Microbe Hunters

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by Paul De Kruif


  Ehrlich was testing the pretty-colored but complicated benzopurpurin dyes on dying mice, but the mice were dying, with sickening regularity, from the mal de Caderas. Paul Ehrlich wrinkled his forehead—already it was like a corrugated iron roof from the perplexities and failures of twenty years—and he told Shiga:

  “These dyes do not spread enough through the mouse's body! Maybe, my dear Shiga, if we change it a little—maybe, let us say, if we added sulfo-groups to this dye, it would dissolve better in the blood of the mouse!” Paul Ehrlich wrinkled his brow.

  Now, while Paul Ehrlich's head was an encyclopedia of chemical knowledge, his hands were not the hands of an expert chemist. He hated complicated apparatus as much as he loved complicated theories. He didn't know how to manage apparatus. He was only a chemical dabbler making endless fussy little starts with test-tubes, dumping in first this and then that to change the color of a dye, rushing out of his room to show the first person he met the result, waving the test-tube at him, shouting: “You understand? This is splendid!” But as for delicate syntheses, those subtle buildings-up and changings of dyes, that was work for the master chemists. “But we must change this dye a little—then it will work!” he cried. Now Paul Ehrlich was a gay man and a most charming one, and presently back from the dye factory near by came that benzopurpurin color, with the sulfo-groups properly stuck onto it, “changed a little.”

  Under the skin of two white mice Shiga shot the evil trypanosomes of the mal de Caderas. A day passes. Two days go by. The eyes of those mice begin to stick shut with the mucilage of doom, their hair stands up straight with their dread of destruction—one day more and it will be all over with both of those mice. . . But wait! Under the skin of one of those two mice Shiga sends a shot of that red dye—changed a little. Ehrlich watches, paces, mutters, gesticulates, shoots his cuffs. In a few minutes the ears of that mouse turn red, the whites of his nearly shut eyes turn pinker than the pink of his albino pupils. That day is a day of fate for Paul Ehrlich, it is the day the god of chance is good, for, like snows before the sun of April, so those fell trypanosomes melt out of the blood of that mouse!

  Away they go, shot down by the magic bullet, till the last one has perished. And the mouse? His eyes open. He snouts in the shavings in the bottom of his cage and sniffs at the pitiful little body of his dead companion, the untreated one.

  He is the first one of all mice to fail to die from the attack of the trypanosome.

  Paul Ehrlich, by the grace of persistence, chance, God, and a dye called “Trypan Red” (its real chemical name would stretch across this page!) has saved him! How that encouraged this already too courageous man! “I have a dye to cure a mouse—I shall find one to save a million men,” so dreamed that confident German Jew.

  But not at once, alas and alas. With gruesome diligence Shiga shot in that trypan red, and some mice got better but others got worse. One, seeming to be cured, would frisk about its cage, and then, after sixty days (!) would turn up seedy in the morning. Snip! went an end off its tail, and the skillful Shiga would call Paul Ehrlich to see its blood matted with a writhing swarm of the fell trypanosomes of the mal de Caderas. Terrible beasts are trypanosomes, sly, tough, as all despicable microbes are tough. And among the tough lot of them there are super-hardy ones. These beasts, when a Jew and a Japanese come along to have at them with a bright-colored dye, lap up that dye. They like it! Or they retreat discreetly to some out-of-the-way place in a mouse's carcass. There they wait their time to multiply in swarms. . .

  So, for his first little success, Paul Ehrlich paid with a thousand disappointments. The trypanosome of David Bruce's nagana and the deadly trypanosome of human sleeping sickness laughed at that trypan red! They absolutely refused to be touched by it! Then, what worked so beautifully with mice, failed completely when they came to try it on white rats and guinea-pigs and dogs. It was a grinding work, to be tackled only by such an impatient persistent man as Ehrlich, for had he not saved one mouse?—What waste! He used thousands of animals! I used to think, in the arrogance of my faith in science: “What waste!” But no. Or call it waste if you like, remembering that nature gets her most sublime results—so often—by being lavishly wasteful. And then remember that Paul Ehrlich had learned one lesson: change an apparently useless dye, a little, and it turns from a merely pretty color into something of a cure. That was enough to drive forward this too confident man.

