Now finally, let us grant that all the claims made for a new drug are true, that with it we can do this or that, as alleged. There still remains the question: do we want to do all these things? Shall we tranquilize the patient merely because the means are at hand, or alert and stimulate him, willy-nilly, when he is deluded or obsessed? Do we really want to lose control of all our mild elderly diabetics through a fistful of pills? Are we to go on creating more resistant infections through giving each new antibiotic a whirl? Shall we blindly accept the asseveration that two drugs with opposing types of action invariably give a nice blended effect when used together in fixed proportions ? Do we need to risk orthostatic hypotension, ileus, visual disturbances, palpitation, paresthesias, etc., merely to obtain blood pressure reduction in a mildly hypertensive patient? How frequently is intravenous iron administration advisable? Do we want often to replace thyroid substance with a quicker-acting compound whose omission may cause distressing withdrawal symptoms? And so on and on.

Do we really need all the time all the things that all the new drugs will give us? With full realization of the probable absurdity of the comparison, I am nevertheless going to liken political man’s possession of his new military weaponry with medical man’s acquisition of his new pharmaceutical arsenal. The time is not yet here when the decision will have to be made whether to drop the hydrogen bomb or not to drop it, but all the world is quivering with fear that such a moment is imminent, and men of good will everywhere are agitating for restriction of the use of this dreadful new power to those activities only of mankind wherein his best survival interests can be selectively aided. To use or not to use the new drugs for all they can do, that too is a question, our peculiar and particular medical question, and ours the solemn responsibility to answer it. For progress in this field will not be halted, and we are only now crossing the threshold into the vast drug sales room of the near future, whose walls and floors and counters and chests and racks and shelves will be loaded with bottles crying out “Use me! Or me! Or me! Or all of us together!” Shall we do it, always in all cases, all of it? Money in immense amounts is invested in the effort to tell us that this is our duty; the symptom is there, the drug is or soon will be available; the two must meet head-on invariably. “Treat your patient with these new drugs, Doctor, treat him, each one of him, or else a new kind of physician will be created who will do it.” In such exaggeration there is truth. Investigations now under way, may bestow power through drugs over metabolic processes as will make nuclear fission seem puny in potentiality for control of the world.

We doctors, while we can, must make the decision whether to give up and merely hand out the pills, or not. No individual can dictate that decision, but remember: all drugs, even the very best, are psychologically or physically potentially toxic agents — and none should be used unless unavoidable.

Publish date: 1959

Progress has been made with such giant strides in recent decades that one is tempted at times to bemoan the smallness of the territories still to be conquered. But for the pharmacologist at least, whatever the feeling may be in other circles, there exists a sufficient and powerful antidote for his ego in the large list of areas in which drugs are still badly needed. The things we might expect from these drugs, drugs that are not yet found or devised, are shown in Tables 3 and 4.

Table 3. Drugs Are Still Needed To Provide Prophylaxis Or Cure In:
common cold	trichomoniasis	infertility
virus influenza	fluke infestations	threatened abortion
brucellosis	pneumonoconioses	hyperemesis gravidarum
virus encephalitides	renal disease	eclampsia
foot-and-mouth disease	portal cirrhosis	endometriosis
leptospirosis	peptic ulcer	menstrual disturbances
rabies	ulcerative colitis	cataracts
trypanosomiasis	many of the psychoses	glaucoma
yellow fever	parkinsonism	impaired hearing
infectious mononucleosis	cerebral palsy	infantile colic
virus hepatitis	migraine	urolithiasis
smallpox	Bell’s palsy	anuna
tetanus	Meniere’s disease	obesity
schistosomiasis	Sydenham’s chorea alcoholism	malignancy
the mycoses	multiple sclerosis and the muscular atrophies and dystrophies and syringomyelia	burns
poliomyelitis		shock of irreversible degree
dengue

-

Table 4. Drugs Are Still Needed To:
prevent atherosclerosis	replace blood-letting in polycythemia vera and blood transfusion in shock
prevent hypertension
prevent development, check progress, even cause retrogression of valvular lesions	correct the defects in hemophilia and in purpura
	combat the circulatory and respiratory dissolution associated with pulmonary embolism
act more selectively in the autonomic nervous system
	combat rheumatic carditis and rheumatoid arthritis specifically
restore circulation in the peripheral vascular diseases
	end the disturbed uric acid metabolism in gout
attack dermatologic lesions effectively systemically	separate the pharmacologic (useful) from thephysiologic (harmful) actions of ACTH
combat anemias other than the simple iron deficiency and pernicious types
	combat intractable pain with non-addicting agents

This is a wonderful list, is it not? All this still left for the pharmacologist to do. And of course he will eventually do most of it, but there is something between him and the practitioner — a great vested interest which must sell to live. This vast pharmaceutical industry has become a familiar and essential ingredient of medical practice, and we should all generously and gladly attempt to be useful to it in recognition of a mutual interest and a shared desire. But this must not be done through yielding independence or sacrificing the intelligent approach!

