HEFFNER: I'm Alexander Heffner, your host on The Open Mind.

I'm delighted to welcome to the program today Nir Eyal.

He is professor of bioethics and director of the Center for Population Level Bioethics at Rutgers.

Welcome Professor.

EYAL: Thanks so much for having me on, Alexander.

HEFFNER: Let me ask you about the human challenge trials that have been underway for some time, not since the beginning of the pandemic, but since you know, for several months.

And I want to ask you for an update on, you know, based on your knowledge, of what these human challenge trials have produced so far.

EYAL: Right now the challenge trials are really only at the preliminary stage.

They are doing what is called the dose collection study in which the trialists start exposing participants at the very low doses of the, to the virus and seeing the do rounds of that.

And with each round, they up it up, a bit, the dosage so that they can make sure that there are no injuries, that the dosage is fairly safe so that they can eventually reach the level of virus exposure that would start giving them the scientific answers that they need.

And right now they're still at that in the UK.

HEFFNER: Professor, this is only occurring at Oxford in the UK so far?

EYAL: Exactly.

The dose collection is occurring at Imperial College, London and Oxford University has announced that it too will engage in a challenge trial.

So later on, we are likely to have the real challenge trial, both at Imperial College and at Oxford University.

HEFFNER: This was contemplated before we saw the efficacy of the mRNA vaccine specifically, before they were tested, not with clinical trials, but in a full population.

And now we know from the United States and Israel, or at least scientists believe that the mRNA vaccines, that is the Moderna and Pfizer vaccines, give folks some amount of immunity and are efficacious again, to a degree that is going to be determined.

Now that we know about the workability of those vaccines and ultimately the feasibility of vaccinating a public, do you think that doing these trials is still ethical and still necessary, the human challenge trials?

EYAL: Yes.

We have vaccines, ones you mentioned - other authorized vaccines in America, J & J and in the UK AstraZeneca, but there remain open questions about them.

We don't have the so-called cooperative protection for these vaccines which is something we could elaborate on later.

We don't know exactly how much they prevent infection and infectiousness in people who get them.

We don't know how well they work in your own populations against every strain of the virus.

So there may well pop up a sprain, maybe one has popped up already in Africa that is avoiding a vaccine protection.

And so we will need to test alternative vaccine boosters in young populations to check how well they work.

We also are not sure what regimens of these vaccines work best.

You remember a debate about whether there should be a long way to between the doses.

Maybe we can minimize and save vaccines by giving just one dose of a vaccine that was planned with two doses in mind.

All those things can be assessed quite well with challenge trials and in the UK they're envisaging challenge trials that would assess the duration of vaccine protection.

What happens to people have already been exposed to the virus in the path that a lot of information that can still be gotten from challenge trials.

HEFFNER: What is the most critical information that you hope such trials would result in that would enable knowledge that we don't possess today?

EYAL: I think that we are starting at this point, very belatedly, to be able to tell that the vaccines work well, most to curb infections.

We no longer need so much the answer to that.

I wish we had that answer much earlier on.

We could have prioritized vaccine distribution differently on that basis.

Many of the decisions would have been different at this point.

I would say the most crucial information for bolstering protection is in countries that have vaccines already, is checking the vaccine success against new viral strains, which evade the authorized vaccines protection, and for countries that don't have good access to our vaccines, either because they're unavailable for sad economic reasons, or just because the delivery would be too complicated in the environments of these countries, cold storage, other issues, they need to develop other vaccines.

The need the development of these other vaccines.

And there are many in the pipeline now, which would have easier delivery and storage and perhaps better pricing, better availability, a crucial issue given how few of, of our, you know, fellow members of humanity have good access to the vaccine.

We now have in America to develop these other vaccines; a challenge trial could help break in.

HEFFNER: Right.

Ultimately, you know, in terms of the mechanics of the challenge trial, can you tell our viewers and listeners how it works and how it's guaranteed, in your mind to be humane or ethical?

You're giving people a dose of COVID that is a survivable, you know, theoretically, a survivable dose, that if they have a bad reaction, they might get sick, but they will still, you know, they will be well, ultimately.

