Authors: Mark A. Jacobson
A
FTER
B
ARRY'S DEATH, THERE
were no more boyfriends. Kevin stopped seeing clinic patients, too, and spent his days in meetings and conference calls, using the time in between to search the library for obscure articles. At home, he was a hermit monk, reading textbooks and journals instead of scripture, writing papers and grant applications instead of copying medieval manuscripts.
Kevin had a new hypothesis. He was convinced it was the most important original idea of his career. Even though the virus had been discovered four years earlier, the technical challenges in developing a method to accurately measure changes in the amount of HIV in a research subject's blood still seemed insurmountable. A promising drug's antiviral activity could be quantified in a test tube but not in an infected patient. In addition, the costly T cell assays Kevin depended upon as the primary outcome measurements in his Phase 1 trials were not precise. The effect of a drug in increasing T cells had to be huge in order for it to be detected.
Kevin delved into immunology literature, had long discussions with Rajiv Singh, and corresponded with a biochemist in Pittsburgh. Then his eureka moment came. There were assays for measuring molecules in serum that reflected the degree of immune system damage inflicted by HIV, and these assays were more precise and less expensive than T cell assays. No one had ever looked at how a proven treatment for HIV, like AZT, might affect the levels of these molecules, and he knew that Burroughs Wellcome had frozen serum samples left over from the AZT trial.
Kevin called a company senior scientist to pitch his idea. Perhaps this could be the best way yet to assess the efficacy of new drugs in patients. Forty-eight hours later, a box of specimens was delivered to Rajiv.
Assisted by two technicians borrowed from a colleague's lab, Rajiv ran assays the next day. He called Kevin at midnight with the results. Kevin spent
all night entering and re-entering Rajiv's data into a statistical software program. Using the secret code indicating which individuals had been given AZT and which placebo, his analysis revealed levels of several proteins were diminished after two months of AZT treatment while remaining the same in those who received placebo. Of far greater significance, the magnitude of these changes predicted the trial participants' survival better than their T cell changes did. Kevin slept an hour, woke up, wrote a manuscript including tables, footnotes, and a reference list, and handed it to Rajiv at the end of the day.
Rajiv came to his house the next morning with his edits scribbled in the margins. They revised the paper, printed three copies, signed away their copyright privileges, and got the packet to an express mail center in time for it to reach the
Lancet
's editorial headquarters in London before the weekend. Within a month, their article was published in what was arguably the
New England Journal
's equal in international prestige.
The day after the
Lancet
broadcast his results in a press release, Kevin spoke by phone to reporters from the
New York Times
and
Wall Street Journal
and was interviewed by two television networks. As the last crew was packing its equipment, Ray sauntered into his office.
“This is a pleasant surprise,” Kevin said. “What brings you here?”
“I have an overwhelming need to tell you how much I appreciate what you do.”
Despite Ray's irony, Kevin didn't doubt his sincerity. Department chiefs were hired and fired based on the success of their faculty.
“Well, Ray,” he said, savoring the moment, “You've always been most generous and kind to me. I hope this is partial repayment.”
Ray cackled and rubbed his hands. He listened greedily as Kevin told him about several other papers he was working on, the journals he planned to submit them to, and a grant proposal he had in mind.
Once the conversation began to dwindle, Ray made a request.
“I'm sure you know about the annual Department dinner party, though I don't think I've ever seen you there.”
“The one at Saint Francis Yacht Club?” Kevin asked, gritting his teeth.
Department of medicine faculty spread out among the various university-affiliated hospitals in San Francisco were all invited to this black tie event. Kevin had never gone, afraid it would make him feel like an impecunious relative visiting the estate of a wealthy cousin, a hillbilly in a tuxedo. Neither had Gwen. In fact, Herb was the only person he knew at City Hospital who regularly attended the affair. But Herb was amused by seeing university politics at play, how avariciously his colleagues sought power within the ivory tower and how jealously they guarded their fiefdoms. Kevin found it repugnant.
