No Cold Cure
By DR. MARGARET JACKSON 46 OME say cinnamon and some say rum, and a marine- on one of the Channel boats recommends a slice of onion clapped to the sole of each foot ; but the common cold
usually runs its course, undeterred by nostrums." This introduction to the topic of cold remedies is taken from The Lancet of March 17th, 1934, and sums up the attitude to the common cold in the medical press for the past half century. The statement was true then, and unfortunately it remains true now—though from time to time hope strikes another match which flames for a moment, flickers and goes out. Scientific prescriptions fare no better that: family remedies. The last twenty years have seen, among the doctors, enthusiasts for vaccines (and a few people still seem to benefit from them) ; opium derivatives, notably dilaudid, though this idea gained no genera! acceptance ; ephedrine, which shrinks the nasal mucous membrane and diminishes the flow of mucus for a time ; and patulin, derived like penicillin from a mould, which was expected to achieve great things but didn't. There were good scientific reasons for trying each of these remedies, but the cold virus is not amenable to reason. The test of time, and in some cases care- fully controlled scientific tests as well, show that the chances of a quick recovery were no greater among the treated than the untreated.
The latest drugs to join the failures are those in the antihistamine
group. Their history goes back to 1910, when the substance histamine was first extracted from ergot. Later histamine was obtained from various plants, and was shown to be a normal con- stituent of the body tissues, -especially the lungs. Research on the " allergy " diseases--such things as asthma, hay-fever, allergic rhinitis, nettlerash and others—led to the interesting discovery that an injection of histamine would provoke an attack of his disease in an allergic subject ; and the next step, of course, was to find a drug—an antihistamine drug which would cut the attack short. There were various candidates for the position: by 1932, no fewer than 165 substances—barbitone, the potassium salts and ascorbic acid among them—had been tried and rejected. The search went on, and in 1937 Ungar, Parrot and Bovet found that some phenolic ethers are potent antagonists of histamine ; since then these drugs have been synthesised in the laboratory and have proved to give good results in the allergic disorders. They have been particularly effective in allergic rhinitis, in which the nose starts pouring out watery secretion almost as freely as a small-bore tap. Antihistamine drugs seem to turn the tap off ; and it was this property which led workers in the United States to suppose they might be effective in cutting short the common cold.
It seems there is no one more suggestible than the man with a
cold, trying a new remedy—unless perhaps it is the man who has given him the remedy to try. The early reports on the antihistamine treatment of colds were encouraging—so encouraging that the American public bought up the drugs in great quantities, quite disregarding the risks of side-effects. These were not negligible: they included giddiness and drowsiness which might turn a good car-drive: into a danger to himself or others ; and at least one American patient became mentally confused. More serious still, these drugs have caused the deaths of several children—some in this country—who have found the tablets, sugar-coated, about the house and mistaken them for sweets. There has been no such wide- spread enthusiasm for antihistamine drugs here as in America, largely because our drug manufacturers, who work in close co-opera- tion with the medical profession, have not attempted to press on the public drugs of which the values and risks were still undecided The whole subject has now been investigated by a team of the Medical Research Council, under the chairmanship of Dr. F. H. K. Green, who have reported on it in the British Medical Journal of August 19th. They have demonstrated that large doses of the antihistamine drugs will neither prevent colds nor influence their course. This decisive study provides a pretty example of scientific ingenuity- Many factors besides the suggestibility of patients and doctors combine to make the investigation of colds difficult. For one thing no animal susceptible to colds has been found except the expensive chimpanzee ; so researchers are driven back on humans. Then colds vary greatly in their course, not only in different people but in the same person at different times ; they may be influenced perhaps by the general health of the subject, his powers of resisting infection, and possibly also by such things as fatigue and exposure to cold or damp. Very likely the infection itself varies, and what we experience as " colds " are, in fact, produced by different viruses, or different strains of the same virus. Moreover the immunity of those who have just had a cold to a fresh cold infection is most uncerta;n, sometimes lasting only a day or two, and sometimes perhaps for months. To give all these variables a chance to cancel out, in the antihistamine trials, a very large number of subjects had to be treated , and, in fact, doctors at 19 centres in England and Northern Ireland and 1,550 volunteers from the general public, took part in the main investigation. The volunteers reported as soon as they felt they had a cold coming, gave a history of their symptoms to the doctor, and were given an envelope with three tablets, to be taken at intervals during the day ; they reported on the two following days and received further supplies of the same tablets ; and reported again for the last time a week after their first visit. Half of them received a chosen antihistamine drug and half dummy tablets containing a trace of quinine ; but neither they nor the doctor knew what they were getting. The packets of tablets were arranged in a random order and then numbered consecutively before they were even delivered to the doctor, why handed out No. 1 to the first patient, No. 2 to the second, and so on, without any clue as to what he was giving. The results in the treated and the controls were remarkably similar, the only difference being that on the first day of treatment a few more improved among those getting the drug than among those getting the dummy tablets. But by the end of the second day the difference had vanished ; it was in any case trifling.
To decide whether antihistamine drugs can prevent colds the Medical Research Council arranged a small experiment in the Common Cold Research Unit, at Harvard Hospital, Salisbury. This is the unit which continuously investigates colds in pairs of volunteers ; they share a comfortable flat for ten days, live com- fortably at the unit's expense, and submit to the introduction into their noses of material which may or may not contain cold virus. The only penalty for a pleasant costless holiday is the chance of getting a cold—and even this is offset by the thought that it proves one's public spirit. In the antihistamine experiment the usual pro- cedure at the unit was changed a little. The volunteers were given ' doses either of the drug or of a dummy for 48 hours, and were then all inoculated with cold virus. The drug had no effect in preventing colds: they were just as common in the treated subjects as the controls. The Medical Research Council's findings are borne out by those of Dr. Gerard Lorriman and Dr. W J. Martin, who report on another antihistamine drug in the same issue of the British Medical Journal, and an American study on students at Minnesota University published earlier this year.
So that seems to be the end of the antihistamine drugs as a cold cure ; and the reasonable man may feel the energy spent on quashing it could have been better directed to learning more about colds. There is, of course, still plenty to learn. Dr. C. H. Andrewes, a leading member of the M.R.C. team, last year propounded in The Lancet eight questions about the common cold: is it a single disease or a group of diseases ; what is the causal agent ; how long can the agent live, either in the human body or outside it ; do we always catch a cold from somebody else, or are we carriers ; how is it spread ; if we are carriers how is it " activated " so that we develop a cold ; what explains the seasonal appearance of colds ; and why does resistance vary from one person to another and from one year to another ? Eight posers, certainly, but he was able to give some of the answers. The agent is certainly a virus, and though there are other viruses which produce cold-like symptoms (influenza and measles, for instance) it seems likely that most colds are caused by a single virus, though this may have various strains. So far it is not certain how long the cold virus lives in the body or how soon it dies outside it, though there is some interesting evidence from isolated places like Spitzbergen where people get colds only when
a ship calls. The answers to the remaining questions are still largely speculative, and until they are answered cures must be sought, as at present, on the hit or miss principle, and investigated in the massive and reliable fashion of the Medical Research Council. In default of a susceptible animal Dr. Andrewes would like to study a company of Spitzbergenites in April, when their susceptibility to colds is probably low and uniform. " Experimental work on cold, is difficult," as he very moderately puts it.
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