Steve:                Welcome to Scientific American Science Talk, posted on January 30, 2015.  I'm Steve Mirsky.  On this episode:

Susan:                In 1990 under-five mortality, 1 in 10 kids in the globe died under five.  Just so unacceptable, so not okay.  That number is 1 in 20 this year, it's expected to be 1 in 20, so cut in half.

Steve:                That's Dr. Susan Desmond-Hellmann, the chief executive officer of the Bill & Melinda Gates Foundation.  She's an oncologist and was formerly chancellor of the University of California at San Francisco, where she remains a member of the faculty.  During her training, also at UCSF, she spent two years as a visiting faculty member at the Uganda Cancer Institute, studying HIV/AIDS and cancer. 

On January 26th Desmond-Hellmann and Scientific American Editor in Chief Mariette DiChristina sat down together here in New York City for a far-ranging discussion about the goals the Gates Foundation set forth in its recently released annual letter.  You'll hear me pipe up as well.

Mariette:            I understand you have some news for us this year about why 2015 is so important as far as public health and development?

Susan:                Yeah, 2015 is a very significant year for the Bill & Melinda Gates Foundation.  And Bill and Melinda just came out with our annual letter, that now has been traditional since 2009, and they take the time to talk about 2015 and what a pivotal year it is.  For us internally, in our own small way, we're turning 15, so we're moving from adulthood, as one does at 15.  But it's a really special time for reflection, as any milestone anniversary is.  And so as a foundation we're asking what's gotten done as a result of our efforts with so many collaborators and others, but really taking stock at 15, and more importantly, what do we aspire to get done in the next 15 years as a result of all of our collective efforts.

                           And Bill and Melinda then look at in the bigger context of the world the millennium development goals in the parlance of the U.N. the MDGs were set with a timing of 2015 as being the finish line for the millennium development goals.  And the U.N. is now in a business process that will lead to September setting a new set of goals for the globe, the sustainable development goals, or the SDGs.  So again, the reflection of the work and the reflection in the annual letter, and for all of us a good chance for stock taking, how do we do on MDGs.  And obviously the timing will be September, where that's done in full throttle.  But a really important time to look at what should be the globe's aspirations for the next 15 years, come 2030, which is hard to do, where do we want to be.

Mariette:            So let's pull – tease that out just a bit more, 'cause I'm very excited to hear about where we ought to be going, and I know the letter had some thoughts about that that were shared already.  So what can we see in the next few years that are coming up?  And then let's talk about how we could start to work together.

Susan:                Well, let's just take one of the areas that we focus on, global health.  It's an area that I think is perhaps one of the most famous of the areas the Gates Foundation works on and where such important progress has been made.  So one metric – we like metrics, as you know – one metric that just so resonated for me, in 1990 under-five mortality, 1 in 10 kids on the globe died under five.  Just so unacceptable, so not okay.  That number is 1 in 20 this year, it's expected to be 1 in 20, so cut in half childhood mortality, mortality in under-fives.  By 2030, 1 in 40 children under five dying.  That's just a remarkable set of numbers that tell us about progress.  So why; childhood deaths continue to be driven by pneumonia, diarrhea, but so often, too often by preventable diseases.  So as a foundation we're strongly focused on vaccination.  Vaccinations for us are so important, can we prevent these diseases, preventable causes of diseases.  So it's not just tackling scientifically the vaccine-preventable deaths; it's an equity issue.

Mariette:            Let's talk about that a little bit while we're on this equity issue of vaccines.  But also I think there's an information issue there; do local cultures feel good about that?  You know, how do we make steps there. 

Susan:                Yeah.  Like everything we do at the Gates Foundation, this is a collaborative effort.  So it starts with local communities; who are the leaders, what does drive their perceptions of vaccine, who's on the front line, front line healthcare workers.  So everything we do is a collaboration; it's with organizations and institutions locally that can understand what the impediments are to vaccination, but essentially it's with the ministries of health in each of these countries if it comes to vaccines.  So the ministry of health has a plan for their country on health, and vaccination is always a seminal part of that plan.  How do we work with them to overcome the obstacles?  Is it a matter of the coaching, the supply chain?  Is it getting those front-line healthcare workers? 

                           So our work is customized for those countries and those ministries and done in collaboration with multiple institutions, from UNICEF and WHO and Save the Children and GAVI, the institution that's now helping with purchasing and delivering of vaccines.  So all of that is required for us to make real that vaccine dream.