So can you, can you take us through the mechanics because this human challenge trial emanating out of the UK was really unprecedented, the first of its kind, internationally that society has ever experienced.

EYAL: In the simplest schema, human challenge trial works as follows.

A few dozen volunteers, much, much smaller number than the numbers we talk about, 60,000 people at some of the field trials, to get the vaccines that we authorized in the fall.

So here, we're talking about a few dozen volunteers give their consent to the following scheme: They are randomized to receive either the vaccine or control.

So, a placebo like we had in the trials in full, or perhaps another vaccine to which you want to prepare this vaccine or another dosing regimen for this vaccine, if that's what you want to prepare, you know, some control.

And then everyone is exposed to the virus, in the typical way, it's going to, you know, a swab in the nose with a little virus culture on it.

If there are very different results between the active arm, the arm you want to check, the vaccine arm and the control arm, you say, okay, let's look, the difference between the make a lot of difference.

A lot of people got infected here and not many people got perfected here.

If there isn't much difference the presumed conclusion is, it doesn't make much difference, say this vaccine is not much better than placebo.

This dosing regimen is not much better than what you're comparing it to.

This is the design.

How do you keep the safe?

I mean, you know, when you're exposing people to something that kills millions around the world, the main key to doing that, there are a lot of medical care is offered and safety and a lot of doctors.

And the main key, the simplest thing is subject selection.

You simply find, focusing only on people who are young and without the comorbidities, but also up the chance for severe outcomes.

We can calculate how much that would increase safety in the study.

And simply that factor, according to a recent article, published in Clinical Infectious Disease would make these trials much safer, then, this is my comparison, than a hundred times safer, or depending on they had the kind of a margin of about the risk of the challenge trials, all done could be safer, then 500 times safer, then living liver, living, right liver lobe donation.

That's an intervention that doctors offer consenting adults routinely, oftentimes talking about it as low risk, but whether or not it's low risk or high risk, we already agree that an adult person can with full consent, do this thing, donate a right liver lobe, which has a one in 200 chance of killing them, and has a fair chance of causing injuries.

But we think, we just, for somebody else, it would mean life, it's okay to approach them with that request.

It's not unethical.

These trials, are two orders of magnitude or perhaps more, perhaps three, safer than this routine intervention.

And they would help save, if you think about the scale of a pandemic, would help save not one life.

But if we expedite response, if we improve response, we're talking about easily thousands and thousands of lives saved.

HEFFNER: We're in this period in the United States of I would not call it the honeymoon period, but a period of, of peak vaccination, distribution, and immunity building.

And it remains to be seen, Nir, if ultimately vaccinating 50 to 60 percent of the American public will be sufficient to returning to public settings in the fashion we were prior to the emergence of COVID-19.

We just don't really know yet because we don't know the answers to some of those questions that I think you hope these challenge trials will produce the answers to.

One of them is the duration of immunity.

We were told during the invention of the mRNA vaccinations and these vaccines, that they were not like the smallpox vaccine or the polio vaccine in that it could give you lifelong immunity.

We were told this was a unique specimen, a unique kind of vaccine.

And I wonder what your reflection is at this moment, scientifically and bioethically, because we are in this moment where the CDC has issued the unmasking guidance.

And yet only 50 percent at most has been doubly vaccinated, fully vaccinated, of the American people.

Internationally, COVID continues to be a conflagration and disaster and many countries that have not vaccinated their citizens.

So it leaves us in this rather precarious and an unusual position.

And I just wonder what your assessment of this stage is?

EYAL: Challenge trials can give information about the duration of immunity, more accurately than field trials.

Basically in the field trial, the way it works is you give people a vaccine versus control, and then you send them back to their ordinary lives and you're waiting for enough of them to get exposed naturally, you don't know when exactly they got exposed, how they got exposed, how much they got exposed.

Challenge trials are very, very controlled there everybody's in the medical facility, you know, exactly where they got exposed, and it's easy to assess the duration of immunity.

