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From IAVI to GAVI: A Conversation with Seth Berkley on the Future of Vaccines and Global Health

Speaker: Seth F. Berkley, Incoming CEO, Global Alliance for Vaccines and Immunization (GAVI)
Presider: Laurie Garrett, Senior Fellow for Global Health, Council on Foreign Relations
June 30, 2011
Council on Foreign Relations

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LAURIE GARRETT:  Greetings, everybody.  Welcome.  Thanks so much for joining us today for the Global Health Program's special session here.  For those of you -- I don't know if any of you have not met me before, but I'm Laurie Garrett, and I run the Global Health Program here at the Council on Foreign Relations.

And before I get into the meat of today's discussion, "From IAVI to GAVI:  A Conversation with Seth Berkley on the Future of Vaccines and Global Health" -- Seth Berkley -- just a couple bits of housekeeping.

First of all, this is on the record, so keep that in mind when you ask your questions.  You might not want to reveal anything.  And we will be posting a transcript of this conversation on the CFR website in case there's particularly enlightening and brilliant comments that come forth from Dr. Berkley that you may wish to share with others.

Please turn off any device that makes a noise.  That'd be nice for everybody.

And procedurally, I'm going to have a conversation with Seth for about half an hour, and then we're going to open it up to all of you in the room.  So keep track of questions as they arise in your head, and be ready to flip your card to indicate you have a question to pose.  And I will make every effort to call on them in the sequence in which I notice the cards flipping.  But don't start yet.  (Laughter.)

I don't know if Seth really needs an introduction to folks in this room, but let me just say a couple of quick things and then move right to our conversation.  I have to in the interest of fair disclosure admit that Seth and I are very good friends and we've known each other an awfully long time.  So unlike most of the roundtables I do here in meetings, I can't really claim to pose hostile witness questions or anything of that nature.

DR. SETH BERKLEY:  Never stopped you before.

GARRETT:  Never stopped me before.  (Laughter.)

And Seth has made an arc over time that, you know, has been -- I guess in retrospect you could say it looks like a series of strategic plans, each building upon the other.  But I don't believe there was anything strategic about it whatsoever.  It just happened that way, from an EIS officer for the CDC working in Uganda, then Rockefeller Foundation -- and by the way, we have Ariel Pablos-Mendez, who currently for a few more microseconds runs the health endeavor at the Rockefeller Foundation until he takes over as number two at USAID; you didn't hear it from me -- and from the Rockefeller to IAVI, the International AIDS Vaccine Initiative, and now on to GAVI, moving to Geneva.

And I want to start right off the bat by saying a few things about where things stand and then asking Seth for a few questions.

The -- GAVI just had its replenishment meeting.  And for those of you that weren't following this, it was pretty remarkable.  GAVI was hoping that the donor community, public and private, would come up with something in the neighborhood of $3.7 billion to support vaccines and got 4.6 billion (dollars).  That never happens in a recession.  And that's certainly not the trajectory that any other of the major global health players is experiencing at this time.

When Seth was at Rockefeller Foundation, that was when you really started seeing the need for a vaccine initiative around HIV/AIDS.  And if I understand it right, you started everything there.  And then in 1996, IAVI actually was born, and Seth left Rockefeller to take over IAVI.  And at that time, I mean, I don't think that we would find anybody who was particularly optimistic about the AIDS vaccine picture in 1996.  It looked awfully grim.  And there were a number of pretty dramatic deceits along the way that made the whole effort to come up with an AIDS vaccine seem like a wild shot in the dark.  Indeed, there was a book of that exact title by Jon Cohen referring to the search for an AIDS vaccine.

But very recently we've had a couple of big breakthroughs that were funded by and organized by IAVI.  About a year ago, the long-standing neutralizing antibody initiative, the search for antibodies that actually kill HIV, panned out with the first real indications that there may be circumstances under which neutralizing antibodies actually do emerge.

And then very recently, for those of you that may not, like me, be in a situation where you're compelled to read Nature, Science and about a hundred other scientific journals on a routine basis -- (chuckles) -- you may have missed this I think profoundly important paper published in Nature in May regarding the use of an unusual set of -- an unusual and new strategy in order to actually effectively create a completely protective or what seems at this point completely protective immune response in Rhesus monkeys against SIV, the simian equivalent of HIV.

So I think the first thing I'd like to ask you, Seth, is how you would assess, as you're about to depart IAVI, this moment and this stage that we're in in this pursuit for an AIDS vaccine.

BERKLEY:  So thank you, Laurie, and thank you, everybody, for coming, and I look forward to having a conversation with all of you.

Let me start by saying that I'm not at GAVI yet, so I have been -- it's been announced that I'm going to go there.  I've been in a transition mode during this last three or four months where I've been attending many of the GAVI meetings and engaged and trying to learn and have conversations with people.  But -- so I will be able to offer opinions and knowledge from where I am, but I'm not yet sitting in position and so don't have full knowledge of everything going on.  So I just wanted to make that clear, particularly since we're on the record.  I never figured out what's on the record and off and how that gets decided.

Second, since it is on the record, the request initially for resources was for 3.7 billion (dollars), and that was against a larger budget of 7.6 billion (dollars).  And we were actually funded at 4.3 (billion dollars), so it was a little bit less than you mentioned.  But I just want to put that into perspective -- and I'm sure we'll come back to this -- which is, you know, the secretariat and the partners put down a budget and what they thought realistically could be done during this time period.

But this did not cover -- and as you can imagine, doesn't come close to covering -- the real need and the long-term goals of GAVI, which is to, you know, try to get immunizations to every child living in the poorest 72 countries.  And so that doesn't include, you know, just getting to 80 percent or 90 percent; ideally, you'd want to get to a hundred percent.  You'd particularly want to outreach to children living in poor areas, stigmatized children, and that's much more difficult and much more expensive.  Plus, there's interest in trying to deal with HPV as a -- an intervention, which hasn't gotten the attention it should.  And that's an important one, and there's a lot of new vaccines coming out.  So --

GARRETT:  You do remember I asked you about HIV.

