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| James Miller, PhD |
James Miller, PhD, is curator and head of the Applied Research Department at the Missouri Botanical Garden, as well as an adjunct professor at the University of Missouri-St. Louis. Miller studies the genetics of tropical plants and the natural products they generate.
What is the role of genetic data in determining relationships and understanding plants in the wild?
Well the incorporation of molecular methods to the study of relationships and classification of organisms has really led to a Renaissance in our thinking about how things are related to one another. Largely, being able to incorporate DNA sequence data into our thinking has, in some ways, confirmed the results of three or 400 years of study and told us that most of our thoughts about how species should be grouped into genera, and how genera should be grouped into families, were probably correct. But throughout history there have always been groups of organisms that were particularly problematic.
Their relationships were enigmatic. We weren't sure where they fit into the overall scheme. If we can get good DNA, and we sequence a gene or two and compare that to other organisms, we can solve those problems very cleanly and very efficiently. Once we have that molecular data, all of a sudden it often answers a lot of the questions about other characteristics. About their basic morphology, anatomy, pollen structure or whatever. We're in the midst right now of a complete Renaissance in the higher level classification of plants, in understanding their evolution, understanding how they are relating to one another.
Are there impacts, as far as conservation and understanding the range of species and how to conserve them and how to monitor them?
One thought that kicks around in the arena of conservation biology is that we're not going to able to conserve all of the genetic diversity that is out there. Hence, it is important to understand relationships and that a genetically very distinct organism probably has a very unique genome, and becomes of greater importance to save than one of a particularly species or group. If there are lots of species of oaks, for example, we can conserve most of those genes by ensuring that we can serve some of those species. But then you get something that is really distinct and has no close living relatives. Then it takes on a greater conservation importance.
Is there an example in the plant world of something like a keystone species in plants? Or is that really more of an animal concept?
Well the word 'keystone' species gets defined a whole bunch of different ways in biology. Botanists would probably use the term slightly differently than animal folks do. I think that animal folks think of keystone species as species that really have a huge impact and modify and restructure the environment. Botanists think of a keystone species as plants that are common enough and recognizable enoughto characterize as dominant in an environment.
Can you define economic botany?
Economic botany is simply the study of useful plants; plants that are used by humans as medicines, as food, as construction materials, as fibers, or any of the other dozens of ways that humans use and interact with plants. So it's the interaction of people with their natural environment.
What is ethno botany?
Ethno botany is barely distinct from economic botany. It's essentially the science that studies how people use plants.
Can you give us a definition of bio prospecting?
Bio prospecting is a terms that's used to describe a series of discovery efforts in looking for new products, which may be pharmaceutical, may be nutritional, may be agricultural, all from natural organisms.
And can you give a definition of genetic diversity?
Well genetic diversity is the sum total of the genes and their variance that exist in nature.
Can you just give a brief overview of the Applied Research Department and what some your goals are here?
The applied research department is really the economic botany program here at the garden. Hence the real mission is to study how plants may be useful. To translate the taxonomic information that results from the rest of the research programs into information that would essentially be, "why would anybody else care about all this diversity?" Well we care about it because of its sources of new medicines, new agricultural products, they are the medicinal plants we use; its construction, its fibers, its dyes. We care about them because they may be sources of new materials. But we also care about them because the ability to identify and recognize those plants is important in our everyday lives. We need to be able to identify toxic plants, every city has a poison control center and parents sort of shriek in horror with the thought of their kids coming in with a handful of stuff they have been eating and they don't know what it is. So there are all sorts of applications for our need to be able to identify plants and study their potential use.
Is there a sustainability component to that mission as well?
Very much so, because as the carrying capacity of the earth reaches its limit--probably during our lives--as populations expand, they come into greater and greater conflict with the maintenance of natural areas. We know, and there is a lot of discussion about, the overall biological diversity that is threatened and lost as a result of that. One of the things that gets ignored or doesn't get as much attention in those discussions is that human populations rely on and use a lot of plant species out in nature. And many of these things are being extracted from the wild at greater rates than the background production. So, while there still may be forests and natural areas maintained in an area, the plants used as medicines by the local population maybe differentially extracted, used and exploited. The plants that are preferential to use as cooking, firewood, get pulled out and pushed to extinction while there is still vegetation left. So we're left thinking, gee, the vegetation in this area still looks OK. There are still forests left. In fact people are differentially extracting the useful plants. So we are very concerned with sustainability issues.
