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Diplomacy in Action

Feeding the Future: How Infectious Diseases Undermine Our Battle To Achieve Food Security


Remarks
Dr. Cynthia Baldwin
Washington, DC
July 9, 2010

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Andrew Reynolds:  Good morning, ladies and gentlemen, and welcome to the State Department, our outside guests, our colleagues from the State Department USAID welcome as well. My name is Andrew Reynolds, I'm the deputy to our science and technology adviser to the Secretary of State, Nina Fedoroff, who would like to be here, but she is in Santa Fe today, the Santa Fe Institute, for a meeting.

To those who are newcomers to our series, this is a lecture series we began two years ago, co�'hosted with the Oceans Environment Scientific Bureau of the State Department to feature our Jefferson Science Fellows, and these folks are very special to us. Tenured professors from universities all around the country, who come to the State Department and AID for one year on assignment, embedded in an office in the State Department or AID, with the idea that they bring their subject matter expertise and their networks to, to the proposition of foreign policy and development, and we also ask that when Jefferson’s return to their chairs they stay with us as subject matter experts and consultants, and thus we continue to benefit. It's the gift that keeps on giving.

We appreciate the Jeffersons particularly because their universities support their time here in Washington. We help them with their per diem costs, their apartment costs and travel, but the salaries and benefits from these distinguished professors of science and engineering are all borne by their universities, and our program is rather unique. The National Academy of Science is our administrative agent for this program, and that gives us great convening power and reach to the university community.

The program is now five years old. We have 10 fellows working at State and AID this year, and we will soon be saying good�'bye to them as they return to their chairs in August. We will be welcoming twelve new fellows, in August, from universities around the country, to be interviewed both at State and AID again, and to begin their work in September.

So, it is something we want all to know about, and we have with this capacity now, these 10 will make 41 alumni, university professors from all over the country that we are looking to to continue to support our proposition of development and diplomacy, and the important work of science, technology and engineering in those activities.

With the 12, that takes us of course to 53, so it is a growing community, and I can tell you, we are beginning to feel not only the primary effects but now secondary effects as we see fellows, alumni begin to team with each other on the particular issues of the day that are so important to us.

Cynthia Baldwin is a special person because you don't often have a veterinary specialist in your midst in this community, and her issues hit between some of the great issues and intersections of those issues, principally food security, watershed management, of course the whole notion of nutrition and the developing world, and I think what she has to say to us this morning will be quite profound, particularly the implications of zoonotic diseases, and how animal diseases cross to humans.

Cynthia was embedded in the Office of Environment and Science policy, International Research and Biotechnology at USAID for this past year, and she has traveled rather extensively. You know from her bio, where she has been educated, Cornell; she is now at the University of Massachusetts, Amherst. We also have a Jefferson alumni from Amherst who is a nutritionist, specialist in nutrition, Kyla Dashetty and I'm sure that the two of them will be talking extensively after this experience here together in separate years.

I will ask without further ado for Cynthia to come forward, but I would like to say one last thing, and that is that yesterday, the Secretary of State and the administrator of AID, Rajiv Shah, greeted the Jeffersons, the 10, absent one who is having a bout with his health, and gave great gratitude for the time they have spent here with us, and Administrator Shah particularly singled out the two Jeffersons who have worked at USAID, Wayne Pennington, who has spoken to this forum before, and Cynthia, who will finish our series for this year. We'll start up again probably in September or October. But, I wish all of you the very best. I look forward to continuing to see you here, and I hope that you will give us all the �'�' give all our Jeffersons a round of applause for the great service that they have given the State Department and AID this year, and we are looking forward to having them in the future as well. Thank you very much.

[applause]

Cynthia Baldwin: I assume that is supposed to be on there. Okay. Good morning. It is my pleasure to be giving the final Jefferson Science Fellow lecture in the series this year and, I want to thank Andy and the entire staff’s office for giving me this opportunity. As Andy said, I'm a professor at University of Massachusetts, Amherst. I did work at one of the CGIAR centers in Africa for seven years in the ’80s, working on animal diseases. Those same two diseases that we're trying to develop vaccines for are still in need of vaccine development, and those are two of the examples I will be talking about today.

So, I just wanted to also mention that all of the remarks that I am making are things that are publicly available. It doesn't reflect the "feed the future" initiative, necessarily, of the administration. These are not policy comments. These are really my own comments, and we just made a play on words in terms of the title, you know, where are the impediments to actually being able to relieve the constraints in terms of food security worldwide, and infectious diseases in animals, as Andy mentioned, many of which go into humans, is one of those major constraints.

So, as we know from �'�' someone gave me advice for giving talk a talk to always start with a quote, so I looked around and then eventually I thought, well, who better than Secretary Clinton's quote. "The question is not whether we can end hunger, it is whether we will." But as I said, there will be some fairly major hurdles in being able to do that.

So, if we're thinking about the issue of hunger, one of the first things that we need to consider is how do we actually measure that? In the International Food Policy Research Institute, which is a member of the Consultative Group for International Agriculture Research, these are the CGIAR centers I alluded to which have been funded by multi�'lateral aid, but U.S. aid has been the primary donor since their interception in the ’70s, and so IFPRI, which is a fairly new member of this group, took on the task of if you want to �'�' if you want to end something, it is good to be able to measure it so you can see what progress you are making, and so using these three criteria, they set about doing that. So, it was the proportion of undernourished people in the people in the population, the mortality in children less than five years of age that was related to inadequate diet, and the proportion of underweight children less than five years of age, and they released their �'�' the findings of their study last autumn, and this map shows those results.

