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Outbreak Week: Vaccines for Outbreaks in the Modern World: Michael Ryan and Ebola Case Study


All right, everybody. Welcome to this
event, which is part of Outbreak Week, which is
spearheaded by the Harvard Global Health Institute. Today we are exploring
vaccines for outbreaks in the modern world. My name is Carmel Shachar,
and I’m the Executive Director of the Petrie-Flom
Center for Health Law Policy, Biotechnology,
and Bioethics at Harvard Law School. We have the pleasure of
co-sponsoring this event along with the Harvard Global
Health Institute, as well as the Center for
Communicable Disease Dynamics over at the TH Chan
School of Public Health. So I’m here to do two things,
to first of all tell you that if Outbreak
Week is something that you find very exciting,
there’s no shame in that. I, too, think that Outbreak
Week is really fascinating. I wish that it happened
more than once a year. But if you like
these kind of events, please go to the
Petrie-Flom Center’s website and sign up for our newsletter. We host a bunch of events
in the health care, health law, biotechnology,
bioethics space. So chances are, if you
like Outbreak Week, you’ll like some of
our upcoming events, and we would love
to see you there. We also have a blog,
Bill of Health, that kind of explores
a lot of these issues that you might find interesting. But I also want to
plug this event. I think vaccines is
such an important topic. I was remarking to people that,
yesterday, at our media event, looking at the role
of media in outbreaks, we kept on going back to
the topic of vaccines. And people kept on
talking about how that was one of the
more difficult topics to responsibly and
appropriately cover. The other story
that I want to raise is that vaccines have become
such a contentious issue that, two years ago,
when I got a puppy and took the puppy to the vet,
the vet kind of looked at me and went, how do you feel
about giving your dog vaccines? And I was like, yeah! Is that even an option? And the vet was
like, oh, my gosh. You have no idea how
many of my patients fight me because they are
afraid their puppy will grow up to be autistic. Now, I don’t know what an
autistic dog looks like. I think researchers
who study autism might be very excited
to find out that you can cause autism in dogs. But it really goes
to show that there is an immense amount of emotion
associated with vaccines, right, that people are afraid
enough to even try to avoid getting their dogs vaccinated. And so a serious
exploration of this topic, especially in the context
of pandemics and outbreaks, is so very necessary. I won’t take up too
much more of your time, except to introduce
somebody who has been really instrumental to bringing
this event to fruition as well as the rest
of Outbreak Week. And that person
is Ashish Jha, who is the Dean for Global
Strategy and the KT Li Professor of Global Health
at the Chan School of Public Health, as well as the director
of the Harvard Global Health Institute. So join me as I welcome
him to the stage. [APPLAUSE] All right. Good afternoon, everybody. Welcome to Outbreak Week. It’s already been a
very exciting week. We’ve had lots of amazing,
incredible events. We have a total of eight events
this week with 10 partners, none who are as deeply engaged
with us on so many of these as the Petrie-Flom Center. So thank you for being
such great partners. So, Outbreak Week. It’s commemorating
the 100th anniversary of the 1918 flu pandemic. You’ll see some of us sporting
these very stylish T-shirts. The speakers have
all gotten one. And I have three
extra that I’m going to give out based on
your ability to answer the questions I’m going to ask. Now, here’s the issue. One of these questions
has been asked before. And if you’ve heard me say
it, you are disqualified. And I’m going to go
on the honor system. I’m looking at Jono
Quick back there. Don’t even answer
the question, Jono. I’m just kidding. I’m not giving you a hard time. But I have three questions,
give out three t-shirts. And then I will introduce
our first keynote speaker. But let me ask you
guys– first question. This is the one
I’ve asked before. This pandemic is often
known as the Spanish Flu. For those of you who
have not heard me talk about this before, why
is it called the Spanish Flu? Professor Larson? Except you already are going
to get a T-shirt as a speaker. But you can still answer. Get somebody else then. Actually, do you mind if I
see if anybody else knows? And then I’ll have you do it. Yes. [INAUDIBLE] Yes, please. [INAUDIBLE] That’s exactly right. So Spain was one of the
very few countries that didn’t censor the outbreak. And the question for you
is, one, more as a followup. Why was Spain the
country that did not? Because Spain was not involved
in the World War One, I guess. Here’s a T-shirt. It was. Perfect. [APPLAUSE] It was neutral in the war and,
therefore, it didn’t censor. So some of the very few
cases that we heard about were coming from Spain. So it got labeled
the Spanish Flu. The downside of
being transparent. OK. Second question. And, again, open to anybody. This one I haven’t done before. What was the strain of the
flu of the 1918 pandemic? First hand up? Back there? Yeah. But I won a T-shirt yesterday. Oh, then you’re disqualified. [LAUGHTER] I’m sorry. There are a lot of
disqualifying factors here. That’s right, you did
win a T-shirt yesterday. OK. Anybody else? What was the strain? Yes. [INAUDIBLE] It was. So T-shirt over there. And [INAUDIBLE] of
your colleagues. There we go. And last but not least,
how many flu pandemics have we had in the 20th century? Or actually, not the 20th
century, in the last 100 years. Here? Yes. Four. Four. And for a– you’ll get
the T-shirt either way– for a bonus, can you
name which years? I’ll give you 1918. I only know a few. ’68. Can you name the
last one we had? 2009, H1N1. And then ’58 and ’67, I believe,
were the two other years. ’57. ’57 and ’68. I knew I [INAUDIBLE]. Your biggest
T-shirt [INAUDIBLE].. My T-shirt! [LAUGHTER] I was– you don’t know
how I got my T-shirt. All right. So a few little trivia. Again, thank you
all for coming here. We are super excited
about this event. We are going to
talk about vaccines. And vaccines are
incredibly complicated. They are also arguably
the greatest public health intervention that we’ve had. I mean, along with
sanitation and clean air, I would argue vaccines are one
of the very few things that saves lives, saves
money, is really an incredible advancement. This is Outbreak Week. So we think about
vaccines classically as a preventive thing. But we have been
learning that vaccines are incredibly important
in the middle of outbreaks. We think it had a
really important role in the last
outbreak, in the DRC. It’s been playing a very
important role in this one. But vaccines are complicated. They’re complicated
in their science. They’re complicated
in how people accept them, or don’t, or
have confidence in them, and interact with them. There’s a lot of
complexity around both the science and the sociology
and the psychology of vaccines. And we’re going to try to
explore some of those issues today. But as we get started, let
me very quickly introduce a gentleman who really has
been extraordinarily engaged at the forefront and in
the leadership of thinking about preparedness,
response, et cetera. And that’s Mike Ryan. He’s the Assistant
Director General for emergency
preparedness and response at the World Health
Organization. And he’s been at the forefront
of managing acute crises for 20 years. Involved in acute
illnesses, he’s been involved in
12 Ebola outbreaks in one form or another,
was part of UNMEER– for those of you
who know, UNMEER, the United Nations Mission
for Ebola Emergency Response in 2014-2015– and is also a professor at
University College Dublin. And when Mike agreed to come,
we were absolutely thrilled. We couldn’t think of anybody
better to kick us off. So, Mike, grateful
for your coming. Thank you so much
for being here. [APPLAUSE] [SIDE CONVERSATION] OK. First, note to self. Don’t have someone with perfect
eyesight print out your speech. Anyway. Thank you, Carmel and Ashish. And good afternoon,
ladies and gentlemen. It is indeed a great
honor and pleasure for me to be here at Harvard to
join a conversation with you on vaccines for outbreaks
in the modern world. This is a very timely and
very important conversation. My name is Mike
Ryan, and I’ve been– spent the last 25 years
fighting epidemics. I attended the screening
of Contagion last night. And in the introduction,
we were told that, I think, yesterday was exactly
the 100th anniversary since the authorities
in Massachusetts shut down all the schools,
banned all public gatherings, in the face of the spread and
impact of the 1918 influenza pandemic. Sort of a sobering reminder 100
years later of the way in which epidemics not only
impact health, but our social, political, and
economic stability, even today. I’m noted for having
a terrible memory– well, a terribly
selective memory. I’ve always rationalized
this by thinking there must be some evolutionary
advantage to short memories, the value of putting awful
events behind us so we can move on as individuals
and communities. And we all have personal
experience of that. There’s one huge disadvantage
to this behavior. We forget the pain, the
suffering, and the loss. And we, as Jim Kim
and the World Bank has put it speaking
of epidemics, often move from
panic to neglect. Saying “best to put things
behind us and move on” might have saved a lot of
political skins in the past, but maybe not so much anymore. Remembering the 1918
pandemic and other epidemics, it’s important to remember
those who were lost, the brave health workers
who stood in the front line. It’s essential to remember them. But if we examine these events,
we can learn the lessons and be better prepared
for the next one. As WHO’s Director
General, Dr. Tedros, says, our job is to keep
the world safe. However, there’s where
another human frailty kicks in beyond memory loss. It’s the, “I know what I
should do, but I never do it” syndrome. How many times in
