I was deliberately infected with Zika to test a vaccine. Human challenge trials like my one could save millions of lives by developing prophylactics more quickly.
It started, as good things rarely do, with a tweet: there was a human challenge trial looking for healthy men, 18–40, near me. Previously, I had worked for 1Day Sooner, an organization that advocates for the right of volunteers to participate in human challenge trials, so it felt only fair that I should take part in one myself. Well, I was a man 18–40, of sound body and nominally sound mind. I signed up.
Challenge trials were a subject of intense controversy during the Covid-19 pandemic. It’s easy to see why: challenge trials involve attempting to deliberately infect the subjects with the disease in question. Malaria challenge trials used to close volunteers into rooms with hundreds of malarial mosquitoes, which was as pleasant as it sounds. (They’ve since begun to use a small box of mosquitoes with a hole for your arm – or a syringe). This may seem like a violation of the most basic principle of medicine, the idea that you’re supposed to heal people, not hurt them. But without deliberate, controlled, and monitored infections, scientists are forced to rely on studying wild infections – which means many more patients need to be infected (and harmed or even possibly killed) to provide the same quality of data that a human challenge trial could collect.
Of those people who are exposed in the wild, many of them may be reluctant to participate in a study, or they may only show up once symptoms begin and it’s too late to study the disease’s earliest stages. Before a treatment is shown to be good enough, ethicists worry that patients could be unethically pressured into ineffective trials – but once a good enough treatment is identified, doctors may be obliged to give it to everyone who needs it, making it impossible to study other treatments or even maintain a control group. On top of that, prospective participants who do become sick don’t necessarily want to sign up for all the poking and prodding that scientists would like to do.
Toward the end of the screening call for the trial I had applied to, I was asked if I had any questions or safety concerns about getting Zika virus. I didn’t know anything about Zika other than that it was probably a neglected tropical disease and causes birth defects. But, during my previous work, I had published a meta-analysis on the safety of human challenge trials in general, and knew that severe adverse events, the medical term for bad things, were extremely rare in such trials.
As it turns out, this was broadly correct. Zika is a Flaviviridae-family virus, like Dengue or yellow fever. It was first isolated in the Zika forest of Uganda in 1947. At the time, America had bigger problems – especially the natural outbreak of smallpox two years later. But the year-old CDC (Centers for Disease Control and Prevention) tracked it, and tried to understand more about it. Zika wouldn’t have an outbreak among humans until 2007, so it stayed a fairly low priority. It almost never kills, after all.
The primary reason that we care about Zika is that if someone is infected while pregnant then their baby can be born with microcephaly. Microcephaly, abnormal smallness of the head, is a fairly serious birth defect, the kind that can lead to lifelong medical issues. But for those of us who aren’t currently pregnant, getting Zika is not too scary. The advice the CDC gives for those who are infected is pretty basic: sleep, fluids, acetaminophen (paracetamol), and if you’re taking meds for something else already, talk to a doctor. About what my mother would advise for a cold. As a mild spoiler, Zika is somewhat worse than the average cold.
Given how much the CDC makes Zika sound like a cold – for those who aren’t pregnant – I wasn’t too concerned about getting it. My lack of concern would continue through my first, second, and third screenings. Each time I would fill out an informed consent form that tested my ability to understand that I would receive no ‘direct benefits’ from the study – except for $4,875 in cash. Many bioethicists are worried about cash compensation, seeing it as coercive to offer people ‘too much’ money to do something, and this is presumably related. A common approach is to not offer any compensation for getting ill, but instead only for time and travel: in this framing the money isn’t for doing the study itself. Later, the joys of bureaucracy created an unexpected delay in payment, which didn’t cause me issues – I’m a graduate student used to inconsistent income, so I keep a pot of savings to cover the wait for expense reimbursements – but I wonder why the bioethicists aren’t concerned about whether I needed that check to make rent.
During these screenings I learned that I was allowed to receive Zika and immediately quit the study and walk out the door – and, if I wanted, to get on a plane. While I appreciate my freedoms as an American, I’m not sure I should be legally able to start a Zika outbreak in my choice of preferred metropolitan areas.
I confirmed that I understood that drawing blood might result in pain. I misread that I would spend my seven days wearing blue hospital scrubs, mistaking an option for a requirement. I listed on my Comprehension Assessment Quiz that the reason that some trial subgroups would have mosquitoes feed on their arms was to study mosquito transmission (shocking, I know), but until after I was actually enrolled I didn’t understand what time of the day I would be let out or what medicine I might want to have prepared for when I returned home with a rash.
