Senator COPELAND. They kill those with which they come in contact?

1

Prof. SMYTH. Complete disinfection or germicidal action in vivo

The CHAIRMAN. Just a minute. Senator Copeland asked you a question.

Prof. SMYTH. I am a little hard of hearing. I am sorry. Senator COPELAND. They are to kill those with which they come in contact?

Prof. SMYTH. Yes.

Senator COPELAND. You are not expecting any more of them?

Prof. SMYTH. Antiseptics are supposed to inhibit the action of organisms with which they come in contact, but, according to the derivation of the word-my interpretation of it, at least-they need not kill those organisms. Their effect may remain as long as they are in contact with the organisms, but if that contact is broken up, if the contact has not been too long, the organisms may revive. That is possible even with bichloride of mercury, which is usually considered as a germicide. Bichloride of mercury acts on bacteria entering into chemical_combination, forming the so-called "albuminate of mercury." If that combination does not last too long, further chemical treatment may break that up, and your organism may still be alive, even though the material came intimately in

contact.

Complete disinfection or germicidal action in vivo is not necessary or always possible. Nature can and does care for comparatively heavy infections. It may be hindered rather than helped by relieving it of all responsibility; for example, as people grow in strength and resistance, and the body grows in its resistance to microorganisms by overcoming that resistance. To produce immediate death in the first application may prevent the development of desirable reactions, and that is the natural way for the body to recover and remain healthy after an infection, by the development of the immune reaction material, killing or inhibiting the majority of the organisms, and the infection, but not all may leave sufficient cells there to act as stimulators to the body cells to produce immune reaction to enable the body cells to overcome other invasions.

My point is that if we by the use of some materials kill all of the organisms at once, as may be required by the provisions of this bill, we may interfere with nature rather than help nature, so-called.

Again, it is impossible, with our present technique, to set up in vitro laboratory test conditions even simulating the conditions in open wounds with the presence of dead tissue shielding germs or buffering chemical action, and the continued diluting effect of secretions, let alone conditions in body cavities and deep sinuses, and yet the bill says that we must use tests testing by methods simulating as nearly as practicable the conditions of such use.

My point is that it is not practicable as yet. No standard tests have been developed that do approach these conditions.

Senator COPELAND. Doctor, read the rest of it.

Prof. SMYTH (reading):

Or, in the absence of such methods, when tested by a standard method, it does not have the germicidal effect within the duration so prescribed of a 1 to 80 dilution of phenol used by a standard testing method for 10 minutes at 37° Centigrade.

I will come back to that later.

It is recognized-and I grant it-that the present accepted test methods are a distinct advance over the former hygienic laboratory phenol coefficient test at 20 degrees, and that in turn was an improvement over the original Rideal-Walker test. However, these methods-and they are the methods that must be referred to here as standard at the present time-are no doubt capable of further improvement, and an act of this kind should not be static in the specification of any one method which may later be changed.

The methods in use today recognized as standard have been so but a very few years. The plans are in the air-fibro-bacteriologists have plans to suggest to modify these methods that would make the requirement of the equivalent of a 1-to-80 phenol test for 10 minutes obsolete. Putting that in the bill makes it static-putting that in the body of the bill. The body of the bill should not, in my opinion, have any static test of that kind which may be subject to modification at a later date, and which would require rewriting the bill.

Provisions in regulations are not static, and a method standard at the time is not necessarily static, but referring to a definite standard method is. The only static languages are dead languages. Static sciences are fixed, not developing sciences, as is the science of bacteriology.

Senator COPELAND. Doctor, read in connection with what you have just said line 23 of page 14.

Prof. SMYTH. Section (j).

* * All testing methods for the purposes of this paragraph shall be prescribed by regulations as provided by section 22.

I am referring, however, to the fact that this law requires a specific yardstick, 10 minutes, 1 to 80 phenol, 37 degrees. Methods may be modified to get that same result, but this requires that condition, that is, meeting that condition. In other words, any color so long as it is red; but you can obtain red color by any mixture of pigments you want. Any tests may meet this static condition, and that is what I object to, for all microorganisms. They are very excellent for some. I want the possibility of flexibility of the act. I do not object to that being used in many cases.

Senator COPELAND. Doctor, you have to start somewhere, and you start here, but if those methods are found not to be right, provision is made for their change. You see, on page 14, lines 5 and 6, and also on the same page, lines 23, 24, and 25.