Do not, I implore you, gain all the accretions to your pharmacologic knowledge from the paid sales representative, whose training is necessarily not comparable with yours, or accept the receipt of his sample as a mandate to use it. And do not believe the bromide that no one can keep up with medical advances today, for there are numerous existing abstract, year book, review and other services which make it quite possible to do so sufficiently well for practical and satisfying purposes. The expenditure of only a minimal amount of time is required too, if one’s time slices are adequately cut with this in mind. Most of you are keeping up better than you are told that you are.

And then there are the advertisements, the gorgeously colored spreads that make it difficult to find the reading matter in many of our journals. Please, if you must study the more gaudy of them at all, do so with a sour skepticism and a jaundiced and cynical eye. Be advised and aware that in some instances the journal references embodied in these advertisements are to preliminary findings that do not apply at all directly to the clinical claims that are made, and that in other instances the references are to publications that have actually been written by the pharmaceutical house staff itself for the inexperienced investigators who have made the clinical trials. The fact is that there are not enough existing facilities, and fully qualified clinical research workers, to perform the kind of studies that every new drug should have before it is made available for uncontrolled use in practice.

Publish date: 1959

During each of the past ten years the pharmaceutical industry has produced an average of approximately 400 new products. In the most recent year of record, 1957, the number is said to have been precisely 400, and 51 of these were single new chemicals. Many of the agents are produced in refined form in amounts that are absurdly small in relation to the bulk of the crude materials from which they are processed. Some typical yields of useful and familiar materials of different sorts are shown in Table 1. Add to the comparisons afforded in this table the fact that many entirely synthetic compounds are obtained through even more exhausting and expensive manipulations than are required in refining crude materials; and consider in addition the huge sums expended in research and promotion in order to make available, and to bring into the physician’s awareness, the packaged drugs awaiting his prescription — think of these things and it will easily be realized that the pharmaceutical manufacturers are obliged to interest themselves vitally in what it is that makes a new product acceptable to the doctor. To supply one observer’s version of what the requirements are, is the purpose of this presentation.

Table 1. Refined Yields From Crude Materials
Product	Source	Recovery per 1,000,000 parts of crude material
Copper	Ore	10,000
Magnesium	Sea water	1,270
Uranium	Ore	700
Reserpine	Plant root	500
Typical antibiotic	Fermentation broth	100
Vitamin B12	Fermentation broth	1

Source Of The Drug

I should say that if the new drug proposed for your use is, or is derived from, an old folk remedy the chances are good that it is worth paying attention to — not trying at once, willy-nilly, but at least watching to the extent of asking to see the records of its unbiased and controlled trials in specialized clinics. For the record of such agents is impressive, as is shown in the listing in Table 2 of valuable drugs obtained from folk medicine.

Table 2. Drugs Derived From Folk Medicine
atropine	ergonovine	pilocarpine
caffeine	ergotamine	quinidine
cocaine	ipecac	quinine
codeine	iron salts	reserpine
colchicine	morphine	salicylates
digitalis	papaverine	scopolamine
emetine	physostigmine	theophylline
ephedrine		tubocurarine

If a drug is offered because it has been discovered by search among the chemically close relatives of an active drug for another one of the same sort, you will be well advised to be hesitant in accepting it until full trials have been made by others better placed for such trials than yourself. Good drugs have often been developed through such approaches admittedly, but since these searches are usually begun merely to turn up for competitive reasons another drug as good as the one of established value, there is no obligation to believe a priori that the new agent is better than the old. It may be just as good and no more toxic, and this in itself may sometimes assure it a place in the armamentarium since there are instances in which there is advantage in having two strings to one’s bow — but let the qualified investigators determine the facts of the case while you continue to use the agent whose worth you know. Now, if the new drug has been evolved in attempting to improve an original compound through chemical modification, I should advise again to delay transferring patients to it until its clinical status has been proved by investigators qualified to make the controlled trials. There is a tendency among sales representatives of some pharmaceutical houses to maintain that certain chemical configurations reliably confer specific pharmacologic attributes upon compounds in which they are incorporated. But the actual fact is that invariability and predictability have not yet been achieved in this field of structure-activity relationships. One wants to know in each instance, first, whether the chemical configuration in question has really been shown by disinterested investigators to possess the attributes claimed for it; second, whether the structure to which it has been attached is one that is likely thereby to have the desired pharmacologic action conferred upon it or strengthened in it; and, third, whether the attachment has been made at a point that will potentiate or may actually weaken and possibly even pervert the action of the basic structure. These things the individual practitioner surely will not know.

Publish date: 1959