The San Francisco Call. Newspaper, June 5, 1898, Page 18

SAN FRANCISCO, SUNDAY, JUNE 5, 1898. . CURE FOR DREADE Dr. Pillsbury of the Cooper Medi- cal College has at last succeeded in finding and separating the poison of the bacilli of tubercu- losis after years of careful ex- periments. T last the alkaloid of bacilll tu- berculo: has been discovered. T is another great step toward the production of a cure for the dreaded white plague, mption, and unless all chemiial turn out to be erroneous will make in the history of medical sci- con laws an era ence. The wonde n who has accomplished this 11 achivement is Dr. Ernest S. ictor in bacteriology of 1 College, this city. He has been working on his theory for several years, and now feels that as accomplished something that'is resuits beneficial to sure to produc the human race. “I do not claim to have produced a ure for consumption,” said Dr. Pills- , “but I do claim to have isolated poison that produces such deadly v I cannot find any record of body else ever having done this be rom lobster is much more deadly than consumption. In combating this ptomain poisoning medical science sim- ply makes use of the old and well un- derstood chemical law of “poison and antidote,” which In reality is nothing more than a certain manifestation of nature's law—balance. The nature of ptomain poison be- ing known the antidote has already been found and whenever it is admin- istered before the patient is in his ath agony” a cure follows just as certain as the administering of quinine cures certain fevers by acting as an antidote to the poison produced by the malaria baclili. It is on these lines that the dreaded diphtheria is cured. The so-called antitoxin that is injected into the pa- tient is nothing more nor less than the antidote for the poison that causes the disease. It is on exactly these same lines that BACILLI OF TUBERCULOSIS MAGNIFIED I1250 TIMES. Tubercular Nodule in Liver of a Guinea Pig Showing Effect on the Tis- sue of the Poison Generated by Tubercle Bacilli. From growth made on a subject by Dr. E. Pillsbury. fore, so I feel that I can claim the right of discovery. “My future work will be along lines that have been proved to be ccessful in’other deadly diseases, diphtheria for instance. “‘Of course it may take me a long time to find out the exact nature of the poison I have isolated, and on the other hand, I may do it in a few weeks. After that to figure out an antidote should not be such a very di ult matter. Chemical laws are pretty well under- stood, and when a certain component is known we can always fizure out what will neutralize it. It has ver failed yet.” In order that the lay mind may fully grasp the importance and meaning of Dr. Pillsbury’s discovery some expla- nation will be necessary. The ordinary concept in which the deadly b: lus does its work’ is that it simply destroys the fleshy tissue, much after the fashion of chewing or tearing. But while this is done to a great extent death always results long before enough of the tissue disappears to have produced death. Add to this the condition and general appearance of a consumptive patlent and everything points to the work of poison that has been generated by the bacilli. This same phenomenon has already been observed in other forms of bac- terlal poisoning, and it is pretty well understood and can be combated to a certaln extent. This form of poisoning is called “Ptomain poisoning,” and the difficulty of curing it lies entirely in the fact that it Is -so rapid in Its work the patient frequently dies before a doctor can be summoned. The ptomain is the poi- son generated by the bacilli that have come into existence In decomposing meat or fish—the most deadly variety being found in shell fish. If-this poison is injected into any liv- ing vreature and the known antidote ministered within a few minutes no evil results will follow. But if the pa- tient ‘'be neglected for even a few hours death is almost certain. On this basis, common ptomain pols- n of the way 0000000000000 0000000000000000000000 DR. ROSENAU’S OPINION OF THE DISCOVERY. Only results can show that. timate. before.” 0000000000000 “Dr. Pillsbury has certainly made a most important discovery, but o1 its relative importance we cannot of course judge at present. Should it prove the means of discov- ering a cure for consumption its importance is of course beyond es- There have been a ‘umber of extracts made from the pure bacilli, but I never heard of anybody ever making a pure alkaloid QOOO‘OOOOOOOOOOOOQOOOOOOOOD°°°°°°°°° Dlj. Pillsbury hopes to be able to ob- tain a cure for consumption, and it mi{fl admitted that chemical sclence poi to the ultimate success of his work. ’1_'110 discovery and isolation of the poison, or alkaloid, is surely the first step toward finding an antidote, What this will be in the case of-baeilli tuberculosis poison cannot, be even guessed at just at the present stage of development. It may be or- ganic or it may be inorganic. . of course, e It may some simple alkaloid of the same character as genuine, or it may be some form of antitoxin similar to that n1r\\v 80 successfully used in diphthe- ria. The principal difference between 0000000000000 OOOOO HOW TO ISOLATE BACILLI TU with hydrochloric acid. Baryta water. ide. state. tuberculosis. 