Prof. SMYTH. Yes; testing methods to test the action of phenol 1 to 80 at 37 degrees, 10 minutes. Those methods are called for specifically, as I interpret the act, and as I know it has been interpreted by others. In fact, no specific test method should appear in the body of the act, nor does a method for any other drug so appear in this act.

The state of our knowledge in germicidal and inhibitory action is still developmental and cannot predicate all uses. Phenol may be a very excellent yardstick for the phenol derivatives. It may not be a satisfactory yardstick for some of the metallic disinfectants, and I think the act would be more flexible and result in less confusion if a specific yardstick. phenol, 10 minutes, 1 to 80, 37 degrees, was not there. That requires all of our new test methods that you may

develop, methods suited, in compliance with that provision, and that is a provision put in the act, as I interpret it-I may be wrong

Senator COPELAND. Would you prefer to have it written in the act that the given germicide must be capable of killing the staphylococcus aureus after an application of 10 minutes, or whatever it might me?

Prof. SMYTH. No

Senator COPELAND. You do not want any test?

Prof. SMYTH. I think if you will renew your questions when I am through we may come to a clearer understanding.

If specific tests for germicides, as this test, should appear in the act, why not tests for the action of stimulants, narcotics, diuretics, or laxatives? A laxative may not always produce in a given dose or method of use, and the same with other types of drugs, so why should we require that a bactericide always, under all conditions, kills germs in vivo? We admit the use of laxatives somewhat stronger than others. Tests show that under reasonable conditions they may be efficient, but we cannot prove that they will always be efficient. Why may it not, if active and standard under in vitro test conditions, be recommended for use in the body, where it may act as a bactericide, or merely as an antiseptic, or may, under peculiar conditions, fail to do even this effectively? Action depends on reaction between three elements: Drugs, tissue, and germ. Drug action in vitro may be standardized, and I approve of standardization, but germ resistance in vivo and tissue resistance are variable and far from standard, and are not even always predictable.

Need a germicide, as a mouth wash, spray, and so forth, which will never remain undiluted in contact with infective material in vivo for longer than a fraction of a minute, be required to do as efficient work as a 1 to 80 phenol solution in vitro in 10 minutes?

Whether your material is to be applied for a short or a long time, the action obtained must be that of 1 to 80 phenol in 10 minutes. I object to that.

When used prophylactically, bactericides will seldom be called upon to combat the massive dosage in hundreds of millions of germs used in standard vitro tests, so why should their use in this way as preventatives not be permitted if they are proved to be effective against much smaller dosages, the dosages met with against which we use preventatives, against which household antiseptics are used, and disinfectants, not generally the massive dose met with in severe, acute infections, and met with in the standard tests. The standard tests are all right. I do not object to the standard tests, but I object to a specific standard test being specified, making the bill static. If those tests are regulated subject to modification, that is a different matter, and I do not read in this bill that they are.

In the present tests in general use one organism is used, staphylococcus aureus, and that of a "standard" resistance as measured against phenol 1 to 80 at 37 degrees centigrade. Is this "standard" strain one of an average resistance, or decidedly more resistant than average? I have tested a number of freshly isolated staphylococcus strains, and by that I mean freshly obtained from diseased conditions in the body, and at least half of them have a lower resistance than this so-called "standard" strain, and their use would pass as sat

isfactory a germicide which must be condemned when tested with the "standard" strain. Personally I approve of the use of a resistant strain and massive dose as a test organism, but I am not sure that materials not killing this strain in a given time should necessarily be condemned, or not killing any one type or several types of organisms.

While phenol may be the best yardstick to measure the action of germicides against some organisms, are we sure that it is the best for all? We are not. We feel very definitely that it is not. Disinfectants or germicides are known to act differently against different organisms and under different conditions, so, can any in vitro test with one comparitor, one organism, staphylococcus, and one disinfectant, phenol, be sure to give an answer for all such substances acting on all germs under all body conditions?

