Microbe Hunters

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by Paul De Kruif


  Just the same, here were a few guinea-pigs, sure—except for this iodine—to have died of diphtheria; and they were alive! I often ponder how terrible was the urge forcing men like Behring to try to cure disease—they were not searchers for truth, but rabid, experimenting healers rather; ready to kill an animal or even a child maybe with one disease to cure him of another. They stopped at nothing. . . For, with no evidence save these few dilapidated guinea-pigs, with no other proof of the virtues of this blistering iodine tri-chloride, Behring proceeded to try it on babies sick with diphtheria.

  And he reported: “I have not been encouraged by certain carefully instituted tests of iodine tri-chloride on children sick with diphtheria. . .”

  But here were still some of those feeble but cured guinea-pigs, and Behring clutched at some good his murderous gropings might do. The gods were kind to him. He pondered, and at last he asked himself: “Will these cured animals be immune to diphtheria now?” He took these creatures and shot an enormous dose of diphtheria bacilli into them. They stood it! They never turned a hair at millions of bacilli, enough to kill a dozen ordinary animals. They were immune!

  Now Behring no longer trusted chemicals (think of the beasts that had gone down to the incinerator!) but he still had his fixed notion that blood was the most marvelous of the saps coursing through living things. He worshiped blood; his imagination gave it unheard-of excellences and strange virtues. So—with more or less discomfort to his decrepit cured guinea-pigs—he sucked a little blood with a syringe out of an artery in their necks; he let the tubes holding this blood stand until clear straw-colored serum rose over the red part of the blood. With care he drew this serum off with a tiny pipet—he mixed the serum with a quantity of virulent diphtheria bacilli: “Surely there is something in the blood of these creatures to make them so immune to diphtheria,” pondered Behring; “undoubtedly there is something in this serum to kill the diphtheria microbes. . .”

  He expected to see the germs shrivel up, to watch them die, but when he looked, through his microscope, he saw dancing masses of them—they were multiplying, “exuberantly multiplying,” he wrote in his notes with regret. But blood is wonderful stuff. Some way it must be at the bottom of his guinea-pig's immunity. “After all,” muttered Behring, “this Frenchman, Roux, has proved it isn't the diphtheria germ but the poison it makes—it is the poison kills animals, and children. . . Maybe these iodine-cured guinea-pigs are immune to the poison tool”

  He tried it With sundry guttural gruntings, with a certain poetic sloppiness, Behring got ready a soup which held poison but had been freed of microbes. Huge doses of this stuff he pumped from a syringe under the hides of his decreasing number of desolate cured guinea-pigs. Again, they were immune! Their sores went on healing, they grew fat. The poison bothered them no more than had the bacilli which made it. Here was something entirely new in microbe hunting, something Roux maybe dreamed of but couldn't make come true. Pasteur had guarded sheep against anthrax, and children from the bites of mad dogs, but here was something incredible—Behring, giving guinea-pigs diphtheria and then nearly killing them with his frightful cure, had made them proof against the microbe's murderous toxin. He had made them immune to the stuff of which one ounce was enough to kill seventy-five thousand big dogs. . .

  “Surely it is in the blood I will find this antidote which protects the creatures!” cried Behring.

  He must get some of their blood. There were hardly any of the battered but diphtheria-proof guinea-pigs left now, but he must have blood! He took one of the veterans, and cut into its neck to find the artery; there was no artery left—his numerous blood lettings had obliterated it. He poked about (let us honor this animal!) and finally got a driblet of blood out of a vessel in its leg. What a nervous time it was for Behring, and I do not know whether it is Behring or his beasts who is most to be pitied, for every morning he came down to the laboratory wondering whether any of his priceless animals were left alive. . . But he had a few drops of serum now, from a cured guinea-pig. He mixed this, in a glass tube, with a large amount of the poisonous soup in which the diphtheria microbes had grown.

  Into new, non-immune guinea-pigs went this mixture—and they did not die!

  “How true are the words of Goethe!” cried Behring. “Blood is an entirely wonderful sap!”

