Five Quarts: A Personal and Natural History of Blood (14 page)

Not all of Paul Ehrlich’s pursuits were academic, however. Five years into his tenure at the Charité Hospital, the then twenty-nine-year-old confronted a malady for which a cure is not always welcomed: lovesickness. The object of his infatuation was Hedwig Pinkus, a petite beauty ten years younger than him, the daughter of a prominent family from his hometown of Silesia. Though he squeezed in trips to visit her, Paul, for the most part, courted Hedwig through daily letters. An excerpt from one reveals a charmingly besotted man of science: “Although I am not allowed, dear Hedwig, to delight in your presence,” he wrote on March 2, 1883, “the thought of you has not left me for one moment. I must confess I am of no use at all for anything else, but I cannot help it. I have never been as unscientific as now. . . . My microscope is rusting, my beloved dyes are becoming moldy, the laboratory is collecting dust, and the [lab] animal keeper is shaking his head in disbelief.” Married in August 1883, the Ehrlichs settled down in Berlin; within a year the two became three with the birth of their daughter Stefanie.

A year before the birth of a second daughter, Marianne, Ehrlich’s life was shattered in March 1885 with the suicide of his revered mentor and ally, Dr. Frerichs. The pain of this loss was compounded by the frosty relationship he developed with his new boss, Frerichs’s successor, Dr. Carl Gerhardt. A stern taskmaster, Gerhardt decreed that Ehrlich must now devote the entirety of his time to patients. This abruption of his research could not have come at a worse moment. Ehrlich, using a dye called methylene blue in experiments with frogs, had just succeeded in staining
living
nerve tissue. This was a major technical breakthrough, for he, like other scientists, had always worked with inert samples of tissue and blood. Vital staining, as this was called, allowed him to begin examining the effect of chemical compounds on live cells, the important next step toward the crowning achievements of his career (a subject continued in the following chapter). But for now, this work would have to be shelved. Unable to pursue what he most loved, Ehrlich, miserable under Gerhardt’s command, finally resigned his post at the Charité after two years.

A tender moment between Paul Ehrlich (portrayed by an almost unrecognizable Edward G. Robinson) and his wife, Hedwig (Ruth Gordon), in a scene from the 1940 Warner Bros. film
Dr. Ehrlich’s Magic Bullet

Complicating his decision—or perhaps, in a certain way, simplifying it—he’d developed a persistent cough from which he’d been unable to recover. Shortly after his resignation, he discovered evidence of tuberculosis in his own sputum (likely contracted from patients’ TB cultures), a finding that was sadly ironic because, just a few years earlier, he had invented the heat-dried staining method employed to make such a diagnosis. With a firm nudge from his worried wife, Ehrlich decided then not only to put his career on hold but also to take the radical step of leaving Germany altogether. At age thirty-four, he formalized plans to move his young family to Egypt, where he hoped he’d recuperate more quickly in the warm, dry climate.

Many years later Paul Ehrlich looked back on these final weeks in Berlin. During his lowest moments while working under Dr. Gerhardt, he recalled, those times when he felt bitter, dejected, he’d sneak away to his dusty laboratory, open the dye cupboard, and drink in the bright colors. He’d remind himself, “These here are my friends, who will never desert me.”

S
EVEN

Detectable

BLOOD NEVER SLEEPS. EVEN WHEN WE’RE DEAD TO THE world, sad and torpid lumps under the covers of a sickbed, our blood is mounting its most vigorous defense. Here’s the drill: Approximately thirty minutes after we launch into sleep, the killers come out in full force—the “killer” T cells. Killer cells are lymphocytes, one of the five broader varieties of white blood cells. Their territory is our bloodstream and the connecting lymphatic tissue. Killers are created for a single purpose: to destroy foreign agents—viruses, bacteria, toxins. When a killer cell comes upon a virus, for example, it gloms onto it, then secretes proteins that riddle the germ like Swiss cheese, slaying it—mission accomplished—but at the same time sacrificing itself. Killers are most numerous at night, though they operate around the clock, as do their fellow T cells, the “helpers” and “suppressors,” which also perform crucial roles in our defense. (All three T cells take their
T
from the thymus, the butterfly-shaped gland located between the heart and breastbone, where they mature.) The other kind of lymphocyte, the B cells, which develop in the bone marrow, also emerge during deep sleep. And they, too, exist to make mincemeat of microbial bodies, but their methods are less direct. B cells produce preprogrammed weapons called antibodies, which head off into the blood to carry out their orders.

Our blood works not only to destroy the uninvited, but also to repair. In sleep, our circulatory system is infused with growth hormone, a product of the pineal gland and essential in helping rebuild damaged tissue. Growth hormone also rouses additional infection-fighting substances called cytokines, which, like a densely worded paragraph, can make us sleepy. It’s an extraordinary give-and-take. As sleep bolsters our immune system, our immune system bolsters sleep.

So, as it turns out, our moms were right all along.

Get back in bed this instant.
Or,
All you need is a good night’s sleep.