  All the time the laboratory was growing. To the good people of Frankfort Paul Ehrlich was a savant who understood all mysteries, who probed all the riddles of nature, who forgot everything. And how the people of Frankfort loved him for being so forgetful! It was said that this Herr Professor Doktor Ehrlich had to write himself postal cards several days ahead to remind himself of festive events in his family. “What a human being!” they said. “What a deep thinker!” said the cabbies who drove him every morning to his Institute. “That must be a genius!” said the grind-organ musicians whom he tipped heavily once a week to play dance music in the garden by the laboratory. “My best ideas come when I hear gay music like that,” said Paul Ehrlich, who detested all highbrow music and literature and art. “What a democratic man, seeing how great he is!” said the good people of Frankfort, and they named a street after him. Before he was old he was legendary!

  Then the rich people worshiped him. A great stroke of luck came in 1906. Mrs. Franziska Speyer, the widow of the rich banker, Georg Speyer, gave him a great sum of money to build the Georg Speyer House, to buy glassware and mice and expert chemists, who could put together the most complicated of his darling dyes with a twist of the wrist, who could make even the crazy drugs that Ehrlich invented on paper. Without this Mrs. Franziska Speyer, Paul Ehrlich might very well never have molded those magic bullets, for that was a job—you can watch what a job!—for a factory full of searchers. Here in this new Speyer House Ehrlich lorded it over chemists and microbe hunters like the president of a company that turned out a thousand automobiles a day. But he was really old-fashioned, and never pressed buttons. He was always popping into one or another of the laboratories every conceivable time of the day, scolding his slaves, patting them on the back, telling them of howling blunders he himself had made, laughing when he was told that his own assistants said he was crazy. He was everywhere! But there was always one way of tracking him down, for ever and again his voice could be heard, bawling down the corridors:

  “Ka-de-reit!. . . Ci-gars!” or “Ka-de-reit!. . . Min-er-al wa-ter!”

  5

  The dyes were a great disappointment. The chemists muttered he was an idiot. But then, you must remember Paul Ehrlich read books. One day, sitting in the one chair in his office that wasn't piled high with them, peering through chemical journals like some Rosicrucian in search of the formula for the philosopher's stone, he came across a wicked drug. It was called “Atoxyl” which means: “Not poisonous.” Not poisonous? Atoxyl had almost cured mice with sleeping sickness. Atoxyl had killed mice without sleeping sickness. Atoxyl had been tried on those poor darkies down in Africa. It had not cured them, but an altogether embarrassing number of those darkies had gone blind, stone blind, from Atoxyl before they had had time to die from sleeping sickness. So, you see, this Atoxyl was a sinister medicine that its inventors—had they been living—should have been ashamed of. It was made of a benzene ring, which is nothing more than six atoms of carbon chasing themselves round in a circle like a dog running round biting the end of his tail, and four atoms of hydrogen, and some ammonia and the oxide of arsenic—which everybody knows is poisonous. “We will change it a little,” said Paul Ehrlich, though he knew the chemists who had invented Atoxyl had said it was so built that it couldn't be changed without spoiling it. But every afternoon Ehrlich fussed around alone in his chemical laboratory, which was like no other chemical laboratory in the world. It had no retorts, no beakers, no flasks nor thermometers nor ovens—no, not even a balance! It was crude as the prescription counter of the country druggist (who also runs the postoffice) excep
ting that in its middle stood a huge table, with ranks and ranks of bottles—bottles with labels and bottles without, bottles with scrawled unreadable labels and bottles whose purple contents had slopped all over the labels. But that man's memory remembered what was in every one of those bottles! From the middle of this jungle of bottles a single Bunsen burner reared its head and spouted a blue flame. What chemist would not laugh at this laboratory?

  Here Paul Ehrlich dabbled with Atoxyl, shouting: “Splen-did!”, growling: “Un-be-liev-a-ble!”, dictating to the long-suffering Miss Marquardt, bawling for the indispensable Kadereit. In that laboratory, with a chemical cunning the gods sometimes bestow on searchers who could never be chemists, Paul Ehrlich found that you can change Atoxyl, not a little but a lot, that it can be built into heaven knows how many entirely unheard-of compounds of arsenic, without spoiling the combination of benzene and arsenic at all!

  “I can change Atoxyl!” Without his hat or coat Ehrlich hurried out of this dingy room to the marvelous workshop of Bertheim, chief of his chemist slaves. “Atoxyl can be changed—maybe we can change it into a hundred, a thousand new compounds of arsenic!” he exclaimed. . . “Now, my dear Bertheim,” and he poured out a thousand fantastic schemes. Bertheim? He could not resist that “Now my dear Bertheim!”