So, if they are red, they are extremely alarming in terms of hunger, and you can see there are several countries in Africa, Sub-Saharan Africa. There is five that are extremely alarming, and following that is the alarming situation of another group of orange countries, and also include countries in South Asia. Also, Haiti, it is difficult to see, and then we get to the serious, where it involves some Latin American, South American countries and so on, and these in gray are ones in which there was no data for. So, you can see there is a concentration of hunger, according to the index that they used in Sub-Saharan Africa and South Asia.

So, if we now look at that with another study that IFPRI did where they actually looked at poverty, these are people in extreme poverty that earn less than $1.25 a day. I guess, as you would expect, again, the red is where there’s more than 3000 people, and so this is the density map here, and again you see this concentrated in Sub-Saharan Africa and also South Asia, again. So, we have those two things which I think you would expect, is that poverty and hunger pretty much go hand in hand.

This is another quote that I thought was interesting, is the silent hunger crisis, because it affects one sixth of all humanity, and it poses a serious risk for world peace and security, and since that is one of the main things the State Department is concerned with, I thought it was an appropriate quote, and this is �'�' that point is illustrated by the various food security, end security crisis, shortages and increased prices that occurred in 2008, where there were actually food riots around the world, and these are just a few of the countries where this unrest occurred.

This is guarding bags of rice in Indonesia, and this is in Haiti. That's just two examples. So when we think of how to get out of, you know, to eradicate poverty and hunger, agriculture provides a means to reduce both of those, and in terms of agriculture, agriculture can include cash crops, but in terms of food crops, there is also a variety of different sectors involved.

And I want to focus on animal source food today, and its role in preventing under nutrition, which is one of the criteria for hunger in Africa, and so some of the things that animal source proteins provide that you can't get just from crops is some important micronutrients. They also facilitate absorption of iron from other foods, as well as providing iron themselves. They are also calorie-dense foods, and it’s been shown that if you increase milk, meat or fish �'�' so animal sourced protein �'�' or eggs, I neglected to write eggs there �'�' in children under five years of age, and most importantly, children under two years of age, it makes a huge difference in terms of their cognitive development, and it also reduces stunting, so stunting is a reflection of malnutrition, where the children are not growing normally, to the normal height.

And in older children, these are studies which were done both in east and west Africa, and also there are studies under way in older children showing that if you can provide animal source food to them in classrooms, it increases their energy and their ability to learn, their interest in the subjects and so on. And the other point I want to make is that in, you know, many areas in the world, but particularly in areas in Sub-Saharan Africa, there are pastoralist groups, like the Masai and Zimbru and so on that depend really on animals as primarily their only source of food, and I just wanted to mention that some of these studies about the nutrition and the effect have been supported by USAID through the global livestock CRISP, which is a five-year program that just ended, and was a program among university faculty in the U.S. who then went into these studies in Africa.

So, as I said, I want to focus on livestock today, and a recent study that just came out. I went and heard a presentation on this recently that showed that if you look at case studies, like where has agriculture succeeded in Africa, because there are certainly many instances where it has not succeeded, and what are the biggest reasons for succeeding or not succeeding, and these are the three things that that study showed: that it’s access to markets, it is pests of crops, which includes infectious diseases, and infectious diseases of animals are the three main constraints that they have identified.

So, if we look at livestock, and specifically cattle, here is another IFPRI map. These are very useful maps to overlay when you are looking at these sort of parameters, and you will see that cattle figure in Sub-Saharan Africa quite widely. This, again, is a density map, with the darker red being the more animals, and you will see in South Asia a very high density of cattle, and in South Asia and India particularly, they have talked about undergoing the white revolution, playing off the green revolution, of course, which was to increase crop yields. In this case, it’s milk yields, and increasing the dairy industry in India.

So, in Sub-Saharan Africa, the infectious diseases of cattle affect food availability, which would be obvious in terms of meat, milk, and many of the pastoralist groups, the Masai, for instance, actually use blood as part of their diet, and also they affect food availability in terms of having the animals available for planting crops and so on is also very important.

It also, the infectious diseases affect the ability to trade animals, so one of the ones across international borders, and one of the ones in cattle that is very important worldwide is foot and mouth disease, which is a viral disease in cattle. But, some of the other ones I'm going to mention today also are. And so in some cases, animals, there is markets going from Sub-Saharan Africa, like east Africa, Ethiopia, for example, to the Middle East. In some cases they want to import the animals live, because of religious reasons; in other cases, it is meat. It is easier to deal with the infectious diseases if it is actually at the level of meat, you can reduce the risk substantially. But when there is a big demand for the live animals, then it becomes a real problem to further spread these diseases.

And I would also just like to mention in terms of impact on domestic agriculture, some of these infectious diseases, such as foot and mouth, have always been a very large concern for USDA, and they have continued, even though we don't have foot and mouth disease here in cattle in this country. The USDA facility at Plum Island off Long Island in New York State, has always worked for a long time on trying to develop a better vaccine for foot and mouth disease because of the threat to our borders, and I think if you reflect back a few years ago, what happened when it came into Great Britain, what an incredible impact it had on the economy in that country, and also in other countries in Europe, and that it spread very rapidly. The ability to contain it required actually volunteer veterinarians from throughout the world who came and volunteered their time just to try to get that disease under control, primarily in England, although it did spread a little bit further, so that you had a whole army of veterinarians returning, coming, volunteering to come and try to control that one single disease.

And finally, as I mentioned already, humans get infected from animal diseases through what we call zoonotic infections, and that means they are infections, infectious diseases that are transmitted from animals to humans. They don't spread human to human generally, although there may be some exceptions that when we think of influenza, but in general, these diseases just go from animals to humans.

