The Demon Under the Microscope Read online

  The British had created the hospital by converting what had been the town’s casino, swathing the ornate chandeliers in white linen, replacing the gaming tables with phalanxes of beds, and transforming the private card rooms—the salles privés—into operating rooms. The bedding was boiled and bleached, the wards scrubbed spotless, the nurses were plentiful, the physicians included some of the empire’s best. And the patients were dying in droves.

  The problem here, as it was in the Ukraine, was the rampant infection of wounds. British soldiers—regardless that they received the best care in the world—were dying almost as fast as the German soldiers were in Domagk’s filthy field station. As the flood of wounded poured in, it soon became clear that more British soldiers were dying from wound infections than from enemy bullets. Something had to be done. So the army turned to Sir Almroth Wright, hoping that England’s greatest bacteriologist and expert in infectious disease could solve the problem.

  It was something of a gamble. The military administrators knew that there was no love lost between Sir Almroth and the army. The scientist had already resigned his commission once, a decade earlier, very publicly, creating what to the military administration had seemed like a totally unnecessary scandal in the press. The problem then had been hesitation. The British generals had balked at inoculating troops leaving for the Boer War with a vaccine Wright had created and which he swore would provide protection against typhoid fever. The generals were worried that Wright’s vaccine was unproven, that British soldiers would be used as guinea pigs, that side effects would put more soldiers out of action than the medicine would save. They were correct on the first two points at least. They sent the men off without vaccinations, and fifteen thousand of them died of typhoid in South Africa, where disease killed twice as many British soldiers as the Boers did. After that, Wright was allowed to test his vaccine on British soldiers in India, where it proved a success. It was a public embarrassment. Wright was not shy about pointing out that those thousands of soldier typhoid victims might have lived but for the bullheadedness of their commanders, and he resigned his commission in 1902. His successful vaccine, however, earned him a knighthood and his vindication: During the First World War, millions of doses of his antityphoid vaccine were given to British troops with spectacular results. Typhoid was negligible in Flanders compared to what they had seen in the Boer War.

  That success seemed to give Sir Almroth a maddening sense that he was always right about everything. After leaving the military, he had gone off and started a vaccine research laboratory in London, at St. Mary’s Hospital—the Inoculation Department, he called it—and did his best to forget about the army. Sir Almroth was not the military type in any case. He was a lover of poetry, a freethinking Irishman who took tea with George Bernard Shaw (Sir Almroth, it was said, was the model for the character of Sir Colenso Ridgeon in Shaw’s The Doctor’s Dilemma), a man who demanded that everything be proved to work scientifically and to his personal satisfaction before he would implement it. In other words, he was unlikely to take orders. There was no guarantee that even in a time of war he would return to service. But the potential renown associated with solving the wound-infection problem far outweighed the risks of putting Sir Almroth in a uniform. The approach was made by Sir Alfred Keogh himself, director-general of Army Medical Services, who used as bait the combination of a commission for Wright as a colonel, an appeal to his humanitarian impulses, and the promise of substantial research funding. As it turned out, he did not need to try very hard. Sir Almroth, among his many other characteristics, was a patriot. He readily agreed for the good of his nation to set up a laboratory for wound-infection research in Boulogne.

  True to form, however, once he got to Boulogne, the Old Man, as his research assistants affectionately called him, refused to shine his buttons or tuck in his shirt. He was negligent when it came to saluting. He was the despair of Sergeant Clayden. The low point came when Sir Almroth walked into the hospital one day with a large tear in the seat of his pants. Clayden, horrified, hid Sir Almroth in a side room while he made repairs. Wright was simply not regular army.

  But he was brilliant. It was likely that Sir Almroth knew more about the causes and cures of infections than anyone in Britain. Now he intended to use this opportunity—the chance to create the world’s first dedicated laboratory for military medicine—to quickly solve the problem of wound infections. He thought at first that it could be done relatively easily by using the same techniques he had used to solve the typhoid problem. All he had to do was find out which bacteria were causing wound infections, create a vaccine against them, and inoculate the soldiers. Problem solved.

  Once on the ground in Boulogne, he surveyed the small amount of space he had been given in the lower floors, sniffed the air, and started demanding changes. He refused to stay in the stink and talked himself into space on the top floor, in a former fencing school. This, too, was less than perfect. There was no electricity up there, or proper gas, or heat, or even running water, but it was large and airy, and there was good natural light. Here he and his crack team of researchers—young men he imported from his lab in London, saving them from becoming cannon fodder on the front lines—began putting together a research facility. The place they had come from, the Inoculation Department at St. Mary’s, had been so productive, so successful in advancing basic knowledge and making vaccines that they had nicknamed themselves “the House of Lords.” His assistants included some of the nation’s brightest young scientists, such as Alexander Fleming, who would later discover the medical properties of penicillin, and Leonard Colebrook, who would become one of England’s most renowned physicians.

