This was really a tremendously important discovery, and, so far as anthrax was concerned, Pasteur rested upon it for about five years, or until he had completed his studies of chicken cholera. These latter experiments taught him that bacteria could be weakened in the laboratory, yet their immunizing properties remained preserved. And after their completion, he read a new and deeper significance into his old experiments on anthrax in hens.

From his old experiments he reasoned that the comparatively low temperature of sheep and horses was favorable to the growth of anthrax bacilli, while the high temperature of hens was unfavorable. And after his observations on chicken cholera had taught him that artificial attenuation of germs could be brought about by prolonged cultivation outside the body of the susceptible animal, he wondered whether the same effect on a germ (the anthrax bacillus) could not be produced by heat. We shall let his colleague, Chamberland, tell what happened as a result of experiments made along these lines:

"At the extreme temperature (107 degrees to 109 degrees F.) the bacteria (anthrax bacilli) yet live and reproduce themselves, but they never give any spores. Thenceforth, when trying the virulence of the phials after six, eight, ten or fifteen days, we found exactly the same phenomena as for chicken cholera. After eight days, for instance, our culture, which originally killed ten sheep out of ten, only kills four out of five; after ten or twelve days it does not kill any; it merely communicates to animals a benignant malady which preserves them from the deadly form.

"A remarkable thing is that the bacteria whose virulence has been attenuated may afterwards be cultivated in a temperature of 87 degrees to 95 degrees F., at which temperature they give spores presenting the same virulence as the bacilli which formed them."

With attenuated anthrax bacilli in his possession Pasteur was now ready to immunize large domestic animals against virulent inoculation; and on May 31, 1882, on a farm at Pouilly le Fort he performed his crucial and epoch-making experiment on sheep. On that day in the presence of a number of distinguished spectators he inoculated twenty-five normal, unprepared sheep. Several days later "the carcasses of twenty-two unvaccinated sheep were lying side by side; two others were breathing their last; the last survivors of the sacrificed lot showed all the characteristic symptoms of anthrax. All the vaccinated sheep were in perfect health."

Pasteur had thus discovered another way to attenuate germs and had devised one more method of immunization against a major disease. From here it was but a step, though a remarkable one, to his greatest triumph.

At the very time that Pasteur was putting through his famous immunization of sheep against anthrax, he was beginning his studies on rabies (hydrophobia). A letter from his wife of May 25, 1882, shows that he was then investigating the paths of infection and the localization of the virus of rabies. After a prolonged series of observations he came to the conclusion

that to produce disease the virus must have its seat in the nervous system, especially in the medulla oblongata of the brain. He proved the validity of this belief by direct experiment; and concluded that after the first virus had reached this vital spot it must propagate itself there to the point where symptoms of disease would result.

By passing rabic medullas from rabbit to rabbit he greatly increased the virulence of the infectious matter; and, this done, he desired to decrease its virulence. What he had learned from chicken cholera and from anthrax gave him the clue of how to effect this purpose. Under special conditions and at a temperature of 73 degrees F. Pasteur dried the medulla of a rabbit that had just died of rabies after inoculation. He found that after fourteen days of drying the virus had been completely extinguished. "This now inactive medulla was crushed and mixed with pure water, and injected under the skin of dogs. The next day they were inoculated with medulla that had been drying for thirteen days. and so on, using increased virulence until the medulla was used of a rabbit dead the same day. These dogs might now be bitten by rabid dogs given them as companions for a few minutes, or submitted to the intracranial inoculations of the deadly virus; they resisted both."

This was in 1884; and in the four years that intervened between his studies on chicken cholera and his successful protection against rabies, Pasteur (so far as the principle was concerned) had practically traversed the gamut of immunization methods as we know them today. His antirabic inoculation was his most brilliant achievement, for here he had devised the technique of a method without having at his disposal the isolated! germs of the disease to be protected against. Again, he had succeeded in obtaining an immunity without making the immunized animal sick in the process.

