by Matt Richtel
At this point, I’d like to take a moment to show proper respect for some other plagues.
Bubonic plague in the lab. (Pete Seidel)
The 1918 flu pandemic killed up to 50 million people worldwide, according to the Centers for Disease Control, nearly 700,000 in the United States. The CDC says that it is still not totally clear what made this flu so deadly. It has been hard to study in part because it is deadly to even deal with. But one important theory is that what made it so deadly is that the flu virus in humans—to which we’d adapted some immunity—had combined with a genetic variant from birds. What this meant was that many human beings did not have an antibody to combat the flu, even among the massive pantheon of antibodies we all get born with. This is what the CDC says: “Influenza experts believe that a pandemic is most likely to be caused by an influenza subtype to which there is little, or no, preexisting immunity in the human population. There is evidence that some residual immunity to the 1918 virus, or a similar virus, is present in at least a portion of the human population.”
But not everybody died. That’s because some people could mount an immunity. Some people did have the right antibody somewhere in their infinity machine. All hail the value of diversity!
Another big daddy of a plague was the Black Death, a killer of millions of people, including, at one point, as much as half the world’s population in the fourteenth century. The Smithsonian magazine describes three different ways the plague attacks: through the skin, attacking lymph nodes (bubonic); through the blood; through the lungs. The deadly nature of the plague owed to several mutations in the bacteria that made it elusive to the immune system and easy to transfer. Our immune system, in the case of the lung version, was virtually helpless.
And a quick but important word about the bird flu that scared the living daylights out of infectious disease specialists in 1997. A three-year-old boy died in Hong Kong, and then seventeen more people died, struck down by a terrible virus found in birds. The idea was completely heretical when Dr. Keiji Fukuda, an influenza specialist from the Centers for Disease Control, landed in Hong Kong to do the forensics, but it turned out to be true—and all the live birds in the local markets were killed to avoid further contamination.
There is a key aspect to that flu that is consistent with other deadly viruses. The people who died weren’t overcome by the flu itself but by their immune system’s response to the flu. The immune system went into hyperdrive to stop what it perceived as an extraordinary foe. Massive inflammation followed.
“It was a cytokine storm,” Dr. Fukuda said. “People were dying from having an overwhelming response.”
But by the early 1980s, we’d seen flu before. GRID, or AIDS, or whatever the hell it was called, was something new. If you prefer your cup half full, there was a bit of good news. This potential pandemic happened as science had begun to get a handle on the immune system.
A massive machinery had started whirring that would change everything about how cancer was treated. It was all because of AIDS.
“AIDS was the 9/11 of immunology,” a developmental biologist told me. “We suddenly got this panic and everybody started throwing money at immunology.”
23
The Phone Call
Ron Resio, former multiple PhD muscleman, died of AIDS in 1984. Bob Hoff, his friend and onetime sex partner, attended the service, a Navy funeral because Ron had served his country. It was the first funeral of someone who died of AIDS that Bob would attend. Later, Bob reached a point where he couldn’t attend another friend’s funeral; by then, he had attended dozens.
In the D.C. area, “five or six guys were dying a week,” Bob recalled. “People would disappear on a daily basis. It was an onslaught.”
In 1984, 3,454 people died of AIDS. It was going to get much worse. More than four times that amount would die four years later, and then the disease exploded globally.
Regularly, Bob said, American gay men would die, and their parents, disavowing their sons’ sexuality, would disown the surviving partner, wouldn’t invite him to the funeral, or would clean out the house and not give the partner his things back. The parents had decided they were self, and the surviving lover was other, an alien in their midst, and that their son had been an alien too, estranged even in death.