  In Boulogne they set to work turning the fencing school into a laboratory. They divided the central arena with rough wooden walls, installed oil heaters for the winter, created lab benches out of spare tables, scavenged chairs and glassware—Sergeant Clayden proving himself a talented scrounger—substituted spirit lamps for gas flames to heat their experiments, and installed a makeshift water system with a tank on the roof. Soon every surface was packed with microscopes and racks of test tubes. Sir Almroth was famous for inventing lab techniques on the fly (he perfected the art of sterilizing needles in hot olive oil, for instance, which he found worked admirably if it was brought just to the point where it browned bread crumbs). If they needed specialized equipment, they made it out of whatever was available—fashioning a glassblowing apparatus out of an old gas can and a foot bellows, for instance. Within a few weeks, in the late fall of 1914, they were doing first-rate science.

  The only problem was that none of the vaccines they tested were able to prevent or cure wound infections. Instead of a quick and brilliant victory, after a few months at Boulogne, Sir Almroth found himself in the equivalent of a trench war. “We have just got to begin at the beginning instead of trying short-cuts to cures,” Wright said. He took several steps back, refocusing his laboratory on a systematic study of exactly what happened during wound infections, hoping that if they could discover precisely where the infecting bacteria came from, how infections started and how they proceeded, and how the body fought back, a point could be found to attack and defeat the infection.

  Their first discovery was that the British had prepared for the wrong war. The empire’s approach to battlefield medicine was based on what had been learned during the Boer War in South Africa fifteen years earlier. There the British physicians had carefully treated wounds with the most modern and systematically applied antiseptics, washes and ointments, topical medicines that killed bacteria on contact, and sterile surgical techniques. It seemed to work. Wound infections had not presented a major military problem in the Boer War. The doctors thought they had solved the problem.

  They were wrong. Their techniques worked only because of the nature of the South African dirt and the types of wounds the men suffered. The Boer War took place mostly in the dry, rocky veld; British soldiers were generally injured by high-velocity Mauser bullets shot at a distance by Boer farmers. The wounds were relatively simple and clean. Treatment with a bit of antiseptic and the right dressing led to quick cures. Flash forward more than a decade to Flanders, to European farmland soaked with fall rains, and to wounded arriving shredded by shrapnel, and none of the African techniques worked. The explosive shells of World War I drove muddy, richly manured soil deep into ragged cavities in the flesh. Like the German soldiers in the Ukraine, the British wounded in Flanders often fell into stagnant water pooled in the bottoms of bomb craters, and there they would lie for hours, sometimes days, before evacuation. In Flanders there was no such thing as a clean wound. Wright’s group found that the dirt in the wounds was alive with fecal bacteria common to horses and cows. They found that it was impossible to clean the wounds effectively. They found most wounds heavily colonized within a day or two by a dozen kinds of barnyard bacteria, several of which were able to cause deadly infections, including the germs that caused tetanus and gas gangrene; various strains of Staphylococcus and Streptococcus; a miscellany of other fecal and skin bacteria. By the time a doctor saw the soldiers, it was already too late as far as infection went; the wounds were dangerously septic from the very start. This, Wright believed, was why his vaccines did not work: There were too many kinds of bacteria involved, there too many targets to attack even with a mixed vaccine, the bacteria were too well established by the time the vaccine could be administered.

  Then Wright’s group showed that gangrene infections were the result of a stepwise process. Through a series of what one historian calls “very elegant experiments” using a seemingly limitless number of wounded men as, in a sense, laboratory animals, they tracked the progress of infection, gathering daily samples of tissue and fluids, assaying the types and numbers
of bacteria, measuring the body’s immune response by counting the numbers of white blood cells present at various sites in the wound, then matching their findings to the patients’ general health. They found tetanus bacteria growing in the wounds of a third of the patients, strep in half of them, and the organism that causes gas gangrene in 90 percent. They found that the infections often started with the men’s soiled clothing: The shells blasted muddy cloth into the wound, giving the bacteria in the dirt an excellent place to start growing. They drew blood and mixed it with feces, simulating the bacterial array found in the fields, then put the mixture in a special flask they made by heating the bottom of a test tube in a flame until it was soft, and drawing the glass out to a half dozen points, making hiding spots for bacteria, a simulacrum of a deep, ragged wound. When they added antiseptics to the flask, they found that even enormous doses failed to kill bacteria in those hiding spots. Dousing deep wounds with even the strongest antiseptics, in other words, was not going to stop wound infections in Flanders. They found that a few bacteria always escaped in deep crevices, and that the human body quickly washed the antiseptics away in any case, “quenching” their power to kill bacteria with blood serum and lymph. Because strong antiseptics killed human cells just as well as they killed bacteria, applying them to deep wounds was actually counterproductive, because the antiseptics killed many of the body’s key defenders, white blood cells called leucocytes, along with the bacteria. It was essential to keep those white blood cells alive and active. “The leucocyte is the best antiseptic,” Sir Almroth would tell any surgeon who would listen to him. His tests showed that the antiseptics they were pouring into wounds were not only missing a lot of bacteria but were making things worse by throwing off the proper immune response. In order to kill every dangerous germ in a deep wound, Sir Almroth figured, it would be necessary to pump in enough antiseptic to kill the patient.

