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U.S. Department of State

Diplomacy in Action

Biodiversity in Health and Medicine


Remarks
Dr. Nicholas Farrell
Washington, DC
May 24, 2011

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Dr. Alex Dehgan: Good morning. It's my pleasure to introduce Dr. Nicholas Farrell. Dr. Farrell is a graduate of University College, Dublin. He attained his Ph.D. from Sussex University, completing postdoctoral fellowships at Simon Frazier University and the University of British Columbia. He's currently a professor of chemistry at Virginia Commonwealth University and is working as a Jefferson Science Fellow in the Office of Science and Technology at USAID. And it has been a true pleasure to have him there.

His research interests are in the broad area of medicinal inorganic chemistry. Dr. Farrell developed specifically medicinal uses of inorganic compounds including in the development of antiviral and anti‑parasitic drugs. But his major research has been on platinum‑based anti‑cancer agents which are an important part of one particularly successful anti‑cancer drug. He developed the first genuinely structural novel platinum drug to enter clinical trials in 30 years, BBR3464, which arose from his laboratory research. And he has received continuous funding over the last 20 years from the American Cancer Society, the National Science Foundation and the National Institutes of Health.

Dr. Farrell, through his research, challenged the existing paradigms to develop the first genuinely structural novel platinum agents. It's not easy to challenge paradigms. And that and the fact that this has entered human clinical trials makes him a very rare species in terms of academics. Generally less than one in 10,000 molecules actually get to that stage. He has written and co‑edited three books in the area of platinum anti‑cancer agents and medicinal inorganic chemistry, 200 referee papers and review chapters. He has received, him and his collaborators, have received over 60 patents and this is a guy who really has taken things from the bench to application and he was honored as a distinguished research scholar of Virginia Commonwealth University in 2003 and 2004. He developed the graduate program in chemical biology at Virginia Commonwealth University and was chair of the first Gordon Research Conference on metals and medicine.

And‑‑but what was interesting is he began his independent research career in Brazil and spent I think seven years working in Brazil and his laboratory has hosted and continues to host many international scholars and major collaborations that involve scientists from Australia, Brazil and the Czech republic. He continues his passion for such work today.

During his time in Washington has become the co‑founder and president of a Diaspora network of Irish scientists in the U.S., the Wild Geese Network of Irish Scientists, and I think even President Obama, would lift a glass of Guinness to him.

So with that I'd like to introduce you to Dr. Nick Farrell and his talk today on biodiversity in health and medicine.

[applause]

Nicholas Farrell:

[Irish language] After yesterday, at least everybody should know a few words of Irish. If the Queen of England and the President of the United States can learn a few words of Irish, I'm sure everybody else can. I said, "Welcome, my friends."

Thank you very much, Alex, for the introduction and also for the opportunity for the year to assist in building this important Office of Science and Technology within development. Within the context of these Jefferson Science lectures, they are public lectures, I was trying to think of what would be appropriate. We had a very energetic lecture from Suresh [Garimella] and a very stellar lecture from Nick Suntzeff. And so I felt that I should maybe talk about this area which is of interest to me of biodiversity in relation to climate change in health and medicine.

So first of all, just to situate ourselves, what do chemists do? We consider ourselves the central science. When I was Chair of the department, this is the sort of slide I would give to the dean and the president; hey, you've got to give us money. We are‑‑we do feel we're‑‑we drill down‑‑I'm trying to use all the phrases I've learned in Washington over the year.

By the way, first of all a shout out to my God daughter Emily Bailey who's here and who has been a great source of fun. It's been good to catch up with her during this year in D.C.

So we do new materials; people are interested in hydrogen storage. It's all very well to make materials for hydrogen storage but unless we solve the problem of actually cleaving water and producing hydrogen from water, we won't have hydrogen economy. And so chemists are involved‑‑it's very much involved in green chemistry. Tomorrow I think there's an American Chemical Society meeting somewhere in town on prospects for green chemistry. I saw that in the continuing list that comes across my desk from the Fellows.

