by Matt Richtel
Jason and immunotherapy were headed for a date.
45
The Other Shoe
On December 11, 2013, Jason came to Dr. Brunvand’s boxy office at the Colorado Blood Cancer Institute for an eighty-minute meeting that seemed slated for joy. Jason had survived more than twenty-two months without a relapse after taking brentuximab during 2012 and experiencing a full year of remission in 2013; at twenty-four months, he’d have hit a state of remission considered significant and predictive of full recovery.
“How are you feeling, Jason?”
“All right. Good days and bad days. Some days are awesome. I get a ton of shit done, and then I’ll just be exhausted.”
Understandable, Dr. Brunvand told him. His body had been through three years of hell. But now Jason was down to taking only acyclovir, a medication to prevent cold sores and worse.
“You’re turning the corner, Jason.”
He just had to make it another six weeks and the ordeal would be over.
A week later, back in Vegas, Jason got a massage. He woke up the next day with swelling under his left armpit, where the armpit meets the shoulder. It’s known as the axilla. It lasted a month. He came back to Denver to get it checked out. Now he was only a few weeks from being in the clear. He got a scan of the inflamed area.
On February 2, Jason was pumped up. He was feeling good and going to make a night of it with his oldest friend (and part of the high school gang), Bob Nesbit, and watch our beloved Denver Broncos play the Seattle Seahawks in the Super Bowl. The bad news: The Broncos got destroyed, 43–8. The good news: It was over pretty quickly, practically by the end of the first quarter. Jason had a blast with Bob and was feeling pretty good, despite the outcome of the game.
The next day, he was at the grocery store in Boulder with his mother when his cell phone rang. It was Poppy Beethe, Jason’s nurse from the cancer center.
“Hey, Poppy! What’s the word?”
“Jason, I’ve got some bad news.”
“What? Tell me.”
“The tests have come back. Why don’t you come in and meet with us.”
February 11, 4:30 P.M., Jason went to Dr. Brunvand’s office to learn his fate. “I’ve got it, don’t I?”
“Look, Jason, we’re not out of options.”
They were long past pussyfooting around.
“We have options,” Dr. Brunvand repeated, “but there is no standard therapy at this point.”
“So what does that mean?”
“You made it a year disease-free after taking brentuximab. So we can try that again.”
Jason listened and just felt so beyond defeated. He couldn’t begin to stomach the idea of putting himself through the hell of chemotherapy again when the cancer kept coming back.
Dr. Brunvand explained that there were two other drugs that might help. One of them was aimed at causing the cancer to overexpress a molecule called CD30 so that it could be more easily targeted by the brentuximab.
“They have risks, Jason. They can actually lead to other malignancies. But those risks aren’t any worse than the malignancies that you’ve already got.”
“And if I don’t do it? If I can’t put myself through it again?”
“Median survival is less than six months.”
Dr. Brunvand proposed they start in six days. He had the impression that Jason was on board.
“Rick, I can’t do it.”
He called me and told me he was done. Enough already. The guy I had known as the ultimate competitor was ready to redefine the battle. It wasn’t about fighting anymore, it was about not suffering. It was about peace.
“I won’t spend the last months of my life feeling like shit.”
“I feel you, Greenie. It makes a lot of sense.”
“It’s just so wrong. I was so close. I feel fine. I feel great.”
He said he wanted to talk about it some more.
Two of Jason’s best friends, Noel and Tom, and I started a text conversation. We decided that it was time to get the gang together, the members of the Concerned Fellows League. We set a date. Tom would come from Minnesota and I from San Francisco, and Noel would host in Boulder with just a few of Jason’s oldest and closest. We told Jason that we were having a reunion, without putting so fine a point on it: We’d be coming together to say goodbye to Jason.
