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What kind of person signs up to be infected with the coronavirus on purpose?

A new study looks at who signs up for Covid-19 human challenge trials — trials where people are infected with Covid-19 on purpose to help speed up vaccine development.

Moderna vaccines in boxes on a refrigerator shelf.
Human challenge trial volunteers hope to speed up vaccination.
Ivan Romano/Getty Images
Kelsey Piper is a senior writer at Future Perfect, Vox’s effective altruism-inspired section on the world’s biggest challenges. She explores wide-ranging topics like climate change, artificial intelligence, vaccine development, and factory farms, and also writes the Future Perfect newsletter.

In early March, the United Kingdom exposed dozens of volunteers to Covid-19 — on purpose. The aim of this so-called human challenge trial, the first of its type in the world for Covid-19, was to study how large a dose of the virus is necessary to infect someone. The volunteers quarantined for two weeks after their deliberate exposure, and last week, the first of them was released in good health.

Such human challenge trials have been part of humanity’s arsenal against disease for a while now. But in the case of their deployment in the fight against Covid-19, such trials have sparked ethical debates, largely revolving around concerns over whether the people who volunteer to participate know what exactly they’re getting into. A new study that dives deep into the motivations of human challenge trial participants seeks to allay some of those concerns.

To back up for a second: How exactly is a human challenge trial different from regular vaccine trials? In a normal vaccine trial, drug companies have to vaccinate tens of thousands of people and then wait until some of them get sick in the course of their everyday lives. For the coronavirus vaccine trials, that process took several months.

In a human challenge trial, people sign up — and are compensated — to get infected with the virus right away. That speeds the process up and enables scientists to get results on vaccine effectiveness potentially months sooner than a normal vaccine trial.

There’s a lot at stake here. Those months saved could potentially prevent countless hospitalizations and deaths. More than 300,000 Americans have died from Covid-19 since September; if we’d had the vaccine sooner, many could have been saved.

Researchers already use such trials to test malaria vaccines. Early in the pandemic, the organization 1 Day Sooner — a nonprofit that advocates for people who want to participate in high-impact medical research — collected thousands of signups from volunteers eager to participate in human challenge trials for the coronavirus vaccines.

The surge of volunteers has been heartening — but it also raised a big question: What kind of person signs up to get the coronavirus on purpose? Research funded by 1 Day Sooner and conducted by researchers from Johns Hopkins, Rutgers, and Georgetown not yet peer reviewed and available as an online preprint gives us some answers.

Who signs up for a human challenge trial?

The researchers, who surveyed almost 2,000 people who signed up to be considered for a Covid-19 human challenge trial last spring and summer, were particularly interested in whether people who sign up to get the coronavirus on purpose tend to be unusually economically desperate (which would suggest they might be motivated primarily by the compensation), unusually bad at risk assessment, or unusually altruistic.

Ethicists have reservations about human challenge trials on new pandemic diseases. Human challenge trials are common for testing vaccines against diseases like malaria, for which we have a highly effective treatment. There is no highly effective treatment for Covid-19.

Some have argued that it’s hard for people to truly consent to such studies or that the trial process might unjustly exploit the financial desperation, bad judgment, or self-destructive tendencies of the volunteers.

The new study provides a clearer picture of the kind of person who signs up for human challenge trials, and addresses some of these fears.

The study found that the volunteers are, on average, unusually altruistic. Compared to the general population, they are unusually likely to donate to charity, volunteer, donate blood, and be signed up to donate bone marrow. Their leading motivations for signing up for the human challenge trial were, “I wanted to help others and potentially save lives,” and, “I wanted to contribute to the progress of medicine.”

What about worries the volunteers are bad at risk assessment? The study found that, overall, they weren’t. Participants in the study were surveyed on many different categories of risk-taking, from physical (do they take risks with their safety and health, like motorcycling or skydiving?) to financial (do they gamble?) to social (do they tend to challenge authority figures and disagree openly with the people around them?).

When it comes to physical health, the study found, the people who signed up for human challenge trials actually were more cautious than the control group, and they weren’t any more likely to gamble or take risks in other categories. The one category of risk-taking behavior where they stood out was the category called “social risk-taking” — a tendency to question authority and be willing to speak out even when others disagree.

There were no signs from the study that people signed up for human challenge trials because they take the coronavirus lightly or don’t care if they get it. And the people who signed up tended to be better off financially than the average American, assuaging worries that the financial payouts for study participation might induce people to participate despite a lack of understanding of the risks.

Instead, participants seem to have largely signed up not for the money but because they believed they could bring the pandemic to an end a little faster.

When I talked with a couple of acquaintances who signed up with 1 Day Sooner, I heard many of the same themes that the survey detected.

Miranda, who asked that her last name not be used for the piece, lives in Pittsburgh with her husband and her dog; we know each other through the effective altruist community, a group of people interested in how to do as much good as possible. She signed up for 1 Day Sooner back in July. “Helping it happen would save lives,” she told me. “It’s sort of the same reason I wear a mask and social distance — I want to protect other people from the virus.”

“I wanted to do something about the crisis,” Shaked Koplewitz, a finance worker in New York, said. “Just taking a risk (which objectively wasn’t a huge risk) in order to actually help improve something in a meaningful way was important to me.”

“Challenge trials with the novel coronavirus can attract volunteers with background conditions, attitudes, and motivations that should allay key ethical concerns,” the study concludes.