“I wish you'd come this year.”
Kevin shrank back.
“Please. It would mean a lot to me if you and Gwen came.”
There was no graceful way to refuse. In any case, Ray had craftily made it more bearable for Kevin by adding Gwen to his entreaty. Kevin capitulated.
At dusk on a Sunday evening, Kevin, Gwen, and Herb stood on a deck jutting over the bay. Alcatraz, a mile away, glowed red as the sun was setting behind the Golden Gate Bridge.
Herb and Gwen were on their third glass of chardonnay. Kevin was abstaining. The three huddled together in the chilly wind. Herb glanced through open double doors into the yacht club bar.
“Check out those heavy hitters,” he said, pointing to a quartet of fiftyish-year-old men chatting amicably.
“Who are they?” asked Kevin.
“Milton, Reuben, Strummel, and West. Each one has a major lab on the Hill. Collectively, their grants must bring in ten million dollars a year
just in overhead
to the university. They're golden boys.”
“So what does that get them?” asked Gwen.
“That and a dollar get them a cup of coffee in the cafeteria,” said Kevin. “The university keeps all the overhead.”
“Not true,” said Herb. “They get choice space. Their needs are taken very seriously by Ray's boss and by the deans and chancellor above him. Those guys have to be kept happy. They could get recruited away to Harvard or Stanford.”
“Heavy hitters,” mused Kevin.
“There's another one,” Herb said.
He pointed to the far side of the room where a man with a shock of white hair held forth to a fawning coterie of listeners.
“Boughton, an interventional cardiologist. Commands the highest pro fees in the entire department of medicine.”
“We're heavy hitters, too,” said Kevin, aggrieved now. “Between the three of us, don't our grants bring in a couple of million dollars in overhead a year?”
Herb looked doubtful.
“Two million? OK, one. That has to buy us a seat at the table.”
“Maybe a step stool in the kitchen,” Herb chortled.
Kevin was getting angrier. Gwen took his arm.
“Don't worry, dear,” she said, mimicking a lush, aristocratic 1930s film actress. “You'll get a seat. Now please be calm. You won't make a scene will you, darling?”
Kevin finally smiled. Herb laughed so hard he stumbled dangerously near the water.
Kevin looked again at the men in tuxedos and said, “I don't want a seat at the table. I can't relate to those people.”
“I think they're interesting,” said Herb.
“So do I,” said Gwen, staying in character. “Don't be a stick in the mud, dear.”
“Myrna Loy in the
Thin Man
, right?” said Herb. “That is fantastic, Gwen.”
Ray appeared, beckoning them inside.
“My, my,” he said once they had shut the door. “You're better behaved here than at my house.”
He patted Kevin on the back and said, “Time for you to meet some of your upper-echelon colleagues.”
Herb and Gwen followed as Ray escorted him to the four heavy hitters.
“Ethan,” Ray said brightly, stretching out the man's name to indicate what a rare pleasure it was to encounter him.
The tallest of the four, a pinched-faced man, responded courteously.
“Ray,” he said with the slightest nod of acknowledgment and no smile.
The other three men gave Herb an infinitesimally less cordial nod of recognition. They eyed Kevin and Gwen with unconcealed arrogance.
“You've all read about Kevin Bartholomew in the newspapers, haven't you?” Ray said as he pushed Kevin into their circle. “I won't hog him to myself when he has the opportunity to meet the department's most illustrious scientists.”
“You have a lab at City Hospital?” asked a short, pugnacious man.
“No,” Kevin replied. “Rajiv Singh does our assay work on the Hill.”
The short man tugged the sleeve of one of his companions. They were close enough to Herb and Gwen for them to hear him whisper, “In the
basement
of the Hill.”
The other heavy hitters stared quizzically at Kevin.
Herb whispered to Gwen, “You're nothing in their world if you don't have your own lab.”