BERKLEY:  Yes, I'm going to get there, but I wanted to make sure that we corrected that.

The -- you know, the interesting thing in terms of the Rockefeller Foundation at the time was it was involved when IAVI was formed with the Children's Vaccine Initiative -- we can come back to -- and then establishment of GAVI as well.  And some of the principles between IAVI and GAVI were born at a time when the public and private sector weren't engaged very well together in working on these -- on these products.  And I think that was really the birth of IAVI, was this recognition that AIDS vaccines were potentially an important intervention.  But the public sector didn't do that so well, and there weren't those fora where the groups could come together and work in an aligned fashion.

So IAVI was established.  It started out -- the first thing was just trying to come up with a belief that an NGO could play a role in this type of initiative.  There were people at the time who thought that science -- this was big science, it belonged to governments or only belonged to large pharma companies, NGOs wouldn't have a role to play.  And I think over time, we changed that paradigm.  There's now a lot of other public-private partnerships working on these issues, and in all the vaccine areas.

But for IAVI particularly, the field has moved.  It isn't just IAVI, and I think that's important, because our role is to ensure, which doesn't mean we have to do.  So when Merck was moving forward on a candidate, we didn't work on that same candidate.  Others did; we didn't, because our job was to try to make sure the field did.

So what's happened to change the field?  Well, after a lot of time of investments and a lot of going back upstream, three things have happened that have made it really an extraordinary time.  One is, for the first time, a vaccine worked in humans.  That was the RV 144.  Many people found that to be a surprise.

This was a vaccine tested in Thailand.  It was made up of two components, one which was pretty weak.  And the second component had been tested alone as an efficacy trial.  And so there was some -- and didn't work.  And so there was expectation that this vaccine would not work.  But in fact, it provided modest protection.  And the world is trying to understand what that means.  But for the first time, you don't have to say, is it possible?  It is possible in a scientific trial.

The second thing that happened was the neutralizing antibody issue that you talked about.  And the big problem with HIV is the variability.  Normally, you'd like vaccines to produce neutralizing antibodies.  We didn't know how to do that.  The first vaccine tested gave 100 percent of people antibodies, but they didn't broadly neutralize.

And we were able to go back.  People had discovered that there were broadly neutralizing antibodies in humans.  There had been four of them that had been isolated, and in fact, John Moore, over there, worked extensively on a number of these.  And the question was, if there were four, there must be more.  And we began a program working with partners around the world to isolate more antibodies.

And the exciting thing now is that there are dozens of new antibodies that are very potent, very broad, potent down to the level of something like 20 nanograms per ml.  If you combine multiple ones, they cover all strains.  The challenge is, how do you induce those antibodies?  What do you inject to make those antibodies?  But we know they come from humans.  We know, therefore, humans can make them.  And so the exciting idea now is to try to, in a high-throughput way, make these antibodies.

The third thing that's happened that's really exciting is that the Merck candidate, which was the best of the cellular immunity candidate, didn't work.  In fact, there was some evidence to suggest that people who got the vaccine might have had increased risk of HIV.

Today, there are six more approaches that look better than the Merck candidate in the best of the animal models -- this was in the SIV system.  You mentioned one of them they're quite excited about.  And so those are now moving rapidly towards testing, some of them more complicated than others.  CMV, the one you talked about, is particularly complicated.  But you know, we feel very optimistic that, you know, this problem will be solved.  Of course, the question is when, and I can't predict science.

GARRETT:  What kind of shape are you leaving IAVI in?

BERKLEY:  Well, I'd like to think that the organization is in very good shape.  It's been well-financed.  Of course, it is a tough financial time.  I think the big challenge now is how we shift from -- we started out as a product-development partnership.  We shifted then to upstream research, and Wayne Koff, CSO, is sitting right there.  And now the challenge is, how do we go into high-throughput industrial-like screening?  Because we've got these exciting findings, we now have targets.  We have structures, and how do you turn that into vaccines?

And so in a sense, the main strength of IAVI over the years has been kind of reinventing itself over and over.  That's the flexibility of a public-private partnership.  And so IAVI, in essence, is now reinventing itself to try to do this high-throughput work.

GARRETT:  Obviously, you can't tell us who's taking over, but what kind of a person is IAVI looking for?  What kind of leadership?

BERKLEY:  I think the challenge -- and obviously, it's up to the board.  I'm not going to make that decision.  But I think we have a very strong science team and, you know, very strong science leadership.  And so I think the priority is going to be somebody who can provide overall management of the organization, charismatic leadership of the organization.  Obviously, critical to deal with fundraising and our partners in the south, which is a very important part of what we do.

GARRETT:  Good luck on that.  So OK.  (Laughter.)  Let's turn to GAVI.  And given your caveat that you're not actually in the driver's seat yet, so I can ask anything I care to ask but you could decide what parameters you can answer.  To repeat your financial situation, you're inheriting GAVI at a very good time.

But in a recent assessment put together by our sister organization in Washington, CSIS, assessing GAVI's performance, they stated, quote:  Despite GAVI's often impressive results, the alliance's -- that's a key word, alliance -- message and brand identity have often been difficult to discern, muddled by several factors:  One, that I -- that GAVI is in fact a complex alliance and not a single bounded entity; that it is immunizations, and not GAVI, that are on everyone's top concern list; that the GAVI board comprises a contentious mix of prominent, independent opinion leaders, the pharmaceutical industry, GAVI grant recipients, foundation and governments owners, international organizations and civil society -- that's a mouthful -- and that GAVI has remained principally a finance mechanism, an operation whose visible, on-the-ground achievements are implemented by ministries of health, NGOs and technical partners like UNICEF, World Bank and WHO.

All right, so you're stepping in.  It's well-funded but it's got some essential structural issues.  What do you think you're walking into?

