Colombia is estimated to comprise 10% of the world's flora and fauna, and is ranked seventh among all other countries worldwide in terms of absolute species diversity. Providing habitat to some 813 identified endemic species - 331 of which are threatened and/or endangered - Colombia is one of twelve "mega-biodiversity" countries recognized for its variety of distinct ecosystems¹.

     In view of its relative biological wealth, the potential for expanding Colombia's capacity to develop genetic and biochemical resources - or, "bioresources" - as well as to provide such resources to a growing international biotechnology market merits serious consideration. In support of such capacities, this report focuses on: (1) recent and emerging trends within the international biotechnology market; (2) the interrelationships between the biotechnology market and commercial demand for genetic and biochemical materials from wild sources; and (3) practical steps that Colombia might take to develop and engage in this market.

     Colombia is a party to the 1992 United Nations Convention on Biological Diversity (UNCBD) and the Andean Community's 1996 Decision 391 on a Common Regime on Access to Genetic Resources (Decision 391). Both of these commitments demonstrate Colombia's interest in the conservation and sustainable use of its biological resources as well as economic development for its people. Significantly in this regard, the central purpose of Decision 391 is to "…regulate access to the genetic resources of the Member Countries and their by-products… (Article 2).

Trends in the international biotechnology market

     One of the fastest-growing sources of commercial demand for genetic and biochemical resources is the still-nascent international biotechnology industry. "Biotechnology" is generally defined as "any technique that uses living organisms or substances from those organisms, to make or modify a product, to improve plants or animals, or to develop microorganisms for specific uses." The term is often used synonymously with "recombinant DNA technology," a fact that underscores biotechnolgy's reliance on new tools and techniques that make possible analysis and modification of the genetic makeup of organisms including bacteria, fungi, plants and animals.

     Over the past twenty years, biotechnology has supported countless scientific discoveries and improved the quality of life for people worldwide. As an example, recombinant DNA techniques underlie development of the polymerase chain reaction (PCR). PCR enables the rapid amplification of genetic material in large quantities which, among other things, facilitates the identification of individuals from small traces of blood, hair, or other tissue ("genetic fingerprinting"). PCR also enables the diagnosis of wide-spread diseases such as HIV.

     Despite its short history, the biotechnology industry has become a central component of the economies of many industrialized countries. Rather than a stand-alone economic sector, the biotechnology industry is best understood as a group of economic sectors that benefit from applications of biotechnological research. A list of applications within these sectors appear below in Figure 1.

     Relative to other economic sectors, the international biotechnology sector has witnessed extraordinary growth in both revenues and sales. Continued growth is expected to be sustained in coming years by, among other trends, (1) demographic expansion of the elderly population in industrialized countries (that consumes a disproportionately large amount of prescription and over-the-counter (OTC) drugs, and (2) an increase in corporate partnerships and improved capitalization of small and innovative biotechnology companies. In the U.S., for example, Standard & Poor's anticipates "…industry-wide revenue growth in 1998 to approximate the 19% growth seen in 1997. Annual revenue growth rates could accelerate to 20% to 25% range in 1999-2000."

     The leadership of U.S. companies undertaking cutting-edge biotechnological research is evidenced by increasing investment in U.S. companies by larger European and Japanese pharmaceutical interests. Whether by international or domestic corporations, the rise in such partnerships reflects a growing trend in which large, established pharmaceutical, agricultural, and other "life science" companies with name-brand recognition partner with smaller, start-up biotechnology research companies. Through this arrangement, large companies receive the innovative research critical to the development of new products that they then manufacture and market, and smaller biotechnology research companies receive additional revenues to fund expensive research efforts. The rise in these types of partnerships also bodes well for continued industry growth.

     The nature of biotechnological research and development precludes the identification of specific applications that might be developed from a given area or type of biodiversity (which in most cases includes a large percentage of unidentified species). Accordingly, discoveries based on genetic and biochemical resources sourced from Colombia might be applied to any one of the sectors identified above in Figure 1. Notwithstanding this important observation, this discussion focuses on two specific sectors: "biopharmaceuticals" and "green pharmaceuticals."