New analytical techniques are important. They allow us to do smaller quantities and things in real time. We're very much involved personally in biological processes; chemical biology structure, biology synthetics, these are some of the themes I'll go through today and show you the evolution of and after product development.

The State Department and the U.S. government likes acronyms. I think academics like compound disciplines so we're chemical biologists and chemical physicists and biomedical engineers and so on and so forth but there are differences.

And finally, again, my own particular interest is in medicine and drug development. Chemists have a mutualistic agnostic relationship with medicine. We help them, of course, in terms of drug development, but we're also responsible for keeping down the numbers of students who go to medical school by failing them in organic chemistry.

[laughter]

And this is an obligation we take very seriously.

[laughter]

So, what‑‑the start of this was actually‑‑what started me thinking along these lines and what I would do for a different science lecture was actually a paper that Alex sent to us towards the end of last year that came out in "Nature", on the role of biodiversity in global change and particularly in the transmission and emergence of disease. And so I picked up on that and this is not actually from that‑‑from the 2010 paper. This is merely a paper that is probably best and it shows the interaction, the complicated interaction between climate change, human change and what we call biodiversity. So they start off with human activity. We talk about the culture intellectual benefits that we do in our daily life and the economic benefits but also the economic consequences and the other consequences of our existence, if you well. And our global changes come with CO2 cycles. They come with greenhouse gases. And this is the area over here on the left of climate change that we tend to be involved in.

And how this cycles back then into effects on ecosystems and our ecosystem goes in services of what we use and what we benefit from in our daily lives and it struck me that I never really thought about it before but I end up thinking and saying to you that our natural product discovery is actually an ecosystem good, if you want to put it that way.

So that's the interest. And then with respect to disease transmission, most infectious diseases involve a host and a pathogen so there's some sort of mutualistic relationship between a least two species. And this is the proportion of the global number of species currently threatened with extinction, up to 20 percent of mammals, 10 percent of plants and so this will‑‑obviously the consequence would be that we would affect our host vector relationships by having these species extinguished. Now that can be good or bad; that's fine. It could be evolution but nevertheless this is the situation and this paper, particularly the nature of the 2010 paper was a rigorous analysis of the literature and what's real and what's not real.

So some of the biodiversity loss involved in increasing disease transmission is shown in this table. This is the "Nature" paper here that Alex sent out. Abundance of host of vector change and the concentration of host or vector or behavior of the host or vector changes the mechanism of disease transition‑‑of disease transmission and these are referenced of the paper. So there's now a host of strong evidence that this is happening.

One case study done in Panama was on the hantavirus which is a flu‑like virus which can cause flu‑like symptoms but also can cause cardiopulmonary effects which are more serious. And they're under experimental removal of species the experimentally reduced animal diversity cause an increase in host species' density but also an increase in seroprevalence within host. So this is a good example that analyzes‑‑this is a good, solid example of where there is clear evidence that changing the concentration of host will change the ability to transmit as the disease and produce more seropositive hosts because of the non‑hosts are removed. So I thought that was interesting.

Finally, they have done drivers and locations of emergence events for zoonotic infectious diseases over the period up to 2005 and have calculated the various contributions to emergence demands from land‑use changes, human use susceptibility, agricultural infest‑‑intensification, anti microbial agent use and so on and so forth. And again, the vast majority of these events are documented in a scientifically rigorous manner to have occurred, and the consequences for new disease emergence is something that we will see in the future. So this is one area where we are now trying very rigorous analysis, if you will, to the effects of climate change and biodiversity on disease transmission.