And it is indicated that 60 percent of human infections �'�' or actually, it was zoonotic in nature, and these �'�' so I just listed, this could be from wildlife, but also domestic animals, so since we're focusing on cattle here today, some of the ones that come from cattle are brucellosis -- which is also known as undulant fever -- leptospirosis, fever, which is also a problem in Sub-Saharan Africa -- and bovine tuberculosis. NIH has a program on ecology of infectious diseases which supports studies looking at the interaction between wildlife domestic animals and humans in terms of tuberculosis spread. Also, E. coli, with which you are all familiar, and African trypanosomiasis, which is also known as sleeping sickness. So, that's just to name a few of those important diseases. And here is an illustration showing the African trypanosomiasis, which is known as sleeping sickness in humans, is typically fatal both in cattle, resulting in wasting disease, and also in humans.

So, the top infectious diseases that affect cattle and therefore food security in Sub-Saharan Africa include East Coast Fever, which is unrelated to the current heat wave in Washington –

[laughter]

-- and the other ones that continued. In my time at USAID, I did interviews throughout Africa with various sectors that are involved in livestock, and these are the diseases that continually emerged as among the top constraints in terms of raising cattle and thus providing animal source food.

So, again, trypanosomiasis, one that the African Union considers the main one, is contagious bovine plural pneumonia; also, again, tuberculosis, Rift Valley fever, helminthes, and foot and mouth. And what you will see here in this list is that these infectious agents take on various forms. They can be protozoan parasites, ones that live inside your cells, as well as extracellular ones; they can be bacteria, as in the case of CBBP, tuberculosis, or viral in the case of Rift Valley fever, and foot and mouth or also intestinal worms, which are what hell minutes are.

And each type of infectious disease has things, may have things in common in terms of trying to make a vaccine, but also its own unique challenges, so, some of the diseases in cattle that I have mentioned are transmitted by vectors, so this would include tsetse flies, so tsetse flies can bite, infect cattle and then bite humans and transmit it that way, so the cattle are acting as a reservoir; also ticks. This is just a mass of ticks on this calf, and then of course ticks spread all around on this Holstein, and another vector which I didn't show is mosquitoes for Rift Valley fever, so if they are vector transmitted diseases, some of the things that have been used successfully, for instance, in decreasing the instance of malaria in humans are bed nets, and they have been very effective in getting the prevalence of malaria down, but by no means has it eradicated it, which is really the goal for malaria.

And so in Kenya, this is a picture from Kenya, where people are farming cattle in tsetse�'controlled areas and they make this insecticide�'impregnated, sort of bed nets for cattle, if you like, but this in itself is a low tech solution, but it poses additional problems, because then you have to of course cut and carry all of the feed for these animals that are kept in these enclosed facilities.

Similarly, for the tick transmitted diseases that include East Coast Fever, you put these cattle, you dip them for ticks, much as you would do for your dog or your cat, but these chemicals used for the dipping are very harsh on the environment, they are dangerous for the people who have to do this, and again, these are things that are not sustainable solutions. They have to be continually implemented.

So, what are the options for the ultimate control of infectious diseases that, you know, don't depend on things like mechanical isolation of the animals, and there is at least three areas. One is to breed resistant animals. Many of the indigenous breeds of cattle show a greater resistance to some of the infectious diseases in Sub-Saharan Africa, but the problem is that their resistance is only partial, and the animals tend to make much less milk, or have less meat, for example.

The second way is genetically modify the animals. We have heard a lot about genetically�'modified organisms in terms of crops, and now we're really in the age, for some years now been able to genetically modify animals. Recently the genome of cattle was sequenced and annotated. This was on the cover of Science in April, 2009, which my lab participated in, and so now that we actually have the genome sequence for cattle, some of these things may be a little bit easier to tackle. So, genetically�'modified animals of course are going to provide a real heyday for people who are against genetically�'modified crops. Now when we move to animals, we are probably going to compound the problems. I don't personally, from my own speaking, as a scientist, I don't see any danger whatsoever from genetically�'modified animals or crops, but not everyone perceives it that way.

So, finally, of course, developing vaccines, and the question here is why has it been so difficult to develop these, some of these vaccines, and I'm going to give you a couple of examples, and I just wanted to point out the White House fact sheet that came out a couple of weeks ago for the GA, and indeed mentioned in terms of looking at the whole food security issue, included a mention of livestock vaccines as a possible breakthrough.

So, some of the vaccines you would be familiar with that we have been trying for years to make include those against cancer, HIV and malaria, and we have still not succeeded, despite the fact that some of the earliest vaccines here were done by Jenner more than one hundred years ago, where there were vaccines made against smallpox using cowpox virus, which is a related virus, but some of these are very difficult.

So, why is it so difficult to make vaccines? Why if we have them against some things, why can't we have them against everything? It is because the mammalian immune system, which is conserved in animals �'�' so if you look at the immune system in a cow, it is very similar that in a human, there are idiosyncrasies of that and you do have to have appropriate tools and reagents to study it, but in general, they are quite similar. But they’re extraordinarily complex, and when you �'�' when someone gets some sort of immunological challenge, something that we refer to as an antigen, there are many different outcomes, and I put in -- in capitals there, "allergies," and when I teach this sort of thing at the university, I always say to my student audience �'�' of course on a volunteer basis, they don't have to respond �'�' how many people have allergies, and there will be a proportion, you can respond if you like, proportion who have allergies, and then the next question I asked, are there other people in your family who have allergies, and usually you see this sort of thing is in a family. So, there is �'�' there are genetic differences which pre�'dispose you to allergies, and we're all, we're all exposed to those allergens. We all walk around outside in the summer and the spring when there is incredibly dense pollen, but we don't all have allergies. Allergies are an immune response. They serve no good purpose, but they are nevertheless an immune response.

