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Fixation of complement in tuberculosis
Ailgust, 1920]
TUBERCLE
tinl difference between the first- and the ' la ter· horn ; and the comparatlvely great susceptibility or the former to tuberculosis in adult life must, therefore, be referral! to still obscure endogenous factors. Practically all the evidence at present II.vnilable as to the prevalence oC tuberculosis in the first-born points in the words of W. C. Rivers, .. hack to <1iathesis" [7]. Dut wha.t is diathesis? [1] II. BRltllWER. Berlin, 18B5. I I Die Actio. Jogie der chronischen Luugenschwlud, sucht." (2J K. PltAaSON. London, 1907. I I A l"irst Study of tho StAtistics of Pulmonary
Tuberculosis." [3] S. HA~IlIl:N. Copenhagen, 1915. "Med· 'deJellier fro. Den Antropologiske Komlte," (4J D. F. WEEKS. London, 1912. .. The Inheritance of Epilepsy: Problems In Eugenics. "I [5] S. HAN9EN. Copenhagen,1920. .. Tuber. kulosen og de FijrsWidte Blirn.," UgtJkrijt J
o
PO~IUon."
lUXATION OF COMPLEMBNT IN TUBERCULOSIS. Fixation of complement is the order
oC the day in every modern bacteriological laboratory. We employ it in resea.rch in almost every bacterial and protozoal disease with varying success. In tho cuse of syphilis the reaction has now passed the experimental stage, and is more or less standardisod in method. In the case of bacterial dlseases, however, hope of succoss is still deferred. It may Le that there is some inherent difference between 11Il,cterial and protozoal protoplasm-its "ohlivionr Is certainly very different as regards reaction to drugs. Wha.tever be the explanation, it is clear that fIxation of complement with 0. nonspecific lecithin compound as antigen, nnd 1\ syphilitio serum o.s antibody, is II different proJlosition from that of 1\ tubcrculous . antigen and antibody reaction. Hxntion of complement in tuborculosh~ has now been tested fairly extenlively since Wassermann and Druck's
523
early and rather disappointing efforts. A large number of publications have appeared during the last five or six yoMs, most of them exploring the question of the composition of the antigen. A recent article by Petroff" has helped to curry the inquiry still further. It is n. closely reasoned account of tho difficulties which confront the serologist in this field of work. He rightly emphasises the fa.ct that complement fixation in tuberculosis cannot be compared with the ' Wassermann test even though both reactions may ultimately prove to be colloidal in nature. In reviewing tho whole question at least four problems confront us. In tho first place we require an antigen which is sufflciently sensitive to detect early active cnses, but which wiII not react with arrested cases. Petroff divides up his antigena into four groups: (1) Suspensions of tubercle bacilli living or dend, intact or pulverised; (2) filtrates of broth cultures of tubercle bacilli (e.g., Besredka's antIgen, potato filtrate, and old tuberculin); (3) ether-alcohol extracts of bacilli; and (4) extracts of tuberculous organs. lie has taken great care in the preparntion of these antigen" especially in endeavouring to obtain pure Iipins by ether-alcohol extraction, and finda methyl alcohol much moro satisCuctory than the ethyl alcohol commonly used. Petroff believes that positive results can be obtained with any tuberculous antigens, and furthermore makes the suggosth'o remark tho.t "prohably this means that any antigen representing in its phyeico-chcmieal state II. ·proper dispersed phase is a good antigen." From a. comparative .table we learn that ~ glycerin extro.ct of iho whole tubercle bacilli gives the best results. Secondly, n. method of performing tho test is required which will give us some quantitative estimation of tho reaction. This of course involves elaborate standardlsatlon of method and cannot be satisfactorily carried out in the present stato or our knowledge of tuberculous antigens and antibodies. Thirdly, wo need 0. test which will not ho confused with fixation of 0. comI Am,r. Rev. 01 Tub., 10~0, 3, GR3.
