CIESIN Reproduced, with permission, from:Farnsworth, N. R., and D. D. Soejarto. 1985. Potential consequence of plant extinction in the United States on the current and future availability of prescription drugs. Economic Botany 39 (3): 231-40.

Potential Consequence of Plant Extinction in the United States on the Current and Future Availability of Prescription Drugs[1]

NORMAN R. FARNSWORTH AND DJAJA DOEL SOEJARTO[2]


This paper attempts to answer the question: What is the dollar value that can be placed on a single plant species now growing in the United States, should it become extinct? Based on available botanical and prescription survey data and data on global studies of plants as a source of new drugs for human use, the value of a single species is calculated to be $203 million, and the total value of plant species growing in the United States that may become extinct by the year 2000 AD is calculated to be about $3.248 billion.


All drugs used by humans are derived by synthesis, from inorganic chemicals, or from living organisms. Those obtained from living organisms are derived from plants, microorganisms, or animals. This paper addresses only drugs obtained from the higher, or flowering plants.

The question that the paper will attempt to answer is "what is the dollar value that can be placed on a single plant species now growing in the United States, should it become extinct?" In some respects one might believe it impossible to place a dollar value on a single plant species, especially when faced with the number of variables that must be considered in calculating such a number. However, an attempt will be made to give a reasonable estimate, which will be based on a number of assumptions, some of which may not be entirely supportable with hard data. If nothing else is gained from this exercise, it could serve to shed some light on a method that could be used to calculate such a value, since data are available that could convert some of the assumptions used into fact. Given more data, the final cost estimate could be routinely calculated on an annual basis and eventually a final value would have a greater degree of credibility.

There are several groups of data that form the basis for calculating a dollar value for a single flowering plant species in the United States that may become extinct, with respect to its potential for drug use.

BOTANICAL DATA

The number of species of flowering plants currently known to exist on this planet is about 250,000. Estimates have been made as low as 215,000 for species already named and described (Cronquist, 1981) and as high as 500,000 for species described plus an estimate of still unnamed and undescribed species (Schultes, 1972; Tippo and Stern, 1977). For purposes of this exercise, however, a conservative figure of 250,000 species will be used (Ayensu and DeFilipps, 1978).

Since the subject of this paper is restricted to endangered or threatened plant species growing in the United States, the number of species recognized for this area will be taken as 20,674 (Kartesz and Kartesz, 1980). (Since no estimate for the continental United States is available, the statistics on flowering plants provided by Kartesz and Kartesz for the area covering the continental United States, Alaska, Canada, Hawaii, and Puerto Rico are used here.)

It has been suggested that about 10% of all species of flowering plants could be extinct by the year 2000 AD (Melville, 1978). This represents 25,000 species. On the basis of the same assumption, one could project that 2,067 species of flowering plants now growing in the United States would be extinct in the year 2000 AD.

PRESCRIPTION SURVEY DATA

A second type of data will be used that have been acquired through analysis of a recognized prescription survey in the United States. Annual data have been analyzed for the years 1959-1973, and extrapolation of certain of these data will be made to project the Current status of plant-derived drugs in the United States through the year 1983.

The National Prescription Audit (NPA; a product of IMS America Ltd., Ambler, PA 19002) was used to obtain certain necessary data. These data represent the number of new and refilled prescriptions dispensed from community pharmacies in the United States each year. It was necessary for us to obtain the raw data concerning thousands of names of drug products prescribed throughout the United States and to identify those containing crude plant extracts, semipurified mixtures of active principles, single active principles, or active principles that had been chemically modified. In the latter instance, the prescription drugs encountered in the NPA data could not have been prepared without the availability of starting material that was extracted from one or more plants. A summary of these data follows.

Over the period 1959-1973 an average of 25.36% of all prescriptions encountered in the survey contained one or more active principles still derived from higher plants. The percent was never lower than 23.12 and never higher than 28.22, during any single year, which is a remarkably stable situation (Farnsworth and Morris, 1976).

Since the total number of new and refilled prescriptions dispensed each year from community pharmacies was known, the number containing plant-derived active constituents could be readily calculated. The resulting number could then be multiplied by the average prescription price for each year, which would give a dollar value at the consumer level for plant-derived prescriptions in the United States.

