In 1796, English physician Edward Jenner noted that milkmaids who caught cowpox from their cattle seemed to escape a much deadlier scourge: smallpox.
So the doctor collected pus from a cowpox blister on one of those milkmaids, rounded up his gardener’s 8-year-old son and rubbed the gunk into a fresh cut on the boy’s skin. The lad developed a trying but not lethal cowpox infection, and once he recovered, the doctor repeated the exercise — but this time, with the real thing. Smallpox.
The boy did not become infected. And the world’s first vaccine — and, arguably, its first “human challenge trial” — was born.
It’s in this same spirit of discovery — and risk — that more than 30,000 people from 140 nations have volunteered to be infected with the novel coronavirus. Young and healthy, they hope their sacrifices will speed vaccines to market and save thousands of lives.
Pasadena man eager to volunteer
“I was stricken by the very core idea: We can put ourselves on the line, at risk, to help countless other people by getting a COVID vaccine sooner,” said Sunash Sharma, a 23-year-old software engineer from Pasadena who signed up to be a “human challenge trial” volunteer at 1daysooner.org.
“That really spoke to me. A lot of people have been talking about ‘the end of human compassion’ lately, and I saw that this would be a chance for me and thousands of other volunteers to show that humanity is better than we think.”
Sharma hasn’t told his mother yet. Neither has 34-year-old cinematographer Antonio Cisneros of Los Angeles.
“My dad, he’s almost 70, and my mom, too,” Cisneros said. “Without a vaccine, I’m just counting the days till I get a really scary phone call.
“If you look at the death rate per day, it’s a massive number — thousands, sometimes tens of thousands. Even if we only lower the amount of time it takes to get a vaccine by one day, that’s still saving thousands of lives. The sooner that happens, the better the planet will be.”
Some 5,000 people per day have been dying of COVID-19 worldwide over the last several weeks, according to data. If volunteers help vaccines get into circulation just one month earlier than they otherwise might, it could save 150,000 lives. If they shave three months off the process, it could save 450,000 lives. And so on.
“There’s always going to be a risk with any medical procedure,” Sharma said. “But I’m more able to weather this than a lot of people. I’d rather it be me than someone else.”
What’s a human challenge trial?
Developing a safe and effective vaccine the traditional way can take years — and sometimes decades.
After a potential vaccine is developed in the lab, it’s first tested on animals. Is it safe? Does it provoke an immune response? If the answers appear to be yes, it moves on to Phase 2 testing, involving a small group of human volunteers, then a larger, more representative group.
If the candidate still provokes an immune response without severe side effects, it’ll move to Phase 3 — the meticulous, time-consuming, marathon run. It’s this phase that “human challenge trial” volunteers hope to collapse into a matter of months.
Typically, tens of thousands of people are needed for this phase, some who will get the experimental vaccine, and some who won’t, said Arthur Caplan, bioethics professor at New York University. Those people go forth into the world, and researchers watch to see who, by natural infection, gets the disease and who doesn’t.
“It can be hard to get people infected fast enough to get an answer to the question, ‘Is the vaccine doing anything?’ ” Caplan said. “Normally, this whole thing takes years.”
The coronavirus pandemic makes things trickier because many people are wearing masks and self-isolating, actively trying to avoid infection. That would likely drag Phase 3 out even longer, as researchers wait for enough natural infection to produce statistically significant results.
“If, instead, all of the study participants are exposed to the pathogen under highly controlled conditions, we could rely on a much lower number of volunteers and, with luck, develop a safe, effective and broadly available vaccine in a much shorter period of time,” 1DaySooner explains in its pitch to volunteers. “This is one way in which a coronavirus human challenge trial might prove useful.”
Informed participants would get either the vaccine candidate, or a placebo. After enough time for the vaccine to take effect, participants would be deliberately exposed to the coronavirus, then carefully monitored. That would show the vaccine’s efficacy — or lack thereof — far more quickly, and with far fewer participants, than standard Phase 3 trials, 1DaySooner says.
Depending on the pandemic’s long-term trajectory, that could save thousands, or even millions, of lives.
There’s no shortage of opportunity for human challenge trials. Eighteen candidate vaccines are in the early phases of clinical trial as of July 2, and another 129 are in development, according to the World Health Organization.
But … is it ethical?
The boy in Edward Jenner’s smallpox experiment obviously couldn’t, and didn’t, give informed consent. And some worry that the coronavirus and its long-term effects are so poorly understood that those stepping forward to be human guinea pigs can’t truly give informed consent either.
“These volunteers know that Covid-19 can cause suffering and even death, yet they are stepping forward, willing to risk their lives,” wrote Michael Rosenblatt, chief medical officer of Flagship Pioneering, former chief medical officer at Merck and former dean of Tufts University School of Medicine, in Slate.
“In this situation, however, their sacrifice cannot be justified. Volunteers need to be protected from both known and unknown risks.”
Human challenge studies are generally contemplated only when a lifesaving treatment or intervention is available should the vaccine candidate fail, he argued. But there’s no cure or treatment for COVID yet, “making viral challenge particularly risky and ethically questionable,” he wrote.
Richard M. Carpiano, professor of public policy and sociology at UC Riverside, shares Rosenblatt’s fears.
“The major concern I have is that we simply don’t know enough about COVID-19 yet,” Carpiano said by email. “Findings are only just beginning to emerge about non-fatal and/or long-term impacts on body systems. While the news is very much focused on cases, ICU admissions, and deaths, less attention is being paid to the significant number of people reporting impairments — lingering impacts — weeks afterward.
“We don’t yet know enough about how long these might persist, their severity, progression, etc. Hence, COVID-19 has potential for impacting long-term health and quality of life.”
There may be good uses for challenge trials, he said, “but given the risks and uncertainties … a coronavirus vaccine seems like a bad use for them.”
‘No doubt it’s dangerous’
Other experts, however, disagree.
“It boils down to, is there a need to do it?” said Caplan of NYU. ” I think there is.”
The risk of dying from COVID-19 among people aged 20-29 is 1 in 3,300, according to the Lancet Journal of Infectious Disease. That’s about the same as the risk from kidney donation, Caplan said. And risk can be reduced by giving challenge trial participants lower or weaker doses of the virus.
“There were plenty of doctors, nurses and cleaning people with poor protective equipment who went in to care for people with COVID and were exposed to the virus,” Caplan said. “If we let them do that, why not let people do this?”
Otto Yang, an infectious diseases expert at UCLA’s Geffen School of Medicine, is inclined to agree.
“There’s no doubt it’s dangerous. Even a young person can get critically ill,” Yang said. “I don’t know that the right answer is.
“But the situation is, the pandemic is out of control. People are dying. Arguing that a human challenge trial is not ethical because people could suffer harm kind of ignores the fact that people are suffering harm every day because of this virus.
“A vaccine that’s successful would interrupt, or slow it down, a lot. The sooner that we get one, the more lives are saved.”
Source: Orange County Register
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