Just like the moment a mosquito bites, the shot of dengue virus I received in my arm was so quick and painless that afterward I wasn't even sure it happened at all.
A few years ago, I wrote a story about a young woman who was infected with malaria by 200 mosquito bites to test a potential vaccine. At the time, it was bewildering to me that someone would be willingly agree to take on so much risk and put themselves through so much discomfort for only a modest sum of money.
Yet many people choose to participate in clinical trials for new drugs every year. In fact, it is required in the United States medical system and throughout the world that drugs be tested on human participants in three phases of clinical trials to evaluate their safety and effectiveness before they can be approved for use.
Over half a million clinical trials have been registered on the US government's ClinicalTrials.gov since the clinical-trial-tracking site launched in February 2000. And nearly $100 billion is spent every year on the business of running clinical trials. The vast majority of the trials, and the money that goes into them, don't result in a new drug approval.
So when an ad popped up in my Instagram feed suggesting I could earn up to $3,425 for participating in a 5-month-long dengue study at the Johns Hopkins University Center for Immunization Research (CIR), I was intrigued.
I wanted to know more about the business and ethics of human medical experimentation. And I was willing to put myself through a little pain to find out. It turns out that within the industry there are constant debates about the roles of risk, race, paternalism, economics, and exploitation in making clinical trials work. But despite all that, clinical trials still rely on some sense of altruism in healthy participants to function.
Informed and uninformed consent
Dengue fever is the most-common mosquito-borne viral illness in the world. The World Health Organization estimates that up to 400 million infections happen each year, and new research suggests that climate change is increasing the burden of dengue around the world (Proc. Natl. Acad. Sci. U.S.A. 2025, DOI: 10.1073/pnas.2512350122). Yet it's still considered a neglected tropical disease, in part because there's no specific FDA approved treatment for severe dengue. When paired with other conditions such as malnutrition or HIV, which unfortunately are common in some of the areas where dengue is prevalent, it can be deadly.
The trial I applied for was taking place in Baltimore, which isn't exactly a dengue hot spot. In fact, cases of dengue infection in the U.S. are extremely rare, but it's relatively common for Phase 1 and 2 drug trials to take place in the U.S. even when the disease burden is located elsewhere. Often the U.S. has the academic expertise and funding to conduct these trials that lower-income countries do not.
I had volunteered to be injected with dengue virus as part of a Phase 2 clinical trial to test the efficacy of an experimental drug at preventing severe dengue infection. There were two cohorts in the study. One group would receive the drug intravenously or a placebo a day before being given the dengue virus, and the other would receive the drug or placebo a few days after being given the dengue virus.
Before I could volunteer for anything, the CIR needed my consent — a lot of it. On two separate occasions, I reviewed a dense packet of information detailing the risks I was agreeing to, my rights as a research participant, and a code of conduct before being given an open-book test on the content, on which I needed to score 70% or better to continue.
"We always say consenting is really an evolving process, and it needs to be," says Anna P. Durbin, director of the CIR. Durbin is the principal investigator on the dengue trial I was participating in, though I never met her in person during any of the times I was at the facilities. She also oversees several other trials taking place at the CIR.
Unfortunately, history is fraught with examples of research being done on people without their consent. In World War II, the Nazis performed horrific medical experimentation on Jews and other people imprisoned in concentration camps. The U.S. has its own history of unethical medical study too. The Tuskegee study, which took place from the 1930s to the 1970s, withheld syphilis diagnosis and treatment from Black Americans and then monitored them over years as their health deteriorated. The Willowbrook experiments, which began in 1956 and lasted for 14 years, purposely infected children with mental disabilities with hepatitis.
But then, in 1978, the U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research published the Belmont Report. This landmark document outlined three core ethical principles of human research: respect for persons, which mandates informed consent and autonomy of research participants; beneficence, a fancy term for the philosophy of "Do no harm"; and justice, which ensures the benefits and risks of human research are distributed fairly.
That, in turn, led to regulation in the U.S. requiring that medical research on human participants be evaluated for good ethics by Institutional Review Boards (IRBs).
Durbin, a member of the Johns Hopkins School of Public Health IRB, says that evaluating a clinical trial's ethics requires a detailed discussion.
"What we're really concerned with is how the volunteers are informed. Are all of the procedures ethical? What are the risks? How are they being mitigated? That sort of thing," she says. If a proposed study doesn't answer those questions sufficiently, then it's back to the drawing board to alter the methodology.