AIDS killed and society turned on gay men as if they were nonself, alien. (Wellcome Collection)
This was exactly how members of the prominent gay community in Washington, D.C., felt they were suddenly being treated by President Ronald Reagan. Bob knew all the operatives, who in turn knew Reagan and Nancy, the first lady, and the operatives knew that Reagan liked them; some speculated his son was gay. “We couldn’t believe he flipped on us,” Bob said. Reagan’s administration was widely criticized for its slow response to the AIDS crisis. This turned Bob, a lifelong Republican from Iowa, into a Democrat. Gay men were sick, and other people treated them as if they were toxic.
The community banded together. Bob, a lawyer by trade, had a real estate license. He tried to get gay men to buy property before they became sick “because money speaks.” He wanted them to have some power, a voice. He and his lover at the time had a house on Fire Island, a gay mecca outside New York City that was the setting for weekly dinner parties and sometimes a refuge. At one point a friend who was in the Air Force got booted out for his sexuality and his condition, AIDS, and he showed up at Bob’s house on Fire Island. That night Bob was upstairs in the house when he heard a thump, but he didn’t pay too much attention to the sound at the time. The airman, too distraught to go on, had mainlined cocaine, “committed suicide in my living room.”
One day in 1984, he recalled seeing a guy named Bill who had been “the most beautiful man I’d ever seen.” Now Bill weighed 95 pounds and was a walking purple lesion. Death was everywhere and inevitable.
There really was no treatment, nothing that could be done. The scientists at NIH, led by Dr. Fauci, had thought maybe they could use the bone marrow—the source of immune system cells—of Ron Resio’s twin brother to bolster Ron’s immune system. The idea was that they’d take out Ron’s marrow, which seemed unable to handle the virus, and replace it with healthy marrow that matched Ron’s own. No such luck. “The virus destroyed the transplanted marrow,” Fauci said. It brought certain death.
In late May of 1984, Bob went in for a regular physical. His doctor saw evidence of an irregular heartbeat and sent him for a follow-up. False alarm. He got the news in a phone call at his government office on June 8.
“Bob, I have some good news and some bad news. The good news is, we got a misreading on the heart test. The bad news is, you’re HIV-positive.”
Just like that.
“It didn’t come as a surprise,” Bob said matter-of-factly as he recalled the moment. “I was as exposed as anybody. I realized I was not going to get through it. I had a year or two to live. It was a death sentence, and there was nothing I could do.
“I realized I was just like everybody else.”
He was most certainly not.
24
CD4 and CD8
At the highest level, there are two ways to understand and stop the spread of a pathogen like a flu virus or HIV. One path is to examine the chemistry, the biology, and the response of the immune system—the antibodies, the hard science. The other is to look at the circumstances surrounding a disease or outbreak, the epidemiology. What behaviors and broader factors seem associated with the disease? Does it happen in poorer areas with filthy water, or where certain foods are consumed, or where the air quality has changed?
Is it associated with sex?
In the first few months of the AIDS outbreak in 1981, the epidemiology said: “This is happening among clusters of men having very, very active sexual contact and, very soon thereafter, we found it was in injection drug users,” in the words of Dr. Fauci.
This limited information still had great value to immunologists. It said that they were likely dealing with a virus. This was so for two reasons: I
t was transmissible like a virus, and importantly, it was unlike a bacteria or a parasite—in part because those can typically be seen in the tissue. Remember that a virus hides in cells. That can make it very hard to detect, even with sophisticated tests. The virus does slip out of cells as it goes from one to the next, but if you don’t know what you’re hunting for, “it’s like looking for a needle in a haystack,” as Dr. Fauci said.
Then at the end of 1984, there was a remarkable meeting at the CDC in Atlanta attended by some of the brightest minds in medicine. One attendee, Jack Dunne, described the mood: “Everybody is like: What the fuck? Nobody gets this. It was pre-terror.”
One woman got up in front of the packed lecture hall, with perhaps a thousand people in attendance, and offered head-twisting epidemiology. She put up a graph with two axes. On the y-axis was the severity of the disease, and on the x-axis was “the number of fisting [anal fist-fucking] events per week.”
The intimation was, there was something involving the ripping of tissue.
