Microbe Hunters

by Paul De Kruif

  But he did make a magic bullet! Alchemist that he was, he did something more outlandish than that, for he changed a drug that is the favorite poison of murderers into a saver of the lives of men. Out of arsenic he concocted a deliverer from the scourge of that pale corkscrew microbe whose attack is the reward of sin, whose bit is the cause of syphilis, the ill of the loathsome name. Paul Ehrlich had a most weird and wrong-headed and unscientific imagination: that helped him to make microbe hunters turn another corner, though alas, there have been few of them who have known what to do when they got around that corner, which is why this history has to stop with Paul Ehrlich.

  Of course, it is sure as the sun following the dawn of to-morrow, that the high deeds of the microbe hunters have not come to an end; there will be others to fashion magic bullets. And they will be waggish men and original, like Paul Ehrlich, for it is not from a mere combination of incessant work and magnificent laboratories that such marvelous cures are to be got. . . To-day? Well, to-day there are no microbe hunters who look you solemnly in the eye and tell you that two plus two makes five. Paul Ehrlich was that kind of a man. Born in March of 1854 in Silesia in Germany, he went to the gymnasium at Breslau, and his teacher of literature ordered him to write an essay, subject: “Life is a Dream.”

  “Life rests on normal oxidations,” wrote that bright young Jew, Paul Ehrlich. “Dreams are an activity of the brain and the activities of the brain are only oxidations. . . dreams are a sort of phosphorescence of the brain!”

  He got a bad mark for such smartness, but then he was always getting bad marks. Out of the gymnasium, he went to a medical school, or rather, to three or four medical schools—Ehrlich was that kind of a medical student. It was the opinion of the distinguished medical faculties of Breslau and Strasbourg and Freiburg and Leipsic that he was no ordinary student. It was also their opinion he was an abominably bad student, which meant that Paul Ehrlich refused to memorize the ten thousand and fifty long words supposed to be needed for the cure of sick patients. He was a revolutionist, he was part of the revolt led by that chemist, Louis Pasteur, and the country doctor, Robert Koch. His professors told Paul Ehrlich to cut up dead bodies and learn the parts of dead bodies; instead he cut up one part of a dead body into very thin slices and set to work to paint these slices with an amazing variety of pretty-colored aniline dyes, bought, borrowed, stolen from under his demonstrator's nose.

  He hadn't a notion of why he liked to do that—though there is no doubt that to the end of his days this man's chief joy (aside from wild scientific discussions over the beer tables) was in looking at brilliant colors, and making them.

  “Ho, Paul Ehrlich—what are you doing there?” asked one of his professors, Waldeyer.

  “Ja, Herr Professor, I am trying with different dyes!”

  He hated classical training, he called himself a modern, but he had a fine knowledge of Latin, and with this Latin he used to coin his battle cries. For he worked by means of battle cries and slogans rather than logic. “Corpora non agunt nisi fixata!” he would shout, pounding the table till the dishes danced—“Bodies do not act unless fixed!” That phrase heartened him through thirty years of failure. “You see! You understand! You know!” he would say, waving his horn-rimmed spectacles in your face, and if you took him seriously you might think that Latin rigmarole (and not his searcher's brain) carried him to his final triumph. And in a way there is no doubt it did!

  Paul Ehrlich was ten years younger than Robert Koch; he was in Cohnheim's laboratory on that day of Koch's first demonstration of the anthrax microbe; he was atheistical, so he needed some human god and that god was Robert Koch. Painting a sick liver Ehrlich had seen the tubercle germ before ever Koch laid eyes on it. Ignorant, lacking Koch's clear intelligence, he supposed those little colored rods were crystals. But when he sat that evening in the room in Berlin in March, 1882, and listened to Koch's proof of the discovery of the cause of consumption, he saw the light: “It was the most gripping experience of my scientific life,” said Paul Ehrlich, long afterwards. So he went to Koch. He must hunt microbes too! He showed Robert Koch an ingenious way to stain that tubercle microbe—that trick is used, hardly changed, to this day. He would hunt microbes! And in the enthusiastic way he had he proceeded to get consumption germs all over himself: so he caught consumption and had to go to Egypt.