  For the next two years the whole staff, Japs and Germans, not to mention some Jews, men and white rats and white mice, not to mention Miss Marquardt and Miss Leupold—and don't forget Kadereit!—toiled together in that laboratory which was like a subterranean forge of imps and gnomes. They tried this, they did that, with six hundred and six—that is their exact number—different compounds of arsenic. Such was the power of the chief imp over them, that this staff never stopped to think of the absurdity and the impossibility of their job, which was this: to turn arsenic from a pet weapon of murderers into a cure which no one was sure could exist for a disease Ehrlich hadn't even dreamed might be cured. These slaves worked as only men can work when they are inspired by a wrinkle-browed fanatic with kind gray eyes.

  They changed Atoxyl! They developed marvelous compounds of arsenic which—hurrah!—would really cure mice. “We have it!” the staff would be ready to shout, but then, worse luck, when the fell trypanosomes of the mal de Caderas had gone, those marvelous cures turned the blood of the cured mice to water, or killed them with a fatal jaundice. . . And—who would believe it?—some of those arsenic remedies made mice dance, not for a minute but for the rest of their lives round and round they whirled, up and down they jumped. Satan himself could not have schemed a worse torture for creatures just saved from death. It seemed ridiculous, hopeless, to try to find a perfect cure. But Paul Ehrlich? He wrote:

  “It is very interesting that the only damage to the mice is that they become dancing mice. Those who visit my laboratory must be impressed by the great number of dancing mice it entertains. . . ” He was a sanguine man!

  They invented countless compounds, and it was a business for despair. There was that strange affair of the arsenic fastness. When Ehrlich found that one big dose of a compound was too dangerous for his beasts, he tried to cure them by giving them a lot of little doses. But, curse it! The trypanosomes became immune to the arsenic, and refused to be killed off at all, and the mice died in droves. . .

  Such was the grim procession through the first five hundred and ninety-one compounds of arsenic. Paul Ehrlich kept cheering himself by telling himself fairy stories of marvelous new cures, stories that God and all nature could prove were lies. He drew absurd diagrams for Bertheim and the staff, pictures of imaginary arsenical remedies that they in their expert wisdom knew it was impossible to make. Everywhere he made pictures for his boys—who knew more than he did—on innumerable reams of paper, on the menu cards of restaurants and on picture post cards in beer halls. His men were aghast at his neglect of the impossible; they were encouraged by his indomitable mulishness. They said: “He is so enthusiastic!” and became enthusiastic with him. So, burning his candle at both ends, Paul Ehrlich came, in 1909, to his day of days.

  6

  Burning his candle at both ends, for he was past fifty and his time was short, Paul Ehrlich stumbled onto the famous preparation 606—though you understand he could never have found it without the aid of that expert, Bertheim. Product of the most subtle chemical synthesis was this 606, dangerous to make because of the peril of explosions and fire from those constantly present ether vapors, and so hard to keep—the least trace of air changed it from a mild stuff to a terrible poison.

  That was the celebrated preparation 606, and it rejoiced in the name: “Dioxy-diamino-arsenobenzol-dihydro-chloride.” Its deadly effect on trypanosomes was as great as its name was long. At a swoop one shot of it cleaned those fell trypanosomes of the mal de Caderas out of the blood of a mouse—a wee bit of it cleaned them out without leaving a single one to carry news or tell the story. And it was safe! So safe—though it was heavily charged with arsenic, that pet poison of murderers. It never made mice blind, it never turned their blood to water, they never danced—it was safe!

  “Those were the days!” muttered old Kadereit, long after. Already in those days he was growing stiff, but how he stumped about taking care of the “Father.” “Those were the days, when we discovered the 606!” And they were the days—for what more hectic days (always excepting the days of Pasteur) in the whole history of microbe hunting? 606 was safe, 606 would cure the mal de Caderas, which was nice for mice and the hindquarters of horses, but what next? Next was that Paul Ehrlich made a lucky stab, that came from reading a theory with no truth in it. First Paul Ehrlich read—it had happened in 1906—of the discovery by the German zoologist, Schaudinn, of a thin pale spiral-shaped microbe that looked like a corkscrew without a handle. (It was a fine discovery and Fritz Schaudinn was a fantastic fellow, who drank and saw weird visions. I wish I could tell you more of him.) Schaudinn spied out this pale microbe looking like a corkscrew without a handle. He named it the Spirocheta pallida. He proved that this was the cause of the disease of the loathsome name.