“My own hypothesis was that the people who were sickest used amyl nitrate,” Dunne said. Amyl nitrate, known colloquially as poppers, relaxes muscles like those in the anal cavity to allow easier sex. Bob Hoff and his cohort used them all the time.
“Everybody was trying to figure out the mechanism of action.”
Meanwhile, there was, of course, one more big-picture data point: Everybody was dying. “I refer to them as the dark years. It was terrible, horrible. This was an inexorable process,” Dr. Fauci said.
How did this infiltrate the body and befuddle the immune system?
On the hard sciences side, a clue had showed up with the very first patients.
The 1970s, that decade of explosive learning about the immune system, had yielded important clues about the depth and subtlety of the immune system. One such clue is that the T cell itself is much more complex and multifaceted than had been previously understood. In fact, it became clear in the 1970s that there were fundamentally different kinds of T cells, core immune cell soldiers and generals.
“To that point, one T cell looked the same as another T cell under a microscope,” Dr. Fauci said.
The two main kinds of T cells that had been discovered were known with characteristic blandness as CD4 and CD8. CD4 T cells are called helper cells, and they induce action by other immune system cells; CD8 cells are killers. They do the dirty work. Or, if you prefer, CD4 cells are the generals and CD8 cells are the soldiers.
The initial tests suggested to researchers that men infected with this syndrome had sharply lower counts of CD4. Given that relatively little was known about the immune system, it was goddamn lucky that one of the things known was implicated.
“It was curious that their CD4 cells were way down, and some of them even had an increase in CD8,” Dr. Fauci pointed out.
It looked a bit like the immune systems of the ailing had very few generals left.
There was another lucky break. It had to with a discovery made a few years earlier that, on its face, had nothing at all to do with AIDS or T cells. It concerned cancer.
In 1965, a physician and pioneering scientist named Robert Gallo arrived at the NIH and started treating children with acute leukemia. “Mostly unsuccessfully,” he wrote in a journal history. It was rough, dealing with terminal cases—“a vivid experience and one which made me absolute in a decision to be fully involved in laboratory research and not return to clinical medicine.”
In the course of studying leukemia, Dr. Gallo started looking at retroviruses in animals. These viruses were known to cause leukemia in some animals. That’s why he was studying them. It wasn’t known if there was such a thing as a human retrovirus. Dr. Gallo wrote that looking for one was “an unpopular goal at this time, considering the decades of attempts and failures.” The effort to fight cancer had been down this road before; plus, there was “little evidence” of leukemia-causing viruses in primates.
Finally, retroviruses were generally easy to identify in animals, so if there had been one in humans, shouldn’t it be more self-evident?
What is a retrovirus? A nasty little bastard, typically more cunning than your usual viral fare.
Understanding the retrovirus requires the slightest explanation of basic genetics. DNA is the biological master plan. It dictates an organism’s characteristics and traits. RNA helps execute the plan. I think of DNA as the architectural blueprint, and the RNA is the general contractor. RNA puts the plan into action, and it instructs lots of “subcontractors,” like cells and proteins.
A retrovirus adds a new and unexpected twist.
In a retrovirus, the RNA turns viral; it has contracted a virus. The viral RNA is equipped with a special enzyme that causes a process called reverse transcriptase, which turns the RNA into DNA. In other words, the virus causes the process to go in the opposite, or reverse, direction from the typical genetic process by which DNA instructs RNA. Here RNA has become DNA, and that DNA integrates into the nucleus of the cell and into an organism’s own DNA. Thus this virus has essentially co-opted the organism to make copies of itself—copies that are hard to detect. It squirts out of the cell as viral RNA, infects another cell, and the cycle goes on.
