Five Quarts: A Personal and Natural History of Blood (13 page)

In the year following his Nobel Prize, Ehrlich did indeed create the world’s first magic bullet when he invented an effective cure for the most hideous plague of his day, syphilis, the sexually transmitted, blood-borne disease that, for centuries, had been as stigmatizing as AIDS would one day become. He formulated an injectable arsenic-based drug that was later called Salvarsan by the German manufacturer. (Salvarsan would eventually be replaced by penicillin as the first-line syphilis treatment.) Ehrlich’s original name for the medication was “606,” for the simple fact that it was the six hundred sixth preparation he had tested, the number also quietly acknowledging his sheer persistence even after 605 failures. While the discovery made Ehrlich world famous, it also marked the beginning of a new set of difficulties, placing the scientist at the center of an ethical debate. From one camp, Ehrlich was vilified for his willingness to save “immoral” people who, some believed, deserved to die. And from another, he was held personally responsible for the drug’s adverse side effects, including numerous fatalities, most of which resulted from doctors’ errors—incorrect dosing and poor administering. In reality, the magic bullet was not magic for all. Produced as a powder that had to be carefully measured then dissolved in sterile water prior to each intravenous injection, Salvarsan was also difficult to manufacture. Ehrlich, in an effort to minimize the risks, had taken the extraordinary step of patenting Salvarsan (one of the world’s first therapeutic drug patents), not for personal gain—in fact, he never directly profited from the drug—but to enforce a consistent quality in its production. What made this whirl of difficulties bearable, he later confessed, was the first postcard he received from a cured patient.

Twenty-five years after his death in 1915, the doctor’s life story was dramatized—no, make that
melo
dramatized—in a Warner Bros. film,
Dr. Ehrlich’s Magic Bullet,
starring Edward G. Robinson in the title role. Hollywood—and hindsight—treated him kindly. The 1940 movie, with an Academy Award–nominated screenplay by John Huston, is notable for being the first to address the taboo subject of syphilis. Ehrlich is presented as a selfless, courageous German Jewish doctor with an American accent to set him apart, I presume, from the vaguely anti-Semitic government bureaucrats, all of whom have heavy German accents. (This reflected the politics of World War II more than the reality he’d faced.) Robinson, best known for portraying gangsters, gives Ehrlich a saintly aura, culminating in the near apotheosis of his deathbed scene. Looking and sounding robust—though the funereal piano score leaves no doubt whatsoever that he’s about to kick the bucket—Robinson-as-Ehrlich summons his scientific disciples to his bedside: “The magic bullet will cure thousands,” he tells them. “But there can be no final victory over diseases of the body unless the diseases of the soul are also overcome.” A pause and a benevolent smile as the master musters his final strength. “We must fight them in life as we fought syphilis in the laboratory. We must fight! Fight! We must never, never stop fighting!” His eyes close as violins swell above the piano, then bells ring as if signaling Ehrlich’s entrance into heaven. And the screen goes black.

By all published accounts, Paul Ehrlich’s real life did lend itself to this kind of glorification. Most glowing of these works is a memoir written by Martha Marquardt, who served as the doctor’s devoted secretary during his final thirteen years. (Her loyalty to the man continued long past his death, as it turned out. At the risk of imprisonment, she smuggled Ehrlich’s private letters, scientific papers, and original manuscripts out of Germany at the height of Hitler’s regime, thus saving them from certain destruction.) In point of fact, Marquardt wrote two versions of her memoir: the original, a slim volume of reminiscences from 1924, and a substantially revised, English-language edition from 1951, incorporating the documents she’d rescued. In this latter work, the additional material allowed her to write more of a full-fledged biography. But there was another compelling reason for the new edition. As Marquardt noted in the preface, all but a few copies of the original were burned by the Nazis.

The moment she entered the lab first thing in the morning, she wrote, Ehrlich would nod courteously then start rattling off correspondence. Midsentence, though, he’d often abruptly halt, as if listening for something just out of range of human hearing, and then begin rummaging through the cork-stoppered bottles atop his immense worktable. Not finding what he sought on top, he’d open the cupboards underneath. Here were still more bottles—“innumerable they seemed, filled with rare and precious chemical substances.”