     The "biopharmaceutical" industry develops, produces and markets vaccines, therapeutic drugs, diagnostic products, and other medical therapies. U.S. biopharmaceutical sales in 1997 alone totaled $13 billion, according to the accounting firm Ernst & Young - up from $10.8 billion in 1996. While demand for biopharmaceutical drugs is distributed internationally, U.S. pharmaceutical companies command a relative advantage in supply: "Of 152 major global drugs developed between 1975 and 1994, almost half were of U.S. origin. The second leading contender, the United Kingdom, developed only 14 percent of the globally important drugs launched during that period."

     Green pharmaceuticals - also referred to as "botanicals" - are broadly defined as herbal, botanical, and other preparations from plant-derived substances that have therapeutic qualities. In the context of the U.S. market, green pharmaceuticals came to be regulated as "dietary supplements" following the U.S. Food and Drug Administration's passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994. Globally, it is estimated that sales of green pharmaceuticals in 1997 totaled $16.5 billion, with consumer demand led by Europe (46%) and followed by Asia (18%), North America (18%), and Japan (15%).

     The costs of green pharmaceuticals are covered under insurance plans in many cases in Europe and Japan, where health claims are allowed to an extent not seen in the U.S. market. While green pharmaceuticals comprise only a subset of over the counter healthcare products, Figure 2 confirms leading demand in this market from Europe and Japan.

     The U.S. FDA is currently deliberating proposals to consider the history of use for herbal and botanical preparations with an established history of use as a proxy for the first phase of clinical trials required for new drugs. Together with the spread of green pharmaceutical marketing and sales from specialty shops and multilevel marketing to mass marketing outlets, this contributes to optimistic forecasts of 12-18% growth in the U.S. green pharmaceutical market over the next three years.

     There are compelling reasons for Colombia to focus on developing national capacity in these two sectors. First, as demonstrated by the preceding growth figures, sustained growth and demand are expected to continue well into the next decade. In addition to the favorable demographic trend and the strong state of biotechnology capitalization, "[t]here are currently more approved products generating more revenue - as well as many more products in later stages of development - than at any other time in the industry's history."

     Second, as evidenced most recently by the downturn in the U.S. stock market in the fall of 1998, growth in the biotechnology industry is not generally affected by short-term market swings in the same manner as other consumer goods and services. Sustained demand in biotechnology is supported by end user products that are deemed essential goods (i.e. medicine and healthcare services) as well as by long (10 - 20 year) research and development efforts requiring consistent funding support.

     Third, the high percentage of industry revenues that are invested back into research and development far in advance of production and marketing means that the industry is accustomed to high-risk, up-front payments, portions of which are expensed for natural products sourcing. In fact, research and development expenditures in the biotech industry are among the highest relative to other high-tech industries, including electronics, aerospace, computers, and automobiles. Given that many smaller biotech companies have yet to roll-out products in the market, research and development spending as a percentage of sales was estimated to equal 69% industry-wide by Ernst & Young. As illustrated in Figure 3 (below), biopharmaceutical research and development expenditures have more than doubled over the past decade. In 1999, U.S. pharmaceutical companies are expected to spend $20 billion in research and development; by comparison, the underwater "Chunnel" linking London and Paris cost approximately $12 billion.

     Fourth, both biopharmaceuticals and green pharmaceuticals are what economists refer to as "elastic goods." Unlike coffee, bananas, and other "inelastic goods," demand for biopharmaceuticals, green pharmaceuticals and many other high-technology goods increases as consumer incomes rise. Many economists point to engagement in an international market for such goods as an important step for diversifying and building sustainable economies in developing countries.

Figure 3: Research and Development Investments by PhRMA Member Companies (US$ Billion)

Interrelation of international biotechnology market and bioresource demand

     While the fast-growing international biotechnology market is financially strong, growth in demand for end-user products does not translate directly to demand for raw genetic and biochemical samples, extracts and compounds from wild sources. The interrelationship between these two is complex, and many varied estimates, assumptions, methodologies, and qualifications must be viewed with a critical eye in order to assess the extent of commercial demand for a given set of bioresources, such as those preserved in Colombia.

     The development of new biopharmaceuticals can take two paths, referred to here as "rational drug design" and "natural products screening". Rational drug design involves chemical synthesis of molecules deliberately designed to match the structure of proteins and receptors implicated in a given disease or malady. Rational drug design remains the industry's primary development process. On the other hand, natural products screening involves testing large quantities of chemical extracts from plants, insects, fungi or microorganisms for specific bioactive properties. Once bioactivity is detected, active chemical constituents are isolated and purified for further screenings. A flow-chart describing natural products screening and the drug development process is included in Figure 4 (below).