Now, my own particular interest is in drug development, as Alex has pointed out. I'm not a natural product chemist, although I have slept in Holiday Inns but it's of interest to me to look at this and we can do many tables and it's quite fascinating to see that over 50 percent of our commercially available jobs have a bioactive compound or have some biological origin. We can‑‑I can spend the rest of the time‑‑it's three hours, right? I can spend two hours talking about all the drugs. We've got vinblastine from Periwinkle. We have many, many others. This is just a snapshot. The question is, how we continue to take advantage of this biodiversity in medicine, particularly bring in new techniques. And that's what I'm going to try to get at today.

Because, of course, we are linked with traditional knowledge and innovation and this because the vast majority of natural products have come to us from the science traditional employer by remedies traditionally employed by various cultures. Most of them are plant derived but lately we're moving in other directions, folk or tradition, medicinal uses indicate the presence of biologically active constituents and represent leads that could shortcut the discovery of modern medicines. And it's been calculated that at current extinction rates and looking at our development of major anti‑cancer drugs, we are losing one major drug every two years. And so the problem, especially in government circles, where everything seems to be like immediate‑‑there's no immediacy in life but unfortunately there is immediacy in the government, I have to say that.

Drug development is a long process. It just is. Most drugs in the United States take 10 to 12 years from initial observation to final approval. We ourselves in BBR3464 we were over there on the far right but before pharmaco‑kinetics told us we had to go back to go. We got as far as phase two clinical trials in humans and they found some metabolic problems that we had to resolve and go back. But it is important because this red box, this iterative medicinal chemistry that we're talking about is based on inspiration from the initial leads which come from natural products. And most‑‑some of the drugs that I showed you are not necessarily the first ones we've seen but they've been a second generation, if you will.

So given that it's‑‑again, my theme of continuity‑‑the first anti‑cancer agent was actually developed from studies of mustard gas which is astonishing but this is true. And between the wars, people start‑‑began to study the effect of mustard gas in cells and found that it affected proliferating cells from‑‑and again, in a series of iterative interactions, and nitrogen mustard. Mustard gas is based on sulfur. And nitrogen mustard was approved by the FDA in 1949 as the first clinically approved anti‑cancer drug in the United States. And of course, before the mid 40's, you also had a situation where cancer may not have been that important on the horizon as bacterial infections because people were dying of bacterial diseases.

So DNA and inactivation wasn't considered a model action of the drug, even as early as the '50s when the DNA structure came out. And this thing with development--has developed to‑‑I have to talk one slide, two slides about platinum. I'm not actually going to talk a little bit, but I indulge in myself to talk about two slides about platinum. But again, platinum compounds are the most commercially important and the most useful anti‑cancer agents at the moment. They were discovered by Barney Rosenberg from an apparently unrelated effect. He looked at the effect of filamentous growth in bacteria. Filamentous growth in bacteria as a phenomenon where the bacteria, they grow longer and longer and so you can do this effect with X‑rays, carcinogens. He shows this as an electric field. On the left is an electron micrograph of bacteria and on the right is these long sausage like rods which can be visualized under a simple visual microscope. And from that observation in his lab, he figured out that it was a platinum electrode which was dissolving in the medium to produce compounds and he made the intuitive instinct that it could have an effect on DNA and therefore might be an anti‑cancer agent. And he pushed and pushed and pushed and the National Cancer Institute did a Phase I clinical trials and it showed activity in testicular canceled cancer and it was licensed by Bristol‑Myers. But when he approached the pharmaceutical companies, initially they told him to go away. And if he had presented a proposal to the National Cancer Institute to develop platinum compounds against cancer, they would have told him to take a sabbatical and take rest as well.

But it's this combination‑‑one of the things we talk about is innovation. And I really think what we should be talking about is how we create more people like Barney Rosenberg because he‑‑it's all right to make an innovative solution to a question but he saw the solution before there was even a question. He saw an answer to something and that's an art. And I think that we tend to ‑‑‑we're losing them. So I like to give this as an example because it's a great example of a relatively unrelated affect and there's a series of questions and questions and questions and ended up with a major class of anti‑cancer drugs.

