Now, in front of me, in a vented, pressurized hood, lay one of those guileless creatures: a small white mouse. Its breaths were heavy in sleep. Encircling its nose lay a tiny clear plastic mask, providing the mouse with isoflurane, a powerful anesthetic capable of keeping the animal motionless while I performed the risky procedure. But the problem was, the animal was not motionless, at least not entirely. Just as I leaned in to inject it with a highly concentrated, lab-adapted aggressive strain of HIV, the mouse jerked. In that moment, the unthinkable happened: I accidentally poked my finger with the needle.
It was the third year of my doctoral studies. I was working on an innovative gene therapy approach to treat HIV. The idea was to knock out a gene that HIV needs for entering cells. We could knock out this gene in stem cells and then infuse them in a patient. All the immune cells that matured from the progenitor cells could then be resistant to HIV. The hope was that this therapy would create a functional cure the likes of which had been seen in only one man: the Berlin patient. At the time, we didn’t know who he was. All we knew was that we wanted to replicate his experience in others who had HIV. To test the therapy, we were injecting those modified stem cells into mice. But these weren’t just any mice. They were genetically engineered to have no immune systems of their own. When the human stem cells are injected, they develop a working human immune system, or, at least, as human an immune system as you can have inside a mouse. The exciting thing was, we could inject these mice with HIV itself. We didn’t have to use some other, related virus. We could use the real thing. In our study, we took this a step further. We didn’t want to cure just any HIV. We wanted to cure the most aggressive, pathogenic strain we could find. If we could cure that virus, we could have a cure for all strains.
But now, the fact that we were using an aggressive strain of HIV seemed like a huge mistake to me. Not only could I be infected with HIV but I could be infected with a super strain of the virus able to cause AIDS at a rapid pace.
I was completely alone in the windowless room, the hum of the vent hood, a device designed to protect me from pathogens, filling my ears. I sat for a moment and looked at the mouse. My first instinct was to pretend that none of this had happened. I didn’t want to admit to anyone that I could be so foolish. Protocol dictated that I should immediately call for help and then remove my gloves so I could wash the wound for fifteen minutes, using a special soap designed to kill viruses and bacteria. But what about the mouse? I had no idea what to do. This was made further ridiculous by the fact that I had written the safety procedure. A single line haunted me: “All HIV infections will be performed with a minimum of two people attending.” A safety mechanism designed just for this moment. Under the conditions I had outlined, I shouldn’t have to worry about the mouse because someone else would be there to help. I had gone against my own procedure.
I couldn’t simply leave the animal there. Turning to my left, I looked at the mouse’s littermates. They were all under anesthesia, sleeping peacefully in the cage. If they were left under anesthesia too long, they would die. So would this mouse lying in front of me.
These weren’t just lab animals to me. I had been there on the night each of them was born. I had held their tiny pink bodies in both of my hands as I injected millions of human stem cells into a vein that ran down their cheek and was no thicker than a human hair. I had watched them nervously as they grew up, knowing that some of them would die. Now, three months later, I was about to inject them with a virus responsible for the deaths of millions of humans. My relationship with these mice was not simple. Every blood draw, every procedure, I cared for them. I used anesthesia when other researchers didn’t bother. I didn’t want them to suffer even for a moment. If they suffered for reasons beyond my control, I put them down, even though each one was priceless to me, representing weeks of work.
On the other hand, HIV works quickly when injected. While only a small percentage of accidental needle sticks occurring in a hospital result in an infection, my case was different. In the majority of needle-stick cases, the person whose blood is drawn is on antiviral drugs and therefore has no detectable virus in the blood. My case was the opposite. The needle I held contained a highly concentrated form of the virus, designed to maximize the infectious dose given to each mouse. Some studies have shown that the chances of transmission are reduced if the exposed person receives antiviral therapy within one hour. The clock was ticking.
Almost as if someone else possessed me, I calmly carried out my experiment that day. I acted as if nothing had happened. I quickly lifted the skin of the animal’s belly before me, injected it, and gave the mouse the prescribed dose of HIV. Exactly like the dose I had just, accidentally, stuck in my own hand. Relieved, I threw the needle in a bottle of bleach and stopped the anesthesia flowing to the mouse in front of me. I gently placed him on his back in his cage, careful to make sure that no bedding was covering his nose, potentially blocking his airway. I watched as his cage mates smelled and prodded him with their whiskers. I waited a minute, observing his respiration leap from the slow drug-induced pace to his normal frantic breaths. He woke with a jerk, flipping onto his paws. He would be fine, but would I?
Inexplicably, I then finished injecting each of the remaining mice with virus, repeating the same procedure that had just resulted in my accidental needle stick. I cleaned the hood and put away the anesthesia equipment and my tools. I took off my gown, mask, hairnet, and booties. Then, as soon as I grasped the door handle, my hand began to shake. Once outside the mouse room, I began to break down. I washed my hand for a timed fifteen minutes, furiously rubbing the iodine mixture into the tiny puncture just barely visible on my finger. I left the labyrinth of the basement lab and stepped out into the warm California sunshine. Traffic swarmed around me as I crossed the street to the office of my academic advisor, Paula Cannon.
“I’ve had a needle stick,” I told her. There was laughter seeping in from the hall as students joked with one another. Paula’s response was characteristic: She was calm and collected. She made a quick call to the clinic and off we went. Inside the main building of Children’s Hospital Los Angeles, Paula distracted me with funny stories, complained of her husband, and bragged about her kids. Having lost my mom some years before, Paula had become a surrogate mother. She was an advisor, a mother, and a friend all rolled into one. I loved her. She stayed by my side as I got the antiviral drugs I needed.