This was indeed an advance over the first attempts at protective inoculation. A century before a human being could be immunized only by conferring upon him a serious disease with a certain proportion of mortality. Then, with Jenner, it became recognized that a non-mortal slight ailment would give the same protection. Afterwards Pasteur worked out methods that could be employed in the laboratory; to attenuate various known bacteria and with these weakened strains to protect against malignant disease with only the development of a transient indisposition intervening. And finally, still by methods of attenuation, he came to immunize against a disease (rabies) without making an animal the least bit ill thereby.

By this time, too, the underlying principle was becoming clearer and clearer. The germs of disease arouse the infected body to the production of antagonistic substances or change the reacting capacity of the tissues of the body. This altered reaction (allergy, as we know it today) or an excess of antagonistic substances persists after the disease passes; and, persisting, they successfully combat the full or partial development of (Continued on page 375)

2. General Impressions of the Framingham Community Health and Tuberculosis Demonstration.

The officers in charge of the Demonstration have accepted what appears at present the soundest current viewpoint, that the most effective practical procedure for the control of tuberculosis lies in the development of machinery for its early detection and for the hygienic care of individuals affected or threatened with the disease, while at the same time taking such opportunities as offer to minimize the spread of the infectious agent. The first step along this line must be a determination of the actual prevalence of tuberculous infection, and this end has been accomplished with a high degree of success by the organization of medical examination drives, by the organization of a tuberculosis consultation service, and by the establishment of infant, school, industrial and other clinics. Efforts along this line have been strikingly successful in giving us for the first time a fairly complete picture of the amount of tuberculosis actually existing in a typical American community.

The conclusion that in the medical examination drives nearly one per cent. of the persons examined were suffering from active tuberculosis while somewhat over one per cent. more were arrested cases, is an important one. This finding, if assumed to be representative of the whole community and compared with the death rate for the town, would indicate a ratio of 9 or 10 active cases during the year to one reported death. The best way to estimate this factor would in our judgment to be compare the number of active cases under observation during a given year with the number of deaths occurring among that group of cases. The actual experience of the Demonstration has been that two hospital beds have been required for each reported death; but the period is too short and the number too small to warrant far reaching deductions. Furthermore, it should be noted that it would have been difficult to fill this indicated ratio of beds without the effective machinery for locating cases, at the disposal of the Demonstration. On a basis of the active advanced cases in which the need for hospitalization was most acute, the ratio indicated by the Framingham experience would be nearer one bed each reported case. The careful analysis of death certificates showing that the actual deaths from tuberculosis in Framingham were 22 per cent. in excess of the reported deaths from this disease also constitutes a valuable contribution, although the small number of cases involved makes it impossible to apply this conclusion in any general way.

to

In connection with the problem of diagnosis, the officers of the Demonstration

have prepared a scheme of diagnostic standards for tuberculosis which has attracted wide attention.

The most important of all the practical contributions made by the Demonstration is the working out of a plan for medical consultation service which is clearly the most promising means yet devised for securing a reasonably complete knowledge of the amount of tuberculosis existing in a given community. This work has been carried on by Dr. P. C. Bartlett with admirable scientific skill and exceptional tact and judgment. The physicians of the community almost without exception avail themselves freely of this service and aside from the direct results in the detection of early and doubtful cases, the stimulating effect upon the local medical profession constitutes an invaluable service to the cause of public health in Framingham. The consultation service plan has attracted wide attention throughout the country and under the auspices of the State Department of Health and the State Tuberculosis League such a service has been offered for three months in the Cape Cod district of Massachusetts with great success. The plan is already in operation, or is proposed, in sections of Illinois, New York, Ohio, Oklahoma, Vermont and Wisconsin.

The success of this organized campaign for the discovery of tuberculosis is indicated by the fact that nearly 200 cases are now under observation in Framingham as compared with 27 at the beginning of the Demonstration, and it is particularly encouraging to note that during the first year 42 per cent. of the new reported cases were of an advanced type, while in the second year only 16 per cent. of the cases were advanced, and in the first five months of 1919 only 23 per cent.

The machinery adopted for the treatment of cases of tuberculosis after they have been discoverd has been modelled along generally accepted lines, involving sanatorium treatment, or hygienic advice furnished through the service of a public health nurse, as circumstances may dictate in the individual case. There has been nothing here that is particularly novel, but the work has been accomplished efficiently and successfully along the lines indicated by the best current practice.