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  Ehrlich was thirty-four years old then, and if he had died in Egypt, he would certainly have been forgotten, or been spoken of as a color-loving, gay, visionary failure. He had the energy of a dynamo; he had believed you could treat sick people and hunt microbes at the same time; he had been head physician in a famous clinic in Berlin, but he was a very raw-nerved man and was fidgety under the cries of sufferers past helping and the deaths of patients who could not be cured. To cure them! Not by guess or by the bedside manner or by the laying on of hands or by waiting for Nature to do it—but how to cure them! These thoughts made him a bad doctor, because doctors should be sympathetic but not desperate about ills over which they are powerless. Then, too, Paul Ehrlich was a disgusting doctor because his brain was in the grip of dreams: he looked at the bodies of his patients: he seemed to see through their skins: his eyes became super-microscopes that saw the quivering stuff of the cells of these bodies as nothing more than complicated chemical formulas. Why of course! Living human stuff was only a business of benzene rings and side-chains, just like his dyes! So Paul Ehrlich (caring nothing for the latest physiological theories) invented a weird old-fashioned life-chemistry of his own; so Paul Ehrlich was anything but a Great Healer; so he would have been a failure—But he didn't die!

  “I will stain live animals!” he cried. “The chemistry of animals is like the chemistry of my dyes—staining them while they are still alive—that will tell me all about them!” So he took his favorite dye, which was ethylene blue, and shot a little of it into the ear vein of a rabbit. He watched the color flow through the blood and body of the beast and mysteriously pick out and paint the living endings of its nerves blue—but no other part of it! How strange! He forgot all about his fundamental science for a moment. “Maybe ethylene blue will kill pain then,” he muttered, and he straightway injected this blue stuff into groaning patients, and maybe they were eased a little, but there were difficulties, of a more or less entertaining nature, which maybe frightened the patients—who can blame them?

  He failed to invent a good pain-killer, but from this strange business of ethylene blue pouncing on just one tissue out of all the hundred different kinds of stuff that living things are made of, Paul Ehrlich invented a fantastic idea which led him at last to his magic bullet.

  “Here is a dye,” he dreamed, “to stain only one tissue out of all the tissues of an animal's body—there must be one to hit no tissue of men, but to stain and kill the microbes that attack men.” For fifteen years and more he dreamed that, before ever he had a chance to try it. . .

  In 1890 Ehrlich came back from Egypt; he had not died from tuberculosis; Robert Koch shot his terrible cure for consumption into him, still he did not die from tuberculosis—and presently he went to work in the Institute of Robert Koch in Berlin, in those momentous days when Behring was massacring guinea-pigs to save babies from diphtheria and the Japanese Kitasato was doing miraculous things to mice with lockjaw. Ehrlich was the life of that grave place! Koch would come into his pupil's crammed and topsy-turvy laboratory, that gleamed and shimmered with rows of bottles of dyes Ehrlich had no time to use—for you may be sure Koch was Tsar in that house and thought Ehrlich's dreams of magic bullets were nonsense. Robert Koch would come in and say:

  “Ja, my dear Ehrlich, what do your experiments tell us to-day?”

  Then would come a geyser of excited explanations from Paul Ehrlich, who was prying then into the way mice may become immune to those poisons of the beans called the castor and the jequirity:

  “You see, I can measure exactly—it is always the same!—the amount of poison to kill in forty-eight hours a mouse weighing t
en grams. . . You know, I can now plot a curve of the way the immunity of my mice increases—it is as exact as experiments in the science of physics. . . You understand, I have found how it is this poison kills my mice; it clots his blood corpuscles inside his arteries! That is the whole explanation of it. . . ” and Paul Ehrlich waved test-tubes filled with brick-red clotted clumps of mouse blood at his famous chief, proving to him that the amount of poison to clot that blood was just the amount that would kill the mouse that the blood came from. Torrents of figures and experiment Paul Ehrlich poured over Robert Koch—

  “But wait a moment, my dear Ehrlich! I can't follow you—please explain more clearly!”

  “Certainly, Herr Doktor! That I can do right off!” Never for a moment does Ehrlich stop talking, but grabs a piece of chalk, gets down on his knees, and scrawls huge diagrams of his ideas over the laboratory floor—“Now, do you see, is that clear?”

