Can We Really Make a Safe Vaccine in 18 Months?

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S1: Thinking about the nature of time right now can be pretty confusing and you would not be alone if you occasionally forgot what day it was. But while so much of the world has paused or at best slowed down to a crawl, there are places where people are sprinting to treat patients, to manufacture personal protective equipment, to get enough testing to the public. These are all crucial things that need to happen.

S2: But perhaps the most crucial is a coronavirus vaccine.

S3: The ultimate the ultimate solution to a virus that might keep coming back would be a vaccine. We may have cycling with another season. We likely will have interventions. But the ultimate game changer in this will be a vaccine.

S2: A vaccine against Koven, 19, could confer immunity, allow us to protect health care workers, and would mean that we could really, truly carve out some kind of safe version of normal. But making a vaccine is not a speedy process.

S4: On average, vaccines can take a decade to develop.

S1: That’s Tim Lahey. He’s an infectious disease doctor and director of clinical ethics at the University of Vermont Medical Center.

S4: It just takes a year for the animal study. It takes a year for the Phase 1 human trial, a year or two for the Phase 2 trial, and then a few years for the Phase 3 trial.

S1: But that typical cautious timeframe doesn’t work in a worldwide pandemic. Right now, there are 60 some coronavirus vaccines in the development stage, according to the World Health Organization. And of those, some are moving along much faster than we’d normally see. Are there currently coronavirus vaccines being tried on humans?

S4: Yes, there are three trials in the United States and there’s a group in Oxford that’s just ramping up to do phase one clinical trial.

S1: Does it worry you the speed at which all this is happening?

S4: You know, I guess it’s reassuring and concerning how quickly vaccine development is happening. You all want a vaccine so that the threat of covered can finally fall back into the shadows.

S5: But we don’t want to rush so quickly that we actually lose the ability to make sure the vaccine is safe.

S4: Or a vaccine that you want to give to. You know, maybe a million, two million.

S5: Tens of millions of people who might be susceptible to getting Cauvin 19. It’s got to be really, really, really safe.

S1: Tim knows we have to rush. He gets it. And as much as the scientist in him wants to take 10 careful years, the clinician in him knows we can’t do that.

S4: I think this is an occasion to be aggressive about vaccine development. And it is the right time to think about how can we accelerate? Which rules can we bend? Is there some way we can do this differently from normals that we can get a vaccine? Not in 10 years, not in five years, but in one or two.

S2: Today on the show, how we get to a corona virus vaccine. Researchers agree that some corners need to be cut, but every decision to pare down the vaccine testing process comes at a cost. I’m Lizzie O’Leary and this is What Next TBD, a show about technology, power and how the future will be determined. Stay with us.

S1: I want to kind of back up and do a thought exercise with you. So let’s pretend there is no global pandemic. I’m not interviewing you from my closet. There is no pressing need to develop a vaccine. You know, tomorrow. Let’s just say we want to develop a safe, effective vaccine. Where do you start and kind of how does the process begin to make sure things are safe?

S4: There is a really well established, careful, methodical and super slow way to develop vaccines. And so if there wasn’t this global pressure to get this done yesterday, we would develop a bunch of different vaccines in test tubes and make sure they had just the right characteristics. We would test them in at least one and maybe more than one animal model. After we had sacrificed enough mice and maybe some guinea pigs, we would have a careful review of the data from those studies. And then we would really slowly and carefully move toward human.

S1: Phase one trials in the first phase of human trials. The vaccine would be tested on a very small group of people in phase two. That group gets bigger and is tailored to reflect the population the vaccine is intended for and then only if the vaccine is really promising. You move on to phase three.

S4: Usually this doesn’t happen. Usually something goes wrong in either the mouse you tested it and get sick or it’s not strong enough in humans or something like that. But let’s say you’re lucky and you decide after years of work to move forward into the gold standard study. Then you conduct Phase 3 randomize placebo controlled double blind clinical trial. This often can involve thousands of subjects and oftentimes it’s in people who aren’t just healthy volunteers. Maybe there are people who are a little more likely to get the infection that you’re trying to protect them from. You know, this could be sexually active young adults who need protection from human papillomavirus or older adults with immunocompromised who are at risk of getting pneumonia. And then you give them the vaccine or a placebo. Nobody knows who got which one. And then you follow them over time to see if they get the actual infection. And it doesn’t always work sometimes. We’ve had vaccines against staph infections, for instance, where they did all of this and thousands of people were vaccinated and then nothing.

S1: I mean, this feels like such a painstaking, slow approach. What is the utility of of moving at this sort of glacial pace?