Mariette:            And let's look at the science side of the vaccine equation.  What things are we looking forward to seeing soon on that front?

Susan:                Well, I'm excited about the science in vaccinology, and I think that this science reflects something that I love about science in general, because I think you could call it science, you could call it innovation.  So it starts with some of the grants that the research group in the foundation has been giving out are meant to drive a better understanding of vaccine immunology; what does responsiveness to a vaccine look like, how do boost that immunology understanding?  So maybe you need one dose instead of two or three, which is major in the countries that we operate.  Are there some science things that we can do to make modeling better, so that you don’t always have to go to human trials, or you could do smaller, shorter human trials, which again drive a lot of expense?  So the innovation starts with the basic immunology, understanding how human beings respond to a vaccine.

Then you get into things that are innovative and incredibly pragmatic: what are the best adjuvants; do you need an adjuvant; can a vaccine stack the deck, so again, you don’t need a booster; are there vaccines that can be delivered without needing refrigeration; are there vaccines that can be delivered orally instead of requiring an injection.  So these are often translational, but again, essential and important. 

And then the last thing I'll mention on vaccines is the manufacturing behind vaccines; can new low-cost manufacturers really boost productivity.  Because often we want the cost of the vaccine to be very, very low, and that productivity, and something I learned in my 14 years in biotech, that productivity is driven by fantastic process sciences and process engineering.

Mariette:            Can you just, for the people who may be unfamiliar with the term, explain what "adjuvant" means?

Susan:                Well, an adjuvant is something that you add when you're giving a vaccine in order to boost the response.  So you are basically trying to suggest to the body's immune system, ramp it up a little bit, and an adjuvant is just what it sounds like, which is an add-on that's meant to boost that immunity.

Mariette:            Looking ahead, also in the letter, I saw that there was an amazing – in addition to what I think sounds like a profound reduction in early childhood deaths, which is something to really look forward to.  Also one of women during childbirth.  Could you tell us a little bit more about that and how that will be achieved?

Susan:                Yes.  Another one of the aspirations in the letter is between now and 2030 to cut by two-thirds maternal mortality.  This has frankly been an area that's been more challenging than the under-five mortality, and so important and so challenging.  It is essential to think about all aspects of that.  For example, one of the areas that the foundation is now funding is family planning, so that a woman, or a young woman in particular, can decide when she wants to become pregnant, that that's a decision that she can make, and she can space her children.  And so I think it starts with that.

We also have a big focus on nutrition.  So a mom having a good nutritional status when she's pregnant, again, very helpful.  And then again, working with local groups, with ministries of health, to make sure that a woman can deliver at a facility, where things are there available should she need the kind of care that having the baby at home wouldn't enable her to have.

Mariette:            Now a couple of weeks ago I got to speak with President Carter about the Carter Center's announcement with Guinea worm, getting down to 126 cases in 2014 from 3.5 million in 1986.  And the letter also speaks about perhaps seeing the end of diseases, such as polio and then tropical parasites like Guinea worm.  Can you speak about some of the advances there that you're working on?

Susan:                You know, disease eradication is really a special and wonderful thing.  It is special and wonderful because it's rare.  So in our history, in humankind's history there's been one human disease eradicated, smallpox in the '70s.  And I love reading and I love medical history and so I read Bill Foege's book House on Fire.  And I would recommend it to any of your readers if they want to read about the reality of disease eradication.  Bill does a great job in that book of allowing the reader to see this was not a gimme, how incredibly hard in India in the most difficult circumstances smallpox was eradicated, what that has meant to the globe, that we don’t have to worry about smallpox anymore.

And so there are two diseases I'll mention on this front in the short-term that are in our sights.  One is Guinea worm, and President Carter and the Carter Foundation have just done a magnificent thing without a pill, without a vaccine, largely through education.  But really a deep, deep understanding of the transmissibility, what exactly happens, what are simple, affordable tools that you can use, like filtering your water to prevent retransmission, and dedication to understanding where those last kilometers are and how to stamp that out.  So some of this is innovation and technology on disease tracking, something very important today.

So Guinea worm is in the world's sights for eradication, and then the other one is polio.  Last year India celebrated three years polio-free in India.  Really remarkable.  And in 2014 there was a 75 percent reduction in polio cases in Africa.  And so in sub-Saharan Africa polio eradication is within sight.  A lot of good things have to happen, it's enormously challenging to do this, but Nigeria made great strides to only six cases of polio in 2014 and a major, major improvement.