  There was no dignity about Paul Ehrlich! Neither about his attitudes, for he would draw pictures of his theories anywhere, with no more sense of propriety than an annoying little boy, on his cuffs and the bottoms of shoes, on his own shin front to the distress of his wife, and on the shirt fronts of his colleagues if they did not dodge fast enough. Nor could you properly say Paul Ehrlich was dignified about his thoughts, because, twenty-four hours a day he was having the most outrageous thoughts of why we are immune or how to measure immunity or how a dye could be turned into a magic bullet. He left a trail of fantastic pictures of those thoughts behind him everywhere!

  Just the same he was the most exact of men in his experiments. He was the first to cry out against the messy ways of microbe hunters, who searched for truth by pouring a little of this into some of that, and in that laboratory of Robert Koch he murdered fifty white mice where one was killed before, trying to dig up simple laws, to be expressed in numbers, that he felt lay beneath the enigmas of immunity and life and death. And that exactness, though it did nothing to answer those riddles, helped him at last to make the magic bullet.

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  Such was the gayety of Paul Ehrlich, and such his modesty—for he was always making; straight-faced jokes at his own ridiculousness—that he easily won friends, and he was a crafty man too and saw to it that certain of these friends were men in high places. Presently, in 1896, he was director of a laboratory of his own; it was called the Royal Prussian Institute for Serum Testing. It was at Starlit, near Berlin, and it had one little room that had been a bakery and another little room that had been a stable. “It is because we are not exact that we fail!” cried Ehrlich, remembering the bubble of the vaccines of Pasteur which had burst, and the balloon of the serums of Behring which had been pricked. “There must be mathematical laws to govern the doings of these poisons and vaccines and antitoxins!” he insisted, so this man with the erratic imagination walked up and down in those two dark rooms, smoking, explaining, expostulating, and measuring as accurately as God would let him with drops of poison broth and calibrated tubes of healing serum.

  But laws? He would make an experiment. It would turn out beautifully. “You see! here is the reason of it!” he would say, and draw a queer picture of what a toxin must look like and what the chemistry of a body cell must look like, but as he went on working, as regiments of guinea-pigs marched to their doom, Paul Ehrlich found more exceptions to his simple theories than agreements with them. That didn't bother him, for, such was his imagination, that he invented new little supporting laws to take care of the exceptions, he drew stranger and stranger pictures, until his famous “Side-Chain” theory of immunity became a crazy puzzle, which could explain hardly anything, which could predict nothing at all. To his dying day Paul Ehrlich believed in his silly side-chain theory of immunity; from all parts of the world critics knocked that theory to smithereens—but he never gave it up; when he couldn't find experiments to destroy his critics he argued at them with enormous hair-splittings like Duns Scotus and St. Thomas Aquinas. When he was beaten in these arguments at medical congresses it was his custom to curse—gayly—at his antagonist all the way home. “You see, my dear colleague!” he would cry, “that man is a shameless badger!” Every few minutes, at the top of his voice he yelled this, defying the indignant conductor to put him off the train.

  So, in 1899, when he was forty-five, if he had died then, Ehrlich would certainly still have been called a failure. His efforts to find laws for serums had resulted in a collection of fantastic pictures that nobody took very seriously, they certainly had done nothing to turn feebly curative serums into powerful ones—what to do? First, this to do, thought Ehrlich, and he pulled his wires and cajoled his influential friends, and presently the indispensable and estimable Mr. Kadereit, his chief cook and bottle-washer, was dismounting that laboratory at Steglitz—they were moving to Frankfort-on-the-Main, away from the vast medical schools and scientific buzzings of Berlin. What to do? Well, Frankfort was near those factories where the master-chemists turned out their endless bouquets of pretty colors—what could be more important for Paul Ehrlich? Then there were rich Jews in Frankfort, and these rich Jews were famous for their public spirit, and money—Geld, that was one of his four big “G's,” along with Geduld—patience, Geshick—cleverness and Glück—luck, which Ehrlich always said were needed to find the magic bullet. So Paul Ehrlich came to Frankfort-on-the-Main, or rather, “WE came to Frankfort-on-the-Main,” said the valuable Mr. Kadereit, who had the very devil of a time moving all of those dyes and that litter of be-penciled and dog-eared chemical journals.