“Rajiv and I are a couple,” Kevin said with a straight face.
The heavy hitters were startled by this disclosure.
“We collaborate,” he explained, “as co-principal investigators.”
Ray stepped in and said, “Kevin's moving to the In-Residence series. I've just put him up for promotion to full professor,
two
years early.”
They were agape now.
“Congratulations,” said Ethan, circumspectly.
Ray mentioned a dean Kevin had to talk to and led him away.
“What was that about?” Gwen asked Herb.
“I'm not sure, but it's a hell of way to let someone know they're going to be the first person in university history with
out
an NIH-funded lab to be put up for In-Residence promotion
early
. And I heard Ray say â
Two
years early.' That is serious chutzpah. Ray really laid down the gauntlet. He's daring the system to make a paradigm shift and allow clinical researchers to have equal footing with basic science researchers. For Kevin's sake, I hope he can pull it off.”
“Kevin won't care whether he's promoted early or not. I don't get why this is a big deal?”
“Ray's trying to change the institutional ground rules of social Darwinism here,” said Herb, still astonished.
“So?”
“If he's successful, you might be next.”
“Me? Hardly. I don't have a quarter of the publications Kevin has. Anyway, I could care less, even less than he does.”
“Right,” he said, not bothering to hide his disbelief.
K
ATHERINE CAME TO
S
AN
Francisco on Labor Day, and for the rest of the week, Kevin quit working at noon. They went out to lunch, then spent the afternoons wandering through the city's more affluent neighborhoodsâPacific Heights, the Upper Haight, North Beach, and the Marinaâenjoying the bay views and Victorian architecture. Katherine was fascinated by the houses, especially once Kevin told her what they cost. He had been in a few of these places and helped her imagine the furniture, people, and dramas inside. It was so relaxing they put off talk of Douglas until the weekend.
They were having a late brunch on Saturday when Katherine brought up her son's conflict over coming out. He had only told his mother he was gay.
“How's Ben dealing with it?” Kevin asked.
“Denial, to the extent he can. He's unhappy, but at least he's not angry at Douglas. I'll give him that.”
“Should I write to him?”
“Ben?”
“No, Douglas,” Kevin giggled. “My consoling Ben because his son is queer would be pretty hilarious.”
“It would be lovely if you wrote Douglas. Just be sure to address the envelope to me.”
She shook her head and laughed. Seeing his sister free of worry unleashed an impulse to run his fingers through her long, thick hair. He couldn't find a trace of gray. He looked at her muscular arms and the faint creases around her eyes. He was proud of her vitality at forty-two. He wanted to say how much their shared history meant to him. He was searching for the right words when the doorbell rang. It was Gwen, stopping by on her way home from the airport after a thirty-six hour trip to the East Coast.
Gwen had never met Kevin's sister. More than their obvious resemblance, she was struck by Katherine's apparent equanimity. If she was anxious about her brother, she wasn't going to let it show.
“I would have flown back last night,” Gwen said, “But I had the chance to go out to dinner with some HHS folks.”
“Any money headed our direction?”
“We'll see.”
As Kevin and Gwen discussed the likelihood their ideas for new clinic services would get federal funding, Katherine listened with interest.
“Is the government taking responsibility for finding a treatment?” she asked.
“There's a ton of grant money,” said Kevin. “NIH, even the FDA, is giving it away to anyone with a reasonable hypothesis to test. The fuel is there. What's missing is the right tool.”
“Tool?”
“We're not going to be able to cure this infection any time soon. The best we can hope for are medications that can control it, which means the effectiveness of a new drug has to be judged by how much it reduces the amount of virus in people's bodies.”
“That makes sense.”
“Unfortunately, we don't have an accurate method for measuring that. There's no gold standard. Labs all over the world are working on ways to quantify the virus. But so far their assays are too complicated and expensive to use in trials, and their results aren't anywhere close to reproducible.”
“Hey, wasn't that what your paper in the British journal was about?”