our own lives do we look back on a
personal disaster, knowing that we knew
it could happen. We knew that we could have
done something about it, but we just didn’t. And yet again, as a society,
we suffer the same issue. We face future shocks, sometimes
knowing we could do something to avert them, but
we don’t seem to be able to summon the
collective energy and resolve to
change that future. That’s where I think we are
with epidemics and pandemics. We know we have a problem. It scares us. But we have not as
yet put together a coherent set of actions that
would avert such a disaster. Yes. To use the American
vernacular, we do stuff. We train epidemiologists,
nurses, physicians. We make small-scale investments
in drugs and vaccine development. And interestingly, we have
developed a small army of shroud-wavers who
regularly scare us to death, be it in the media
or in the public eye. But in reality our efforts
are often piecemeal. They’re undergeared and
suffer a fairly shocking lack of ambition and resolve. In saying that, I have
profound admiration for all of those
in many sectors, public and private,
who continue to try to get us ready for the
next pandemic, for those in the front lines of
epidemic response as I speak, and for those policymakers
who are trying to make us move
forward towards a safer world for all our children. Today as I speak, hundreds
of brave health workers risk infection and physical
attack in DR Congo, fighting Ebola. Others toil against cholera
in Zimbabwe and Niger and other countries. They are doing so
armed with no more than their commitment and hope. But they do have vaccines. In Pakistan and Afghanistan,
hundreds of thousands of health workers are
tracking polio viruses and vaccinating millions
of children in an effort to eradicate this
horrific disease. All around the
world, children have been vaccinated
against killer diseases like measles and diphtheria. In fact, vaccination has been
the single most– as he said– effective health intervention
ever developed and delivered. Interestingly, the other
great health protectors have been water, sanitation,
improved housing, better nutrition, none of
which have been delivered by the health sector per se. Millions of lives have
been protected and saved by vaccination over
the years, and we should take a moment to
remember those pioneers who have given us those gifts. However, I think we
should also be concerned. While we have the wonderful
tool of vaccination, all is not well. So my shroud-waving
moment has now arrived. We continue to see vaccines
under-utilized due to failing, weak, and inequitable
health care delivery systems around the world, as well as
the mistrust of those lifesaving interventions is
growing, in many places due to misinformation. In the last couple
of years we’ve seen major outbreaks of
measles and diphtheria, despite the availability
of cheap and high quality vaccines. We have seen polio
eradication threatened and the uptake of
new vaccines like HPV fall well short of
their expectations. Before I come on to talk about
what new vaccines we need and are developing
for outbreaks, I must stop here
and say, we must use the vaccines we already
have in a more effective way. And again, we are back
to human frailties, the “I want the new thing,
not the thing I already have” syndrome. Let’s look at a few examples. Firstly let’s look at yellow
fever, or yellow jacket, as it was called
in the Americas, a devastating disease that’s
been a scourge of humanity for centuries. We have a cheap, safe,
and effective vaccine, which is in the EPI protocol
for at-risk countries. Yet vaccination rates remain
terribly low in many places, with a constant
threat of epidemics. WHO and its partners
have maintained a strategic stockpile of yellow
fever vaccine for many years, supplying countries facing
yellow fever epidemics. But this isn’t a
long-term solution. Routine population-based
vaccination is the answer to avert
what yellow fever outbreaks in the modern world. Our Ending Yellow fever
Epidemics, or EYE strategy, calls for this ramp-up
in routine immunization, in addition to
large-scale catch-up campaigns and maintaining
global strategic stockpiles, et cetera. But getting support
for this vital strategy has proved exceptionally
challenging. In addition, WHO works
with its ICG partners to maintain strategic stockpiles
of meningitis, cholera, and smallpox vaccine, and
sophisticated mechanisms to distribute them on the
basis of epidemiologic need. Let’s take a quick
look at cholera, where I can explore
another of the aforementioned human frailties,
the Magic Bullet Syndrome. When it comes to vaccines,
rarely are vaccines effectively purely in their own right. Take cholera, a disease for
which we have a good vaccine. Yes, it’s a good vaccine,
but only really useful when used in conjunction
with other measures, like the provision of
water and sanitation. The cholera vaccine can protect
populations in the short term while we improve
water and sanitation. But we never seem to get around
to the water and sanitation bit. So we’re often left to
repeatedly use vaccination as a short-term,
last line of defense. It’s heroic stuff. It’s great for a movie script,
but wasteful and misguided, and predicated on our
passion for magic bullets. We need to recognize
that vaccination in the face of
epidemics must be seen as one of a coordinated
series of interventions that collectively protect,
preserve, and restore health. So as we look to our
future and the risks it may hold for high impact
epidemics and pandemics, we all see that,
once again, vaccines present a major
opportunity for us to stop these things in their
tracks, prevent their spread, protect the health
of individuals, preserve our societal
cohesion, economic prosperity, and political stability. All laudable goals, but not
deliverable without a step change in the way we
look at the problem and invest in the solutions. We are, however,
making progress. And now, at last,
to the strengths of the human condition,
ingenuity, passion, resolve, and solidarity, the other side
of the human frailty equation. Despite the challenges,
we have and are exploring the biotechnology and
communications revolutions to develop new
and more effective countermeasures for epidemics. Our ability to predict
and detect epidemics is getting better. New diagnostic
tools are giving us more rapid ways to confirm
disease, even at the bedside. And we are, at last, investing
in new and faster vaccine technologies for many
epidemic diseases, not least of which is influenza. We have the capacity
to rapidly develop Candida vaccines for influenza. But we still struggle
with the timelines for producing enough
of them quickly enough and distributing them equitably
enough to make a difference. Right now, even in the
best case scenario, it will take us six months
to go into full production of a pandemic
vaccine, way too long for a virus that will probably
have circled the world at least once in that time and killed
hundreds of thousands. Beyond this problem is
the ethical problem. Who gets the vaccine? Those most in need? Those most at risk? Or those who can pay? We need to shorten
the time scales and come up with ways to
distribute vaccine equitably. This is happening
on both fronts. We see tentative investments
in universal influenza vaccine, which is very welcome. But this will take years,
if not decades, to deliver. In the meantime, there are
other things we can do. Using things like–
and there are many more experts in the room than me– nucleic acid vaccines,
where production could begin simply
after distributing a required genetic sequence. Only problem is we don’t
have the manufacturing platforms, as yet, that we
could switch production to. So the problem is
not the technology. The problem is the platform. Beyond influenza,
there’s a number of other high-threat pathogens
with pandemic potential. They have been carefully
prioritized through WHO’s R&D blueprint, working with partners
in the global coordination mechanism in order to accelerate
the development of vaccines. We’ve seen the creation
of the Coalition for Epidemic Preparedness
Interventions that makes targeted investments
with the private sector for the development
of specific vaccines from our priority
list of pathogens. Vaccines are under
development or have been tested for a
number of pathogens, including Ebola, Marburg, MERS,
SARS, Nipah, and Zika viruses. This is a new departure,
as many of these were orphan diseases
only a few years ago. With limited interest in
the development of vaccines, in some cases, the
target vaccination may end up being the animals
who transmit the virus to humans and not the humans themselves. Another interesting
option for us as we go forward for outbreaks. After I finish, I think
Lydia, Marc, and John– sounds like a title of a song– will speak to Ebola vaccines. We’re seeing major steps
forward in Candida vaccines as we speak, with more
than 11,000 people being vaccinated in the most
recent and still ongoing epidemic of Ebola in
DR Congo, using EBOV, under an investigational
use protocol with a ring vaccination strategy. You cannot imagine how difficult
that is to do in the middle of a shooting war, to bring
vaccine to the field at minus 80 degrees, to do informed
consent with every single person, to identify
every contact, every contact of a contact,
reach every village and vaccinate everybody. For suitable candidates,
or for eligible candidates, our vaccine coverage
is over 99%, which is an incredible effort
on the part of mainly the health workers of Congo and
those who support them, vaccine specialists from Guinea. But none of that works in
this difficult environment unless we know
what the virus is. Again, the need for
good surveillance and excellent mobile labs. Even with this in hand,
we need a community that accepts the
vaccination and not the associated misinformation. Unfortunately, our
efforts in Congo right now are struggling
because a community that’s beginning to
mistrust– has years of mistrust of
massacres, of war, of lack of delivery
of basic services. And our vaccine has
become wrapped up in this political argument. And currently, our
