On the latest episode of the Social Distance podcast, James Hamblin and Katherine Wells ask the infectious-disease expert Stephen Thomas to explain the medical and ethical issues involved in developing a new vaccine.
Listen to the episode here:
What follows is an edited and condensed transcript of their conversation.
Katherine Wells: I don’t actually understand how vaccines are developed on any sort of granular level.
James Hamblin: How do you go from this tiny prototype in eight people where they didn’t seem to be harmed, to a billion people with a needle in their arm? It is a technical process that could go a few different ways, depending on our capacity or willingness to incur risk. We can play it really safe and do it really slow, but lots of people are dying every day of this disease. There are incentives right now to take risks that usually vaccine-development people wouldn’t take.
An idea that is being discussed in vaccine circles is “human challenge trials,” which we’ve done for some other viruses, but they are not being done right now for this coronavirus. They involve giving people one of these test vaccines and then purposefully exposing them, in a standardized way, to the virus. When you have a disease like this, you have to get a huge number of people with the test vaccine and then see what percentage gets sick and what percentage doesn’t. But [with a regular trial] you don’t really know who is actually exposed [to the virus]. How many of those people who didn’t get sick just didn’t get sick because they were staying at home with their huge bag of Purell?
Wells: So a challenge trial would speed up [the development process] because we would know exactly who was exposed?
Hamblin: Right. You could say, 70 percent of the people who got the vaccine were protected, and 30 percent of them got sick. The problem is that would mean people got sick with a disease like this, and potentially even people died or had lasting complications. There’s obviously a big ethical dilemma there. But it could theoretically really speed up this process and make it more scientifically valid more quickly. It’s not happening right now, but some people are proposing that it should.
Stephen Thomas is the chief of infectious disease at SUNY Upstate Medical University. His focus has been on researching vaccines.
Wells: What is a challenge trial? And should we do it?
Stephen Thomas: This is where we give a healthy human being a mild form of the disease that we are trying to study so that we can hasten the development of a countermeasure drug or a vaccine, or we can fill in some critical gap in information that we are not able to fill using standard, benchtop science or small animals like rats and mice. Challenge trials have been around for well over 100 years, and multiple diseases use challenge trials to support their development. Each disease has particular reasons why human challenge makes sense.
Wells: A challenge trial is where you vaccinate someone and then you expose them deliberately to the virus to see if they get it. Is that right?
Thomas: That’s the second step. The first step is exposure without the vaccine.
Hamblin: You have people who have volunteered to be infected. How do you navigate that space about how someone can really consent to that, and who is willing, and why they would be willing to go through that?
Thomas: There needs to be what we call “democratic deliberation.” There needs to be consensus among interested and disinterested parties, to include physicians and scientists and ethicists and regulators, that the disease that you’re talking about is appropriate for a human challenge. You’re not going to have a human challenge model for a chronic, incurable disease. You’re not going to have a human challenge trial where the risk to the individual is unacceptably high—that’s a whole discussion in and of itself. You’re not going to have a human challenge model where the risk to others, not just the person who volunteers, but other people, is unacceptably high.
Then you propose a plan to the ethical review committees and the FDA. Part of that plan is the informed-consent process, where you explain to the potential volunteers what the risks are and what the benefits are. And oftentimes, the only benefit is that they will be advancing science and that they might be able, through their sacrifice, to help somebody else.
Wells: Do you think it’s likely that this global pandemic will create the necessary urgency to make whatever risks worth it? Do you think a challenge is going to happen?
Thomas: There are too many unanswered questions about how we would actually do them. For me personally, I absolutely think it should be thought about, and it should be discussed. Challenge trials, in the right circumstances and under the right conditions, can be incredibly valuable. I put my money where my mouth is, not just because I do challenge trials, but I have volunteered for a challenge trial.
Hamblin: What did you get?
Thomas: Malaria. I was an infectious-disease fellow at the time, and I knew what I was going to do with my life. And I said, “Someday you’re going to have to say that you stepped up and actually did what you’re asking other people to do.”
Hamblin: How did they expose you?
Thomas: I got three vaccinations over a period of weeks and then waited for a month. And then I came back in, and they had five malaria-infected, very hungry mosquitoes in a little cup with a screen on top of it. I put my arm on the top of the cup, and the mosquitoes came up and fed on my blood. And then [the researchers] took the mosquitoes and took the salivary glands out of the mosquitoes, and they confirmed that each of the five mosquitoes had malaria.
Wells: Did the vaccine work, or no?
Thomas: As a matter of fact, it did.
Wells: I imagined that there would be some highly scientific, tech-heavy process. But no, we just take malaria-infected mosquitoes and have them bite you.
Thomas: This is a great point that you raise, because ideally, you would want to deliver the virus the same exact way that somebody would be exposed.
Hamblin: Oh no. So for COVID-19, would people be coughed on?
Thomas: That’s one of the questions: How are you going to deliver the virus?
Wells: How much time do you save by going straight to a challenge?
Thomas: If it worked really well, and the FDA believed that it worked really well, and the FDA said, “Listen, we will give you a license and allow you to sell your vaccine based on challenge data alone.” Then I think that’s one of the scenarios where we potentially could meet this warp-speed benchmark that has been put out there: [a vaccine] by the end of the year.
Wells: I imagine even if we did challenge trials, it’s not guaranteed. A lot of other things would have to go really, really right for us to have a vaccine widely available by the end of the year.
Thomas: That’s correct. Is it possible that we could be on the doorstep of having a vaccine by the end of the year? Sure, it’s possible. Is it likely? No. There’s a lot of open boxes that you have to check between now and then.
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