Thousands willing to be infected for vaccine
The worldwide search for a coronavirus cure has inspired tens of thousands of young people to volunteer to be infected with the coronavirus during human trials of experimental vaccines — a growing movement that critics fear will have dire consequences.
More than 38,000 people mostly in their 20s or early 30s from all over the world have signed up to be part of an operation known as 1DaySooner, which supports “human challenge trials” to test experimental drugs and speed up the process of finding effective vaccines for the coronavirus.
Such trials, in which the immune system is “challenged” by deliberate exposure to an infectious disease, have been used in the past to test vaccines for malaria, dengue fever and other conditions that, with
standard drug treatments, usually clear up. The trials typically involve only 100 to 200 people compared to 30,000 in a standard phase 3 trial.
The nonprofit 1DaySooner is based in Delaware and advocates for the COVID19 challenge trial volunteers who signed up on the organization’s website. The group, which includes a 14member advisory board of medical experts, has not yet set up any challenge trials in the United States, but that is their goal.
The idea would be to coordinate with government officials and research institutions and conduct human trials separately or in combination with the three regular phases of standard clinical trials. Physicians would give volunteers the vaccine, infect them with the virus and monitor how they react. If someone gets sick, he or she would be treated in a hospital with proven drugs, including monoclonal antibodies, the antiviral drug remdesivir and the steroid dexamethasone.
Proponents say these types of trials pose risks that have been deemed acceptable under the circumstances and are valuable because they quickly yield results, dramatically speeding up vaccine development.
But Robert Siegel, an infectiousdisease specialist at Stanford University, said challenge trials are only meaningful if half of the subjects receive a placebo. Since there are relatively few drugs that help COVID19 patients — and not in every case — the people who get the placebo would be guinea pigs in a dangerous experiment, Siegel said.
“Even if the vaccine works perfectly, this makes it almost inevitable that individuals in the control group will be adversely impacted. This includes the risk of dying, the impacts of significant illness, and the longterm consequences of multipleorgan damage,” said Siegel, who contends it is unethical to expose people to disease on only a sneaking suspicion that they will recover. “I personally think that’s a very bad idea.”
Even without the ethical problem, there is a question about whether a challenge trial would be useful after the announcement last week that the pharmaceutical giant Pfizer has produced a vaccine that is 90% effective at preventing COVID19. The findings created worldwide excitement, but they were only preliminary, the result of an interim analysis of clinical trial data.
The lack of certainty is why Antonio Cisneros believes challenge trials are still going to be important. The 34yearold Los Angeles cinematographer volunteered for 1DaySooner after nine uncles, aunts and cousins got the coronavirus, and a close family friend died of it. It is important, he said, to keep looking for better vaccines by testing them on young, healthy people like himself.
“It just makes sense. I am very low risk,” Cisneros said. “Most people who have been damaged or harmed have been over the age of 60, the age of my parents. If we can have a vaccine sooner it might prevent my parents from getting it.”
Abie Rohrig, spokesman for 1DaySooner, said the young, healthy volunteers on the website would likely be safe. He cited a July study in Science that said only 1 in 20,000 people ages 20 to 29 die from COVID19. Other studies, he said, have found an even lower fatality rate for people under age 34.
Rohrig said a higher percentage of people die from donating a kidney or in childbirth.
“Speaking personally, I donated my kidney to a stranger last year, facing a 1 in 3,300 risk of death as well as a risk of longterm complications,” Rohrig said. “I was happy to take on that risk to save a life, and I would gladly offer my consent to take part in a challenge trial that could speed vaccine development by even just one day.”
But the effects of COVID19 can be wildly unpredictable. That’s because the immune system of some adults, including young and otherwise healthy people, overreacts to the presence of the virus, creating serious lung problems. There have also been cases of people being infected twice, including a 25yearold man from Reno.
And then there is the Doctrine of Original Antigenic Sin, a 60yearold concept that suggests a person might not be protected by a strong vaccine if they take a weak one first.
The Pfizer vaccine, developed with the German firm BioNTech, is one of several that are being worked on in the global race to halt the pandemic. Rohrig said there are still many questions, including how long immunity provided by such a vaccine would last.
Other potential problems, he said, are that the Pfizer antibodies have to be kept at 94 degrees below zero, colder than the North Pole in winter. It would, like the other leading vaccine candidates, also require booster shots. Some experts say it will take until the end of 2024 before enough doses of the Pfizer treatment are available for worldwide distribution.
In the meantime, Rohrig said, other potential vaccines should be tested. But he said news of the Pfizer vaccine could make it harder to recruit the thousands of people needed for fullblown clinical trials because people might prefer to wait for it rather than take a chance on getting a placebo.
The solution for that might be a challenge trial, which requires fewer participants, he said, adding that placebos might not be necessary. One governmentfunded challenge trial for COVID19 is being planned in the United Kingdom by a Dublinbased commercial clinical research organization called Open Orphan.
There are nevertheless reasons to be skeptical, given the history of challenge trials. The most notorious was the Tuskegee syphilis study, in which African Americans with syphilis were deceived and deliberately left untreated in an attempt to find out what the disease did to their bodies.
The Tuskegee study, which started in 1932 and continued for 40 years until the deception was uncovered in 1972, has been recognized as the reason for the widespread mistrust among Black Americans of medical researchers, a problem that has made it harder to find people of color to participate in coronavirus drug trials.
Potential disasters have also been avoided by not doing challenge trials.
In the early days of HIV, researchers thought they had found an effective vaccine and many people volunteered to have it tested on them, but the challenge trial was never approved. The treatment was instead tested on chimpanzees, and the animals died. In a more recent case, an ethical panel concluded that a human Zika virus trial would be too risky.
Dr. David Magnis, director of the Stanford Center for Biomedical Ethics, said a challenge trial for the coronavirus could probably be justified, but he wondered whether the reward would be worth the risk.
“To make the risk low enough, you can only do the challenge trials on young, healthy volunteers. But there’s a problem,” Magnis said. “Will the vaccine work on older people, patients with comorbidities? You can’t go from one population and say it works on another population. That’s the real limitation.”
Siegel said there is a much easier and morally defensible way to quickly carry out this research.
“That approach involves giving the vaccine to people at high risk for contracting the virus such as people in groupliving facilities, meatpacking and other plants, and on military ships,” he said. “In this case, neither the experimental nor the control group would be at increased risk due to the experiment.”