Bear in mind that these materials are used in practice against bacteria of very varying resistance, against yeast, fungi, and against the so-called "filterable viruses ", about the resistance of which we know very little. Why not permit the manufacturer to furnish evidence of practical, efficient action in other ways than one, provided his evidence is subject to scientific review and approval, that is, by the committee provided for, not allow a new method of testing to be put into general use, uncontrolled, but allow a new method of testing, allow a manufacturer to suggest a new method. According to this bill, the manufacturer has no method of approach to this committee except at the will of the Secretary of Agriculture.

Why should inhibitory action necessarily be continuously undiminished over the entire period of application, if nature only needs help to combat infections, and how can antiseptics ever be supposed to maintain inhibitory action undiminished over entire periods when there is much diluting secretion in the wound or from the inflamed surface? Any action is aiding nature, even though it may be continually lessened, and may be sufficient to aid nature to

overcome.

I object to the requirement that the inhibitory action be continuous during the entire period of application, because conditions are continually changing in nature. Nature is not static. In any infection, any inflammation, the wound is forcing out secretion continuously, diluting your disinfectant. As an illustration of the harmfulness of static provisions or tests in a law, let me quote from personal experience in an entirely different matter, an entirely different field. Many school ventilation laws, as those in my own State, for example-Pennsylvania-specify conditions now known to be unnecessary, such as 30 cubic feet of outdoor air per minute per pupil, with no recirculation per pupil, and omit or prohibit conditions now known to be helpful or essential, as proper air movement and distribution, and effective temperature control, and standard test methods developed by the Bureau of Mines after these regulations were promulgated. The revision or attempted revision of these codes is a difficult one and in some cases almost impossible, due to the protests of concerns whose installations are built around the antiquated. requirements. I know because I have been serving 2 years on a committee for the State of Pennsylvania to attempt to revise and bring up to date our regulations for school ventilation; and I visualize if the new law is passed containing the definite stipulation

that no matter what tests you use, or no matter what laboratory methods, they all must measure up to the efficiency-the materials must equal the efficiency by one yardstick, phenol, 1 to 80, 10 minutes, 37°. Fixed conditions and the too rigid enforcement of standards may do harm by permitting over or under action and may delay progress and exclude useful preparations.

With the omission of section 8, paragraphs (i) and (j), the proof of claims, as I read it, is provided for in the general provisions of the act by standard methods recognized at the time of testing as standard, and prescribed by the Secretary on the advice of his advisory committee. If they were tested today, they would all be tested, probably, by these methods, as a measurement, but if they were tested next year, this method may be antiquated. I say it is provided for because these materials are classed in the act as drugs and considered in this section 8, which is a section on misbranded drugs. If you gentlemen consider them drugs, they should have had a separate section and not be considered simply as paragraphs_(i) and (j) of section 8. Now, you call for the testing of drugs. You allow variations in other drugs, but you do not allow it in these. Referring to page 6 of the bill, it reads:

No drug shall be deemed to be adulterated under subdivision (2) of this paragraph if its label bears, in juxtaposition with the name of the drug, a statement indicating wherein its strength, quality, and purity differ from the standard of strength, quality, and purity set forth in the appropriate official compendium.

Now you require the testing of drugs by standard methods given in one of two publications, the United States Pharmacopoeia or the Homopathic Pharmacopoeia, publications which themselves are subject to revision, which in fact are revised periodically-automatically, as it were, and there is that revision between those periods, and yet you put in here for disinfectants one static condition, phenol 1 to 80,. 10' 37°. That is what I object to most seriously in this.

Standards vary and must vary for different organisms, just as they do in other things. I have been extremely interested and have concerned myself a great deal in tests in industry of industrial dusts and their effects. It is very hard to develop standards according to all tests. It cannot be done. You must have one standard for a silica dust and another standard for asbestos, which is a silica, and another standard for a coal dust and another standard for toxic metals. If you measure toxic metals as you measure silica dust, you miss the point entirely, because there it is the amount of metal that gets into the system and not the number of particles. If you measure all of these by phenol, 37 degrees, 1 to 80, 10 minutes, you have just

that one method.

I thank you for your attention. I am sorry I have trespassed on your time for so long.

Senator MURPHY. Doctor, have you brought along a suggested substitute for these sections?

Prof. SMYTH. No; the suggestion I make at the end here is that I feel the safety of the public is cared for if these materials are considered as drugs and are handled as you handle drugs, subject to the standards developed or modified from time to time by your committee provided for in section 22. That is where you have the provision. That committee, in the bill, is to be called at the request