Virus trials ethical mire

Most of us have spent the past two years desperately trying to avoid catching covid-19. But in Britain, more than 27,000 people volunteered to get deliberately infected with the virus. Thirty-six of those volunteers were selected for a research trial. In the spring of 2021, they willingly took a nasal spray that would make them sick.

Experiments that involve deliberate infection of human subjects are known as “challenge trials,” and they raise a host of complicated ethical questions. But the grim reality is that additional pandemics are likely, and if we want to prepare for the next one, we should encourage more carefully designed challenge trials to prevent widespread, avoidable deaths. The time to have that debate is now, ensuring that we have the tools in place to rapidly respond to future outbreaks.

So far, two covid challenge trials have been approved in Britain, allowing researchers to better understand a virus that has already claimed the lives of more than 5 million people around the world. They used young, healthy volunteers who were carefully monitored and were at low risk of complications from the virus.

Deliberate infection has a dark past. The world’s first vaccine, developed by Edward Jenner in 1796, was tested by deliberately exposing Jenner’s gardener’s 8-year-old son to cowpox and smallpox. Many of history’s worst regimes — from the World War IIera Japanese empire to Nazi Germany — conducted experiments on unwilling human participants.

Modern challenge trials require mountains of paperwork and are subject to intense oversight. Still, some modern medical ethicists object vehemently to the use of challenge trials, even when participants willingly consent. Several medical journals have published commentary deeming them unethical.

Peter Openshaw, a top British scientist at Imperial College London who helped manage one of the United Kingdom’s challenge trials, told me these experiments yield enormous public health benefits: “You can get unique scientific insights from challenge trials that you wouldn’t get from any other sort of study.”

Modern, ethically rigorous challenge trials have already helped develop breakthroughs on malaria, cholera, typhoid and flu.

So far, however, covid-19 research during the pandemic has relied almost entirely on natural infections — an approach that worked because infections were so widespread during the trials. But if field trials are run during a period of low infection (such as in an early or late stage of a pandemic, or as a new variant emerged, or with a new disease), getting decisive data can be far more difficult.

“If every vaccine has to undergo a field trial involving thousands of people, that really delays progress,” Openshaw says.

Challenge trials address that problem. Because researchers control who is infected, they can get decisive results with tiny groups of people — as few as 100 instead of tens of thousands. Such tests are also much faster, because they don’t need to wait for participants to be naturally exposed to a virus through bad luck. Getting fast, reliable data into the hands of public health officials and policymakers even just a week or two sooner can save countless lives during a rapidly evolving pandemic.

Crucially, challenge trials can also solve puzzles that have baffled scientists for years. Because diseases often present symptoms several days after infection, the early stages post-exposure are rarely observed by researchers. With controlled infections, scientists can quickly and comprehensively understand precisely what happens when covid — or another disease — first enters the body. Understanding those dynamics can help produce better treatments.

There are objections, of course. Medical professionals, who live by the principle to “first, do no harm,” have an aversion to deliberately infecting people with a dangerous pathogen. Some have argued that the risks of covid are severe enough that challenge trials are unjustifiable.

Yet millions of Americans have already willingly exposed themselves to heightened infection risk at mass indoor gatherings. Some people even attend “infection parties.” If a small number of Americans wanted to volunteer for a highly regulated research trial to benefit the rest of the public, why not let them?

Compensation is another thorny issue. Some ethicists argue that too much cash could entice poor people to risk their health for money. This is known as “undue inducement.” (The British study paid participants roughly $6,000 to compensate them for their time.).

“Those claims [about the negative effects of financial enticement] need to be backed up with data,” Jennifer Blumenthal-Barby, a professor of medical ethics at Baylor College of Medicine, told me. “And there’s actually evidence that large amounts of money do not necessarily distort people’s decision-making around participation in research, including risky research.”

She notes that we routinely provide financial incentives for other potentially deadly activities that serve society, from wartime service to working in meat-processing plants.

Given that, the idea that it’s somehow ethically acceptable to ask low-paid grocery store clerks or underpaid nurses with health conditions to unwillingly risk covid exposure while refusing to give healthy, altruistic adults the choice to voluntarily serve humanity with consensual scientific research is dubious at best.

Challenge trials are controversial — for good reason, given the dismal history of human experimentation. But with the proper protections and informed consent, more challenge trials should be encouraged. We would be unwise to unilaterally disarm ourselves by discarding one of the most effective weapons against future pandemics.