BERKLEY:  Well, obviously, there's lots of interesting ways to look at this, and you can look at it on both sides.  So let me start with the advocacy and brand part of it.  It is an alliance, and that's an important component of it.  And when it first started, there was actually not a lot of central funds; there were not a lot of central staff.  Everything was done by the partners.

As the organization has gotten more expansive, as the goals have gotten more expansive, it's needed to hire people.  And it's become more important, as you begin to deal with fundraising, as you begin to deal with anti-vaccine, you know, the anti-vaccine lobby and others, that there is support for immunization.

And so there's been a little bit of a concern, you know, should GAVI exist as a separate entity or should it not?  Is it all -- should all the work be done by the partners, or should GAVI do some?  And I'm talking about the secretariat here.

And I think over time, what we've begun to see is a movement towards a balanced system, where clearly, the partners are doing work and one is working with the partners.  But the secretariat itself has to take on major issues.

And I think looking at what happened around this replenishment, not only did the secretariat step up to the plate, but a number of the partners helped in engaging and creating the type of movement that was critical to get GAVI to where it is now.

I think over time, more of that has to be professionalized.  And I think that's going to be one of the priorities.

In terms of governance, it's a complicated issue.  The governance is both a weakness and a strength.  It's a -- it's a weakness in the conflict you implied by doing this.  And it's very clear that, you know, a number of NGOs have said, you know, my god, you know, GAVI is conflicted because industry is on its board.

Well, frankly, most people sitting around the board table have a conflict.  That's why it's an alliance.  So countries in the south who get, you know, vaccines and money from GAVI are on the board.  WHO has staff supported by GAVI, is on the board.  UNICEF, you know, is our implementation, you know, partner.  The Truman Partner's on the board, industry both north and south is on the board.

So in essence, the alliance part of it is to bring all those people to the table and try to have them align on the interest of engaging in moving immunization forward.  So that's the model.

Now, it occasionally does raise issues in terms of conflict of interest, and there are strong conflict-of-interest provisions.  And one of the things that was quite smart when GAVI and the campaign for GAVI, which was a separate board, were joined a few years ago, they took a lot of the board members who were on the campaign, which was many independent board members, and brought them into the board.

So sitting on the GAVI board were a number of independent board members.  And in a sense, they bring a different voice to the board.  And it's something that's very important and, I think, needs to be supported.  So how that's going to change over time and what's going to happen, I don't know.  But it is important that that has both, you know, useful functions and some functions that need to be watched.

In terms of the financing issue, yes, GAVI is a fund in a sense.  But what GAVI is trying to do is do something very bold, which is to make sure the products that appear, that our children get in the West, basically appear simultaneously in the south -- that no child, because they live in a poor country, doesn't have access to the same vaccines, the same tools that you'd have in the West.

And to do that isn't only about purchasing vaccines.  It's about making sure there's an immunization system in place, supporting the partners that are engaged in that.  And, at the end of the day, it is governments that have to do this type of work.  And so we work closely with governments.  But where necessary, obviously, they're supported by U.N. agencies and by NGOs.

And so the other things that, you know, might have been criticized here is that GAVI hasn't done as good a job as it could working with the civil society sector.  But that's a priority right now and I think we will have to do a better job, particularly in countries that are, you know, in wartime or in, you know, in tough shape now.  And that's important because a lot of the work in polio and other things are occuring in these countries.  And it's important to kind of connect those.

GARRETT:  Well, since the 2008 global recession-financial crisis and ongoing nightmare that is today's global economy, as we all, you know, watch Greece hang by their fingernails, there was an initial prediction that this world financial shake-up would result in a sort of net loss in the amount of money on the table for this enterprise we call global health.

And that is not, in fact, what has happened.  The amount of money on the table has continued to increase, though much more modestly, incrementally, in the last two years.  But what has happened is a tremendous realignment in where the money is going, who the major donors are and who the major recipients are, which is also resulting in a huge realignment in power and in the nature of global governance of health.

Just to give you an idea of what I'm talking about, if you're looking at GAVI and you're saying, about $7.6 billion is either pledged or actually in the bank -- if I may, just for -- (inaudible) -- reasons -- either pledged or already in the bank, that's a nice pot.  Keep that number in your head:  7.6 (billion dollars).

Now let's look at WHO.  WHO has a budget shortfall of 1 billion dollars.  It's currently laying off 20 percent of its staff, if not 25.  And total amount pledged and in the bank is half of what GAVI has, and it's for two years -- it's about 3.9 billion (dollars).

If you look at the Global Fund to Fight AIDS, Tuberculosis and Malaria, it fell far short of its replenishment target.  It didn't even hit what the fund claimed to be the absolute minimum functional amount of money to raise.  If you look at -- on the donor side, the Gates Foundation now represents 68 percent of all private giving for global health.  So 68 percent of all that private money is in one family, one source:  Seattle, Washington.

If you go to the public side, the United States government is 59 percent of all giving.  And we're facing a very bloody summer going into the FY '12 budget fight, which could well result in a marked diminution in the amount of money that the United States puts into global health.  And there are not players out there prepared to leap in on the public side and fill the gap.

So when you put this whole picture together and consider how much  -- how well funded GAVI is compared to the others, you have a real, you know, balance-of-power issue going on that could dictate a lot about what we consider to be the priorities of global health.

BERKLEY:  Well, yes and no.  I mean, it's a complicated issue.  And as we've moved to the right, one of the things that's happened is there's much more respect for how the private sector works, engagement of the private sector, much more "value for money" -- that's a term that comes out a lot.

And one of the reasons that GAVI has seen -- been seen as successful in a recent review of different programs at DFID, for example -- GAVI came out right at the top because of its targeting of the very poor, because of its outcomes, measures and, you know, its cost effectivenss.

And so I think we will see more and more, you know, those types of measurements that are going to be critical.  And one of the things that I think is going to be important is, you know, do we have the data that's necessary to show a valuation of these.  And some of the data is good; some probably isn't.  And I think we have to do a better job of asking the question, what are surveillance systems?  How do we understand the effects?  How do we understand coverage of vaccines?  How do we understand the effects those are having?

