Five Quarts: A Personal and Natural History of Blood (26 page)

The basic science required to hunt down CAF offers no guarantee of a quick return on investment, he continued; it’s just too “high risk” for a biotech company to consider. Enter irony: Levy has received offers to become the head of a few such companies, to which his reaction has always been, “But then who’s going to work on CAF?”

Levy agreed to show me his other work spaces and led me down hallways that interlocked with the puzzling aspect of a hedge maze. Finally ushering me through a door, he said with good humor, “You need roller skates to get from one lab to another,” though, I must say, Levy is not a man one can easily imagine on skates. A Segway, however, is a distinct possibility. He motioned to a glass-front refrigerator, and I peered in at a fleet of vials. “In here, we’ve got cells that are growing the virus. In the old days,” he added dryly, “no one would come in this room.”

“In the old days, no one would come in this room.”
Jay Levy in his laboratory, 1984

In a connected lab, Dr. Levy pointed out two members of his staff, impossibly young-looking postdoctoral fellows, Leyla and Hillary. They gave a quick, friendly wave. “Leyla’s the one who narrowed it down to fourteen proteins,” he said with pride. “It took her four years.” She smiled modestly and I thought,
Remember that face: You might just see it on the cover of
Time
someday.

Although he and his staff hope to get through all fourteen in the next three years, Levy conceded, “We may end up finding we missed it.” His entire body language answered my unasked question: Yes, the hunt would then start over.

As we were stepping out the door, a splash of color caught my eye, a familiar poster,
BE HERE FOR THE CURE.
We’d given away thousands of these back in ’92. I smiled and gestured to it: “That looks good.” Levy said it had been up since the forum. The poster, I noticed, hung right where they turn the lights on every day—
click—
and where they turn them off.

A few days later I visited Chiron Corporation and spoke with a former senior member of Levy’s team, Dr. Susan Barnett. Chiron, whose U.S. headquarters is in Emeryville, just across the Bay from San Francisco, is a global biotech company with a legendary namesake: Chiron was the centaur who’d taught the healing arts to Asclepius, the Greek god of medicine and father of the goddess of cure-alls, Panacea.

Barnett, an effervescent forty-eight-year-old, is Chiron’s project leader for HIV vaccines. She greeted me in the soaring atrium of the life sciences building and led me up a broad stairway to her sleek, uncluttered office. I happened to be meeting Barnett on a day when she was experiencing a heady milestone of her own. In a phone call, she’d just gotten “the thumbs-up” from the FDA for the first Phase I clinical trials of their new HIV vaccine, a product Chiron’s been developing for almost ten years. I do believe that, had Barnett had a confetti cannon, she’d have set it off right then and there. “I’m as excited as a scientist can get,” she admitted. “We’re on the precipice,” she added with a warm smile, although her imagery clearly evoked the perils inherent in taking the leap into human testing. Will it fly or fail?

The company has been in a similar precarious spot before, as Barnett recollected. Back in 1994, when she’d arrived at Chiron from Jay Levy’s lab, the first generation of AIDS vaccines was about to enter Phase II trials, in which efficacy is tested. Under study was not only Chiron’s vaccine but also vaccines developed by other pharmaceuticals, all employing a similar design: the use of a single small part of the “envelope” of the virus.

“And they didn’t go,” Barnett recalled. Indeed, based on dismal Phase I results, the government pulled the plug on this approach to vaccine creation, deeming it hopelessly ineffective.

“That was a pivotal moment,” she told me. “Everybody retrenched and started doing more research.” Her voice had grown sober in the memory. What was a major setback for companies such as Chiron was also a devastating blow to communities and individuals affected by the epidemic. So, yeah, I agreed with Susan, 1994 was not a banner year.

Chiron’s latest, best hope is as different from the failed version as a hybrid car from a 1970s gas guzzler. “We’ve combined everything we have, our best weapons: DNA technology plus protein technology,” Barnett explained, her enthusiasm renewed. The vaccine, designed to protect uninfected people, is administered in two parts. First a series of “prime” immunizations, which is the DNA aspect of the vaccine, at zero, four, and eight weeks, followed by the protein “boost,” probably at twenty-four and thirty-six weeks. A promising concoction is only the beginning of a good vaccine formula, I was coming to realize. The true finesse comes with the administering and the dosing. As Barnett described the protocol, I couldn’t help but hear an echo from Jay Levy. “Vaccinology is an art,” he’d said to me. And now, standing before me, dry-erase marker in hand, was an artist.

At this point Barnett dived into a finer presentation of the relevant mechanisms, complete with visuals, all the while checking in with me with a look:
Okay? Okay? Still with me?
Although phrases such as
trimeric proteins, polymer microparticles,
and
occluded loop
whizzed past me like bullets in a Yosemite Sam cartoon, I had no trouble grasping the principle upon which the vaccine’s potential success rests, an immutable, biological truth: Blood remembers illness.

Existing within our bloodstreams is an elite class of white blood cell—they can be either B or T cells—whose prime function is to retain a “memory” of infectious organisms the body has previously encountered. Should one of these organisms return, memory cells, as they are called, recognize it and rally fellow B and T cells to fight off the invader. This is why we do not get chicken pox a second time.