You can actually, people are talking about challenge trials where you will do a sort of second challenge sometime later, to test whether the immunity lasts.

So yes, they could provide these answers quite credibly.

To me from, I work in a public health school, the most urgent questions remain these uncovered global populations, and Americans, if our vaccine start failing, say against a new strain, but I'm thinking about the big numbers.

That's what I, I think has the biggest ethical justification, ethical urgency.

And I would love for us to answer these questions in particular.

HEFFNER: If you think of the trial stages of what's occurring right now, you also have a few companies that are developing oral.

So a pill, an oral vaccine.

It has not really been adopted anywhere yet.

But I believe they're trial participants, or, you know, there are companies producing this.

But the other question that might be resolved through the human challenge trials or other scholarship is this question of a medical intervention outside of vaccinations.

You know, there were several antiviral drugs proposed to work, and ultimately, they were really not successful in most of their implementation.

So you know, we've been told for, for decades or centuries since we've known the difference between viral and bacterial illness, that it's very hard to make an effective antiviral drug.

The question is, can you ultimately make something, if not an oral vaccination, some sort of over-the-counter oral medicine that could you know, reduce COVID infectiousness and make this much more treatable?

EYAL: In principle charge files could answer these questions about treatment.

It's ethically a harder sell.

HEFFNER: How so?

EYAL: The safety, my assurance about the ethics of these trials is anchored mainly in what I told you earlier.

I think that by recruiting young and healthy people, we are very unlikely to have people who develop severe disease.

To have credible answers as to whether a treatment saved your life when you develop some, your disease, your need for a lot of people to develop severe disease.

So you need to start, I know maybe recruiting people who are not as young, not as healthy and that starts being harder to justify ethically because then you're introducing serious risks.

So the good thing, and the bad thing about challenge trials, is you are not going to have many cases, in all likelihood, no case of severe disease in the trial.

By far that's the likely or scenario.

That also means that you can't learn much about what to do when there is a severe disease.

You need to learn that from other things.

HEFFNER: Right.

Well, do you think that the at-home testing availability combined with the vaccination rates increasing in the U.S. and other countries will be enough to ultimately extinguish COVID because if you have that combination of the at-home testing and vaccinations, then you'll be able to ascertain if you have COVID at a certain stage when it is treatable, and you're more protected, of course, if you were vaccinated and you happen to have a breakthrough infection, but do you see enough interventions, medically speaking, that you believe COVID can be eradicated?

There was this question about whether COVID will ever be eradicated and whether we have to live with it as another kind of chronic illness or flu-like seasonal illness, is the jury out on what the answer to that question?

EYAL: I'm not an epidemiologist.

I'm an ethicist.

From what I read the epidemiologists increasingly believe that we cannot anymore eradicate COVID.

Some of the reasons why we don't have higher vaccination rates in America have to do with population behavior and who knows how people will behave about testing.

When people get to test at home, sometimes that's triggered by their already being symptomatic, but we know that COVID is transmitted even before people are symptomatic.

So it often catches it too late.

Who knows?

I know in my home country, Israel they don't have a hundred percent vaccination, but they have a high percent vaccination and COVID has plummeted.

Not so much thanks to testing, but mainly thanks to these vaccines, which are the mRNA technology, which is just working incredibly well.

And presumably that what the cases show us, there's only, also in curbing transmission, not just protecting the individual who got the vaccine from developments of your disease.

HEFFNER: Since you look at the entire globe, what do you think would be kind of the, the ethical standards, if you will, now, for countries that are 50 percent vaccinated or better, to contribute to help vaccinate countries that are suffering, that continue to have mass deaths daily.

Is there some kind of ethical consensus that you've reached on the public policy that makes sense, so that if it's not eradicated, COVID is at least managed effectively in America and in Europe and in India and in Brazil and, you know, everywhere?

EYAL: It's both in everybody's interests and a strong ethical obligation for everyone to protect everyone around the world for COVID.

It's foolhardy not to share vaccines generously with nations that don't have enough, because A. while the viruses circulating there and replicating itself is worked, it has chances to new date and potentially develop that variant that I'm concerned about that will evade our vaccine protection.