whole operation is at risk because of the
deteriorating insecurity. We’d like to thank all our
partners, including Merck’s, the NIH and the FDA
here in the USA, who have worked so closely with
us, and with the Ministries of Health and all partners
in the Global Outbreak Alert and Response Network,
on the ground, to make this whole
process happen. I’m sure there’s much
more to come in this space as we develop new vaccines,
drugs, and diagnostics, better communication strategies
for community involvement and engagement. In conclusion, I think human
ingenuity, human passion, commitment, and solidarity can
outweigh our human frailties and shortcomings. We have the combined capacity to
prepare for, predict, prevent, and mitigate the impact of the
next big epidemic or pandemic. It’s not a choice
but an imperative. We must succeed, and we
must mobilize every part of our society to do so. The public, academic,
and private sectors are coming together, and
we must stick together to see this through. Our political leaders
must recognize the risks and invest heavily in the
solutions over a sustained time period. We’re in Massachusetts. And as a proud Irishman
who’s a proud Irish-American, I can say appropriately, in
his beloved Massachusetts, I can recall the
words of JFK when he said, “we choose to go
to the moon in this decade and do the other things,
not because they are easy but because they are hard. Because that goal will serve to
organize and measure the best of our energies and skills. Because that challenge is
one we are willing to accept, and one we are
unwilling to postpone, and one we intend to win,
and the others, too.” It’s my fervent hope that when
he said “the other things,” we might honor his
tremendous vision and legacy and deliver another
form of moonshot, vaccines for outbreaks
in the modern world. Thank you. [APPLAUSE] Mike? Do you mind staying up for about
five minutes for questions? Would that be OK? Sure. So we’ll take five minutes
for questions and comments. That was terrific
and really helpful. And I’m going to
ask, first of all– people want to come up to ask
questions here– which is– so since 2014, ’15 with
the Ebola outbreak, it feels like there’s
renewed energy. There’s CEPI, there’s
the roadmap, there’s– how optimistic
are you that we’re on our way towards
that moonshot of making real progress on things? Or are you worried that we’re
going to just fall short, because often the energy runs
out before the day is finished? So how are you
feeling about that? And again, if people want to ask
questions, like two or three, just come on up to the mics. Dr. Tom Greiner, head
of Acute Operations, is currently arriving in Congo. He’s German, and a pragmatist. He regularly accuses me of
being a pathological optimist. So anything I say needs
to be taken in the light of people’s view of me. No, I’m eternally optimistic. I just think we have the pieces,
but we haven’t got the scale. And I think things like the R&D
blueprint, things like CEPI, take us to another level. I think it brings together the
public and the private sector. I see Ryan Morhard over there
from the World Economic Forum. We’re doing work now with the
public, the private sector, everything from
liability management to regulatory pathways. It’s about– it’s a bit
like the Manhattan Project. Each piece is so important. It’s like the International
Space Station. It doesn’t work unless
everything works, in a way. So, yes, hopeful, but I
shudder and I sometimes get scared at the scale,
especially if we talk– I think we’ll get there
with the Ebola vaccines. We’ll get there with
the MERS vaccines. My biggest fear, to be
quite frank with you, is pandemic influenza,
and whether we actually get there in time. We don’t have the– we don’t have the
speed, and the agility, and the scale to deal with
a truly serious pandemic of influenza again. I don’t believe we do. Questions for
Mike, from anybody. All right. I’ll ask one more and we’ll
stop there, since nobody else– Just, by the way, that’s
the Global Emergencies Map as of 2:00 this afternoon. So you’ll see, as one regional
director said to me recently, my region is on fire. I think you can
guess which region. So– oh, actually– You can ask your question first. No, no. Please. Please. Hi. Marian Wentworth. You teased me with
a couple of things that you dropped in
your last answer. And two things are
of interest to me, and I can take just one
answer instead of two. One is, where have
we gotten in terms of thinking about new kinds
of manufacturing platforms? There are so many
different diseases that can cause outbreaks. The whole notion that we can
get exactly right an x-liter facility that can do this,
that, and the other is just– the world can’t afford
that much infrastructure, and nobody is going
to do it anyway. And the other is the
regulatory mechanism, which if you want to leave
that for the panel to answer, I can ask it again. But honestly, we still have
an unapproved Ebola vaccine, even though we’re in
our third outbreak. What does that mean? Yeah. I can answer part of
the second part first. Yeah. The fact that we have an
investigational use vaccine is a credit to
everyone involved. And I can’t tell you
the amount of work that’s going on between
ourselves, Merck’s, FDA, EMEA, trying to push
this thing through. But we have a duty of
care with any new product. And we have to– and this
is part of the process. Can we shorten those
periods, get them right down to the absolute minimum? I think we’re almost
reaching a point where it’s almost impossible to
chop any more chunks out of the process, unless you throw
some of the process overboard. And that always needs to
be carefully considered, given the problems we’ve had in
the past with unsafe vaccines. So we have to be very, very
careful in that regard. In terms of platforms, I agree. There’s a myriad of
different platforms out there, different ways of
approaching vaccine production. I think our biggest
issue is that scale-up. We’re all producing
vaccines and some are producing tissue
culture vaccines, nucleic acid vaccines,
vaccines grown in eggs. And everyone’s on a slightly
different sort of pathway. And in the end, we can’t turn
all of that production capacity into the production of a
pandemic vaccine in real time. We can move from
injectable vaccines to live, attenuated
vaccines, or lots of other different pathways
to get mass vaccination more quickly, with vaccines that
may have more acceptable safety profiles. But the real challenge is,
how do you shorten everything without cutting corners? How do you get from
A to B without going through C, D, and God knows
how many other waypoints? And how do you stay
safe in doing that? And there is no answer. I think the only answer is
we have to find better ways. And I’m not the expert on that. And certainly WHO, within our– we represent 194 member states,
but we are not the innovators. The innovators are
out there in industry. The innovators are
out there in academia. All we can do is provide a safe,
transparent, coordinated space in which these
conversations can happen, and we can come up with
new ways of doing things. Thank you. And that’s a great way
to head it out with. Thank you so much. That was terrific. OK. Good. [APPLAUSE] All right. Well, I love both
the starting off with the human frailties
that hold us back but then the human ingenuity
that really drives us forward. Let me introduce
our first panel. And I’m actually not going
to introduce the panel. I’m just going to introduce
the moderator, Helen Branswell. Those of who know anything
in the global health space know Helen. She’s the infectious disease and
public health writer for STAT. Really got famous in
this space, at least in my mind, for the work that
she did when SARS hit Toronto in 2003, and, since
then, has really been, arguably, the leading
global health reporter in this country or elsewhere. And because she’s local
we keep relying on her. So she was here
yesterday with us. And, Helen, thank you for
moderating this panel. So I’ll turn it over to
you and your panelists. [SIDE CONVERSATION] I’m going to start. And we’re going to try
to pull up a slide. I was actually thrilled to be
asked to moderate this panel. And that’s unusual,
because I hate speaking. I normally write. But I’ve been writing about
Ebola vaccines for a very long time, and specifically the Ebola
vaccine that Lydia Ogden is going to talk to us about. So it felt like an issue
that I really both know about and want to know more about. And I thought it would be
an interesting thing to do. Before I introduce
the panel, I want to ask for a show of hands. Have people come here
with a lot of questions? If you’ve got a question
that you already know that you want to ask, can
you put up your hand, please? You must have a question
in the second row? Mary? You– I always have questions. OK. OK. The reason I ask that is because
I have a lot of questions, but we want to leave time at
the end for audience questions. And if I feel like there’s
a lot of audience questions, I might ask fewer of my own. At any rate– So today, our panel is really
a great combination of people. We have– and maybe, well– we have Lydia Ogden,
who’s the Associate Vice President for Global
Enterprise Policy at Merck. And Merck, of course, is
the maker of the vaccine that’s being used now in DRC. Lydia is also an
affiliate faculty member at Drexel University. We’ve got with us
Marc Lipsitch, who’s the Director of the Center for
Communicable Disease Dynamics and a professor of Epidemiology
at the Harvard TH Chan School of Public Health. John Monahan, who is Senior
Advisor to the University President for Global
Health and a senior fellow at the McCourt School of
Public Policy at Georgetown University. Mike Osterholm, who has a
really long blurb here– and I’m not going to
give you all that– he’s the Director of CIDRAP. And you can read the rest. I would like them all to
come up, if you don’t mind. And each of them are going
to speak to you very briefly, and then we’re going to
get into some questions. [SIDE CONVERSATION] OK. So can you hear me? Is this on? All right. Can you hear me now? All right. The speakers are going to speak