These refrains of countless generations of mothers are grounded not just in the clear messages our bodies send us but also in sound science. And while the mere mention of bed rest as a cure-all inevitably conjures up for me images from childhood, complete with the Vicks VapoRub and those spoonfuls of “grape-flavored” god-awfulness, the fact is, round-the-clock rest as a clinically proven treatment for sickness was first prescribed 150 years ago—the brainchild of a scientist from Paul and Hedwig Ehrlich’s hometown. Hermann Brehmer, a botanist from Silesia, contracted TB during the late 1840s and moved to the Himalayas to live out his final days. The young man’s prognosis was grim. TB, also called consumption, was almost never survivable and, as we now know, this bacterial infection has existed since prehistory; the royal mummies of ancient Egypt show clear evidence of its ravages. Between 1700 and 1900, according to historians, an estimated one billion people died of the disease. Hermann Brehmer did not expect to be an exception. To his great surprise, however, the fresh mountain air and abundant bed rest worked wonders, and he fully recovered. (What Brehmer’s unplanned regimen had done was deprive the bacteria of the conditions they needed to thrive, an immunologist today would explain, thus giving his immune system the edge it needed to fight back.) Following his return to Germany, Brehmer published in 1854 the banner-titled book
Tuberculosis Is a Curable Disease,
in which he espoused his TB “rest cure.” That same year he opened the world’s first tuberculosis sanatorium, the prototype for thousands built in Europe and the United States in the decades to follow. (By the 1940s these facilities had run their course, made obsolete by the widespread availability of antibiotics.) A mainstay of sanatoriums was the sleeping porch, where patients could rest, soak up sunshine, and “take the airs.” Of course, in true Michelin guide style, sanatoriums ran the full range of stars, from squalid public institutions to luxurious resorts for the well-to-do. In fact, when money was less of a concern, patients such as Paul Ehrlich could even make a vacation of their recovery, just as long as they made the commitment to follow doctor’s orders.

Now, one would think that Paul would’ve taken to forced rest like a cat to bathwater. Even Hedwig expected her thirty-four-year-old husband to go partway ’round the bend. In their five years together, she’d scarcely ever seen him take a day off. And yet, even before the Ehrlichs had reached their final destination of Egypt, the good doctor was showing early promise. The couple and their two daughters had first stopped over at a lakeside spa near Venice, and Hedwig, it was later reported, admitted her wonderment at how quickly Paul was adjusting to full-time R and R. “People always think I’m a hard worker,” he remarked at the time, “but they’re wrong. I can be as lazy as a giant snake.”

True enough. As Hedwig well knew, his favorite idle pastime had always been getting lost in books. So as not to disturb her sleep, he’d even divided their Berlin bedroom with a black curtain, which he’d draw and then read behind into the early morning. A perusal of his bookshelves would’ve revealed the breadth of his interests, from erudite leanings—including Greek classics and the latest works by contemporaries such as Friedrich Nietzsche, whose hymn-like verses Paul could recite by heart—to the other extreme, his great love, detective stories.

Every biographer summing up Ehrlich’s life mentions his passion for detective fiction. Martha Marquardt, for instance, revealed that Saturdays at the lab were made sacred by the arrival of the latest issue of the doctor’s favorite crime magazine, with, as she described with an implied
tsk-tsk,
“its cover showing the most lurid pictures of murder.” This weekly serial magazine was probably akin to the American “pulps” that became popular in the early 1900s, such gritty treats as
Detective Story Magazine, Black Mask,
and
The Shadow.
Though they were called pulps because of the cheap, wood-specked paper they were printed on, the stories were sensational and soaked in intrigue. Paul would devour the new issue that same night, Marquardt reported, and it never failed to distract the doctor from his true-life problems.

Ehrlich was also a huge admirer of Sir Arthur Conan Doyle, a signed portrait of whom held pride of place on the wall of his study. He owned copies of many of his books, several of which had been personally inscribed by the Scottish physician-turned-author. As to the when and wherefore of the first “meeting” between Ehrlich and Sir Arthur’s most esteemed creation, the inimitable Sherlock Holmes, my sources do not say. But if one considers that the first Holmes novel,
A Study in Scarlet
(1887), was published just a few months before Ehrlich began his convalescence, it’s not too great a stretch to imagine he brought along a copy of the new whodunit.

“Voilà, hemoglobin.”

While
A Study in Scarlet
is most memorable for presenting the first meeting between Holmes and Dr. John Watson, I take particular notice of what immediately follows this historic handshake. Holmes, in his own estimation, has just made an utterly brilliant discovery about bloodstains. He seizes Watson by the coat sleeve and tugs him into the spacious laboratory to demonstrate said brilliance. Given that arrests were often made long after the commission of a violent act, the detective explains, it had theretofore been difficult for the London police to prove that incriminating stains found on a suspect’s clothing were blood rather than, say, fruit or rust stains. But no longer, as Holmes shows. He pricks his own finger with a needle, draws some blood into a pipette, and stirs a drop into a liter of water. Of course, all evidence of scarlet disappears. But wait. Holmes, re-creating an actual forensics innovation of the time, crushes a few white crystals into the water, followed by several drops of a transparent fluid. In an instant, the liquid takes on a dull mahogany color, and a brownish precipitate collects at the bottom. Voilà, hemoglobin. Holmes is so delighted with himself he’d be patting himself on the back were his hands not occupied with the experiment.

