Getting Sick for Science

One recent morning in Baltimore, Maryland, Alexander Laurenson, 26, strode into a small room to have his arm preyed upon by mosquitoes. To make his skin more attractive to the pests, which are drawn to body odor, he hadn’t showered. And the mosquitoes had been infected with malaria, a disease that kills more than 600,000 people a year worldwide.

Laurenson was part of a study at the University of Maryland School of Medicine to test a new antibody designed to prevent malaria transmission. Specifically, he’d agreed to take part in a human challenge trial, in which volunteers are knowingly infected with a pathogen (an organism that causes disease).

Researchers had secured the room to ensure the mosquitoes wouldn’t escape, with a bug zapper and a few electrified paddles on the wall as extra precautions. One by one, more than 20 volunteers shuffled in to serve as prey.

In Baltimore, Maryland, Alexander Laurenson, 26, walked into a small room to have his arm bitten by mosquitoes. He hadn’t showered so that the mosquitoes would be drawn to his body odor. The mosquitoes had also been infected with malaria, a disease that kills more than 600,000 people a year worldwide.

Laurenson was part of a study at the University of Maryland School of Medicine to test a new antibody designed to prevent the spread of malaria. Specifically, he’d agreed to take part in a human challenge trial. During the trial, volunteers are knowingly infected with a pathogen (an organism that causes disease).

Researchers had secured the room to ensure the mosquitoes wouldn’t escape. They added a bug zapper and a few electrified paddles on the wall as extra precautions. One by one, more than 20 volunteers went in to serve as prey.

Trials like this one have long underpinned the development of vaccines for deadly scourges such as typhoid fever and cholera. Today they’re typically undertaken only with diseases for which there are already fast-acting drugs to aid in recovery. But because of the perceived risk and significant cost involved with these types of trials, they remain controversial.

“A lot of people say, ‘Doesn’t this violate the Hippocratic oath?’ or ‘How can a doctor do this?’” says Seema K. Shah, a bioethicist at Lurie Children’s Hospital, referring to the historical oath that doctors once took promising to help and not harm patients.

Scientists have become enthusiastic about challenge trials, especially since the Covid-19 pandemic. Funding for trials has increased globally, including in the U.S., and countries such as India, Canada, and Australia are developing the capacity for conducting them. Some researchers find it easier today to recruit volunteers willing to shiver, sweat, and puke in the name of helping others (while earning some cash).

“I think it would be unreasonable to value my convenience more than other people’s lives,” says Oscar Delaney, 22, of England, who joined a malaria challenge trial in the United Kingdom last year. “The risk and inconvenience to me is small, but the possible benefit to the world is large.”

Conducting a challenge trial can take as little as a few months, in contrast to the years it often takes to run a traditional trial requiring thousands of subjects to naturally become infected with a disease. And so proponents of human challenge trials ask: If we can speed up the process, shouldn’t we be doing that?

Trials like this one have long supported the development of vaccines for deadly diseases such as typhoid fever and cholera. Today they’re typically done only for diseases where there are already fast-acting drugs to help in recovery. But because of the perceived risk and significant cost involved with these types of trials, they remain controversial.

“A lot of people say, ‘Doesn’t this violate the Hippocratic oath?’ or ‘How can a doctor do this?’” says Seema K. Shah, a bioethicist at Lurie Children’s Hospital, referring to the historical oath that doctors once took promising to help and not harm patients.

Since the Covid-19 pandemic, scientists have become excited about challenge trials. Funding for trials has increased globally, including in the U.S. New countries such as India, Canada, and Australia are developing the capacity for conducting them. Some researchers find it easier today to recruit volunteers willing to shiver, sweat, and puke in the name of helping others (while earning some cash).

“I think it would be unreasonable to value my convenience more than other people’s lives,” says Oscar Delaney, 22, of England, who joined a malaria challenge trial in the United Kingdom last year. “The risk and inconvenience to me is small, but the possible benefit to the world is large.”

Conducting a challenge trial can take as little as a few months. The traditional method can take years and requires thousands of subjects to naturally become infected with a disease. Those who support human challenge trials ask: If we can speed up the process, shouldn’t we be doing that?

The first vaccine in history was developed through a human challenge trial. In 1796, English scientist Edward Jenner wondered whether cowpox, a mild disease, might protect individuals against smallpox, a deadly one. He exposed his gardener’s son to cowpox and then deliberately infected him with smallpox. His theory proved correct, and the experiment lives on in the word “vaccine,” which is derived from vacca, Latin for cow.

A number of challenge trials took place in the following two centuries, many involving infecting vulnerable groups, such as prisoners or soldiers, without consent. But as far back as 1900, U.S. Army physician Walter Reed was pioneering a better way forward when he provided participants in a yellow fever study in Cuba with money and contracts that outlined the risks.