At times it seems that there was a distinction between concerns where my informed consent was treated as sacred and other concerns that nobody has bothered to think about, and the distinction was decided by a drunk rolling dice.
There are five major ways to deal with infections.
Ideally, we’d prevent the infection from occurring, from making the jump to humans, or even from existing in the first place. We can invest in adequate sanitation, so people aren’t infected by the water they drink. We can educate people about cooking food at temperatures high enough to break down pathogens. We can ban the sale of bat meat, a notorious source of disease. Dogs with rabies are euthanized, and people fought the Black Death by killing rats (though that may not have worked). In the modern era, the most exciting approach is gene drives. Using CRISPR and other genetic-modification techniques, it is possible to make a particular piece of genetic code be passed down 100 percent of the time, rather than merely 50. By additionally making all children male, a species with a short life span (such as a malarial mosquito) could be driven to extinction relatively rapidly.
Once it’s too late to prevent an infection occurring in humans, we can still try to contain it and prevent further spread. Nonpharmaceutical interventions like masks, handwashing, and quarantines prevent the infection of others. This was, for decades, our only approach to HIV: encourage people to use condoms, ban men who have sex with men from donating blood, establish needle exchange programs, and look for a better way. And, of course, there are always salespeople telling you to lose weight or take supplements.
Once a patient is infected, we can try to cure the disease. Some cures are specific to the disease: we used to infect people with malaria to cure syphilis – and it worked. There is a wide class of infections that we treat with antibiotics. Agricultural overuse and other factors threaten how effective they are, humans develop new antibiotics, and the race goes on. Antibiotics are still great. But they don’t work on viruses, such as Zika – and we’re still working on improving access to antibiotics in low- and middle-income countries. For viruses like Zika, we can invent antivirals. But we’re still working on producing ones that work as well on viruses as antibiotics work on bacteria.
For those we can’t cure, we can treat symptoms. We may not be able to remove the virus causing a cold from your system, but we can give you painkillers for your headache, tissues for your nose, or cough suppressant medicines. It’s not an ideal solution, but it is part of a realistic answer.
The fifth and final approach is vaccination, which works in advance of someone becoming infected in the first place. Inoculation, the practice of exposing people to a disease to develop immunity, dates back to at least Chinese practices in the 1500s. The Ottomans employed it as well. But these old practices generally involved giving people the virus itself, though perhaps a small sample. Vaccinations today typically give people an inert, irradiated, dead, or weakened form of the virus, so that their immune system can handle the intrusion, then recognize it, purge it, and be ready for it, and thus protected, in future.
Like handwashing or mask-wearing, vaccination aims to prevent an infection before it ever causes a problem. Unlike handwashing or mask-wearing, you don’t need everyone to keep it up every single day; a single vaccine can protect a patient for years or even a lifetime. Since people are generally keen to get vaccines voluntarily, unlike quarantine measures, nobody’s rights need be violated. Unlike wiping out animal sources of disease, we don’t need to make the difficult ethical or political decision to interfere irreversibly with an ecosystem. Vaccination is the only method by which we have ever driven a disease to eradication: we wiped out smallpox and rinderpest and we are close to ending polio. It’s the only path I think is realistic for stopping Zika.
The first vaccine trial that the Western medical tradition recognizes as such was also a human challenge trial: Edward Jenner deliberately exposed his subject to smallpox. Had he not, he could not have proved that his vaccination prevented smallpox, any more than praying prevented smallpox in the numerous people who happened by chance not to get it. He was following in the tradition of James Lind, who conducted the first controlled trial in 1747. Modern randomized controlled trials (RCTs) are the product of centuries of innovation and improvement: subject blinding was added in the eighteenth century, randomization in the nineteenth, and researcher blinding in the early twentieth.
My trial properly began – after all the paperwork and screening and Covid-19 testing was out of the way – on 2nd October with an injection, not a bite. It was quick and easy, sadly unlike the blood draws that came later. I picked my right arm, and while we would check it every day, it rapidly healed and never caused me any problems.
I officially had Zika – or a placebo.
It’s day four.
We’re all in the Center for Immunization Research at Johns Hopkins. From the fourth floor of an isolated building, where I now live, I have a lovely view of a helicopter landing pad. Seeing the helicopter take off is sort of like watching a Marvel movie on an airplane: only exciting because of the alternatives.