Marquardt recalled that the doctor might remain squatting for a good quarter of an hour, his knees pressed to his chest. The sound of his rifling was the tinkling of a tea service. He’d then pick up with both hands a particular bottle, turn it around and around, and smile as he read the label. With the grunts and groans of repositioning, he again stood. At such moments, she remembered, “All written work was forgotten for the time being and he would begin experimenting. Test tube after test tube was taken out of the little box near the Bunsen burner, and minute quantities of various chemical compounds were put into them, solutions were made and heated, alkalis and acids added. Now a delightful violet-blue resulted from the experiment, then it was a bright red; now green, then orange. If he found an interesting reaction he called out:
‘Wonderful! Wonderful!’
and showed it to me as though I understood all about it.”

In Marquardt’s affectionate work as well as in the drier tomes of Ehrlich’s fellow scientists, a telling quirk surfaces: The man loved colors. He was “emotionally swayed” by them, one gentleman wrote. What spring is to a
parfumeur,
colors were to Paul Ehrlich. Though always a busy, busy man, Marquardt revealed, the doctor would still stop to extol the roar of yellows and reds in a bouquet of flowers. They “would make him quite ecstatic,” Marquardt admitted. This quirk carried over into his work habits as well. He wrote daily notes to himself and his staff on precut squares of different-colored construction paper, using various colored pencils. He kept this stationery in his coat pocket and, while he rarely lost his temper, he’d become terribly agitated if his supply ran out. (A similar response arose regarding his stock of Havana cigars, one of which was ever present, a sixth digit on his right hand.) Though surrounded by colors, none were more eye-popping to Dr. Ehrlich than those produced by his chemicals—the pure blues of cobalt compounds, glowing like the core of a torch flame, the delicate sea greens of iron-infused solutions. Far more than a source of pleasure, though, color was the prism through which he viewed and attempted to unravel biological mysteries. Color is the thread that links his disparate scientific achievements.

Born in 1854 in a small village 150 miles southeast of Berlin (an area that’s now part of Poland), Paul Ehrlich was the only son of prosperous Jewish parents who operated an inn. During his midteens, he pursued his keen interest in science under the watchful eye of a cousin on his mother’s side, Carl Weigert, who was nine years older than Paul. Weigert, a famous pathologist, had discovered that aniline dyes—synthetic dyes developed in Germany around 1860 for use in the textile industry—were unexpectedly well suited for staining human and animal tissue. Rather than obscuring details, these intense dyes instead illuminated them, revealing contrast and texture, making microscopic specimens easier to analyze. Weigert introduced his cousin to this important advance, and Paul began experimenting on his own. In 1872 he went off to study medicine at the University of Breslau and, as was customary in those days, transferred to different schools every year to train with the finest teachers. At the University of Strasbourg, while under the tutelage of one of the great anatomists of the nineteenth century, Wilhelm Waldeyer, Paul invented a technique that took his cousin’s discovery one step farther: “selective staining.” Using a dye of his own formulation, he found that each cellular element in a tissue sample reacted differently to his staining and also displayed a different shade, thus permitting extraordinarily sharp definition—akin to what HDTV is to regular television, I imagine. With this method, Paul promptly made his first major discovery: the mast cell, a type of cell common in connective tissue.

Praise for his innovative staining was not unanimous, however. While completing his studies at the University of Leipzig, Paul lived at a boardinghouse whose owner would recall many years later that the young student often looked like a human drop cloth; his hands, face, and clothes were always spotted with inky stains. His bath towels and linens were equally blemished, and no amount of washing could remove the blight. Moreover, even the house’s billiard table, upon which, for lack of flat surfaces, Paul had conducted experiments, was forever splotched with fuchsia, indigo, and lilac. Little could the proprietor have known then that her boarder’s messes would lead to findings that would make a permanent impact on several branches of science. Ehrlich had not been content simply to observe the myriad cells of the human body—as dazzling as he found them—but sought to figure out
why
dyes became fixed in specimens (as they did in fabrics), plus why individual cellular parts reacted so differently to certain dyes. From controlled experiments, he concluded that, rather than a mere physical change, a specific chemical transformation was occurring within the cells. These investigations into the nature of staining were the subject of Ehrlich’s 1878 doctoral thesis and also anticipated the dawning of a new field of biology, cytochemistry, the study of cell constituents. The thesis also contained the germ of a larger theory explaining how—in lay terms—disparate substances bind chemically, which would evolve over the next thirty years into his ideas about the formation of antibodies in human blood; his concept of a magic bullet; and, ultimately, the invention of the syphilis cure. But that’s jumping ahead.