But, there is a good side to this if you happen to be one of the people suffering from allergies, which is that that same type of immune response, the choice to make a response that manifests itself as an allergy, is the same kind of immune response that gives you a better chance for resisting gut worms, helminths. So, if you are an allergy sufferer and you are going to be in a place where you are exposed to worms that live, parasitic worms that live in the gut, then you may have a better chance of not getting those.

On the other hand, the people who don't get allergies, and this is a very simplistic -- what I'm saying are very simplistic statements, but just to demonstrate this, if you don't get allergies, you may tend to make the other type of an immune response, which we have names for these. We call it a Th1, you know, there is a Th2, and if you don't have allergies, you may be better able to resist something like tuberculosis, for example.

And the other reason that it is so difficult to produce vaccines is that infectious disease organisms have developed ways to evade the protective immune responses, and particularly some of these parasitic diseases that have been around for a long time. So, I need to just spend a moment and introduce the immune system again in a fairly simplistic way, but you all probably remember from your high school biology that you talked about phagocytic cells, so phagocytosis was cell eating, pinocytosis was cell drinking, so this is showing you �'�' these are some of the phagocytic cells that circulate in your blood, they are known as macrophages. You also have them in all your organs, so they act as sort of guards.

So, this is a picture of a phagocytic cell, and these green rods are rod�'shaped bacteria, and you can see the cells put out these, these extensions, called pseudopodia, and they can take these macrophages �'�' sorry, the bacteria, and they eat them, and then this diagram, which you can see, they engulf the bacteria, bring it inside, and your cells have bags of enzymes which merge with this compartment to actually kill the bacteria, and the idea is the bacteria is killed, degraded and exocytosis the remains of that.

But, one way that, for instance, brucella, which I mentioned in my list, is able to survive, is the same thing for tuberculosis. They get inside, here is the macrophage, these little gray dots are bacteria, and then this is a scan �'�' a transmission EM that someone in my lab made, where you take a section of this cell, and what you see is here is the nucleus of the macrophage, and this is the cytoplasm, so we are looking sort of at this part, and each of these things is a bacteria living and replicating, so there is a number of organisms that have developed actually to evade this most fundamental and first line of defense in the host.

But, it's the �'�' that part of the immune system, just to back up for a moment, what we refer to as innate immunity, we used to call it natural immunity, so in other words, all of us have phagocytes, but every new organism that they see, they respond in the same way. So, the response never gets more efficient. However, when we look at the acquired immune system, this is the part of the immune system that is actually stimulated by vaccines and this is just a diagram showing you some of the immune organs. So you all have lymph nodes; if you have had an infection, say, in your face, you will find the lymph nodes swell up behind your neck, also under your arm and so on, and they are draining the infections back to the closest lymph nodes to actually start out this acquired or adaptive immune response. Other organs involved in the immune system are the spleen, Paris patches, and so on. So, if you ever wondered what all those organs were for, now you have some idea.

So, what happens when you get a vaccine? When you get a vaccine, what you are doing is actually introducing a component of the infectious agent itself, and you introduce that to the individual, so if this is the point �'�' and we refer to these molecules that induce immune responses as antigens. So you induce antigen A, and what you see if you look, take a blood sample, is you would see the antibody levels rising, so I'm sure that many of you have been diagnosed, or go to the doctor, you get a blood sample taken, and they look for something they refer to as a titer. The titer is looking at how many antibodies you have, and they can take a panel of different viruses, bacteria, whatever, and ask do you have antibodies to those, and it is a way to diagnose and see. If you have the antibodies to those, then you probably are infected with that. You could be recovering from the infection, but if they do it again a couple weeks later and it is higher, then you know you are actually getting the -- you have the infection.

And then eventually, the infection is cleared and those go down, so that's what would happen if you got a vaccine. But on the second encounter with antigen A again here, you get a much more rapid response, the response is much higher, and it is able to control the infection rapidly. So, if this was a vaccine example, this would be the dose you got as the vaccine, and now you are actually exposed to the infectious agent, you get this rapid, higher response, which is able to control the infection.

So, what do these antibodies do, because I think most people, I mean, they read about antibodies in the newspaper, they’re something that most people have probably at least heard of being mentioned. So, antibodies can do things. Say, if this is a virus, this could be a flu virus, they can coat the outside. These little green things are the depiction of an antibody. They can coat the virus and keep the virus from hooking to your own cells �'�' you're the host �'�' and in causing the infection, and that's how something like the flu vaccine that you get every year works. It induces antibodies, you then get challenged with the virus, the antibodies are already there circulating in your blood, in the interstitial fluids and so on, and they will coat the virus and prevent the infection if you have been vaccinated.

They can also help the phagocytic cells be more efficient at eating and destroying things, like viral particles, and this is an example of bacteria, and this is what the live bacteria look like, and after being treated with antibodies, and this is what the killed organisms look like. So, this is kind of the most �'�' antibodies are really the simple, most simple manifestation of the immune response.

So if we now turn to look at one of the diseases I mentioned, African trypanosomiasis, these are the tryps among the blood cells. So what happens? So, just to give you a little bit of background, what you can see is because of African trypanosomiasis, this is where �'�' it is carried by the tsetse fly, and this map of Sub-Saharan Africa shows the pink is where the tsetse fly is, and what you can see is there is very few cattle �'�' this is where the cattle is, it is outside of this tsetse zone, there is only a few places in green where we have tsetse and cattle together, really on the fringes.