     It is important to understand that both rational drug design and natural products screening have benefited from advances in biotechnology. Additionally, both processes are complementary to each other - not mutually exclusive. In other words, while a particular natural products screening program may not result in active compounds for the desired target, it may still provide insight into the nature of bioactivity for the target that is valuable for the design of synthetic drugs for the same target. Likewise, modeling of target molecules in a rational design program can lead to important understandings that inform the criteria used in a natural products screening program.

     Given these interrelationships, it is difficult to pinpoint with precision the biopharmaceutical industry's reliance on bioresources, and estimates vary widely according to how the question is defined. Most sources agree that up to 25% of the prescription drugs brought to market in the U.S. are derived from plant-based sources. Estimated sales of these drugs in the U.S. amounted to $4.5 billion in 1980 and $15.5 billion in 1990, and global sales in 1985 have been estimated at $43 billion. Another estimate regarding reliance on natural products has a similar conclusion:

Preliminary findings of an analysis by National Cancer Institute (NCI) researchers David Newman and Ken Gordon that examined how many chemical structures of new chemical entities worldwide had been approved for medicinal use from 1983-1993, show that more than 30% either came directly from natural products or their original structure came from natural products and would not have been found otherwise.

     Though specific figures could not be obtained, the increase in biochemical prospecting in fungi and microorganisms - taxonomic groups with a much higher estimated level of ecosystem, species, and genetic diversity than plants - suggests that the 25% figure could soon become a conservative estimate if natural product sources other than plants are taken into account.

Click here to see figure 4

     Two principal search strategies exist for identification of bioresources to be included in a natural products screening program. They include (1) random screening, which employs new, automated high-throughput assays and techniques to test mass quantities of bioresources for specific target properties, and (2) screenings informed by ethnobotanical, ecological, and/or biomedical knowledge of the bioresources and their active properties.

     While both strategies have been employed, the current trend in the biopharmaceuticals sector is towards increasing use of random screening. This trend is propelled by technology improvements in high-throughput screening techniques that now allow for screening of up to 10,000 samples per week. Indeed, the benefits of ethnobotanical-based discovery should be considered in light of potential drawbacks:

     There is some empirical evidence that indicates that ethnobiological, ecological, and biomedical information can increase the probability of success in individual primary screening tests by as much as an order of magnitude. But this higher expected success rate is likely to be achieved at the expense of higher research and collection costs and a smaller pool of species that meet the selection criteria. If the prospecting organization is drawing on existing ethnobiological or ecological information, it may also have to accept some limitations on the therapeutic objectives of the program, focusing on potential uses of biological material that have been identified by indigenous cultures or prior scientific research.

     In either case, bringing a new drug to market is a long and costly endeavor, and over-zealous estimates of the value of unimproved bioresources should be tempered with sober understanding of the many steps by which different values can be derived from biological diversity. Overall, PhRMA estimates the average cost to discover and develop one new medicine to equal $500 million over the course of 10-15 years. By most estimates, only one in 10,000 samples screened will contain an extract with desired bioactivity in the preliminary screenings. Taking into account that this extract must then perform positively in a series of additional rigorous trials, it is estimated that only one in 40,000 - 250,000 biological samples screened will result in a marketable product.

     Based on a range of disparate models and assumptions, estimates of the potential current value of bioresources to suppliers vary dramatically. Increasingly, sophisticated economic models are being designed to assist in the cost/benefit analysis of a particular proposed search strategy from the perspective of either the supplier or the commercial prospector. One of the most comprehensive compilations of estimated direct use values of genetic resources in the pharmaceutical sector is reproduced below in Figure 5.

Figure 5: Estimates of direct use values of genetic resources

     In the area of green pharmaceuticals, both search strategies described above are employed. However, since green pharmaceuticals are most often marketed as dietary supplements, the development process is less rigorous, and companies frequently expect a quicker return on their investment in bioactive compound identification and standardization of manufactured product. Since many green pharmaceutical preparations rely on the interplay of various active compounds, ethnobiological information - which frequently includes information about combinations of compounds - may have special value in the green pharmaceutical field.