So we had to‑‑what we did was, we‑‑again, we challenged the paradigm. There were structure-activity relationships and we expanded that and we developed a new type of drug when we showed about crystallography that again it binds the DNA but in a different manner. So if it binds in a different manner, it has different consequences. And we got some crystals‑‑this is a crystal structure and it's nice to get crystals of DNA. Not as nice as Rosalind Franklin. I put in this photograph 51 because some of you may have gone to the play when it was here and this is her famous photograph that she showed to Watson of the DNA helix. So we were able to show a new binding mode and from that we were able to continue our work. So that was nice. That's the end of platinum.

So let's get back to natural products and let's get back to this thing with biodiversity. I'm going to use malaria as an example. And the first part will be history and then again I'm going to try to talk about, try to convince you that the new techniques that make looking at natural product discovery an important role for capacity development.

So we know about quinine. It's an effective muscle relaxant. It was long used by the Indians of Peru. They would mix the ground bark to produce tonic water with sweetwater and so the Spanish and the Jesuits‑‑it's also called Jesuit bark. They extracted it and used it for reducing malarial fever.

The British had a better idea than sweetwater. They mixed it with gin so the story is that gin and tonic came from British soldiers in India having to take quinine every day to reduce their risk of malaria and cutting it with gin to make it palatable because quinine itself is very bitter.

But let's look at the history of quinine because it's interesting. In the 1860's, 1870's people started trying to make the stuff. Otherwise‑‑beforehand, it was an extraction. They had various difficulties and actually lead to the dying industry in some ways.

But finally, in the 1930's, chloroquine was made. And it was shown to have anti‑malarial activities and it was approved as an anti‑malarial and 1947. And during World War II, the United States spent a lot of time trying to break this patent on chloroquine since it's by buyer in Germany. Because the sources of quinine were reduced because they were fighting in Asia and this is where the quinine was coming from. So they weren't actually able to get it. And so there was a real problem in trying to produce quinine for the troops. And so I'm not sure whether they succeeded or not but, happily enough, the war ended.

But since then it has continued‑‑studies have continued from chloroquine. Again, this is my only real chemistry slide so don't worry about the structure. Worry about the green boxes, okay? I'm trying to take it easy on you but it's very hard to do a public lecture on biodiversity and medicine without a chemical structure. That's hard. You're going to have to bear with me for just a little while. But you know, synthesis of naladixic acid, oxalinic acid and then in this natural progression it was found that this naladixic acid had antibacterial properties so this set people of on a roll of looking at these compounds for antibacterial effects, and it ended up with the development of the fluoroquinolones in the late 1960's as the first as having antibiotics. So you can make an argument of this natural history of quinine and looking at products actually ended up with the first man made antibiotics. And that's of interest because they're also the last man made antibiotics and that's a real problem.

Well first of all, again, chloroquine interacts with DNA because it's plain or just the green is sticking into the DNA bases. But the fluoroquinolones interact in a slightly different way. The problem with DNA is it's not linear. It's actually‑‑because if you multiply. 34 nanometers, which is this distance‑‑this is the first nano structure, by the way‑‑by three mill‑‑by three billion, which is the number of base pairs, you get about between a meter and two meters. So DNA in cells a is actually all packaged and super coiled and wound around itself and it's quite complicated. And there are various enzymes that sort of stretch this out for the preliminary agents and the work to be done on it, the transcription and the replication‑‑the replication, I should say. So, it turns out that the quinolones actually act on these enzymes. They prevent the DNA from being unwound. If you're giving a graduate student lecture you always get your friend to make a rope, you know? And you get a rope and you coil it around and then you can show how they as you unwind the rope it sort of coils on the other side.