S4: The answer is that we’ve learned through the years of developing vaccines and drugs that without these safety measures, you can get fooled into thinking that something that is useless actually works because you have such high hopes and you kind of say, well, I have a great mechanism in mind. And so it must do something. But it doesn’t really. The other thing is that not only do you want to know that the thing you’re testing works, but you have to make sure that it’s safe. And it turns out that, you know, major safety concerns, you know, every person who gets that vaccine explodes are obvious. But some vaccines actually have cause some rare side effects that you only see once you’ve tested it in a big group. And so you slowly, slowly increase the number of people who get it. So that is some big bad problem happens. It doesn’t happen to a lot of people. But then if something rare but important happens, you see it in a larger group of people.

S1: Well, this isn’t the first time we’ve needed to develop a vaccine quickly.

S4: I guess I’m wondering, when has that happened in the past, most recently and most compellingly, Ebola exploded in Guinea and other West African countries. And unlike its usual course of just affecting, you know, two dozen, 50 people, suddenly hundreds, thousands of people are affected. And we needed to get a vaccine really quickly. And whenever there’s a sense of urgency like that, that makes you think, OK, which of the rules of vaccine development can I bend when it came to that most recent Ebola outbreak?

S1: The rule that they bent had to do with placebos. Normally when you’re testing a vaccine, you administer a placebo to a control group to make sure that it’s the vaccine that’s having an effect, not some other factor, but because of the urgency of that outbreak. Scientists skip that step.

S6: It was a controversial call in the days of Ebola not to study against a placebo. Some people were saying, hey, you have to know if this vaccine works just like any other. And so we need to use the placebo. Others argued that it would have been unethical to give people a placebo, which we knew wouldn’t work. Against Ebola. If you had something that had come out of the lab that had a reasonable chance of working. And ultimately the latter camp one in Ebola was tested without a placebo. And one of the rationales that’s really important to understand with the Ebola vaccine that’s different from covered 19 is that they knew they were going to give the vaccine only to a small number of people and probably just for a short time. We knew that Ebola was going to flare up cause. Whoa! And then recede back into the shadows again. And so they felt like, well, you know, let’s say we try a vaccine that doesn’t do much good and maybe has small harms. We’ve only done it in a small number of people in this small area. And so that’s safer than if we had a less perfectly tested vaccine that was given to millions of millions of people in the race to develop a vaccine for Koven, 19.

S1: We’re talking about a potentially huge population who will need it. And researchers are debating whether it’s worth taking more risk than usual. In a recent article in the New England Journal of Medicine, a group of scientists argued that it might be necessary to skip a placebo to speed up testing.

S4: I think it’s a natural question to wonder if we didn’t use the placebo to develop the Ebola vaccine. Why do we have to use the placebo to develop the Cauvin 19 vaccine? So this is very different in that we think just about everybody can be infected with Koven 19. And and sure, there are people who are particularly at risk, the elderly people with immune compromised, but nobody’s safe. And so the people likely to get this vaccine are so numerous, it would just be millions upon millions of people. And I think that gives us a special duty to make sure that we know that this is safe.

S1: Tim thinks that this debate over placebo controls is going to ramp up in the coming months. But there’s another potential shortcut being debated now among vaccine researchers. At the end of March, an influential group of epidemiologists published a paper arguing for something called Human Challenge Trials.

S4: The Human Challenge Trial is a trial in which you study a vaccine versus placebo in an infection that you cause yourself. So instead of waiting for that person to breathe in some tuberculosis spontaneously in the air or to get bitten by the mosquito that causes dinghy, you would expose them to the infection. And so dinghy is an example of an infection that people do human challenge trials against, where brave volunteers take out their arm and they get bit by tinky infected mosquitoes after receiving either a vaccine or a placebo. So this is a way you can make sure the person you’re vaccinating has been exposed. And that means that your likelihood of being able to tell if the vaccine protected them is a lot higher. So that allows you to go much faster. You can do this study over a shorter period of time using fewer human subjects and you get your answer a little bit sooner.

S1: These trials are generally done for diseases that have a cure or some kind of treatment. So I don’t know. It seems kind of bananas that you might infect someone with Kobe 19, which has no cure. How do you think about that?

S4: Yeah, this is the key distinction. There are two important differences between covered 19 and the kinds of infections that I think it’s a good idea to do a human challenge studies on. So when is human challenge? Studies are often done and infections that are, you know, cause some risk. That’s why we want to vaccinate against them. But they’re not typically lethal so that the infection you’re inducing in that person is probably to make them miserable. But it’s it’s not going to threaten their life to go participate in that study. So dengue is an example of that. I can just put you out of commission for days and, you know, be a bad story. You remember for years, but you’ll be OK in most cases in Koven, 19. We know it’s lethal. We know that even healthy volunteers would be at risk of death at much lower rates than medically fragile individuals. But still, it’s a it’s a risk of death in the middle of a clinical trial. And then we have no known therapy for covered 19. There’s no antiviral drug today that’s been effective. So if we induce Cauvin 18 infection in a human being and if they are unlucky and they start to get life threatening complications from it, that’s our fault.

S1: Would there be a way to do a human challenge trial for Copan 19?