  So his group focused on ways to keep the immune system as healthy as possible. They invented new techniques as they went, instruments for probing and sampling wounds (including the unfortunately named “lymph leech”) and for testing for and analyzing bacteria and white blood cells.

  Then they started trying to tell surgeons what to do. It was normal surgical procedure to close wounds tightly as soon as possible; Wright’s research showed they were better off keeping the wounds open to the air. It was normal procedure to dress the wounds tightly and change the dressings daily in an attempt to keep things dry; Wright’s research indicated that leucocytes thrived in moist wounds, which meant that the daily changing of bandages was not only exquisitely painful (the old bandages often adhered when they were pulled off) but increased the risk of infection. He recommended gauze soaked in salt water rather than dry bandages—bacteria hated salt, but leucocytes did fine if the concentration was right—plus, a damp salt dressing drew liquid from the wound, keeping fresh fluids flowing from the body, encouraging leucocytes and washing out bacteria. The old system of bandaging was all wrong; Wright’s group came up with new methods and invented a new kind of bandage made from perforated celluloid to cover the gauze, allowing the wound to breathe.

  And that was a critical point. Getting air to the wound was vital. While some wound-infecting germs (like strep) lived in the air, gas gangrene germs, the worst of the invaders, were known to be a species of anaerobe, bacteria that reacted to oxygen as if it were poison. Gas gangrene germs needed airless places to grow, while the body’s tissues thrived on oxygen-rich air. If the goal was to prevent a gas gangrene infection, one of the worst things you could do was to cut off the air to a wound. It created an ideal growth environment for the bacteria.

  And here was perhaps the most important thing Sir Almroth’s group discovered: Wound infections proceeded in stages. First the new, open wound was colonized by aerobic bacteria, strep and staph, which grew quickly in a variety of tissues and loved oxygen. This first wave of infection would scavenge all the oxygen from a wound, clearing the way for anaerobes like gas gangrene germs, which then set up shop—especially in tightly closed wounds—and finished off the patient. Strep infections, his group discovered, were the underlying problem. They figured that 70 percent of the deaths from wound infections could be traced back to strep. If they could stop strep, they could stop wound infections. But they could not. For some unknown reason, no vaccine had ever worked against strep. And no drug existed that could stop a strep infection—or any bacterial infection—once it started in the body. Close the wound tightly and you risk gas gangrene. Leave it open and you invite in strep. The problem was more complex than anyone had thought.

  Now that he had found what he thought was the key to wound infections—and found that he could not come up with a way to directly switch the process off—Wright focused on what could be done around the edges. He tried to get the surgeons to change their operating techniques. The surgeons’ inclination was to leave tissue as intact as possible, then close as tightly as possible. But Wright’s research showed that germs thrived in damaged or dead tissue; therefore it was necessary for surgeons to get more aggressive, cut out anything questionable, carve out a wound until it was free of hidden dirt and recesses, down to tissue you knew was healthy, down to the bone if necessary. Then keep the wound open for a while. Only after a few days, once it had clearly been shown that there was no infection, should a wound be closed to prevent any chance of further infection. “Close to sterilize,” Wright wrote, “rather than sterilize to close.”

  He railed against the fast, wholesale evacuation of the wounded back to England. This, he felt, placed an undue strain on the patients during what might be the most important phase of recovery. The wounded needed to be kept in one place under proper treatment until the danger of infection passed, he argued; sending a patient with a tightly closed, dirty wound to England was often tantamount to sending him off to die.

  Wright was very sure of his results and had no qualms about setting the surgeons straight as forcefully and directly as possible. At first the surgeons simply refused to listen. They were already overworked, thrown into the war, one day running a private practice in London where they might do a half dozen surgeries in a full afternoon, the next day in France cleaning and closing thirty or forty a day. The surgeons were proud of their ability to close with exquisitely small glovemaker’s stitches; the best of them were proud of their ability to stitch below the top layer of skin to avoid scarring. The surgeons liked to leave the patient as intact as possible; as one surgeon said, “If I were to trim away all the badly damaged tissue in some cases, I should have to trim away half my patient.” The surgeons believed in dousing everything inside and out in antiseptic. The administration wanted to ship the wounded back to England as soon as possible to clear desperately needed room for more.