in the order I introduced them. So without further
ado, Lydia, please. Sorry, I sound pretty horrible. [LAUGHTER] So I don’t need this if I’m
speaking from the podium, right? No, not– Or am I speaking from here? [SIDE CONVERSATION] Hi, everybody. I’m Lydia Ogden. I don’t have a lot of remarks. I do have a remembrance. Years ago, my husband
and I were both at CDC. He’s a medical epidemiologist. And we took three of our
four kids to see Contagion. And they said, wow! That’s what you guys do? Do you need something? I just want to push
the mic a little bit. A little bit this way? And I said, well,
that’s what Daddy does. But I deal with the politicians. And they’re even scarier. [LAUGHTER] I joined Merck about
six years ago now. And I was lured
away from the CDC by the promise of using
a vaccine to eliminate cervical cancer worldwide. That’s not what we’re
here to talk about today, but I do want to
underscore what Mike said. We have many, many
wonderfully effective vaccines that are underused. That’s one of them. What I want to do
to set the stage is to share with you why Merck
got involved with the Ebola vaccine development. Because it’s the first
question people ask. We recognized that we
had unique attributes, and we had unique
experience to bring. We had capability. We have a tremendous
bench of scientists, and we had our
Rotateq cell line. And that gave us confidence that
we could work expeditiously, under very dire
circumstances, to bring a desperately-needed
vaccine to people at risk who were in
desperate circumstances. And we had capacity. As a large, multinational
vaccines company– pharmaceutical
company– we can flex and we can surge, but
not without tradeoffs. And I want to come back
to that at some point. Speed does come at a price. And the resources
that are required to do clinical development,
and manufacturing, and navigate the
regulatory system, those resources aren’t trivial. And they’re taken
from other efforts. And that’s an important
point to consider. And again, happy to
talk about that later. And Merck has a longstanding
culture of commitment. We have expertise in
HIV, and I think– I wasn’t there at Merck
when the HIV vaccine failed. I was actually at CDC in HIV. And many of us were really
disappointed about that on the outside. I’ve since learned
from my colleagues at Merck that the disappointment
at Merck was just as profound. And Maryann’s nodding
because she was there. And many people don’t know
this, but we actually did a tech transfer of our Hep B vaccine
to China when there were incredible numbers of infant
deaths from Hepatitis B. So in short, we don’t– we do see this as
our responsibility, not just our corporate
social responsibility but our moral responsibility. And the other thing
I want to emphasize before I turn it over
is this is not something that Merck did alone. The public-private partnership
that Mike mentioned is very, very real. And even private-private
partnership. You know, the
vaccine was initially developed by scientists at the
Public Health Agency of Canada. They transferred it
to New Link Genetics. And New Link came
to us because they knew that we had the capacity
to ramp up manufacturing, which they lacked. But there were also
many, many, many, many other people,
WHO staff, MSF, or Doctors Without Borders
staff, the governments in the initial outbreak
in Guinea, and Sierra Leone, and Liberia, and now DRC,
and many, many, many others. And I will just point
out that J&J and GSK also followed the same path. The last thing I want to
point out is that we– Maryann asked the question
about why we don’t have a licensed vaccine yet. We can come back to
that in some detail. But I will just point
out that any vaccine that CEPI develops– and
hopefully there will be many, many of them– will run these same traps. And so, to Mike’s point,
we have to figure out how to run the traps
better and faster. So I’ll just stop there. [APPLAUSE] Great. Thank you so much. And we will get back
to those issues. And now we’ve got Marc. Thank you, Helen. And thanks to Helen, and
to Ashish, and Carmel, and colleagues for just
organizing a really great program today and all week. I want to talk about
areas in the vaccine space where academic communities,
like ours and like those of many other people in the
room from other institutions, can make some advances
in collaboration with the private
sector, in collaboration with NGOs and others. And I want to do it mainly
in the area of pre– I want to talk mainly about
the idea of pre-planning. I’m not going to talk
about the wonderful work that CEPI and others are
doing in terms of designing vaccine candidates. But I really want to talk
about the next stage that comes after that. Once those vaccine
candidates are ready, what can we be doing
during peacetime, in between major outbreaks,
to improve our readiness to test and deploy those,
especially in settings of new strains of diseases,
or new diseases altogether, where there is no
proven vaccine? And I want to talk
about pre-planning as a theme in three areas. First is in ethics. So as many of you know and
some of you experienced, there was ongoing
debate for months– actually, for most of the time
that the 2014-15 West African Ebola outbreak was going– about the ethics of
how we could do trials, and other ways of examining
the effectiveness of vaccines, and especially therapeutics. Those debates consumed
valuable time. They consumed a lot of energy. They were done by
people who were tired and had lots
of other things that they needed to be doing. And they threatened to
make it hard or impossible to run trials. And in the vaccine
case, as you know, one very successful
trial was run. In the cases of therapeutics,
the record was much more mixed. I think there is– since that time,
there has actually been some progress among
professional research ethicists in thinking about, what are
the ethical limits on what can be done in terms
of randomized trials? Should randomization
always be required? Is a placebo necessary
or allowable? Who should be randomized, and
how should they be randomized? But that conversation
still remains relatively narrow among a
specialized professional group and hasn’t been tested in
terms of its generality and believability to
other stakeholders. So I think moving that
discussion outward and continuing it– because I think there’s not as
much consensus, by a long shot, on the therapeutic side as there
is on the vaccination side– continuing that
debate and discussion with a wider range
of people so that we can settle some of these
questions in advance is essential. The second area is
what I would broadly refer to as pre-planning
of technology. And again, beyond the
technology of creating vaccines, which is
itself essential, but the technology–
if you think about it, a vaccine trial is a technology. A design for a vaccine
trial is a technology. And the invention, on
the fly, at the moment, of the ring vaccination trial
as a way of testing a vaccine was perhaps the biggest
advance in quite a long time in the technology of
how we test vaccines. Ring vaccination had been
used in public health, but not as a vaccine trial. There are many challenges to
doing these vaccine trials in emergencies;
spotty incidents, unpredictable
incidents, urgency, first as the epidemic is growing
and we need a vaccine to stop it and then as the epidemic,
as has happened this time, is shrinking. So we need a vaccine– we need to test the vaccine
before the epidemic goes away. There are a number
of things we can do to expand that
technological space of how we do vaccine trials. And I think that, as a research
frontier, is really important. Also, incorporating other
forms of technology, like genome sequencing
of the pathogen to enhance vaccine trials,
better understanding of correlates of protection. There’s just a paper
that came out yesterday, or the day before,
showing why the way that most correlates of
protection are established is full of biases and
potentially quite inaccurate. It came from a group
in Oxford, in plus one. There’s a lot to
be done in terms of getting us ready to do better
trials and more informative trials. The third piece is logistics
and pre-planning of protocols. And that’s not so much
my area of knowledge, so I won’t speak about it. But as you know, there’s a lot
of effort to develop protocols for better– in advance that can
be tested ethically. Why pre-plan? Just briefly, it saves time. It means that deliberation
is more clear-headed, because people have time
and sleep, which they often don’t during the outbreak. And it also allows people to get
beyond their particular biases, in the sense that they don’t
know which vaccine they may be in favor of at the time. And it’s a much
more neutral process if no one knows
which team they’re on at the time of deliberation. So thank you. I’ll stop there. [APPLAUSE] Thank you very much, Marc. John? Thank you very much. And I think it may
be that universities love anniversaries. So I work at
Georgetown University, and we’ve also had
events commemorating the 100th anniversary of
the terrible pandemic, but not nearly as good as this,
as you guys do at Harvard. And not nearly with the
cool t-shirts, like she has. I may get back to campus and
find t-shirts like that, too. So anyway, thank
you for inviting me. I think, before I talk a little
bit about the three things I think the law
and lawyers might have to say about the
challenge ahead of us, I want to resonate with
a point that Mike made, which is about– there’s a real human cost
to failing to act here. And when we did our
commemorative event, one thing we did was
we asked the archivist of the university, what records
do we have at Georgetown? And among the things that
the archivist brought out– because of course
it’s a Catholic university and we’ve got– Jesuits have kept everything
forever, you know? So we have– they
brought out a box. And sure enough,
it was a box that had the medical records
of all the students who were in the infirmary
during the outbreak. And because it was
an infirmary run by Catholic nuns
and Jesuit brothers, they kept meticulous records,
charting fevers up and down. And it was sobering, because
