Five Quarts: A Personal and Natural History of Blood (15 page)

Ehrlich’s methods and precision caught the attention of his peers, one of whom, fellow Berliner Dr. Emil von Behring, had just made his own startling discovery regarding passive immunity. In experiments completed in 1890, Behring found that if he removed the serum (the plasma without the blood cells and clotting elements) from an animal that had been successfully immunized against diphtheria, and then injected it into a second animal, that animal would also be immune. Serum from the injected animal would, in turn, protect other animals. Taking the next step, however—creating a diphtheria antitoxin to protect human beings—had proved troublesome. Behring wisely enlisted Ehrlich’s help in developing a safe, effective protocol. Ultimately, full-scale production of the lifesaving diphtheria treatment began in November 1894.

Paul Ehrlich in his laboratory

From there, a five-year jump in time finds a world-recognized Paul Ehrlich as the head of his own institute, the newly established Royal Institute of Experimental Therapy, located in Frankfurt—a long distance, both geographically and professionally, from his cramped quarters in Berlin. The institute had been designed to Ehrlich’s every specification, with multiple laboratories, a library, and ample space for a top-notch staff plus countless lab animals, all housed within a grand four-story building. Ehrlich oversaw a broad range of work whose scope was comparable, for its time, to, say, the United States’ National Institutes of Health combined with the Food and Drug Administration. While its opening ceremony in early November 1899 was a splendid public affair, attended by scientists, journalists, politicians, and citizenry, for Dr. Ehrlich personally a much more prestigious, albeit quieter, event would take place four months later.

It is March 22, 1900, and the forty-six-year-old Paul Ehrlich stands before the Royal Society of London—the exclusive scientific association that counts Antoni van Leeuwenhoek and Sir Isaac Newton among its past members. When he speaks of the great privilege it is to be here, this is no mere nicety. He has been invited to this first gathering of the new century to deliver the keynote address, a lecture titled “On Immunity with Special Reference to Cell Life.” He does not disappoint. In this now-legendary speech Dr. Ehrlich elaborates for the first time his “side-chain theory” of immunity, which provides a full accounting of the blood’s ability to protect the body from foreign invaders. Drawing upon the work of peers as well as his experience with ricin and diphtheria, Ehrlich explains that blood cells have on their surfaces ready-made receptor molecules, or “side chains,” that link or bind chemically with certain invading toxin molecules. (He had borrowed the term
side chain
from organic chemistry; it was widely believed that side chains were, like docking ports, the means by which cells took in nourishment from free-floating food particles.) Long story short, this binding neutralizes the toxins. It also triggers production of excess side chains, which are released into the blood as circulating antitoxins to fight the same toxin in the future.

Medical historians today distill Ehrlich’s presentation to three main points, two of which were correct and one that was wrong but forgivable. He was right in theorizing that blood cells have the capacity to form antibodies even before a particular antigen has entered the body. Also right was his conception of these antibodies as, in essence, locks waiting for the right keys; and the related notion that, once a lock was activated, the production of many more antibodies was stimulated. Ehrlich was mistaken, though, in believing that
all
cells could produce such antibodies; in fact, only B lymphocytes can.

Historians also agree that Ehrlich’s argument was not just sound but very convincing. Adding to the impact of his spoken word was a series of provocative drawings. Now, it should be noted that the use of visual aids in a lecture to the Royal Society was not at all unusual, but his were unique for being of imagined constructs, renderings of the theoretical goings-on in the blood. Even though the best microscopes of the day did not allow Paul Ehrlich to see this activity, in his mind’s eye the images were clear. And were now on display. A sequence unfolded: First a standard cell was shown—a light-colored, spongy moon erupting with what looked like sweat beads off the brow of a comic-strip character. These were Ehrlich’s side chains, which frankly did not in any way appear chain-like. Next, some of the sweat beads were gripped by toxins, the villainous elements, which were horned and black. Others then broke free—the heroic antitoxins—and, now resembling lithe, silvery minnows, swam off into the blood.

Ehrlich, aware that not everyone in the audience would share his certainty, cautioned that the forms and shapes in his diagrams should be considered as “purely arbitrary.” At best, they were simply an educated guess. Some scientists did not take this caveat to heart, however. In the weeks and months to follow, critics griped that his ridiculous “cartoons” had conveyed more of a conclusion than a possibility. His chief detractor dubbed them a “puerile graphical representation.” If the criticism was meant to elicit a retraction of some sort, it didn’t work. In fact, whenever Ehrlich subsequently spoke about his side-chain theory, he would take the opportunity to illustrate it. Stories abounded of how Dr. Ehrlich, even in casual conversation with colleagues, would scribble out drawings of the minuscule players of his theory on whatever blank surface was available. When no paper was handy, he’d opt for, say, his hostess’s tablecloth, a listener’s shirt cuff, or the sole of his shoe. If necessary, he’d roll back the carpet, then use chalk on the floorboards. And once, over dinner, in a performance I’m sad to have missed, he storyboarded his entire molecular drama on fifty postcards, an indulgent waiter having kept the doctor in steady supply.

Martha Marquardt, who entered his employ in 1902, adored this quality in her boss. “When his mind was entirely filled with a certain idea,” she wrote, he spoke of it with animation and in a great gallop of words. “He perceived the idea as if it had a physical existence,” and he always wanted visitors to see it along with him. To make sure a person was keeping up, Dr. Ehrlich might tap him or her “lightly on the arm or chest with the point of a coloured pencil, with a test tube, a cigar or his thick-rimmed spectacles which he frequently took off and swung about. . . .” Drawing to a finish, “he stood with his head pushed forward a little, his gentle face upraised,” and “looked penetratingly at the other person with his big bright eyes.”
Do you see what I see?