000000000000 00000000O0 ©00000000000000000 what Dr. Pillsbury hopes to do and what has been so unsuccessfully at- tempted in the past is that his plan is on the lines of neutralizing the poison that produces death, while all other methods have simply been on the anti- septic principle—i. e., an’ effort to de- stroy the bacilli themselves, entirely ig- noring the fact that the tiny organisms o o [ o o o o o o ] o o o o o According to Dr. Pillsbury’s method. The pure washed bacilli culture is washed in water acidulated It is then washed again in pure re-dis- tilled alcohol and then filtered. The fili1ats is then distilled and the residue dissolved in water and p-ecipitated with phosmolybdic acid. Again the product is filtered and the residue broken up with The barium is then precipitated with carbon diox- The filtrate is then evaporated and the residue exhausted with alcchol, which gives the alkaloid in a comparatively pure It is now in the form of white crystals and answers all the usual tests for alkaloids, such as chloride of gold, chloride of platinun, etc., leaving no doubt but that it is the pure alkaloid of ! bacilli i == k] E N S S ST TR S [oJoXoXoXoXOROROROROROROJOOXOJOKO) THE DISCOVERY OF THE ALKALOID OF BACILLUS TUBERCULOSIS. [CXCROXOROXOYOROXOYOROROXOXOROXOKOXO) Puts the Method of Curing Consumption on a Scien- tific Basis—The Disease Can Now Be Studied in the Same Manner as Other Diseases That Are Cured Successfully. Heretofore the Attempts to Cure the Deadly White Plague Have Been Made in the Dark. NOW IT IS OKLY NECESSARY TO [} @® ® ® ® ® ® ® ® ® @ (O] ® [0} ® @ (d © ® ® ® ® FIND AN ANTIDOTE, o ® V.hich Is Almost Sure to @ Be Done in a Short ® Time. ® @® ® © [0JoXOXOJOXOXOROROXOXOXOROROXOROIO] IETIRY I B R R R produced and left in the system any [CJCJOROXOROJOJOXOJOXOJOROXOXOROROJOJOROXCYOXOXOXOXOJOXOXOIO YO XOlo Yo YoYo JoyoJoro oo oo Ioroo o Xoxo) poison. Dr. Pillsbury’s theory will account for the cause of consumptive patients dying even after bacilli had.apparently disappeared from the organism. In making his experiments in his lab- oratory at Cooper Medical College Dr. OOOOOOOOOOOOOOOOOOOO THE ALKALOID OF BERCULOSIS. 000000000000 00D0O00O0OD0O0D0O0O00O 0000000000000 000O0O Pillsbury has used billions and billions of bacilli tuberculosis. In order to get enough -even to make a small test it was necessary to breed them just as a farmer would breed chickens or pigs. This process simply consists of in- Jecting a small number of the living bacilli into a specially prepared veal broth and keeping it at a temperature of about 100 degrees. From the tiny speck at first visible in the compound the microbes spread all through the mass of broth in a few weeks. They were then washed out with al- cohol and water and put into a large Jar for future use. Of course this washing kills them, but it leaves with them all of their or- ganic elements. In this condition the mass of bacilli looks like a jar of corn meal and can be handled in much the same manner. It is from this that the alkaloid is produced. Dr. Pillsbury’s method of preparing the alkaloid, mx polson left o) INSTRUCTOR MPTION IS IN SIGHT O IN BACTERIOLOGY, COOPER [ DR. ERNEST S. PILLSBURY, MEDICAL COLLEGE, IN HIS LABORATORY. Dr. Pillsbury is the man who is entitled to the honor of having made cne of the most important bacteri- ological discover’es of the decade. opened the dcor to the finding of a cure for consump ion, the dreaded white plague. now nearer at hand than ever befor:. tests has bred billions of bi lions of bacilli tuberculosis. in the system by the bacilli, is as fol- lows: The pure washed bacilli cul- ture is washed in water acidu- lated with hydrochloric acid. is then washed again in pure re-distilled alcohol and filtered. The filliate is then distilled and the residue dissolved in water and precipitated with phospho- molybdic acid. Again the product is filtered en up with barium is with carbon te is then sidue ex- which Baryta wa then precip i de. . Th ed with ated filtr: nd the r alcohol, hausted glves the alkaloid in a compara- tively pure state. 