Bob Nesbit picked me up at the airport and we got to Noel’s house in Boulder by early evening. Tom was there, and Ariel Solomon, an absolute prince of a human being who was a year behind us in high school but had long since been part of the gang. Ariel had been a lineman for the Pittsburgh Steelers, had a Super Bowl ring to show for it, and had become a triathlete and still looked the part of a fit giant. In fact, everyone looked and seemed great, just older versions of themselves.
There were some differences. The heavy drinking that at times accompanied our adolescence was mostly gone. Two among our group had dealt with drinking problems, and they went heavy on the seltzer water. These were now open secrets and what dawned fairly early in the evening was some good news. We all seemed much more at ease with our more mature selves than the alcohol-fueled versions that we’d passed off in high school and college. We had a good conversation about family and life, and we waited for the guest of honor.
And waited.
At some point, Jason called or texted to say he was getting there. He’d driven since dawn from Vegas.
He got there by nine, a whirl of Jason, flip-flops, jeans and a flannel shirt, stale smell and a wide smile and a high-pitched laugh, and he immediately launched into a story.
“You guys gotta hear this,” he said. “I was at grief counseling last night with Beth, and I was trying to use it to break up with her.”
“C’mon.”
“I’m serious. I keep telling her that she doesn’t need this shit. But she won’t have any of it. I was thinking maybe I could get the counselor on my side.”
“You’re a savant, Greenstein. No one else could use death counseling to try to get out of a relationship.”
“I know. But it’s not working.”
It was beautiful. Not Jason’s tactics—just Jason being Jason—smiling, laughing (squealing), not taking himself too seriously, late to his own party, living on his terms. He looked damn good.
He had another story to tell. He’d gotten himself locked up by the Vegas cops. What had happened is that over the years he’d amassed a bunch of parking tickets that he’d failed to pay because—well, why bother? Then late one night, with insomnia, he’d gone for a walk. It was hot and he was sweating like hell. He’d wound up in a so-so part of town and was walking sort of aimlessly when he realized that a cop had taken notice of him. Jason was dripping sweat. One thing led to another and the cop wound up checking Jason’s info and discovering he was wildly in arrears on parking tickets. The cop took Jason to the clink, where, exhausted and overcome with the cancer sweats, he sat in a holding cell, waiting to be processed and taking in the tight quarters filled with macho twentysomethings on the brink of coming to blows.
“I had to take a shit the whole time, but there was this little silver bowl in the middle of everything!” Jason being Jason, he was howling, appreciating his own self-made misfortune, and we weren’t sure if we were laughing at or with him. But speaking for myself, I thought he looked as alive as anyone in the room—certainly not like a guy who had six months or less.
Bit by bit, the conversation turned serious. Jason brought everyone up to speed and he recounted what he’d told a few of us: He couldn’t do any more chemo.
“I want to enjoy one more Final Four,” he said. “What do you guys think I should do?”
His question was rhetorical in the sense that I’m not sure our counsel mattered, or even that it should. It was Ariel who took the first crack at answering. “If it was me, I’d do everything I could to fight,” he said. “If you’ve got a chance, you’ve got to take it.”
Ariel hadn’t been so much part of the saga the prior few yea
rs, and certainly had not heard Jason’s recent misgivings about treatment, so his position was totally understandable. Others said they appreciated Jason’s position. It wasn’t a long conversation. Jason seemed burdened by Ariel’s comments. He didn’t like to think of himself as a quitter.
We stayed up late, playing pool and agreeing to get together for breakfast. We’d rekindled our group, our connection ripened by time, and we weren’t quite ready to say goodbye to our founder.
At a restaurant painfully named Eggscetera, we brunched. Beforehand, Bob and Noel and I had talked about taking a moment to let Jason know that we agreed with him that it made sense to hold off on treatment. It’s not that it actually made sense to us; that was irrelevant. Rather, it made sense to us that it made sense to him.
He nodded and took in our counsel. “Ariel got to me a little,” he said. But he was still leaning away from treatment.
In the parking lot, he wanted a parting gift. He wanted to take a picture next to me, side by side, in profile, to see, as he put it: Which of us has the larger nose?