So that's the problem. But as far as I'm concerned here, the question is, we've gone not only from quinine to a class of antibacterials but we've gone from a relatively simple understanding of DNA intercalation to a really sophisticated three dimensional problem of topology of DNA. And again, that's a consequence of this theme of innovation that I'm talking about, is a natural‑‑it's a natural path to something that becomes very, very creative and very complicated from natural products.

And again, I put this in because of my interest in Brazil but the lapacho tree‑‑the lapacho comes from the pink ipe. If you've ever lived in Brazil or visited Brazil, the pink and yellow ipe are these beautiful tropical trees. They're really lovely looking fields in spring and in squares. And this lapacho was an herbal tea made from the leaves of this pink ipe. It was known to treat minor skin injuries and had some carcinostatic properties. The National Cancer Institute tested it, found it wasn't that effective; it wasn't orally active. But a derivative, beta‑lapachone, is now being tested and is also an inhibitor to this topoisomerase. So again, these natural products, they have mechanisms. Some of these mechanisms are quite sophisticated and that's sort of one of my points and I do have one.

Okay, so the problem, coming back to fluoroquinolones, is that there are no new antibiotics and this is‑‑nothing is coming through and you look at the infectious disease side of America, we talk about six drugs by 2020 but even given our current development timeline, that's simply not going happen. It's not going to happen. And so we're also losing sources of inspiration. That would be my one point that we can make if we don't continue to take advantage of natural products and biodiversity.

This is some of the multi resistant strains of bacteria pathogens which are on the rise. S. aureus and tuberculosis of course are the two most serious ones. This from an article by Chris Walsh in "Science" about a year‑and‑a‑half ago.

Okay, so what are we going to do? Well let's sit back a second. We're going to go back to malaria a second. This is a great title. This is how people get grants; they come up with a title like "The Natural History of Antibiotics". That's brilliant. I love this. But let's think about why, why are plants and animals making these things? The general principle is, it's a defense. There may be other reasons but let's assume it's a defense against competing microbes or organisms. But the other question I want you think about for just one moment because this will lead into my second example of malarial drugs is how? How does it this? Well, these molecules are very complicated. It's a rite of passage for every organic chemist to take one of these complicated natural products and for part of their PhD thesis they'll devise syntheses and it'll be, these compounds are picomole or toxic and cancer and there's one nanogram the whole world and I'm going to make it. I sat in an American Cancer Society study section. The organic chemists are quite hard on each other. This guy would come up with this great synthesis for his post doc scholarship, and the organic chemists would say, well, step 22 doesn't work in chloroform. And I had to say, well, if he can get to step 21 I think he'll figure that out so just give him the money.

[laughter]

Anyway -- so I wanted you to think about that because the plants make them or nature makes them the same way as we make proteins. We build them up; they're building blocks. They have enzymes to put one step in front of the‑‑one step together, the next step and build these complicated molecules of‑‑in the right stereochemistry chemistry and so on and so forth.

Now that's going to be relevant to what is now what we're doing in modern‑day times. What I've given you so far is basically history. But one of the latest promises for anti malarial drugs was artemisinin, which was a Chinese herbal extract and was known for some considerable time in China to have, again, fever reducing properties. It's converted into various highly active derivatives and this was very exciting because these compounds were shown to be active against chloroquine resistant malaria.

So they entered into the‑‑into combination. There were indicated by the World Health Organization as only to be used in combination therapy because there was already signs of quick development of resistance. However, natural resistance is developed into the drug as it happens. This is evolution. But also misuse of monotherapy has resulted‑‑just as misuse of antibiotics has resulted‑‑in resistance antibiotics, misuse of artemisinin has also resulted in increasing resistance. So you're stuck.

But let's look at the economics. The growing time is 12 to 18 months. The yield produced is a hectare, is equal to 5 kilograms or a thousand kilograms of dry leaves. That's not a great yield. And we need about 17,000 hectares under cultivation to supply at the moment the world needs of artemisinin, which genetically modified plants‑‑Steve Fondriest isn't here but he was telling me he was involved‑‑when he was in Tanzania, he was involved in an agricultural program to plant artemisinin or the tree‑‑the bushes, the genetically modify bushes‑‑to obtain more drug. But it's still not satisfactory because even the modified plants are dependent on weather; they're dependent on other factors for their yield. The yield is not that high.