There are four men in this cohort, including me, and, depending on the day, 2–12 members of staff. There used to be an air hockey table for us, but the staff have turned it into some kind of workstation for endless reams of paperwork. I see six staff members on most days. I pass on recommendations from when I filled in government forms of my own and explain why a particular mean needs to be population-weighted for a grad student’s homework. These staff give me book recommendations, compliment the hamburgers I cook, and make surprisingly good criticisms of my Magic: The Gathering games. There’s quite a bit of free time during a human challenge trial. Twenty minutes in the morning for blood and a physical, ten minutes at night for another physical, and then the rest of the day is mine. I can catch up on Netflix, get some work done, or correspond with friends.
There are five dorms. The staff claim one of them for when they want to operate in private, and we each get a private five-bed room to ourselves. Spreading my possessions over the four spare beds in my room proves to be roughly as exciting as helicopter watching. The beds are clearly customized for medical needs, with plastic-topped mattresses resilient to whatever residue humans might leave (I avoid thinking too hard about it) and ample storage space underneath. A Dengue study overlaps with ours on the final night, so I will be cruelly deprived of my extra beds. There are lamps and desks, but exercise equipment and the large TVs are all in the shared space.
The instructions we were given said to bring underwear, and that scrubs were provided, and so I showed up with nine pairs of socks and underwear. Apparently scrubs were optional, and most of my fellow participants brought normal clothes. Luckily this isn’t high school, so instead of being teased for my fashion faux pas I get to discover that scrubs are remarkably comfortable (and not having to do laundry is very convenient). I still change back into my jeans as soon as I can.
I had promised to try to do some work during my stay, but besides that and the half hour of tests, I don’t have to do much of anything. Food is delivered for meals, though we also organize a Costco order for those days when the food order doesn’t quite match our preferences. Sam makes a mean scrambled egg, while I cook burgers for us all one evening.
I should introduce my fellow participants.
We’re a small cohort of men (they’d already tested the strains on women). Sam, Max, and Steve (names changed) are all men in their thirties. At least two have been to prison; one is unsure whether he would be let into Canada.
Sam is a lean veteran of the challenge trial process who always has the nurse draw blood in one exact spot, now blackened by use. He’s a natural leader and ready advocate for us, tying the group together. He wears T-shirts and jeans: he knew enough to pack properly, regardless of what the form said.
Max wears a golden necklace and watch, though I don’t have the eye to spot real gold. He has a soft spot for fancy cars: he complains about the repair cost of his Benz and admits he’s previously owned a Saab, a Jaguar, and a BMW. He wants to buy a cargo truck and run his own small fulfillment business (think Amazon deliveries), and thinks that this study will give him the money he needs to get it off the ground. He’s a comical type, a friendly clown with a quick wit and a warm smile, and he flirts gently with one of the staffers.
Steve is quiet. He stays up late watching WWE in the evenings. The sound insulation in the building is perfect, and I am thankful.
The morning blood draw and physical consists of the nurses taking three to nine vials of blood, examining me for a rash, taking my temperature. The morning blood draw becomes our equivalent of the weather: a petty and varying-enough annoyance to provide opportunities for daily grumbling in the absence of any fresh air. While we are technically allowed to abandon the study any time we want, we otherwise aren’t allowed outside at all for the entire nine days. I rapidly develop a hematoma, a distinctive style of bruise that blood draws can sometimes cause, which sticks around for the rest of the study.
It’s hard to draw my blood. I learn that as lovely and charming and personable as staff members Tom and Jane are, they should not be allowed anywhere near my veins. The only person who can reliably get me the first time is an older woman with a war chest of stories and a yellow stress ball. I name the stress ball George.
That day, I would joke with the other residents about how none of us were symptomatic in the slightest. The next, the rash would begin in earnest.
In disability circles, there’s a useful term: the midnight burrito test. If you can’t go and microwave yourself a frozen burrito at midnight, then no matter what they call it, you’re in an institution. The study passed this test.
There is a curious lack of autonomy that I experience for the first time in my adult life. Being asked to provide a semen sample is perfectly reasonable, but I’m sympathetic to my compatriots’ complaints that the network bars adult websites. Our meals are selected for us, though there is an occasional effort to get our input, and sometimes we are even able to pick out what we want from Grubhub. There’s a range from Sweetgreen salads to a delicious Maryland crab place.