That next month, I would take a standard drug regimen that millions of people take worldwide to keep the virus in check. The drugs weren’t cheap. The hospital paid $1,000 for that one month of medication. Even worse were the side effects. I spent the whole month sick to my stomach, constantly vomiting. The medication made me tired. I didn’t feel like myself at all. That whole month, while I complained about the effects of an accident I had created, I kept thinking about the many people who take these drugs every day. Not for a month but forever. Not everyone gets sick from the antiviral drugs, but many do. There are those out there who have trouble not just with the side effects but also finding a drug combination that will bring their virus under control. Even worse are the millions who are infected but have no access to the lifesaving drugs I complained about having to take. This book tells the story of how we have developed a cure but also what we still need to do to bring it to the 34 million people infected with HIV worldwide.
• • •
I was lucky. I didn’t get HIV. We changed the safety practices in the lab and, with help, changed the way we injected mice with the virus to ensure that no one else from our group would get a needle stick. I like to tell this story as it demonstrates my weakness at a moment when I needed strength. I’m about to delve into the lives of two remarkable men, both of whom have been cured of HIV. When discussing their lives, I tell the high points and the low points. As I discuss their weaknesses it seems only fair that I disclose at least one of my own. More than weakness, though, this experience changed how I look at HIV. It altered what was once an abstract scientific concept, a medical problem that needs to be solved, and turned it into a human dilemma.
• • •
Two ordinary men changed the way we approached a cure for HIV. Their stories and those of other people reported on in this book were collected through hours of personal interviews with patients, friends, physicians, and researchers. In some cases, particularly those concerning events from more than a decade ago, memories differed between the parties involved. In some instances I report differing accounts; in others I present the account that best fits the associated facts and documents.
A few individuals, including the first Berlin patient, have asked to remain anonymous and I have respected these requests, altering names and identifying characteristics.
Before 2009, HIV researchers didn’t use the word cure. Even today, there are scientists who cringe at the word. It’s important to define what we mean by cure.
In science we talk about two kinds of cure: a sterilizing cure and a functional cure. A sterilizing cure is just what it sounds like: It “sterilizes” the body. This means that no trace of the virus can be found. A functional cure, on the other hand, doesn’t get rid of all traces of the pathogen. But a cure of either type means that the person does not require medication or therapy. Both types of cure mean a person doesn’t have to worry about the virus growing in his body or destroying her immune system. It is also highly unlikely that the person could infect anyone else.
In people with a functional cure, lying hidden in their bodies, detectable only by the most sensitive tests, will be traces of the virus. Persons receiving this treatment are cured, but they will always carry a small piece of the virus with them. For most, it doesn’t matter if the cure they receive is sterilizing or functional; they simply want to be cured. Both Berlin patients received a functional cure for HIV, which is to say they both still carry the virus inside them and always will. This may sound like a strange cure, but it isn’t. After a child recovers from the rash and fever of chicken pox, the virus responsible, varicella zoster, lies dormant in the nervous system for her lifetime.
Viruses are unique in the disease world for their ability to live within us without causing disease. Before the discovery of the first virus in 1892, plagues were seen as simple cause and effect between microorganism and disease—you get infected, you get sick. This is epitomized in Koch’s postulates, a set of four criteria formulated in 1884 for identifying the relationship between disease and microbe. These guidelines define the cause of a disease in simple terms of abundance and pure infectivity. While the criteria work well for diseases such as anthrax and other bacteria, they were written before viruses were discovered and fail us when we consider the world of viruses we now know. A poliovirus is capable of infecting thousands but causes paralytic disease in only 1 percent—you get infected and you may not get sick. We are only just beginning to understand our shared evolution with viruses. Human genomes are riddled with ancient traces of viruses—viruses that, once multiplied inside us, became trapped in our DNA and then passed down the generations. In fact, about 8 percent of our genetic material can be traced to the skeletons of old retroviruses hidden in our chromosomes. The idea that we can harbor a deadly virus within us without the threat of disease is the basis for the functional cure for HIV. Yet the cure the Berlin patients received is only half the story. The other half is what we do with their cure, how it inspires the people and medicine around us.
When discussing scientific research, it is impossible to include all studies that could be considered relevant. I’ve included research that experts in the field believe is most pertinent and exciting. While most of this research is published, some studies are still in early stages, and therefore the results come from conferences and reports. It’s important to note that these types of data are not as established as that published in academic journals.
This book is about two unique and controversial medical cases. In an effort to keep the conversation balanced, I’ve discussed the scientific issues that make the cases controversial. When appropriate, I’ve featured the opinions of those who performed the research or whose reputations carry considerable weight. Sources for conflicting opinions can be found in the Notes section.
This book also includes frank discussion of how new therapies are brought to market and the difficulties therein. How to maximize the limited funding for science is a key issue currently being debated by the research community. Investment in novel therapies remains inadequate. While we would like to think that the hard part of curing HIV is the cure itself, the real challenge lies in getting that cure to the millions who are living with the disease.
One of the great beauties of science is that each study, no matter how small, takes a step in advancing the field. Similarly, this book rests on the shoulders of the many books, research articles, and reports that have come before it. Each carefully examined case in the story of the cure for HIV represents a piece of the puzzle. I have attempted to put the pieces together.