Microbe Hunters

by Paul De Kruif

  He even went so far as to underestimate the importance of his exact fine searching, but at the end of his treatise he gave a clew to the more imaginative Roux and Behring who came after him. A strange man, this Loeffler! Without seeming to be able to make a move to do it himself, he predicted what others must find:

  “This bacillus stays on a little patch of dead tissue in the throat of a baby; it lurks on a little point under a guinea-pig's skin; it never swarms in millions—yet it kills! How?

  “It must make a poison—a toxin that leaks out of it, sneaking from it to some vital spot in the body. Such a toxin must be found, in the organs of a dead child, in the carcass of a guinea-pig dead of the disease—yes—and in the broth where the bacillus grows so well. . . The man finding this poison will prove what I have failed to demonstrate.” Such was the dream Loeffler put into Roux's head. . .

  2

  Four years later Loeffler's words came true—by what seemed an utterly silly, but what was surely a most fantastical experiment you would have thought could only result in drowning a guinea-pig. What a hectic microbe hunting went on in Paris just then! Pasteur, in a state of collapse after his triumph of the dog bite vaccine, was feebly superintending the building of his million-franc Institute in the Rue Dutot. The wild, half-charlatan Metchnikoff had come out of Odessa in Russia to belch quaint theories about how phagocytes gobble up malignant germs. Pasteurians were packing microscopes in satchels and hurrying to Saigon in Indo-China and to Australia to try to discover microbes of weird diseases that did not exist. Hopefully frantic women were burying Pasteur—he was too tired!—under letters begging him to save their children from a dozen horrid diseases.

  “If you will,” one woman wrote him, “you can surely find a remedy for the horrible disease called diphtheria. Our children, to whom we teach your name as a great benefactor, will owe their lives to you!”

  Pasteur was absolutely done up, but Roux—and he was helped by the intrepid Yersin who afterward brilliantly discovered the germ of the black death—set out to try to find a way to wipe diphtheria from the earth. It wasn't a science—it was a crusade, this business. It was full of passion, of purpose; it lacked skillful lying-in-wait, and those long planned artistic ambushes you find in most discoveries. I will not say Ėmile Roux began his searching because of this pitiful note from that woman—but there is no doubt he worked to save rather than to know. From the old palsied master down to the most obscure bottle wiper, the men of this house in the Rue Dutot were humanitarians; they were saviors—and that is noble!—but this drove them sometimes into strange byways far off the road where you find truth. . . And in spite of this Roux made a marvelous discovery.

  Roux and Yersin went to the Hospital for Sick Children—diphtheria was playing hell with Paris—and here they ran on to the same bacillus Loeffler had found. They grew this microbe in flasks of broth, and did the regular accepted thing first, shooting great quantities of this soup into an assorted menagerie of unfortunate birds and quadrupeds who had to die without the satisfaction of knowing they were martyrs. It wasn't particularly enlightened searching, this, but almost from the tap of the gong, they stumbled on one of the proofs Loeffler bad failed to find. Their diphtheria soup paralyzed rabbits! The stuff went into their veins; in a few days the delighted experimenters watched these beasts drag their hind legs limply after them; the palsy crept up their bodies to their front legs and shoulders—they died in a clammy, dreadful paralysis. . .

  “It hits rabbits just the way it does children,” muttered Roux, full of a will to believe––“This bacillus must be the true cause of diphtheria. . . I shall find the germ in these rabbits' bodies now!” And he clawed tissues out of a dozen corners of their carcasses; he made cultivations of their spleens and hearts—but never a bacillus! Only a few days before he had pumped a billion or so into them, each of them. Here they were, drawn and quartered, carved up and searched from their pink noses to the white under-side of their tails. And not a bacillus. What had killed them then?

  Then Loeffler's prediction flashed over Roux: “It must be the germs make a poison, in this broth, to paralyze and kill these beasts. . . ” he pondered.