Kevin's forehead furrowed.
“Your brother made waves by exploring whether some other markers in people's blood could be a substitute for measuring the virus,” Gwen explained tactfully, “but the FDA shot down his idea. They issued a statement that any surrogate marker like the ones he reported on would have to be validated by a lot more studies before they would even consider allowing it to be the basis for new drug approval. Which basically means until we have a reliable method to measure HIV viral load in a patient's blood, we're going to have
to wait for more trials to show differences between treatment arms in the number of deaths and complications of AIDS that occur.”
“Which will take years,” Kevin said, “With AZT on the market, it's unethical to conduct trials where people get nothing but placebo, which means new trials have to have an AZT control arm, which mean the trials have to be much larger and longer to show statistically significant differences in those kinds of outcomes. So the longer it takes for viral load assays to become reliable, the longer it will take to develop effective treatment, and the more people with AIDS will die.”
Gwen wondered if Katherine shared her brother's belief the infection would eventually be mastered. Gwen was hopeful but not convinced. She glanced at Kevin, who was lost in thought, then to Katherine who turned her eyes to him then back to Gwen, smiling confidently.
Gwen was puzzled. Was Katherine naïvely optimistic or did she have a deeper source of certainty? She decided she needed to get to know Kevin's sister better.
He changed the topic by asking Katherine about the Massachusetts governor running for president. Having just returned from Washington, Gwen didn't want to talk politics. She noticed a coffee cake in a glass baking dish. She knew cooking wasn't in Kevin's repertoire of skills.
“Did you make that?” she asked.
“I did,” Katherine answered. “Have some. Kevin's trying to maintain his boyish figure.”
They all laughed.
That evening, Kevin and Katherine went to a restaurant in the Castro. He had no appetite and became queasy with his first bite of food. Soon a dull ache was throbbing under his left rib cage. The intensity increased rapidly. Over the past year, Kevin had cultivated a stoic approach to physical discomfort. He could ignore nausea, diarrhea, fatigue, the constant sensation of pins stuck in the soles of his feet. But pain like this was outside his range of experience.
The anguish on his face terrified Katherine.
“What should I do?” she implored him.
“Get the car. I don't know how far I can walk.”
He handed her the keys. By the time she returned, the pain had subsided enough that he could stand up and avoid the humiliation of being carried out of the restaurant on a stretcher.
Katherine drove to a nearby private hospital where Kevin's doctor had admitting privileges. Art Krimsky was one of several dozen physicians in the city, unaffiliated with the university, who devoted their practice exclusively to HIV patients.
In the emergency room, Kevin had blood drawn and an intravenous catheter placed. He was transported to radiology for a sonogram of his abdomen, then to a private room where Art was waiting. After pressing gently on his belly and listening with his stethoscope, Art spoke.
“You have pancreatitis, Kevin. You're amylase is 800.”
Kevin was unnerved by Art's grim demeanor. Acute pancreatitis eventually resolves, he thought. It's just pain that has to be gotten through. There's probably a gall stone blocking my pancreatic duct. Sooner or later, it'll pass through.
“I know the drill,” he said. “Nothing to eat or drink. IV fluids and morphine. Surgery if it gets worse. I'll stay put here.”
Art looked away.
“Why are you laying so much crepe?” Kevin demanded.
“Sorry,” Art apologized.
The next morning, Art arrived more somber.
“I called NIH, Kevin. They've seen four cases of pancreatitis in patients on DDI. You're the fifth.”
“OK, I'll lay off it for a while.”
Now Art looked positively glum. He nodded in agreement and patted Kevin on the shoulder. Kevin turned to Katherine whose face was ashen.
“It's not the end of the world,” Kevin declared.
Katherine's eyes welled with tears.
Kevin knew he was missing something. If it's so obvious to them, why don't I get it? And then he did.
“NIH won't give me any more DDI.”
“I'm so sorry,” said Art.