Can you give us some of the examples of partnerships that Applied Research Department has with other institutions and companies in terms of research projects?
One of the core areas of our activities is a series of Discovery programs. They trace their roots back to 1986 when we accepted a contract with the National Cancer Institute to collect and survey African plant species in an attempt to develop new anti-cancer drugs or new AIDS medicines. We have continued that relationship. We are in the midst of a fourth five-year contract. So it's a twenty-year program, and we've collected literally tens of thousands of plants, we haven't discovered any new medicines or put any new medicines on the market. But we have discovered a lot of new compounds, previously unknown to science, with pretty interesting activity. I'm not sure any of them have a great potential of becoming medicines themselves. But some of them operate via mechanisms of action that were previously unknown. So they teach us something about natural products chemistry and they may be lead compounds that, through chemical modification, could eventually become drugs.
We have had a series of relationships through the years: we've worked with a variety of pharmaceutical companies. We've had a more than a ten-year relationship with Bristol-Myers Squibb. There is a program supported by the National Institutes of Health called the international co-operative biodiversity groups. These are multi-institutional partnerships that do natural products discovery. Our program, which is operated both in Suriname and Madagascar in co-operation with Virginia Polytechnic Institute and Conservation International, has worked with local partners to do discovery work in both pharmaceutical and agricultural areas. These are all very interesting programs because, in addition to trying to find novel compounds that are new to science, that have some application, those projects pay a lot of attention to the scientific process and they ensure that we promote conservation of the basic resources upon which the whole endeavor depends. We do so in a way that ensures appropriate economic development in the countries in which we work. The developing countries of the world have very little in terms of scientific resources. Both Suriname and Madagascar are quite poor countries, and these projects do what they can to try and address that problem. At the same time, these countries are home to the vast majorities of the world's biological resources. So there is a very uneven skew there. We also have a series of medicinal plant programs that look, in a variety of programs, at how humans in different cultures use medicinal plants-herbal medicine as opposed to isolated chemical compounds from plants.
The herbal product industry in the United States has grown to be a multi-billion dollar industry. Throughout most of recent history it hasn't been much of interest in this country. But we're following trends where people want something that is more natural; they want alternatives to a Western health care system that they perceive is riddled with a series of problems that don't really meet their needs. There has been an increasing interest in a variety of alternative therapies, particularly herbal medicine. And we have a program that examines a series of largely consumer issues related to that. It's a co-operative effort with the University of Missouri, Columbia. They look at a series of biochemical questions, such as, "Do these herbal medicines work? Are they really efficacious? Do what they claim to do? Are they safe? How do they interact with other drugs?" The Missouri Botanical Garden decided to really look at questions like, "Is the harvesting of these plants in nature sustainable, or are we extirpating the populations throughout their range?" Also, there is a series of consumer issues that ask questions like, "When you go to the store and you buy herbal medicine, does it have the right ingredients? Were the plants that were used to prepare it correctly identified? And is there a reasonable level of purity? Or is there a whole bunch of stuff that isn't supposed to be in there?" And we work with industry to try to develop methods that are appropriate to help them produce better, safer products. It's largely a good industry. There are lots of problems. But it's not an industry that has decades of experience doing this. They are still struggling to develop appropriate methods to ensure reasonable product quality.
It seems like a lot of questions can have overlapping implications serve multiple purposes, especially with the perspective of bio-prospecting and the sustainability issue.
Well I think these natural products Discovery programs actually contribute a lot to insuring and supporting sustainability. At the very basic, first level, if we can demonstrate economic importance and the utility of these plants and their relevance to our health or our nutrition needs, that is going to make people care a little bit more about their conservation from the start. The other thing is, in addition to becoming a center that really supports and facilitates the discovery of new drugs or new foods or new nutritional products as we move forward in this, the blurred line between pharmaceuticals and nutrition sort of becomes a less and less apparent line. The Missouri Botanical Garden has also been a center for helping developing legal and ethical frameworks to do this kind of work. So that we insure that it promotes conservation, it promotes sustainable use of the basic resources, the plants themselves. It insures fair and ethical collaboration with our fellow scientists and promotes their ability to do what they want and accomplish their missions; things that are relevant in the countries in which they work. And the programs insure that any benefit that arises, any financial gains are equitably shared with the countries in which we work. It's important to recognize that it is not just the development capacity of a high-tech, ultra-modern pharmaceutical research lab here in the United States that is necessary to develop new drugs. The raw materials, the biological diversity that exists in these tropical countries, these are an equally essential element in the mixture. And that needs to be recognized at every level of the research process, and it needs to be recognized when you start thinking of sharing the profits that may be produced if you discover a new product.