a lot of those charts ended, right? High fever, death. And I thought, as somebody
who worked at the university, in those days,
you had to write– somebody had to write a terrible
letter to someone’s parents that said, your– in this case,
your son was a student of ours. And something terrible happened. I also thought about all
those nuns and brothers who were working,
not knowing when they were going to get sick or
if they were going to get sick. No one knew. Anyway, I just– sometimes
things like that– at least for me,
holding those records really brought it home
that someday we’re trying to make as few of those
calls as necessary, right? We hope that someday
in the future we can do something that will
at least reduce the number of people hurt by this. So anyway, mike, I
think you were right. It’s good to remember this. So about law. Why is a lawyer
involved in this? I’d say three things. One is my experience is
not so much with Ebola. It was from 2009, H1N1. You’ll hear from our
colleague, Nicki Laurie, who helped guide the
US government and me through the learning
process of how we respond to the H1N1 pandemic. But I will tell you. I’m one of those Washington
creatures you’ve heard about, lawyers who go in and out
of government all the time. I’m one of those people. I had never in my
public service life used my legal skills as
much as I did during the six to nine months that we
were involved with this. It was extraordinary. Because everything
from the contracting, to the distribution,
to figuring out who was responsible for
what, when, how– when we did the vaccine donation
campaign, thank God the pandemic wasn’t as
severe as it could have been. But that vaccine
donation campaign was one of the
most complex things I’ve ever been involved in. The number of lawyers and
the number of billable hours I was involved in, it really–
it was a big takeaway for me. So the second thing
that– let me– the second thing, which is
one of– law does many things. But among them, and when it
works well, it allocates risk. It allocates risk
among different players who need to engage in
a common enterprise. So in this case, you’ve
got at least five sets of players, right? You’ve got the donors, payer
governments in the world that respond right now. You’ve got the manufacturers. You’ve got the host governments. You’ve got the people who
live in those countries. You’ve got the WHO and the
whole international regime. We’ve got to do a better
job of allocating risk, because we know
what our goal is, as rapid and safe a response
as we can possibly have. And getting it wrong is
not really a good option. Because even if we have people
take vaccines that, ultimately, maybe are dangerous but are
better than the alternative, we’re going to have
another one of these. You don’t want a second– we’ve got to do
this as best we can, because we need to
make sure that we’ve got a regime that works. So the last point, really,
is legal readiness. And everybody’s said this
in one way or the other. But I think the
same way you think about the development
of a vaccine as a scientific
enterprise, we need to think about the
legal regulatory regime as an end-to-end exercise. How do you go from day one
to your maximum public health intervention? What are all the legal
and regulatory steps? And I’m not suggesting
this is easy. But if we don’t
do that exercise, we’re going to kid
ourselves, right? Fixing one step is not going
to solve a multi-step problem. Liability’s really important. I know we’re going
to talk about that. But that is only one
of what I would argue are multiple things. So anyway, those
are three thoughts. You know, law is– at
least in my experience, was intimately involved in the
response and the development of vaccines. Two is law is a way
to at least think about how you allocate risk. And then three is we know now– unlike many things in terms of
the next big pandemic outbreak, we can predict the legal
and regulatory issues we’re going to face. And shame on us if we
haven’t figured out a better way to respond. [APPLAUSE] Thank you and good afternoon. Let me, in my comments, try to
provide some framework that I think yet has not
been discussed but I think is critical
for understanding our discussion of vaccines,
both their past, present, and future. First of all, we have
different kinds of vaccines. And I’m not talking about
manufacturing platforms or even agents, but categories of
vaccines that have everything to do about their availability,
because they’re everything to do about the business model. Routine child immunizations
are well understood. They are, in a sense, you
might say the gold standard of vaccines, both in terms
of their availability, their funding, and
their performance. We also, for many
parts of the world, have routine adult vaccines,
such as hepatitis B, hepatitis A, pneumococcal, HPV,
herpes zoster, et cetera, that basically tapped
into another market. But again, part of
a routine program that made their availability
a reasonable business model. Then we have those
travel-related vaccines, or in some cases diseases of
regional critical importance, such as yellow fever,
typhoid, dengue, et cetera, which had to have a
pull, basically, of a very specific population,
such as travelers, which today amounts in the
millions, or, in fact, of regional importance. Where we were lacking
vaccines, and any model for bringing them forward,
was in epidemic diseases. And that was very apparent
in 2014-15 for Ebola. And but for the fact had the
United States government not considered that Ebola could
be used as a bioweapon one day in the future,
funding for that work that made it possible
for that vaccine to even be at the stage it
was at the time of the 2014 outbreak wouldn’t
have been available. And so it was not anticipated to
be an epidemic disease as much as it was a bioweapons disease. So what happened, though, was,
following the 2014-15 Ebola outbreak, it became very
apparent to the world that we were broken when it
comes to the issue of epidemic disease vaccinations. And so as a result, the
WHO, to their credit, convened a group of
experts, and, with that, further developed and came up
with a document in May of 2016 called “An R&D Blueprint for
Action to Prevent Epidemics.” And it was actually a
large vision to say, what is it that we need to do
to have vaccines such as Ebola be available? And with that, they also
published a methodology for how we would determine which
diseases merited prioritization in that scheme. The diseases– there
were eight of them. Crimean-Congo Hemorrhagic Fever,
Mers, Zika, Ebola-Marburg, Nipah, Lassa, Rift Valley Fever,
and one called Disease X, which was, what is the
yet-unexpected disease that we might need to
gear up for very quickly that we don’t even know
the agent is today? Well, I come to you
today with some kind of unique view on this,
because our center, the Center for Infectious Disease
Research and Policy, was tasked by WHO, along
with the Wellcome Trust, to actually develop roadmap
documents for Ebola, Marburg, Nipah, Lassa vaccine,
therapeutics, and diagnostics. And I have spent the
better part of my last 18 months in hundreds and
hundreds and hundreds of hours, along with
our team, working through these R&D roadmaps. I’m happy to report that we
are about to take on Zika. And although it was not one
of the original diseases, we are also going to
be taking on influenza and the new modern vaccines of
influenza coming down the pike. Zika will be all vaccine,
diagnostics, and therapeutics, and influenza will
be just vaccine. But there were some
very valuable lessons learned in this process. And I should say
I’m not surprised that we had to relearn them,
because we already knew these. And that is, in the end,
we have lots of technology. We have lots of
technology potential. What we don’t have
is a business model. We don’t have a public
health proposition that basically takes us
from the most basic R&D to a marketable
product that will be made by a commercial entity,
and will be made available in a way that is constantly
there when we need it, where we need it,
and how we need it. And while CEPI and Carb-X came
along, as two organizations to help us deal with the
issue of moving product through the early
phases up to 2A, that’s like buying 10
feet of the best rope you could ever buy
but everybody’s drowning 25 feet out. We don’t have anything
to take us today from 2A to that finished
product concept and construct. And look no further than Ebola. It’s a classic example. So today I think we
have to talk about– we focus a lot on the
science and technology. That’s where we’re comfortable. But frankly, it’s about
the business model. It’s about the public
health proposition that makes it possible to have
these vaccines be available when we need them,
because there is a reputable and authoritative
private sector company that’s making them in a way that
makes it available for us and it makes money for them. And so I hope we move
it more into that area. Thank you. [APPLAUSE] Great. So let’s get at it. I write about these
issues all the time. And, as I mentioned before, I’ve
been writing about the Ebola vaccine for a very long time. Lydia, why isn’t the Merck– [INAUDIBLE] You reset me, huh? I don’t know who it is. It’s one of us. [SIDE CONVERSATION] I’d like to know why the Merck
vaccine still isn’t licensed. [LAUGHTER] OK. Well, so I think the
first thing I would say– and this is probably
not a point that’s lost on this smart
audience here but is often lost on other people. And that is, when you
certify or license a product, you’re not just licensing the
product but the process that creates that product. And that’s really,
really important. So we had some unexpected
engineering and construction delays with the facility that
we are reworking in Germany to manufacture this vaccine. And we did do our due diligence. And you can either build
capacity to manufacture or you can buy capacity
to manufacture. But in the end, we decided
that the existing facility that we had in Germany
was the right choice, but it needed a lot of work. And then the regulators have to
certify that that facility is up to snuff. So long story short,