In view of the great difficulty of securing adequate sanitary control under such home conditions as are frequently met with, particularly in the later stages of the disease, we desire to emphasize the importance of extending facilities for local hospital treatment. It is our opinion that such treatment can be applied most effectively by the development of hospital facilities within convenient street car radius of the homes of the patients.

From the standpoint of the general environmental causes effecting the spread and

development of tuberculosis, the staff of the Demonstration has. conducted valuable studies of schools, factories, and municipal health conditions, and the general situation as it affects tuberculosis seems to be as satisfactory as could reasonably be expected. Only two important points which directly concern the control of tuberculosis appear so far not to have been covered,the establishment of a central pasteurizing station for the milk supply of the community and the organization of a comprehensive system of industrial clinics for the smaller manufacturing plants. Both of these measures have been contemplated by the officers of the Demonstration, and it seems to us most important that these two gaps should be filled.

Believing that the control of tuberculosis is closely connected with all conditions which tend to build up the health of the community, the officers of the Demonstration have devoted a considerable share of their attention to the formulation of a general health program beyond the specific field of tuberculosis itself. The medical examination drives have yielded some of the most complete data in regard to the prevalence of disease of all sorts in a random section of the population that have ever been collected in this country. These data are of much value as indicating the prevalence of such conditions and the unit costs involved in such examinations. Even more important from the practical standpoint has been the notable development of public health work in Framingham along a wide variety of lines, which has resulted directly or indirectly from the activities of the Demonstration. The amount of money spent for health protection in Framingham has been increased during the life of the Demonstration from 39c. to $2.00 per capita. Half of the latter sum is contributed from public sources by the Department of Health and the Department of Education, and the other half from private sources through the Civic League, and the industrial clinics established by public-spirited manufacturers. The local Health Department has grown to be a strong and effective one and the system of medical inspection of school children organized under the Department of Education represents one of the best examples of such service to be found in the United States. Machinery for protecting the health of infants and children of the pre-school age has been worked out under the auspices of the Civic League, and with the advances made during the present summer includes four infant clinics, and a preschool clinic. On the whole, this work seems somewhat less satisfactory than the other phases of the local health movement, but a foundation has been laid upon which progress will no doubt be made in the future.

The work of the Demonstration has been

extended in certain directions somewhat beyond the field of definite public health activity, and the Committee on Appraisal feels that such appropriations as those made for the Community House of the Civic League and for the maintenance of the Day Camp for subnormal children might well be discontinued in the near future. Valuable as these enterprises are, it seems to us unlikely that they well yield tangible results in the saving of life.

3. Conclusions to be Drawn from the Demonstration in Regard to the Practicability of the Control of Tuberculosis.

The object of the gift made by the Metropolitan Life Insurance Company to the National Tuberculosis Association was not as we understand it, primarily to benefit Framingham or any other local community, but to determine the practicability of the control of tuberculosis by the full application of the best known methods. The . really important question before your committee is not, therefore, the extent to which Framingham has benefited by the development of an admirable scheme of local health organization, but the degree to which this organization has been effective in controlling tuberculosis. Success along this line might obviously be measured in two ways, by a decrease in new cases, or by a decrease in the tuberculosis mortality. With the progress of the Demonstration and the improvement of machinery for finding early cases, the recorded morbidity at first materially increased, but it is interesting to notice that during the first five months of 1919 only 40 new cases came to light, as against 55 new cases for the corresponding months of 1918. Obviously, however, no conclusions can be drawn from this isolated comparison. From the standpoint of mortality, the tuberculosis death rate (after eliminating non-residents, and adding deaths of residents occurring outside of the town) has fallen from 93 per 100,000 in 1917 to 79 in 1918, and to a rate corresponding to 76 for the first five months of 1919. This is an encouraging showing (in view of the fact that the tuberculosis death rate in similar Massachusetts communities has in general materially increased); but again the period is so short and the actual number of deaths so small that no reliable conclusions can be drawn.

The member of your committee representing statistics (E. T. S.) has prepared a computation of the probable errors involved in the problem and concludes after fitting the rates for 1907-1916 to the curve of probable error, and allowing for the mean error in any given rate projected for 19191923, that in order to warrant reasonably safe conclusions one or the other of the following combinations of tuberculosis death rates must be reached during the latter period.

