As Seeley approached the lectern, Kaplan pushed his utilitarian horn-rims up the bridge of his nose.
“Dr. Kaplan, before you describe to the jury the several obstacles that stood in the way of discovering AV/AS, could you describe to us how vaccines work generally-a vaccine we might be more familiar with, like the polio vaccine or the vaccine for measles?”
With a slight tilt of his head, Seeley reminded the scientist to look at the jurors as he spoke.
Kaplan smiled broadly and ran his fingers through coarse, barely combed hair. “The beauty of a vaccine is that it uses the body's own defenses to fight off infection. It makes a weak person strong.”
“And how do you get a vaccine to do that?”
“The starting point for the great majority of vaccines is to take a laboratory sample of the virus, like polio, that you want to create immunity against, and then you weaken or even kill the virus so it can no longer cause the disease. Then”-Kaplan jammed his index finger into the palm of the other hand-“you inject this weakened version into a healthy patient. It's too weak to make him sick, but it's strong enough to stimulate his body to produce antibodies. Once these antibodies are in the bloodstream, they attach themselves to the weakened virus we injected and neutralize it. Effectively, the injected virus triggers its own executioner.”
“What happens after the antibodies neutralize the virus in the vaccine?”
“That's the genius of vaccines: the antibodies stay in the bloodstream so that if our patient later encounters the real, live polio virus, the antibodies are already there to bind with the virus and neutralize it.”
“Is HIV a virus?”
“That's what the letters stand for. Human immunodeficiency virus.”
“Does immunization work the same way with HIV as it does with the polio virus?”
Kaplan threw up his hands. “If only it were that simple! In the early days we all assumed this was how an AIDS vaccine was going to work. What we didn't know-and what sadly we know now-is that HIV is a chronically replicating antivirus, uncontrollable by the host's immune response.”
To this point, heads had nodded in the jury box as the jurors followed along. But now, as Seeley expected, he saw some anxious side glances. This was the point at which Gabriela Vega, helping Kaplan prepare his testimony, cautioned the witness to avoid technical terms. Seeley's first instinct, sitting with them in the Heilbrun, Hardy conference room, was to agree. But then he decided that it wouldn't hurt to remind the jury, and particularly Sansone, that it took more than high-school biology to create AV/AS.
Kaplan said, “The problem is that the HIV envelope glycoprotein displays emphatic antigenic variations, is heavily glycosylated, and is poorly immunogenic.”
The mood in the jury box instantly turned from confusion to frustration. For all of Kaplan's undeniable charm, Seeley was going to have to be more careful.
Seeley forced a laugh into his voice. “Could you translate that into a language the jury and I can understand?”
Kaplan's eyebrows shot upward. He laughed and clapped his thighs. “Of course. I apologize.” He rested his hands on the rail, and spoke directly to the jury. “Four unique hurdles stand in the way of developing an AIDS vaccine.”
In her cross-examination of Chaikovsky that morning, Fischler left the jury with the thought that science had progressed to a point at which Steinhardt's achievement was obvious, even trivial, to anyone working in the field. Now, Kaplan was going to dispel that thought.
“Before you describe these obstacles to the jury, Dr. Kaplan, could you tell us how you came to know about them?”
The smile that played tentatively on the scientist's lips became a self-deprecating grin. “I've been working on the problem of an AIDS vaccine for eighteen years. Our experience is that we overcome one or two of these obstacles, but when we try to attack the next one, we find that the first one's come back.”
“You said ‘we’?”
“My research team.”
“How large is this team?”
“Over the course of our work, it's been as small as six researchers, all of them PhD graduate students or postdocs, and as large as fifteen.”
“And where has this research taken place?”
“At Harvard Medical School, and at the Dana-Farber Cancer Institute's Center for AIDS Research.”
“Why at two institutions?”
Again, Kaplan shrugged. “This is a big job.”
When they were preparing Kaplan for his testimony last night, Seeley asked him how a researcher like Steinhardt, working alone at a small drug company, could get to the finish line ahead of teams of scientists at major, federally funded laboratories. “You have to remember,” Kaplan had told him, “Steinhardt was already publishing papers on this approach when he was at UC.” There wasn't a hint of envy or regret in Kaplan's voice. “And,” Kaplan had said, “some researchers work better alone than others.” “Or,” Seeley had said, “they're less inclined to share the credit.” Kaplan had lifted his eyebrows and tilted his head but said nothing.
“So, Dr. Kaplan, could you tell the jury what these four obstacles are.”
“Remember,” Kaplan said, talking to the jurors as if it were one of his Harvard seminars, “I told you that vaccines work by stimulating the body's immune system to fight off the virus infection? Well, HIV is unique among viruses in that its target is the victim's immune system. It's in the nature of HIV that it destroys the very mechanism that we need to fight off infection. How can you use the immune system to repel a virus if the virus attacks the system itself?”
Kaplan's little tutorial had the jury's close attention and the judge's, too. Thorpe wouldn't think to break the communion between the expert and his audience. Nor would Thorpe have more than two or three questions on cross, none of them harmful. For the first time that day, Seeley relaxed. The case was going well. Cordier's testimony had also been strong, Chaikovsky's only slightly less so, and Kaplan's comments last evening in the conference room had reassured him about Steinhardt's style of research.
“You testified that there are four hurdles, Dr. Kaplan. What are the other three?”
“Recall I said that for polio and the other vaccines, vaccinologists use a weakened form of the virus to stimulate the host's antibodies.”
“Go on.”
“We can't do that with HIV. We can't use a weakened virus, or even a dead one. Because of the virus's effect on the immune system, it would be too dangerous to the person being inoculated. It could be a death sentence.”
“So what can you use?”
“The best you can do is break down HIV into its individual proteins, and use one of them.”
“What are the other two obstacles?” It was a short, smooth ride from here.
“For an antibody-any antibody-to work, for it to neutralize the virus and prevent it from invading cells, it has to bind to the virus particle. The problem is that the surface of an HIV particle is so dense and complicated that it's virtually impossible for the antibody to reach the binding site.”
“Like a crumpled piece of paper?”
“No.” Kaplan shook his head impatiently. “Picture a tiny sphere. An HIV particle, or virion, is only one ten-thousandth of a millimeter wide-the width of a human hair is one-tenth of a millimeter-and it has a surface like a loose piece of cloth covered with dozens of mushrooms. The mushrooms are constantly in motion, always flopping around.” Kaplan waggled his fingers at the jury. “How can an antibody find a binding site if it's hidden under the mushroom caps? But it must bind to a specific site. Hit or miss isn't good enough for it to work.”
“And, the last obstacle?”
“Mutation. With polio, measles, mumps, the virus you're attacking stays the same from one day to the next, and from one host to another. But HIV is different. It's constantly mutating-and not only over time, and not only from one host to another. On a given day, HIV can take on countless different forms in just a single individual.”