     Another important consideration in the area of green pharmaceuticals is that since herbal and botanical preparations typically consist of concentrated quantities of the active ingredients directly from the plant-based source, the green pharmaceutical industry depends on both extractive as well as non-extractive uses of bioresources. In contrast, biopharmaceuticals consist almost exclusively of non-extractive uses. That is, information derived from research on natural products from bioresources is most often the value-added input contributed by a supplier of bioresources. While large qualities of natural product are required in some cases to isolate active compounds, biopharmaceutical companies typically seek to synthesize active compounds so that they no longer require an extractive supply of natural product. It is estimated that less than one percent of biopharmaceuticals on the market rely on extractive use of natural products. The case of the anti-cancer agent, taxol, originally derived from the bark of the Pacific yew tree was one example of such extractive use (however, taxol is now synthesized chemically).

Recommendations for Colombia

     Given the broad universe of potential applications for bioresources, what concrete steps can Colombia take to engage the international market and derive significant value and benefits from the country's biological wealth? In light of the analysis provided above with respect to the international biotechnology market, this section provides recommendations regarding immediate, practical measures that Colombia can take to develop its bioresources. Many of these recommendations also flow from WFED's direct experience with the design, negotiation and implementation of the first conservation-based access and benefit-sharing framework in the United States at Yellowstone National Park.

     In August 1997, Yellowstone signed the first agreement in the U.S. that provides access to biological resources from U.S. public lands for research purposes, under terms that provide for the sharing of benefits resulting from the commercial development of research results. By complying with the requirements of the National Park Service's Research Specimen Collection Permit regulations, the Diversa Corporation of San Diego, California, was permitted access to sample Yellowstone's thermophilic microbiological resources for scientific research purposes. Diversa also agreed to enter into a voluntary "Cooperative Research and Development Agreement" (CRADA) that requires the company to pay Yellowstone National Park $100,000 over five years to support cooperative microbial research and related conservation activities at the Park. In addition, the CRADA also requires Diversa to make an in-kind donation of equipment and scientific training valued at $375,000 over the same period. Finally, Diversa will pay Yellowstone royalties, as high as ten percent, based on the sales of products resulting from Diversa's research involving Yellowstone resources. These royalty payments must be made annually and in perpetuity, regardless of transfers of ownership over the commercial products. Given the tangible nature of arrangements developed in this case, Yellowstone's experience in the still-nascent field of biodiversity prospecting may provide a valuable point of reference for Colombia as the country seeks to develop its bioresource industry.

Recommendation #1: Facilitate research with clear terms of access

     Despite the many estimates of the potential value of bioresources to a mega-biodiversity country such as Colombia, no guarantee can be made with respect to financial or other benefits Colombia might receive from developing its national capacities with respect to bioresources. On the other hand, it is guaranteed that Colombia will not receive any benefits from this market unless it facilitates access to its biological resources for research purposes and develops guidelines for benefit-sharing. It was not until Yellowstone's management realized that research focused on Yellowstone's bioresources was already resulting in commercial benefits -- benefits in which the Park did not share -- that Park management clarified terms of access. This resulted in a program that allowed the Park to capture conservation benefits flowing from research results.

     Of course it is important to know that a strong market for bioresources exists. The preceding overview of the dynamic and fast-growing biotechnology industry demonstrates not only that demand for bioresources exists, but that this demand is expected to continue growing for the foreseeable future. Additionally, as discussed above, specific figures regarding the value of unimproved bioresources are difficult to obtain. However, the experience of Yellowstone National Park serves as evidence that conservation and sustainable use of biodiversity can be supported by research and benefit-sharing programs with the biotechnology industry.

     As discussed earlier, biotechnological research frequently proceeds without clearly identified commercial applications. Accordingly, Colombia's attention is best focused on establishing clear and efficient terms of access for research interests, rather than on which specific industry sectors Colombia's bioresources might best support. This latter question, along with the associated complexities and risks, are best left to be determined by the private sector. Even if specific industry sectors (such as biopharmaceuticals and green pharmaceuticals) were deemed especially well-suited to Colombia's interests, engagement in these markets could not proceed without clear and efficient terms of access that treat private sector entities equitably and efficiently.

