469

The Administrative Control ofTuberculosis.

THE LANCET.

LONDON: SATURDAY, FEBRUARY 15,1913.

IN a review of the annual report for 1911-12 of the MedicalOfficer of the Local Government Board 1 attention was drawn

particularly to Dr. NEWSHOLME’S remarks upon the adminis-trative control of tuberculosis, and as this is certainly amongthe most important medical questions of the day we make nofurther excuse for referring again to the subject, mainly’from the points of view put before us in a most interestingBlue-book. In the year 1898 the practicability of dealing ’with the control of tuberculosis by administrative methods wasfor the first time mentioned by the late Sir RICHARD THORNE

THORNE, at that time medical officer of the Local GovernmentBoard. His Harben lecture on ’’ The Administrative Control

of Tuberculosis, delivered before the Royal Institute of PublicHealth, is believed to have been instrumental in determiningthe formation of the National Association for the Prevention

of Consumption and other Forms of Tuberculosis, whichwas inaugurated at Marlborough House in 1898, under the

patronage of His late Majesty King EDWARD, at that timePrince of Wales. A lively impetus was at once given to the

preventive treatment of tuberculosis, and successive recent

reports of the Registrar-General have contained evidence ofthe great saving of life represented by the diminished fatalityfrom this cause in recent years. Dr. NEWSHOLME presentsin his report two diagrams dealing with tuberculous (andother) mortality in both sexes from the year 1851 to the

present time. If allowance be made for the fact that

formerly the term "consumption" was used more oftenthan now to designate non-tuberculous wasting disease

.accompanied by expectoration, it is probable that the

curves of mortality from pulmonary tuberculosis indicated,in these diagrams are approximately correct. They showfor both males and females a fairly steady decline in

mortality from this cause in the course of the last 40 years.With respect to the average duration of sickness from this

affection, it is believed that for every annual death from

pulmonary tuberculosis there are probably three persons

constantly suffering from that disease.One of the most important things to be settled in the

causation of the disease was seen 15 years ago to be the

relation of human and animal tuberculosis, for on this therewould obviously depend the course of much of the preventivemachinery to be employed. It will be remembered that in

the year 1901 Professor KocH made the statement that

bovine infection was negligible in practice as a cause oftuberculosis in man. In August of the same year a RoyalCommission was appointed to test the accuracy of the state-ment and to report whether the disease in animals and inman were one and the same; whether animals and man could

1 THE LANCET, Jan. 4th, 1913, p. 46.

be reciprocally infected with it ; and under what conditions,if at all, the transmission of the disease from animals

took place, and what were the circumstances favourable orunfavourable to such transmission. For Professor KocH’S

statement had profoundly startled the scientific world, andas a consequence of the reputation of its distinguishedauthor a thorough investigation was felt to be due. It was

promptly set on foot. The relation between human and

animal tuberculosis and the relative frequency of human andanimal infections respectively were inquired into by a EtrongCommission. From the public health point of view in-

vestigations of this kind are of momentous importance,for upon the answer to such questions must depend muchof our routine of public health-e.g., whether the con-

demnation of tuberculous meat is to be justified ; andstill more, whether the enforcement of precautions againstthe tuberculous contamination of milk, butter, and cream

is to be held necessary in future. The result of all

investigations hitherto undertaken has been to establish

the conclusion that infection of animal origin is a consider-

able cause of tuberculosis in the human subject, especially inchildren. The proof of this fact has been one of the mainresults of the labours of the Royal Commission. Among otherfacts emphasised in their report are the following : (a) thatthe excretion of tubercle bacilli has been observed in the milk

of tuberculous cows not suffering from tubercle of the udder,as well as in the faeces of cows suffering from only a slightdegree of tuberculosis ; and (b) that after subcutaneous

inoculation tubercle bacilli travel with great rapidity todistant parts of the body. The presence of bacilli of bovine

origin in certain types of tuberculosis has been clearlydemonstrated, as also has the rarity of bovine bacilli in

pulmonary tuberculosis. Except in rare instances pulmonarytuberculosis in adults is caused by infection of human

origin, but in other types of tuberculosis, especiallyamong children, bovine infection is not infrequently thecause of human tuberculosis. This conclusion has received

the support of all the evidence at present available. As a

factor in effective infection by tuberculosis—i.e., in the pro-duction of non-retrogressive disease-the importance of

dosage is illustrated by the experiments of the Royal Com-mission. The larger the dose of bacilli injected into an

animal of given age and weight, the greater the effect pro-duced, and the larger the dose administered by feeding themore likely is infection to follow. It has been proved thathuman tuberculosis is derived from two sources-tuberculous

animals and tuberculous human beings. The relative pro-

portions of these two dangers have to be exactly determined.That tubercle bacilli are found chiefly in the immediate

vicinity of patients with open tuberculosis is the opinion ofall who have investigated the subject. From the fact of

the wide distribution of the tubercle bacillus it follows that

a very large proportion of the population must have receivedinfection, and some may have developed nodules of disease,and may afterwards give a positive tuberculin reaction,

although the vast majority of them may never suffer from

clinically recognisable tuberculosis. Such ’’ tuberculisation "

needs to be distinguished, for practical purposes, from

tuberculosis. There remains, therefore, much work to be

done.