There is an economics involved and there are many companies making it. There was a large increase in production in 2007, 2008 but that's now gone down for various reasons and the price has also gone down with it. So you might need a stable supply of this drug to not only stabilize the prices but also to stabilize treatment.

One of the more promising areas that will do this is coming from synthetic biology. And this is where I raise the point about‑‑make you think about how cells build up these complicated natural products. Because synthetic biology now designs and builds biological parts; it's a really fascinating field where you're going to take a cell‑‑you're going to engineer a cell; you're going to take all the parts together and make an artificial genome. You can make diesel if you get the right enzymes.

So what this group Amyris Biotechnologies, in collaboration with Brazil, actually, they reengineered yeast so that they figured out the steps of how to make artemisinin from very simple molecules. In fact, they start off with sugar cane so they extract starch from sugar cane. They use the sugars as their starting material. And then they know the pathways or they engineer the enzymes to make the molecules. So they stick the enzymes into yeast cells and then all the way that actually end up making a precursor of artemisinin.

So I think that these people in Amyris were failed medical students because they hate organic chemistry and they decided to engineer cells to do it for them. So it's great but it's a really interesting story. It's one example of synthetic biology which is‑‑promises like everything else to change the way we look at things quite dramatically.

This is another way of looking at it. Atop all these barrels of blues are actually enzymes they threw into the yeast cell to make the various steps. You start off with a small‑‑on the left hand side‑‑a small carbon precursor and you end up with this very complicated molecule which you then taken out of the cells, the yeast, convert it to artemisinin and then you go the rest of the way. Now of course these people are pushing this but this is the type of economics that you can see, if they can get a stable, non‑agricultural source of this drug.

You go‑‑the ACT 1, ACT 9 are all various types because it's not an actually one compound, it's a mixture of closely related derivatives. And the dashed lines are the savings due to the microbial artemisinin. And they can bring down the prices significantly and of course that will do a significant amount for the ability to incorporate these into ACT and the combination therapy and reduce the overall cost. So this is a new dynamic approach, if you will, to looking at malaria problems‑‑drugs.

Now these synthetic biologists are very interesting people. If you go on their Web site, they‑‑first of all‑‑they coined the term about 10 years ago, maybe less. They have an annual meeting. They're very much involved in bioethics. They immediately started an ethics commission immediately in the very first meeting which I thought was a very good thing.

But they're also interested in art. Has anybody gone to Vienna? Peter always goes to Vienna; he spends most of his time in Vienna. The next synthetic biology meeting in about three weeks' time is in Vienna and they have an art from synthetic biology side show just so we can use on our website. So these are actually‑‑what these are‑‑anybody know what these are? These are gel electrophoresis dots. These are DNA visualizing gels and they're designed to produced shapes and numbers and so on and so forth. So there's a‑‑if you go to Vienna in a couple of weeks' time you can go to this art show from synthetic biology, which I think is pretty cool, actually.

So, now the last thing I want to talk about is again looking at newer approaches to looking at biodiversity in medicine. This is actually something that we ended up talking by yesterday and I wanted to talk‑‑thank Flora Katz from NCI because a few weeks ago I called her about this and we've had some very interesting conversations. In fact, we had a meeting with her yesterday and this was brought up.

Some about 1992, NIH started an international cooperative biodiversity group with a number of institutes at NIH, with NSF and now lately over the last few years, with various agencies of the government. USAID was actually involved in the very early stages of this but funding cycles and cultures were different at that time and they did not participate further. But their concept was to really do a systematic approach to national product discovery. And this is taken from their website: They aim to "integrate improvement of human health through drug discovery, creation of incentives for conservation of biodiversity, and promotion of scientific research and sustainable economic activity." You can read this as well as I can.