There's certainly -- recently, we've learned that some of the vaccines that were very effective in wealthy populations have less effectiveness in poor populations.  We have to understand that on the ground.  And although in the past, many have said, you know, well, gee, if it looks good for us, we shouldn't look, I don't think that's the strategy at all.  I think the strategy is, let's try to understand what's happening so that we can do a better job saving lives.

In terms of, you know, funding though, it's hard to compare what GAVI is getting.  It's getting money which then purchases -- or I shouldn't even say purchases -- cofinances vaccines.  All the countries that GAVI works with have to put their own money on the table to buy vaccines.  It's obviously heavily tiered in prices, but it's cofinanced money for countries to buy the most cost-effective intervention.  And that's very different from an organization like WHO that does a lot of functions and normative, you know, activities, et cetera.

I think that the real question for WHO that we all have to worry about is, with the crisis going on there, you know, are they going to be able to retain their core functions?  Are the best-quality staff going to stay or is this going to be a rush to the door of the best-quality staff -- and how that's going to affect the critical normative functions that are necessary.

In terms of, you know, the issues on, for example, the U.S. being 59 percent of all funds for global health, interestingly, in the GAVI replenishment, they did not end up being, you know, that number.  And I think it's important because a number of other key donors stepped up to the plate and I think that's great.  And one of the goals we're going to have over the next few years is to try to continue to expand that buy-in of different governments for vaccines, which are quite cost-effective.

In terms of the Gates Foundation, you know, we would love to see a next generation of private leaders to come out.  We'd love to see the Rockefeller Foundation step back up to the plate in a big way.  I think, you know, it is a tough issue because when you're trying to convince donors to fund when, at the same time, there are these massive movements of money both from governments and large donors, it becomes quite difficult.  But that's a challenge that I think we have to keep pushing on.

GARRETT:  Well, let me push you a little bit more on this question of the balance of power and the priorities in global health because the big push now in the U.N. system is for the NCDs, the non-communicable diseases, and the upcoming United Nations General Assembly special session that will be here in New York in September dedicated to the, you know, emerging disease threats of the emerging-market countries primarily, so that it's really a focus for countries like China, India, Brazil, Mexico, Indonesia, et cetera -- big power block countries.

And at the same time, in our old traditional areas of concern for global health and public health, the funding is directed very much toward two things:  vaccines and anti-retroviral treatment.  There is a kind of threat that we could end up in a situation where global health is about only two things:  on one side, this vaccinology, essentially, and anti-retroviral treatment, which is completely different from the vaccinology side, and then that we seek a multi-trillion-dollar enterprise that is chronic diseases management and prevention.

And it seems like a lot is going to get lost along the wayside, especially if WHO continues to sort of diminish from the scene.

BERKLEY:  It's interesting -- Lincoln Chen, a former colleague of ours, once said that global health is like a sinking ship.  It's, you know, women and children and nothing else -- you know, women and children first, and nothing else.  Clearly, we have to look at all the health, you know, issues that are going on.  And certainly, noncommunicable diseases are becoming more important, certainly, in the middle-income countries, and even in the poor countries as life expectancies go up.

What'll be interesting, though, is how that plays out because one of the things that IAVI had to do was deal with the fact that HIV became more and more a disease of poverty, and so we needed to deal with R&D in those countries.  And I suspect for NCDs, there's not going to be huge amounts of requirements for research and development because there's such a huge market in the West.

I think what's going to have to be is, how do we do implementation of cost-effective interventions in the south?  And there may be an innovation agenda around that, but this may be financed quite differently from immunizations, from diseases of poverty.

The other thing that's interesting, of course, is -- and I -- this is a biased infectious-disease vaccinologist saying this, but more and more, we're finding out that a lot of the chronic diseases turn out to have infectious origins.  And you know, not only now do we have -- the largest vaccine saving lives in the GAVI portfolio is hepatitis B, which is saving lives (through ?) liver cancer.

You know, hep B is -- and HPV now is another vaccine that obviously is going to save lives via cervical cancer and other cancers.  And you know, soon we're going to have, I'm sure, better understanding of type 1 diabetes, and, you know, other diseases that are going to be infectious.

So I think there's going to be a lot of crossover of those, and I think we'll have to see whether this ends up taking away from the rest of the agenda that's critical.  But I -- that doesn't take away from what you said, which is absolutely right, which is, at the end of the day, we need a normative agency that is prioritizing the diseases that are out there and is paying attention to that.  And I hope the WHO is going to continue to play that role.

GARRETT:  I want to leave -- (audio break) -- I want to leave time for the whole group, but I can't take away my role as the questioner without two last quick questions.  The first is, if there's any priority stated by Bill Gates personally, by the Decade of the Vaccines initiative, and overall by GAVI and so on, it is eradication of polio, which of course the Rotary Club has played a major role in.

And we're down to four key endemic countries for polio in the world; that's the good news.  And in three of those, annually we've seen declines.  But, uh-oh, let's talk Pakistan.  Last year, Pakistan had a 62-percent increase in identified polio cases, a dramatic increase in polio deaths.  The minister of health was just indicted on massive corruption charges.  And starting next month, there will be no ministry of health in Pakistan.  It's the only country I know of in the history of modern world that has created a ministry of health and then dissolved it.

And so the government is saying that the way it wants the outside world to engage with Pakistan and Pakistani health issues is on a state-by-state basis.  I personally am trying to imagine the security arrangements necessary for an American vaccinologist to cut a deal with Waziristan so that they can go out into, you know, the contested areas with al-Qaida operatives and carry out vaccination campaigns.  What are we going to do?  How are we going to conquer polio if it's -- all ends up coming down to Pakistan?

BERKLEY:  Well -- (chuckles) -- first of all, interestingly, there has been a -- we didn't talk about, you know, the vertical versus horizontal, which is usually the debate we have.  But there is within the immunization community a quite vertical alignment.  So you have polio eradication; you've got measles elimination; you've got existing vaccines; you've got the new vaccines; and then, you've got the R&D that, you know, the IAVIs and the (ERISes ?) and, you know, others in the world.