  Then, with Koch the master blinking at him, and with the entire small band of maniacs in the laboratory breathless for the result, Behring made his famous critical experiment. He mixed diphtheria poison with the serum of a healthy guinea-pig who was not immune, who had never had diphtheria or been cured from it either, and this serum did not hinder one bit the murderous action of the poison. He shot this mixture into new guinea-pigs; in three days they grew cold; when he laid them on their backs and poked them with his finger they did not budge. In a few hours they had coughed their last sad hiccup and passed beyond. . .

  “It is only the serum of immune animals—of beasts who have had diphtheria and have been cured of it—it is only such serum kills the diphtheria poison!” cried Behring. Healer that he was, you can hear him muttering: “Now, maybe, I can make larger animals immune too, and get big batches of their poison-killing serum, then I'll try that on children with diphtheria. . . what saves guinea-pigs should cure babies!”

  By this time nothing could discourage Behring. Like some victorious general swept on by the momentum of his first bloody success, he began shooting diphtheria microbes, and iodine tri-chloride, and the poison of diphtheria microbes, into rabbits, into sheep, into dogs. He tried to turn their living bodies into factories for making the healing serum, the toxin-killing serum. “Antitoxin” he called such serum. And he succeeded, after those maimings and holocausts and mistakes, always the necessary preludes to his triumphs. In a little while he had sheep powerfully immune, and from them he got plenty of blood. “Surely the antitoxin [he hadn't the faintest notion what the chemistry of this mysterious stuff was] certainly it will prevent diphtheria,” said Behring.

  He injected little doses of the sheep serum into guinea-pigs; the next day he pumped virulent diphtheria bacilli into these same beasts. It was marvelous to watch them. There they were, scampering about with never a sign of sickness, while their companions (who had got no protecting dose of serum) perished miserably in a couple of days. How good it was to see them die, those unguarded beasts! For it was these creatures told him how well the serum saved the other ones. Hundreds of pretty experiments of this kind Behring made (there was little sloppiness now) and his helpers maybe pointed to their foreheads, asking whether their chief would ever have done saving one set of guinea-pigs and killing another set to prove he had saved the first. But Behring had reasons. “We made so many experiments because we wanted to show Herr Koch how far we had come in our immunizing of laboratory animals,” he wrote in one of his early reports.

  There was only one fly in the ointment of his success—the guarding action of the antitoxin serum didn't last long. For a few days after guinea-pigs had got their injections of serum they stood big doses of the poison, but presently, in a week or two weeks, it took less and less of the toxin to kill them. Behring pulled at his beard: “This isn't practical,” he muttered, “you couldn't go around giving all the children of Germany a shot of sheep serum every few weeks!” And alas, his eagerness for something to make the authorities wide-eyed, led him away from his fine fussings with a way to prevent diphtheria—it sent him a-whoring after the pound of cure. . .

  “Iodine tri-chloride is almost as bad for guinea-pigs as the microbes are—but this antitoxin serum, it doesn't give them sores and ulcers. . . I know it won't hurt my animals. . . I know it kills poison. . . now, if it would cure!”

  Carefully he shot fatal doses of diphtheria bacilli into a lot of guinea-pigs. Next day, they were seedy. The second day their breath came anxiously. They stayed on their backs with that fatal laziness. . . Then Behring took half of this lot of dying beasts, and into their bellies he injected a good heavy dose of the antitoxin
from his immune sheep. Miracles! Nearly every one of them (but not all) began to breathe more easily in a little while. Next day, when he put them on their backs, they hopped nimbly back to their feet. They stayed there. By the fourth day they were as good as new, while their untreated companions, cold, dead, were being carried out by the animal boy. . . The serum cured!

  The old laboratory of the Triangel was in a furor now, over this triumphant finish of Behring's sloppy stumbling Odyssey. The hopes of everybody were purple—surely now he would save children! While he was getting ready his serum for the first fateful test on some baby near to death with diphtheria, Behring sat down to write his classic report on how he could cure beasts sure to die, by shooting into them a new, an unbelievable stuff their brother beasts had made in their own bodies—at the risk of nearly dying themselves. “We have no certain recipe for making animals immune,” wrote Behring; “these experiments I have recorded do not include only my successes.” Surely they did not, for Behring set down the messings and the fiascoes along with the few lucky stabs that gave him his sanguinary victory. . . How could this pottering poet have pulled off the discovery of the diphtheria antitoxin? But then, come to think of it, those first ancient nameless men who invented sails to carry swift boats across the water—they must have groped that way too. . . How many of the crazy craft of those anonymous geniuses turned turtle? It is the way discoveries are made. . .