Do you think that is also a good argument against people who might be critical of conservationists by saying it's culturally biased?
I think there is a very simple answer to that question. It's that good, accepted, solid conservation is done via appropriate, sensitive partnerships with people in the countries in which we work. The work is not dictated by an outside party. And it is not just North American or European first world people telling the third world what to do.
Someone from the outside rarely is sensitive enough to a local situation, regardless of where you are on the planet. If we're going to have conservation that works, it has to incorporate and understand the local culture and have the local people buy into it, support it, believe it and feel it's appropriate and that it fits in their lives and addresses their problems. Not just that it solves some concern of someone in another continent.
Can you give us an explanation of a biodiversity hot spot?
Well, 'hot spot' is a term that was coined by the organization Conservation International, it's a very specific thing. If you use that term, it is meant to be a center of endemism, of high biological diversity, of a lot of species that aren't found anywhere else, and it's also an area that is under great threat. It needs to have all three of those characteristics. In a more general sense, what the public may think of as a hot spot--rather than this sort of branded Conservation International term-is simply an area of high conservation concern, and we can define that in a whole bunch of ways. Conservation International defined them one way. Other research and conservation organizations that are interested in the question have slightly different means of identifying them. So if you look at other organizations' maps of priority areas, they won't be identical. But the bottom line is, they are all going to be pretty similar. We all recognize that Madagascar is a really unique place, that it is highly threatened, and that it's one of the world's biological gems, and so on, and the list of major hot spots is not something that anybody would disagree on.
Would you say that the concepts of economic botany and ethno-botany are relatively recent ideas?
No, not at all. The Journal of Economic Botany has been published for many decades. It certainly dates back into the 1930's or 40's. I think the term ethno botany dates back into the 1800's.
Can you talk about whether there are any downsides to bio-prospecting or risks or dangers associated with it?
Well, I suppose there are risks or threats or dangers to any enterprise that is conducted inappropriately, insensitively or outright with wrong methods. I am really a fan of Natural Products Discovery Programs. I think if conducted properly they help support research, they help support conservation, they produce products that help improve human life, to alleviate suffering, to improve nutrition. Most of the criticisms that have been leveled at them have resulted from one or two things. The first is from people who simply don't understand them, don't understand the legal and ethical framework under which the way they operate. People who don't understand patent law, and think it's a misappropriation of traditional knowledge. The second kind of criticism that occasionally comes up is that they don't solve all the world's problems. Well, they do solve some problems in most cases where there have been well-conducted programs. They do make things a lot better, but I think it's pretty unrealistic to expect they are going to solve the conservation and development problems; that is just irrational.
I was hoping you could touch on again on the concept of DNA banking and clarify how that is misunderstood, and, if you could, tell us how that is conducted here and what the information is useful for?
When people hear that we have a DNA bank here at the Missouri Botanical Garden, I think they generally envision some repository with stored samples of DNA that is a genetic library, where you might have some visions of Jurassic Park, that we are going to reconstruct organisms or something. Those could hardly be further from the truth; in fact what we have are small dried samples of leaves that are stored in a freezer, from which we can easily extract DNA. And the purpose of that collection is to support studies of relationships in plants so we can use that to improve our understanding of how plants should be classified. How they are related to one another? In fact, we really prohibit the use of that collection for research in basic genetics or product discovery efforts, because the material that is in there was not collected with that as a specified use in the countries in which we work. We didn't have permission to do those kinds of things. We simply can't allow the material to be used for those.
So you use these samples and archive them to get a handle as much as possible on the range of species that exists, as sort of an inventory on the range of diversity among plants?