And I must say that there's not the cross talk that should exist.  And so, the answer actually is, GAVI is not the group that's doing most of the work on polio eradication; it's Rotary and other groups like that.  And luckily, Rotary, of course, is a, you know, a group that's very closely connected to the community.  And you know, they may be able to work better in those circumstances than can external leaders.  But that doesn't get away from -- (chuckles) -- the point you make, which is, how do you run a health system without some leadership in dealing with issues?  So this is certainly a big problem.

But I think critical for the role of GAVI will be to make sure -- when GAVI was first born, there was this idea that it would be the big umbrella for immunization.  It doesn't mean it has to fund any (of those ?) areas, but it would be a place where you would make connections.  So as you dealt with the states that were having problems with polio eradication, they also probably didn't have strong systems to deal with routine immunization.  And as you know, with routine immunization, you need those to get new vaccines out.

And then obviously, if malaria vaccines appear in September, October at the first crack and first look at the data, which, you know, probably won't happen -- but if it does, you know, it's going to be important to understand the existing process with implementation in different places.  So I think one of the roles of GAVI needs to do is make sure that that alliance includes all of these people.

But I think we will get there on polio.  I think there's a huge focus right now.  And one helpful thing is what's happening in India, because as you know, there's enormous competition between India and Pakistan on most issues.  And India has gotten so serious, so serious about polio using their own resources, driving forward -- and you know, they're down -- they've had one case, you know, one case.  So it's really remarkable the way -- what they've mobilized.  And I think -- you know, the least -- the leaders I've talked to at state level in Pakistan, want the same thing to happen.

GARRETT:  OK, last bugaboo is measles.  Zoe Liberman, who has been working with me, we're developing what we hope will be a very exciting, interactive chart tracking over time outbreaks of vaccine-preventable diseases around the world.  We've been amassing data now for about four years.  And without a doubt, measles is number one.  And it's a combination of anti-vaccine movements in the rich countries where people say, I'm not going to vaccinate my kids.  And the first thing that seems to crop up when vaccination rates go down is measles.

Then, it's also shortages and supply issues for measles vaccine and failure to deliver appropriately.  One analysis, again, published in that great science magazine, Nature, projects that if we stay the course on the bad performance of measles vaccination that we're on right now, by the end of next year, we'll have 600,000 active cases of measles annually, which is an enormous defeat compared to where we were in 2006 down to about 180,000 annually.  So that's, you know, about a five-plus-fold increase.

What are we going to do?  How are we going to deal with measles?

BERKLEY:  So measles is probably the best argument for why there needs to be global health, and why we have to think about it as a global public good.  Because in a sense, measles is the canary in the coal mine for immunization.  It is, you know, highly transmissible.  The vaccine costs 15 cents, so it's not -- you know, shouldn't be an issue in terms of cost.  And what we've know(n), it's been eliminated in North and South America, and yet it keeps being reintroduced from transmissions from outside, and as you say, in groups that don't want to be immunized.

So if we were -- it is certainly plausible -- the world hasn't gotten there -- it's plausible to eradicate measles.  It has the characteristics that are eradicatible.  But -- and a number of the regions in the world, all but one now have targets to try to move towards measles elimination.  And if we don't do that, then we are going to need to continually not only have primary immunization, but probably campaigns to, you know, to deal with missing people and other issues as a way to control this disease.

And you know, what's happening is just a good example of why we have to make sure that we keep, you know, our vigilance up because without it, it's just going to continue to spread like crazy.

And by the way, we've seen this also with -- we've seen outbreaks of pertussis; we've seen outbreaks of diptheria; we obviously saw outbreaks of polio, you know, during an era when immunizations weren't great.  So it's not just measles, but measles is so transmissible.  And you know, it's the example of what we have to do to really try to control these diseases.

GARRETT:  OK.  And again, I'm going to take the questions -- as I see the cards flip, I saw Sylvan (ph) go first, so he will be number one.

Sylvan (ph).

QUESTIONER:  I'd like to bring up a few points.  You mentioned Pakistan.  One of the problems with Pakistan has been the floods.  And since polio is transmitted by feces, the floods were really a tremendous problem and exacerbated that.

I'd like to bring out some other points, and that is, we have spent about $1 billion at this point in eliminating polio.  And our partners are UNICEF and WHO and the CDC and governments.  Social mobilization is tremendously important, as is monitoring and surveillance.  And the other thing that's a real problem is the cold chain, and especially upcountry in various African nations and also in India and other places in Southeast Asia.

So I think that we're making an awful lot of progress, but there's a long way to go.  And so far, we see the end of the road by 2014, hopefully.  If we can eliminate Nigeria and India this next year, that will leave Afghanistan and Pakistan as the final ones where it's endemic.

GARRETT:  I should just point out that, if you didn't hear it, Sylvan (ph) is with Rotary International.

BERKLEY:  So you know, I think it's an amazing story, what the rotarians have done.  And we all -- our hopes are with you for that.  Of course, that doesn't stop the problem, because we would need to continue to immunize for a period of time.  We've actually eliminated Type II polio in the world, at least as far as we can tell.  And some of the new technical, you know, inputs have been to change vaccines to try to deal with Type I and III and now, the transmission of vaccine polio virus, you know, the attenuated polio virus.

And one of the questions is, how are we going to get a post-eradication campaign going?  And so manufacturers are now beginning to look at what it would look like to build, you know, instead of a pentavalent vaccine, maybe a hexavalent vaccine that might include IPV and all the problems associated with that.

QUESTIONER:  How many governments are in the alliance?

BERKLEY:  Well, the GAVI alliance deals with the 72 poorest countries.  And you know, but there are obviously a lot of other governments that are supporting it.  And one of the critical issues is, you know, how that interacts with the broader community, which of course it does through all the alliance partners who are paying attention to countries that are above the cut-off point for where GAVI deals with them.

GARRETT:  Turning to Merck, Mark (ph)?

