Nathalia Holt - Cured: How the Berlin Patients Defeated HIV and Forever Changed Medical Science

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 didnt 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 werent 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 didnt have to use some other, related virus. We could use the real thing. In our study, we took this a step further. We didnt 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 didnt 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 shouldnt have to worry about the mouse because someone else would be there to help. I had gone against my own procedure.

I couldnt simply leave the animal there. Turning to my left, I looked at the mouses 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 werent 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 didnt bother. I didnt 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.