  For a while the searcher came uppermost in him. He forgot about possible savings of babies; he concentrated on vast butcheries of guinea-pigs and rabbits—he must prove that the diphtheria germ drips a toxin out of its wee body. . . Together with Yersin he began a good unscientific fumbling at experiments; they were in the dark; there were no precedents nor any kind of knowledge to go by. No microbe hunter before them had ever separated a deadly poison (though Pasteur had once made something of a try at it) from the bodies of microbes. They were alone in the dark, Roux and Yersin—but they lighted matches. . . “The bacilli must pour out a poison into the broth we grow them in—just as they pour it from their membrane in a child's throat into his blood!” Of course that last was not proved.

  Then Roux stopped arguing in a circle. He searched. He worked with his hands. It was worse, this fumbling of his, than trying to get a stalled motor to go when you know nothing about internal combustion machinery. He took big glass bottles and put pure microbeless soup into them, and sowed pure cultivations of the diphtheria bacillus in this broth; into the incubating oven went the large-bellied bottles––“Now we will try separating the germs from the soup in which they grow,” said Roux, after the bottle had ripened for four days. They rigged up a strange apparatus—it was a filter, shaped like a candle, only it was hollow, and made of fine porcelain that would let the soup through, but so tight-meshed that it would hold the tiniest bacilli back. With tongue-protruding care to keep themselves from being splashed with this deadly stuff, they poured the microbe-teeming broth around the candles held rigid in shiny glass cylinders. They fussed—maybe, or at least I hope so, with the blessed relief of profanity—but the broth wouldn't run through the porcelain. But at last they pushed it through with high air pressure—and finally they breathed easy, arranging little flasks full of a clear, amber-colored filtered fluid (it had never a germ in it) on their laboratory bench.

  “This stuff should have the poison in it. . . the filter has held back all the microbes—but this stuff should kill our animals,” muttered Roux. The laboratory buzzed with eager animal-boys getting ready the rabbits and guinea-pigs. Into the bellies of these beasts went the golden juice propelled from the syringe by Roux's deft hands. . .

  He became a murderer in his heart, this Ėmile Roux, and in his head as he came down to the laboratory each morning were half-mad wishes for the death of his beasts. “The stuff should be hitting them by now,” you can hear him growling to Yersin, but they looked in vain for the ruffled hair, the dragging hind legs, the cold shivering bodies to tell them their wish was coming true.

  It was beastly! All of this fussing with the delicate filter experiments—and the animals munched at the greens in their cages, they hopped about, males sniffed at females and engaged in those absurd scufflings with other males which guinea-pigs and rabbits hold to be necessary to the propagation of their kind. . . Let these giants (who fed them well) inject more of this stuff into their veins, their bellies—poison? Imagination! It made them feel happy. . .

  Roux tried again. He shot bigger doses of his filtered soup into the animals, other animals, still more animals. It was no go, there was no poison.

  That is, for a merely sensible man there would have been no poison in the filtered soup that had stood in the incubator for four days. Hadn't enough animals been wasted trying it? But Roux (let all mothers and children and the gods caring for insane searchers bless him!) was no reasonable man just then. For a moment he had caught Pasteur's madness, his strange trick of knowing what all men thought wrong to be right, his flair for good impossible experiments. “There is a poison there!” you can hear that hawk-faced consumptive Roux shout to himself, to the dusty, bottle-loaded shelves of his laboratory, to the guinea-pigs who would have snickered—if they could have—at his earnest futile efforts to murder them. �
��There must be a poison in this soup where the diphtheria germs have grown—else why should those rabbits have died?”

  Then—I have told scientific searchers about this and they have held their noses at such an experiment—Roux nearly drowned a guinea-pig. For weeks he had been injecting more and more of his filtered soup, but now (it was like facing a night on a park bench with your last dime on the two dice) he injected thirty times as much! Not even Pasteur would have risked such an outlandish dose—thirty-five cubic centimeters Roux shot under the guinea-pig's skin and you would expect that much water would kill such a little beast. If he died it would mean nothing. . . But into the belly of a guinea-pig and into the ear-vein of a rabbit went this ocean of filtered juice—it was as if he had put a bucketful of it into the veins of a middle-sized man.