Human challenge trials and medical ethics

Studies like these should inform a brewing debate about the ethics of human challenge trials. Even though human challenge trials have the potential to save a lot of lives, some ethicists have been hesitant to recommend them.

Virologist Angela Rasmussen at Columbia University argues that the standard of informed consent is hard to meet in a case like this one: “I don’t know that we can actually inform them of all the risks because there’s still so much that’s just unknown about this virus. ... I just don’t see how a subject could provide their fully informed consent.”

When I put Rasmussen’s concerns to the 1 Day Sooner volunteers, they mostly seemed confused by them. Koplewitz told me he thinks of the “informed” in “informed consent” as being about avoiding manipulation and deceit, not about reasoning under uncertainty. “The reason we need to put the ‘informed’ in ‘informed consent’ is, I think, to prevent people being taken advantage of,” he told me. But as long as doctors are presenting patients with everything they know, the fact that there’s a lot that experts still don’t know doesn’t bother him.

“Everyone faces the unknown every day,” Miranda told me. “If someone else feels like they don’t know enough to give informed consent, that’s totally reasonable of them.” But personally? As a young healthy person with no health conditions, she is — statistically — at very low risk. “Even though I can’t know every possible outcome of being infected with Covid-19, I can be informed about the range of my uncertainty and the approximate levels of various risks, and I can informedly consent to face that uncertainty.”

Another concern is that human challenge trials still won’t let researchers skip clinical trials so they shouldn’t be oversold as a magic bullet that would obviate the traditional steps of vaccine testing. This is absolutely true. Human challenge trials are a “supplementary pathway,” as advocate and vaccine developer Stephen Plotkin puts it.

But they might tell us earlier which vaccine candidates are on the right track, letting us scale up manufacturing sooner, and they might enable earlier access to effective vaccines for health care workers and other groups at high exposure risk. Human challenge trials wouldn’t have to fully replace clinical trials to speed them up considerably.

Another concern is that because human challenge trials largely recruit young, healthy volunteers, they only tell us about the progression of the virus (or the effectiveness of the vaccine) in that population. Since what we most want to know is how the virus affects those at risk of death, they might be less useful than hoped.

This, too, is a real constraint of human challenge trials. But if vaccines had been approved only for young healthy people back in September, that would have offered protection to many health care workers — and, since we now know that the vaccines dramatically reduce viral transmission, vaccinating young, healthy people in the fall would have indirectly protected others who are at higher risk.

The limitations and challenges of human challenge trials should be kept in mind, but not overstated; a faster vaccine would save many lives even if it were only approved for the healthy.

All of that makes for a strong case that human challenge trials could ethically have a role in speeding a vaccine. But now that the vaccines are here, are they still defensible? That’s a concern Seema Shah, a bioethicist at Lurie Children’s Hospital of Chicago and Northwestern University, raised with my colleague Sigal Samuels in February. “To me the question is, is the risk of doing a trial like this sufficiently low and justified by the value?” Shah asked. “And I think we’re sort of at a point where we’re pushing the bounds of what’s been accepted in other kinds of research.”

And indeed, the case for human challenge trials last spring is much stronger than the case for them now. And for that reason, it makes sense to focus not on the question of whether we should do those trials now, but on what questions we can answer now to be better prepared to make that call in the early hours of the next pandemic.

Looking ahead to the next pandemic

Skeptics of human challenge trials raise some legitimate concerns. Smart, well-meaning people do disagree on this, and given the stakes, it would be strange if we didn’t have agonized debate over human challenge trials. And to be clear, it’s near impossible to say today whether we can use human challenge trials for the next pandemic because we have no idea yet what it might look like. The specifics of each situation matter a lot.

That said, the Covid-19 pandemic has shined a spotlight on the question of human challenge trials in emergency situations like this one, and new research has clarified some of the key questions that held us back from launching such trials early in the pandemic. And on the whole, I think that the case is strong that such trials are justified under some circumstances.

People consent to risky work all the time, including consenting to work in jobs that expose them to risk of the coronavirus. Many people faced exposure this last year despite not having given informed consent, to save others, out of a sense of duty, or because they had no choice but to work to feed their families. We shouldn’t think of people signing up for human challenge trials as any different from the many other people who risked their health in this last year to carry our society through the pandemic.

While this research is funded by 1 Day Sooner and still preliminary, studies along these lines can play a role in clarifying how a society might ethically do HCTs. The trials do not — as many people feared — draw people who just don’t understand risk assessment, and they also don’t primarily draw financially desperate people. In fact, participants are extensively screened to avoid those concerns. They mostly draw people who are knowingly choosing to take on a small risk to themselves to protect their loved ones, their communities, and the world.

If we’d had vaccines in September, they might have mitigated the devastating winter wave of Covid-19 deaths in the US. I wish we’d done more to make that happen.

But the human challenge trial debate shouldn’t primarily be about relitigating the past. Instead, it should be part of planning for the future.

This likely will not be the last pandemic in our lifetimes, and letting the next one sweep through and destroy lives isn’t a good option. Another year of hunkering down feels unendurable.

The alternative is lightning-fast vaccine development. We should keep working to overhaul our vaccine development process to make use of every tool available to us, from human challenge trials to sped-up mass clinical trials to more manufacturing plants, so that whatever comes next, we’re equipped to rise to the challenge.

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