     Determining clear terms of access does not necessarily require establishing specific parameters for benefit-sharing. Indeed, the establishment of terms of access often precedes the establishment of a benefit-sharing framework. While closely related issues, access and benefit-sharing are best viewed as somewhat distinct conservation and development tools. Specifically, terms of access can be seen as a vehicle through which benefits can be captured. Failure to resolve issues relating to terms of access often results from difficulties encountered in negotiating benefit-sharing terms.

     Finally, development of a bioresource access regime in Colombia may ultimately be dependent on the early establishment of access agreements and contracts for bioresource research projects. Attempts to debate and address every foreseeable permutation of potential research activities while designing general terms of access will never provide policy-makers with the practical experience that results from negotiating and implementing an actual access agreement. Ultimately, benefits from access to Colombia's bioresources may come from a varied portfolio of research activities and specific agreements - not just one or two research projects. It follows that the most efficient means of gaining experience in the market is to engage in it directly - addressing real as opposed to conceptual problems and solutions. A useful analogy in this respect is the case of software licensing. Current software licensing agreements covering networked and internet-based software applications could not have been conceived at the outset of end-user software development. At that early point in software development, many current practices and technologies were still not understood by regulators. Rather, the development of terms of use was (and still is) an iterative process that depends upon knowledge gained from practical experience.

     While terms of access should naturally be designed to promote Colombia's interests with respect to its conservation and economic development objectives, an outline of specific access terms lies outside the scope of this study. Nonetheless, findings relating to the nature of the international biotechnology market do have implications for the design of both access and benefit-sharing terms. These implications are discussed below.

Recommendation #2: Maximize research opportunities relating to bioresources

     Given that end-use applications of bioresources are often not apparent even to researchers themselves, terms of access developed to facilitate research on Colombian bioresources should seek to maximize opportunities for successful research. In other words, terms of access should provide researchers access to the broadest extent of biodiversity when possible, rather than restrict access to specific taxa or geographic areas. This is in recognition of the simple fact that, ultimately, conservation of Colombian biodiversity can only benefit from successful biodiversity prospecting activities. Furthermore, the needs and objectives of biotechnology researchers should be taken into account so that access terms encourage, rather than chill research activities. Most biotechnology research interests seek the following in a potential source of bioresources:

Reliable access

The ability to return to the source of prior samples to compare and confirm their identity is important to many researchers.

Clear terms of ownership and use

In order to protect research investments, researchers seek clear terms of ownership and use regarding research results and research specimens, respectively. Notably, patent and other intellectual property protection sought by research interests is ultimately provided by national and/or international legal institutions, not by national parks or local conservation areas, the entities most often involved in overseeing compliance with terms of access. In the case of Yellowstone National Park, the biological samples taken by researchers remain the property of the U.S. government. Authorized researchers retain the right only to use permitted samples for research purposes. National parks in the U.S. do not have the authority to grant intellectual property rights. Nonetheless, by providing clear terms concerning access to and use of national park bioresources as well as the ownership of research results, the national parks assist in providing research entities the certainty that may be required to invest in and develop products protected by patent. This in turn fosters an incentive for research on the biological resources preserved by national parks like Yellowstone. It is important to note that, while some researchers may seek exclusive access to the bioresources underlying their research, such exclusive access need not be granted. Indeed, Yellowstone National Park's management has no authority to grant exclusive access to federal biological resources.

Minimal transaction costs

Researchers prefer to secure access and terms of use with as little time and resources spent applying for permits, filing reports, and administering unnecessary paperwork. Put simply, minimal transaction costs facilitate research and thereby maximize benefits that may flow from sustainable bioresource use.

Conservation institutions

Finally, cognizant of their dependence on wild biodiversity, many biotechnology research entities are interested in sharing benefits from research and commercialization - provided that benefits flow directly to the national park or conservation institutions involved. Increasingly, the motivation underlying this position may derive from corporate policies developed to ensure companies provide compensation for access to and use of genetic resources on which they depend. Moreover, researchers ultimately benefit from state-of-the-art natural resource management practices - including species inventories and databases systems - which facilitate the efficient and sustainable use of natural resources and related information. Accordingly, many researchers are sympathetic to the additional financial resources required by natural resource managers and conservation institutions to implement such practices.