Because prescriptions are dispensed from other than community pharmacies, that is, from hospital out-patient services, government agencies. mail-order services, and others, a reasonable factor to account for the total plant-derived drug market was determined to be 2 (Farnsworth and Morris, 1976). Thus, for example, in 1973, 1.532 billion new and refilled prescriptions were dispensed from community pharmacies in the United States. At an average cost to the consumer in that year of $4.13 per prescription, a dollar value of $6.327 billion (at the consumer level) for the market could be derived. Thus, in 1973 the 25.2% of prescriptions found to contain active principles derived from plants, could be estimated at $1.594 billion. Multiplying this number by the factor of 2 gave a total value for plant-derived drugs in the United States during 1973 of about $3.188 billion.

Interesting data could be obtained by inspecting the types of plant-derived materials entering into prescription drugs during the year 1980. It was found that about 40 species of higher plants yielded all these drugs (Table 1).

However, 58 additional plant species (or products from them) were found in the 1980 prescription data, even though these species or compounds from them are not recognized by the Food and Drug Administration (FDA) as being efficacious for any medical condition (Table 2). Eventual studies may give them "drug" status in the United States, but it is difficult to consider these 58 species as legitimate "drugs" for purposes of calculations.

An additional 300 or so species of flowering plants are sold as herbal teas in the United States, mainly through health food outlets. According to FDA regulations, all of these herbal teas are considered to be "foods," and not "drugs" but it is obvious that the consumer purchases herbal teas because it is believed that they produce therapeutic effects. In 1979 the market value for herbal teas sold in health food outlets in the United States was $150 million, an increase of 32% over the previous year (Anonymous, 1980). Since these 300 or so species of flowering plants entering into the herbal tea market are not recognized as "drugs," they were also not used in the calculations that follow.

As can be seen in Fig. 1, the survey data from 1964-1973 indicate that there was a linear increase in the total number of new and refilled prescriptions dispensed from community pharmacies in the United States. However, from 1974-1980. the total number of prescriptions progressively decreased. The explanation for this is that most likely federal health programs, nursing homes, mail order prescription sales, and hospital out-patient services began to take a significant share of prescriptions from the community pharmacies, a phenomenon which seems to have made its impact in 1974. However, it seems reasonable to assume, since the increase in total prescriptions dispensed from community pharmacies was a progressive linear function for a 10-yr period, that the impact of prescriptions being acquired through noncommunity drug outlets from 1974-1980 would be represented by the difference in the actual prescription numbers and the projected continuation of the increasing linear plot as shown in Fig. 1. This presumption had to be made, since data presented in the NPA survey are representative only of that portion of the prescription market measured by community pharmacy dispensing activities. Data obtained by extrapolation, as shown in Fig. 1, indicate that prescription sales would be estimated at about 2.0 billion in 1980.

As indicated previously, the average number of prescriptions each year that contained active principles derived from higher plants, over the period of 1959-1973 was calculated to be 25.36%. Hence, by extrapolation (Fig. 1), the number of prescriptions dispensed during 1980 that contained active principles from flowering plants was determined to be about 507 million.

In 1980, the average prescription price was about $8.00 (Anonymous, 1981), which means that the cost to the consumer for new and refilled prescriptions containing plant-derived active principles in that year was about 507 million x $8 = $4.056 billion. Using the previously defined factor of 2 that adjusts the number of community pharmacy-dispensed prescriptions to all drugs dispensed in the United States, the cost for drugs derived from higher plants in 1980 would be about $8.112 billion.

PRESUMPTIVE DATA

From this point, a third type of data must be considered in order to estimate the cost for each plant species growing in the United States that may become extinct, relative to its drug potential. Some numbers could probably be derived in a more factual way through an enormous amount of literature work, but this is beyond the capability of our staff at this time. Thus, certain numbers are being suggested that are derived from our knowledge of scientific studies that have been reported on the pharmacological effects of plant extracts. We estimated that about 5,000 species of flowering plants throughout the world have been exhaustively studied as a source of new drugs for human use. In making this estimate, unpublished data from pharmaceutical firms throughout the world were taken into consideration. It must be taken into account that one can never completely discount any plant, no matter how exhaustively it has been tested for biological effects, as being completely devoid of one or more useful drugs. For example, the National Cancer Institute has tested extracts from more than 35,000 species of higher plants for anticancer activity against one or two tumors in laboratory animals (Douros and Suffness, 1980). Negative results on any of these plants do not preclude them from being devoid of usefulness to treat human cancer. More than 400 different animal tumor systems are known, and it is not entirely clear which of these are most predictive for human cancer. It is impossible to test every plant for its effects against every known type of animal tumor. Further, the solvent or solvents used to prepare extracts from these plants may not extract sufficient amounts of the active principles to produce a significant effect. It is unrealistic to test an endless number of extracts, each prepared with different solvents, to exhaust all possibilities that an active principle is present or absent from the test extracts.