So, as a result of the tsetse fly itself, there is a program under way by the African union to try to eradicate the tsetse fly, this is a very big challenge, but the tsetse fly carrying the tryps prevents the ability to have cattle in this, all of these areas here, in the pink area, so you can see a large area of Sub-Saharan Africa is excluded from raising cattle. And as I said, it also infects humans, and there’s 70 to 300,000 new human infections each year, and so it affects 36 countries in Sub-Saharan Africa.

So, what happens? Well, this is an electro micrograph of a piece of the parasite, and it has something on its surface called VSG for short, which is a variable surface glycoprotein, and what you find is that coating, which is the target for the antibodies, changes with time after infection. So you can see here, most of the parasites are black, there is one white guy emerging, then he �'�' there is a group, a wave, an increase in those, and now a blue one, and so on, so I �'�' what you find is that the parasite, it’s the same parasite, but it has a set of genes, and I won't go through the molecular biology of this, but it can switch which gene it is choosing to express, so to the immune system, the tryp, the same tryp, trypanosome can look blue, then pink, then green, and so what this means is the immune system does make a very effective antibody response, and the antibody response �'�' so here is the blue tryps coming up with one coat; the antibodies are made, and the tryp, this infection is cleared. But at the same time, the immune system is making that first set of antibodies, the tryp is already switching genes, and now presenting a different coat. And so the antibodies, again, these, you know, depicted as the blue coat here can't clear the pink, and so on, so you get these recurrent waves of parasites coming up in the blood of the infected individual or animal.

So, because of this, it is a very complex system. There is over one thousand different coats that the parasite could express. It may be necessary to turn to transgenics, and there is �'�' recently, the National Science Foundation funded a project with the Gates Foundation. Some animals, like African Buffalo, and also some of the non�'human primates have a natural resistance mechanism which when coupled with antibodies can actually control �'�' it is not that they don't get infected, they do get infected. They do have that first wave, but then they are able to control the infection, and so they are looking at taking genes from baboons and putting them into cattle, so that now the cattle will have their antibodies as well as these other genes which code for an innate resistance mechanism.

So now to conclude with the second example, East Coast Fever, also known as theileriosis in cattle, this was also mentioned in Secretary Clinton's speech two weeks ago when she was talking about the research strategy for the feed the future initiative, so East Coast Fever, it is a parasite, protozoan parasite related to the malaria parasite of humans, but it doesn't affect humans. It is in eleven countries in Sub-Saharan Africa. There is a million cattle that die per year, one cow every 30 seconds, and you can see there is $300 million lost from animal deaths, and also another 20 million �'�' I'm sorry, 20 million small holder farmers affected, and another 100 million that could be saved from not having to go through the chemical tick dips if we actually had a good vaccine for this.

And this one is very different. The tryps, if you remember from that picture with the red blood cells, they live free with the blood among the cells. In the case of East Coast Fever, this is a very tricky parasite. Like malaria, it can live inside of host cells, so these would be �'�' these are the cow lymphocytes, these are the cells of your immune system, these are the white blood cells, you expect them to be protecting, so what this parasite has done is it's figured out how to get inside those cells and live, and these �'�' these �'�' this is called the shyzon (phoenetic) stage, again, it is a tick�'transmitted disease, it has many stages, but at this stage, these are replicating inside. This is the nucleus of the lymphocyte, so they are replicating inside these lymphocytes, and what they do is they, what we call transform the lymphocyte, so they make it, it is like a cancer cell that continually replicates with no outside provoking it from any other. You don't need special stimuli. Normally, we expect our cells to divide when we tell them to do this. In this case, just like a cancer cell, they divide every 21 hours. So, very quickly, they overwhelm the animal, so that within less than 21 days the animal is dead after getting bitten by the infected tick. So, it is a very rapid, very devastating disease in cattle.

So, to fight an infection like this, where you have the actual infection inside of the host cell, you need another type of lymphocyte, which we refer to as T cells or T lymphocytes, and also our killer cells, and these cells can recognize that the parasite is in the cell by things that are presented on the surface and actually kill that cell, and then it can crawl over and kill the next cell, but �'�' so how do we know that if we could, it’s actually possible to produce a vaccine to East Coast Fever, and one of the demonstrations is something called infection and treatment, and it is possible to kill that parasite with, for instance, long acting tetracycline, so you can infect a cow �'�' and this is a vaccine that just been launched by the Gates Foundation, it is one that was made 30 years ago by the Kenya Agricultural Institute, funded by ODA money then, and what you can do is you actually infect the animal, you let it go for a few days, so it actually has the actual live infection, and then you treat it with the long acting tetracycline, and so it is �'�' in a way, it is a vaccine of sorts in that this animal will now be solidly immune to any challenges by those same strains, and it is called the infection and treatment vaccine.

But the problem with East Coast Fever is similar to the problem with HIV and malaria, in that there is great genetic diversity among the parasites, so that in this infection and treatment there is a certain number of parasites, these East Coast Fever parasites introduced, but there are many more out there, and there is the chance for genetic recombination to continue to generate additional diversity.

Another problem, just like with tryps, is that the wildlife, the African Buffalo can serve as a reservoir, and again, like tryps, the African Buffalo do get solidly infected with the parasite, but then it is able to control it. So, the initial stages, the first 10 days, look exactly like what happens in a cow, and this is something I worked on when I was in Africa. We had captive African Buffalo. But then it controls it, whereas the cow goes on to die in a couple of weeks.

So, what this means is that if you �'�' if these are the killer lymphocytes and it is looking for something on the parasite cell, each lymphocyte sees a very specific parasite antigen, so if these are continually changing on the surface of the infected cell, this lymphocyte that recognizes, you know, the star antigen, for example, wouldn't be able to kill this other strain of parasite, and so on.