Recommendation #3: Negotiate benefit-sharing packages case-by-case

     As noted in Recommendation #1, separation of access and benefit-sharing terms is a useful technique that can help clarify confusing and contentious issues and facilitate the first step: providing efficient terms of access. With respect to the next step - the design of benefit-sharing terms - the findings of this study, combined with lessons drawn from Yellowstone National Park's experience, suggest that benefit-sharing packages are best negotiated on a case-by-case basis.

     The vast diversity of biotechnology applications and sectors means that the types and amounts of potential benefits Colombia could capture from the market will vary according to the specific research and use context. The biotechnology industry is comprised of companies of various sizes, ranging from small start-up research groups to well funded international corporations. Further, biotechnology research interests include private corporations, universities, as well as public and non-profit institutions, each of which operates according to different objectives and institutional procedures. While terms of access can be designed generally, to provide access by most types of research entities, benefit-sharing packages should be designed in accordance with the needs and capacities of specific research partners and the risk environments and markets in which they operate.

Recommendation #4: Pursue the broadest range of complementary benefits up-front

     While royalty payments from product sales may provide considerable support for conservation and sustainable use activities, these potential benefits are often far removed (10-20 years) and characterized by increased risk. In contrast, there are a host of additional benefits that can be realized up-front and packaged in ways that complement Colombia's existing capacities and strengths. In the case of Yellowstone National Park, a package was negotiated that guaranteed the Park $475,000 in direct benefits over five years, irrespective of whether the research company succeeds in bringing any products to market. In-kind benefits such as technical training and support have resulted in the DNA analysis of Yellowstone's wolves. This analysis has allowed the development of pedigrees for wolf packs and improved information for management of this keystone species.

     Apart from these direct benefits, additional indirect benefits may also be valuable. As an example, Diversa's CRADA also requires improved reporting of scientific information resulting from Diversa's research - information that would otherwise be inaccessible to Yellowstone's resource managers. The availability of such new scientific information has prompted other researchers and institutions to provide support for the development of information management systems, such as internet-based databases. These and other types of benefits can support further research and discovery, as well as public education programs.

     Other potential conservation benefits can be realized through benefit-sharing programs, specifically with respect to knowledge regarding Colombian biological resources and existing technological capacities. Relative to many other countries in the Andean region, Colombia's population is well-educated and has a high-level of scientific and technical capacity. Colombia also boasts a number of major scientific institutions that operate at an international level of technical sophistication. At the same time, less than half of Colombia's plant species (let alone fungi, or microorganisms) have been identified to date. It follows that technical cooperation and assistance in the area of taxonomy would be a benefit with high potential value to Colombia, and one that may be realized in the immediate-term through equitable and efficient access agreements.