Even though 35,000 or more flowering plant species have been reported to be "devoid of anticancer properties," the possibility of these plants containing active principles useful as tranquilizers, antihypertensives, antimalarials, antiulcer agents, contraceptives or dozens of other types of drugs, cannot be discounted. It is simply impossible to test any plant or any chemical compound, for every conceivable type of drug effect. This is a real problem in estimating the dollar value of any plant that becomes unavailable through extinction.

However, in using the number 5,000 as representative of the number of species that have been exhaustively studied for the presence of useful drugs, we have a constant that can be used for calculations. Subsequently, it will be shown that the actual dollar value will be considerable, whether the number is 5,000, 10,000 or 50,000.

ESTIMATION OF THE RELATIVE VALUE OF A SINGLE PLANT SPECIES

If 5,000 species of flowering plants have been thoroughly examined on a worldwide basis as sources of useful drugs, and only 40 of these plants are currently used in the United States as sources of drugs, one can anticipate that for every 125 plants subjected to a thorough pharmacological examination, one will eventually become important as a drug source.

As indicated previously, it is projected that 10% of all species of flowering plants in the United States will become extinct by the year 2000 AD (if appropriate measures are not taken to prevent this from happening) and this would involve 2,067 species. Thus it can be calculated that 2,067/125 = 16 species of useful drug plants will have been eliminated through extinction from the flora of the United States.

Based on the previously calculated dollar value of new and refilled prescriptions provided to the American consumer in 1980 at about $8.112 billion, this would place the value of each of the 40 species of plants from which these prescription drugs are derived at about $8.112 billion/40 = $203 million per species.

Thus, for the projected 16 useful drug plants that may become extinct in the United States by 2000 AD, a total value can be calculated at about 16 x $203 = $3.248 billion for the year 2000 AD (in 1980 dollars).

VALIDITY OF THE EXERCISE

Even though several aspects of the exercise described here are based on reasonably sound data, it was necessary to utilize what appear to be common sense projections in order to arrive at a final dollar value.

Not being authorities in the field of economics, we are not certain whether the calculations that we have presented are valid if based on the price of prescriptions to the consumer. Since we presume that the consumer is the person most affected if drugs are available or are not available, we would have to believe that our presumption is valid. It would be virtually impossible to determine the cost of prescriptions based on the actual cost of raw material.

In this exercise, all the projections are based on the assumption that drugs from plants are discovered by random sampling of plants and testing them for drug value. Drugs obtained from flowering plants are not discovered by any one formula. Most of them probably are derived through folklore, a few by screening on a semirandom basis, and a large number on the basis of serendipity. Thus, in estimating that perhaps 5,000 species of plants have been thoroughly studied for their potential as drugs, this number has been derived from global research, and might not apply proportionately to plants that grow in the United States (including Alaska, Hawaii and Puerto Rico). Scientists in Japan investigate plants growing only in Japan as a source of drugs; scientists in the Soviet Union investigate only plants growing in the Soviet Union; Indian scientists investigate only plants growing in India; scientists in the People's Republic of China investigate only plants growing in China; French scientists investigate only plants that grow in France, or in one or more countries formerly under French rule; but American scientists, for some strange reason, rarely investigate American plants as a source of drugs. Thus, only a fraction of the 20,670 species of plants known to grow in the United States have been thoroughly studied for their drug potential. Of the 40 species of plants that are known to produce more than 25% of the drugs entering into prescriptions in the United States today, only 3 are indigenous to the United States. Further, in 1974 the research and development budget for the entire pharmaceutical industry in the United States was about $0.723 billion (Farnsworth and Morris, 1976). In 1974 there was only one pharmaceutical company that had a research program targeted to investigate plants as sources of new drugs and less than $200,000 per year was involved in that effort. In 1980 there were no pharmaceutical companies in the United States that had targeted programs to develop new drugs from plants. There are many reasons for this that have recently been discussed (Farnsworth and Bingel, 1977; Tyler, 1979), but this is a subject too complex for this paper. The point is that it is difficult to project how many drug plants will become extinct in the United States by the year 2000 AD, when there is virtually no effort being made to explore the flora of this country for purposes of drug development. All that can be said is, if 2,067 species of flowering plants become extinct by the year 2000 AD, 16 species should have produced drugs had the 2,067 been thoroughly investigated. Hence, at the current rate of extinction, given the lack of interest in exploring the flora of this country for new drugs, about 16 new drugs will be lost forever.