  Of course Paul Ehrlich (who knew everything) read about that, but it particularly stuck in Ehrlich's memory that Schaudinn had said: “This pale spirochete belongs to the animal kingdom, it is not like the bacteria. Indeed, it is closely related to the trypanosomes. . . Spirochetes may sometimes turn into trypanosomes. . .”

  Now, it was hardly more than a guess of that romantic Schaudinn that spirochetes had anything to do with trypanosomes, but it set Paul Ehrlich aflame.

  “If the pale spirochete is a cousin of the trypanosome of the mal de Caderas—then 606 ought to hit that spirochete. . . What kills trypanosomes should kill their cousins!” Paul Ehrlich was not bothered by the fact that there was no proof these two microbes were cousins. . . Not he. So he marched towards his day of days.

  He gave vast orders. He smoked more strong cigars each day. Presently regiments of fine male rabbits trooped into the Georg Speyer House in Frankfort-on-the-Main, and with these creatures came a small and most diligent Japanese microbe hunter, S. Hata. This S. Hata was accurate. He was capable. He could stand the strain of doing the same experiment a dozen times over and he could, so nimble was this S. Hata, do a dozen experiments at the same time. So he suited the uses of Ehrlich, who was a thorough man, do not forget it!

  Hata started out by doing long tests with 606 on spirochetes not so pale or so dangerous. There was that spirochete fatal to chickens. . . The results? “Un-heard. . . of! In-cred-i-ble!” shouted Paul Ehrlich. Chickens and roosters whose blood swarmed with that microbe received their shot of 606. Next day the chickens were clucking and roosters strutting—it was superb. But that disease of the loathsome name?

  On the gist of August, 1909, Paul Ehrlich and Hata stood before a cage in which sat an excellent buck rabbit. Flourishing in every way was this rabbit, excepting for the tender skin of his scrotum, which was disfigured with two terrible ulcers, each bigger than a twenty-five-cent piece. These sores were caused by the gnawing of the pal
e spirochete of the disease that is the reward of sin. They had been put under the skin of that rabbit by S. Hata a month before. Under the microscope—it was a special one built for spying just such a thin rogue as that pale microbe—under this lens Hata put a wee drop of the fluid from these ugly sores. Against the blackness of the dark field of this special microscope, gleaming in a powerful beam of light that hit them sidewise, shooting backwards and forwards like ten thousand silver drills and augers, played myriads of these pale spirochetes. It was a pretty picture, to hold you there for hours, but it was sinister—for what living things can bring worse plague and sorrow to men?

  Hata leaned aside. Paul Ehrlich looked down the shiny tube. Then he looked at Hata, and then at the rabbit.

  “Make the injection,” said Paul Ehrlich. And into the ear-vein of that rabbit went the clear yellow fluid of the solution of 606, for the first time to do battle with the disease of the loathsome name.

  Next day there was not one of those spiral devils to be found in the scrotum of that rabbit. His ulcers? They were drying already! Good clean scabs were forming on them. In less than a month there was nothing to be seen but tiny scabs—it was like a cure of Bible times—no less! And a little while after that Paul Ehrlich could write:

  “It is evident from these experiments that, if a large enough dose is given, the spirochetes can be destroyed absolutely and immediately with a single injection!”

  This was Paul Ehrlich's day of days. This was the magic bullet! And what a safe bullet! Of course there was no danger in it—look at all these cured rabbits! They had never turned a hair when Hata shot into their ear-veins doses of 606 three times as big as the amount that surely and promptly cured them. It was more marvelous than his dreams, which all searchers in Germany had smiled at. Now he would laugh! “It is safe!” shouted Paul Ehrlich, and you can guess what visions floated into that too confident man's imagination. “It is safe—perfectly safe!” he assured every one. But at night, sitting in the almost unbreathable fog of cigar smoke in his study, alone, among those piles of books and journals that heaped up fantastic shadows round him, sitting there before the pads of blue and green and yellow and orange note paper on which every night he scrawled hieroglyphic directions for the next day's work of his scientific slaves, Paul Ehrlich, noted as a man of action, whispered:

 

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