1t is now in the form of white crystals and answers all the usual tests for alkaloids, such as chloride of gold, chloride of plat- inum, ete., leaving no doubt but that it is the pure alkalcid of bacilli tuberculosis. As a still further proof that it is the alkaloid of the bacilli tuberculosis, Dr. Pillsbury injected a small amount of it into a guinea pig, and although there was not the slightest trace of the or- ganism in the mixture, the animal dis- played all the symptoms of consump- tion. A number of scientific medical men in this city were questioned in regard to what they thought of Dr. Plllsbury’s discovery, and while a few were in- clined to be skeptical of the ultimate result, all agreed that the discovery was a most important one and almost sure to lead to beneficial results. Dr. Gustav Eisen of the Academy of Sciences thought the discovery of the alkaloid almost as important as the discovery of the bacilli itself. Reason- ing from our present chemical knowl- edge it is the most important step toward a cure for consumption that has ever been made. Dr. Roseneau of the Governraent Quarantine Station said: “Dr. Pills- bury has certainly made a most in- portant discovery, but of its relative fmportance we cannot of course judige at present. Only results can show that. Should it prove the means qf discev- ering a cure for consumption its fin- portance is of course beyond estimate. There have been a number of extracts made from the pure bacilll, but I never heard of anybody ever making a pure alkaloid before.” Dr. Pillsbury realizes that he has a big task before him to figure .ut the nature of and the antidote for the alkaloid he has discovered. But he makes no secret of his work, and is ornly anxious that others shall take it up, and the sooner a cure for consump- tion is discovered the sooner humanity will be benefited. Following is a technfcal paper writ- ten for The Call by Dr. Pillsbury,giving his reascns for thinking that he is on the right road toward the discovery of a cure for consumption: T is now known that instead of bac- teria being harmful from their con- suming to any marked extent the proteids of the organism and there- any of the organs of istenance, the patho- acteria is due to the chemical products of their metabolism, a soluble chemical fer- ment w p the complex pro- telds of its yme of the spiit pro- ducts bein snous, or the L cell may conts specific poison as a tion or excretion, a product of assimila- tion. It should not be hard for us to realize that these little plants may produce poi- sons that have such powerful effects when we realize the favorable conditions of the sofl and temperature of their suscep- tible host, both being ideal conditions for , the rapid muitiplication of bacteria. The ‘“period of incubation” fectious disease is the time required from the inception of the few bacterla of variable virulence for them to over- come the natural resistance of the host and produce, in their peculiar way, suffi- cient poison to cause systematic disturb- ances. Some of these chemical products com- bine with certain forming salts— such products are ptomaines or bacterial alkaloids. If the word ptomaine was dropped and instead the term bacterial alkaloids used. their composition would not seem quite so indefinite to so many; for the better known alkaloids derived from the higher plants as atropine from the bellndonnae, strychnine from the seed of strychnos, nux vomica, or mor- phine from the poppy, are in daily use, and their effects pretty well understood. The bacterial alkaloids are, like the al- kaloids of the higher plants, variable in their action in different individuals of a specles and, of course, vary greatly in their effects upon the different genera of the animal kingdom. As an instance of this I ean cite S. ‘Weir Mitchel, who has shown that many birds are insusceptible to the toxic action of opium, while a single drop of the aqueous extract will throw a sparrow into a profound stupor. Guinard has shown that in the cat morphine produces violent hyperexcitability, great restiessness, agi- tation, hallucinations, dilated pupils, and if the dose be very large tetanic convul- slons develop. Harley found that on dogs morphine acts much as upon man. In the horse two to three grains of morphine produce sometimes a slight drowsiness, sometimes no perceptible effect. This instance of so famillar a drug varying so in its action on different ant- mals shows us that even leaving out the question of sultability of soll and assum- ing what is not so, that all animals offer similarly favorable conditlons for the de- velopment of bacteria, we can with good reason assume that the poisons developed of an in- by the so-called pathogeuic bacteria af-- fect only such animals as are susceptible to the action of their specific poisons. Rabbits have a great natural resistance to the action of tuberculosis. Two white rabbits T inoculated in October, 1897, re- inoculated in November and again in Jan- uary with very virulent cultures of the tubercle bacilli did not succumb. One killed in March, the other in May, showed only slight tubercular lesions at the points of injection. Guinea pigs inoculat- ed with the same cultures died In twenty and twenty-three days with tubercles dis- seminated throughout the abdominal cav- ity. Other instances may be given almost without end and all confirm the theory effects of nfectious dis- elaborate experi- mentation that an may become ac- customed