Over time, that model became standard, and by the latter part of the 20th century, challenge trials began to be more accepted, says Joshua Osowicki, a pediatric infectious-disease physician at the Murdoch Children’s Research Institute in Melbourne, Australia.

The first vaccine in history was developed through a human challenge trial. In 1796, English scientist Edward Jenner wondered whether cowpox, a mild disease, might protect individuals against smallpox, a deadly one. He exposed his gardener’s son to cowpox. Then he deliberately infected him with smallpox. His theory proved correct. The experiment lives on in the word “vaccine,” which comes from vacca, the Latin word for cow.

A number of challenge trials took place in the following two centuries. Many of the trials involved infecting vulnerable groups, such as prisoners or soldiers, without consent. But as far back as 1900, U.S. Army physician Walter Reed was pioneering a better way forward. During a yellow fever study in Cuba, he provided participants with money and contracts that outlined the risks.

Over time, that model became standard. By the latter part of the 20th century, challenge trials began to be more accepted, says Joshua Osowicki, a pediatric infectious-disease physician at the Murdoch Children’s Research Institute in Melbourne, Australia.

Fast-forward to the spring of 2020, during the Covid pandemic. As the world scrambled for a vaccine, some scientists called for challenge trials to speed up the process. A fiery debate broke out among the public health community, with opponents arguing that the risks of infecting volunteers with a poorly understood virus were too great.

Those in favor prevailed. In 2021, after months of deliberation, the world’s first Covid-19 challenge trial began at Imperial College London, with 36 adults who were exposed to the virus and then monitored for two weeks. The trial revealed important new information about Covid, including that the virus had a shorter incubation period than originally thought. And the success wound up breathing new life into the field of challenge trials, says immunologist Christopher Chiu, who ran the trial.

Fast-forward to the spring of 2020 during the Covid pandemic. As the world hurried to develop a vaccine, some scientists called for challenge trials to speed up the process. A debate broke out among the public health community. Opponents argued that the risks of infecting volunteers with a poorly understood virus were too great.

Those in favor prevailed. In 2021, after months of deliberation, the world’s first Covid-19 challenge trial began at Imperial College London. Thirty-six adults were exposed to the virus and then monitored for two weeks. The trial revealed important new information about Covid, including that the virus had a shorter incubation period than originally thought. And the success wound up breathing new life into the field of challenge trials, says immunologist Christopher Chiu, who ran the trial.

In recent years, more money has been made available to build the costly facilities that successfully contain dangerous pathogens for these trials. The University of Melbourne recently opened the first one dedicated to human challenge trials in the Southern Hemisphere. Scientists in Australia are also pioneering challenge trials to evaluate vaccine candidates for Streptococcus A, a deadly bacterial infection. And in Antwerp, Belgium, a facility with 30 beds opened as part of a $57 million project to develop the next generation of Covid vaccines through challenge trial research.

Eleven days after the mosquitoes bit him, Laurenson from the malaria study was worried about the nausea and headache he was experiencing. Before his infection, he’d received the highest dosage of the trial’s antibody. Had the experimental product failed?

At the lab, Laurenson’s test came back negative for malaria; he simply had a stomach bug. The antibody had worked after all.

His malaria exposure will preclude him from future trials involving that disease, but he wants to take part in another trial soon. He’s surveying the options: shigella bacteria, which infects children’s intestines, or the influenza virus? He’s leaning toward the flu.

In recent years, more money has been made available to build the expensive facilities that successfully contain dangerous pathogens for these trials. The University of Melbourne recently opened the first one dedicated to human challenge trials in the Southern Hemisphere. Scientists in Australia are also pioneering challenge trials to evaluate vaccine candidates for Streptococcus A, a deadly bacterial infection. And in Antwerp, Belgium, a facility with 30 beds opened as part of a $57 million project to develop the next generation of Covid vaccines through challenge trial research.

Eleven days after the mosquitoes bit him, Laurenson from the malaria study was worried about the nausea and headache he was experiencing. Before his infection, he’d received the highest dosage of the trial’s antibody. Had the experimental product failed?

At the lab, Laurenson’s test came back negative for malaria. He simply had a stomach bug. The antibody had worked after all.

His malaria exposure will disqualify him from future trials involving that disease, but he wants to take part in another trial soon. He’s looking at the options: shigella bacteria, which infects children’s intestines, or the influenza virus? He’s leaning toward the flu. 

Brent Crane is an investigative reporter. With reporting by Chrisanne Grisé.

Brent Crane is an investigative reporter. With reporting by Chrisanne Grisé.