So �'�' and this is just a diagram to show you what happens, and I just want to explain that if �'�' that really this concept is something that you are familiar with also. So, you know, people that go for a transplant of some sort of organ or tissue, they go and they have to get tissue typing, and they have to find someone who is what we call a match.

What that means is that it is these molecules, which are called major histocompatibility molecules �'�' histocompatibility meaning blood compatible, that are on all of your cells, but we have great variety. If you were to look at the people in this room, it is very unlikely that anyone would have the same set of this tissue typing, we used to refer to these as tissue typing antigens on their surface, but it’s these molecules which present pieces of the thing that is inside them. So, whether it is a virus or a bacteria or a protozoa that can live inside of a host cell, small pieces of proteins known as peptides are out on the surface of these typing antigens, and so the problem is that if you transplant a kidney from one person in the room to someone else who isn't the same �'�' isn't matched in terms of these molecules, that person's immune system, which would be these killer lymphocytes, would see that molecule as being foreign. It thinks it is infected with something, and it kills the organ, and that's why the organ or the tissue dies.

So, it is the same kind of �'�' the concept is the same for when you have things like viruses. All viruses live within cells, so you have to induce these killer, these killer lymphocytes by using something that mimics this, and it is very difficult, and normally, what we �'�' in order to get this kind of presentation to these killer lymphocytes, it requires using a live vaccine, but the characteristics of vaccines that are desirable are ones that are actually killed, so that they don't have to be refrigerated. In other words, they are known as thermal stable. Also, when you have a lot of, as I said, a lot of different variations, genetic variations of the parasite, then you need to be sure that you have all the components, and you can reliably produce them. And also, as in the case of the infection and treatment, you are actually given the infection, and there is some concern that you’ll make a reservoir of the disease. And so this has been difficult, but it certainly is not impossible. For East Coast Fever, it is the same problem with malaria.

So, how would you get improved vaccines? Well, at first it will require identification of strains of the parasite in the challenged area. That's really simple to do now. You can sequence, you know, the organism in hours, whereas when I was a post-doc at ILRAD, one, just one of the thousand genes of that organism, post docs spent two years just sequencing that. I mean, we can do it in seconds now compared to what we could. So, there’s no real impediment any longer to be able to go out and look at the number of different parasites. And then we would �'�' of course, the most efficient way to develop a vaccine, you can't have a vaccine made of a thousand different individual antigens, is to find things that are common among them, and then we have methods now where we can do, use to sort of present the antigen so it resembles the live infection.

So, just to summarize, for -- the role of livestock in food security is that they provide food in terms of meat, milk and micronutrients, and these pictures were provided me by, to me by the International Laboratory for Research on Infectious Diseases in Nairobi. Also, they can provide draft power, so it helps in growing crops; also, transportation and nutrients in terms of the manure to act as fertilizers, and finally, the importance of livestock in developing countries as shown by developing markets. So, this is obviously an informal market, where you have an individual selling milk to another individual, but the markets for livestock trade and then increasing incomes, reducing poverty, is great in Sub-Saharan Africa.

So, I just would like to acknowledge the Jefferson Science Fellows program, Andy for introducing me, Nina's Fedoroff for running it, and all the people in the staff's office, and also the office at USAID, where I worked for the year, which is the International Research and Biotechnology Office and Rob Bertram [applause] is the office head, and also I would like to thank all of my colleagues there for a very enjoyable year. Thank you.

[applause]

Andrew Reynolds:

Well, I remembered something in my own education, was that in human medicine you learn one anatomy, in veterinary medicine, you learn five, and an immunologist like this is a rare person to have, and I hope that Cynthia remains in our community well into the future. We have some time remaining, and we are recording. If you have questions for Cynthia, please go to the microphone and identify yourself, and ask your questions. And thank you very much, Cynthia.

Cynthia Baldwin:

Thank you.

Andy Reynolds:

Don't be bashful.

Stella Williams:

Thank you very much, doctor �'�'

Andy Reynolds:

Would you identify yourself, please?

Stella Williams:

My name is Stella Williams. I'm chair of the Steering Committee of the African Women for Agricultural Research and Development. We are housed at ECROT in [unintelligible] in Kenya, and since you worked in Nairobi, I'm sure you know that.

I have two questions. The first question is you said you have been involved with CGIAR for a long time, C�'G�'I�'A�'R, and my question is after so many years of experiments in agriculture, especially in the area of animal health, how come you didn't have on your list of constraints the gender prospect, because I think it goes hand-in-hand with the lack of market, because it’s really missing, and it is one of the reasons why Africa's grain revolution is lacking.

The second question is how many of these institutions in East and West Africa or in Sub-Saharan Africa are you actually collaborating with in their own laboratories there in Sub-Saharan Africa? Thank you.

Cynthia Baldwin:

So, I think �'�' the gender issue of course is very important in, you know, in the Feed the Future initiative, which you can read about on the web site at the State Department, and I think the last slide was illustrating the informal markets first that women are very able to develop, and I think it is appreciated very much the role that women have in that. I wasn't trying to make a general seminar about all of the problems, just to show where the impact of infectious diseases affects agriculture.

And the second question was about why, why is there not a vaccine developed? I'm sorry. I've lost track. I didn't have a pencil to write it down. Was the second one about why there is �'�'

Stella Williams:

How many of these institutions are you collaborating with right there in Sub-Saharan Africa?

Cynthia Baldwin:

Oh. Oh. The national research institutes.