A rate of 30 or less for any 1 year

A rate of 45

A rate of 60 A rate of 75 A rate of 90

or less for any 2 years

or less for any 3 years
or less for any 4 years
or less for all 5 years.

It is obvious that rates between 70 and 80 for 1918 and 1919 cannot possibly be considered as significant, and it could scarcely have been expected in dealing with a disease of the nature of tuberculosis that any conclusive results could be reached in a period so short as three years.

4. Conclusions in Regard to the Advisability of Continuing the Framingham Demonstration.

It seems clear that if the Framingham Demonstration should cease on January 1, 1920, the local community will have benefited materially and many important contributions will have been made to the practical control of tuberculosis; but that the main question for which the Demonstration was endowed will remain unanswered. In the judgment of your committee this would be a most unfortunate contingency. Our best authorities on tuberculosis have been subject during the past few years to a growing skepticism in regard to the adequacy of methods which have been advocated for the control of this disease and have turned eagerly to the Framingham Demonstration as the first real opportunity to set their doubts at rest. If the experiment should be abandoned at this time it would be necessary to begin all over again somewhere else, for a test of the best methods now available is absolutely essential for future progress in this field.

If on the other hand is should be possible to continue the Demonstration for a sufficient period to yield results of statistical accuracy, your committee feels confident that the question as to the soundness of the current anti-tuberculosis program will be definitely answered one way or the other. The foundation has been well laid; a program for the control of tuberculosis by early diagnosis and hygienic care has been organized on ideal lines; local sentiment both in medical and lay circles has been successfully developed in support of the campaign; and all conditions are favorable to its success. Given a sufficient period for the continuance of the Demonstration and for the study of the results obtained, both morbidity and mortality records should furnish a clear answer to the question of whether or not such a program is effective.

In addition to the fundamental conclusion as to the practicability of the control of tuberculosis by the methods used in Framingham, a continuation of the Demonstration should throw important light upon the theoretic factors which contribute to development of tuberculosis as a disease, and should therefore make it possible to modify our program along more purposeful lines in the future. The investigations

the

made at Framingham have as yet led to no far-reaching conclusions in regard to these factors. The most suggestive point that has been brought out is perhaps the variation in disease incidence among different race stocks. The combination of a very high proportion of tuberculin reactions with a low mortality among Italians and the precisely opposite condition among persons of Irish race stock is of considerable significance. The study of the subsequent history of the large number of arrested cases now under the observation of the Demonstration constitute, in itself, an invaluable opportunity to determine some of the factors which convert latent into active disease.

In the continuation of the work of the Demonstration, we would urge that special attention be paid to the intensive study of environmental conditions, in the home, the factory, and the community, with a view to throwing more light than has yet been obtained upon the possible effect of each condition upon the spread of tuberculous infection and the development of active disease. We are inclined to believe that the detailed study of even a few hundred cases should yield results of real value in this connection; - if correlated with observation of the environmental conditions surrounding a properly selected control group of families free from tuberculosis. 5. Recommendations in Regard to the Continuance of the Demonstration in the Future.

The statistical calculations cited above have led us to the conclusion that the Framingham Demonstration should be continued for a period of at least five years in order to render the attainment of definite results of reasonable certainty. It is, of course, possible that the prolongation of the Demonstration experiment through 1922 might be accompanied by a tuberculosis death rate of 60 or less for all of the three years involved, but since a death rate of 60 corresponds to only 12 deaths, it is obvious that a chance combination of circumstances might easily interfere with such a result. In this contingency we should once more face the possibility that a large sum of money had been spent without the attainment of the primary object in view. The effect of such an experiment should be cumulative, and each year added to its life greatly increases the chances of ultimate success. A five-year period should, we believe, yield results reasonably certain to answer the question as to the practicability of the control of tuberculosis. If successful, it would furnish for the first time a definitely established working program for the practical control of tuberculosis. If unsuccessful, it would indicate with equal clearness the need for the adoption of measures of a different sort from those that have recently been recommended as adequate and necessary.