QUESTIONER:  Thank you.  I'd like to explore the aspirations you had at IAVI and how those relate to those at GAVI.  You know, as you know, one of GAVI's four missions is to affect some market-shaping events.  And the organization has actually done that in a way that I'm not exactly sure that the organization knows that it's done that.

And that's, when people are now thinking about developing vaccines, it's not like they just focus on the developed countries.  They now have an obligation to think about how they're going to get the vaccines to low-income countries.  And as you know, decisions that are made very early on in the development process have a big impact on the product profile, the affordability, the scale of manufacture -- all kinds of things that are relevant to GAVI's mission.

But I think -- the aspiration that I would be interested in hearing about is what you hold for the future of GAVI.  And that, do you imagine GAVI being the organization that would deliver all new vaccines as they're developed?  And if so, what do you need to do to prepare for that?

My fear is that if there's not a path forward, and some of the recent bumps in the road have I think caused some concern on the part of vaccine developers, that, will they be able to continue to sustain this momentum towards thinking about the developing world early on in the development process?

BERKLEY:  So it's an excellent question.  You know, does GAVI have to be the only group thinking about that?  Well, of course not.  And if there was a malaria vaccine, what role does the global fund have to play, you know, versus that of GAVI?  But I think GAVI would like to think of the fact that as new products come out, they should be rolled out in those 72 countries.  And then, what is the mechanism to make sure they're available?

In an ideal world, what you've got is, new vaccines come in at a higher cost; GAVI can help with that, and I'll talk in a second about the market-shaping part.  Hopefully other vaccines now have become much more inexpensive over time, through technological changes, through process-engineering improvement, such that, you know, as those vaccines become more inexpensive and are able to be paid for, you can replace with these more expensive new products.

Now, one of the interesting things is that the market-shaping mechanism of GAVI is many-fold.  One is obviously buying for a very large number of countries and being able -- very important to vaccine manufacturers, as you know, is knowing what the demand is and being able to say, over time, we're going to purchase this quantity.

And the AMC, for example, has been a very helpful innovation doing that.

GARRETT:  Define, please?

BERKLEY:  Sorry, the Advance Market Commitment.  So for pneumococcal vaccines, a decision was made to create a different structure, to create an artificial market where GAVI managed it for a group of donors.  But what they would do is buy the vaccine at a fixed price with the agreement with the manufacturers that at the end, it would have a tail price that was much lower than would normally be expected.

And to do that, they, you know, top up the price.  And the idea is that the company would get up-front money that would allow them to pay back their R&D, their innovation costs such that they would drop down to that lower price rather quickly.  It was quite exciting innovation.

You know, and of course, setting that price is a problem.  Which brings me back to the point I'd like to make about this, which is, you know, large companies managed initially with low-volume, high-price strategies.  And then the idea was that manufacturers in the south would do, you know, high-volume, low-cost price.

The manufacturers -- (inaudible) -- got much more sophisticated.  They are now producing a lot of the world's vaccines, but they are beginning to feel stretched as they've become competitive.  And there's multiple vaccine producers in the south.  They end up having such thin razor margins that they now can't invest in innovation.

And so one of the questions, and this is true, I think, around ARVs as well, are we creating an environment that over time will get rid of innovation?  And this will be a problem for the world.

So I don't have a solution yet, but certainly, as we begin to think about all of these market shapings, we have to think about what a healthy vaccine market looks like.  And that is a healthy market for both the producers in the north, which tend to take care of themselves, have to up to this point, but also the producers in the south.

And at the end, what we'd like is Ramsey pricing, where we have quite steep price tiering all the way from low levels, basically at cost-plus in the poorest countries, what the market will bear in the rich countries, and then each level down, a different price so that you maximize both the return, but also the accessibility of vaccine to everybody who needs it.  But we're a long way from getting to that stage.

GARRETT:  The Rockefeller Foundation, Robert (sp).

QUESTIONER:  All right.  Thanks so much.  So far, Laurie and Seth, this has been really interesting.  And I wanted to go back to a point that you touched upon earlier, namely the kind of vertical-horizontal divide.

And I was reading the CSIS-CGD paper this afternoon.  And I was thinking to myself, you know, a lot of these recommendations that they make in that paper come out of the fact that this initiative -- or, sorry, this alliance was set up, you know, at the kind of, the heyday, the peak of the vertical approach.

And so I was wondering, you know, if you were to set it up again today, now, would you set it up in the same way?  Probably not, but what, you know, what specific things would you seek to change?

And then kind of building upon that and looking to the future, particularly in light of Gary's (sp) comments in terms of the global-health governance, what does GAVI look like in 10 years?  What should it look like?  Should it continue to exist?  Should it be eventually brought back into the WHO?  Should it be merged with other institutions?  What's the kind of successful vision for GAVI?

BERKLEY: So that's a complicated set of questions.  In terms of the vertical-horizontal, you know, I've got to believe that immunization is one of the critical system-building interventions that have occurred around the world.  I mean, it's the one intervention we've gotten to every person on earth, you know, during the smallpox era and during the polio era as well.

It certainly has built health workers and cold chain and distribution and surveillance and all of those things -- laboratories for polio eradication, et cetera.

So in a sense, although it is vertical, it's vertical with lots of horizontal roots.  And that's why people have talked about kind of it being diagonal.

You know, what's GAVI going to look like in 10 years?  I don't know.  I would suspect that, you know, in a different world, you might have had the governance structured slightly differently.  But it is critical to have the key players to be part of the discussion.

And I think in a world where there's nervousness in some of the U.N. bodies with interacting with industry, we can't have that.  We have to have industry engagement; we have to have the broad range of partners engaged.  And so I think there may be, you know, slight changes in -- you know, in actual mechanisms or how it functions.  But the concept of bringing everybody together to solve a problem and aligning them and driving that forward, I think, will remain.