Previously it was pointed out that 58 species of plants without recognized efficacy as drugs were identified in the 1980 National Prescription Audit as entering into prescriptions in that year. The value of these plants is questionable in terms of therapeutic effect, but they do have an economic value. Also, as previously indicated, the "herbal tea" business in the United States was in excess of $150 million in 1979 (Anonymous, 1980), and this figure has not been used in calculating the economic value of extinct species.

Important drugs to some are the laxatives. It is known that the entire laxative business in the United States in 1980, exclusive of prescription sales, amounted to about $331 million (up 10.3% from 1979), and about half of the available products contain plant principles (Gossel and Wuest, 1981). Further, in 1977, global sales at the manufacturer's level for vincaleukoblastine and leurocristine, 2 useful anticancer alkaloids from the Madagascan periwinkle, Catharanthus roseus (L.) G. Don (Syn.: Vinca rosea L.) were about $35 million (G. H. Svoboda, pers. comm., 1981). Catharanthus roseus is a pantropical species, originating in Madagascar, but found growing throughout the United States as an ornamental plant. Most of the C. roseus used for the production of vincaleukoblastine and leurocristine is now grown under cultivation in Texas (G. H. Svoboda, pers. comm., 1981).

Finally, indirect support for the validity of some of the approximately 16 species of plants predicted to disappear as sources of new drugs through extinction by the year 2000 AD, can be put forth. If we can equate the period 1950 through 1981, about 31 yr, to the period 1984 through 2000 AD, about 16 yr. some type of relationship can be made, at least for prescription drugs from flowering plants being marketed in the United States. The amount of research interest in the United States in discovering drugs from flowering plants probably was at its peak during the years 1953 through 1960, with a rapid decline to virtually no interest in 1981. During this 31-yr period, the following drugs from higher plants were discovered or developed into prescription items. First and most important was the use of diosgenin as a starting material for the synthesis of virtually all of the anovulatory contraceptive agents used by women, followed by the antihypertensive and tranquilizing alkaloids, reserpine, deserpidine, and rescinnamine, from Rauvolfia serpentina (L.) Benth. ex Kurz and other Rauvolfa species, followed by the useful antitumor agents leurocristine and vincaleukoblastine from Catharanthus roseus, and ending with the laxative agents sennosides A and B from Cassia species and the cardiotonic agent acetylgitoxin from Digitalis species. Thus, at least 9 useful drugs derived from higher plants were developed and/or discovered during the 31 or so years from 1950 through 1981, and these were brought to life with very little direct investment of time and/or funds by the pharmaceutical industry in this country.

In addition, about 40 additional useful steroid drugs were introduced to the marketplace from 1950-1981, which would not have been possible if diosgenin was unavailable as a starting material for their synthesis. If a reasonably organized effort were made in the search for new drugs from plants of the American flora during the next 16 yr, it would not seem unreasonable to anticipate an average of one new drug each year being developed from the predicted 2,067 species to be extinct by the year 2000 AD.


1 Received 10 May 1984: accepted 2 March 1985. The original version of this paper was presented at the symposium, "Estimating the Value of Endangered Species: Responsibilities and Role of the Scientific Community," Annual Meeting, American Association for the Advancement of Science. Washington, DC, January 4, 1982.

2 Program for Collaborative Research in the Pharmaceutical Sciences, Health Sciences Center, University of Illinois at Chicago, Chicago, IL 60612.

ACKNOWLEDGMENTS

The authors are indebted to IMS America, Ltd., Ambler, PA, for their cooperation in making the National Prescription Audit data available for use in preparing certain parts of the analyses.

LITERATURE CITED

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Anonymous. 1981. The Lilly Digest. Eli Lilly and Co., Indianapolis, IN.

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Cronquist, A. 1981. An Integrated System of Classification of Flowering Plants. Columbia Univ. Press, New York.

Douros, J. D., and M. Suffness. 1980. The National Cancer Institute's natural products antineoplastic development program. Recent Results Cancer Res. 70: 21-24.

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_____, and R. W. Morris. 1976. Higher plants---the sleeping giant of drug development. Amer. J. Pharm. 148: 46-52.

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