521
'.tUBERCLE '
plemen t in any other disease, especially syphili s. This means tho.t, for the presen t at any rate, all comple ment jixation tests ,for tubercu losis must be contro lled by 0. Wasse rmann test, and of course such 00 proceeding greo.tly adds to tho labour s of the bacteriologist unless be is working in conjun ction with other serologlats. Fourth fy, any test ueviseu must posses s technic al precision withou t on the other hand being too complicated for routine use. On this ground Petroff has render ed good service. IIo has exercised great care in obtaini ng the best possible labora tory conditi ons as to prepar ation of salt solutio n, cleansi ng or glass ware, storing of sera, standa rdisati on and pooling of comple ment. Efforts to separa te the tuberc ulous antibo dy from serum have not 'yet roache d the stage of publicatio n, but the author is investi gatins the point. He believes in commo n with most scrolog ists that these antibo dies are carried down with the Slobulin
portion.
On tho mecha nism ot tho reactio n Petroff has much of interes t to discuas. As might be expected he inclines strong ly to the view that the antigen untlbody-com plemen t reactio n is an elaborato colloidul systom in which comple ment pla.ys the IJllrt of an absorp tion phenom enon. Finally , and by no moans least import ant, Petroff issues '0. word of 'warn ing as to the clinical interpreta.tion or comple ment fixation results . This warnin s might be taken to heart hy cllnlclans and pathol ogists alike. Pathol ogists' reports offer no royal road to diugnosia. Each in hls own way must tread the pninlu l l)ath of practic al experience. Otherw ise the search for a. moans of carly diagnosis in tuborc ulosis will contin ue to be in the future what it has been in the past, 0. Ions experience in diaillusion mont.
(August,'102 0 .. AS YOU WERE ."
In the March numbe r of the ...1merithere is an editori al annota tion by Dr. Allen 1\. Krause in which he tn.kes stock of tho presen t positio n in Americo. and compares it with that of ten yeo.rs ago. Ie his views expres s the genera l consen sus of expert tuberc ulosis opinio n in tho U.S.A., we are confro nted with the fact that the problem of tuberc ulosis is being tackled beyond the Atlant ic on lines strikin gly diverg ent from those along which the campa ign in this countr y is being conduc ted. I ndeed , this divergence seems so marke d that there is little prospe ct of these lines meeting. howev er much the~' mo.y he prolonged. Dr. Krause write s:II • • • could our depart ed heroes or tuborc ulosis of only ten )'ellrs al:0 scan its (Thc Amcrican Rexieu: of T"btrculosis) pnges, they would perforce ruh their eyes. For thoir tUborculoslll proble ms have slunk to the rear. Tbo tubercl e bacillu s is no longer tuberculosis i it has become 0. mere inciden t of tuberc ulosis . . That tubercle bacilli are in men no lon,:::cr hurries a. chill down our spine. This fact we have come to accep t-just 0.8 we accept our sins, our hates and our lusts, our coveto usness and our pride. )Iora\ science cannot deny their existen ce: good morals deman d that they lie dormn.nt nnd concea led . . . Brush Ul) {or an hour on the tuberc ulosis oxhort ationa that ushere d in the centur y and promis ed to the popula ce 0. new world. How? lly slaugh tering cattle, h}' nboHshing spittin g, and by tcachin~ and taking care of tho sick for 0. row month s. But human nature is can. tankor ous. Its human right to spit far and wide will not be yielded to 0. shadow y peril . . . the kor to tho problem HQS buried in the condit ion ct tho social mass: in urban and rura] general health and sanitat ion, in Wl\ge~ and the cost or commo dities, in hoUsin~ and in rents, in hours of work, o.ntl ideals and habits of play and rccron_ tion. . . . It is his reactio n to hill (the pa.tient's) enviro nment tha.t brin~!'t him to the sanato rium; it is his reactio n
cd11. llcvietv of Tuberculosis
TUBERCLE
tinl difference between the first- and the ' la ter· horn ; and the comparatlvely great susceptibility or the former to tuberculosis in adult life must, therefore, be referral! to still obscure endogenous factors. Practically all the evidence at present II.vnilable as to the prevalence oC tuberculosis in the first-born points in the words of W. C. Rivers, .. hack to <1iathesis" [7]. Dut wha.t is diathesis? [1] II. BRltllWER. Berlin, 18B5. I I Die Actio. Jogie der chronischen Luugenschwlud, sucht." (2J K. PltAaSON. London, 1907. I I A l"irst Study of tho StAtistics of Pulmonary
Tuberculosis." [3] S. HA~IlIl:N. Copenhagen, 1915. "Med· 'deJellier fro. Den Antropologiske Komlte," (4J D. F. WEEKS. London, 1912. .. The Inheritance of Epilepsy: Problems In Eugenics. "I [5] S. HAN9EN. Copenhagen,1920. .. Tuber. kulosen og de FijrsWidte Blirn.," UgtJkrijt J
o
PO~IUon."