  Toward the end of the year 1891, babies lay dying of diphtheria in the Bergmann clinic in the Brick Street in Berlin. On the night of Christmas, a child desperately sick with diphtheria cried and kicked a little as the needle of the first syringe full of antitoxin slid under its tender skin.

  The results seemed miraculous. A few children died; the little son of a famous physician of Berlin passed out mysteriously a few minutes after the serum went into him and there was a great hullabaloo about that—but presently large chemical factories in Germany took up the making of the antitoxin in herds of sheep. Within three years twenty thousand babies had been injected and like a rumor spread the news, and Biggs, the eminent American Health Officer, then in Europe, was carried away by the excitement. He cabled dramatically and authoritatively to Dr. Park in New York:

  DIPHTHERIA ANTITOXIN IS A SUCCESS; BEGIN TO PRODUCE IT.

  In the excitement of this cure, those sad ones, who had lost dear ones through the first enthusiasm about the dangerous injections of the consumption cure of Koch, forgot their sorrow and forgave Koch because of his brilliant pupil Behring.

  4

  But there were still criticisms and muttered complaints, and this was natural, for the serum was no surefire, one hundred per cent curative stuff for babies—any more than it was for guinea-pigs. Then too, learned doctors pointed out that what happened under the hide of a guinea-pig was not the same—necessarily—as the savage thing going on in the throat of a child. Thousands of children were getting the diphtheria serum, but some children (maybe not so many as before perhaps?) kept dying horribly in spite of it. Doctors questioned. . . Some parents had their hopes dashed. . .

  Then Ėmile Roux came back into the battle. He discovered brilliantly an easy way to make horses immune to the poison—they did not die, they developed no horrid abscesses, and, best of all, they furnished great gallon bottles full of the precious antitoxin—powerful stuff this serum was; little bits of it destroyed large doses of that poison fatal to so many big dogs.

  Like Behring—perhaps he was even more passionately sure than Behring—Roux believed in advance this antitoxin would save suffering children from death. He thought nothing of prevention, he forgot about his gargles. He hurried to and fro between his workroom and the stables, carrying big-bellied flasks, jabbing needles into those patient horse's necks. Just then, a particularly virulent breed (so Roux thought) of diphtheria bacillus was crawling through the homes of Paris. At the Hospital for Sick Children, fifty out of every hundred children (at least the statistics said so) were being carried blue-faced to the morgue. At the Hospital Trousseau as many as sixty out of a hundred were dying (but it is not clear whether the doctors there knew all these deaths to be from diphtheria). On the first of February, 1894, Roux of the narrow chest and hatchet face and black skull cap, walked into the diphtheria ward of the Hospital for sick children, carrying bottles of his straw-colored, miracle-working stuff.

  In his study in the Institute in the Rue Dutot with a gleam in his eye that made his dear ones forget he was marked for death, there sat a palsied man, who must know, before he died, whether one of his boys had wiped out another pestilence. Pasteur waited for news from Roux. . . Then too, all over Paris there were fathers and mothers of stricken ones, praying for Roux to hurry—they had heard of this marvelous cure of Doctor Behring. It could almost bring babies back to life, folks said—and Roux could see these people holding out their hands to him. . .

  He got ready his syringes and bottles with the same cold steadiness the farmers had marveled at, long before, in those great days of the anthrax vaccine tests at Pouilly-le-Fort. His assistants, Martin and Chaillou, lighted the little alcohol lamp and hurried to anticipate his slightest order. Roux looked at the helpless doctors, then at the little lead-colored faces and the hands that picked and clutched at the edges of the covers, the bodies twisting to get a little breath. . .

  Roux looked at his syringes—did this serum really save life?