Most of the information discussed by an IRB must be communicated to the participants.
"We have to make sure that you know what's going to happen to you when you're in a study," Durbin says. "Are you being compensated or not? That's important information. What happens to your samples? Can you withdraw or can't you withdraw? Who's going to see your information?"
That's a lot for participants to understand. And if they don't understand it, they can't ethically consent. That's why I had to take two tests before I could volunteer.
"I still think our consent forms are too long, but I think it's also difficult to exactly know what to take out to make sure that people are fully informed," Durbin says.
Taking a calculated risk
Thanks to the consent forms, I felt as if I had a good grasp of the study. But I was still nervous.
I was going to receive experimental monoclonal antibodies — lab-made proteins that mimic the natural antibodies your immune system makes to fight off an infection — or a placebo . But getting the antibodies would come with no guarantee of long-term protection from dengue.
The day of dosing featured a grueling process of getting an IV infusion and repeatedly being pricked for blood draws over 5 hours while my arms bruised. Ultimately, discomfort was all I suffered on this day. Phase 1 clinical trials had all but confirmed the drug in development was safe.
The next day, a nurse injected my arm with a genetically modified version of the DENV-3 serotype of the dengue virus designed to give only mild illness rather than full-blown "break-bone fever," as the illness is known colloquially.
I was told that the symptoms of dengue are a lot like flu symptoms, but that dengue also comes with a full-body rash, achy bones and pain behind the eyes. A week after the injection (and after an unfortunately timed weeklong bout of COVID-19), I developed all these symptoms.
More concerning to me than the mild illness was that the consent forms also warned of a property of the dengue virus called antibody-dependent enhancement. Viruses with antibody-dependent enhancement are more dangerous the second time someone gets the disease because the virus can take advantage of a person's imperfect antibodies from a previous infection to better infect cells. So if I were to ever get dengue again, I would be at a much greater risk for severe disease. That's a risk I now carry with me for the rest of my life. What exactly made that risk acceptable?
Nir Eyal, a bioethicist at Rutgers School of Public Health, says that studies conducted on people with a medical condition take into consideration the "risk-benefit balance" when determining what is appropriate. Outside of a study setting, "sometimes it's worth taking a very risky substance when it's very beneficial for you; dangerous [chemotherapy] is worth it sometimes if your cancer is bad enough and you have no alternatives," he says.
For clinical trials on healthy people, the calculus is different. Eyal says calculating the appropriate level of risk happens in three stages. The first stage is to "minimize the risks, maximize or promote the benefits as much as you can," he says. For example, the genetically modified serotype of the dengue virus I was given was designed to give as mild a clinically relevant disease state as possible.
Not all risks can be designed away though, so the second stage, and the most important one according to Eyal, is to ask: Are the risks to the individual proportionate to the potential benefits for society?
"I'm not asking, Are the risks for the individual okay in light of the benefits to the individual?" he says.
The person participating in the trials is allowed to incur some risk, without receiving any medical benefit in return, so long as it's for the greater good.
The third stage of determining acceptable risk for a clinical trial is to ask, are the absolute risks to the individual simply too high, no matter how much value the trial may have for society?
But Eyal says he doesn't see the need for an upper threshold of risk to an individual in a clinical trial. He believes that as long as an individual is properly informed, that individual should be able to take on as much risk as they are willing, provided there is enough benefit to society.
"The first participants of some of the U.S. malaria challenge trials were researchers who wanted to develop the vaccine, and they volunteered," he says.
Eyal's views on the upper limits of risk in clinical trials aren't universally held by the ethicists and researchers who make the decisions to approve clinical trials. Presently, IRBs tend to lean conservative when it comes to acceptable risks to participants — perhaps justifiably so, given the field's history of medical abuse.
That cautiousness has led to questions about the role of paternalism in clinical trial design and implementation. It's a hot topic in discussions about clinical trial ethics.
Pay and paternalism
In compensation for being poked and prodded, looking and feeling like garbage for a few days, and making the 2½-hour round trip into the CIR facilities a total of 17 times over 5 months, I was paid roughly $3,500. That's money I'll have to pay taxes on later. Now, after all is nearly said and done, I feel it was worth my effort. That money is funding a vacation and a few upgrades around the house.
But $3,500 means different things to different people. For folks fortunate enough to have plenty tucked away in savings, it may not be compelling. And for others struggling to pay bills, it could mean keeping a roof over their head or food on the table.