So it really might come back to bite us if we don't help roll-out the vaccines globally, as fast as possible.

It's also important for our economy to open up markets around the world for our products.

And it's a strong, ethical obligation.

I mean, look at the horrors that are going ongoing in India right now, in Peru and in Vietnam and Nepal, Brazil, terrible, terrible situations, and an obvious ethical case for doing a lot about them as much as we can really.

HEFFNER: And when you speak to fellow ethicists on this question, is there a specific regimen that you're imploring?

I mean, is there a specific way of kind of calculating this and couching it ethically in terms of what countries ought to be first on that list?

And you know, some of it probably is correlated with the variant distribution and you know, where variants have a greater risk of not just being imported within that country further, but around the world.

EYAL: There has been work published last summer in Science magazine that said that the main criteria should be not the one used by Covax, an initiative associated with WHO and Gavi, but rather the following one: don't just give it proportionately to every country.

Canada doesn't need any more vaccines and has kind of has ordered way more than its population needs in vaccines as the U.S. and other rich countries.

Instead distribute it based on the need, the medical need of the population given for example, infection rates, given predictions of future infection rates in the population, incident rates.

So that to me is an approach that makes more sense than just giving it, you know, according to the number of citizens.

HEFFNER: Right.

EYAL: Going into further details, you have an interesting proposal to subjective also specifically it to the issue of the variants, which affect greater externalities, if you will, for other nations.

And one could fine tune it in many additional ways.

For example, one important consideration is African countries are said not to have had very high incidents so far, but in some of these countries, it seems just to be a matter of under-representation of the numbers.

So in fact, there is more COVID there than we assume.

So you can't just read the numbers off of what the health ministry assumed the numbers are.

HEFFNER: Right.

EYAL: Next question.

HEFFNER: And there's also a question about the ethical evaluation of distributing in a country that is unaccountable for its COVID numbers.

Like, do you trust distribution in the hands of a population?

Peru is an example of vastly undercounting its death toll, only to be demonstrated as one of the most fatal counts in the world.

But reporting that many months later in terms of an accurate count of fatalities.

Let me ask you this before we conclude we'll you can't discuss bioethics today without considering the consequences of gain of function research, because there is not a clear understanding of the origin of COVID-19, you know, that initially it was said by many scientists, this crossed over from an animal, from a bat to another animal, to a human.

Now with the absence of any animal, which they did have, in MERS of middle Eastern or SARS, the original COVID in emanating from Asia.

There, there is no real scientific evidence of the lab leak, but there's also no scientific evidence that it came from, you know, a natural source.

So we believe Wuhan and the Institute did engage in this gain of function research that can put populations at greater risk of becoming infectious as a result of higher risk research.

I just want to your ethical snap understanding of gain of function research, and whether it is ethical or whether it should be halted?

EYAL: I'm not going to commit in any way to the origins of this epidemic.

I don't know the answer.

In general, about gain of function research, my position is that it's more dangerous than contributing to safety.

In a word, you can use it to develop safety precautions, but they would be often very specific to the variant that would attack you.

And the chance that the variant that you develop is the one that otherwise would have attacked the population, and therefore that any protections that do develop to fight well against this variant, are going to work well against future independent attacks on the population by a new base of that strain is relatively low.

More pronounced is the probability that there will be a leak from the lab, that some-- HEFFNER: We're out of time here.

But I just want to ask you very quickly is gain of function research more high risk, is gain of function research more dangerous than a human challenge trial?

EYAL: Oh, for sure.

HEFFNER: Yeah.

I mean, I just want to put it in perspective because there was a large force of people who said human challenge trials are wrong.

They're ethically wrong, they're dangerous.

But in reality, I would agree with you and you're approaching it from the scientific and ethical lens that, that one is far more a danger, what Kevin Esvelt at MIT calls an information hazard, when you're seeing what kind of infections you can build, in effect, bioengineering that is dangerous.

Nir Eyal, thank you for your insight today.

We really appreciate it.

EYAL: Thank you so much, Alexander.

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