Now on the other hand, Pakistan was a very bad year in 2014 with a lot of unrest, a lot of difficulty, and Afghanistan remains a place where polio is endemic.  So I think that the experience with polio shows how challenging it is to eradicate diseases, but to have Guinea worm and polio in our sights is a wonderful thing for the globe.

Mariette:            I'd like to ask you just one more question about that.  I mean you mentioned a very important factor.  I mean the Foundation has been so involved in public health issues, but sometimes it's really hard to disentangle those from unrest that an area might be experiencing, or even violence.  Are there some lessons we might share with folks about how you do that or how you go about that?

Susan:                Yeah, I think it is such an important thing that it's not mysterious when you say the three countries left in the world that still have endemic polio are Nigeria, Afghanistan, and Pakistan.  So it's not uncommon in the world of public health or global health that we have a scientific remedy, and things that get in our way aren't science or technology-related.  So I do think that it goes back to the point I made earlier, about partnership and collaboration.  There's a part that's civil society related and the people in those towns, in those villages, in those rural areas demanding a better life for their children, demanding that they have access to something that can protect them and their families, that’s where this disease eradication starts.  And understanding the impediments, understanding how to overcome them and that they might not be science impediments is a critical lesson that was actually learned in smallpox, and we continue to relearn in disease eradication.

Mariette:            While we're on the topic of disease eradication, I know the Foundation has spent an awful lot of time and effort on malaria with others.  And one of the predictions is that we might finally find some of the keys to getting to really crack that nut.  Can you speak to that a bit?

Susan:                Well, the big bet for 2030 on malaria is that by 2030 we'll have some of the tools that we need to make it possible to think about malaria eradication.  I mean I think it's important not to over-promise, and malaria I've read some of the history.  We've thought we could crack malaria over and over again, and we were wrong.  And so what I'm excited about now is a deep understanding of the life cycle of the malaria parasite, a deep understanding of the role of mosquitoes in transmitting malaria, a real tackling of resistance, be it resistance to insecticides or resistance to anti-malarials is behind this, and a serious effort on a malaria vaccine is all part of what the Foundation is focused on and investing in.  And the final thing is, like in so many areas, improvements in the diagnostic side.

Mariette:            You mentioned a deep understanding a couple of times in our conversation so far, which I don’t want to put words into your mouth, but could we say that that involves basic research and understanding of the underpinnings, the mechanisms that underlie any particular disease and the mechanisms in the body?

Susan:                You know, you don’t have to put words in my mouth; I will tell you.  And, you know, my background, I'm an oncologist, I'm a cancer doctor, and I lived through a training where the best we could do is ever-increase the doses of chemotherapy.  Even needing bone marrow transplant to rescue patients from these big, big doses of chemotherapy.  In fact, I was at the Uganda Cancer Institute in global health, and the Ugandans had a name for Adriamycin, they called it "saba saba," and saba saba is the word for the big red spark that comes out when you're being bombed.  So they call their chemotherapy, which Adriamycin is red, for people who don’t know that, and the Ugandans knew it was so powerful that they call it saba saba.  I mean that just tells you everything you need to know about traditional chemotherapy.

                           So I got to live through an era where we used a deep understanding of cancer to markedly improve cancer therapy to targeted therapy, and now we're in a new revolution with cancer immunology.  So I'm not a basic scientist, and I love basic science more than virtually anybody I know, 'cause I've seen what can happen if you get it.  So when I look at the global health issues that we're trying to tackle – I just talked about one, malaria.  If we understand transmissibility, where's the malaria coming from, what's the role of the human host, what's the role of the mosquito; if we understand the immunology of the attempts that have been done on vaccinology previously in malaria, why didn’t they get us where we want to go in malaria?  Understanding basic mechanisms of resistance, what if we could swap out therapy as fast as we can today in HIV, because we understand the mechanisms of resistance?  So malaria, the more we understand at a molecular level what's going on, the better we will be at making tools to solve malaria.

Another disease that the foundation has been deeply focused on is tuberculosis.  And tuberculosis is something that frankly I haven't thought about in a while in my career.  And when I look at the investments we are making as a foundation and what we need to make progress in tuberculosis, we need so many things; we need shorter therapy, we need more effective therapy, we need therapy for resistant tuberculosis, we need to deeply understand the relationship between HIV and TB co-infection, which is so important in sub-Saharan Africa. 