It looked to me like a tie—for last.
We hugged and I headed to the airport. I doubted I’d ever see Jason again.
Part VI
Homecoming
46
Bob
Bob Hoff, one of the oldest living asymptomatic HIV sufferers, had fallen deeply in love with one of the longer-living sufferers of HIV who was, by contrast, symptomatic. His name was Brian Baker, the disc jockey and record-store employee mentioned earlier. He had been diagnosed in 1992 and narrowly survived the pandemic thanks to the discovery of the cocktail. By this time, in 2014, they were living together and talking about getting married.
It had been love at first sight, at least for Bob.
That first sighting had been in 2001 at the gay pride parade in D.C., and Bob had seen Brian walking down the street and thought, “Look at that f-ing gorgeous man!” Bob took a picture of him. That seemed to be the end of that. The next year, Bob was in Chicago at the International Mr. Leather contest, and he saw Brian again. Bob’s friends told him to stop being so shy and go up and say hello.
Bob approached, told Brian he’d taken his picture, and then explained to Brian that he liked to paint portraits. “Last year, at gay pride, I took a picture of you. Would you mind if I painted that picture?”
“It was the cheesiest pickup line I ever heard,” Brian said. He fell for it.
They had been together ever since. In 2010, Bob proposed to Brian, and they agreed to marry at some point when it was practical. On November 23, 2015, they were wed at the courthouse in D.C.
Shortly thereafter, Bob went in to the NIH for his usual assessment. He was in the waiting room when Dr. Migueles walked by. Bob jumped and shouted a greeting. He held up his wedding ring. “I finally convinced Brian the timing was right to tie the knot!”
The two men hugged. Then Bob told his wedding story, tears in his eyes.
“I was so, so happy for him,” Dr. Migueles said.
Bob Hoff joyfully settled down and is still alive.
Bit by bit, test by test, Dr. Migueles and the team working at the NIH had spent some twenty years in a painstaking process of identifying the lifesaving quirk in the immune systems of Bob and other controllers. In fact, when Dr. Migueles was first hired, he’d made that inventory of possible mechanisms—strain of virus, number of T cells, genetic profile, etc.—and they’d assiduously gone down the list, eliminating those factors that weren’t sufficiently distinct to explain the issue.
One clue that seemed crucial had to do with the strong association of elite control with the HLA-B57 gene, which is present in 10 percent of the population in North America, but present in about 70 percent of elite controllers. There are numerous HLA genes and genetic variants, so the enrichment of one in particular in this group is striking. HLAs, or human leukocyte antigens, are encoded by HLA genes and are central to the way the body’s surveillance network distinguishes self from alien. HLA, it turns out, has to do with how molecules in the immune system present HIV to the CD8 T cells; those are the soldiers, the fighters, the killers. HLA-B57, compared with other HLAs, might be more likely to present the virus in such a way as to provoke a more effective and lifesaving response. But B57 was not the definitive answer, since up to 30 percent of elite controllers do not have B57 and 10 percent of patients with typical HIV disease carry it.
“Genetics are operative but not sufficient,” Dr. Migueles said they realized. His endgame was much more ambitious: He and the team at the NIH, and other scientists around the world, wanted to create a vaccine for HIV. To do that, they had to know how HLA-B57 was involved in fighting off HIV. Otherwise, they couldn’t reproduce the results. If they could understand the mechanism, “you don’t have to have B57,” he said.
One by one, they ticked off the list of mechanisms they had hypothesized twenty years earlier might explain viral control and be reproducible in some way in the creation of a vaccine.