  Reading this history, you might think there was only one good kind of microbe hunter: the kind of searcher who stood on his own absolutely, who paid little attention to the work of other microbe hunters, who read nature and not books. But Paul Ehrlich was not that kind of man! He rarely observed nature, unless it was the pet toad in his garden, whose activities helped Ehrlich to prophesy the weather—it was Mr. Kadereit's first duty to bring plenty of flies to that toad. . . No, Paul Ehrlich got his ideas out of books.

  He lived among scientific books and subscribed to every chemical journal in every language he could read, and in several he couldn't read. Books littered his laboratory so that when visitors came and Ehrlich said: “I beg you, be seated!” there was no place for them to sit at all. Journals stuck out of the pockets of his overcoat—when he remembered to wear one—and the maid, bringing his coffee in the morning, fell over ever-growing mountains of books in his bedroom. Books, with the help of those expensive cigars, kept Paul Ehrlich poor. Mice built nests in the vast piles of books on the old sofa in his office. When he wasn't painting the insides of his animals and the outside of himself with his dyes, he was peering in these books. And what was important inside of those books, was in the brain of Paul Ehrlich, ripening, changing itself into those outlandish ideas of his, waiting to be used. That was where Paul Ehrlich got his ideas—you would never accuse him of stealing the ideas of others!—and queer things happened to those ideas of others when they stewed in Ehrlich's brain.

  So now, in 1901, at the beginning of his eight-year search for the magic bullet he read of the researches of Alphonse Laveran. Laveran was the man, you remember, who discovered the malaria microbe, and very lately Laveran had taken to fussing with trypanosomes. He had shot those finned devils, which do evil things to the hind-quarters of horses and give them a disease called the mal de Caderas, into mice. Laveran had watched those trypanosomes kill those mice, one hundred times out of one hundred. Then Laveran had injected arsenic under the skins of some of those suffering mice. That had helped them a little, and killed many of the trypanosomes that gnawed at them, but not one of these mice ever got really better; one hundred out of one hundred died and that was as far as Alphonse Laveran ever got. But reading this was enough to get Ehrlich started. “Ho! here is an excellent microbe to work with! It is large and easy to see. It is easy to grow in mice. It kills them with the most beautiful regularity! It always kills mice! What could be a better microbe than this trypanosome to use to try t
o find a magic bullet to cure? Because, if I could find a dye that would save, completely save, just one mouse!”

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  So Paul Ehrlich, in 1902, set out on his hunt. He got out his entire array of gleaming and glittering and shimmering dyes. “Splendid!” he cried as he squatted before cupboards holding an astounding mosaic of sloppy bottles. He provided himself with plenty of the healthiest mice. He got himself a most earnest and diligent Japanese doctor, Shiga, to do the patient job of watching those mice, of snipping a bit off the ends of their tails to get a drop of blood to look for the trypanosomes, of snipping another bit of the ends of the same tails to get a drop of blood to inject into the next mouse—to do the job, in short, that it takes the industry and patience of a Japanese to do. The evil trypanosomes of the mal de Caderas came in a doomed guinea-pig from the Pasteur Institute in Paris; into the first mouse they went, and the hunt was on.

  They tried nearly five hundred dyes! What a completely unscientific hunter Paul Ehrlich was! It was like the first boatman hunting for the right kind of wood from which to make stout oars; it was like primitive blacksmiths clawing among metals for the best stuff from which to forge swords. It was, in short, the oldest of all the ways of man to get knowledge. It was the method of Trial and Sweating! Ehrlich tried; Shiga sweat. Their mice turned blue from this dye and yellow from that one, but the beastly finned trypanosomes of the mal de Caderas swarmed gayly in their veins, and killed those mice, one hundred out of every hundred! That man Ehrlich smoked more of his imported cigars, even at night in bed he would awake to smoke them; he drank more mineral water; he read in more books, and he threw books at the head of poor Kadereit—who heaven knows could not be blamed for not knowing what dye would kill trypanosomes. He said Latin phrases; he propounded amazing theories of what these dyes ought to do. Never had any searcher coined so many utterly wrong theories. But then, in 1903, came a day when one of these wrong explanations came to help him.