This was generally understood when Dr. Gallo entered the picture. He was the first to discover a retrovirus in human beings. It was called human T-lymphotropic virus type I. HTLV. This is a retrovirus that infects T cells. We understand much more about it now than was grasped then. We know now that the virus is inside a measurable portion of the population, up to 1 percent in some regions of the world, according to the National Centre for Human Retrovirology in London. The organization notes that most people have the virus inside them for years and do not suffer disease from it. Somehow the immune system keeps it in sufficient check; only one person in twenty develops disease.
One such disease is adult leukemia. This is what Dr. Gallo was looking for, and he found it, a link to cancer. He also discovered an important marker of the retrovirus that explains in part why I’m telling the story. Sufferers had a low CD4 count.
The earliest researchers of this deadly plague, not yet even called AIDS, had their first clue. It had a characteristic shared by a recent discovery of a human retrovirus. “People argued: It attacks CD4 positive T cells. Something is killing them. Maybe it’s another form of retrovirus,” Dr. Fauci said.
HIV is the virus that causes AIDS. The story of the discovery of this core connection has been told many times and very well, and I won’t repeat it here in a lesser fashion. In the utmost shorthand, it was discovered through key work by Dr. Gallo and Luc Montagnier and Françoise Barré-Sinoussi in France, and many others less celebrated who made key contributions. (There was a dispute over exactly who deserves the credit and whether Dr. Gallo’s work was complicated and overlooked by the Nobel Prize committee, but that’s a discussion for a different book.)
Small buds of HIV infecting a human immune cell. (NIH)
What is relevant here is that a collection of great scientists figured it out, and their work was built on the incredible significance of Dr. Gallo’s discovery of HTLV—“the sine qua non,” Dr. Fauci said. “Without it we would’ve been nowhere with HIV.
“What happened next happened very quickly.”
A test was developed to screen for the disease. You’d think that would have been a positive development, but initially at least the news was not just bad but terrifying. For years, Dr. Fauci said, the men coming to the clinic for treatment were in the final stages of their lives, but their numbers were relatively small, suggesting HIV was somewhat contained. But when scientists and doctors started administering the test to seemingly healthy people, they discovered that the infection was widespread.
“To our amazement and horror, we found out the sick people were just the tip of the iceberg. Thousands and thousands and thousands of gay men who were not sick tested positive for the antibody,” Dr. Fauci said.
There were 16,908 deaths related to AIDS in 1987, acco
rding to the New York Times, 20,786 in 1988, 27,409 in 1989, and 31,120 in 1990.
The sufferers of HIV and AIDS were society’s throwaways.
There was at least one extraordinary exception. Magic.
25
Magic
On November 7, 1991, Stephen Migueles, a medical student at the University of Miami, was ironing a shirt and watching the news when one of the world’s greatest athletes, Earvin “Magic” Johnson Jr., appeared on television for a special announcement. Magic wore a dark suit, a white shirt, and a gray tie with a hint of red.
“Because of the HIV virus that I have attained, I will have to retire from the Lakers.”
The eventual Dr. Migueles was riveted, like so many, but perhaps his interest went deeper. Dr. Migueles worked in the AIDS ward trying to stop one of the deadliest viruses ever with the equivalent of Band-Aids.
Dr. Migueles brought extra baggage. He was coming out of the closet. No easy task for him, having grown on up in a Hispanic, deeply Catholic family.
“I knew what I was, but I hadn’t blossomed into my full self, if you will,” he told me. He’d come out to his family and it hadn’t gone well. At the time, his parents were devastated.
Then he was watching the men in the ward die. “I was trying to be true to myself, and I saw people around me who had come out and were proud of who they are and dying because of it. It was a scary crossroads.”
Magic Johnson’s revelation meant something to Dr. Migueles. “He was more mainstream,” Dr. Migueles said, but that wasn’t all. “Most people you learned about who had AIDS were celebrities and seen as dying. Magic seemed to be a little different, seemingly robust. He looked like he was doing great.”
He was lucky, of course. Only days after Magic’s announcement, Freddie Mercury, the operatic rocking lead singer of Queen, announced he had AIDS. He died on November 24, 1991.