The kind of studies that the garden's DNA bank promotes help to improve our understanding of classification of plants, which is of fundamental importance as we think about their conservation biology, as we think about aspects of their basic science. It goes back to the sampling programs that we're talking about. If we're looking for new pharmaceuticals, what we want is a sample, a random selection of species with the idea that we'll get a good representative sample of the chemical diversity that exists in nature. If we don't understand how plants are related to one another, we aren't going to do a very good job doing that.
Can you tell us a little bit about that technique what how that is done and what the information is that is contained there?
Plant taxonomists and the botanists here at the Missouri Botanical Garden use herbarium samples, which are press-dried or pieces of plants that are mounted on a standard size of acid-free paper with a label that contains information about where they were collected and what they look like at the time of collection. It's the basic data to support our studies, and it's the basic data that we use to study inventory efforts that tell us what plants exist in a given area, to study the taxonomy of a given group of plants a genus or family. We assemble all the specimens and we can understand how their morphology varies from place to place, how they are distributed geographically and the things that we need to know in order to construct a reasonable classification. The same specimens also serve as the permanent records for material that we collect in the sampling programs. So that if we send a sample to the United States National Cancer Institute to be developed or analyzed for anti-cancer activity, there is always an associated herbarium specimen that is housed, archived, here at the Missouri Botanical Garden. So if there is ever any question about the material that was ground up and studied chemically at the NCI, we always have a permanent record here. We can go back and look at it again and again to confirm its identity or to answer questions if they may arise in the future.
Are there many other centers in the US that do this sort of thing, or is this unique?
Well there are lots of herbaria out there that have collections of pressed, dried plants. There are thousands of them in the United States. But most of them are small teaching or reference collections of plants that occur in a specific usually very restricted area. What is different about this place is not that we have pressed, dried or herbaria specimens, but the magnitude of the institution. We have around 5.2 million collections here, which makes this one of the half-dozen largest institutions of this type in the world. It is also a collection that has enough geographical representations that we can ask questions about the plants pretty much anywhere on the planet and there is a good enough representation here that we can at least get some good information about this, as opposed to your typical state university that may have adequate resources to answer questions about the plant diversity of the state in which it occurs, but it isn't going to tell you much about the biodiversity of Australia or of Indonesia.
What is the role of data management in your work, and in botany and the study of biodiversity in general, and what is the importance of that component?
Well the kinds of taxonomic research that we do here at the garden are rather age-old endeavors. People have been doing this for hundreds of years: going out and collecting and drying specimens of plants, and originally handwriting the labels, and later typing labels with manual typewriters. Only in the past couple of decades have we incorporated computers to help manage our data. And it's made a fundamental change in the way we think about the endeavor. For one thing, every time a botanist goes outinto the field and gathers new data, our level of knowledge changes. Print literature is static, so we've printed a published flora catalogue of the plants that occur in a given area. By definition, it's immediately out of date. There is always new information. Being able to move to an electronic format to manage our data and to produce products allows us to keeps things much, much more up to date and to have a much more flexible interface with the public.
What about the issue of bio-complexity? Is that something that is involved here now?
No, I don't think so. There are two more things that I would love to talk about. One is the technology question in drug discovery. The other is an overall view in the world of medicinal plants. I think both of those are relevant and interesting. One of the things that fuels these Natural Products Discovery Programs in recent years has been a series of massive breakthroughs in technology. If you wanted to look for new drugs in the United States in the 1960's, you used whole-animal models, and it took lots of animals to analyze a single plant, and you looked at the statistical differences and how you could improve outcome. With the advent of molecular biology, we can look at how plant extracts interfere with the activity of individual enzymes. With the advent of computers and robotics, we can mechanize the entire process. So you've gone from a world in the 1960's where it would take you months to analyze literally a handful of samples, to a very mechanized, discovery-based world today,in which it is possibly to analyze ten of thousands of extracts againsta single target in a given week. Well, if you are looking at something where your chances of making a discovery are one in tens of thousands, obviously today it's a viable venture, but in the 1960's it was a real shot in the dark. The other thing is that there has been a new breakthrough with a company with work with out in Southern California from a group called Sequoia Sciences. It allows us to take a plant extract, which is essentially a soup of hundreds of different chemical compounds that interfere with one another, that interact with one another. An automated fractionation method allows us to break that down into essentially a library of individual compounds. Then, because screening has gotten to a point where it is automated and we can look at hundreds or tens of thousands of compounds a week, we can then take that library and screen it one compound at a time, rather than screening these crude extracts and hoping that the one interesting compound will somehow register through the noise.