Hopefully, WHO will be strong and remain a very strong partner, and its fiscal situation will get better.  We have new leadership at UNICEF, very exciting new leadership at UNICEF who is reigniting their focus on immunization, which they had, you know, under Jim Grant and, you know, (some of them ?), but it's somewhat gone down.  And there's a real interest in now reestablishing that.  So I think it's a very exciting time for this field.

GARRETT:  I'm reminded of all the economists who poke a million reasons into why they hate the World Bank, but when they're really pressed, they say, if it didn't exist, we'd have to create it.  And I think that's how many people feel about WHO.

Laura from -- sorry -- Laura from FSG.

QUESTIONER:  Hi, Seth.  I'm Laura Herman with FSG.  And I want to follow up on that comment around GAVI being so uniquely diagonal, and your reference to the data that is collected around the effectiveness of the intervention.  And it seems like there's a great opportunity, in the spirit of more work that GAVI might do, to take on a learning agenda for the field in terms of vaccinations and thinking about a shift from (a valuation/evaluation ?) that sort of purely addresses the need from an accountability perspective to (a valuation/evaluation ?) that might better inform the field in terms of GAVI's own work and the work of its partners.  And I'd love your comments on sort of the appetite for that within GAVI.

BERKLEY:  I think that's exactly the spirit that GAVI should be seen in.  And I -- the one thing I didn't say to Robert's point was that the advantage GAVI is, is that it is a public-private partnership.  It is an independent Swiss foundation.  And so it should have the flexibility to reach out in different directions, to try different experiments.  And it has; it's done a lot of innovative work in financing; it's done innovative work in terms of, you know, how to engage with groups on the ground.  And it certainly should do innovative works in how we learn from this in the broader experiences.  And so my hope is, is that we will continue to do that, and do that better.

It's interesting, because as we think about doing HPV, that's going to be a huge challenge, because we don't have simple delivery systems.  And one of the questions is, what does that partnership look like?  Are we going to use -- is it -- is it a vaccination program, or is it a program to reach adolescent girls who also need, you know, information on family planning, who need, you know, sex education, who need nutritional information to be good mothers; it may mean --

GARRETT:  (Identity cards ?)?

BERKLEY:  -- rubella vaccines, you know, et cetera, et cetera?  So there's a way to look at that.

And I think we're seeing the same thing now with both diarrhea and pneumonia, because these are vaccines we have against specific organisms, but they have to be seen as part of a continuum of interventions to try to reduce deaths from these illnesses.  And so we have a lot of learning to do.

GARRETT:  Emmanuel from IRC.

QUESTIONER:  Thanks.  I'm Emmanuel d'Harcourt from IRC, and I appreciate your comment on the kind of last-mile countries in which IRC primarily works.

So I had a question regarding -- which echoed some of the earlier ones about implementation versus a financing-new-vaccine focus, which at least publicly has been what GAVI has been most associated with.

So I was curious to know -- while I understand that it might not be GAVI's sort of mission, would be curious to hear from you how -- what interest there is on the implementation issues -- for example, things such as the technology, the handheld -- are there local technologies that could -- that's been vastly underused -- with the whole performance-based financing issues -- you know, in that article in The Lancet about the effects, sometimes, of that on both locally and on the national scale; and the issues such as, for example, campaigns and these serious side effects they can have on their health system versus the kind of building aspect that routine vaccination has.

So we certainly, as an organization, believe that GAVI should have a role and that more attention to this would be helpful.  But it'd be curious to know how this fits in with your priorities.

BERKLEY:  And as I said, I'm not there yet, so I can't speak on behalf of the organization.  But I would say that there certainly is interest in trying to understand how to do this work better.  And so one example would be on, you know, trying to figure out -- understanding diseases and understanding immunization coverage -- for example, if there were simple ways to do surveys.

For example, people do filter-paper surveys now for HIV prevalence as routine part of activities.  If you could, at the same time in that filter paper, do a routine survey and look at, you know, a diptheria or tetanus coverage, or you know, pertussis or something that would allow you to say, gee, here's what we think -- here's what we -- what the statistics tell us is coverage, but here is real data that can validate that system -- not as a routine thing, but as a study -- that would be a very useful tool.

The folks at -- out in Seattle -- Chris Murray's group -- is looking at trying to get better data at country level (and/in ?) strengthening systems.  They're using verbal autopsies as a mechanism to try to do disease surveillance, and understand what the incidence of disease -- all of these are going to be critical tools.

But these may not be things that GAVI's doing.  It may be what we're doing with our alliance partners.  So these may be Gates Foundation-funded things, or WHO-funded things.  But they're things that should be rolled out in-country so that they can be used.

GARRETT:  Let me jump in on that.  One of the questions we all have is, how reliable is any data that we're using to assess health achievements, health needs, when it comes to child mortality and infant mortality?  If you look at Chris Murray's data, as you pointed out, it's not at all clear how much of the contribution to declines, which have been substantial, in child mortality is due to immunization versus such simple things as access to classrooms to go to school, or the proximity to a safe drinking water pump.

So how will you go about reliably assessing the effectiveness of GAVI's efforts?

BERKLEY:  I think that's -- you know, you've articulated the question.  And the point is that we won't run the other way from those questions.

I remember when we did -- I was on the World Development Report team in 1993, the original Global Burdens of Disease.  And you can imagine the controversies.  And we basically said, you know what, fine.  Here's the rules.  You can only die once, right?  So they -- no, because, you know, you had -- if you added up all the deaths from diarrhea, from HIV, from TB, you'd -- people would be dying three times over.  So you only die once.

And then, if you don't like the data, give us better data.  And so we just took a stab at it, and what that led, is it led people to do other studies and do other work, and improve upon it.  That's the type of process we have to have.

And so if we come in and say religiously, you know, we saved this number of lives or this many people or whatever, then forget it.  It's got to be evidence-based, and we have to have a process that's about continuous improvement.  And if somebody can prove that the numbers are wrong, we have to accept that.

And my prediction in the next six months is, you're going to see some very interesting numbers come out that are going to change a number of the groups that have been advocating for diseases.  And I think we're going to see new data all the time that's going to show that.  (I think we have ?) some interesting ones recently.