Already renowned for his histological staining, the newly minted doctor was invited in 1878 to join the staff of the prestigious Charité Hospital in Berlin, where he worked under the supervision of Friedrich von Frerichs, an esteemed clinician. Though Ehrlich had a full roster of patients, Dr. Frerichs recognized the young man’s talent and energy and encouraged him to spend more time on original research. Ehrlich continued experimenting with aniline dyes but turned his attention from animal tissue to human blood, which, in a clinical setting, was readily available. The study of blood, too, was still fresh terrain. Although two centuries had passed since Antoni van Leeuwenhoek’s discovery of red blood cells, progress in the field of hematology had been sluggish. From today’s vantage point, it appears that Ehrlich was the right scientist at the right time and place, equipped with the right tools, to transform the entire discipline. Ensconced in his closet-sized hospital lab, the twenty-four-year-old quickly invented a simple method for preparing blood specimens. Well, simple for him. First he would take great care to spread a small drop of blood on a glass slide in the thinnest possible layer. He then allowed it to air-dry. Next, as he reported in a published paper, he heated the blood smear on a copper hot plate “for one or several hours” at 120 to 130 degrees Celsius, thereby fixing it and preserving the delicate cellular elements. Finally, he added one of his staining solutions. “Using such techniques,” Ehrlich concluded, “one can obtain with most dyes very beautiful and elegant pictures.”

Of great immediate significance were his “pictures” of white blood cells. Though a predecessor, the British microscopist William Hewson (1739–1774), had discovered white blood cells a hundred years earlier, he had supplied only sketchy details. (Medical historians now explain that white cells had been overlooked for so long not only because they’re far outnumbered by red cells, which make up 45 percent of blood volume, with white just 1 percent, but also—for me, the more convincing reason—because they are almost transparent.) Hewson also correctly surmised that white cells serve an infection-fighting role, in concert with the lymphatic system. Confirming Hewson’s theory, another British William, physician William Addison, demonstrated in 1843 that blood collected from an injured person’s wound had far more white cells than blood taken from elsewhere in that person’s body. Clearly, white cells were converging, but for exactly what purpose? Subsequent scientists, leading up to Ehrlich’s generation, discerned that white cells were, indeed, the army of the blood—helping defend the body against bacteria, fungi, and viruses. But it was Paul Ehrlich who first identified its main soldiers. By using his technique of selective staining, he differentiated the two broad classes of white cells, leukocytes and lymphocytes, and discovered three of the five specific types of white cells now known. He found he could illuminate each of these three using a different kind of dye. The names Ehrlich gave the cells were mini tributes to the dyes themselves: the eosinophil, which stained red from the eosin dye; the basophil, blue from a base dye; and the neutrophil, a pinkish color from a neutral dye.

Ehrlich’s heat-fixed blood-staining technique soon became standard practice, helping to usher the science of hematology into the modern age. Adopting his methodology, other scientists joined Ehrlich in making finer and finer distinctions about the behavior and function of both red and white blood cells, particularly in diseases such as anemia (characterized by a lack of hemoglobin) and leukemia (an overabundance of white cells). Likewise, quantitative blood counts were now possible and allowed for quick, accurate diagnoses of life-threatening conditions. The modern-day routine blood test called a CBC (complete blood count) is a direct descendant of Ehrlich’s innovation.

For his accomplishments, Ehrlich is now often lauded as the “father of hematology,” a fact that calls for a small digression. Medical historians, I’ve noticed, demonstrate an almost comical penchant for assigning paternity to branches of science even if the field is already well populated with fathers. In my studies, Ehrlich is the fifth father of hematology I’ve come across, but this in no way minimizes his contribution. Among these patriarchs, though, Ehrlich stood out in one respect: He didn’t dote. While it is not unusual for a scientist to devote his or her life’s work to one specialty, Ehrlich tended to make discoveries and then, as I see it, abruptly move on. But he described it with greater eloquence: “One must not stay in a field of work until the crops are completely brought in, but leave still some part of the harvest for the others.” He moved on, again and again, to great success. Historians, in fact, also remember him as the father of histology, immunology, experimental oncology, and the aforementioned chemotherapy and cytochemistry.