it has been longer than what we would have liked,
but we do have the stockpile, and we are using the
stockpile even now in DRC. So we are hopeful, along with
WHO and our other partners, that we will be
able to see our way through this current
outbreak and be able to get on track
with our manufacturing so that we have that stockpile,
that cushion that we all need to assure us going forward. You know, last
year in November I was talking to one of
your colleagues at Merck, and was told that Merck had
had a self-imposed deadline of funding the end of 2017 and
that you were going to miss it. And when I was
speaking to her, she couldn’t give me a
commitment of when you were going to be able to file. She said that she
felt good about 2018. Actually, I think she said
high level of confidence, but wouldn’t commit to it. Will the dossier
go in this year? So like I said, we’ve had
some unexpected delays. And we are learning from
those delays as we go along. I mean, I think the
other important point to underscore here is that,
unlike a clinical trial that might be solely under
Merck’s control for one of our commercial products,
we are doing this in concert with partners. And that’s really,
really important. And when you’re doing anything
in concert with partners, everybody has a learning
curve individually. And we have a partnership
learning curve as well. And cleaning the data and
making sure those data are correct and consistent
and ready for filing is not an inconsequential task. So I’ll just point that out. Not to make excuses– we are hoping–
fingers crossed– that all of those
deadlines will be crossed, that the regulators
will be satisfied with the manufacturing
process and with the dossier. And that’s likely to be 2019. Can you give me a
queue number of 2019? No. No. I’m sorry? There’s just too
many unknowns and too many things that are
unforeseen and, frankly, that could go wrong. Did you want to jump in this? Yeah. Could I just add a
framework question here– I mean, a comment? I think that– I won’t put Lydia on the spot. But when one looks at the
finances of Ebola vaccine– first of all, this is a
single antigen vaccine. We obviously would hope to one
day have a multivalent vaccine, since we surely will likely
encounter additional Ebola strains and Marburg. Second of all, what
we’ve done here is, fortunately, with a
lot of upfront funding from governments that
got us to where it’s at, plus the fact that
there’s a token involved. But if we were to make those
whole long-term business proposition at the
rate that we use Ebola vaccine under our
current recommendations, there’s no business model. I mean, it doesn’t sustain
itself going forward to get a return on investment. And I think this is
one of the challenges that we’re facing right now. And I would argue that, when
you ask the question of Merck– I think, fortunately, Merck
has done what it’s done and the US government,
Canadian government, and others have done what they’ve
done to pull these forward. I think this is really
an important point, and it’s one that we often miss. Can I just– Yeah. Moderator’s privilege. Go ahead, Nancy. I have a question. Not just to get you out of this,
but one other thing about Ebola is it was a terrible outbreak. But what got the US
public’s imagination and turned it into a firestorm
was the threat of cases coming here, right? And it ignited a lot of
energy and enthusiasm and maybe focus on
some of these issues. That’s died down. Can you think about
balancing that understanding, which does bring resources–
which, in the end, it’s resources and time and
money that drives some of these things– versus the actual risk, which,
in some of the settings, the public perception of
risk may not be fully true. And so can you think aloud about
how you balance the need for it to be front and
center in the public? Otherwise they
won’t care about it. But we also don’t necessarily
want people frantic all the time, worried
about the Ebola getting into the United States? Is that for anybody in
particular, or is it for me? Well, I was talking
to Mike, because– but, I mean, I think
from all of you. It’s sort of a perspective
from pharma, too. I mean, Merck partly
got into this because of the goodness of its heart. But there is an interest
in the PR coming up with an Ebola vaccine
that’s going to save it, which is good for the company. It may not be the interest
of why you did it. But I just wonder
how you all weigh those equations when you think
about the development of Ebola vaccine. So can I just say that,
to that last point– and I’m really trying
to be objective here. I know that we didn’t get
into it for the image boost. And I have to say I
don’t think that we have really experienced that. Every situation you
deal with, whether it’s a concern over HPV vaccine, or
what’s the price of your drug, or this or that– there’s nobody saying, oh, isn’t
that the company has stepped up to do Ebola? What I do mean about it is it’s
a positive thing for a vaccine for people to believe
that, in fact, we know that you
can control Ebola with great infection control. But, in fact, a
vaccine is a step up. And so it may not
be directly Merck, but it is good for vaccines,
for the Ebola vaccine, to be seen as a reality. Yeah. Although, what I keep
saying to people is vaccines don’t save lives. Vaccination does. We can have the best
vaccine in the world. And if we don’t have the
systems to deliver it, then it won’t matter. John, I think you wanted to– I think Mike probably wants to. No. Well, I just wanted to
comment, because I think Nancy raised a very important point. But let me take you to the
future and not the past. First of all,
sitting here, I have to just say this because
I’ve never had a chance to say this in my career. I’m sitting front of Mike Ryan,
who I believe is the Indiana Jones of public health. [APPLAUSE] You’re amazing. But you know what my
biggest fear about Ebola has always been? When it hits
[INAUDIBLE] and blows. And Ebola of the 21st century
is very different than Ebola of the past 50 years. We have the
urbanization of Africa. We have the fastest growing
region in the world right now in sub-Saharan Africa. And the urbanization
of this disease makes it a very
different disease when it was in rural
Africa for all these years. So while right now I believe,
from a market standpoint, if we had an
Ebola-prepared Africa– which I have advocated
for a number of years– where we’re vaccinating health
care workers, emergency room, taxi drivers, burial team
people in advance, if possible– that may not be practical
but it, on the other hand, would put some rods
in the reaction. But this, even with
the DRC problem we have now– which Mike
very nicely laid out is a real challenge–
that’s nothing compared to if it got into
our major metropolitan areas. That would be so significant,
that not having a vaccine would be an absolute public
health malpractice issue. Mike, did you want
to say something? Sorry. This is taking a
different approach. No, that’s OK. It’s probably more useful. You’ve probably never heard
me say something like this before or ever again. And I’m certainly not one
that’s in the business of praising pharma, per
se, when it’s not deserved. But taking your point, Michael,
with the business model– fully accept it. That’s our biggest gap. But we vaccinated 20,000
people in the last 12 weeks or 14 weeks in Congo. And that wouldn’t have happened
without the company that’s driven that with us. And for that, they
deserve eternal credit. And again, I have
to say they’ve been very, very transparent with us
on the problems they’ve had. We’ve had monthly
teleconferences at the highest level– the highest level
of organization. And I’ve actually rarely
witnessed such transparency on what are real
manufacturing issues and real proprietary
issues in the company. It doesn’t mean we’re there yet. And there’s a lot
of work left to do. And we’d like this to be
faster, so my frustration can be obvious. But at this particular
moment, given the interactions we’ve had,
I think we are where we are. I think the company
deserves– and a lot of people in the company from
Germany, across the States, deserve a lot of credit. You won’t hear me say
this in many fora. In terms of WHO and
pharma, I’ve always had a rather checkered past. But when people do
good things, they deserve to receive the
appropriate recognition for that, even though
we’re not there and we expect a lot more from
our partners in Mercks and J&J and others for Ebola
vaccines in the future. So thank you, Lydia. Thanks, Mike. So just to be
clear, my questions were not criticisms
of the company. I was trying to get
some information out ’cause I want to know. Could I just– And I’m sure all of you do, too. Go ahead. I’m sorry. Could I just– I think embedded
in a number of the comments– I mean, it’s not about Merck– is the politics
of doing something like this is hard, right? I mean, the things that,
in general, governments don’t do well are sort
of long-term risks that don’t have sort of an
immediate threat, right? In sort of long-term
planning, the world is filled with real
crises that we’re ignoring because we have
more immediate crises that capture political. I know that’s sort of
stating the obvious, but I think that’s
behind all of us here. Whether it’s in the United
States or other countries, we shouldn’t kid ourselves. Because the only
way you can really ramp up enthusiasm or focus
on this is to have a crisis. And we saw what
happened here in the US. That’s a double-edged sword. I mean, you can
make the most of it. But you shouldn’t kid yourself. There’s a lot of downside to it. So I hate to say it. It just seems like it is– at least in my experience,
that it seems like that is a cycle that is
likely to repeat itself. The question is,
given that cycle what can we do to make
the most of the time so we do have attention? And how do we get the
most done in the times, frankly, when we don’t have
the political attention that we need? Can you talk a bit
about clinical trials? Because Marc pointed out when
he was at the podium that we should [INAUDIBLE] and there
may be some progress being made in terms of– A little louder, please? Sorry about that. Marc was saying