Notes

1. World Conservation Monitoring Centre (WCMC), 1999, National Biodiversity Profiles - Colombia, internet URL: http://www.wcmc.org.uk.
2. Barnum, Susan R., 1998, Biotechnology: An Introduction, Wadsworth Publishing Company, Belmont, CA, at 1, quoting U.S. Congress Office of Technology Assessment.
3. Based in part on categories outlined in DRI, 1998, U.S. Industry and Trade Outlook 1998, McGraw-Hill, New York.
4. Joy, Richard, 1998, Standard & Poor's Industry Surveys - Biotechnology, September 3, 1998, at 1.
5. Supra note 4, at 5-6.
6. Brock, Thomas D., 1997, "The Value of Basic Research: Discovery of Thermus aquaticus and Other Extreme Thermophiles," Genetics, Vol. 146, August 1997, at 1207.
7. All dollar figures used in this study are expressed in U.S. dollars.
8. Supra note 4, at 7.
9. Pharmaceutical Research and Manufacturers of America (PhRMA), 1999, Leading the Way in the Search for Cures, PhRMA, Washington, DC, at 6.
10. See United States Food and Drug Administration, 1999, "An FDA Guide to Dietary Supplements," internet URL: http://www.verity.fda.gov.
11. Yuan, Robert, 1998, "Herbal Pharmaceutical Industry," Genetic Engineering News, Vol. 18, No. 19, November 1, 1998, quoting Elizabeth Sloan, Ph.D., Applied Biometrics, Stuart, Florida.
12. Id.
13. Supra note 4, at 5. "A 1998 survey of biotechnology products by the Pharmaceutical Research and Manufacturers of America (PhRMA) found that 350 biotechnology medicines were being tested in human clinical trials by biotechnology and pharmaceutical companies in the United States: this was a 23% increase over the previous year." (at 18).
14. Id, at 15.
15. Supra note 9, at 14.
16. Supra note 9.
17. Anderson, Elizabeth, Eve Stacey, Jackie Autwarter, and Ray A. Goldberg, 1992, "INBio/Merck Agreement: Pioneers in Sustainable Development," Harvard Business School case study, President and Fellows of Harvard College, Cambridge, MA, quoting U.S. Office of Technology Assessment, "Technologies to Maintain Biological Diversity," March 1987, at 4. The range of up to 25% was corroborated by author's personal communication with Sarah Radcliffe, Biologics and Biotechnology Department, Pharmaceutical Research and Manufacturers of America (PhRMA), March 15, 1999 and personal communication with Edgar Aseby, President and CEO, Andes Pharmaceuticals, Inc., March 17, 1999.
18. Reid, Walter V., et al., (eds.), 1993, Biodiversity Prospecting: Using Genetic Resources for Sustainable Development, World Resources Institute, Washington, DC, at 7-12, quoting Peter P. Principe, "Monetizing the Pharmacological Benefits of Plants," and Peter P. Principe, 1989, "The Economic Significance of Plants and Their Constituents as Drugs," 1-17 in H. Wagner, H. Hikino, and N. R. Farnsworth, (eds.), 1989, Economic and Medicinal Plant Research, Vol. 3, Academic Press, London, U.K.
19. Feinsilver, Julie M., and Ignacio H. Chapela, 1996, "Will Biodiversity Prospecting for Pharmaceuticals Lead to the Discovery of "Green Gold""? Commentary, 225-229 in Pan American Health Organization (PAHO), Biodiversity, Biotechnology, and Sustainable Development in Health and Agriculture: Emerging Connections, at 225.
20. From Artuso, Anthony, 1996, "Economic Analysis of Biodiversity as a Source of Pharmaceuticals," in Pan American Health Organization (PAHO), Biodiversity, Biotechnology, and Sustainable Development in Health and Agriculture: Emerging Connections, Scientific Publication No. 560, Washington, DC, 1996, at 169. "IND" refers to "investigational new drugs" reviewed clinical trials by the U.S. Food and Drug Administration.
21. Author's personal communication with Sarah Radcliffe, Biologics and Biotechnology Department, Pharmaceutical Research and Manufacturers of America (PhRMA), March 15, 1999.
22. Reid, Walter V., 1997, "Technology and Access to Genetic Resources," 53-70 in John Mugabe, et al., (eds.), 1997, Access to Genetic Resources: Strategies for Sharing Benefits, ACTS Press, Nairobi, Kenya.
23. Supra note 20, at 174.
24. Pharmaceutical Research and Manufacturers of America (PhRMA), 1999, The Value of Pharmaceuticals, PhRMA, Washington, DC.
25. Author's personal communication with Edgar Aseby, President and CEO, Andes Pharmaceuticals, Inc., March 17, 1999. Also, see supra note 19, at 226: "The [National Cancer] Institute's rule of thumb regarding natural products samples is that out of 10,000 samples tested, only 1 activity may proceed to the next level of sophistication (preclinical pharmacology). Of every 10 that get to preclinical pharmacology, 1 becomes an investigational new drug (IND). Of every 10 investigational new drugs, only 1 or 2 get to the market. As a result, the odds of getting a drug to market from any given sample are 1 in 250,000."
26. See supra note 18, at 17, and supra note 20 for examples of economic models applied to such estimates.
27. From Lesser, William, 1998, Sustainable Use of Genetic Resources Under the Convention on Biological Diversity: Exploring Access and Benefit Sharing Issues, CAB International, New York. References provided therein.
28. Author's personal communication with Robert Yuan, Professor of Microbiology, University of Maryland, and founder and principal, Marco Polo Technologies, March 15, 1999.
29. For a detailed description of the background and substance of the Yellowstone case, see Preston T. Scott, 1998, "Biodiversity and Bioprospecting in the National Parks: The Yellowstone Experience," WFED, Washington, DC, available in plain html text format at http://wfed.org/briefing.htm or as an Adobe Acrobat (.pdf / 2.1 or higher) document at http://wfed.org/briefing.pdf.
30. Author's personal communication with David Olson, Conservation Science Program, World Wildlife Program - US, March 17, 1999.
    

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