United Kingdom has given approval to a trial
that will expose healthy volunteers to COVID-19.
Infection is guaranteed
with a so-called challenge trial.
Challenge trial.
As the pandemic progressed over the last year,
you may have heard this term challenge trial come up.
The idea was that by deliberately exposing people
to the virus, you could help speed up the development
of a vaccine, and it turns out a lot of people
were up for this.
Everybody feels terrible right now.
Here's something that may help the world
be a little bit better, so I was like, great,
that sounds good to me.
Let me sign up right now.
Ultimately, challenge trials did not end up being used
to develop the vaccines that are now in circulation,
but now, researchers in the UK are turning
to the challenge method, saying it will allow them
to test the long-term effectiveness of the vaccines
and learn more about the disease overall.
It's restarted a controversy in the scientific community
over the safety, efficacy and morality of the practice.
I spoke to some very smart people on both sides
of the argument,
in an attempt to answer a question with big implications
for humanity's future.
Okay, so we're here to talk about human challenge trials,
but I guess, first let's talk about typical vaccine trials.
How do typical vaccine trials work?
Yeah, so once a vaccine candidate has been studied
in animals and in the laboratory,
it moves into human studies,
the idea is that once you're vaccinated
with either a placebo of the actual candidate,
you're exposed in society to the pathogen,
and we want to see that most of the infections
and disease occurred in people with the placebo,
to determine that the vaccine
is actually protective and efficacious.
So with a human challenge study,
we deliberately infect humans, human volunteers,
and look at, essentially, what happens to them.
You say I've got the viral agent, COVID, whatever it is,
and I'm going to give it to people.
This is Art Caplan.
He's a researcher at NYU,
who's pretty firmly in the pro-challenge trial column.
Well, historically vaccines are tested in large trials.
Usually you're talking 30, 40, 50, 60,000 or more subjects.
You could spend six, seven, eight years trying to get data.
A challenge study basically is a way to speed up
the trial process.
You may be able to get answers as quickly as exposing 500,
600 people, maybe over a period of six months to a year.
So are human challenge trials new
or have they been done before?
Human challenge trials are not new.
Scientists have been doing them for quite a long time,
decades, looking at various diseases, malaria, cholera,
influenza are some of them.
Walter Reed did it, as a matter of fact,
with his malaria experiments in Cuba.
They deliberately let mosquitoes bite them to get malaria,
to test antidotes.
Assumingly, again, they don't want to kill you,
although people have died in challenge studies.
We have a tradition in space medicine of saying,
"Gee, I wonder how long people can survive
"extreme gravitational forces.
"Let's put 'em in a centrifuge until they pass out."
So there are many areas of medicine, healthcare,
even public health,
where we do expose people to risk deliberately,
in order to learn.
This is the infamous trolley problem in bioethics,
which is should you sacrifice one person
to save five people?
This is Liza Dawson, the chief of bioethics
at the Walter Reed Army Institute of Research.
She's not really opposed to challenge trials,
but where COVID is concerned,
she's basically in the anti column.
One of the issues is that we have less ability
to predict what will happen to people as a consequence
of COVID infection, something like 10 to 20% of,
depending on the numbers,
have longterm consequences of COVID infection.
That's not to be sneezed at,
and people of all ages seem to be susceptible
to longer-term consequences of COVID.
We are rolling the dice that something terrible might happen
or something fairly bad might happen to people
in these trials.
Well, I do understand the critics
and some of their points of view,
it's never easy to defend deliberately giving someone
something that makes them sick.
That violates a core norm of medical ethics, do no harm,
but I'm not really buying into the it causes more harm
to do a challenge study.
It feels psychologically different
to give somebody a disease, as opposed to saying,
"Gee, I don't know how you got it.
"Maybe it was on the subway
"or maybe you should've worn a mask
"or maybe a new variant appeared."
We may feel psychologically, we didn't do it, nature did it.
Nonetheless, at the cemetery, they don't care.
You're relying on nature to infect you
but it's not like people aren't exposed.
I'm not sure that that's significantly morally better
than just saying, I'll give you the disease
and we'll get a faster answer.
And there are a lot of volunteers who feel the same way.
The organization, One Day Sooner,
which advocates for people's right to participate
in challenge trials,
says it's had almost 40,000 people contact them,
offering to take part if such a trial were to be conducted.
Two of those volunteers are Lena Jewler,
a recent graduate of Johns Hopkins, and Gavriel Kleinwaks,
a PhD student in Colorado.
Safe to say, they're both in the pro column.
So speaking personally,
why would you be willing to be part of a challenge trial?
I think, initially, I was looking at this as a person
who does human subjects research,
and a person who likes to participate
in human challenge research,
so one of the cool things about being a student at Hopkins
is that you have access to participate
in this really cool research,
and I've always found that fascinating, just as a person,
to participate, to say, okay,
I'm contributing to the science
that may help someone else the road, and then,
the challenge aspect of it,
I was really swayed by this argument
of this is so much more efficient,
this is so much more effective.