You could basically write 50 R01 grants, to use the parlance of a basic scientist, for tuberculosis, and I would be so much more bullish on our ability to solve it and to make a difference.  So I'm excited that the Gates Foundation thinks that investments in basic science are part of solving these really big global problems, but like with everything else we do, we depend on National Institutes of Health, Howard Hughes Medical Institute, Welcome Trust, and others, thinking about those basic bets on deep understanding, and they may not be disease-related.  So they can be basic science questions and answers that help us understand fundamentally how the body works.

Mariette:            I'm so glad you're making the point about basic research, because for instance, I'm often reminded of Elizabeth Blackburn, the Nobel laureate and telomere research, and she started by studying pond scum.

Susan:                That's right.

Mariette:            And whoever would have thought that that would have led to a deep knowledge of how we age and how we might have longer, healthier lives, right? 

Susan:                Well, the Rous sarcoma virus and Bishop and Varmus's work, that again, was not at all directed at Herceptin, the breast cancer drug, opened up everything that was possible for us to make that drug.  And so I love Liz Blackburn's stories about pond scum because they help teach us that a fundamental enzyme that you think about now with Alzheimer's and cancers started with her work on pond scum.

Mariette:            Right.  And then had huge impact elsewhere, and financial ones, for people who don’t think basic research is worth funding.

Susan:                Well, having been at Genentech, the world's first biotech company, I often loved to tell the story of recombinant DNA technology and how in 1975 that probably seemed like, okay, sure, Herb Boyer and Stan Cohen, you discovered something about how DNA can be recombined.  That sounds esoteric, that sounds meaningless.  They created, then starting in 1976, an entire industry.  So from every perspective, if you like solving disease problems like I do, and if you like business, which I also do, it's fundamental that technology breakthroughs create opportunities.

Mariette:            I'd like to just hitch back to something you mentioned before, you talked about your time in Uganda.  Were you there a couple of years?

Susan:                A couple of years, yes.

Mariette:            And I'm also thinking about the threat of equity, which we've been talking about.  Were there some lessons maybe that you got there that you are applying more broadly to how we deal with equity issues in the U.S. and elsewhere where the Foundation is working?

Susan:                Well, absolutely.  So I-

Mariette:            And tell us what you were doing in Uganda also.

Susan:                Yeah.  I was loaned to Makerere University with my husband, Nick Hellmann, as faculty members starting in 1989 through a Rockefeller funded project to study heterosexual transmission of HIV and Kaposi sarcoma.  And the – let's talk about equity, because I think that it's a fundamental value of the Gates Foundation.  It's one of the reasons I'm at the Gates Foundation, that all lives have equal value resonates for me.  And what that translates into is ambition.  The huge difference that the generosity that Bill and Melinda has brought to this field has made, and a big shift now, 25 years from the time I started in earnest in global health is ambition.  So thinking about bringing molecular biology to problems that the globe has, thinking about basic immunology breakthroughs and better vaccines and better treatments and better diagnostics for these diseases, and that that should be made available for people who are poor just makes me feel like the world is going to be a better place. 

                           What I learned working in Uganda is there are incredible colleagues, incredible colleagues who need to be part of all solutions.  So I worked with some tremendous colleagues in the medical school, Makerere Medical School, very famous in East Africa.  And when we put our heads together the best things would happen.  And so that's a lesson that I remind myself at the Gates Foundation, that people who are there in the field who know what it's really like will tell us when our solutions make no sense, will make massive contributions to the innovation that we seek, and always are better placed, not just pragmatically, which is obvious, but often scientifically to think creatively and in an innovative way about solving problems.

Mariette:            You also just mentioned HIV, and one of the things I remember that was in the letter was forcing HIV to a tipping point in the coming years.  Can you speak to what the tipping point is and how we might see that?

Susan:                Yeah.  The tipping point is a point in time when more people go on therapy that are newly diagnosed with HIV.  That's the tipping point described in the letter.  And it is also I think in a reflection of how far we've come with HIV that if you're in a rich country it no longer is a death sentence.  Unfortunately, if you're in a poor country, because of cost and access issues, it remains an enormous issue and the logistics of lifelong antiretroviral therapy, logistics including cost and the impediments to lifelong antiretroviral therapy are a huge issue in sub-Saharan Africa and a huge issue globally.  So like with other illnesses, continuing to push on innovation, continuing to push on better tools to solve HIV is an important part of our HIV focus.  But the tipping point of having, again, created by science and innovation, highly active antiretroviral therapy getting to more people that are newly diagnosed, that says something about how far we've come.