S4: Ethically, you’d have to be incredibly meticulous about the way you did it. But I think it’s a Aneel you could thread. So you’d have to. 1 make sure that person has their eyes open about the risks that they’re getting into. And you know, when if somebody decides that, hey, they want to they want to protect society and they’re willing to take that risk after being well informed, OK, then. Then that’s one hurdle. The second is, how do you make sure that if they do contract covered 19, that they can’t spread it to somebody else? And then you would need to make sure that you do the study correctly so that out the end of that risk, you know, you will know the answer of whether the vaccine worked. So sometimes you can test a vaccine or a drug and maybe you don’t know exactly how often that infection happens. So you make a guess about how big this study has to be in order to do it. And then if it turns out that you were wrong about how often it happened and the study just couldn’t show you the difference between the placebo and the vaccine, well, then, yeah, you know, you roll your eyes and you say, oh, shoot, we just, you know, wasted a lot of time. But, hey, we’ll try again. If we’re going to risk somebodies life in order to get this answer, we need to make sure we know that we’re going to get the answer at the end so that it was worth it.

S1: The best researchers in the world are split on much, it happened here. I asked him to explain to me who is in which camp.

S7: The topic of whether you should do a human challenge trial against COVA 19 vaccines is heating up in scientific circles right now. And already giants in their field have squared off on opposite sides of the question. There’s a vaccine giant by the name of Stanley Plotkin of the University of Pennsylvania, who has said that we should take the risk of going forward rapidly with human challenge trials in the belief that the risks of not going so fast are even greater. On the other side are scientists such as Matthew Mimili is a scientist at the NIH who is sounding a note of caution. These camps are sort of arguing back and forth. And to me, that’s fantastic. Probably the answer is some third path. You know, it’s not do it exactly the way Plotkin wants to or do it exactly the way Emily wants to. But instead, how can each of their approaches be refined by the arguments of the others so that we find a way that neither of them quite thought about, but as balances those risks and benefits.

S1: This week, more than 30 members of the House of Representatives wrote a letter to the FDA in support of this human challenge idea. I wonder what the role of politicians is in deciding whether this happens or not and how you feel about that.

S6: As an infectious disease doctor, I thought it was a fascinating political move to have a bunch of politicians vote on whether it would be scientifically advisable to do something like human challenge trials for at 19.

S4: Ordinarily, we look at the data and we decide on the basis of the evidence and scientists evaluation of the evidence. Asking a bunch of politicians seems to me like a great way to get a confusing answer about it. These are not scientists. I really don’t think that they’re qualified to address that question.

S1: So when you say fascinating political move, you’re being snarky.

S4: I’m. I would never be snarky, lazy. I have no idea what you’re talking about.

S1: Are you going to let me pin you down on even a theoretical timeline? When you think a vaccine might happen?

S7: Tony Foushee estimated that it would take a year to 18 months to develop Cauvin 19 vaccine. And many commentators in the field thought that was pretty awesomely optimistic.

S6: I think if the full weight of his National Institute of Allergy and Infectious Diseases is put behind really thoughtful, really accelerated trials, I think it is possible we could get an answer within that timeframe. But if we do business as usual, I think the naysayers are right. It will take longer than that.

S1: Do you think we’re gonna get this right?

S7: I sure hope we can get this right. Lizzie, this is a frightening epidemic as an infectious diseases doc. I’ve seen scars and murders and taking care of plenty of people with contagious diseases. But this is the first plague that has really made me nervous. So I hope that we get lucky in at least one of the vaccine candidates that we’re studying now is the one and the one that can protect our particularly fragile neighbors from getting hurt.

S8: As a scientist, though, I know that there are always three possibilities that could help you. It could harm you or I could do nothing. And I want to make sure that we don’t get deluded by our optimism into forgetting that.

S1: Tim LaHaye, thank you very much.

S9: Thanks for having me.

S2: Tim Lee, he is an infectious disease doctor, ethicist and vaccine researcher at the University of Vermont Medical Center. And that’s our show for today.

S10: What next? TBD is produced by Ethan Brooks and hosted by me, Lizzie O’Leary, and is part of a larger what next family. TBD is also part of Future Tense, a partnership of Slate, Arizona State University and New America. And speaking of Future Tense, I want to let you know about a great series of online events they’re hosting right now called Social Distancing Socials every Tuesday and Thursday at 4:00 Eastern. Or hosting fun, smart, challenging conversations on the most pressing tech and science issues of the day. I’ll be there May 7th. I’m going to talk to FEC Commissioner Ellen Weintraub about the movie, The Social Network and how Facebook has evolved to be at the center of so much of our political world. So I hope you join us. If you want more information on these socials, just go to Slate dot com slash live. Before I go, I want to recommend that you go back and listen to Tuesdays episode of What Next? It’s a little break from coronavirus. This one is about the 2020 Senate races, which, yes, are still happening. So you’d be paying attention. What next will be back on Monday. Thanks for listening. Talk to you next week.