I face a decent bit of culture shock. I’m surprised to hear that President Davo has been shot, and having lived in DC for too long I feel a flash of shame that there exists a president whose policies I am not familiar with. Still, I listen in, curious. I should have anticipated that President Davo is, in fact, a rapper. Max likes my ‘fancy-ass’ accent, and I tell him it’s ’cause I am fancy: I did my undergraduate degree at Oxford, with Latin rituals and formal dinners and zero exposure to practicality. They welcome me to the family, easily and without expectation or any calculation of mutual future benefit. It’s a nice break from DC.
Initially, I had assumed that I would be in the hospital while sick, and depart it when healthy. Instead they held me long enough to be confident that I would not infect the local mosquitoes, and then sent me home (after my nine days) with instructions to return regularly for more blood draws. I departed with a mild rash on my forehead and upper arms, a headache I rate two out of ten, and minimal other symptoms. It was on the journey home when I was hit by the fatigue, the headache started to be a problem, and the itch became painful and kept escalating. It was nothing too serious, but I admit I would have quite liked to have been in the control group that was injected with saline instead of Zika. I knew that becoming ill was a likely outcome, but that doesn’t make it fun.
At the start of this piece, I said I wasn’t fussed with the risk. Looking back at this later, I’m supposed to call this hubris. I still itch across most of my upper body. I’m alternating acetaminophen and ibuprofen. As I edited this piece weeks after the trial, I struggled with fatigue that made it difficult to work. Being released from the hospital only to develop worse symptoms is more than a little strange, but it did mean being taken care of by my partner and eating homemade meals at the worst moments, both of which I enjoyed. All in all, though, I don’t think it was hubris at all. The risks were reasonable, the pay made up for the itch, and I think the benefit to science doubly so.
It’s not that Zika is the most important disease in the world. The first death was reported in 2016. As of a 2019 meta-analysis there had been just 51, and with a case fatality rate of under .02 percent, there likely will not be that many more. Malaria, the better known mosquito-borne disease, kills more than half a million people every year.
But I’m not the most important person in the world, either. Zika is stressful and painful for thousands of people, a headache for policymakers, and a cause of brain malformations in infants. Since it can be sexually transmitted, it can’t be eradicated purely through measures that target mosquitoes. A vaccine for Zika isn’t humanity’s biggest priority, but I’m proud to contribute my small part.
One of the issues raised in a bioethics report that delayed my trial is that, unlike firefighters, human challenge trial participants don’t receive social recognition or status for the risks they take on. Apparently, that would help these trials be more ethical.
Personally, I’m satisfied with the $4,875 and the knowledge that I did something good. Still, it helps that a lack of recognition was not my experience. Due to Covid-19 protocols I was not allowed visitors, but my friends and colleagues were impressed by what I was doing, praised me, and supported me during my recovery. My mother and partner were unhappy with my decision, but without everyone’s support it would have been much more challenging. It was a nice (though strange) week: less stressful (but more boring) than work, better paid than a vacation.
There are a handful of weirdos doing human challenge trials because they’re motivated by a love of humanity or science, myself included. But most people do it for the same reason they do any job: for the pay and the working conditions. Challenge studies will hire someone with a criminal record or the intent to spend eight hours a day working remotely on a different job. You can relax and catch up on classic sci-fi movies, play some PS2 games, or talk some strangers into a round of cards. It beats standing up and bagging groceries all day any day.
One point I took away is how thankful I am for my independence as a healthy adult who isn’t in prison, boot camp, or school. I can choose my own food, decide on my own medical care within a very broad range (including a wide array of legal scams and frauds), and enjoy fresh air. While I certainly prefer it when the organization with control over my life is well-staffed with people who like and respect me (the alternative is terrible), I’m still happy to be back in my cramped, cheap room with my choice of cheap grocery-store snacks.
While my autonomy was reduced during the study itself, I’m glad I had the freedom to do it. I believe it is the right of an adult to take a risk for the greater good. I also believe more people going through these studies and sharing these experiences can only help to make trials better aligned with participants’ actual wants and needs. Zika will continue deforming babies and killing vulnerable adults until we end it. I would happily have signed up for another study, on hepatitis C, if I qualified. It’s a bittersweet feeling to be ineligible to be given another painful disease, knowing that another will go in my place one way or another – whether it be another willing challenge trial participant or another unwilling victim.