To understand what Bob is teaching us, Dr. Migueles contrasted him with what we now know about how most people react to HIV. Like Bob, they also recognize and confront the virus. They might even recognize and mount a response to the same pieces of virus. The key difference between the immune responses in patients like Bob and the mainstream way of attacking HIV appears to involve the quality and strength of the response. Bob’s CD8 T cells proliferate, or reproduce themselves, to high levels when they reencounter HIV. As they do so, they increase their killing machinery and load their guns to become even better killers. These serial killers efficiently destroy any infected cells in their midst in a focused fashion. The CD8 T cells from most other individuals with HIV mount a much weaker response and have lower killing ability. HLA-B57 and a few other “protective” HLAs probably predispose a person’s immune system to have this impressive response to the virus in a way that we still do not understand, but one does not need HLA-B57 to develop this major immune system offensive.
So at that point, the immune system makes a calculation that we now know to be central to the very essence of our defense network. It decides whether such a powerful offensive would be worth it. Would it make sense to create an all-out offensive that might destroy HIV but at the risk of creating so much damage to self that it would not be worth it? Should the immune system go nuclear?
No, it should not. At least that’s the calculation, Dr. Migueles explained. The immune system decides that the consequences of such a nuclear war would be “radioactive” fallout—inflammation, autoimmunity, massive internal strife, maybe death.
So the immune system puts on the brakes.
“It gets toned down,” Dr. Migueles explained. “This stunning tolerance mechanism is a way for the host to decide: ‘This fight is too big. It’s a fight that will kill this person.’ So it settles for a less robust response. It cohabits with the virus, thinking, ‘At least it’ll kill me slowly.’ What this research has taught me,” Dr. Migueles continued, “is when you study autoimmune disease or cancer, how many similarities there are.”
The immune system is making trade-offs to keep the peace, to maintain homeostasis, to let the individual live as long as is practical. It’s just math.
Given what they had learned, Dr. Migueles and Dr. Connors started looking for the best approach to a vaccine. One idea was to get the CD8 cell to “ignore the inhibitory signal.” Could they turn off the brakes on the immune system the very way that the cancer pioneers were trying to turn off the brakes so the system would attack cancer?
In theory, yes. But, so far at least, they can’t figure out what molecule or molecular mechanism controls the braking system that is slowing the immune system in its fight against HIV.
There was another way to attack the problem, albeit a long shot.
In 2014, the NIH team helped other researchers take the lymphocytes from an elite controller and infuse them into a late-stage HIV sufferer. This notion was dangerous. That’s because the immune system of the receiving pa
tient might well reject the cells as nonself, just like any failed transplant. It was no small decision to try the experiment. On the other hand, the subject slated to get the cells had a multidrug resistant virus and few options, the kind of person who throughout history has grudgingly welcomed an immune system experiment because the alternative—likely dying anyway—wasn’t so great either.
They took the cells from an elite controller (not Bob) and put them into the patient.
Dr. Migueles got a pleasant surprise. The B27-matched CD8 cells stayed active for around eight days. Plus, the study subject’s concentration of HIV virus dropped twofold before returning to his baseline. “It was safe, and it appeared to have a transient immune effect on the virus,” Dr. Migueles said.
It was a far cry from a cure, though, and the donor cells eventually disappeared. It has its own massive side effects, or potential ones. At the least, it continued to advance the idea that it’s possible to build a mousetrap that is better than the AIDS cocktail.
Bob Hoff offers another lesson, and it has to do with the health of the entire society.
Were it not for people like Bob Hoff, the human species would have been wiped from the earth eons ago for the simple reason that the species cannot survive without diversity. After all, it was the diversity of Bob’s immune system that allowed him to survive.
Imagine previous pandemics—hundreds of years ago, when there was no modern medicine. In those times, in those eras, the diversity of the human immune system gets credit for our survival. Some people didn’t die of the Spanish flu or the Black Plague. Some people had a genetic predisposition, combined with a set of circumstances, that allowed them to survive.
From a purely scientific standpoint, Bob’s legacy hasn’t turned out to be the Holy Grail, not yet the way that Dr. Fauci and Dr. Migueles dreamed it might be. If Bob’s white blood cells—his immune system—hold the key to a more natural way to fight HIV, the researchers haven’t been able to tease it out.