470

In the year 1911, before notification was universally com-

pulsory, about 35,000 cases of tuberculous phthisis wereknown to exist in this country, 13,000 of which occurred inPoor-law practice, 12,000 were notified under the new

hospital regulations, and 10,000 were reported under localActs or by voluntary arrangements. Dr. NEWSHOLME ex-

presses the belief that the enforcement of notification of all

recognised cases of the disease from the beginning of 1912will furnish more complete information of its incidence

than has previously been obtainable. Although the experi-ence of the first quarter under the new régime probablyrepresents a considerable accumulation of cases, it is

interesting to learn that within the first three months

of 1912 more than 38,000 cases of pulmonary tuberculosiswere notified in England and Wales. We now also know

from a valuable report of the Public Health Committee ofthe London County Council that during 1912 there were33,444 cases of tuberculous phthisis notified in the county,while it is estimated that there are in the area 50,000 personssuffering from tuberculosis. A complete scheme for dealingwith this mass of disease has been prepared, and similar

steps are being taken all over the country to make diagnosis,prevention, and treatment go together upon a coordinatedand economical plan. So that if much remains to be done,

at any rate, much is doing.

The History of the Enzyme.THE belief was expressed more than a decade ago that the

group of unorganised ferments which it is now agreed tocall enzymes probably played an important role in the

defence of the human organism against pathogenic micro-

organisms, and further, that their action possibly as proteo-lytic agencies went so far as to destroy toxins. Our know-

ledge has developed a great deal since, and modern researcheshave advanced along lines which have strengthened this

belief, for at the present time the view rapidly gainsground that the enzyme furnishes a factor of the utmost

biological importance to the human organism. For us,

the great interest attached to the enzyme is, of course,

its function in the human host, but it is curious to

reflect that the first really serious study given to these

mysterious manipulators of molecular alignment arose

not out of pathological curiosity, but from a considera-

tion of certain changes occurring in industrial processes.The story of the enzyme was developed during the study ofalcoholic fermentation, and we owe most of our knowledgeof the occurrence and mode of action of the enzyme to the

brewing industry. To know the pathology of beer was of vitalimportance to the success of the brewer, and the questionwas attacked with such perseverance, skill, and activity thatit is doubtful whether at the present time any other industrystands on a sounder or less empirical basis than brewing. The

pathology of beer was, in fact, studied with such success thatthe diseases to which it was in the old time heir are now

practically eliminated-at all events, in the hands of the pro-gressive technologist. The enzymes concerned were, in the

first place, diastase of malt, and, in the second, zymase of

yeast. It was the study of the latter enzyme which

demonstrated how misleading was the distinction between

organised and unorganised ferments. The vitalistic theory-of ferments was badly shaken when it was shown that it was,not the cell but the secreted substance of the cell which

effected the changes summed up in the term " fermentation." The inference of this was that the work of the enzyme is.-

chemical and not physica.1, and attention forthwith was.

given to the part played by the enzyme in intracellular-

metabolism.

At one time the list of ferments was a comparativelysmall one. The enzyme diastase (or amylase, according tomodern nomenclature), which was found to be responsible-,for changing starch into sugar, as in the brewing process, is.

probably our oldest acquaintance. It was first observed in

1814, and in 1831 it was discovered that saliva possesseda similar property which we know now to be due to,

the enzyme ptyalin. A similarly acting enzyme was.

found in the pancreas in 1845 and in the intestinal

juice in 1895, so that the existence of animal diastases

was established. The more complicated lysis of pro-

teins, as performed by pepsin and pancreatin or trypsin.,does not appear to have received serious attention until 1860.

Enzymes were afterwards isolated from plants which

showed a similar hydrolytic action, and then the hydro-lysing action of acids simulating enzymes upon both carbo-

hydrates and proteins came prominently into notice. In

the present day we seem to be going a step farther, for it

appears that the work of hydrolysis can be done bymetallic ferments, colloids, or by radiations, in the form

of ultra-violet rays, or radium emanation, all of which has

vast suggestion in the treatment of disease by certain-

modern methods. It is probable that the list of enzymes.with which we are now familiar is only a small

representation of the number of these activities which

actually exist both in the animal and plant kingdoms, but atthe present time we may say broadly that some fifty distinctvarieties have been recognised of which the individuality andmode of action have been made clear. Since little is known

concerning the nature of the enzymes, their classification so,far is based on the chemical reactions which they bringabout. The modern nomenclature of the enzymes is of

interest. It is generally agreed now to give them the.

termination " ase," as, for example, lactase, the enzymewhich converts lactose into galactose ; lipase, the enzyme.which converts fat into fatty acids and alcohol. The

substance acted upon, which gives the root name to the

enzyme, is called the substrate. The terminology adopted’has exceptions in the classic examples of pepsin and

trypsin.It is extraordinary what a variety of actions the-

enzymes are capable of performing. Thus, in addition.

to those already mentioned, there are enzymes which

convert urea into carbon-dioxide and ammonia (urease) ;further, there are those which oxidise purins, alcohol,aldehyde, phenol, tyrosin (the oxidases) ; another group.sets free oxygen from hydrogen peroxide (the peroxidases.and catalases, the action of which is analogous to that ofthe colloidal metals); again, there are enzymes which

convert cellulose into sugar, as in the digestive process of

graminivorous feeders (cellulase), and enzymes like chymosin-