Steve:                On the Ebola front it's a very small data set, but the folks who either contracted it here, healthcare workers, or were diagnosed once they got back here, they all did very well.  So what does that tell us about the role of poverty in the Ebola crisis in Africa?

Susan:                Well, what appears to be differential mortality I think tells us something really fundamental about access to the basics.  And you can look at that through two lenses, neither of which make you feel good.  One is how did this epidemic spread, get so big so fast.  It was the absence of a working health system in these three countries, so fundamental basics of a health system weren't in place.  And secondly, why has survival been so poor?  What we're talking about are the basics of intravenous fluids and the ability to have an IV, as we call it.  So some of those basic things need to be in place for people.

                           So I think it's the Ebola points out to us the inequities that are there on basic health systems for spotting epidemics and a really low bar for the kinds of things people need to survive when they're very, very sick.

Steve:                Yeah, 'cause I think part of the freak-out here about Ebola was the mortality rate that we all heard about, but it turns out that mortality rate is related to this basic healthcare issue.

Susan:                It's related to basic healthcare, it's related to a rapid diagnosis; so you have to be seen in the front lines, you have to have the ability to tell the difference between Ebola and malaria or other things that cause fevers much more commonly in these countries that have been affected.  So yeah, absolutely, people here were worried because they were hearing 70 percent, 80 percent mortality, and that's not been the case in the United States, or in the United Kingdom.

Mariette:            Now you remind me of the Global Citizen initiative, just saying to continue to push, because we've already talked about quite a lovely number of activities.  How do you get focused on so many by harnessing the crowds around you?

Susan:                Well, I'll tell you, and we've mainly been talking about global health, there's also farming and banking and education in the annual letters.  So the ambitions at the Gates Foundation could be called audacious, and yet it's so important that – and I love the Global Citizen part of the annual letter.  Possibly it's my favorite part of the annual letter, for two reasons.  One is the concept of Global Citizen reflects something that's always been true with the foundation, and that is we're trying to kind of set up conditions.  You know, our investments are small given the problems that we care about and the problems the world is dealing with.  So we're trying to set up the conditions, if kids survive to the age of five, they have a chance.  You know, if mom survived childbirth they have a chance to have a family that doesn't have to go without mom.  I mean these are just basic fundamental equity issues. 

But even though we believe strongly in the bets we're placing and the investments we are, the Gates Foundation by ourselves can't do anything.  So it definitely, you know, the words that have been used, I think by Hillary Clinton, "It takes a village."  In this case the village is the globe.  So first of all, none of what's written about in the letter is possible without a global effort, and we're really humble about our role in this, and we need to be, so it takes everybody. 

But the second thing is what Global Citizen can do is to bring in people who have big hearts.  We're optimists and we believe people have big hearts, and often those people with big hearts don’t know what to do.  So they'll say, "Well look," me, or my kids and me, or my family, "we're reading about this, and we're reading this letter, and we're moved to action.  But we don’t know what that needs to look like.  We actually care, but we're puzzled."  You know, for example, a teenager, a college student may say, "Look, I'm in the middle of my studies.  I'm not going to fly to Uganda or Ethiopia and do this" or to India.  So what Global Citizen allows us to do is to say, "Look, we do believe people care about these issues.  We do believe people care about equity." 

So sign up, so it's GlobalCitizen.org, you can sign up and be part of a movement, and in doing so two things can happen; one is you can get more information about this, so you can read, you can study, you can educate yourself about the globe.  And in doing so, you can be selective; we don’t know what's going to move you.  I've talked to people about the banking part of the annual letter, and using now ubiquitous cheap cell phones to access insurance, to access loans, to be able to save for a health emergency or to send your kids to school.  What a beautiful thing that poor people haven't had access to.  If that gets you excited, terrific.

If on the other hand you're really excited about education and seeing if kids all over the world, adults all over the world could have access to really high-quality online education as a result of efforts that are going on globally to improve that kind of curriculum development and those kind of products, terrific.  So I think the Global Citizen reflects not only our understanding, none of this happens without a global effort and multiple partnerships, collaborations and a lot of teamwork.  But also that everyone across the globe can be involved in their own way.  And they can customize their involvement in ways that reflect their own finances, their own intellect, their own interests, and their own passions.

Steve:                That's it for part one of the Scientific American conversation with Gates Foundation CEO Susan Desmond-Hellmann.  We'll be right back with part two.

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