And so it's based on the belief that discovery and development of pharmaceutical and other useful agents can, under appropriate circumstances, promote scientific capacity development and economic incentives. And if I remember, I will show you‑‑I will tell you at the end, I really believe in this from my observation of Brazil in 30 years, what they were able to do 30 years ago and what they're able to do today.

So they have in full place intellectual property considerations and ethical considerations and so they fund groups to examine natural products and natural product development. One example that was actually advertised quite heavily at the science meeting in February‑‑if anybody went, there was a session on ‑from ICBG at the science meeting in Washington here. And Julia Kubanek down at Georgia Tech studied Fijian seaweed. I never thought of this when I was a graduate student. I mean really, you know? This is great stuff; you do your fieldwork in Fiji. That's pretty attractive to graduate students, right? So what she found was that there are these seaweed‑‑they protect themselves against fungus by marshaling chemical defenses. And it's not throughout the‑‑it's not throughout the seaweed; it's only in little patches. New techniques can actually examine those patches and the technique that they used was electrospray ionization mass spectrometry. Now, you don't have to know what that means but it measures the size of molecules. And it's fascinating, again, to see the development of techniques because with my white hair I tend to find myself saying to students, you don't remember, but --, or you're too young. And I hate saying that but it's true. But you know, when I was a graduate student, the mass spectrometer was in this huge room, valves and everything else and now they're hand held. And with this technique you can detect cocaine on a finger. It's fascinating. You can detect residues from biowarfare.

And so, John Fenn from Ireland who actually did most of the work at Yale was awarded the 2002 Nobel Prize for development of this technique. And it's really revolutionized‑‑you couldn't do proteomics without it and it's revolutionized also this area. And I like to show a photograph of John because he was a stickler for the English language and I remember one day I was rushing around and he said to me, "Nick, you look very frazzled. What's the matter?" I said, "I have a grant to write, John. It's due today." And he looked at me and said, "You're one of the lucky ones. Most of us write proposals." So, now at least in our department we always write proposals. We don't write grants.

But this is an interesting story because you see, if you think of it, quinine's story and even the artemisinin and you‑‑the traditional idea of natural products was, you ground up the bark or you ground up the leaves. And if you're ever in the Department of Chemistry, it was the natural products chemistry. There was always some room with a sack full leaves or something like that. But now this is different because what you can do is, what they're able to do it with his hand held mass spectrometer is spray the seaweed and measure the molecules that come off it. Just as you can do this‑‑ they're actually developing this. I think it's an Indiana group that's developing it‑‑Garth Crooks, right? Yes. And I don't know where‑‑how long it is on the commercial side of things but it's pretty close, if not being done, right?

Male Speaker:

[inaudible]

Nicholas Farrell:

Grain. Yes, grain, right. Right. Right. So what they're able to do with the seaweed example is actually show the seaweed reacting to an attack, you know? They're reacting to a fungus and they're producing molecules, just like we have an adrenaline rush. You know that adrenaline rush you get at the fourth meeting of the day? Oh no, sorry. [laughs] That was wrong; the first meeting of the day. So you can actually examine in real time the response, now, of a host, in this case this the seaweed to vector a fungus or an attack. That's really just fascinating that you can do that. And they discovered a whole host of new molecules in response to this attack by the fungus. Some of them have anti malarial activity.

This was the big news that came out of a science meeting in February. Now they're right over here on the left at this stage and good luck to them; they've got a long way to go. But nevertheless I think it's fascinating that new techniques can develop this whole new area, what Flora calls ecological chemistry. And it's being able to see in real time the response of a species to attack. I think it's fascinating.