When Dr. Ehrlich did read
A Study in Scarlet,
I can’t help but wonder if he noted the characteristics he and Sherlock Holmes shared: how both men’s hands, to borrow Watson’s words, were “invariably blotted with ink and stained with chemicals”; how, although they both brought a broad background in the sciences to whatever subject was at hand, each possessed an enthusiastic “knowledge of sensational literature”; and how both men incessantly smoked strong tobacco (no, not even TB could make Ehrlich give up cigars). There may have even been aspects of this character’s life that Ehrlich dreamed of having for himself—the unquestioned autonomy, for instance; the instant respect; and, perhaps above all, that gloriously spacious laboratory.

Brushing aside all speculation now, the fact is, when the Ehrlichs returned to Berlin in the spring of 1889, Paul was a new man—free of TB, hale and hearty, raring to jump back into full-time work. Just one snag: Nobody was hiring. Though far from his dream scenario, he made the best of the situation. With the financial backing of his father-in-law, the thirty-five-year-old opened his own research laboratory, which may sound more glamorous than it was. In truth, it was a rented apartment, close to where he and his family lived. And his staff rounded out to a whopping one, a valet named Fritz, although Paul’s nephews, Felix and Georg, did pitch in now and then. Picking up where he’d left off the year before, Ehrlich resumed his experiments with vital staining and began creating new histological dyes. He christened Stieglitz blue and Lutzow blue for nearby streets. A more informal term—
exploders
—arose to describe a common mishap: the bursting of the dye-filled glass flasks that were heated on the apartment’s kitchen stove, leaving indigo spattered about the room.

Elsewhere in the small apartment, Ehrlich launched into what was for him a new line of research, work that was related to a larger “hot theory” being addressed by scientists in Berlin, as elsewhere: that all infectious diseases were caused by toxins, a by-product of foreign microorganisms. Scientists had just concluded that this was the case in diphtheria, for instance; the diphtheria bacterium secreted a toxic substance that attacked the walls of the throat, producing the blockage that left its victims, mostly children, choking to death. Soon after, it was found that a toxin was also the culprit in tetanus. Scientists then cast a suspicious eye on TB (although, eventually, no toxin was implicated). Ehrlich, a man who “approached research like a detective on a trail,” as the distinguished American hematologist Maxwell Wintrobe wrote in 1980, began focusing on one small aspect of the whole. He mounted his own quantitative study of a toxin, but rather than something infectious, Ehrlich chose something addictive: cocaine.

At the time, cocaine was legal and readily available, whether in pure form from a pharmacist or, as was the case in Anytown, USA, at the corner drugstore as the extra little kick in a glass of Coca-Cola. Coincidentally, the second Sherlock Holmes story,
The Sign of Four
(1890), had just been published, and it opened with Holmes casually injecting himself with a syringe of cocaine, the influence of which, he confessed to Watson, he found “transcendentally stimulating and clarifying.” Its popularity notwithstanding, Ehrlich knew that at certain levels cocaine had toxic effects. But what levels caused what effects? For answers, Ehrlich enlisted mice as his guinea pigs. Rather than injecting the cocaine into their bloodstreams, he instead found it easier and safer to feed it to them. He soaked biscuits with varied but precise quantities of a cocaine solution. Satisfied with this methodology, Ehrlich shifted to a series of experiments using a much deadlier plant derivative, the toxin ricin. Derived from castor plant beans, ricin is more potent than cobra venom, even in minuscule amounts. Today it is regarded as one of the most dangerous weapons of bioterrorism.

Although Ehrlich would end up with a lot of dead mice, he eventually produced survivors that were immune to not just normally lethal amounts of ricin but also doses hundreds of times stronger. Within the bloodstream of these supermice, Ehrlich had triggered circulating “antitoxins” (a type of antibody) that would “paralyze” the poison the next time the mice ingested it. In short, they’d been vaccinated. With this, Ehrlich was not, however, introducing into the world a new concept. A hundred years earlier one of his scientific heroes, the British physician Edward Jenner, had demonstrated an effective but far cruder instance of induced immunity. He’d found that a human being deliberately exposed to a mild form of smallpox, by way of scrapings from sores, would survive exposure to the deadly form of the disease. Although the how and why were unclear, Jenner had proven, figuratively speaking, that an umbrella against drizzle could be as effective in a downpour. In turning to this puzzle a century later, Ehrlich brought to the table his own specialty: great scientific rigor. With his ricin experiments, he developed a scrupulous methodology, juggling multiple factors. As a result, he knew exactly how much of the toxin was required to elicit immunity, according to a specific dosing schedule over a certain number of days. Likewise, he knew what amounts were too little or more than necessary. When his supermice had offspring, Ehrlich discovered something else of significance. The antitoxins were being passed on by the mother, from placenta to fetus as well as through suckling—textbook examples of passive immunization, in which an individual receives antibodies from another. (In active immunization, by contrast, protective antibodies are generated by one’s own immune system.)