Memory cells are a vaccinologist’s ally because they can be tricked. A vaccine, in other words, can plant false memories. If Chiron’s AIDS vaccine is a success, it will convince memory cells that they’ve already encountered HIV when they have not. (Chiron’s product contains a noninfectious facsimile of portions of the virus.) If a vaccinated person is then exposed to actual HIV, the memory cells will, in theory, initiate a massive immunological response, killing the virus. This expectation is fairly well grounded. The immune system’s “secondary response” is usually faster, larger, and more specifically tailored than the first, or primary, immune response. And, again, in theory, the protection should last. Unlike suppressors, killers, and other white blood cells, memory cells live for decades before dying.

Those are some pretty big ifs, I had to admit to myself, especially since HIV can mutate so rapidly and hides so well in the body. It takes only one—just one—infected T cell to restart a cascade of viral replication. “So,” I asked Susan, “what does your gut say?”

“I think we’re going to get good immune responses. That’s my gut. And yet,” she added, “I’m not stopping research until I see some human data.” Even in the best-case scenario, she noted, it would be six to ten years before licensure.

I remembered how, ten or twelve years ago, researchers often bridged the notion of a preventive vaccine with a “therapeutic” one, meaning that what would protect the uninfected should also aid the infected. Did this still hold water today? Mentioning my partner, I asked Barnett, “Could this vaccine be used in people with HIV as well?”

She put down the marker and returned to her desk, quiet every step. She sat, then said, “It’s complicated.”

It’s unlikely, in other words. And, as she went on to clarify, it’s simply not part of Chiron’s plan. Of course, there is a scenario in which the vaccine might be used in a person with HIV: if a trial participant becomes infected. As I knew, slip-ups will be necessary for determining ultimately whether an AIDS vaccine is a success, although this is a harsh reality that Barnett and I did not discuss.

Barnett had worked with Jay Levy for four years and counts him as a valued colleague but she is also an outsider, so she seemed the right person to ask, “What’s your take on CAF?”

“Well,” she said, stretching the word almost to its breaking point. “What Jay’s been going toward, it’s a noble quest.” She leaned forward in her chair. “His work on CAF has been seminal. He showed that this factor specifically inhibited HIV.” Furthermore, other scientists, following Levy’s lead, began searching for CAF and discovered something unexpected, chemokines, chemical substances that also inhibit HIV. Even more important, Barnett emphasized, they discovered why chemokines inhibit the virus: They bind to the same receptors on the T cell as HIV does, so, in essence, it cannot “dock.”

“Now we know
where
HIV binds,” she said, her voice and eyes sharing the same fire. “Now we know
how
HIV gets into the cell.” She let that steep for a moment, then recapped: “So we went from his initial discovery to discovering beta chemokines to discovering the receptors for them to discovering how the virus gets into the cell.

“And for me, designing a vaccine,” she added, “if I know how the virus binds, then I can figure out how to block it.” She sat back, smiling, gently shaking her head in wonder. “So that is pretty amazing. He doesn’t have the factor, but look at all the research it has stimulated.”

I liked her use of
noble quest,
but I doubted Jay Levy would’ve liked its ring. Built into the phrase is an acceptance that the destination may never be reached, that the journey may be all. When I’d spoken with the man three days back, doubt never once entered the discussion. “When we find the factor,” Levy had said, “it’s gonna be a hell of a discovery.”
Amen,
I’d thought. “People will say, ‘God, they spent twenty years on this thing.’ Well, that’s not unusual—factor VIII took years to be discovered. And penicillin! Interferon’s another example. That’s what’s going to happen here.”

He added, “That’s what keeps me going.”

“Keeps you on the odyssey?” I said.

“That’s right,” Dr. Levy replied. “I haven’t met the Muses yet.”

FOR ME, IT’S NOT THE MUSE’S CLEVER WEAVING OF THE TIME-TOSSED tale or the hero’s cunning escape from the Cyclopes or even his sweet reunion with his wife after twenty years away. No, what brings me back to
The Odyssey
time and again is a passage right at the halfway point in the story, when Odysseus and his surviving crew are so utterly, epically lost that their only hope of ever finding home is to journey into hell itself to ask directions of a dead, blind prophet. Directions from a blind man. That doesn’t sound promising.

Considering all they’ve gone through since leaving Troy, their descent to the underworld isn’t particularly perilous. There Odysseus stands at a rocky pinnacle where the River of Flaming Fire and the River of Lamentation meet, and he carves a narrow trough in the ground at his feet. Following careful instructions, he performs a lengthy ritual that culminates in his pouring fresh blood into the pit. Souls instantly swarm, craving a drink, a ghostly multitude of old men, unmarried youths, “once-happy girls with grief still fresh in their hearts,” and a “great throng of warriors killed in battle,” including one of his own fallen men. Their faces are contorted, desperate. Though Odysseus finds the sight heart wrenching, he brandishes his sword to keep them back. The prophet Teiresias must drink first of the blood.

Odysseus and his men flee the Cyclopes

Once sated, Teiresias does indeed prophesy a safe route back to Ithaca and, looking far ahead in the hero’s journey, adds, “Death will come to you far away from the sea, a gentle Death. When he takes you, you will die peacefully of old age.” With that, the prophet withdraws and Odysseus is free to leave this wretched place, to return to his ship and head for home, where his beloved awaits. And yet, in what I’ve always seen as an act of great kindness, he lingers and allows a number of the other souls to taste the remaining blood. Whereas the vital fluid had restored the prophet’s ability to see the future, for these souls it has the opposite effect: Blood restores memory. One by one, they come, drink of it hungrily, and share their recollections of life on earth.