  But that was the way Roux carved his name on those tablets which men while they are on earth must never allow to crumble; for, though the rabbit and the guinea-pig stood the mere bulk of the microbe-less broth very-well, and appeared perfectly chipper for a day or so afterwards, in forty-eight hours their hair was on end, their breath began to come in little hiccups. In five days they were dead, with exactly those symptoms their brothers had, after injections of the living diphtheria bacilli. So it was that Ėmile Roux discovered the diphtheria poison. . .

  By itself this weird experiment of the gigantic dose of feebly poisonous soup would only have made microbe hunters laugh. It was scandalous. “What!—if a great flask of diphtheria microbes can make so little poison that it takes a good part of a bottle of it to kill a small guinea-pig—how can a few microbes in a child's throat make enough to do that child to death? It is idiotic!”

  But Roux had got his start. With this silly experiment as an uncertain flashlight, he went tripping and stumbling through the thickets, he bent his sallow bearded face (sometimes it was like the face of some unearthly bird of prey) over a precise long series of tests. Then suddenly he was out in the open. Presently, it was not more than two months later, he hit on the reason his poison had been so weak before—he simply hadn't left his germ-filled bottles in the incubator for long enough; there hadn't been time enough for them really to get down to work to make their deadly stuff. So, instead of four days, he left the microbes stewing at body temperature in their soup for forty-two days, and when he ran that brew through the filter—presto! With bright eyes he watched unbelievably tiny amounts of it do dreadful things to his animals—he couldn't seem to cut down the dose to an amount small enough to keep it from doing sad damage to his guinea-pigs. Exultant he watched feeble drops of it do away with rabbits, murder sheep, lay large dogs low. He played with this fatal fluid; he dried it; he tried to get at the chemistry of it (but failed); he got out a very concentrated essence of it though, and weighed it, and made long calculations.

  One ounce of that purified stuff was enough to kill six hundred thousand guinea-pigs—or seventy-five thousand large dogs! And the bodies of those guinea-pigs who had got a six hundred thousandth of an ounce of this pure toxin—the tissues of those bodies looked like the sad tissues of a baby dead of diphtheria. . .

  So it was Roux made Loeffler's prophecy come true; it was that way he discovered the fluid messenger of death which trickles from the insignificant bodies of diphtheria bacilli. But he stuck here; he had explained how a diphtheria germ murders babies but he had found no way to stop its maraudings. There was that letter from the mother—but Roux's researches petered out into various directions to doctors how to grow germs pure out of children's throats at the bedside, and into suggestions for useful gargles. . . He hadn't Pasteur's tremendous grim stick-to-itiveness, nor his resourceful brain.

  3

  But away in Berlin there toiled another Ėmile—the Germans leave off the last “e”—Emil August Behring. He worked in Koch's laboratory, in the dilapidated building called the “Triangel” in the Schumann street. Here great things were stirring. Koch was there, no longer plain Doctor Koch of Wollstein, but now a Herr Professor, an eminent Privy Councilor. But his hat still fitted him; he peered through his spectacles, saying little; he was enormously respected, and against his own judgment he was trying to convince himself he had discovered a cure for tuberculosis. The authorities (scientists have reason occasionally to curse all authorities no matter how benevolent) were putting pressure on him. At least so it is whispered now by veteran microbe hunters who were there and remember those brave times.

  “We have showered you with medals and microscopes and guinea-pigs—take a chance now, and give us a big cure, for the glory of the Fatherland, as Pasteur has done for the glory of France!” It was ominous stuff like this Koch was always hearing. He listened at last, and who can blame him, for what man can remain at his proper business of finding out the ways of microbes with Governments bawling for a place in the sun—or with mothers calling? So Koch listened and prepared his own disaster by telling the world about his “Tuberculin.” But at the same time he guided his youngsters in fine jobs they were doing—and among these young men was Emil August Behring. How Koch pointed the gun of his cold marvelous criticism at that poet's searchings!