Dr. Ehrlich never actually got to view the drama within the blood. But what was to him the most likely scenario involving the most likely suspects can now be clearly photographed with an electron microscope, the same technology used to produce those ugly mug shots of minute insects, with their bulbous compound eyes. The electron microscope, thousands of times stronger than the traditional compound microscope, has also captured images of a tinier but more horrific bug: HIV, the virus that does its damage to the immune system by hijacking helper T cells and forcing them to churn out as many copies of itself as possible, a process that kills the cells. I remember the odd sense of relief I felt upon first seeing the micrograph of HIV on the cover of
Time
magazine, dated August 12, 1985, one month after I’d moved from Seattle to San Francisco’s Castro district, ground zero of the epidemic. It showed the virus, magnified 135,000 times, attacking a T cell, according to the caption, although the grayish clump looked more like something pulled from a vacuum cleaner bag.
There’s the culprit,
I thought, staring at the black-and-white photo.
Now we just need to annihilate it.

I’ve since seen many similar images, some taken at magnifications three times as powerful. Like the dazzling shots of far-off galaxies taken by the Hubble Space Telescope, the original black-and-white micrographs are often colorized to highlight specific features of the virus. Three-dimensional computer graphics provide even finer details of HIV’s internal and external architecture. I know that these images have been invaluable to scientists in their growing understanding of HIV and in crafting new models for fighting it, but, to me, the greater the complexity of the virus, the bleaker the chances seem of surviving it. The discovery of a cure feels farther off in my lifetime and unlikely in Steve’s.

During rough patches, Steve admits that his life seems to creep forward in three-month intervals, alluding not to the turn of seasons but to the stretches between his getting blood work, the panoply of tests that measure the virus’s activity and how well his immune system and organs are holding up. The findings provide an assessment of his current drug regimen and help determine the course for the next twelve weeks. Seeing his doctor for the results is always anxiety producing.

Thinking back fourteen years, I don’t remember Steve ever having a slim patient file, although at some distant point in our shared past that must’ve been the case. Now it’s a thick sheaf that’s plopped onto the desktop at the start of each appointment. Once the pleasantries are over, Dr. Hassler opens the file and the three of us huddle over the latest labs, a three-page printout of more than fifty separate tests. The results run down the center of each page in one of two columns:
WITHIN RANGE,
under which most of Steve’s liver and kidney function results, for example, are listed; and
OUTSIDE OF RANGE,
where the grimmer numbers, T helper percentages, white cell counts, and the like, are clustered. To make the bad numbers easy to spot, this column is shaded a pale red, a stripe top to bottom. The most recent pages are bound to a thick pile of Steve’s past results, and a quick fanning of the stack creates a crude animation of a red ribbon, many years long.

Across the Bay Bridge and thirty miles from my home, I step from my car and approach IDL, Immunodiagnostic Laboratories. The broad one-story building, here on the outskirts of San Leandro, is situated in a secluded industrial complex. The building proper is faced entirely in black reflective glass, making it impossible for me to glimpse any activity within. What’s more, while a sign confirms that I am definitely at the correct address, I can’t find a front entrance or even the appearance of a door.
How apropos,
I think;
the lab where Steve’s blood is tested is testing me.
Stumped about how to get inside, I stare at the building. All I see is myself, looking back.

I walk around to what appears to be the rear of the building and, at last, locate a doorbell.

A head shoots through a cracked-open door: “You got a delivery?”

“No, an appointment,” I reply.

“Well, this is shipping.” Nevertheless, the young man agrees to take me through the building to the front office, where I’m left to wait in a blah-colored reception area that is conspicuously missing a receptionist. The phone rings over and over. I know she exists because I spoke with her yesterday.

“IDL,” the woman had answered.

I’d hastily dialed the number stamped atop the lab request form Steve takes to the phlebotomist and hadn’t quite formulated the nature of my request, nor to whom I wished to speak. The Chief Blood Tester? Blood Docent? “I’m wondering,” I stammered, “could I come out and just take a look around?”

“A look around what?” she returned pleasantly.

“Well, at the lab. Get a sense of the process involved with testing blood. Maybe, if it’s not too much trouble, take a tour of the facility.”

Long pause. “A tour?” I pictured her scanning the room, thinking,
Heavens, what guidebook does he have?
“Um, well, we don’t
give
tours. Are you sure you have the right phone number?”

Oh, yeah, yeah, yeah, I explained, I didn’t need any blood tests myself but was interested in seeing how they’re done. The more I spoke, the odder it must’ve sounded. As if she’d finally caught on, the receptionist said, “Oh, are you with the FDA or something?”

Before I could deny anything, she’d transferred me to IDL’s medical director, the head honcho, Edward Winger. He, thankfully, understood my desire to see what happens to blood in the in-between, after it’s drawn but before the results are sent on. Sure, he could show me how it all works. “How about ten-thirty Friday?”

Before hanging up, I thought,
Oh, go ahead, just ask:
“My partner just had his blood drawn,” I began, “and I assume you’ll have it by the time we meet. Would it be naÏve of me to think that I could actually see his blood being tested?”

His burst of laughter supplied a thorough answer, but, lest I had any doubts, Dr. Winger added, “Yes, it would be naÏve of you. We don’t track the blood by a person’s name.”

“Oh, for confidentiality purposes, you mean,” I said. “That makes sense.”

“But also,” Dr. Winger added, “almost all of the testing is done late at night.”

Night? So the workers come out to count the blood only after sundown. How vampiric. Well, no wonder parking was so easy.

Dr. Winger enters the reception area. He’s a tall, thin man in his fifties. He has silver-blue eyes behind delicate wire-rimmed frames. Shaking his hand, I find it cool and powdery-dry, as if he has just pulled off a latex glove.