Historically, the review boards that oversee clinical trial development have been hesitant to incentivize participation via large cash awards. This comes from a fear that setting compensation too high will unduly influence those who need the money to participate in something they wouldn't otherwise be willing to do, according to Durbin, though she disagrees and has advocated for higher pay.
Josh Morrison, president and cofounder of 1Day Sooner, an organization that advocates for clinical trial participants, says the logic behind compensation restriction is "wrong and patronizing and unfair to the people who join studies because they need the money."
1Day Sooner was born out of the COVID-19 pandemic as a coalition of folks who wanted to help by participating in COVID-19 challenge studies. In the post pandemic world, 1Day Sooner now serves as a voice for participants in conversations with those who guide clinical trial development.
Morrison says that attitudes of paternalism and elitism underlie IRB fears over high compensation. But if all the efforts are made to ensure that a study is ethical in the first place, "paying more money to people doesn't affect that." It's only when studies are inherently unethical that high compensation might trick people into participating, Morrison says. And that shouldn't ever happen. Compensation should be based on the time and effort spent participating in the trial and not the risk inherent to a study, because these studies should never be excessively risky in the first place, Morrison says.
Jill Fisher, a bioethicist at the University of North Carolina at Chapel Hill, feels that arguments over patient compensation can sometimes ignore a bigger picture.
"There's all this worry that if you offer people money, they will feel compelled to do something they don't really want to do otherwise, but on the other hand, I'm more worried we're going to exploit people if we don't pay them enough," Fisher says.
Fisher has been studying the ethics and demographics of clinical trial participation in the U.S. for over 20 years. And she says that while there isn't sufficient data to determine how many people are participating in clinical trials each year, we do know who is most likely to participate.
"It's mostly Black or African American participants enrolling in these studies, especially in the Northeast and then the Midwest, and then a lot of Hispanic or Latino participants in the Southwest and the Southeast," she says, adding that those who choose to participate often don't have other reliable income sources or reliable access to affordable health care.
On the day of my IV infusion, two other trial participants were at the facilities with me. One was a graduate student at Johns Hopkins who said they wanted to do something more for science. The other participant was there "just to get some bread." Durbin asked me not to interview or provide identifying details of any of the other participants in this trial for the story, and I agreed.
"I've spoken to hundreds of people who participated in these studies. On one hand, most of them are really grateful that they have an opportunity to earn income in this way," Fisher says. "But at the same time, you could feel grateful for an opportunity but also feel exploited. And I think a lot of them do."
According to several of the sources I spoke to, many people who participate in one trial end up participating in another. Some rely on clinical trials as one of their primary forms of income, but this is rare. More often, participants feel like there's a good reason for them to be involved in a clinical trial beyond the paycheck.
"It's not either-or. People can both have altruistic motivations and care about the money," Morrison says.
Firsthand testimony
For Jacob Hopkins, altruism was key in choosing to become part of a trial. Back in 2020, Hopkins became the very first person to receive a COVID-19 challenge as part of a weeks-long inpatient clinical trial taking place in the UK.
"Since taking this huge step into the world of clinical trials and the advocacy side of things for it as well, it's become a complete sort of new passion of mine," he says.
Meanwhile, Roopesh Chavda, who has now participated in two COVID-19 challenge trials, doesn't consider being a part of clinical trials a passion but does think it helps do some good for the world. It "wasn't necessarily about the money," he says. " But I would never do something like this without being paid compensation, because there are risks."
Hopkins was unemployed when he participated in his clinical trial, Chavda could work remotely during his facility stay, and I had my employer's blessing to take the time to participate in a trial.
For those who feel like they have to participate in clinical trials out of need, there are people like Durbin, Eyal, Fisher, Morrison, and the staff I had the pleasure of working with who are trying hard to improve the experience of being a trial participant little by little.
I felt welcomed, valued, and respected during my time as a trial participant. And I hope sharing that experience will encourage others to consider volunteering themselves.
A version of this story was republished with permission from Chemical & Engineering News. Copyright ©2025 by the American Chemical Society. "How do drug trials really work? I got dengue fever to find out" was first published on May 22, 2022 and appeared in Volume 103, Issue 21. https://cen.acs.org/pharmaceuticals/drug-development/drug-trials-really-work-dengue/103/web/2025/10
Max Barnhart is an assistant editor at Chemical & Engineering News. Previously, he was a AAAS Mass Media Fellow at NPR.
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