold again will be interrupted. And when the status of bioflavonoids is settled, one wonders how soon the next “cold cure" will interfere with basic research.
The problems focused by the sale of antihistamines and bioflavonoids have significance far beyond the common cold. “Cures” for other unsolved diseases such as arthritis, asthma, acne, cancer, and obesity are promoted in the same way and are subject to the same abuses.
Who is involved in the chain reaction which permits the hit-and-run marketing of new remedies and which interrupts long-range research? First, there is the doctor who reports a poorly designed study of the proposed remedy. Carefully controlled research is difficult and expensive. But physicians testing new drugs on the common cold or on other diseases where no prevention or cure is available must be responsible for rigorous experimental design and precise interpretation of the results.
The second step is the approval for publication of poorly controlled experiments on new drugs by the uncritical editorial boards of certain medical journals. Medical journals vary in the quality of studies they will accept for publication. The reports of initial uncontrolled experiments always seem to appear in the same group of medical journals. Such publication is an essential, though usually unintentional, step in the chain reaction, and rejection of these articles could block the promotion of useless remedies.
The third, fourth, and fifth steps involve the manufacturer and advertiser of the “cure” and the communications media of press, magazines, radio, and television. It is important to point out that many drug manufacturers never market or advertise drugs until they have conclusive evidence of effectiveness and lack of toxicity. Moreover, many of them provide research grants for basic research not related to the marketing of a specific drug. Other manufacturers take advantage of poor research on preventive or curative drugs. Some even go so far as to warp the conclusions from good theoretical research to fit their product. The questionable techniques and unwarranted claims made by certain advertisers have already been documented. It is of interest here that antihistamine drugs for colds have been recommended by Parents’ Magazine, and Citroid Compound has received the seal of approval of the Good Housekeeping Institute. The press, magazines, radio, and television are not blameless in their uncritical acceptance and forceful presentation of highly questionable material.
A sixth step involves the enforcement agencies — the Food and Drug Administration and the Federal Trade Commission. The Federal Communications Commission also has indirect control over advertising through responsibility for approving or withholding the licenses of radio and television stations. None of these agencies has complete authority for protection of the public against false claims of drug effectiveness. The Food and Drug Administration, which has the most direct responsibility, has been denied the prestige it deserves and the manpower it needs for adequate enforcement of existing law.
The next step in the chain reaction concerns the Fluted States Congress. Existing law does protect the public against poisoning and short weight, but does not shield it from unwarranted therapeutic claims. Moreover, the Food and Drug Administration has jurisdiction only over the claims made on the actual label on the drug container. Advertising claims are the responsibility of the Federal Trade Commission. It is hard to understand why we see so many claims made in advertising that may not be put on the label of the bottle. It would seem reasonable that since both involve the use of the same substance for the same disease, both should be judged by the same enforcement agency, using the same criteria. Legislative provision has to be made for unified administrative responsibility.
The final step in the chain reaction depends upon the willingness of the consumer to purchase the drug. Extravagant advertising claims and repealed annoying symptoms combine to make it difficult for the consumer to exercise judgment. Sometimes he just is indifferent and says, with S. J. Perelman, “I don’t know anything about medicine, but I know what I like.” But even if the consumer is well informed and desires protection, it is too much to expect him to have the technical information necessary for precise judgments concerning the value of a new drug.
Where can the chain reaction be blocked most effectively? First, the profession of medicine must put its own house in order. It must apply more rigorous experimental design to the testing of new drugs, and elevate the standard of research publications. It must demand laws which will protect the public and thereby prevent interruption of long-range common cold research.
Most drug manufacturers, advertisers, and representatives of the press, radio, and television will refrain from marketing worthless remedies. But this is not enough. The marketing of worthless drugs by a single combination of these industries can blacken the name of all of them. Past experience would indicate that industry cannot police itself effectively enough to protect the consumer.
But the physician cannot do it alone, and the enforcement agencies seem to lack the legislative authority to do the job. The citizen, who no longer enjoys riding on the common cold merry-go-round, must demand of his legislators laws which will really protect him, and, having obtained such laws, must see that they are effectively enforced.