Now Tom Miller's here. This is a Tom Miller memorial slide because one of the great things about the Jefferson Science Fellows is meeting a group of diverse people. I've had‑‑not enough time‑‑a very pleasant time with Tom and if you spend any time with Tom you become an insect guy. And this is slide will show an interaction between three species: An ant, a fungus and bacteria. And these are these leaf cutter ants and again I thank Flora Katz for bringing this to my attention. So what happens is, the ant eats the leave and then breaks it down. But to protect attack, it eats‑‑it breaks down the cell leading to carbohydrates and then it eats the fungus. But then to protect themselves, the fungus against attack, they actually produce antibacterial molecules. They actually‑‑they have actinomycetes on their skeleton which live in the integuments of the ants and they protect the fungus from invasion of other pathogens so that the ants maintain their food supply intact without attack from another‑‑from another species. This is a full slide of the system. Here's your ant eating his leaf as food; here's the ant getting the fungus. And then these are‑‑these are‑‑the white dots are these microbicide factories which they have on a skeleton. These white dots are all over the skeleton of this particular ant. They should have FDA approval for making this stuff, they make so much of it.

Here is the iconic slide of the actinomycetes in the middle and then you see all the perfectly clear around it and the parasites put around the edge. So this is a system, a three system mutualism of ant, fungus and bacteria. We're now able to examine that in great detail, and partly due to molecular biology and new instrumental techniques.

So, what were seeing, I think, is a seat change in how we can examine biodiversity and the role of biodiversity in natural product development. As I say, I came to my‑‑I never even thought of it until I started doing this but it's‑‑you may even think about the products as an ecosystem good. Maybe other people have thought of that before. I never really made the connection.

We spend a lot of time here in the Ronald Reagan building talking about climate change and the emphasis is on reduction of emissions from deforestation and degradation. But both‑‑and then it's sort of left that we maintain biodiversity. But both aspects of disease transmission emergence in health as well as natural product discovery I think are linked by the commonality of host‑vector relations. We're now able to examine, examine host‑vector relationships in natural product production. And I think these are great explorations of‑‑for capacity development. We're spending a lot of time discussing how to engage with universities and help develop capacity and again, we have this bad habit of academics; we write these abstracts and then the morning of a talk you say, what did I actually say I was going to talk about? We talked about the role of innovation but 30 years ago in Brazil, organic chemists were fine. They were ahead of the game because they had their natural products and they could make them. You can see discussions from Brazil of the use of the number of patents that have been produced for the natural products and whether it's been economically beneficial. When I was there a friend of mine wanted to patent and nobody knew what to do. It was impossible. There was no organization. There was no tech transfer. There was no law. It was very difficult to do. So I think that it's a long‑term process, not immediate, but I think that especially in Africa and Asia there is significant benefit to think of capacity development through this area.

And also, what we're seeing is again, I think that what's of interest to me as a chemist is that it's now a dynamic approach. You can study things in real time rather than the previous static approach of isolation. I think this offers tremendous interest for the future.

So I think there's‑‑biodiversity in medicine is an area which deserves more thought in terms of long‑term strategies for capacity development in developing countries, as well as being a thoroughly exciting area of interest if you can get to Fiji for your fieldwork.

I went to this art show a few weeks ago, this Alexis Rockman show on art and science and he's inspired by the climate change apocalypses and so forth and this is one of his paintings it's called Evolution and I don't think he had this particular thing in mind but I thought, if things end up like this I'm sure there will be a tremendous diversity of genes and natural products within this new, brave new world, if there's anybody around to take advantage of it. But in the meantime I think we should take advantage of what we have.

So it only remains for me to thank you for your attention, to advertise that‑‑Kathy O'Connor was supposed to be here so I‑‑but unfortunately couldn't make it so I do have to advertise Dublin City of Science next year. We were hoping the president would mention it but it didn't get into his speech, I'm afraid. That's a pity. And to thank my various people who have funded me over the years and as they say in Virginia, thank y'all for your attention. Thank you.



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