GARRETT:  Can't wait.  Well, let's hear from bench science, or as close to it as we can get.  John Moore from Cornell.

QUESTIONER:  Thanks, Laurie, but this isn't going to be a bench-science question though.  So both you and Seth have mentioned the existence of the anti-vaccine movement, which undoubtedly has a now-very-quantifiable impact on vaccine uptake in America and Europe, and for other reasons in part of Africa.

And it is a movement, and it's an organized movement with a leadership that in many cases makes substantial incomes from it.  And it's fostered on the Internet, which is hard to deal with.  But it's also promoted in the media and in celebrity news programs, magazines, newspapers and so on.

And yet, I don't see a fight-back against them of any organized way.  I don't see any centralized effort to depropagandize the myths that they perpetuate.  Do you see a role for GAVI or any other organization in providing central scientific leadership in this fight?

BERKLEY:  It's an excellent question, and I would say that probably half of those people have your email address, so I know that -- I know somebody that's corresponding with them and fighting with them.

But you know, the challenge has always been, you also validate people by having fights with them on these issues.  And often, we've made the situation worse by taking on groups, particularly if data doesn't matter.  I mean, that's one of the problems.

And so I think the answer is, this needs a careful look.  Certainly, the pharmaceutical companies have looked at it and have gotten alarmed, and tried to do something.  But then, that was hard because they end up being the brunt of the attack.

And so governments have tried and have worked together.  And you know, I don't know yet if GAVI has had any role to play in working with other governments.  But I think it's an important area.  I suspect it's one that we will cheer on rather than lead, but you know, I'll have to answer that once I get there and understand what the program has been.  But it's a real problem.

GARRETT:  From the U.N., Priya.

QUESTIONER:  Hi, thanks.  I'm Priya.  I work at the office of the secretary-general in the U.N.  I was at the Pacific Health Summit last week, which you were also at, and I heard you spoke -- speak.  And one of the big focuses was on middle-income countries and how these countries could access GAVI prices -- maybe not the vaccines themselves, but the prices.

And I'm wondering how you might think about engaging the developing-country vaccine manufacturers to provide some type of vaccines for middle-income countries, even if it's just a portion of the countries that are most in need.

BERKLEY:  So again, in an ideal world -- and I don't know whether this is going to be GAVI's function or not -- you probably create another tier of graduating countries out of GAVI, and then the next income up.  So let's say if GAVI stops at 1,500 or 2,000, maybe between 2,000 and 3,000, 3,500, these are very poor countries. But they can probably afford a little bit more than GAVI.  So one of the issues is trying to get price tiering for them.

Somebody could create a revolving fund for those countries that would allow them to purchase -- take the advantage of purchasing in large quantities and drive down price over time.  It would help the pharmaceutical industry if you could give them reliable quantities of vaccines and allow them to again scale their process engineering such that they could produce vaccines cheaper, at least for the ones that will, you know, scale to a cheaper vaccine.  And so I think that's waiting to happen. What the right mechanism to do that is, I don't know.

One of the exciting things that happened is a number of the vaccine manufacturers, as part of their commitments to the GAVI replenishment, have announced that they will continue GAVI pricing for graduates, because one of the problems was you'd graduate, you'd have to take over your vaccine price but you wouldn't get the GAVI price; you'd now have a price that was much higher, a middle-income price, or you'd have to buy it in the open market.  So I think that's going to help.

But what we can't, probably, have is that price extend all the way up, because, you know, that will kill the manufacturers.  And right now PAHO has been one of the -- you know, the issues that's been interesting.  PAHO has demanded universal pricing for all of the PAHO countries, from the poorest country up to the richest countries, and that's created a difficult situation for manufacturers.  For the first time on the rotavirus, the GSK pricing that they've offered GAVI, the agreement was made that they would accept that that price was way below what the PAHO price was for it.  So I think we're beginning to see these changes and acceptance of tiering, and that's going to be something we're going to have to work on actively.

GARRETT:  Our last question comes from the Earth Institute, Millennium Project, Columbia University, all of the above.  Yolana (sp).

QUESTIONER:  I was thinking that a lot of things have happened in global health the last 10 years, and of course GAVI and Global Fund and Bill Gates were probably the three most important things that happened in that space.

With the increased funding through the Global fund, it also became a great mechanism to build capacity in the countries to actually build their own health plans.  How do you see moving forward, and everything we have learned -- good and bad lessons, both from GAVI and the Global Fund -- how do you see it moving forward in terms of really strengthening that capacity and having a more health systems -- or a system approach for Global Fund and GAVI, and how to really -- how should I say -- capitalize on the fact that GAVI has this flexibility and can play a much more catalytic role than the U.N. agencies or WHO?

BERKLEY:  Again a complicated question.  I'd expect no less.

What's interesting is that GAVI has gotten into the health systems financing platform with the World Bank, with the Global Fund and with some technical assistance from WHO.  Now, I have to say I don't know a lot about that.  I don't understand it fully.  And I know there's been some concern that if we get into too broad a platform, that we might not be able to help drive forward immunization, which has to be one of our critical requirements.

So how do we make sure that we coordinate with the rest of the donors, support the national health plans, but also make sure that, you know, the (cold chain ?) we talked about or other systems are in place to do the immunization that's necessary, particularly as countries are scaling up all of these new antigens.  We went from six antigens, you know, up to right now WHO has 33 antigens on their list.  So it's been a huge change and we're going to have to build systems to do that.

So in principle, certainly I'm supportive of looking at it as a sustained system and we do have flexibility, but we don't want to lose the immunization part of that in that process.  And I think that's going to be the challenge.

GARRETT:  Well, on behalf of everybody in the room, I wish you a safe moving experience, as minimal amount of hassle, minimal amount of Swiss tariffs and other nastiness that -- (chuckles) -- can occur when you move from the United States to Switzerland.  And thank you very much, Seth Berkley, for joining us here today.  (Applause.)

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