Stella Williams:

[inaudible]

Cynthia Baldwin:

Well, I don't have any specific collaborations with any of the institutes, but I can say very proudly that my very first Ph.D. student, which I had in Kenya, Thomas Kirauki is now the director of the International Primate Research Institute, which is in Nairobi, on the outskirts of Nairobi and Karen. It is an incredibly successful institute. He has been able to get his own NIH funding, as well as welcome trust funding. He is a Kenyan, and also has people from Harvard collaborating with him, CDC, NIH and so on, who come out to Kenya to do the unique sorts of experiments on things like malaria, trypanosomiasis, and so on. So, that's �'�' to me, that's an example of a wonderful success example, where he has been able to generate outside funds and has international recognition and collaborations. So, that's one of them, I know.

I'm also familiar with, certainly, with the Kenyan Agricultural Research Institute, and when I'm out there go and meet with them, as well as the people at AU�'IBAR, which is the animal resource part of the African Union, and I recently attended their meeting in Uganda. And as well, I have met with many of the chief veterinary officers while I was there, and also traveled to Uganda and Ethiopia, as well as Kenya, to do that, and to talk to them about what they felt their constraints were in terms of livestock, infectious diseases.

Andrew Reynolds:

Andy Reynolds from the S&T Advisors' Office [STAS]. Cynthia, one of the most telling points you made for me was the cultural problem of having livestock move alive, as transporters. That's the vector, basically. And I'm wondering if, back to the one core thing you mentioned, youth, infants under five and particularly less than two, requiring protein sources for cognizance and mental capability.

Are there substitutes in the short run, vegetable proteins, that could serve this purpose nutritionally while you get your hands around the much more difficult problem of societies that really depend on their livestock for more than one thing, and as you said, it is much more easily managed if you are dealing with finished meat products rather than a moving cow.

So, my question is what about short-term substitution in nutrition, with vegetable, while you are working on these more difficult issues of transgenics and viral vaccine production and so forth? Thank you.

Cynthia Baldwin: Well, certainly, I mean, people are vegans and they survive, so it is possible, but it is more difficult to get an appropriately balanced diet and the micronutrients that are needed by being on a diet that has no animal source food in it. So, that's the short answer.

Male voice: [unintelligible] National Academies. Just �'�' I don't know how to ask this question, it is such a big one, but the human resource factor in Africa in terms of expertise, advanced training and so on, USAID of course used to do a lot of funding of advanced training; it’s substantially gone away.

Did you look �'�' can you say something about the human resource development situation specifically in Africa, and whether �'�' whether USAID's policy has evolved, and if there is going to be more investment in that, and of course USAID is only one of many global players, so more broadly, is human resource development a major problem for developing solutions to the kinds of problems you’ve laid out?

Cynthia Baldwin:  Yes. I think that's well recognized. I think that the past program that USAID and the number of people they funded in agricultural sciences who then returned to Africa and assumed positions of power, that that group of people are really aging, approaching retirement and so on, and we don't necessarily have the same group replacing them coming up, so I think that is well recognized and often talked about in various circles here in Washington, not only at USAID but other places as well, so that is a problem that is recognized.

In terms of the CGIAR centers, that is something, at least when it was what was ILRAD and is now ILRI, we were able to do things where we trained a lot of, a lot of African Ph.D. students there, some of whom in those labs, so that is something in terms of capacity, building those labs provide an opportunity for that.

So, they may register with the University of Nairobi, for example; other ones would be registered in Brussels or the UK or so on, where they would work with someone at the institute and then go out and spend a few months in residence, because the European system is quite different than our system. They could spend a few months in residence and then defend their Ph.D. there. So, I think the CGIAR centers have also contributed enormously, and in a way I think that is underappreciated to capacity building in Africa, but there is no doubt that, you know, there is a huge need to continue that.

Male voice: Cynthia, I have a question regarding the early detection. A few years ago, I remember I worked with some colleagues in an AP model doing, looking at the spread of like mad cow disease. That AP model was developed in, I think Australia, it was called Ozza Spread. [spelled phoenetically]

My question is to what extent early detection is important in preventing the spread of these zoonotic diseases. If that is important, what research or action is being done to train the workers with developing some templates and some basic training to enable them to do the early detection, because that, I remember from at least that Ozza Spread model, was very critical. Beyond a certain point was really exponential, and it is like a treaty for end zone early detection, and then the exponential spread starts. Thank you.

Cynthia Baldwin: So for diseases, infectious diseases that are what we refer to as emerging infectious diseases, so ones that are not already widespread, that is, you know, detection, diagnosis, participatory epidemiology, as it is known, that is very crucial and that is another great need in Sub-Saharan Africa, for that sort of capacity building, particularly as it relates to diagnosing animal diseases and the new push towards what is referred to as one health or one medicine, where we are looking at veterinary and human diagnostics together. Will probably help with that. So, that early detection of infectious disease is emerging as very important.

In the case of the two examples I gave, trypanosomiasis and East Coast Fever, it is already endemic. It is everywhere, in the wildlife reservoirs and so on, so the threat is there. At this point, I'm not sure it is a matter of detection so much as a way to get it back under control. In other words, it is already �'�' the crisis has already happened and it has spread.

Stella Williams: Stella Williams again. Actually, John made me come back to the microphone. The USAID and Bill Gates Foundation is actually responsible for a lot of the sponsoring of the program that I'm involved in, and every year we choose 60 fellows out of the first time 1000, the second time 500, and just recently, [inaudible] where we did the selection, 60 out of over 700, and one of the funding in terms of human resources that the USAID is paying for is for us to give these young women, these African scientists with their Bachelor's degree or Master's or Ph.D., an opportunity to serve in a laboratory like Cynthia's, to give them money for science placement, either for three months or six months or nine months, and so my question is after this presentation, Cynthia, can I discuss with you if there is a possibility for some of our fellows with money from USAID to come to your laboratory for science placement?