  And what a house of microbe hunters it was, that dingy Triangel! Its walls shook under the arguments and guttural cries and incessant experiments of Koch's young men. Paul Ehrlich was there, smoking myriads of cigars, smearing his clothes and his hands and even his face with a prismatic array of dyes, making bold experiments to find out how baby mice inherit immunity to certain vegetable poisons from their mothers. . . Kitasato, the round-faced Japanese, was shooting lock-jaw bacilli into the tails of mice and solemnly amputating these infected tails—to see whether the creatures would perish from the poisons the microbes had made while the tails were still attached. . . And there were many others there, some forgotten and some whose names are now famous. With a vengeance the Germans were setting out to beat the French, to bury them under a vast confusion of experiments, to save mankind first.

  But particularly, Emil Behring was there. He was a little over thirty; he was an army doctor; he had a little beard, neater than Koch's straggly one, but with less signs of originality. Just the same Behring's head, in spite of that prosaic beard, was the head of a poet; and yet, though he was fond of rhetoric, no one stuck closer to his laboratory bench than Behring. He compared the grandeur of the Master's discovery of the tubercle bacillus to the rosy tip of the snow-capped peak of his favorite mountain in Switzerland, while he probed by careful experiments into why animals are immune to microbes. He compared the stormy course of human pneumonia to the rushing of a mountain stream, while he discovered a something in the blood of rats—this stuff would kill anthrax bacilli! He had two scientific obsessions, which were also poetical: one was that blood is the most marvelous of the juices circulating in living things (what an extraordinary mysterious sap it was, this blood!)—the other was the strange notion (not a new one) that there must exist chemicals to wipe invading microbes out of animals and men—without hurting the men or the animals.

  “I will find a chemical to cure diphtheria!” he cried, and inoculated herds of guinea-pigs with cultivations of virulent diphtheria bacilli. They got sick, and as they got sicker he shot various chemical compounds into them. He tried costly salts of gold, he tried naphthylamine, he tested more than thirty different strange or common substances. He believed innocently because these things could kill microbes in a glass tube without damaging the tube, they would also hit the diphtheria bacilli under a guinea-pig's hide without ruining the guinea-pig. But alas, from the slaughter house of dead and dying guinea-pigs his laboratory was, you would suppose he would have seen there was little to choose between the deadly microbes and his equally murderous cures. . . Nevertheless, being a poet, Behring did not have too great a reverence for facts; the hecatombs of corpses went on piling up, but they failed to shake his faith in some marvelous unknown remedy for diphtheria hidden somewhere among the endless rows of chemicals in existence. Then, in his enthusiastic—but random—search he came upon t
he trichloride of iodine.

  Under the skins of several guinea-pigs he shot a dose of diphtheria bacilli sure to kill them. In a few hours these microbes began their work; the spot of the injection became swollen, got ominously hot, the beasts began to droop—then, six hours after the fatal dose of the bacilli, Behring shot in his iodine tri-chloride. . . “It is no good, once more,” he muttered. The day passed with no improvement and the next morning the beasts began to go into collapses. Solemnly he put the guinea-pigs on their backs, then poked them with his finger to see if they could still scramble back on their feet. . . “If the guinea-pig can still get up when you poke him, there may be yet a chance for him,” explained Behring to his amazed assistants. What a test that was—think of a doctor having a test like this to see whether or no his patient would live! And what an abominably crude test! Less and less the iodine-treated guinea-pigs moved when he poked them—there was now no longer any hope. . .

  Then one morning Behring came into his laboratory to see those guinea-pigs on their feet! Staggering about, and dreadfully straggly looking beasts they were, but they were getting better from diphtheria, these creatures whose untreated companions had died days before. . .

  “I have cured diphtheria!” whispered Behring.

  In a fever he went at trying to cure more guinea-pigs with this iodine stuff; sometimes the diphtheria bacilli killed these poor beasts; sometimes the cure killed them; once in a while one or two of them survived and crawled painfully back to their feet. There was little certainty of this horrible cure and no rime or reason. The guinea-pigs who survived, probably wished they were dead, for while the tri-chloride was curing them it was burning nasty holes in their hides too—they squeaked pitifully when they bumped these gaping sores. It was an appalling business!