lUXATION OF COMPLEMBNT IN TUBERCULOSIS. Fixation of complement is the order
oC the day in every modern bacteriological laboratory. We employ it in resea.rch in almost every bacterial and protozoal disease with varying success. In tho cuse of syphilis the reaction has now passed the experimental stage, and is more or less standardisod in method. In the case of bacterial dlseases, however, hope of succoss is still deferred. It may Le that there is some inherent difference between 11Il,cterial and protozoal protoplasm-its "ohlivionr Is certainly very different as regards reaction to drugs. Wha.tever be the explanation, it is clear that fIxation of complement with 0. nonspecific lecithin compound as antigen, nnd 1\ syphilitio serum o.s antibody, is II different proJlosition from that of 1\ tubcrculous . antigen and antibody reaction. Hxntion of complement in tuborculosh~ has now been tested fairly extenlively since Wassermann and Druck's
523
early and rather disappointing efforts. A large number of publications have appeared during the last five or six yoMs, most of them exploring the question of the composition of the antigen. A recent article by Petroff" has helped to curry the inquiry still further. It is n. closely reasoned account of tho difficulties which confront the serologist in this field of work. He rightly emphasises the fa.ct that complement fixation in tuberculosis cannot be compared with the ' Wassermann test even though both reactions may ultimately prove to be colloidal in nature. In reviewing tho whole question at least four problems confront us. In tho first place we require an antigen which is sufflciently sensitive to detect early active cnses, but which wiII not react with arrested cases. Petroff divides up his antigena into four groups: (1) Suspensions of tubercle bacilli living or dend, intact or pulverised; (2) filtrates of broth cultures of tubercle bacilli (e.g., Besredka's antIgen, potato filtrate, and old tuberculin); (3) ether-alcohol extracts of bacilli; and (4) extracts of tuberculous organs. lie has taken great care in the preparntion of these antigen" especially in endeavouring to obtain pure Iipins by ether-alcohol extraction, and finda methyl alcohol much moro satisCuctory than the ethyl alcohol commonly used. Petroff believes that positive results can be obtained with any tuberculous antigens, and furthermore makes the suggosth'o remark tho.t "prohably this means that any antigen representing in its phyeico-chcmieal state II. ·proper dispersed phase is a good antigen." From a. comparative .table we learn that ~ glycerin extro.ct of iho whole tubercle bacilli gives the best results. Secondly, n. method of performing tho test is required which will give us some quantitative estimation of tho reaction. This of course involves elaborate standardlsatlon of method and cannot be satisfactorily carried out in the present stato or our knowledge of tuberculous antigens and antibodies. Thirdly, wo need 0. test which will not ho confused with fixation of 0. comI Am,r. Rev. 01 Tub., 10~0, 3, GR3.