to various well-known poisons by the administration of gradually in- creased doses and that the serum taken from these animals and injected into a normal animal together with an otherwise fatal dose of the same poison will so nul- lify its poisonous effects that the second animal will be unharmed. Further, suc- cessive injections of serum from such ac- customed or immunized antmals will pro- duce a condition of immunization against this same poison. What this ‘“defensive proteld” sub- stance is that is generated in the blood to produce this immunity. to, or neutraliza- tion of, the poison is not yet known, but its effect is that of a chemical and physio- logical antidote. This is also shown by Nuttall and Lubarsh, who found that the bactericidal power of the animal serum did not correspond to the immunity of thas animal furnishing the serum. Now since it has been shown that the effects of infectious diseases are due to the bacterial alkaloids in some Instances at least and perhaps ferments In others, does it not follow that the scientific treat- ment of such diseases would consist in the administration of the chemical and physiological antidotes of the specific al- kalold, the prevention of reinfection by the local use of antiseptics, and the scien- tific nourishment of the body? Neurin is an Interesting poisonous bacte- rial alkaloid. In frogs very small amounts cause complete paralysis of the extremi- ties. The heart beats more and more slowly and finally stops In diastele. If at this point atropine be Injected the heart Dbegins to beat again. Behring made a great stride when he used the serum of an animal immunized against the diphtheria poison to neutral- ize an infection of diphtheria fn another animal; but his followers incorrectly translated his discoveries—thought he had cured the diphtheria by killing the diph- 0000000000000 00000000O000O00NO0000000000 WHAT DR. EISEN THINKS. 0000000000 “I think the discovery of the alkaloid almost as important as the discovery of the bacilli itself. Reasoning from our present chem- ical knowledge it is the most important step toward a cure for con- sumption that has ever been made.” 000000000000000000000000Q0QQ0000000O0 In isclating the zlkalod, or active principal, of bacilli tuberculosis he has Scientifically a cure is Dr. Pillsbury has worked years at his theory and in order to make his theria bacilli by the germicidal action of the serum. So we have ‘‘Aseptolin-Ed- son” and like antiseptic mixtures. The folly of such solutions is apparent when we realize that to inject sufficient to make the blood a germicidal solution it would be death to the blood. Koch thought to cure consumption by gradually increased doses of a crude solu- tion of the very poison produced by the bacillus tuberculosis and to produce an immunity such as may be done with the self-limited infectious diseases. If it was possible to do this with consumption the patient should get well of himself, for surely the disease lasts long enough. But this has been found to be impossible ~it would be like injecting morphine into a “dope” fiend. Injecting sufficient tubercle bacilli—even dead ones—into animals which have been considered immunized against tubercu- losis produces the characteristic abcess, and proves that Killing the bacteria is not sufficient to cure the disease. The many preparations of serum, such as “Anti-tubercle Serum,” “Anti-phthisic Serum” and similar so-called consumption cures taken from the horses and mules which recelved repeated injections of crude tuberculine for the purpose of pro= ducing an artificial immunity are no bet~ ter. than similar serums taken from white rabbits which have as much natural im- munity as is acquired by these horses and mules. T believe consumption, the terrible white plague, is curable, but not on that basis. I have separated by a modification of Sonnenschein’s process an alkaloid from tubercle bacilli in pure culture, but so far have not separated sufficient for full testing. When the physiological effects of the pure alkaloid are known it will be an easier step to produce its antidote, which may be organic or inorganic. Syphills is a disease having many points in common with tuberculosis in its path- ological lesions, but it is considered cur-~ able, and justly so. Its antidote has been discovered, accidently perhaps, but still we have a specific for the disease. In quinine we have an antidote for the toxine produced by the malarial para- site. 1 belleve the day is not far distant when the physician will diagnose the infectious disease to which he is called, not by the fever chart but by a chemical analysis of the urine, which carries off these bacterial alkaloids in solution, and he will treat and cure his patient by the hypodermic administration of the physio- logical and chemical antidotes of the known bacterial alkaloids. ERNEST S. PILLSBURY, M.D. Curator of Bacteriology, Cooper Medical College. Q0000000000 ] i