Cynthia Baldwin: Absolutely. I would welcome any from your program, and I'm very familiar with the award program. I've been out to Kenya twice and met with Helga Reckay there, who runs the program in Kenya, and Meredith Soul in my office at USAID is involved in that, was just in Tanzania last week selecting the new awardees, and also I have other colleagues in Kenya who have been women scientists who have been part of the selection program. So, I am very familiar with the program. Thank you. And I would very much welcome to have someone in my lab.

Diana Cahill: Hello, my name is Diana Cahill, I'm an intern in the International Health and Biodefense Office here. I have two questions. The first is a number of the emerging zoonotic diseases that you were discussing, the trypanosomiasis, it works, because it outwits our immune system by changing its surface proteins, and brucella and tuberculosis do the same by defeating our lysozymes. In that case, it seems that the next generation of vaccines and our final defeat of these disease outbreaks will be by attacking the internal mechanisms of these antigens �'�' well, not antigens, but anyway, what research do you see on this frontier, and how are we pushing forward in this mechanism?

Cynthia Baldwin: It is �'�' for some of these infections, like brucella, that is actually one of the things that I work on in my lab, there actually are two vaccines available that are very good and they are used throughout the U.S., it is mandatory to have your animals vaccinated, and we have not eliminate brucellosis, despite this campaign going on for decades now, but we certainly can reduce it.

But in terms of �'�' I think what you are getting at is the fact that in both cases, those are live vaccines, and so those vaccines, at least one of them is very pathogenic in humans, so it can fully cause disease in humans, and there are many veterinarians who have injected themselves by mistake while trying to inject animals and have become very ill from that. So, that's one of the drawbacks of the live vaccines that is needed to stimulate the appropriate immune response against things that live inside cells, like brucella, [unintelligible] or East Coast Fever.

And so the drawback is not only in the case like of brucella, where it is a danger to humans and humans get infected through the vaccine, but also the idea of having to have a cold change, so in other words, you have to keep life vaccines often refrigerated, and you can try to do things which are freeze drying them, but then the viability of the vaccine is greatly reduced.

So, the new generation vaccines are things that we refer to as subunit vaccines, for example, with East Coast Fever, if we look, if we identify the strains and can come up with a restrictive number of these antigens that stimulate the immune system that are common to them, you can use them as subunit vaccines with -- in appropriate ways that are given during the injection with something we refer to as adjuvant, which kind of fools the immune system into thinking that it is a live, a live infection, and you can get the presentation out on those tissue typing antigens.

Another way is to put those antigens, you would take something, say, something very dangerous to humans, for example, like HIV, but you can isolate just the gene that codes for a particular protein that is needed to stimulate the T cells, and you can put that into something that is much more innocuous, so we can take live bacteria, even though HIV is a virus, we can take the gene from that, put it into the bacteria, and present it that way. And the bacteria, while live, is one that, that your immune system would be able to cope with and stop from replicating, but the goal is to get enough initial replication when you have infected with that, that you get the HIV antigens out there. So, your body thinks that it has been exposed to HIV, it makes the appropriate T cell immune response to control that, but it actually hasn't been, and it can control this, what we refer to as a vector vaccine, and so that's another approach.

Diana Cahill: Thank you. I'm sorry. My second question, in the case of onchocerciasis, which is river blindness, one of the NTDs that we are focusing on, Mectizan �'�' or Merck was able to donate its doses of Mectizan or Ivermectin to stop human transmission, because they saw a parallel market in animal vaccines. Are there other zoonotic diseases for which this would be a viable option for development?

Cynthia Baldwin: Could you say that again? So that the interest was in the human �'�'

Diana Cahill: Yes.

Cynthia Baldwin: Well, the problem with these vaccines that affect animals, or these diseases that affect animals, in some cases, like trypanosomiasis and East Coast Fever, it is specifically a problem with Sub-Saharan Africa. In something like foot and mouth disease, where there is a potential to spread to the U.S., throughout Europe, the whole world, that is much more economically viable for a pharmaceutical company, to put in money for research on such a vaccine and to actually sell it.

In cases where they are restricted to Africa, you already restrict the market and the interest in some ways, and even for animal vaccines, the amount of profit there is in it is extremely small compared to the profit for human vaccines, but one of the points I would like to make is that just because you're protecting an animal doesn't mean it is any easier than making a vaccine for humans, and we may not value the life of our cow as much as we value the life of our child, but it still is �'�' it costs the same to make those, and it is just as difficult and takes as much time.

So, that's probably been part of the problem in developing vaccines for veterinary use. There is much more interest in vaccines for companion animals, dogs, cats, horses, because again, people are willing to spend in general more money on their companion animals than they are on their food animals.

Andy Reynolds: I think I would like to say two things in thanking Cynthia once more. First of all, the lectures bring together a diverse group of people, and hearing this testimony today, we really are very blessed in this country, because people that work in agriculture, fish inspection service, food inspection service, for example, are the silent heroes. They are at the front lines of all we eat and consume in this country, and here is the research that makes this possible, and I think we should be grateful for that.

The only thing I would like to say, it is nice to have Stella Williams here, for example, who has already now met Cynthia and will be talking about bringing students to the University of Massachusetts, but also to know that Diana Cahill is here, an intern this summer with the State Department, so we see a next generation of young scientists, as I'm sure you are, coming through and having a taste of what diplomacy development really means, and perhaps a future career path for you.

So, this is a perfect lecture to finish the series this year. We'll see you again in the fall, after the heat, and with our new Jefferson fellows. So once more, a round of applause for Cynthia Baldwin.

[applause]



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