before that we should be doing work in peace time. And yet it seems like,
during peace time, all the people who have to
do this work when there’s an outbreak go back to doing
their full-time jobs, which actually preoccupy
them all the time. We know there’s going
to be another outbreak, and yet there doesn’t seem
to be sort of that framework that every time
there is an outbreak, we say, oh, we needed to have
plans for clinical trials. I mean, I think right
now people are arguing about the therapeutic
clinical trials and how they should be run,
if they can be run in DRC. What’s it going to take
to get that work done? And is it actually
feasible to think that you could design
studies and just pull them off the shelf, and put in
the name of the country, and get the regulatory
agencies to sign the paper, and then you’d be able to go? Do you have a thought, Mike– Marc? I’ll start. I don’t think it’s
feasible to do that in the most simple way
that you sort of caricatured in and your last question. But I think there’s a long
way between what we’re doing and that. So I think that
academics are supposed to not think about
just the thing that’s happened yesterday–
although, it’s very hard given how many things seem to be
happening every day these days. But we’re supposed
to be spending time thinking about
contributing to the long-term. And setting up the plans
for clinical trials to be more effective,
debating the ethics of them, is a very, very cheap
activity compared to, say, making any one vaccine. But it has to be done. And I think some of the things
I mentioned in my brief comments were some of the
things that I think are relatively low-hanging fruit. Figure out how to do
correlates protection better. It’s not easy,
but it’s something a lot of bright people
could think about. Figure out how to get some
more consensus on the ethics of randomized trials. This is not something
we should be debating at the last minute
without a really deep base to draw on. So I think there’s
a lot we can do. But the time to find
out if it worked is not going to be in a
simultaneous war and epidemic. And the way to– well, it just needs
to keep going. And I think therapeutics
are much harder. But there’s a lot
that we can still do. I’m cognizant of the time. So I’m going to jump
around a little bit. John, I wanted to ask you
about issues of liability. You were talking about, in your
very interesting presentation, about how complex all the
legal aspects of this are. I think– and correct
me if I’m wrong– the vaccine is
currently being used, and WHO has got an
insurance policy to– so WHO is insured in
case of liability. But at some point
in time, somebody is going to have to figure out
who is liable, should anything go wrong with this vaccine. I don’t understand
the– you know, we’re talking about
there’s no business model. How can one ask a company
that has stepped up and is not going to
make any money off of this vaccine to be liable? But is that what would happen? I mean, will Merck have to
assume liability at a point? I mean, I think in the
current situation– again, I defer to Mike and Lydia. But it’s my understanding
that WHO does have clinical trial
insurance because of the use of the vaccine. Under its current authority,
the Compassionate Use Authority with all the research protocols
and all the other elements of it gives the
opportunity for insurance. But I think the larger
question you’re asking is, OK, say we have a
product and we want to do something larger scale. And what do you do
about adverse events? I think, if you’re going to
stick with a business model– and Mike may see it differently. But if you stick
with a business model where we’re going to
rely on private companies to take substantial
risk, you’re going to have to de-risk
that if you’re going to expect them to put
out products that are not going to have a market, ultimately. So now, how do you do that? Does that mean that you
leave the people who are harmed without any recourse? I don’t think that’s
required at all. You can have compensation
schemes, but that costs money. That would require
the public community– the public health community
we’ve been talking about that’s struggling to even
develop these products– to think longer term, which
is not only do you want to compensate people because
it’s the right thing to do, but you want to
make sure that if– ’cause something bad
will happen someday. It’s almost as inevitable
as another disease coming. You don’t want to not have
people take a product when we need it for
public health reasons as well as for their
own protection. So I think there’s
no single answer. I think liability is
really complicated. But I don’t see any
alternative but to negotiate a resolution, or at
least a way forward that involves all the main
players I talked about before. And, Lydia, you may
see it differently. But I don’t see how
we can avoid it. And I don’t see how
we keep companies like Merck at the table under
the current business model as we’re up front about
risk and allocating it. Right. So I do want to just put
in a plug for the work that WHO has been leading in
concert with the World Economic Forum and with the
involvement of CEPI and Ashish to look at this very
question about liability and compensation for
unlicensed products used in outbreak situations. Because in my now almost
35 years in public health, this is the first time I’ve seen
real progress on this front. And I was particularly persuaded
of the importance of this, not because Merck was
necessarily at risk, because we self-insure. But because if there
are people harmed by a product in a
developing country, the systems of justice
and adjudicating that claim and that potential
harm are rickety at best. And we, of course, would want to
make sure that that person was fairly compensated. And there was just
no system to do that. So the work that WHO and WEF and
CEPI are leading in this area is critically important. Do I have a fond hope that
we might actually one day move from beyond
unlicensed products and outbreak
situations to products licensed, like
our Ebola vaccine, hopefully, in 2019, as I said? In outbreak
situations, yes I do. Because until that happens, we
are still on the hook for that. Can I just– not to harp on
clinical trials too much, but clinical trials–
randomized clinical trials– are part of the solution to
de-risking these products. The reason you do a
big clinical trial is, in part, to find
out if the product is safe under the
conditions of exposure. The vaccines in
recent history that have turned out to be dangerous
and have not been licensed– one of the RSV vaccines, a
staph aureus vaccine, and now there’s been the debate
about the adverse events with the dengue vaccine– all those adverse
events that happen are only under
conditions of exposure, which means using them
in a field phase three type of setting. And so the point
is that when people argue that it’s unethical to do
a randomized trial because it’s putting people at risk– which some people have argued,
especially for therapeutics but also for vaccines– the flip side of that is, if
you don’t do a proper trial, you don’t actually know whether
you’re putting them at risk when you give it to them. Also, I just want to
add to Lydia’s point, is that I do think
the model of what WHO and CEPI and World Economic
Forum, Ashish and others is doing is, if we’re going to ever
get to that long list of things that we have to sort out, you
have to get people together in a safe environment where
they can talk through the pros and cons there. Unless you want to do it
in the midst of a crisis, the only way to do it
is through that process. I don’t want to get
into all the details, but I really feel like that’s
the only way in which you’re going to have a meaningful– you have a chance to
have a set of policies ready in advance as
opposed to on the fly. OK. I’m going to ask a
couple more questions, and then I’m going to
throw it to the floor. Mike was talking about surge
and you can do all– actually, both the Mikes were
talking about the fact that you can do all the
work you want with CEPI and come up with great ideas. But if you don’t
have the capacity to actually make the
product, you’re really not going to be very far along. And that’s something
that I’ve been wondering for a very long time. Because this vaccine is
a perfect example of you can have something
that looks good, it’s more or less ready to
go, and it still takes– I’ve been writing about
this vaccine for 8– 13 years now. And it’s going to
be a while yet. Mike, what’s the answer? Is there an answer? Actually, there is. It’s called missiles. How do we secure, purchase,
and use missiles in the world? The vast majority of them
are bought by governments, from private sector companies
under very strict requirements. Liability is worked
out well in advance. Now, occasionally they get in
the hands of bad people, which is terribly unfortunate. Bottom line is we have to
redefine how we’re going to look at epidemic vaccines. They are a common good. They should be under the
purview of government programs– like defense contractors are– where, from, a
worldwide perspective, we guarantee a purchase of so
much vaccine down the road. We cover the cost of the
good manufacturing practice certified facility,
where hopefully we can use it for other things
with the similar platform. But until we come
to that point, we’re going to struggle in
the business model. I don’t see any
other way around it. And I think that’s going
to be the sea change. Now, again, that’s not
child immunizations. That’s not adult immunizations. That’s not for travel. There’s a money market there
that will allow for those to continue just as they are. But for epidemic disease
ones, they will not. And I think that, until we get
to that point of understanding that we need to change that
entire business model approach, we’re going to struggle. I’ll tell you right now. CEPI– I’m making a prediction. As some of you in
the room know, I was very involved with the
very first meetings of CEPI, a very strong supporter,
have been there all along. I feel the same
way about Carb-X. I predict that, in five years,