521
'.tUBERCLE '
plemen t in any other disease, especially syphili s. This means tho.t, for the presen t at any rate, all comple ment jixation tests ,for tubercu losis must be contro lled by 0. Wasse rmann test, and of course such 00 proceeding greo.tly adds to tho labour s of the bacteriologist unless be is working in conjun ction with other serologlats. Fourth fy, any test ueviseu must posses s technic al precision withou t on the other hand being too complicated for routine use. On this ground Petroff has render ed good service. IIo has exercised great care in obtaini ng the best possible labora tory conditi ons as to prepar ation of salt solutio n, cleansi ng or glass ware, storing of sera, standa rdisati on and pooling of comple ment. Efforts to separa te the tuberc ulous antibo dy from serum have not 'yet roache d the stage of publicatio n, but the author is investi gatins the point. He believes in commo n with most scrolog ists that these antibo dies are carried down with the Slobulin
portion.
On tho mecha nism ot tho reactio n Petroff has much of interes t to discuas. As might be expected he inclines strong ly to the view that the antigen untlbody-com plemen t reactio n is an elaborato colloidul systom in which comple ment pla.ys the IJllrt of an absorp tion phenom enon. Finally , and by no moans least import ant, Petroff issues '0. word of 'warn ing as to the clinical interpreta.tion or comple ment fixation results . This warnin s might be taken to heart hy cllnlclans and pathol ogists alike. Pathol ogists' reports offer no royal road to diugnosia. Each in hls own way must tread the pninlu l l)ath of practic al experience. Otherw ise the search for a. moans of carly diagnosis in tuborc ulosis will contin ue to be in the future what it has been in the past, 0. Ions experience in diaillusion mont.
(August,'102 0 .. AS YOU WERE ."
In the March numbe r of the ...1merithere is an editori al annota tion by Dr. Allen 1\. Krause in which he tn.kes stock of tho presen t positio n in Americo. and compares it with that of ten yeo.rs ago. Ie his views expres s the genera l consen sus of expert tuberc ulosis opinio n in tho U.S.A., we are confro nted with the fact that the problem of tuberc ulosis is being tackled beyond the Atlant ic on lines strikin gly diverg ent from those along which the campa ign in this countr y is being conduc ted. I ndeed , this divergence seems so marke d that there is little prospe ct of these lines meeting. howev er much the~' mo.y he prolonged. Dr. Krause write s:II • • • could our depart ed heroes or tuborc ulosis of only ten )'ellrs al:0 scan its (Thc Amcrican Rexieu: of T"btrculosis) pnges, they would perforce ruh their eyes. For thoir tUborculoslll proble ms have slunk to the rear. Tbo tubercl e bacillu s is no longer tuberculosis i it has become 0. mere inciden t of tuberc ulosis . . That tubercle bacilli are in men no lon,:::cr hurries a. chill down our spine. This fact we have come to accep t-just 0.8 we accept our sins, our hates and our lusts, our coveto usness and our pride. )Iora\ science cannot deny their existen ce: good morals deman d that they lie dormn.nt nnd concea led . . . Brush Ul) {or an hour on the tuberc ulosis oxhort ationa that ushere d in the centur y and promis ed to the popula ce 0. new world. How? lly slaugh tering cattle, h}' nboHshing spittin g, and by tcachin~ and taking care of tho sick for 0. row month s. But human nature is can. tankor ous. Its human right to spit far and wide will not be yielded to 0. shadow y peril . . . the kor to tho problem HQS buried in the condit ion ct tho social mass: in urban and rura] general health and sanitat ion, in Wl\ge~ and the cost or commo dities, in hoUsin~ and in rents, in hours of work, o.ntl ideals and habits of play and rccron_ tion. . . . It is his reactio n to hill (the pa.tient's) enviro nment tha.t brin~!'t him to the sanato rium; it is his reactio n
cd11. llcvietv of Tuberculosis