  “Yes!” shouted Ėmile Roux, the human being.

  “I don't know—let us make an experiment,” whispered Ėmile Roux, the searcher for truth.

  “But, to make an experiment, you will have to withhold the serum from half at least of these children—you may not do that.” So said Ėmile Roux, the man with a heart, and all voices of all despairing parents were joined to the pleading voice of this Ėmile Roux.

  “True, it is a terrible burden,” answered the searcher that was Roux, “but just because this serum has cured rabbits, I do not know it will cure babies. . . And I must know. I must find truth. Only by comparing the number of children who die, not having been given this serum, with the number who perish, having received it—only so can I ever know.”

  “But if you find out the serum is good, if it turns out from your experiment that the serum really cures—think of your responsibility for the death of those children, those hundreds of babies who did not get the antitoxin!”

  It was a dreadful choice. There was one more argument the searcher that was Roux could have brought against the man of sentiment, for he might have asked: “If we do not find out surely, by experiment on these babies, the world may be lulled into the belief it has a perfect remedy for diphtheria—microbe hunters will stop looking for a remedy, and in the years that follow, thousands of children will die who might have been saved if hard scientific searching had gone on. . .”

  That would have been the final, the true answer of science to sentiment. But it was not made, and who after all can blame the pitying human heart of Roux for leaving the cruel road that leads to truth? The syringes were ready, the serum welled up into them as he gave a strong pull at the plungers. He began his merciful and maybe life-saving injections, and every one of the more than three hundred threatened children who came into the hospital during the next five months received good doses of the diphtheria antitoxin. Praise be, the results were a great vindication for the human Roux, for that summer, the experiment over, he told a congress of eminent medical men and savants from all parts of the world:

  “The general condition of the children receiving the serum improves rapidly. . . in the wards there are to be seen hardly any more faces pale and lead-blue. . . instead, the demeanor of the children is lively and gay!”

  He went on to tell the Congress of Buda-Pesth how the serum chased away the slimy gray membrane—that breeding place where the bacilli made their terrible poison—out of the babies' throats. He related how their fevers were cooled by this marvelous serum (it was like some breeze blowing from a lake of northern water across the fiery pavements of a c
ity). The most dignified congress of prominent and celebrated physicians cheered. It rose to its feet. . .

  And yet—and yet—twenty-six out of every hundred babies Roux had treated—died, in spite of this marvelous serum. . .

  But it was an emotional time, remember, and Roux, and the Congress of Buda-Pesth were not assembled to serve truth but to discuss and to plan and to celebrate the saving of lives. They cared little for figures then; they cared less for annoying objectors who carped about comparing figures; they were swept away by Roux's report of how the serum cooled fevered brows. Then, Roux could have answered such annoying critics (with the applause of his famous audience): “What if twenty-six out of a hundred did die—you must remember that for years before this treatment fifty out of a hundred died!”

  And yet—I, who believe in this antitoxin, I say this, twenty years after—diphtheria is a disease having strange ups and downs of viciousness. In some terrible decades it kills its sixty out of a hundred; then some mysterious thing happens and the virus seems to weaken and only ten children are taken where sixty died before. So it was, in those brave days of Roux and Behring, for in a certain hospital in England, in those very days, the death rate from diphtheria had gone down from forty in a hundred to twenty-nine in a hundred—before the serum was ever used!

  But the doctors at Buda-Pesth did not think of figures and they carried home the tidings of the antitoxin to all corners of the world, in a few years the antitoxin treatment of diphtheria became orthodox, and now there is not one doctor out of a thousand who will not swear that this antitoxin is a beautiful cure. Probably they are right. Indeed, there is evidence that when antitoxin is given on the first day of the disease, all but a few babies are saved—and if there is delay, many are lost. . . Surely, any doctor should be called guilty, in the light of what is known, who did not give the antitoxin to a threatened child. I would be quick to call a doctor to give it to one of my own children. Why not, indeed? Perhaps the antitoxin cures. But it is not completely proved, and it is too late now to prove it one way or another to the hilt, because, since all the world believes in the antitoxin, no man can be found heartless enough or bold enough to do the experiment which science demands.

 

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