So we're seeing each chemical within an environment where it's not interfered with by other things. And what that has done is improved the discovery rate dramatically, allowing us to find biologically active compounds in rather common widespread plants that have been screened lots of times with crude mixtures in the past. So I think we're sort of entering a second renaissance of natural products drug discovery, with a series of methodologies that have been developed over the last 20 years; they re enabling us to make some pretty exciting discoveries on a regular basis.
In addition to the programs we have looking for new pharmaceutically useful compounds, we also care a lot and have a number of programs that are devoted to studying how humans use medicinal plants, herbal medicines. One of the things that we tend to forget in the United States, because we rely on pure isolated compounds that we buy at the local pharmacy, is that 80% of the developing world relies on medicinal plants as their primary health care to meet their needs. Western pharmaceuticals are largely unaffordable to them. And it's in the developing world that human population is increasing at an astronomical rate, and that's where the real conflict between human populations and biological diversity is occurring. The useful plants in those habitats are being extracted at even greater rates than those things that form the real backbone of the forests. So we are very concerned about possible threat and extinction of those medicinal plants. A cornerstone of US foreign policy is the idea of food security. That if food becomes inadequate to feed populations in an area it leads to political chaos and instability. We really need to start thinking about medicinal plants in a similar way, and think about medicinal plant security. If all of the herbal medicines of South Africa suddenly are collected to the point where they go extinct, that's going to have an enormous impact on the rural populations in a country like that. We need to be very, very concerned about ensuring that the plants that are the backbone of their healthcare system are there in the future.
Is that something that is like going to be on the table at one of the next international conventions?
We have a series of small projects that are aimed at addressing parts of this issue. Like everything else in the world, we need catalogues of those plants. We need field surveys. We need to identify which species are common, and which ones are in fact threatened. It's not the majority of the world's plant species that are at threat. The problem is that we don't have the lists. We don't have the lists of what are all the species out there. We don't have the list of which ones are common and which ones are scarce. And we need to get through that very basic inventory exercise and until we do, we're really working with a blurry set of priorities.
As we think about the issue of sustainability, useful plants play a critical role in several ways. First of all, we need to get a larger percentage of the population to realize that a pretty significant of the medicines that they take come from plants. The new genes that improve the foods that they eat all come from wild plants. We'll get people to care a little bit more about the whole conservation and sustainable resource issue.
What is the other half of the equation?
That at the same time, the useful plants that are out there-be they plants that are used as herbal medicine or wild foods by rural, undeveloped populations-face an even greater conservation threat than most of the plants that aren't used by humans. Things that are used as firewood can be deferentially extracted to the brink of extinction long before forests themselves appear threatened. So that is another element that needs to go into this sustainability equation.
So people need to understand that they need plants and rely on plants for these different things, but at the same time we don't want to over harvest?
We want people to care about these plants, but we also have to realize that some of these plants out there, because of human use, really require some special conservation attention.
What do you most want teachers out there to understand about your work, about what you do here, or about the field of ethno-botany?
Well, the concept of biological diversity, caring about the world's organisms because they are repository of genes and because there are multiple species and we ought to be concerned about the diversity out there-this is all a very new concept. Throughout human history we have cared about plants because they were useful to us, and in fact if you go into any botanical library and you go back and look at the surveys that were done of plants, they were done because of the medicinal plants, because of the edible plants, things like that. The idea of, "let's catalogue the biological diversity of Ecuador for it's own sake," that's a very new construct. At the same time, we have come to realize, with modern tools, that those plants that we have just thought of as not being very useful may in fact harbor useful chemicals, useful genes, things that have yet simply to be discovered. So the core issue is that we need to understand diversity as it exists in nature and at multiple scales: everything from the genetic level through an ecosystem. It's something that fundamentally affects every aspect of our lives, from the food we eat to the medicines that provide our health care, and so on. So if we don't address those issues and we're in a lot of situations still pretty much in a black box. We're going to do a lousy job, and we're going to be written in the history books in a chapter that really talks about the generation that let all this get lost.