CEPI or Carb-X both will probably give us nothing. Nothing. Because they’re
going to pump out a lot of very good 2A products
maybe a little further along. But there’s no business
model down the road. And that’s what we
have to work on next. We fixed that first
part of the rope. Now we got to figure out how
to tie two ropes together to get it 25 feet out. And until we do
that, we’re going to have the same meetings,
the same discussions, the same outcome, and we’re
all going to sit there and Helen’s going
to say, it’s now been 13 years since I’ve
been writing about this. It’s been 13 years. It’ll be 18 years. 18 years, OK. So I think it’s
the business model. And there’s, fortunately,
discussions going on today about this very issue. OK. My last question,
and then I’m going to throw it over to you folks. Lydia, if Merck knew in the
fall of 2014 what it knows now, do you think you guys
could have stepped up? Yes. No doubt. As I said, we saw it as
our moral responsibility. Now, I do want to
underscore a point– as alluded to earlier, this
is not without tradeoffs. And I think that’s another
important point for everybody in this room to consider. Manufacturing
companies like mine typically run on a
fairly lean model. And there isn’t a lot of
bench for the scientists or for the processes, et cetera. And what that means is we had
to pull scientists working on other issues of
public health importance in order to work on this issue. And for some of those
products– potential products– we’ll never get that time back. There are very, very
real indirect costs. And the tradeoff of a
production of an Ebola vaccine for a measles
vaccine may not be a really good tradeoff, right? And I’m not trying to
scaremonger or poor-mouth. But there are very,
very real tradeoffs that have to be considered. And my company, thankfully,
was able to do this. But our CEO has been
really clear that, if someone came to us– again,
to Mike’s point that he just made– we’d have to think really
long and hard about that. I mean, this was a tremendous
direct and indirect cost to the company. All right. Great. Can I add one piece to this? Sure. Let me thrown another monkey
wrench into this issue. I had predicted this was
going to happen a year ago. And I think people
thought I was a wing nut. Well, they still do. [LAUGHTER] And, Mike, you may
want to comment. Well, looking– my mother’s
a Ryan, by the way, OK, so gives you sense
some camaraderie here. I worried desperately
at the roadmap meetings that the Chinese were
going to come forward with their licensed
vaccine, which we had no clue what the hell it meant. It was not part of a WHO review. And today we’re watching the
politics of the world change dramatically, where
we as a country are pulling out with global
health security support and the Chinese are
coming in right behind us. And I raised the issue
at the time and said, we’ve got to get the
Chinese at the table here. We’ve got to have
them part of this. Because what if they
should come in and supplant the entire Western world’s
efforts on Ebola vaccine by suddenly the DRC
just saying, we’re going to to with the
Chinese licensed product? Stay out, the rest of it. Which WHO has no
authority to change that. If the country decides,
it’s their choice. And I think I’m predicting,
with these epidemic vaccines over the next two
years, you’re going to see the Chinese come in
on more and more of these. And it’s not just on
a humanitarian basis. It really is an economic,
political basis. Because they are coming
in with support in a way that we, as a country, did
and we’re doing right now. And this is going
to be part of it. So just mark my word. We could have a very different
panel up here next year if we have the same meeting,
which probably two of the seats should be occupied by Chinese
leaders as opposed to us. All right. Surely there are people– Richard? I want to take us back to
1918, when most of the deaths were in what we now call
the developing world– China, and so on. So how do we ensure
equity in a world where there is not an Ebola
outbreak but a real pandemic? Because we’re not
talking about a pandemic. We’re talking about
an epidemic here. How do we ensure that? Is it going to come from
Chinese manufacturers? By the way– they did this
with the H5N1 vaccine, so it’s not something new. They were pushing that
very, very strongly. So what is the model– the business model– to ensure
that equity takes place, and it’s not just
the vaccine going to those who have the money? Because most of the
disease is going to occur in that part of the world. I think that’s the end of it. Well, in my Walt
Disney World scenario, we will have a game-changing flu
vaccine one day that, if given, will protect against
H1, H2, H3, H5, H7, and H9, which are likely to be
the next pandemic candidates. And it will be one that we
will have already pre-deployed for seasonal flu, which
will have at least 10 to 20 years of protection. If we had that, we
would fundamentally change the epidemiology
of pandemic influenza as much as we eradicated
smallpox from the world. And I do not believe that
that is an unrealistic dream. I think,
immunologically, we have reason to believe we can do it. Again, it’s a business model. So I think the question
is, in the meantime, until we get to that point,
we’re pretty much screwed. And I don’t know if
there will be equity. I don’t think it will happen. Second of all, though,
I think we can take this off the map as a challenge
if we just, again, put ourselves to the mission. And I loved your quote
from John Kennedy about, why we are we doing it? It’s not because it’s easy. It’s because it’s hard. And I think that that’s
exactly what this is. So my question is, really,
what is the business model for smallpox vaccine? If I’m not mistaken,
governments– including the United States
government– possess large– It’s a missile. What is it? It’s a missile. Yeah, right. I mean, is that pretty
much the answer, that we need to think about
a long list of diseases the way we think
about smallpox, which is to say to buy and most
likely never use but just keep repurchasing it
whenever it expires, massive amounts of
vaccine for many diseases? I mean, that’s one of
the simplest answers. It’s also probably the
most expensive answer. But, I mean, is that it? Well, I would say
first of all, none of the diseases we’ve
mentioned actually fit into the smallpox
category, with the exception of should smallpox return– which I think there
surely is a possibility. Because we can make smallpox
virus de novo today. We don’t need to
have the old virus. And someone could do that. But I think the
message here is these are vaccines that will be used. Lassa takes its toll every year. Nipah is one that is very
real and is going to continue to be a growing challenge. So all the diseases
we’ve talked about here– what we have to have
is the pipeline so that the vaccine
being used is replaced by a vaccine coming in, and
potentially of expanding it. So that’s more active than
just a stockpile of an advanced smallpox vaccine. No. Go ahead. Go ahead, John. This is probably only
a little facetious. I think the way
to think about it may not be in terms of biology. But think in terms of
the political economy at the Defense Department. Think of what governments invest
over the long-term in something that they may not need
to use right away. But you build public support. You have a set of players that
consistently come to the table every year because it matters. I mean, there are other
examples, but that’s one. So I would actually like
to suggest that talk Dr. [INAUDIBLE] may have
something to add here that’s worth hearing. But just simply observe that the
public purse is not unlimited. And even though DOD has a
budget and BARDA has a budget and CDC has a budget,
they all probably would argue they don’t have
all the budget they need. So if we want to have missiles
for all these diseases, the money’s going to have
to come from somewhere. And it should be a global– Anything you want to add? It should be a global budget. Let me make this clear. We’re not talking about taking
out of the current budgets. We’re talking about this is a
new, strategic investment that has to say– you know, for some of you who
are old enough in the room, you remember the old
oil Fram commercial. You can pay me now or
you could pay me later. And I think that this
is on– any cost benefit analysis is going to be cost
beneficial to actually take care of these epidemic diseases. And it should be
shared by the world. This should not be a
United States-based effort. I mean, we surely are a leader. But it has to be– and
I think to the extent that governments
around the world get involved with
defense spending, they need to be involved
with this spending. So just to get you out
of Walt Disney World, many things are cost
beneficial that our government and other governments
don’t fund. They don’t do. You know, we just
have to be realistic. These are political,
public decisions. But I think smallpox
and flu are maybe different from all these other
ones that we’re talking about, in the sense that
we really, ideally– if any country needs a
stockpile of those two, then probably all countries
need a stockpile of those two. But for diseases that are less
transmissible– for Ebola, for example– we don’t need a shot for every
human being in the world, or even anything close to that. What we need is
every human being in the world to
contribute some tax dollars to provide enough
to stop the next outbreak, the next few outbreaks. Amen. I would like to thank
you folks very much. I’m sorry to have
to cut it off now. But I think we ran out of time. Thank you very much. Thank you. [APPLAUSE] All right. So that was terrific. Thank you all. We’re going to take about
a five, seven minute break. There is coffee and some
tasty goodies outside. And when we come
back, we’re going to hear from somebody
who was referred to over and over again– Nicki Lurie– who really led
the preparedness and response effort for our country
for eight years. So let’s be back here
in eight minutes.

Stephen Childs

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