I would say the very first place my mind went was...
So I'm Jewish, and in our philosophical traditions,
it said that to save a single life,
it's as if you've saved an entire world.
In the argument for challenge trials,
the original argument back in March,
it was estimated that developing a vaccine...
Every day sooner that you develop a vaccine
saves 10,000 lives,
and I thought that that's amazing.
I would do whatever it took to develop a vaccine
one day sooner, which is why the organization
is called that.
We all know what it means to donate your time.
We all know what it means to donate your money,
but this was an opportunity I felt to donate health,
to try to share some of my health with others.
So there are reasonable arguments on either side
of the ethics debate and a lot of people are willing
to take the risk,
but some offer a different kind of criticism
of challenge trials,
that they wouldn't actually accomplish their goal
of speeding up vaccine development.
That's the big beef put forward by Charles Weiier,
a Canadian bioethicist.
He says the current UK study is the perfect example
of just how long challenge trials can take.
What they're doing,
so they've spent a number of months
developing the challenge strain,
so making sure they've got a stable strain,
where they haven't introduced mutations
through the manufacturing process.
The second step is what they're just embarking on now
to actually figuring out the protocol
for how they're gonna administer this virus,
and so they're just beginning that process now,
with incremental steps of increasing dose of virus.
Each of those steps is going to take at least a month,
and so we're many months away from them being at the point
where they can even test the vaccine.
The advocates have challenged studies by and large.
They haven't talked about all this preparatory work
that needs to be done.
Even from the first article that was published about this,
they talked as if next week, we could just start doing this.
Right, you just pump a room full of COVID-19
and then everybody gets it.
Yeah, right, and of course,
these studies are much more complicated than that.
And then there's the fact that we've got the current slate
of COVID-19 vaccines in record time,
without using challenge trials.
The reason why we got a vaccine so quickly
was because of a decade's worth of work
on related coronaviruses that cause SARS
and that cause MERS, and I think we had the genome
of SARS-CoV-2, the novel coronavirus,
published on January 10th, I think, of 2020.
Three days later, we had our first candidate vaccine.
63 days later, that vaccine was tested for the first time
in human beings.
By September of last year,
we had six large phase three trials
planning to involve 280,000 people.
The monumental size of the achievement here
would be difficult to overstate.
Well, that's traditional vaccine development
with new technology and it just highlights my point.
Challenge studies are just the wrong technology
for a rapidly moving pandemic.
But some still see challenge trials
playing a crucial role in the pandemic, ironically,
precisely because we now have working vaccines.
As soon as things start to look very promising,
and we basically are in a situation where those people
who are in a large scale trial, let's just use COVID,
are gonna start to say, wait a minute,
I don't want to be in the placebo group anymore,
I want to drop out,
and you can't finish the study ethically.
You've got to let those people know
you're in the placebo group.
You can be pretty certain
that nearly everybody will drop out
because you're not going to hang around in the placebo group
are very likely, so the studies that we have undergoing,
that are underway now, of COVID vaccines, are falling apart,
because people are dropping out of them left and right,
and so we're not going to get the answers that we might want
to things like how long does this vaccine last,
in terms of protection,
or do we know whether it's protecting us
against new variants of the virus that appear.
Some also see challenge trials as a path
to developing new vaccines
that improve on the existing ones.
Obviously, at this point,
we've got three approved vaccines in the US,
and maybe eight or nine total globally,
but there's still a lot of benefit to these sorts of trials.
We can expand the total pool of how many different types
of vaccines we have available, and that's important,
because a lot of the vaccine candidates we have now,
like the MRNA vaccines, they're hard to transport,
they take two doses,
all of these things that if we continue to try new vaccines,
we can find better vaccines that are easier to distribute
and that has a lot of equity implication.
We can get those to rural areas,
different countries with less infrastructure.
So that's like the big draw here.
Predicting the future is more of an art
than a science, especially when it comes to global crises.
Almost no one would have guessed
that we'd have several working vaccines for a coronavirus
within a year,
so it's impossible to say exactly what role challenge trials
will play moving forward,
but if there's anything that we've learned
from the pandemic,
it's that the question of which path is the more ethical one
often doesn't have an obvious answer.
The other thing about challenge trials I'll say,
'cause I don't want to dismiss them,
I'm not trying to dismiss their importance,
is if we get to a safer way to do challenge trials,
then I'm all in favor of using them, once they're safer.
Communities broadly would need to understand
what that's about and basically endorse it,
which is part of the recommendations from the WHO
and others, but if they're safer,
such that we're not asking people to take those risks,
I think they could be really important tool in the toolbox,
and just as we do them now in malaria trials,
they're a tool in the toolbox,
but they're not the whole story.